U.S. patent application number 16/275220 was filed with the patent office on 2019-09-19 for systems, devices, and methods for bodily fluid sample collection, transport, and handling.
The applicant listed for this patent is Theranos IP Company, LLC. Invention is credited to Brian Argyres, Michael Chen, Elizabeth A. Holmes, Adrit Lath, Clarissa Lui, Zachary Morrison, William Westrick, Daniel Young.
Application Number | 20190287657 16/275220 |
Document ID | / |
Family ID | 65898502 |
Filed Date | 2019-09-19 |
![](/patent/app/20190287657/US20190287657A1-20190919-D00000.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00001.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00002.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00003.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00004.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00005.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00006.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00007.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00008.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00009.png)
![](/patent/app/20190287657/US20190287657A1-20190919-D00010.png)
View All Diagrams
United States Patent
Application |
20190287657 |
Kind Code |
A1 |
Holmes; Elizabeth A. ; et
al. |
September 19, 2019 |
SYSTEMS, DEVICES, AND METHODS FOR BODILY FLUID SAMPLE COLLECTION,
TRANSPORT, AND HANDLING
Abstract
Bodily fluid sample collection systems, devices, and method are
provided. The device may comprise a first portion comprising at
least a sample collection channel configured to draw the fluid
sample into the sample collection channel via a first type of
motive force. The sample collection device may include a second
portion comprising a sample vessel for receiving the bodily fluid
sample collected in the sample collection channel, the sample
vessel operably engagable to be in fluid communication with the
collection channel, whereupon when fluid communication is
established, the vessel and/or another source provides a second
motive force different from the first motive force to move a
majority of the bodily fluid sample from the channel into the
vessel.
Inventors: |
Holmes; Elizabeth A.; (San
Francisco, CA) ; Lui; Clarissa; (Menlo Park, CA)
; Chen; Michael; (Sunnyvale, CA) ; Young;
Daniel; (San Francisco, CA) ; Lath; Adrit;
(Sunnyvale, CA) ; Morrison; Zachary; (San
Francisco, CA) ; Argyres; Brian; (San Mateo, CA)
; Westrick; William; (Palo Alto, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Theranos IP Company, LLC |
Healdsburg |
CA |
US |
|
|
Family ID: |
65898502 |
Appl. No.: |
16/275220 |
Filed: |
February 13, 2019 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
14737412 |
Jun 11, 2015 |
10248765 |
|
|
16275220 |
|
|
|
|
14446080 |
Jul 29, 2014 |
|
|
|
14737412 |
|
|
|
|
PCT/US2013/000268 |
Dec 5, 2013 |
|
|
|
14446080 |
|
|
|
|
29466440 |
Sep 8, 2013 |
D732686 |
|
|
PCT/US2013/000268 |
|
|
|
|
29466441 |
Sep 8, 2013 |
D733314 |
|
|
29466440 |
|
|
|
|
29466442 |
Sep 8, 2013 |
D733315 |
|
|
29466441 |
|
|
|
|
29466443 |
Sep 8, 2013 |
D733316 |
|
|
29466442 |
|
|
|
|
29466710 |
Sep 10, 2013 |
D733317 |
|
|
29466443 |
|
|
|
|
29466440 |
Sep 8, 2013 |
D732686 |
|
|
29466710 |
|
|
|
|
29466441 |
Sep 8, 2013 |
D733314 |
|
|
29466440 |
|
|
|
|
29466739 |
Sep 11, 2013 |
D733318 |
|
|
PCT/US2013/000268 |
|
|
|
|
29466442 |
Sep 8, 2013 |
D733315 |
|
|
29466739 |
|
|
|
|
29466443 |
Sep 8, 2013 |
D733316 |
|
|
29466442 |
|
|
|
|
14447099 |
Jul 30, 2014 |
|
|
|
14737412 |
|
|
|
|
PCT/US2013/000268 |
Dec 5, 2013 |
|
|
|
14447099 |
|
|
|
|
29466440 |
Sep 8, 2013 |
D732686 |
|
|
PCT/US2013/000268 |
|
|
|
|
29466441 |
Sep 8, 2013 |
D733314 |
|
|
29466440 |
|
|
|
|
29466442 |
Sep 8, 2013 |
D733315 |
|
|
29466441 |
|
|
|
|
29466443 |
Sep 8, 2013 |
D733316 |
|
|
29466442 |
|
|
|
|
29466710 |
Sep 10, 2013 |
D733317 |
|
|
29466443 |
|
|
|
|
29466739 |
Sep 11, 2013 |
D733318 |
|
|
29466710 |
|
|
|
|
14098177 |
Dec 5, 2013 |
9386948 |
|
|
14737412 |
|
|
|
|
61852489 |
Mar 15, 2013 |
|
|
|
61733886 |
Dec 5, 2012 |
|
|
|
61786351 |
Mar 15, 2013 |
|
|
|
61875030 |
Sep 7, 2013 |
|
|
|
61875107 |
Sep 8, 2013 |
|
|
|
61852489 |
Mar 15, 2013 |
|
|
|
61733886 |
Dec 5, 2012 |
|
|
|
61786351 |
Mar 15, 2013 |
|
|
|
61875030 |
Sep 7, 2013 |
|
|
|
61875107 |
Sep 8, 2013 |
|
|
|
61733886 |
Dec 5, 2012 |
|
|
|
62011023 |
Jun 11, 2014 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 9/06 20130101; A61B
5/150022 20130101; A61B 5/15113 20130101; B01L 2200/185 20130101;
A61B 5/150305 20130101; A61B 5/150412 20130101; A61B 5/15074
20130101; A61B 5/150351 20130101; G16H 10/40 20180101; A61B
5/150503 20130101; A61B 5/15109 20130101; A61B 5/15105 20130101;
A61B 5/15142 20130101; G06Q 10/0832 20130101; A61B 5/150251
20130101; A61B 5/150343 20130101; A61B 5/150732 20130101; B01L
3/502715 20130101; B01L 2300/185 20130101; B01L 7/04 20130101; A61B
5/150755 20130101; B01L 2200/16 20130101; B01L 2300/022 20130101;
B01L 2300/1883 20130101; A61B 5/150389 20130101; A61B 5/150992
20130101; B01L 2300/024 20130101; A61B 5/150786 20130101; A61B
5/15117 20130101 |
International
Class: |
G16H 10/40 20060101
G16H010/40; G06Q 10/08 20060101 G06Q010/08; A61B 5/15 20060101
A61B005/15; A61B 5/151 20060101 A61B005/151; B01L 9/06 20060101
B01L009/06 |
Claims
1-8. (canceled)
9. A method for use with a bodily fluid sample from a subject, the
method comprising: shipping a plurality of sample containers from a
first location to a second location, wherein each of said sample
containers contains a biological sample between about 500 .mu.l to
about 10 .mu.l, wherein shipping of the plurality of samples
containers is accomplished using a first frame sized to fit in a
shipping container, said first frame comprises a plurality of
openings each sized and shaped to engage at least one of the sample
containers and hold the sample containers in a desired orientation;
obtaining data from each of the sample containers; providing a
plurality of processing frames at the second location; using said
data from the sample containers to determine which of said
processing frames receive which of said sample containers and
provide sorting information for the sample containers; and moving
said sample containers from the first frame to the processing frame
based on data provided by the sample containers and based on said
sorting information.
10. The method of claim 9 wherein each of the sample containers
further comprises at least one sample container information storage
unit, wherein obtaining data from the sample containers comprises
simultaneously scanning a plurality of sample container information
storage units simultaneously.
11. The method of claim 10 wherein said scanning occurs when the
sample containers are in the shipping frame.
12. The method of claim 10 wherein said scanning comprises scanning
an underside surface of each of the sample containers.
13. The method of claim 9 further comprising providing at least one
database at a server, wherein determining which processing frames
receive which of the sample containers comprises referencing the
data with said at least one database at said server.
14. The method of claim 13 further comprising providing at least
one database of subject identifiers at a server. wherein said data
from the sample containers comprise at least one sample container
identifier, and wherein said determining comprises matching said at
least one sample container identifier with at least one of said
subject identifiers.
15. The method of claim 9 further comprising providing a plurality
of sample container processing procedures wherein said data from
the sample containers comprise at least one sample container
identifier, and wherein said determining comprises matching said at
least one sample container identifier with one of said sample
container processing procedures.
16. The method of claim 9 wherein at least some of the sample
containers contain sample having a first anticoagulant and at least
some other of the sample containers have a second, different
anticoagulant.
17. The method of claim 9 wherein moving said sample containers
comprises using a robotic manipulator.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Patent Application
Ser. No. 62/011,023 filed Jun. 11, 2014, U.S. patent application
Ser. No. 14/447,099 filed Jul. 30, 2014, U.S. patent application
Ser. No. 14/446,080 filed Jul. 29, 2014, and U.S. patent
application Ser. No. 14/098,177 filed Dec. 5, 2013. All of the
foregoing are fully incorporated herein by reference for all
purposes.
BACKGROUND
[0002] A blood sample for use in laboratory testing is often
obtained by way of venipuncture, which typically involves inserting
a hypodermic needle into a vein on the subject. Blood extracted by
the hypodermic needle may be drawn directly into a syringe or into
one or more sealed vials for subsequent processing. When a
venipuncture may be difficult or impractical such as on a newborn
infant, a non-venous puncture such as a heel stick or other
alternate site puncture may be used to extract a blood sample for
testing. After the blood sample is collected, the extracted sample
is typically packaged and transferred to a processing center for
analysis.
[0003] Unfortunately, conventional sample collection and testing
techniques of bodily fluid samples have drawbacks. For instance,
except for the most basic tests, blood tests that are currently
available typically require a substantially high volume of blood to
be extracted from the subject. Because of the high volume of blood,
extraction of blood from alternate sample sites on a subject, which
may be less painful and/or less invasive, are often disfavored as
they do not yield the blood volumes needed for conventional testing
methodologies. In some cases, patient apprehension associated with
venipuncture may reduce patient compliance with testing protocol.
Furthermore, the transportation of small volumes of sample fluid,
while still maintaining sample integrity, can be problematic.
SUMMARY
[0004] At least some of disadvantages associated with the prior art
are overcome by at least some or all of the embodiments described
in this disclosure. Although the embodiments herein are typically
described in the context of obtaining a fluid sample such as but
not limited to a blood sample, it should be understood that the
embodiments herein are not limited to blood samples and can also be
adapted to acquire other fluid(s) or bodily sample(s) for
analysis.
[0005] In one embodiment described herein, a device is provided for
collecting a bodily fluid sample. In embodiments, the bodily fluid
may be blood. In embodiments where blood is collected, this
embodiment may be useful for accurately collecting small volumes of
bodily fluid sample that are often associated with non-venous blood
draws. In one non-limiting example, the sample volume is about 1 mL
or less. Optionally, the sample volume is about 900 uL or less.
Optionally, the sample volume is about 800 uL or less. Optionally,
the sample volume is about 700 uL or less. Optionally, the sample
volume is about 600 uL or less. Optionally, the sample volume is
about 500 uL or less. Optionally, the sample volume is about 400 uL
or less. Optionally, the sample volume is about 300 uL or less.
Optionally, the sample volume is about 200 uL or less. Optionally,
the sample volume is about 100 uL or less. Optionally, the sample
volume is about 90 uL or less. Optionally, the sample volume is
about 80 uL or less. Optionally, the sample volume is about 70 uL
or less. Optionally, the sample volume is about 60 uL or less.
Optionally, the sample volume is about 50 uL or less.
[0006] In one non-limiting example, this device can be used to
split the bodily fluid sample directly into two or more different
portions that are then deposited into their respective sample
vessels. In one non-limiting example, the device comprises a first
portion having at least two sample collection channels configured
to draw the fluid sample into the sample collection channels via a
first type of motive force, wherein one of the sample collection
channels has an interior coating designed to mix with the fluid
sample and another of the sample collection channels has another
interior coating chemically different from said interior coating.
The sample collection device includes a second portion comprising a
plurality of sample vessels for receiving the bodily fluid sample
collected in the sample collection channels, the sample vessels
operably engagable to be in fluid communication with the collection
channels, whereupon when fluid communication is established, the
vessels provide a second motive force different from the first
motive force to move a majority of the bodily fluid sample from the
channels into the sample vessels. The sample vessels may be
arranged such that mixing of the fluid sample between the vessels
does not occur. This device may be used to collect blood or other
bodily fluid. Blood collection from veins may be relatively rapid;
however, non-venous blood draws may take a longer period of time to
obtain a desired volume of sample and the early introduction of a
material such as an anti-coagulant which may coat the channels, can
prevent premature clogging of the channels during collection.
[0007] In another embodiment described herein, a device is provided
for collecting a bodily fluid sample. The device comprises a first
portion comprising a plurality of sample collection channels,
wherein at least two of the channels are configured to
simultaneously draw the fluid sample into each of the at least two
sample collection channels via a first type of motive force. The
device may also include a second portion comprising a plurality of
sample vessels for receiving the bodily fluid sample collected in
the sample collection channels, wherein the sample vessels have a
first condition where the sample vessels are not in fluid
communication with the sample collection channels, and a second
condition where the sample vessels are operably engagable to be in
fluid communication with the collection channels, whereupon when
fluid communication is established, the sample vessels provide a
second motive force different from the first motive force to move
bodily fluid sample from the channels into the sample vessels. In
embodiments, motive force to move a bodily fluid may include motive
force derived from capillary action, from reduced pressure (e.g.,
vacuum or partial vacuum drawing fluid into a location having
reduced pressure), from increased pressure (e.g., to force a fluid
away from a location having increased pressure), from wicking
material, or from other means.
[0008] In a still further embodiment described herein, a method is
provided comprising metering a minimum amount of sample into at
least two channels by using a sample collection device with at
least two of the sample collection channels configured to
simultaneously draw the fluid sample into each of the at least two
sample collection channels via a first type of motive force. After
a desired amount of sample fluid has been confirmed to be in the
collection channels, fluid communication is established between the
sample collection channels and the sample vessels, whereupon the
vessels provide a second motive force different from the first
motive force use to collect the samples to move bodily fluid sample
from the channels into the vessels. In some alternative
embodiments, devices that use only a single channel to collect the
body fluid or devices that have a plurality of channels but do not
collect them simultaneously are not excluded. Optionally, the
collection of sample fluid is performed without the use of a
wicking material.
[0009] In one embodiment, there is a discrete amount of time
between sample collection and introduction of the sample into a
sample pre-processing device. In one non-limiting example, the
process is a non-continuous process. The sample collection occurs
in one processing station and then the sample is taken to a second
station. This second station may be in the sample building.
Optionally, the second station may be located at another location
where the sample needs to be walked, driven, flown, conveyor-ed,
placed in a transport device, or placed in a transport container to
reach the second location. In this manner, there is a discrete
break in the processing to allow for time associated with sample
transport.
[0010] In another embodiment herein, separator gel(s) can also be
included in the sample vessels such that the gels will separate
cell-free fractions of whole blood from the cellular or other solid
or semi-solid portions of the sample. Such a gel or other similar
separator material may be included in the sample vessel prior to,
during, or after sample has been introduced into the sample vessel.
The separator material may have a density between that of the cells
and solution components, so that the material separates the sample
components by flowing to a position between the solution and
non-solution sample layers during separation such as by
centrifugation. Following centrifugation, the separator material
stops flowing and remain as a soft barrier between the layers. In
some embodiments, the separator material can be further processed
to harden into a more rigid barrier. In on non-limiting example,
the separator material may be a UV-curable material such as but not
limited to thixotropic gel of sorbitol-based gelator in a
diacrylate oligomer. The sample vessel may have the entire vessel
or optionally, on that portion with the UV-curable material exposed
to UV light for a period of time such as but not limited to 10 to
30 seconds to harden the material. Such hardening may involve
cross-linking of material in the UV-curable material. Optionally,
the UV curable material may be used in conjunction with traditional
separator gel material such that only one side (the solution side
or the solid side) is in contact with the UV cured material.
Optionally, the UV cured material may be used with a third material
such that the UV cured material is between two separator materials
and is not in direct contact with the solution and non-solution
portions of the sample.
[0011] Samples of bodily fluid may be collected by the devices
disclosed and described herein. Methods of collecting bodily fluid
using these devices are disclosed and described herein. Samples of
bodily fluid, e.g., samples that have been collected by the devices
and/or methods disclosed and described herein, may be transported
from a sample collection site to one or more other sites.
[0012] In at least one embodiment described herein, methods are
provided for the physical transport of small volumes of bodily
fluid in liquid form from one location to another location. By way
of nonlimiting example, the samples are collected in liquid form at
a collection site, transported in liquid form, and arrive at an
analysis site in liquid form. In many embodiments, the liquid form
during transport is not held in a porous matrix, wicking material,
webbing, or similar material that would prevent sample from being
extracted in liquid form at the destination site. In one
embodiment, small volume of sample in each sample vessel is in the
range of about 1 ml to about 500 microliters. Optionally, small
volumes are in the range of about 500 microliters to about 250
microliters. Optionally, small volumes are in the range of about
250 microliters to about 100 microliters. Optionally, small volumes
are in the range of about 100 microliters to about 50 microliters.
Optionally, small volumes are in the range of about 80 microliters
to about 40 microliters. Optionally, small volumes are in the range
of about 40 microliters to about 1 microliter. Optionally, small
volumes are in the range of about 1 microliter to about 0.3
microliters. Optionally, small volumes are in the range of about
0.3 microliters or less.
[0013] As disclosed and described herein, a transport container may
include a component configured to receive and retain a sample
vessel. In embodiments, a component configured to receive and
retain a sample vessel may be configured to receive and retain a
plurality of sample vessels. In embodiments, such a component may
comprise a flat sheet, such as, e.g., a tray. In embodiments, such
a component (e.g., a flat sheet) may comprise an opening (e.g., a
slot, aperture or receptacle) having an internal surface configured
to accept a sample vessel. In embodiments, a transport container
may include a component comprising a plurality of openings (e.g.,
slots, apertures or receptacles) each having an internal surface
configured to accept a sample vessel. In embodiments, such an
internal surface may be, at least in part, substantially
complementary to the outer surface, or a portion thereof, of a
sample vessel.
[0014] In another embodiment described herein, the transport
container may provide a high density of sample vessels per unit
area held in a fixed manner during transport, but removable at the
destination location. In one non-limiting example, the sample
vessels are positioned in an array where there are at least six
sample vessels per square inch, when viewing the array from top
down. Optionally, there are at least eight sample vessels per
square inch, when viewing the array from top down. Optionally,
there are at least ten sample vessels per square inch, when viewing
the array from top down. Any traditional techniques that ship
multiple samples typically use large bags where the sample vessels
therein are in a loose, unconstrained manner. In some embodiments,
the transport container can hold certain sample vessels such as
those from the same subject, closer together relative to horizontal
or other spacing to adjacent sample vessels so that they can be
visually identified as being from a common subject. Optionally, the
transport container has openings to receive carriers that hold one
or more sample vessels together, wherein those vessels have a
common denominator such as but not limited to being from the same
subject.
[0015] In embodiments, the sample vessels are adapted to aid in
maintaining the samples in liquid form. In embodiments, the sample
is treated prior to its arrival in a sample vessel in a manner
adapted to maintain the sample in liquid form. For example, a
sample vessel may include an anti-coagulating agent, or a sample
may be treated with an anti-coagulating agent prior to, or during,
transport to or into a sample vessel. In embodiments, an
anti-coagulating agent may be selected from the group consisting of
heparin (e.g. lithium heparin or sodium heparin),
ethylenediaminetetraacetic acid, 4-hydroxycoumarins, vitamin K
antagonist (VKA) anticoagulant, an anti-coagulant, or other
additive. In addition to the high density per unit area, some
embodiments of the transport container also contain a high
diversity of samples, including those that contain samples from a
plurality of different subjects. By way of non-limiting example,
the transport container may have four samples from one subject, two
samples from another subject, and so-on until the majority or all
of the available openings in the transport container are
filled.
[0016] It should be understood that each of the samples can be
destined for individually selected analysis and at least in one
embodiment, are not grouped in the transport container based on
tests to be performed. By way of non-limiting example, not all of
the samples in the transport container are collected for the same
test. A traditional test system may only group together for
transport those samples destined for the exact same test. In at
least one of the embodiments herein, there is a diversity of
samples, each designated to receive its own set of tests. In such
an embodiment, grouping in the transport container is not
restricted to only those samples targeted for the same test. This
can further simplify sample processing because sample transport
does not need to be further segregated based on tests to be
performed. Some embodiments of the transport container contain
samples from at least three or more different patients. Some
embodiments of the transport container contain samples from at
least five or more different patients. Some embodiments of the
transport container contain samples from at least ten or more
different patients. Some embodiments of the transport container
contain samples from at least twenty or more different
patients.
[0017] By way of non-limiting example, one embodiment described
herein may optionally use tray(s) that have slots for holding the
sample vessels and/or sample vessel holders. In one embodiment, the
tray may also double as a holding device during storage in a
cooling chamber while awaiting more samples or transport. In one
embodiment, the tray can itself also be cleaned and sterilized,
because in some embodiments, the tray is removable from the
transport container. In some embodiments, the tray in the transport
container may be held in manner parallel to a cover of the
transport container. Optionally, the tray may be held inside the
transport container at an angle to the cover of the transport
container. Optionally, the tray is irremovably fixed to the
transport container. Optionally, the tray is integrally formed with
the transport container itself. Optionally, multiple trays of same
or different size or configuration may be placed inside the
transport container.
[0018] In yet another embodiment described herein, methods are
provided for shipping small volume sample vessels using a transport
container with integrated thermal control unit and/or material that
provides active and/or passive cooling. In one embodiment, the
thermal control material may be but is not limited to embedded
phase change material (PCM) material that maintains the temperature
at a prior, or desired temperature. By way of non-limiting example,
the phase change material can oppose changes in temperature around
the critical temperature where the material would undergo a phase
change. If the PCM is embedded, the vessel and the passive cooling
element may be one and the same. Optionally, the transport
container may use an active cooling system. Optionally, the
transport container may use an active cooling system to keep and/or
extend cooling time associated with a passive cooling component. In
embodiments, a transport container may include material having a
high heat capacity (i.e., high as compared to material such as a
plastic or polymeric material), and may include a mass of such a
high heat capacity material effective to maintain at least a
portion of the transport container at or near to a desired
temperature for an extended period of time.
[0019] Optionally, the method comprises a single step for
transferring multiple sample vessels from different subjects from a
controlled temperature storage area into a transport container. By
way of non-limiting example, this single step can transfer
twenty-four or more sample vessels at one time from a storage
location into a fixed position in the transport container.
Optionally, this single step can transfer thirty-six or more sample
vessels at one time from a storage location into a fixed position
in the transport container. Optionally, this single step can
transfer forty-eight or more sample vessels at one time from a
storage location into a fixed position in the transport container.
In such embodiments, the tray may be initially in a controlled
thermal environment such as but not limited to a refrigerator
wherein samples from various subjects are collected over time until
a desired number is reached. In one such embodiment, the tray
holding the sample vessel(s) in the transport container is the same
tray holding the sample vessels in the storage area. Optionally,
the tray may be the same as the storage holder that is used to hold
samples prior to loading into the transport container. Because the
same tray which holds the sample vessels will be used in the
transport container, there is reduced risk that samples will be
lost during this transfer, left out in a non-regulated thermal
environment, or the like. Because substantially all sample vessels
in the tray are accumulated in the controlled thermal storage area
and then transferred in a single step, the samples all experience
substantially the same thermal exposure while being transferred
from the control thermal storage area into the transport container.
Because sample vessels experience substantially the same exposure,
there is less variability sample-to-sample due to different
exposure times.
[0020] Optionally, the method comprises using an individually
addressable sample vessel configuration. Optionally, groups of
sample vessels such as those in a common carrier may be addressed
in the pre-defined groups. Optionally, even sample vessels in a
common carrier may be individually addressed. Although not a
requirement for all embodiments herein, this can be of particular
use when loading and/or unloading samples, sample vessels, and/or
sample holders from the tray.
[0021] Some embodiments may use yet another container (an
"outerbox") outside the transport container to provide further
physical protection and/or thermal control capability. One or more
of the transport container can be placed inside the outerbox and
the combination may be shipped from one location to a destination
location. By way of non-limiting example, this can be in the form
of a corrugated plastic outerbox, where the outerbox is configured
to at least partially encase or enclose a transport container. In
embodiments, an outerbox provides thermal insulation for a
transport container enclosed therein. Some embodiments may use
closed-cell extruded polystyrene foam outerbox. Some embodiments of
the outerbox may be formed from thermoformed panels. In some
embodiments, an outerbox may have grips, handles, pads, wheels,
latches, stays, and/or other features useful in holding,
manipulating, securing, protecting, transporting, or otherwise
controlling the position, orientation, and/or access to the
contents of the outerbox. Some embodiments of the outerbox may have
its own active and/or passive thermal control unit. In embodiments,
an outerbox provides cooling and thermal insulation for one or more
transport containers enclosed therein. One or more embodiments of
the outerbox may be configured to house one or more transport
containers. Optionally, this container can also provide additional
thermal control to the transport container by providing a thermally
regulated environment between a desired temperature range to the
transport container(s) therein. Optionally, this temperature range
is between about 1 to 10.degree. C., optionally 2 to 8.degree. C.,
or between 2 to 6.degree. C.
[0022] In yet another embodiment described herein, a method is
provided for thermally characterizing the transport container after
a number of cooling cycles. By way of non-limiting example, after
certain number of cycles, the transport container may be thermally
characterized to ensure that the container is continuing to perform
within a desired range.
[0023] Some embodiments of the container and/or tray may include a
thermal change indicator. In one non-limiting example, the
indicator is integrated on a visible surface of the transport
container, tray, and/or on the outerbox. In one non-limiting
example, thermochromic ink may be used as an indicator of thermal
change, particularly if the thermal change resulted in temperatures
outside a desired range. In one embodiment, this indicator may be
configured to have the entire box and/or tray change color. The
change can be reversible or irreversible. Optionally, the indicator
is positioned to be on only select portions of the transport
container and/or tray, not the entire container or tray.
[0024] In one embodiment described herein, a method is provided
comprising collecting a bodily fluid sample on a surface of a
subject, wherein collected sample is stored in one or more sample
vessels; providing a transport container to house at least two or
more sample vessels in a first orientation; and arranging to have
the sample vessels shipped in the transport container from a first
location to a second location, wherein each of the sample vessels
arrives at the second location holding a majority of its bodily
fluid sample in a non-wicked, non-matrixed form that is removable
from the sample vessels in liquid form and wherein the amount of
sample in each of the sample vessels does not exceed about 2 ml. In
embodiments, the amount of sample in each of the sample vessels
does not exceed about 1 ml, or does not exceed about 500 .mu.L, or
does not exceed about 250 .mu.L, or does not exceed about 100
.mu.L, or does not exceed about 50 .mu.L, or less.
[0025] In another embodiment described herein, a method is provided
for shipping a plurality of sample vessels, the method comprising:
providing a container configured to house at least five or more
sample vessels each containing capillary blood; and arranging to
have the sample vessels shipped in the transport container from a
first location to a second location, wherein each of the sample
vessels arrives holding a majority of its capillary blood in a
liquid, non-wicked form that is removable from the sample vessels
for further processing, and wherein the amount of capillary blood
in each of the sample vessels does not exceed about 2 ml. In
embodiments, the amount of capillary blood in each of the sample
vessels does not exceed about 1 ml, or does not exceed about 500
.mu.L, or does not exceed about 250 .mu.l, or does not exceed about
100 .mu.L, or does not exceed about 50 .mu.L, or less.
[0026] In another embodiment described herein, a method is provided
for shipping a plurality of sample vessels for containing
biological sample, the method comprising: providing a container
configured to house at least five or more of the sample vessels,
wherein the amount of sample in each of the sample vessels does not
exceed about 2 ml; and shipping the container and sample vessels
from a first location to a second location, wherein each of the
sample vessels arrives at the second location holding a majority of
its biological in a liquid, non-wicked form that is removable from
the sample vessels for further processing. In embodiments, the
amount of sample in each of the sample vessels does not exceed
about 1 ml, or does not exceed about 500 .mu.L, or does not exceed
about 250 .mu.L, or does not exceed about 100 .mu.L, or does not
exceed about 50 .mu.L, or less.
[0027] In another embodiment described herein, a method is provided
for shipping a plurality of sample vessels containing capillary
blood, the method comprising: providing a container having a
thermally-regulated interior region that is configured to house at
least five or more sample vessels in a controlled configuration
such that at least one cooling surface of the container is directed
towards the sample vessels and transmits a controlled release of
thermal cooling in accordance with a temperature profile that
maintains the interior region between about 1 to 10.degree. C.
during transport and without freezing the blood samples; and
shipping the container from a first location to a second location,
wherein each of the sample vessels arrives holding a majority of
its capillary blood in a liquid, non-wicked form that is removable
from the sample vessels for further processing.
[0028] In another embodiment described herein, a method is provided
for shipping a plurality of blood sample vessels, the method
comprising shipping a container having a thermally-controlled
interior that is configured to house 10 or more sample vessels in
an array configuration, wherein each of the vessels holds a
majority of its blood sample in a free-flowing, non-wicked form and
wherein there is about 1 ml or less of blood in each of the vessels
and each of the vessels has an interior with at least a partial
vacuum atmosphere; wherein sample vessels are held in the array
configuration to position said sample vessels at controlled
distance and orientation from a cooling surface, wherein there is
at least one preferential thermal pathway from the surface to the
sample vessel.
[0029] In another embodiment described herein, a method is provided
for shipping a plurality of sub-1 ml sample vessels, the method
comprising mixing sample with anti-coagulant prior to transferring
sample into each of the sample vessels; associating each of the
sample vessels with a subject and a panel of requested sample
tests; and shipping a thermally-controlled container that houses
the plurality of sub-1 ml sample vessels in an array configuration,
wherein each of the vessels holds a majority of its sample in a
free-flowing, non-wicked form, wherein vessels are arranged such
that there are at least two vessels in each container is associated
with each subject, wherein at least a first sample includes a first
anticoagulant and a second sample includes a second anticoagulant
in the matrix.
[0030] In another embodiment described herein, a method is provided
comprising a) placing said plurality of sample vessels in a
temperature controlled transport container comprising a controlled
uniform thermal profile, high heat of fusion material configured to
be in thermal communication with the sample vessels, wherein the
material does not cause freezing of sample fluid in the sample
vessels; b) placing said thermal profile transport container in a
product cavity defined by at least top and bottom walls of a
transport container; c) placing an active cooling device in thermal
communication with said cavity whereby said cooling device is
adapted to cool said cavity upon activation, said sorption cooling
device comprising an absorber positioned so as to dissipate heat
generated in said absorber outside of said product cavity; d)
activating said cooling device to initiate cooling of said cavity;
e) transporting said transport container from a first location to a
second location; and f) removing said product from said cavity.
[0031] In another embodiment described herein, a method of shipping
a plurality of sub-1 ml sample vessels is provided comprising:
shipping a thermally-controlled container that houses the plurality
of sub-1 ml sample vessels in an array configuration, wherein each
of the vessels holds a majority of its sample in a free-flowing,
non-wicked form and wherein vessels are arranged such that there
are at least two vessels in each container is associated with each
subject, wherein at least a first sample includes a first
anticoagulant and a second sample includes a second anticoagulant
in the matrix.
[0032] It should be understood that any of the embodiments herein
can be adapted to have one or more of the following features. In
one non-limiting example, the bodily fluid sample is blood.
Optionally, the bodily fluid sample is capillary blood. Optionally,
collecting the bodily fluid sample comprises making at least one
puncture on the subject to release the bodily fluid, wherein the
puncture is not a venipuncture. Optionally, collecting comprises
using at least one microneedle to make at least one puncture on the
subject. Optionally, collecting comprises using at least one lancet
to make at least one puncture on the subject.
[0033] Optionally, the puncture may be formed by finger prick.
Optionally, the puncture is formed by pricking skin on a forearm of
the subject. Optionally, the puncture is formed by pricking skin on
a limb of the subject. Optionally, the puncture is formed by
pricking at least one ear of the subject. Optionally, the surface
is the skin of the subject. Optionally, other non-finger alternate
sites can be targeted to obtain at least one biological sample from
the subject. Optionally, a solid non-coring penetrating member may
be used to release the biological sample from the subject.
Optionally, other embodiments may have a coring device that may be
but is not limited to a coring needle or other coring penetrating
member to both cause a release of liquid biological sample and to
obtain a non-liquid sample in the coring penetrating member, such
as but not limited to a tissue sample. Some embodiments may use at
least one coring penetrating member and at least one non-coring
penetrating member. Some embodiments may use a blade for creating
the wound. Some may use a puncture-type motion while others may use
a cutting type motion. Any of these penetrating member(s) may be
configured for use for one or more of the target sites thereon.
[0034] Optionally, the transport container has an interior that is
initially at sub-atmospheric pressure. Optionally, the
sub-atmospheric pressure is at least a partial vacuum. Optionally,
the interior of the transport container is at a sub-atmospheric
pressure that is at least at a pressure below ambient pressure.
Optionally, the sub-atmospheric pressure is selected to provide
sufficient force to draw a desired volume of sample into the sample
vessel. Optionally, the transport container contains at least five
or more sample vessels. Optionally, the transport container ships
bodily fluid samples from a plurality of different subjects.
Optionally, information associated with each of the sample vessels
determine what tests will be run on the bodily fluid sample
therein. Optionally, the transport container is placed inside
another container during shipping. Optionally, the method further
comprises pre-processing sample in the sample vessels prior to
shipping to the second location. Optionally, at least a portion of
the sample may be collected and dried, such as but not limited to
collection on a paper sample collector. There may be multiple
"spots" on the collector for the sample to be collected and then
shipped on such paper sample collection member. The dried sample
may be shipped together with the container having the liquid
sample. Both may be coded with the same identifier or at least one
that associates both collectors with the same subject.
[0035] Optionally, the transport container has a sample vessel
array density of at least about 4 vessels per square inch.
Optionally, a cooling surface in the transport container provides a
temperature profile within a desired range for sample vessels in
the vessel. Optionally, the sample vessels are individually
addressable. Optionally, the method further comprises using a
cooled tray to hold the samples vessels in a cooling chamber prior
to loading the vessels into the container and the same tray is used
to hold the sample vessels in the vessel, wherein the samples are
placed into container with the cooled tray. Optionally, sample
vessels are arranged such that there are at least two vessels in
each container with bodily sample fluid from the same subject,
wherein at least a first sample includes a first anticoagulant and
a second sample includes a second anticoagulant in the matrix.
Optionally, the fluid sample comprises capillary blood for use in
testing by FDA-cleared or FDA-certified assay devices and
procedures, or testing by a CLIA-certified laboratory. Optionally,
the fluid sample comprises blood for use in testing by FDA-cleared
or FDA-certified assay devices and procedures, or testing by a
CLIA-certified laboratory. Optionally, a housing providing a
controlled thermal profile and high heat of fusion material
providing at least one cooling surface facing the vessels.
Optionally, a high heat of fusion material is embedded in material
used to form the vessel. Optionally, a controlled thermal profile,
high heat of fusion material comprises about 30% to 50%.
Optionally, a controlled thermal profile, high heat of fusion
material comprises about 10% to 30%. Optionally, the method further
comprises a housing of metallic material having a resting
temperature less than ambient temperature.
[0036] Optionally, the method further comprises scanning an
information storage unit on each sample at the receiving site and
automatically placing the vessel into a cartridge. Optionally, the
method further comprises scanning an information storage unit on
each sample at the receiving site and automatically placing the
vessel into a cartridge. Optionally, the method further comprises
using the same tray to hold sample vessels in the array
configuration when in a refrigeration device prior to transport and
in the transport container during transport. Optionally, the method
further comprises using a tray for holding the sample vessels that
comprises a highly thermally conductive material. Optionally, the
tray comprises a plurality of slots having a shape to hold sample
vessels holders in a preferential orientation. Optionally, the tray
is configured to directly engage sample vessel holders. Optionally,
a tray locking mechanism is used to hold the tray within the
vessel, wherein the tray locking mechanism releases the tray only
upon application of magnetic force. Optionally, the method
comprises maintaining a temperature range in the 2.degree. C. to
8.degree. C. during transport. Optionally, the method further
comprises a temperature control material that maintains above
freezing but about 10.degree. C. or less during transport.
Optionally, the method comprises using a temperature threshold
detector to indicate if the sample vessel reaches a temperature
outside a threshold level. Optionally, the method further comprises
scanning a vessel in the tray prior to shipping to determine if a
processing step on the sample had not been performed; using a
processor to perform or re-perform a step. Optionally, the method
further comprises a single-step loading of the sample vessel(s)
into the tray and then a single-step loading of the tray into the
transport container.
[0037] Optionally, the transport container has a first surface
configured to define a thermally conductive pathway to the
controlled thermal profile, high heat of fusion material in the
transport container. Optionally, the first surface is configured to
be in direct contact with another surface cooled by a sorption
cooling device. Optionally, the method comprises simultaneous bar
code scanning of sample vessels in the tray. Optionally, the method
comprises simultaneous bar code scanning undersides of sample
vessels in the tray. Optionally, the method comprises bar code
scanning rows of sample vessels. Optionally, the method comprises
bar code scanning undersides of rows of sample vessels. Optionally,
the method comprises shipping a plurality of the sample vessels in
an inverted orientation. Optionally, the method comprises shipping
a plurality of the sample vessels wherein blood cells and plasma
are separated by a barrier material in the sample vessels.
Optionally, the method comprises opening the transport container by
unlocking it and opening it, wherein at least one hinge holds two
pieces together. Optionally, the tray has at least one magnetic
contact point for removing the tray from the vessel. Optionally, a
computer controlled end effector is used to load and/or unload
sample vessels from the transport container, wherein before,
during, or after unloading, a reader obtains information from at
least one information storage unit attached to one or more sample
vessels. It should be understood that although the transport
container is often used for transport, it can also be used as a
storage container for the tray and/or sample vessels when the
transport container is not used for transport. Accordingly, the
uses for the container are not limited to transport and other
suitable uses for any of the embodiments are not excluded.
[0038] In yet another embodiment herein, a thermal-controlled
transport container is provided for use in shipping a plurality of
sample vessels, the transport container comprising: a container
having at least a top, bottom, and side walls together defining a
cavity, wherein at least one of said top, bottom and side walls
comprises a phase change material; a frame sized to fit within the
cavity and defining openings configured for holding a plurality of
sample vessels and having sidewalls configured to be in contact
with sidewalls of the sample vessels, wherein vessels are arranged
such that each patient has at least a first sample with a first
anticoagulant and a second sample with a second anticoagulant in
the matrix.
[0039] In another embodiment described herein, a thermal-controlled
transport container is provided for use in shipping a plurality of
sample vessels, the transport container comprising: a) a bottom
container portion comprising a bottom wall and at least a first
sidewall defining a cavity adapted to contain a product therein; b)
a top container portion comprising a top surface and a bottom
surface and adapted to combine with said bottom container portion
to define a product cavity, said top container portion forming a
top wall for said vessel; wherein at least one of said top, bottom
and side walls comprises a phase change material.
[0040] In another embodiment described herein, a thermal-controlled
transport container is provided for use in shipping a plurality of
sample vessels, the transport container comprising: a) a bottom
container portion comprising a bottom wall and at least a first
sidewall defining a cavity adapted to contain a product therein; b)
a top container portion comprising a top surface and a bottom
surface and adapted to combine with said bottom container portion
to define a product cavity, said top container portion forming a
top wall for said vessel; c) a holder for defining a plurality of
sample vessel holding spaces to position the sample vessels in a
pre-determined orientation; wherein at least one of said top,
bottom and side walls comprises a phase change material.
[0041] In another embodiment described herein, a transport
container is provided for shipping sample vessels, the container
comprising: a generally rectangular floor; generally parallel sides
projecting from longitudinal edges of the floor; generally parallel
ends projecting from end edges of the floor and bridging the sides;
a cover fittable over the sides and ends and forming therewith and
with the floor a generally closed space; a sample vessel holder
removably coupled to the floor in an interior of the container and
configured to define vessel-holding spaces. Optionally, the vessel
holding spaces are configured to hold air-evacuated blood
collection tubes having an interior volume of about 2 ml or less.
In at least one embodiment, the vessel holding spaces are
configured to hold vessels such as but not limited to air-evacuated
collection tubes having an interior volume of about 1 ml, or less
than about 500 .mu.L, or less than about 250 .mu.L, or less than
about 100 .mu.L, or less than about 50 .mu.L, or less.
[0042] In another embodiment described herein, a thermal-controlled
transport container is provided for use in shipping a plurality of
sample vessels, the transport container comprising: means for
holding a plurality of sample vessels in at least one fixed
orientation; means for thermally controlling temperature of the
sample vessels to be within a desired range of about 0.degree. C.
to 10.degree. C.; wherein the means from holding the plurality of
sample vessels is removable from the transport container.
Optionally, the vessel holding spaces are configured to hold
air-evacuated blood collection tubes having an interior volume of
about 2 ml or less. In embodiments, the vessel holding spaces are
configured to hold air-evacuated collection tubes having an
interior volume of about 1 ml, or less than about 500 .mu.L, or
less than about 250 .mu.L, or less than about 100 .mu.L, or less
than about 50 .mu.L, or less.
[0043] It should be understood that some embodiments may comprise a
kit that includes a transport container as recited in any of the
above. Optionally, the kit includes a transport container and
instructions for their use.
[0044] In one embodiment described herein, a method is described
for providing a whole blood sample and/or partition thereof from a
sender to a recipient. The method comprises transporting a package
comprising a sample vessel comprising one or more channels that
contains (a) a whole blood sample and/or partition thereof in fluid
state having a volume less than or equal to about 200 microliters
(ul) and (b) one or more reagents used for preserving one or more
analytes in the whole blood sample and/or partition thereof for
analysis until at least when whole blood sample and/or partition
thereof reaches the recipient, and wherein the depositing results
in delivery of the sample vessel to the recipient. By way of
non-limiting example, transporting the sample vessel may occur by
using a parcel delivery service, a courier, or other shipping
service.
[0045] In one embodiment described herein, a method is described
for preparing a whole blood sample for delivery to a sample
processing station. The method comprises depositing a sample vessel
having a whole blood sample in fluid state and a volume less than
or equal to about 200 ul with a delivery service for delivering the
sample vessel to the sample processing location for processing the
whole blood sample. The sample vessel may be prepared by (a)
drawing the whole blood sample from a subject with the aid of a
capillary channel and (b) placing the whole blood sample into the
sample vessel, wherein the whole blood sample is preserved in fluid
state with one or more reagents contained in the capillary channel
and/or the sample vessel.
[0046] It should be understood that any of the embodiments herein
may be adapted to have one or more of the following features. By
way of non-limiting example, the sample in some embodiments may be
a semi-solid or gel state. This may occur after the sample is in
the sample vessel. Optionally, the delivery service is a mail
delivery service. Optionally, the blood sample is collected from
the subject at a point of care location. Optionally, the point of
care location is a home of the subject. Optionally, the point of a
care location is the location of a healthcare provider.
[0047] In another embodiment described herein, a method for
processing a whole blood sample comprises receiving at a processing
station from a parcel delivery service, a sample vessel having a
whole blood sample less than or equal to about 200 ul, wherein the
sample vessel is received at the processing station with the whole
blood sample in a fluid state; and performing, at the processing
station, at least one pre-analytical and/or analytical assay on the
whole blood sample in a fluid state.
[0048] It should be understood that any of the embodiments herein
may be adapted to have one or more of the following features. By
way of non-limiting example, the assay has one or more steps.
Optionally, the sample vessel is included in a housing having one
or more environmental control zones. Optionally, the housing is
adapted to control a humidity of each of the environmental control
zones. Optionally, the housing is adapted to control a pressure of
each of the environmental control zones.
[0049] In yet another embodiment described herein, a
computer-implemented method is provided for queuing a blood sample
for processing at a processing location. The method comprises (a)
identifying, with the aid of a geolocation system having a computer
processor, the geolocation of a transport container having the
blood or other bodily fluid sample; (b) estimating, with the aid of
a computer processor, delivery time of the transport container to
the processing location; and (c) based on the estimated time of
delivery, providing a notification for preparative work for
processing the sample at the processing location.
[0050] In yet another embodiment described herein, a method is
described for preparing a whole blood sample for delivery to a
sample processing station. The method comprises depositing a sample
vessel having a whole blood sample in fluid state with a delivery
service for delivering the sample vessel to the sample processing
location for processing the whole blood sample, wherein the sample
vessel is prepared by (a) drawing the whole blood sample from a
subject using a device and (b) placing the whole blood sample into
the sample vessel.
[0051] Optionally, depositing may encompass pick-up and/or drop-off
of a sample vessel. Optionally, processing may include
pre-analytic, analytic and post-analytic processing of a sample.
Optionally, delivery service may include a subject's delivery
service or a third party delivery service. Optionally, the whole
blood sample is preserved in fluid state with one or more reagents
contained in the capillary channel or the sample vessel.
[0052] In yet another embodiment described herein, a method is
provided for processing a whole blood sample at a processing
station. The method comprises receiving, at the processing station
from a delivery service, a sample vessel having a whole blood
sample, wherein the sample vessel is prepared by (a) drawing the
whole blood sample from a subject using a collection device and (b)
placing the whole blood sample into the sample vessel. The method
also includes performing, at the processing station, at least one
pre-analytical or analytic assay on the whole blood sample.
[0053] It should be understood that any of the embodiments herein
may be adapted to have one or more of the following features. By
way of non-limiting example, with the aid of a computer processor,
providing a time for completion of the processing from the
estimated time of delivery. Optionally, the method includes queuing
the sample vessel for processing upon estimating the time of
delivery of the sample vessel at the processing location.
Optionally, the geolocation of the sample vessel is identified with
the aid of a communications network.
[0054] In one embodiment described herein, a computer-implemented
method is described for providing an estimated time of completion
for the processing of a blood sample. The method comprises
receiving information about a transport container transported
through a delivery service to a processing station that is for
sample processing, the transport container having a blood sample
removed from a subject. The method also includes calculating, with
the aid of a computer processor, a position of the blood sample in
a processing queue at the processing station, wherein the
predicting is based on (i) information about the position of blood
or other bodily fluid samples from other subjects in the processing
queue and (ii) information about the geographic location of other
sample vessels having blood samples from other subjects in relation
to the sample vessel having the blood sample removed from the
subject. The method includes predicting a time for processing the
blood sample at the processing station upon delivery of the sample
vessel by the delivery service to the processing station; and based
on the predicting and an estimated time of delivery of the sample
vessel to the processing station, providing the subject or a
healthcare provider associated with the subject an estimated time
for processing the blood sample from the subject, the estimated
time measured from the point the sample vessel is deposited with
the delivery service. Optionally, the sample is transported to a
plurality of processing stations. It should be understood that
processing as used herein is to be broadly interpreted and may
include pre-analytical, analytical, and/or post-analytical
step(s).
[0055] In yet another embodiment described herein, a
computer-implemented method is described for providing an estimated
time of completion for the processing of a blood sample from a
subject. The method comprises receiving information about a
transport container transported through a delivery service to a
processing station that is for sample processing, the transport
container having at least one blood or bodily fluid sample removed
from the subject. The method also includes calculating, with the
aid of a computer processor, a position of the blood sample in a
processing queue at the processing station, wherein the predicting
is based on (i) information about the position of blood samples
from other subjects in the processing queue and (ii) information
about the geographic location of other sample vessels having blood
samples from other subjects in relation to the transport container
having the blood sample removed from the subject. The method
includes predicting a time for processing the blood sample at the
processing station upon delivery of the transport container by the
delivery service to the processing station; and based on the
predicting and an estimated time of delivery of the transport
container to the processing station, allocating one or more
resources at the processing station for processing the blood sample
upon delivery to the processing station.
[0056] It should be understood that any of the embodiments herein
may be adapted to have one or more of the following features. By
way of non-limiting example, the transport container has an
information storage unit that allows identification of the
transport container by the delivery service and/or the processing
location. Optionally, the information storage unit is a
radiofrequency identification (RFID) tag. Optionally, the
information storage unit is a barcode. Optionally, the information
storage unit is a microchip. Optionally, the transport container
comprises one or more sensors for collecting one or more of the
temperature of the bodily fluid sample (e.g., a blood sample), the
pressure of the sample vessel, the pH of the sample, the turbidity
of the sample, the viscosity of the sample, or other characteristic
of the sample. Optionally, the processing location processes
collected bodily fluid samples on an on-demand basis. Optionally,
the transport container includes a geo-location device for
providing the location of the sample vessel. Optionally, the
anti-coagulating agent is selected from the group consisting of
heparin, ethylenediaminetetraacetic acid, an anti-coagulant, or
other additive. Optionally, the transport container, wherein the
container holding spaces are configured to hold air-evacuated blood
collection tubes, are configured to hold air-evacuated sample
collection tubes having a partial vacuum of at most about 30%
vacuum, or at most about 40% vacuum, or at most about 50% vacuum,
or at most about 60% vacuum, or at most about 70% vacuum, or at
most about 80% vacuum, or at most about 90% vacuum.
[0057] In embodiments described herein involving a first vessel and
a second vessel, in certain embodiments, the interior volume of the
first vessel and second vessel is each 1000, 750, 500, 400, 300,
250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9,
8, 7, 6, 5, 4, 3, 2 microliters, or less. In embodiments described
herein involving a first vessel and a second vessel, in certain
embodiments, the interior volume of neither the first vessel nor
the second vessel exceeds 1000, 750, 500, 400, 300, 250, 200, 150,
100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4,
3, or 2 microliters. In embodiments described herein involving one
or more vessels, in certain embodiments, the interior volume of
each of the one or more vessels is 1000, 750, 500, 400, 300, 250,
200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7,
6, 5, 4, 3, 2 microliters, or less. In embodiments described herein
involving one or more vessels, in certain embodiments, the interior
volume of none of the one or more vessels exceeds 1000, 750, 500,
400, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20,
15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters.
[0058] In embodiments described herein involving a first vessel and
a second vessel, each containing a portion of a small volume bodily
fluid sample, in certain embodiments, neither the first vessel nor
the second vessel contains a portion of the small volume bodily
fluid sample having a volume of greater than 500, 400, 300, 250,
200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7,
6, 5, 4, 3, or 2 microliters.
[0059] In embodiments described herein involving a vessel
containing a small volume bodily fluid sample, in certain
embodiments, the volume of the small volume bodily fluid sample in
the vessel is no greater than 500, 400, 300, 250, 200, 150, 100,
90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or
2 microliters.
[0060] In embodiments described herein involving one or more
vessels containing bodily fluid sample, in certain embodiments, at
least one of the one or more vessels contains bodily fluid sample
which fills at least 99, 98, 97, 96, 95, 90, 85, 80, 75, 70, 60,
50, 40, 30, 20, 10, or 5% of the interior volume of the vessel. In
embodiments described herein involving one or more vessels
containing bodily fluid sample, in certain embodiments, all of the
one or more vessels contains bodily fluid sample which fills at
least 99, 98, 97, 96, 95, 90, 85, 80, 75, 70, 60, 50, 40, 30, 20,
10, or 5% of the interior volume of the vessel.
[0061] In embodiments described herein involving a sample
collection site and a sample receiving site, in embodiments, the
sample collection site and sample receiving site may be in the same
room, building, campus, or collection of buildings. In embodiments
described herein involving a sample collection site and a sample
receiving site, in embodiments, the sample collection site and
sample receiving site may be in different rooms, buildings,
campuses, or collection of buildings. In embodiments, a sample
collection site and a sample receiving site may be separated by at
least 1 meter, 5 meters, 10 meters, 50 meters, 100 meters, 500
meters, 1 kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20
kilometers, 30 kilometers, 50 kilometers, 100 kilometers, or 500
kilometers. In embodiments, a sample collection site and sample
receiving site may be separated by no more than 5 meters, 10
meters, 50 meters, 100 meters, 500 meters, 1 kilometer, 5
kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30
kilometers, 50 kilometers, 100 kilometers, 500 kilometers, or 1000
kilometers. In embodiments, a sample collection site and a sample
receiving site may be separated by at least 1 meter, 5 meters, 10
meters, 50 meters, 100 meters, 500 meters, 1 kilometer, 5
kilometers, 10 kilometers, 15 kilometers, 20 kilometers, 30
kilometers, 50 kilometers, 100 kilometers, or 500 kilometers and no
more than 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1
kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20
kilometers, 30 kilometers, 50 kilometers, 100 kilometers, 500
kilometers, or 1000 kilometers. In embodiments, a first location
described herein may be a sample collection site and a second
location described herein may be a sample receiving site.
[0062] In embodiments described herein involving a vessel
containing at least a portion of a small volume bodily fluid sample
being transported from a sample collection site to a sample
receiving site, in embodiments, the bodily fluid sample may be
maintained in liquid form during the transport of the vessel. In
embodiments described herein involving two or more vessels, each
containing at least a portion of a small volume bodily fluid
sample, being transported from a sample collection site to a sample
receiving site, in embodiments, the bodily fluid sample in each of
the vessels may be maintained in liquid form during the transport
of the vessels.
[0063] In embodiments described herein involving one or more
vessels being transported from a sample collection site to a sample
receiving site, in embodiments, the one or more vessels may be
transported in a transport container. In embodiments described
herein involving one or more vessels being transported in a
transport container, in embodiments, the one or more vessels may be
positioned in an array in the transport container, and the array
may contain at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30,
35, 40, 50, or 100 vessels per square inch, when viewed from the
top down.
[0064] In embodiments described herein involving transporting one
or more vessels in a transport container, in embodiments, the
transport container may contain bodily fluid samples from at least
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, or 100
different subjects.
[0065] In embodiments described herein involving a vessel
containing at least a portion of a bodily fluid sample, in
embodiments, the vessel may contain an anticoagulant. In
embodiments involving two or more vessels which each contain a
portion of a bodily fluid sample from a subject, in embodiments, at
least one or all of the vessels may contain an anticoagulant. In
embodiments, when two or more vessels which each contain a portion
of a bodily fluid sample from a subject also each contain an
anticoagulant, the vessels may contain the same anticoagulants or
different anticoagulants. An anticoagulant in a vessel may be, for
example, heparin or EDTA.
[0066] In methods described herein involving the transport of a
bodily fluid sample in one or more vessels from a sample collection
site to a sample receiving site, in embodiments, the bodily fluid
sample may arrive at the sample receiving site no more than 48
hours, 36 hours, 24 hours, 16 hours, 12 hours, 8 hours, 7 hours, 6
hours, 5 hours, 4 hours, 3 hours, 2 hours, 60 minutes, 45 minutes,
30 minutes, 20 minutes, 15 minutes, 10 minutes, or 5 minutes after
the bodily fluid sample was obtained from the subject.
[0067] In methods described herein involving transporting at least
a vessel from a sample collection site to a sample receiving site,
in embodiments, the method may further comprise centrifuging the
vessel before it is transported. In methods described herein
involving transporting a plurality of vessels from a sample
collection site to a sample receiving site, in embodiments, the
method may further comprise centrifuging the plurality of vessels
before they are transported.
[0068] In methods described herein involving transporting at least
a first vessel from a sample collection site to a sample receiving
site, in embodiments, at the sample receiving site and prior to the
removal of sample from the first vessel, the first vessel is
inserted into a sample processing device comprising an automated
fluid handling apparatus. In methods described herein involving
transporting at least a first vessel and a second vessel from a
sample collection site to a sample receiving site, in embodiments,
at the sample receiving site and prior to the removal of sample
from the first vessel, the first vessel and second vessel are
inserted into a sample processing device comprising an automated
fluid handling apparatus. In embodiments, when a vessel comprising
a sample is inserted into a sample processing device comprising an
automated fluid handling apparatus, sample may be removed from the
vessel by the automated fluid handling apparatus. In embodiments,
prior to the insertion of a vessel comprising a sample into a
sample processing device comprising an automated fluid handling
apparatus, the vessel is inserted into a cartridge, and the
cartridge is then inserted into the sample processing device. A
cartridge may accommodate any number of vessels containing sample,
such as at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, or
100 vessels. A cartridge may further comprise one or more reagents
for performing one or more laboratory tests with the sample. In
embodiments, a cartridge may comprise all of the reagents necessary
to perform all of the tests that are to be performed with the
sample(s) in the cartridge.
[0069] In embodiments, a portion of a portion of a bodily fluid
sample of a vessel may be of any amount. For example, in
embodiments, a portion of a portion of a bodily fluid sample of a
first vessel may be a portion of a first vessel original sample or
a portion of a first vessel dilution sample. In another example, in
embodiments, a portion of a portion of a bodily fluid sample of a
second vessel may be a portion of a second vessel original sample
or a portion of a second vessel dilution sample.
[0070] In embodiments provided herein involving transporting one or
more vessels, each containing at least a portion of a bodily fluid
sample from a sample collection site to a sample receiving site, in
embodiments, one or more steps of any number of laboratory tests
may be performed with a portion of the at least a portion of the
bodily fluid sample in the vessel. For example, in embodiments, one
or more steps of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40,
50, 60, 70, 80, 90, 100, 200, 300, 400, 500, or 1000 or more
different laboratory tests may be performed with a portion of the
at least a portion of bodily fluid sample. Each different
laboratory test may use a separate portion of the bodily fluid
sample, or in embodiments, more than one different laboratory test
may be performed with a particular portion of the bodily fluid
sample. The different laboratory tests may be of the same type,
different types, or a mixture of same and different types. The one
or more vessels may be, for example, a first vessel or a first
vessel and second vessel.
[0071] In embodiments, when a bodily fluid sample from a subject
transported according to systems or methods provide herein is used
for more than one laboratory test, each of the laboratory tests may
use the equivalent of no more than 50, 40, 30, 25, 20, 15, 10, 9,
8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.1, 0.05, or 0.01 of neat bodily
fluid sample (e.g. undiluted whole blood, saliva, or urine) per
test.
[0072] In embodiments provided herein involving obtaining at a
sample collection site a plurality of vessels collectively
containing a small volume bodily fluid sample from a subject, in
embodiments, the total volume of the small volume bodily fluid
sample obtained from the subject between all of the vessels of the
plurality of vessels may be no greater than 500, 400, 300, 250,
200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7,
6, 5, 4, 3, or 2 microliters.
[0073] In embodiments provided herein involving transporting a
vessel containing at least a portion of a bodily fluid sample from
a sample collection site to a sample receiving site, removing at
the sample receiving site from the vessel an original sample, and
then generating a dilution sample from the original sample, in
embodiments, the dilution may be generated step-wise or serially.
In embodiments, the dilution sample may have a total volume of no
more than 1000, 900, 800, 700, 600, 500, 400, 300, 250, 200, 150,
100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4,
3, or 2 microliters. In embodiments, the dilution sample may be
diluted at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 50, 100, 200,
300, 400, 500, 1000, 5,000, 10,000, 50,000, or 100,000-fold
relative to the original sample.
[0074] In embodiments provided herein involving transporting at
least a first vessel and a second vessel, each containing a portion
of the small volume bodily fluid sample obtained from the subject,
from a sample collection site to a sample receiving site, in
embodiments, at the sample receiving site, a first vessel original
sample may be removed from the first vessel and a second vessel
original sample may be removed from the second vessel. From the
first vessel original sample a first vessel dilution sample may be
generated. From the second vessel original sample a second vessel
dilution sample may be generated. The first vessel dilution sample
and second vessel dilution samples may have the same or different
volumes and degrees of dilution. In embodiments, multiple different
dilution samples may be generated from one or both of the first
vessel original sample or second vessel original sample. The
different dilution samples may be used for one or more different
laboratory tests, which may be of different types. In embodiments,
a first vessel dilution sample may be diluted at least 2, 3, 4, 5,
6, 7, 8, 9, 10, 15, 20, 50, 100, 200, 300, 400, 500, 1000, 5,000,
10,000, 50,000, or 100,000-fold relative to the first vessel
original sample and have a total volume of no more than 1000, 900,
800, 700, 600, 500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60,
50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2 microliters,
and a second vessel dilution sample may be diluted at least 2, 3,
4, 5, 6, 7, 8, 9, 10, 15, 20, 50, 100, 200, 300, 400, 500, 1000,
5,000, 10,000, 50,000, or 100,000-fold relative to the second
vessel original sample and have a total volume of no more than
1000, 900, 800, 700, 600, 500, 400, 300, 250, 200, 150, 100, 90,
80, 70, 60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2
microliters.
[0075] In embodiments provided herein involving obtaining at a
sample collection site a vessel, the vessel containing a small
volume bodily fluid sample obtained from a subject, in embodiments,
volume of the small volume bodily fluid sample in the vessel may be
no greater than 500, 400, 300, 250, 200, 150, 100, 90, 80, 70, 60,
50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, or 2
microliters.
[0076] In embodiments provided herein involving obtaining at a
sample collection site a vessel, the vessel containing a small
volume bodily fluid sample obtained from a subject and transporting
the vessel from the sample collection site to a sample receiving
site, in embodiments, the small volume bodily fluid sample may be
divided into any number of portions, such as, 2, 3, 4, 5, 6, 7, 8,
9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400,
500, or 1000 different portions. The portions may be diluted in the
same or in varying amounts, and may be used for, for example, 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90,
100, 200, 300, 400, 500, or 1000 or more different laboratory
tests.
[0077] In embodiments provided herein involving obtaining at a
sample collection site at least a vessel containing at least a
portion of a small volume bodily fluid sample from a subject, in
embodiments, the obtaining step may include collecting the small
volume bodily fluid sample from the subject (e.g. from a
fingerstick or venous draw).
[0078] In embodiments provided herein involving performing at least
a portion of a laboratory test in an assay unit, in embodiments,
the assay unit maybe movable, such as by a fluid handling
apparatus. In embodiments including two or more assay units, in
embodiments, the assay units may be independently movable.
[0079] In embodiments provided herein involving transport of one or
more vessels containing a bodily fluid sample, in some embodiments,
the vessels may have any of the characteristics of vessels
described herein, or of other vessels suitable for the storage of
bodily fluids. In some embodiments, the vessels may be loaded with
bodily fluid sample by any of the devices or methods provided
herein, or by other suitable techniques for loading a vessel have a
small interior volume. For example, in certain embodiments, a
vessel to be transported according to a system or method provided
herein may be loaded with a sample by a syringe or a pipette
tip.
[0080] Optionally, at least one embodiment of a sample collection
device herein can separate a single blood sample into different
vessels for different pre-analytical processing. This can be
achieved through fluid pathways in the device and/or through
different inlet ports on the device.
[0081] In at least another embodiment described herein, a method is
provided for use with a bodily fluid sample from a subject, the
method comprising: shipping a plurality of sample containers from a
first location to a second location, wherein each of said sample
containers contains a sample of about 500 uL or less and wherein
interior volume of each of the sample containers is about 600 uL or
less, wherein shipping of the plurality of samples containers is
accomplished using a first frame sized to fit in a shipping
container, said first frame comprises a plurality of openings each
sized and shaped to engage at least one of the sample containers
and hold the sample containers in a desired orientation; obtaining
data from each of the sample containers; providing a plurality of
processing frames at the second location; using said data from the
sample containers to determine which of said processing frames
receive which of said sample containers; and moving said sample
containers from the shipping frame to the processing frame based on
data provided by the sample containers and based on sorting
information; and handling the processing frame to simultaneously
process the sample containers processing frame.
[0082] Optionally, obtaining data comprises simultaneously scanning
a plurality of sample container IDs simultaneously. Optionally,
scanning occurs when the containers are in the shipping frame.
Optionally, scanning comprises scanning an underside surface of the
shipping containers. Optionally, determining which processing
frames receive which of the sample containers comprises referencing
the data with at least one database at a server. Optionally,
determining comprises matching container ID with subject ID.
Optionally, determining comprises matching container ID with
pre-processing procedure. Optionally, at least some of the sample
containers contain sample having a first anticoagulant and at least
some other of the sample containers have a second, different
anticoagulant.
[0083] This Summary is provided to introduce a selection of
concepts in a simplified form that are further described below in
the Detailed Description. This Summary is not intended to identify
key features or essential features of the claimed subject matter,
nor is it intended to be used to limit the scope of the claimed
subject matter.
INCORPORATION BY REFERENCE
[0084] All publications, patents, and patent applications mentioned
in this specification are herein incorporated by reference to the
same extent as if each individual publication, patent, or patent
application was specifically and individually indicated to be
incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0085] FIGS. 1A-1B show perspective views of a sample collection
device according to one embodiment as described herein.
[0086] FIGS. 2A-2C show perspective views of a sample collection
device without a cap according to one embodiment as described
herein.
[0087] FIGS. 3A-3B show side and cross-sectional views of a sample
collection device according to one embodiment as described
herein.
[0088] FIGS. 4A-4B show side and cross-sectional views of a sample
collection device according to one embodiment as described
herein.
[0089] FIGS. 5A-5B show perspective views of a sample collection
device according to another embodiment as described herein.
[0090] FIGS. 6A-6B show side views of a sample collection device
according to one embodiment as described herein.
[0091] FIGS. 7A-8B show side and cross-sectional views of a sample
collection device according to one embodiment as described
herein.
[0092] FIGS. 9A-9C show side cross-sectional views of a sample
collection device at various stages of use according to one
embodiment as described herein.
[0093] FIGS. 10A-10B show perspective views of a sample collection
device according to one embodiment as described herein.
[0094] FIGS. 11A-11Z show views of various examples of sample
collection devices according embodiment as described herein.
[0095] FIG. 12 shows a schematic of a tip portion of a sleeve and
associated balance of forces associated with one embodiment as
described herein.
[0096] FIGS. 13A-13D show views of various collection devices with
an upward facing collection location according to embodiments as
described herein
[0097] FIGS. 14-15 show various views of a collection device with a
single collection location according to one embodiment as described
herein.
[0098] FIGS. 16-17 show perspective and end views of a sample
collection device using vessels having identifiers according to one
embodiment as described herein.
[0099] FIGS. 18A-18G show various views of sample vessels according
to embodiments as described herein.
[0100] FIGS. 19A-19C show view of various embodiments of a front
end of a sample collection device.
[0101] FIGS. 20A-21 show various embodiments of sample collection
device with an integrated tissue penetrating member.
[0102] FIG. 22 shows a perspective view of a collection device for
use with a blood vessel or other tissue penetrator and sample
collector according to an embodiment described herein.
[0103] FIG. 23-28 show various view of collection devices for use
with various sample collectors according to embodiments described
herein.
[0104] FIGS. 29A-29C show schematics of various embodiments as
described herein.
[0105] FIGS. 30-31 show schematic of methods according to
embodiments described herein.
[0106] FIG. 32 shows a schematic view of one embodiment of system
described herein.
[0107] FIGS. 33 to 37 show yet another embodiment of a collection
device described herein
[0108] FIGS. 38A-39 show various views of a thermally controlled
transport container transport device according to at least one
embodiment described herein.
[0109] FIGS. 40A-40C show schematics of various embodiments
described herein.
[0110] FIG. 41 shows a perspective view of one portion of a
transport container having a plurality of sample vessels therein
according to at least one embodiment described herein.
[0111] FIG. 42 is an exploded perspective view of one portion of a
transport container having a plurality of sample vessels therein
according to at least one embodiment described herein.
[0112] FIG. 43 shows a perspective view of a transport container
according to yet another embodiment described herein.
[0113] FIG. 44 shows a schematic of a sample collection and
transport process according to one embodiment described herein.
[0114] FIG. 45 shows a schematic of a sample collection and
transport process according to yet another embodiment described
herein.
[0115] FIG. 46 shows a sample collection device according to one
embodiment described herein.
[0116] FIG. 47 shows a schematic view of one system for unloading
sample vessels from a transport container according to one
embodiment described herein.
[0117] FIG. 48 is a graph showing the stability of an analyte in a
sample in a vessel provided herein.
[0118] FIGS. 49 to 51 show one non-limiting example of tests
according to at least one embodiment described herein.
[0119] FIGS. 52 to 55C show various views of devices and systems
according to embodiments herein.
[0120] FIGS. 56A to 59B show various views of sample transport
devices according to at least some embodiments herein.
[0121] FIG. 60 shows a view of a system according to at least some
embodiments herein.
DESCRIPTION OF THE SPECIFIC EMBODIMENTS
[0122] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory only and are not restrictive of the invention, as
claimed. It may be noted that, as used in the specification and the
appended claims, the singular forms "a", "an" and "the" include
plural referents unless the context clearly dictates otherwise.
Thus, for example, reference to "a material" may include mixtures
of materials, reference to "a compound" may include multiple
compounds, and the like. References cited herein are hereby
incorporated by reference in their entirety, except to the extent
that they conflict with teachings explicitly set forth in this
specification.
[0123] In this specification and in the claims which follow,
reference will be made to a number of terms which shall be defined
to have the following meanings:
[0124] "Optional" or "optionally" means that the subsequently
described circumstance may or may not occur, so that the
description includes instances where the circumstance occurs and
instances where it does not. For example, if a device optionally
contains a feature for a sample collection well, this means that
the sample collection well may or may not be present, and, thus,
the description includes both structures wherein a device possesses
the sample collection well and structures wherein sample collection
well is not present.
[0125] As used herein, the terms "substantial" means more than a
minimal or insignificant amount; and "substantially" means more
than a minimally or insignificantly. Thus, for example, the phrase
"substantially different", as used herein, denotes a sufficiently
high degree of difference between two numeric values such that one
of skill in the art would consider the difference between the two
values to be of statistical significance within the context of the
characteristic measured by said values. Thus, the difference
between two values that are substantially different from each other
is typically greater than about 10%, and may be greater than about
20%, preferably greater than about 30%, preferably greater than
about 40%, preferably greater than about 50% as a function of the
reference value or comparator value.
[0126] As used herein, a "sample" may be but is not limited to a
blood sample, or a portion of a blood sample, may be of any
suitable size or volume, and is preferably of small size or volume.
In some embodiments of the assays and methods disclosed herein,
measurements may be made using a small volume blood sample, or no
more than a small volume portion of a blood sample, where a small
volume comprises no more than about 5 mL; or comprises no more than
about 3 mL; or comprises no more than about 2 mL; or comprises no
more than about 1 mL; or comprises no more than about 500 .mu.L; or
comprises no more than about 250 .mu.L; or comprises no more than
about 100 .mu.L; or comprises no more than about 75 .mu.L; or
comprises no more than about 50 .mu.L; or comprises no more than
about 35 .mu.L; or comprises no more than about 25 .mu.L; or
comprises no more than about 20 .mu.L; or comprises no more than
about 15 .mu.L; or comprises no more than about 10 .mu.L; or
comprises no more than about 8 .mu.L; or comprises no more than
about 6 .mu.L; or comprises no more than about 5 .mu.L; or
comprises no more than about 4 .mu.L; or comprises no more than
about 3 .mu.L; or comprises no more than about 2 .mu.L; or
comprises no more than about 1 .mu.L; or comprises no more than
about 0.8 .mu.L; or comprises no more than about 0.5 .mu.L; or
comprises no more than about 0.3 .mu.L; or comprises no more than
about 0.2 .mu.L; or comprises no more than about 0.1 .mu.L; or
comprises no more than about 0.05 .mu.L; or comprises no more than
about 0.01 .mu.L.
[0127] As used herein, the term "point of service location" may
include locations where a subject may receive a service (e.g.
testing, monitoring, treatment, diagnosis, guidance, sample
collection, ID verification, medical services, non-medical
services, etc.), and may include, without limitation, a subject's
home, a subject's business, the location of a healthcare provider
(e.g., doctor), hospitals, emergency rooms, operating rooms,
clinics, health care professionals' offices, laboratories,
retailers [e.g. pharmacies (e.g., retail pharmacy, clinical
pharmacy, hospital pharmacy), drugstores, supermarkets, grocers,
etc.], transportation vehicles (e.g. car, boat, truck, bus,
airplane, motorcycle, ambulance, mobile unit, fire engine/truck,
emergency vehicle, law enforcement vehicle, police car, or other
vehicle configured to transport a subject from one point to
another, etc.), traveling medical care units, mobile units,
schools, day-care centers, security screening locations, combat
locations, health assisted living residences, government offices,
office buildings, tents, bodily fluid sample acquisition sites
(e.g. blood collection centers), sites at or near an entrance to a
location that a subject may wish to access, sites on or near a
device that a subject may wish to access (e.g., the location of a
computer if the subject wishes to access the computer), a location
where a sample processing device receives a sample, or any other
point of service location described elsewhere herein.
[0128] As used herein, a "bodily fluid" may be any fluid obtained
or obtainable from a subject. A bodily fluid may be, for example,
blood, urine, saliva, tears, sweat, a bodily secretion, a bodily
excretion, or any other fluid originating in or obtained from a
subject. In particular, bodily fluids include, without limitation,
blood, serum, plasma, bone marrow, saliva, urine, gastric fluid,
spinal fluid, tears, stool, mucus, sweat, earwax, oil, glandular
secretions, cerebral spinal fluid, semen, vaginal fluid,
interstitial fluids derived from tumorous tissue, ocular fluids,
placental fluid, amniotic fluid, cord blood, lymphatic fluids,
cavity fluids, sputum, pus, meconium, breast milk and/or other
secretions or excretions.
[0129] As used herein, "a bodily fluid sample collector" or any
other collection mechanism can be disposable. For example, a bodily
fluid collector can be used once and disposed. A bodily fluid
collector can have one or more disposable components.
Alternatively, a bodily fluid collector can be reusable. The bodily
fluid collector can be reused any number of times. In some
instances, the bodily fluid collector can include both reusable and
disposable components.
[0130] As used herein, "a sample collection unit" and/or any other
portion of the device may be capable of receiving a single type of
sample, or multiple types of samples. For example, the sample
collection unit may be capable of receiving two different types of
bodily fluids (e.g., blood, tears). In another example, the sample
collection unit may be capable of receiving two different types of
biological samples (e.g., urine sample, stool sample). Multiple
types of samples may or may not be fluids, solids, and/or
semi-solids. For example, the sample collection unit may be capable
of accepting one or more of, two or more of, or three or more of a
bodily fluid, secretion and/or tissue sample.
[0131] As used herein, "non-wicked, non-matrixed form" means that a
liquid or suspension is not absorbed by or pulled into a webbing,
mesh, fiber pad, absorbent material, absorbent structure,
percolating network of fibers, or the like which alters the form of
the liquid or suspension or traps components of the sample therein
to an extent that the integrity of sample in liquid form is changed
and the sample cannot be extracted in liquid form while still
maintaining sample integrity for sample analysis.
[0132] The term "sample handling system," as used herein, refers to
a device or system configured to aid in sample imaging, detecting,
positioning, repositioning, retention, uptake and deposition. In an
example, a robot with pipetting capability is a sample handling
system. In another example, a pipette which may or may not have
(other) robotic capabilities is a sample handing system. A sample
handled by a sample handling system may or may not include fluid. A
sampling handling system may be capable of transporting a bodily
fluid, secretion, or tissue. A sampling handling system may be able
to transport one or more substance within the device that need not
be a sample. For example, the sample handling system may be able to
transport a powder that may react with one or more sample. In some
situations, a sample handling system is a fluid handling system.
The fluid handling system may comprise pumps and valves of various
types or pipettes, which, may comprise but not be limited to a
positive displacement pipette, air displacement pipette and
suction-type pipette. The sample handling system may transport a
sample or other substance with aid of a robot as described
elsewhere herein.
[0133] The term "health care provider," as used herein, refers to a
doctor or other health care professional providing medical
treatment and/or medical advice to a subject. A health care
professional may include a person or entity that is associated with
the health care system. Examples of health care professionals may
include physicians (including general practitioners and
specialists), surgeons, dentists, audiologists, speech
pathologists, physician assistants, nurses, midwives,
pharmaconomists/pharmacists, dietitians, therapists, psychologists,
chiropractors, clinical officers, physical therapists,
phlebotomists, occupational therapists, optometrists, emergency
medical technicians, paramedics, medical laboratory technicians,
medical prosthetic technicians, radiographers, social workers, and
a wide variety of other human resources trained to provide some
type of health care service. A health care professional may or may
not be certified to write prescriptions. A health care professional
may work in or be affiliated with hospitals, health care locations
and other service delivery points, or also in academic training,
research and administration. Some health care professionals may
provide care and treatment services for patients in private or
public domiciles, community centers or places of gathering or
mobile units. Community health workers may work outside of formal
health care institutions. Managers of health care services, medical
records and health information technicians and other support
workers may also be medical care professionals or affiliated with a
health care provider. A health care professional may be an
individual or an institution that provides preventive, curative,
promotional or rehabilitative health care services to individuals,
families, or communities.
[0134] In some embodiments, the health care professional may
already be familiar with a subject or have communicated with the
subject. The subject may be a patient of the health care
professional. In some instances, the health care professional may
have prescribed the subject to undergo a clinical test. The health
care professional may have instructed or suggested to the subject
to undergo a clinical test conducted at the point of service
location or by a laboratory. In one example, the health care
professional may be the subject's primary care physician. The
health care professional may be any type of physician for the
subject (including general practitioners, referred practitioners or
the patient's own physician optionally selected or connected
through telemedicine services, and/or specialists). The health care
professional may be a medical care professional.
[0135] The term "rack," as used herein, refers to a frame or
enclosure for mounting multiple modules. The rack is configured to
permit a module to be fastened to or engaged with the rack. In some
situations, various dimensions of the rack are standardized. In an
example, a spacing between modules is standardized as multiples of
at least about 0.5 inches, or 1 inch, or 2 inches, or 3 inches, or
4 inches, or 5 inches, or 6 inches, or 7 inches, or 8 inches, or 9
inches, or 10 inches, or 11 inches, or 12 inches.
[0136] The term "cells," as used in the context of biological
samples, encompasses samples that are generally of similar sizes to
individual cells, including but not limited to vesicles (such as
liposomes), cells, virions, and substances bound to small particles
such as beads, nanoparticles, or microspheres. Characteristics
include, but are not limited to, size; shape; temporal and dynamic
changes such as cell movement or multiplication; granularity;
whether the cell membrane is intact; internal cell contents,
including but not limited to, protein content, protein
modifications, nucleic acid content, nucleic acid modifications,
organelle content, nucleus structure, nucleus content, internal
cell structure, contents of internal vesicles, ion concentrations,
and presence of other small molecules such as steroids or drugs;
and cell surface (both cellular membrane and cell wall) markers
including proteins, lipids, carbohydrates, and modifications
thereof.
[0137] As used herein, "sample" refers to an entire original sample
or any portion thereof, unless the context clearly dictates
otherwise.
[0138] The invention provides systems and methods for multi-purpose
analysis of a sample or health parameter. The sample may be
collected and one or more sample preparation step, assay step,
and/or detection step may occur on a device. Various aspects of the
invention described herein may be applied to any of the particular
applications, systems, and devices set forth below. The invention
may be applied as a stand alone system or method, or as part of an
integrated system, such as in a system involving point of service
health care. In some embodiments, the system may include externally
oriented imaging technologies, such as ultrasound or MRI or be
integrated with external peripherals for integrated imaging and
other health tests or services. It shall be understood that
different aspects of the invention can be appreciated and practice
individually, collectively, or in combination with each other.
[0139] Referring now to FIGS. 1A-1B, one embodiment of a sample
collection device 100 will now be described. In this non-limiting
example, the sample collection device 100 may include a collection
device body 120, support 130, and base 140. In some instances, a
cap 110 may be optionally provided. In one embodiment, the cap may
be used to protect the opening, keeping it clean, and for covering
up the bloody tip after collection. Optionally or alternatively,
the cap may also be used to limit flow rate during transfer of
sample fluid into the sample vessels by controlling the amount of
venting provided to the capillaries. Some embodiments may include
vents pathways (permanently open or operably closable) in the cap
while others do not. Optionally, the collection device body 120 can
include a first portion of the device 100 having one or more
collection pathways such as but not limited to collection channels
122a, 122b therein, which may be capable of receiving sample B.
FIG. 1A shows that sample B only partially filling the channels
122a, 122b, but it should be understood that, although partial
fills are not excluded in some alternative embodiments, in most
embodiments, the channels will be fully filled with sample B when
the fill process is completed. In this embodiment, the base 140 may
have one or more fill indicators 142a, 142b, such as but not
limited to optical indicators, that may provide an indication of
whether sample has reached one or more vessel housed in the base.
It should be understood that although this indication may be by way
of a visual indication, other indication methods such as audio,
vibratory, or other indication methods may be used in place of or
in combination with the indication method. The indicators may be on
at least one of the vessels. There may be variations and
alternatives to the embodiments described herein and that no single
embodiment should be construed to encompass the entire
invention.
[0140] Although not shown for ease of illustration, the support 130
may also include one or more fill indicators showing whether a
desired fill level has been reached in the channels 122a and 122b.
This may be in place of or in addition to fill indicators 142a,
142b. Of course, the one or more pathway fill indicators can be
positioned on a different part and is not limited to being on
support 130. It should be understood that although this indication
of fill level in one or more of the channels 122a and 122b may be
by way of a visual indication, other indication methods such as
audio, vibratory, or other indication methods may be used in place
of or in combination with the indication method. The indicator may
be on at least one of the collection pathways. Optionally,
indicators are on all of the collection pathways.
[0141] In the present embodiment, the support 130 can be used to
join the body 120 and the base 140 to form an integrated device. It
should be understood that although the device body 120, support
130, and base 140 are recited as separate parts, one or more of
those parts may be integrally formed to simplify manufacturing and
such integration is not excluded herein.
[0142] In some embodiments herein, a cap 110 may be optionally
provided. In one non-limiting example, the cap may be fitted over a
portion of the collection device body 120. The cap 110 may be
detachable from the collection device body 120. In some instances,
the cap 110 may be completely separable from the collection device
body 120, or may retain a portion that is connected to the
collection device body, such as but not limited to being hinged or
otherwise linked to the collection device. The cap 110 may cover a
portion of the collection device body 120 containing exposed ends
of one or more channels therein. The cap 110 may prevent material,
such as air, fluid, or particulates, from entering the channels
within the device body, when the cap is in place. Optionally, the
cap 110 may attach to the collection body 120 using any technique
known or later developed in the art. For instance, the cap may be
snap fit, twist on, friction-fit, clamp on, have magnetic portions,
tie in, utilize elastic portions, and/or may removably connect to
the collection device body. The cap may form a fluid-tight seal
with the collection device body. The cap may be formed from an
opaque, transparent, or translucent material.
[0143] In one embodiment, a collection device body 120 of a sample
collection device may contain at least a portion of one or more
collection pathways such as but not limited to channels 122a, 122b
therein. It should be understood that collection pathways that are
not channels are not excluded. The collection device body may be
connected to a support 130 that may contain a portion of one or
more channels therein. The collection device body may be
permanently affixed to the support or may be removable with respect
to the support. In some instances, the collection device body and
the support may be formed of a single integral piece.
Alternatively, the collection device body and support may be formed
from separate pieces. During the operation of the device the
collection device and support do not move relative to one
another.
[0144] Optionally, the collection device body 120 may be formed in
whole or in part from an optically transmissive material. For
example, the collection device body may be formed from a
transparent or translucent material. Optionally, only select
potions of the body are transparent or translucent to visualize the
fluid collection channel(s). Optionally, the body comprises an
opaque material but an opening and/or a window can be formed in the
body to show fill levels therein. The collection device body may
enable a user to view the channels 122a, 122b within and/or passing
through the device body. The channels may be formed of a
transparent or translucent material that may permit a user to see
whether sample B has traveled through the channels. The channels
may have substantially the same length. In some instances a support
130 may be formed of an opaque material, a transparent material, or
a translucent material. The support may or may not have the same
optical characteristics of the collection device body. The support
may be formed from a different material as the collection device
body, or from the same material as the collection device body.
[0145] The collection device body 120 may have any shape or size.
In some examples, the collection device body may have a circular,
elliptical, triangular, quadrilateral (e.g., square, rectangular,
trapezoidal), pentagonal, hexagonal, octagonal, or any other
cross-sectional shape. The cross-sectional shape may remain the
same or may vary along the length of the collection device body. In
some instances, the collection device body may have a
cross-sectional area of less than or equal to about 10 cm.sup.2, 7
cm.sup.2, 5 cm.sup.2, 4 cm.sup.2, 3 cm.sup.2, 2.5 cm.sup.2, 2
cm.sup.2, 1.5 cm.sup.2, 1 cm.sup.2, 0.8 cm.sup.2, 0.5 cm.sup.2, 0.3
cm.sup.2, or 0.1 cm.sup.2. The cross-sectional area may vary or may
remain the same along the length of the collection device body 120.
The collection device body may have a length of less than or equal
to about 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm,
4 cm, 3 cm, 2 cm, 1 cm, 0.5 cm, or 0.1 cm. The collection device
body 120 may have a greater or lesser length than the cap, support
or base, or an equal length to the cap, support, or base. There may
be variations and alternatives to the embodiments described herein
and that no single embodiment should be construed to encompass the
entire invention.
[0146] In one embodiment, the collection pathways such as but not
limited to channels 122a, 122b may also have a selected
cross-sectional shape. Some embodiments of the channels may have
the same cross-sectional shape along the entire length of the
channel. Optionally, the cross-sectional shape may remain the same
or may vary along the length. For example, some embodiments may
have one shape at one location and a different shape at one or more
different locations along the length of the channel. Some
embodiments may have one channel with one cross-sectional shape and
at least one other channel of a different cross-sectional shape. By
way of non-limiting example, some may have a circular, elliptical,
triangular, quadrilateral (e.g., square, rectangular, trapezoidal),
pentagonal, hexagonal, octagonal, or any other cross-sectional
shape. The cross-sectional shape may be the same for the body,
support, and base, or may vary. Some embodiments may select a shape
to maximize volume of liquid that can be held in the channels for a
specific channel width and/or height. Some may have one of the
channels 122a, 122b with one cross-sectional shape while another
channel has a different cross-sectional shape. In one embodiment,
the cross-sectional shape of the channel can help maximize volume
therein, but optionally, it can also optimize the capillary pulling
forces on the blood. This will allow for maximized rate of filling.
It should be understood that in some embodiments, the
cross-sectional shape of the channel can directly affect the
capillary forces. By way of non-limiting example, a volume of
sample can be contained in a shallow but wide channel, or a rounded
channel, both containing the same volume, but one might be
desirable over the other for filling speed, less possibility of air
entrapment, or factors related the performance of the channel.
[0147] Although the channels may have any shape or size, some
embodiments are configured such that the channel exhibits a
capillary action when in contact with sample fluid. In some
instances, the channel may have a cross-sectional area of less than
or equal to about 10 mm.sup.2, 7 mm.sup.2, 5 mm.sup.2, 4 mm.sup.2,
3 mm.sup.2, 2.5 mm.sup.2, 2 mm.sup.2, 1.5 mm.sup.2, 1 mm.sup.2, 0.8
mm.sup.2, 0.5 mm.sup.2, 0.3 mm.sup.2, or 0.1 mm.sup.2. The
cross-sectional size may remain the same or may vary along the
length. Some embodiments may tailor for greater force along a
certain length and then less in a different length. The
cross-sectional shape may remain the same or may vary along the
length. Some channels are straight in configuration. Some
embodiments may have curved or other shaped path shapes alone or in
combination with straight portions. Some may have different
orientations within the device body 120. For example, when the
device is held substantially horizontally, one or more channels may
slope downward, slope upward, or not slope at all as it carries
fluid away from the initial collection point on the device.
[0148] The channels 122a, 122b may be supported by the device body
120 and/or the support 130. In some instances, the entire length of
the channels may be encompassed within the combination of the
device body and the support. In some instances, a portion of the
channels may be within the device body and a portion of the
channels may be within the support. The position of the channels
may be affixed by the device body and/or the support. In some
embodiments, the channels may be defined as lumens inside a hollow
needle. In some embodiments, the channels are only defined on three
sides, with at least one side that is open. Optionally, a cover
layer separate from the body may define the side that would
otherwise be open. Some embodiments may define different sides of
the channel with different materials. These materials can all be
provided by the body or they may be provided by different pieces of
the collection device. Some embodiments may have the channels all
in the same plane. Optionally, some may have a shape that takes at
least a portion of the channel to a different plane and/or
orientation. Optionally, some channels may be entirely in a
different plane and/or orientation.
[0149] In some instances, a plurality of channels may be provided.
In some embodiments, one channel splits into two or more channels.
Optionally, some channels split into an even larger number of
channels. Some channels may include a control mechanism such as but
not limited to a valve for directing flow in the channel(s). At
least a portion of the channels may be substantially parallel to
one another. Alternatively, no portion of the channels need be
parallel to one another. In some instances, at least a portion of
the channels are not parallel to one another. Optionally, the
channels may be slightly bent. Optionally, channels may have one
cross-sectional area at one location and a smaller cross-sectional
area at a different location along the channel. Optionally,
channels may have one cross-sectional area at one location and a
larger cross-sectional area at a different location along the
channel. For some embodiments of the Y design, it may be desirable
that the channels would have vents placed appropriately to define
the sample for each vial such that there would not be sample pulled
or cross contamination from other channels. By way of non-limiting
example, one embodiment with vents is shown in FIG. 11I.
[0150] A base 140 may be provided within the sample collection
device. The base may be connected to the support 130. In some
instances, a portion of the base may insertable within the support
and/or a portion of the support may be insertable within the base.
The base may be capable of moving relative to the support. In some
instances, a sample collection device may have a longitudinal axis
extending along the length of the sample collection device. The
base and/or support may move relative to one another in the
direction of the longitudinal axis. The base and/or support may be
capable of moving a limited distance relative to one another.
Alternatively, the base may be fixed relative to the support. The
base may be provided at an end of the sample collection device
opposite an end of the sample collection device comprising a cap
110. Optionally, some embodiments may include an integrated
base/vessel part so that there are no longer separate vessels that
are assembled into the base pieces. There may be variations and
alternatives to the embodiments described herein and that no single
embodiment should be construed to encompass the entire
invention.
[0151] A base 140 may house one or more vessel therein. The vessels
may be in fluidic communication with the channels and/or may be
brought into fluidic communication with the channels. An end of a
channel may be within the vessel or may be brought within the
vessel. A base may have one or more optical indicator 142a, 142b
that may provide a visual indication of whether sample has reached
one or more vessel housed in the base. In some embodiments, the
optical indicators may be optical windows that may enable a user to
see into the base. The optical window may be formed from a
transparent and/or translucent material. Alternatively, the optical
window may be an opening without any material therein. The optical
window may enable a user to directly view a vessel within the base.
The vessel within the base may be formed from a transparent and/or
translucent material that may enable a user to see if a sample has
reached the vessel of the base. For example, if blood is
transported along the channel to the vessels, the vessels may
visually indicate the presence of blood therein. In other
embodiments, the optical indicators may include other features that
may indicate the vessel has been filled. For example, one or more
sensors may be provided within the base or vessel that may
determine whether a sufficient amount of sample has been provided
within the vessel. The one or more sensors may provide a signal to
an optical indicator on the base that may indicator whether the
sample has been provided to the vessel and/or the amount of sample
that has been provided to the vessel. For example, the optical
indicator may include a display, such as but not limited to an LCD
display, light display (e.g., LED display), plasma screen display
that may provide an indication that the vessels have been
sufficiently filled. In alternative embodiments, an optical
indicator need not be provided, but alternative indicators may be
provided, such as but not limited to an audio indicator or
temperature controlled indicator can be used to indicate when the
vessels have been filed.
[0152] FIGS. 2A-2C provide views of a sample collection device 200
without a cap 110. The sample collection device 200 may include a
body 220, support 230, and base 240. The body may be connected to
the support. In the present embodiment, the base 240 may be
connected to the support at an end opposing the end connected to
the body. The body may support and/or contain at least a portion of
one, two, or more channels 222a, 222b. The channels may be capable
of receiving a sample 224a, 224b from a sample receiving end 226 of
the device.
[0153] The body 220 may have a hollow portion 225 therein.
Alternatively, the body may be formed from a solid piece. The
channels 222a, 222b may be integrally formed into the body. For
example, they may be passageways that pass through a solid portion
of the body. The passageways may have been drilled through, or
formed using lithographic techniques. Alternatively, the channels
may be separate structures that may be supported by the body. For
example, the channels may be formed of one or more tube that may be
supported by the body. In some instances, the channels may be held
in place at certain solid portions of the body and may pass through
one or more hollow portion of the body. Optionally, the body 220
may be formed from two pieces joined together to define the
channels 222a and 222b therein.
[0154] The channels 222a, 222b may include one or more features or
characteristics mentioned elsewhere herein. At least a portion of
the channels may be substantially parallel to one another.
Alternatively, the channels may be at angles relative to one
another. In some embodiments, the channels may have a first end
that may be at a sample receiving end 226 of the sample collection
device. The first end of a channel may be an open end capable of
receiving a sample. In some embodiments, the ends of each of the
channels may be provided at the sample receiving end of the sample
collection device. One, two, or more channels may have a first end
at the sample receiving end of the sample collection device.
Separate channels can be used to minimize the risk of cross
contamination of blood between one channel and another channel.
Optionally, the channels may have an inverted Y configuration with
the channels starting with a common channel and the splitting into
two or more separate channels. This Y configuration may be useful
in situation where contamination is not an issue. Optionally, an
alternative method to a Y configuration would be a straight channel
and have the sample collection vessels move to sequentially to
engage the same needle from a straight channel.
[0155] In some instances, a plurality of channels may be provided.
The ends of the channels at the sample receiving end may be in
close proximity to one another. The ends of the channels at the
sample receiving end may be adjacent to one another. The ends of
the channels at the sample receiving end may be contacting one
another, or may be within about 0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5
mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 12 mm, 15 mm, or 20 mm of one
another edge to edge, or center to center. The channels may diverge
from one another from the sample receiving end. For example, the
other ends of the channels opposing the ends of the channels at the
sample receiving ends may be further apart from one another. They
may be greater than or equal to about 3 mm, 4 mm, 5 mm, 6 mm, 7 mm,
8 mm, 9 mm, 10 mm, 12 mm, 15 mm, 20 mm, 25 mm, or 30 mm apart from
one another edge to edge or center to center.
[0156] In some embodiments, the body 220 may have an elongated
shape. The body may have one or more tapered portion 228 at or near
the sample receiving end 226. The sides of the body may converge at
the sample receiving end. The tapered portion and/or sample
receiving end may be curved. Alternatively, edges may be provided.
A surface of the tapered portion may be provided at any angle
relative to the longitudinal axis of the device. For example, the
tapered portion may be about 5 degrees, 10 degrees, 15 degrees, 30
degrees, 45 degrees, 60 degrees, or 75 degrees relative to the
longitudinal axis.
[0157] The sample receiving end 226 of the device may be contacted
to a sample. The sample may be provided directly from the subject.
The sample receiving end may contact the subject or a sample that
is contacting or being exuded from the subject. For example, the
sample receiving end may contact a drop of blood on a subject's
finger. The blood may enter the channels. The blood may be
transported through the channels via capillary action, pressure
differential, gravity, or any other motive force. The blood may
travel through the channels from a sample receiving end to a sample
delivery end. The sample delivery end may be in fluid communication
or may be brought into fluid communication with one or more vessels
housed within a base of the device. The sample may pass from the
channels to the vessels. The sample may be driven into the vessels
via pressure differential, capillary action, gravity, friction,
and/or any other motive force. Optionally, the sample might also be
blood introduced with a pipette, syringe, etc. . . . . It should be
understood that although FIG. 2B shows that sample B only partially
filling the channels 222a, 222b, but in most embodiments, the
channels will be fully filled with sample B when the fill process
is completed.
[0158] FIGS. 3A-3B show an example of a sample collection device
300 prior to bringing the channels 322a, 322b into fluid
communication with one or more vessels 346a, 346b housed within a
base 340 of the device. The sample collection device may include a
cap 310, body 320, support 330, and base 340. The body and/or
support may support and/or encompass at least a portion of one,
two, or more channels. The base may support and/or encompass one,
two, or more vessels.
[0159] In one embodiment, a body 320 and/or support 330 may support
one or more channels 322a, 322b in the sample collection device. In
one example, two channels are provided, although descriptions
relating to a two-channel embodiment may apply to any number of
channels including but not limited to 1, 3, 4, 5, 6, or more
channels. Each of the channels may have a first end 323a, 323b that
may be provided at a sample receiving end 326 of the device. The
first ends of the respective channels may be open. The channels may
be open to ambient air. When the first ends of the channels contact
a fluid, such as blood, the fluid may be drawn into the channels.
Blood may be drawn in via capillary action, or any other of the
techniques described elsewhere herein. The blood may travel along
the length of the channels to the respective second ends 325a, 325b
of the channels. The channels may be fluidically segregated from
one another. For example, a fluid may enter a first channel 322a
via a first end 323a, pass through the length of the channel, and
exit the first channel at the second end 325a. Similarly, fluid may
enter a second channel 322b via a first end 323b, pass through the
length of the channel, and exit the second channel at the second
end 325b. The first and second channels may be fluidically
segregated so that fluid from the first channel does not pass into
the second channel and vice versa. In some embodiments, the fluid
may pass to the second ends of the channels without exiting
initially.
[0160] The channels 322a, 322b may have a diverging configuration.
For example, the first ends 323a, 323b of the channels may be
closer together than the second ends 325a, 325b of the channels.
More space may be provided between the second ends of the channels
than between the first ends of the channels. The first ends of the
channels may or may not be in contact with one another. The first
ends of the channels may be adjacent to one another.
[0161] A base 340 may be connected to a support 330 of the sample
collection device. The base 340 may or may not directly contact the
support. The base may be movable relative to the support during use
of the device. In some embodiments, the base may slide in a
longitudinal direction relative to the support. In some instances,
the base may slide in a longitudinal direction relative to the
support without rotating. In some instances, the base may slide
co-axially with the support without rotating. In some instances, a
base may rotate while moving relative to the support. A portion of
the base may fit within a portion of the support, or vice versa.
For example, a portion of the base may be insertable into a portion
of the support and/or a portion of the support may be insertable
into the base. One or more stop feature may be provided in the base
and/or the frame to provide a controlled degree of movement between
the base and the support. The stop feature may include a shelf,
protrusion or groove.
[0162] The base 340 may be capable of supporting one or more
vessels 346a, 346b. The base may have a housing that may at least
partially surround the one or more vessels. In some instances, the
vessels may be completely surrounded when the base is engaged with
a support 330. The base may have one or more indentation,
protrusion, groove, or shaped feature to accept the vessels. The
base may be formed with a shape that is complementary to the shape
of the vessels. The vessels may be maintained in an upright
position relative to the base.
[0163] The same number of vessels may be provided as the number of
channels. For example, if N channels are provided, then N vessels
may be provided, wherein N is a positive whole number (e.g., 1, 2,
3, 4, 5, 6, 7, 8, or more). Each channel may correspond to a
respective vessel. In one example, a sample collection device may
have a first channel and a second channel, as well as a respective
first vessel and second vessel. A first channel 322a may be in or
may be configured to be brought into fluid communication with a
first vessel 346a, and a second channel 322b may be in or may be
configured to be brought into fluid communication with a second
vessel 346b.
[0164] In some embodiments, each vessel may have a body 349a, 349b
and a cap 348a, 348b. In some instances, the vessel body may be
formed from a transparent or translucent material. The vessel body
may permit a sample provided within the vessel body to be visible
when viewed from outside the vessel. The vessel body may have a
tubular shape. In some instances, the vessel body may have a
cylindrical portion. The bottom of the vessel may be flat, tapered,
rounded, or any combination thereof. The vessels may comprise an
open end and a closed end. The open end may be a top end of the
vessel, which may be at the end of the vessel closer to one or more
channel. The closed end may be a bottom end of the vessel, which
may be at the end of the vessel further from one or more channel.
Various embodiments of vessels may be described in greater detail
elsewhere herein.
[0165] A base 340 may have one or more optical indicators, such as
optical windows 342a, 342b. The optical windows may be positioned
over the vessels 346a, 346b. In some instances, the optical windows
may be positioned over the vessel bodies. A single window may
provide a view to a single vessel or to multiple vessels. In one
example, the same number of optical windows may be provided as
vessels. Each optical window may correspond to a respective vessel.
Both the optical window and vessels may be formed of an optically
transmissive material that may permit a user to view whether a
sample has reached the vessel from outside the sample collection
device.
[0166] In some embodiments, there may be optical windows of the
channels 322a and 322b so that a user may observe when a desired
fill level has been reached in the channels. Some embodiments where
the body 320 is entirely transparent or translucent, there may be a
marker or indicator mark along the channels to note when a desired
fill level has been reached.
[0167] The vessels may be sized to contain a small fluid sample. In
some embodiments, the vessels may be configured to contain no more
than about 5 ml, 4 ml, 3 ml, 2 ml, 1.5 mL, 1 mL, 900 uL, 800 uL,
700 uL, 600 uL, 500 uL, 400 uL, 300 uL, 250 uL, 200 uL, 150 uL, 100
uL, 80 uL, 50 uL, 30 uL, 25 uL, 20 uL, 10 uL, 7 uL, 5 uL, 3 uL, 2
uL, 1 uL, 750 nL, 500 nL, 250 nL, 200 nL, 150 nL, 100 nL, 50 nL, 10
nL, 5 nL, or 1 nL. The vessels may be configured to contain no more
than several drops of blood, a drop of blood, or no more than a
portion of a drop of blood.
[0168] The vessels may contain a cap 348a, 348b. The plug may be
configured to fit over an open end of the vessel. The cap may block
the open end of the vessel. The cap may fluidically seal the
vessel. The cap may form a fluid-tight seal with the vessel body.
For example, the cap may be gas and/or liquid impermeable.
Alternatively, the cap may permit certain gases and/or liquids to
pass through. In some instances, the cap may be gas permeable while
being liquid impermeable. The cap may be impermeable to the sample.
For example, the cap may be impermeable to whole blood, serum or
plasma. In some instances, a portion of the cap may fit into a
portion of the vessel body. The cap may form a stopper with the
vessel body. The cap may include a lip or shelf that may hang over
a portion of the vessel body. The lip or shelf may prevent the cap
from sliding into the vessel body. In some instances, a portion of
a cap may overlie a top and/or side of the vessel body. Any
description herein of vessels may be applied in combination with
the sample collection device. Optionally, some embodiments may
include an additional part in the vessel assembly such as cap
holder. In one embodiment, the purpose of the cap holder is to
maintain a tight seal between the cap and vessel. In one
embodiment, the cap holder engages an attachment, lip, indentation,
or other attachment location on the outside of the vessel to hold
the cap in position. Optionally, some embodiments can combine the
function of both the cap and the cap holder into one component.
[0169] One or more engagement assemblies may be provided. The
engagement assembly may include a channel holder 350 and/or a
force-exerting component, such as a spring 352 or elastic. In one
embodiment, the holder 350 may keep the adapter channel 354 affixed
to the support. As will be described elsewhere herein, the adaptor
channel 354 may be formed integrally with the collection channel or
may be a discrete element that may be a stand-alone piece, part of
the collection channel, or part of the vessel. In one embodiment,
the holder 350 may prevent the adapter channel 354 from sliding
relative to the support. The holder 350 may optionally provide a
support upon which a force-exerting component, such as a spring,
may rest.
[0170] In one example, the engagement assemblies may each include a
spring 352 which may exert a force so that the base 340 is at an
extended state, when the spring is at its natural state. When the
base is at its extended state, space may be provided between the
vessels 346a, 346b and the engagement assemblies. In some
instances, when the base 340 is in its extended state, the second
ends of the channels may or may not contact the caps of the
vessels. The second ends of the channels 325a, 325b may be in a
position where they are not in fluid communication with the
interiors of the vessels.
[0171] A sample collection device may have any number of engagement
assemblies. For example, the same number of engagement assemblies
may be provided as number of channels. Each channel may have an
engagement assembly. For example, if a first channel and a second
channel are provided, a first engagement assembly may be provided
for the first channel, and a second engagement assembly may be
provided for the second channel. The same number of engagement
assemblies and vessels may be provided.
[0172] In one embodiment, the engagement assembly may house an
adapter channel 354 such as but not limited to an elongate member
with angled, tapered or pointed end 327a and 327b. It should be
understood that in some embodiments, the ends 327a and 327b are
part of a needle that is formed separate from the channels 322a and
322b and then coupled to the channels 322a and 322b. The needles
may be formed of the same or different material from the body
defining the channels 322a and 322b. For example, some may use a
metal to form the needles and a polymer or plastic material for the
body defining channels 322a and 322b. Optionally, some embodiments
may form the ends 327a and 327b on a member that is integrally
formed with the channels 322a and 322b. In some instances, the
second end of the channel may be configured to penetrate a
material, such as a cap 348a, 348b of the vessel. In some
embodiments, a portion of the adaptor channel 354 may be insertable
within the collection channel or a portion of the collection
channel may be insertable within the adaptor channel, or the two
may be configured to align flush. Optionally, some embodiments may
integrally form the adapter channel 354 with the collection channel
322a. It should be understood that FIGS. 3B (and 4B) shows that
sample B only partially filling the channels 122a, 122b, but, in
most embodiments, the channels will be fully filled with sample B
when the fill process is completed. There may be variations and
alternatives to the embodiments described herein and that no single
embodiment should be construed to encompass the entire
invention.
[0173] FIGS. 4A-4B show an example of a sample collection device
400 having channels 422a, 422b that are in fluid communication with
the interior of vessels 446a, 446b within the device. The sample
collection device may include a cap 410, body 420, support 430, and
base 440. The body and/or support may support and/or encompass at
least a portion of one, two, or more channels. The base may support
and/or encompass one, two, or more vessels.
[0174] In one embodiment, a body 420 and/or support 430 may support
one or more channels 422a, 422b in a sample collection device. For
example, a first channel and second channel may be provided. Each
of the channels may have a first end 423a, 423b that may be
provided at a sample receiving end 426 of the device. The first
ends of the respective channels may be open. The channels may be
open to ambient air. When the first ends of the channels contact a
fluid, such as blood, the fluid may be drawn into the channels. The
fluid may be drawn in via capillary action, or any other of the
techniques described elsewhere herein. The fluid may travel along
the length of the channels to the respective second ends 425a, 425b
of the channels. In some embodiments, the fluid may reach the
second ends of the channels via capillary action or other
techniques described herein. In other embodiments, the fluid need
not reach the second ends of the channels. The channels may be
fluidically segregated from one another.
[0175] In some embodiments, the fluid may pass to the second ends
of the channels without exiting when the channels are not in fluid
communication with the interiors of the vessels 446a, 446b. For
example, the fluid may be drawn into the channel via capillary
action, which may cause the fluid to flow to or near the end of the
channel without causing the fluid to exit the channel.
[0176] A base 440 may be connected to a support 430 of the sample
collection device. The base may be movable relative to the support
during use of the device. In some embodiments, the base may slide
in a longitudinal direction relative to the support. In one
example, the base may have (i) an extended position where the
channels are not in fluid communication with the interior of the
vessels, and (ii) a compressed position where the channels are in
fluid communication with the interior of the vessels. A sample
collection device may be initially provided in an extended state,
as shown in FIG. 3. After the sample has been collected and flown
through the length of the channel, a user may push the base in to
provide the sample collection device in its compressed state, as
shown in FIG. 4. Once the base has been pushed in, the base may
naturally remain pushed in, or may spring back out to an extended
state, once the pushing force is removed. In some instances, a base
may be pulled out to an extended state, or may be pulled out
completely to provide access to vessels therein.
[0177] The base 440 may be capable of supporting one or more
vessels 446a, 446b. The base may have a housing that may at least
partially surround the one or more vessels. In some instances, the
vessels may be completely surrounded when the base is engaged with
a support 430. The base may have one or more indentation,
protrusion, groove, or shaped feature to accept the vessels. The
base may be formed with a shape that is complementary to the shape
of the vessels. The vessels may be maintained in an upright
position relative to the base.
[0178] The same number of vessels may be provided as the number of
channels. Each channel may correspond to a respective vessel. In
one example, a sample collection device may have a first channel
and a second channel, as well as a respective first vessel and
second vessel. A first channel 422a may be in or may be configured
to be brought into fluid communication with a first vessel 446a,
and a second channel 422b may be in or may be configured to be
brought into fluid communication with a second vessel 446b. The
first channel may initially not be in fluid communication with a
first vessel and the second channel may initially not be in fluid
communication with the second vessel. The first and second channels
may be brought into fluid communication with the interiors of the
first and second vessels respectively when the base is pushed in
relative to the support. The first and second channels may be
brought into fluid communication with the first and second vessels
simultaneously. Alternatively, they need not be brought into fluid
communication simultaneously. The timing of the fluid communication
may depend on the height of the vessel and/or the length of the
channel. The timing of the fluid communication may depend on the
relative distances between the second end of the channel and the
vessel.
[0179] In some embodiments, each vessel may have a body 449a, 449b
and a cap 448a, 448b. The vessel body may have a tubular shape. In
some instances, the vessel body may have a cylindrical portion. The
bottom of the vessel may be flat, tapered, rounded, or any
combination thereof. The vessels may comprise an open end and a
closed end. The open end may be a top end of the vessel, which may
be at the end of the vessel closer to one or more channel. The
closed end may be a bottom end of the vessel, which may be at the
end of the vessel further from one or more channel.
[0180] A base 440 may have one or more optical indicators, such as
optical windows 442a, 442b. The optical windows may be positioned
over the vessels 446a, 446b. In some instances, the optical windows
may be positioned over the vessel bodies. Both the optical window
and vessels may be formed of an optically transmissive material
that may permit a user to view whether a sample has reached the
vessel from outside the sample collection device. In some
embodiments, the vessels may incorporate markings on the vessels
themselves to indicate fill level requirements.
[0181] The vessels may contain a cap 448a, 448b. The cap may be
configured to fit over an open end of the vessel. The cap may block
the open end of the vessel. The cap may fluidically seal the
vessel. The cap may form a fluid-tight seal with the vessel body.
For example, the cap may be impermeable to whole blood, serum or
plasma. In some instances, a portion of the cap may fit into a
portion of the vessel body. The cap may include a lip or shelf that
may hang over a portion of the vessel body. In some embodiments,
the cap may have a hollow or depression. The hollow or depression
may assist with guiding a second end of the channel to a center of
the cap. In some instances, when the sample collection device is in
an extended state, a second end of a channel 425a, 425b may lie
above the cap of the vessel. The second end of the channel may or
may not contact the vessel cap. In some instances, the second end
of the channel may rest within a hollow or depression of the cap.
In some instances, the second end of the channel may partially
penetrate the cap without reaching the interior of the vessel.
Optionally, some embodiments of the cap might include a crimping
piece to hold vacuum.
[0182] A second end of a channel may have an angled, tapered or
pointed end 427a and 427b. It should be understood that in some
embodiments, the ends 427a and 427b are part of a needle that is
formed separate from the channels 422a and 422b and then coupled to
the channels 422a and 422b. The needles may be formed of the same
or different material from the body defining the channels 422a and
422b. For example, some may use a metal to form the needles and a
polymer or plastic material for the body defining channels 422a and
422b. Optionally, some embodiments may form the ends 427a and 427b
on a member that is integrally formed with the channels 422a and
422b. In some instances, the second end of the channel may be
configured to penetrate a material, such as a cap 448a, 448b of the
vessel. The cap may be formed of a material that may prevent sample
from passing through in the absence of a penetrating member. The
cap may be formed from a single solid piece. Alternatively, the cap
may include a slit, opening, hole, thin portion, or any other
feature that may accept a penetrating member. A slit or other
opening may be capable of retaining sample therein, when the
penetrating member is not in the slit or opening, or when the
penetrating member is removed from the slit or opening. In some
instances, the cap may be formed from a self-healing material, so
that when a penetrating member is removed, the opening formed by
the penetrating member closes up. The second end of the channel may
be a penetrating member that may pass through the cap and into the
interior of the vessel. In some embodiment, it should be clear that
the penetrating member may be hollow needles that allow sample to
pass through, and not just needles for piercing. In some
embodiments, the piercing tip can be a non-coring design such as
but not limited to a tapered cannula that pierces without coring
the cap material.
[0183] One or more engagement assemblies may be provided. The
engagement assembly may include a channel holder 450 and/or a
force-exerting component, such as a spring 452 or elastic. In one
embodiment, the holder 450 may keep the adaptor channel 454 affixed
to the support. As will be described elsewhere herein, the adaptor
channel 454 may be formed integrally with the collection channel or
may be a discrete element that may be a stand-alone piece, part of
the collection channel, or part of the vessel. In one embodiment,
the holder 450 may prevent the adaptor channel 454 from sliding
relative to the support. The holder 450 may optionally provide a
support upon which a force-exerting component, such as a spring,
may rest.
[0184] In one example, the engagement assemblies may include a
spring 452 which may exert a force so that the base is at its
extended state, when the spring is at its natural state. When the
base is at its extended state, space may be provided between the
vessels 446a, 446b and the engagement assemblies. The second ends
of the channels 425a, 425b may be in a position where they are not
in fluid communication with the interiors of the vessels.
[0185] A sample collection device may have any number of engagement
assemblies. For example, the same number of engagement assemblies
may be provided as number of channels. Each channel may have an
engagement assembly. For example, if a first channel and a second
channel are provided, a first engagement assembly may be provided
for the first channel, and a second engagement assembly may be
provided for the second channel. In one embodiment, the same number
of engagement assemblies and vessels may be provided.
[0186] When the base is pressed in, the spring 452 may be
compressed. The second ends 425a, 425b of the channels may
penetrate the caps of the vessels. The second ends of the channels
may enter the interior of the vessel. In some instances, a force
may be provided to drive the fluid from the channels into the
vessels. For example, a pressure differential may be generated
between the first and second ends of the channels. A positive
pressure may be provided at the first end 423a, 423b of the
channels and/or a negative pressure may be provided at the second
end of the channels. The positive pressure may be positive relative
to the pressure at the second end of the channel, and/or ambient
air. The negative pressure may be negative relative to the pressure
at the first end of the channel and/or ambient air. In one example,
the vessels may have a vacuum therein. When the second end of a
channel penetrates a vessel, the negative pressure within the
vessel may pull the sample into the vessel. In alternative
embodiments, the sample may enter the vessel driven by capillary
forces, gravity, or any other motive force. In embodiments, the
vessel does not have a vacuum therein. There may be variations and
alternatives to the embodiments described herein and that no single
embodiment should be construed to encompass the entire
invention.
[0187] In some instances, different types of motive forces may be
used at different stages of sample collection. Thus, one type of
motive force may be used to draw the sample into the channel, and
then a different type of motive force may be used to move sample
from the channel into the vessel. For example, a capillary force
may draw the sample into a channel, and a pressure differential may
drive the sample from the channel into the vessel. Any combinations
of motive forces may be used to draw sample into the channel and
into the vessel. In some embodiments, the motive force(s) used to
draw sample into the channel is different from motive force(s) used
to draw sample into the vessel. In some alternative embodiments,
the motive force(s) may be the same for each stage. In some
embodiments, the motive force(s) are applied sequentially or at
defined time periods. By way of non-limiting example, motive
force(s) to draw sample into the vessel is not applied until the at
least one channel has reach a minimum fill level. Optionally,
motive force(s) to draw sample into the vessel is not applied until
the at least two channels have each reach a minimum fill level for
that channel. Optionally, motive force(s) to draw sample into the
vessel is not applied until all channels have each reach a minimum
fill level for that channel. In some embodiments, the motive
force(s) are applied simultaneously.
[0188] Some embodiments may use a pressurized gas source coupled to
the sample collection device and configured to push collected
bodily fluid from the one or more channels into their respective
vessels. Optionally, some may use a vacuum source not associated
with the vessels to pull sample fluid towards the vessels.
[0189] Additional, some embodiments of the channel may be
configured such that there is sufficient capillary force within the
channel such that once filled, the force is greater than that of
gravity so that sample does not escape from the channel based only
on gravitation force. An additional motive force is used to break
the hold of the capillary action of the channel(s). Optionally, as
described elsewhere herein, a device such as but not limited to a
sleeve may contain the bodily fluid from exiting the channel at the
end closest to the vessel, thus minimizing any loss until transfer
to the vessel is initiated.
[0190] Optionally, other materials such as but not limited to a
lyosphere, sponge, or other motive force provider may be used to
provide motive force that draws sample into the vessel. When
multiple forces are being used, this may be a primary, secondary,
or tertiary motive force to draw sample into the vessel.
Optionally, some embodiments may include a push-type motive force
provider such as but not limited to a plunger to move the sample in
a desired manner.
[0191] Some time may elapse after a sample has been introduced to a
channel for traveling along the length of the channel. A user may
introduce a sample to the sample collection device and may wait for
the sample to travel the length of the channel. One or more optical
indicator may be provided, which may indicate whether the sample
has reached a desired fill level, such as not limited to the end of
the channel. In other embodiments, the user may wait a
predetermined amount of time before pushing in the base. The base
may be pushed in after the user has determined the sample has
traveled a sufficient length of the channel and/or a sufficient
amount of time has passed since the sample was introduced. After
the base is pushed in, the channels may be brought into fluid
communication with the vessels, and sample may flow from the
channel into the vessels. An optical indicator may be provided so
that a user may know when the vessels have been filled.
[0192] Once the vessels have been filled, they may be transferred
to a desired location, using systems and methods described
elsewhere herein. In some instances, the entire sample collection
device may be transferred. The cap may be placed on the sample
collection device for transfer. In other embodiments, the base
portion and/or support portion may be removable from the rest of
the device. In one example, the base may be removed from the sample
collection device, and the vessels may be transferred along with
the base. Alternatively, the base may be removed from the sample
collection device to provide access to the vessels, and the vessels
may be removed from the device and transmitted. The removal of the
base may involve some disassembly of the sample collection device
to detach the base. This may involve using sufficient force to
overcome detents or stops built into the device to prevent
accidental disengagement. Optionally, some other positive act such
as but not limited to disengaging a latch or other locking
mechanism may be performed by a user before detaching the base.
Optionally, some embodiments may allow for removal of the vessels
without removal of the base, but allow for access to the vessels by
way of openings, access ports, or open-able covers on the base.
[0193] In some embodiments, one or more of the channels and/or
vessels may comprise features described elsewhere herein, such as
separation members, coatings, anti-coagulants, beads, or any other
features. In one example, the sample introduced to the sample
collection device may be whole blood. Two channels and respective
vessels may be provided. In this non-limiting example, each of the
channels has a coating such as but not limited to an anti-coagulant
coating in the channel. Such an anti-coagulant coating can serve
one or more of the following functions. First, the anti-coagulant
can prevent whole blood from clotting inside the channel during the
sample collection process. Depending on the amount of whole blood
to be collected, clotting could prematurely clog the channel before
sufficient amount of blood has been brought into the channel.
Another function is to introduce anti-coagulant into the whole
blood sample. By have the anti-coagulant in the channel, this
process can begin earlier in the collection process versus some
embodiments which may only have it the vessels 446a or 446b. This
early introduction of anti-coagulant may also be advantageous in
case the whole blood sample will be led along a pathway that may
have portions that are not coated with anti-coagulant, such as but
not limited to, the inner surfaces of a needle connected to the
channels 422a or 422b. Optionally, some embodiments may include
surfactants that can be used to modify the contact angle
(wettability) of a surface.
[0194] In some embodiments the inner surface of the channel and/or
other surfaces along the fluid pathway such as but not limited to
the sample inlet to the interior of a sample collection vessel may
be coated with a surfactant and/or an anti-coagulant solution. The
surfactant provides a wettable surface to the hydrophobic layers of
the fluidic device and facilitate filling of the metering channel
with the liquid sample, e.g., blood. The anti-coagulant solution
helps prevent the sample, e.g., blood, from clotting when provided
to the fluidic device. Exemplary surfactants that can be used
include without limitation, Tween, TWEEN.RTM.20, Thesit.RTM.,
sodium deoxycholate, Triton, Triton.RTM.X-100, Pluronic and/or
other non-hemolytic detergents that provide the proper wetting
characteristics of a surfactant. EDTA and heparin are non-limiting
anti-coagulants that can be used. In one non-limiting example, the
embodiment the solution comprises 2% Tween, 25 mg/mL EDTA in 50%
Methanol/50% H20, which is then air dried. A methanol/water mixture
provides a means of dissolving the EDTA and Tween, and also dries
quickly from the surface of the plastic. The solution can be
applied to the channel or other surfaces along the fluid flow
pathway by any technique that will ensure an even film over the
surfaces to be coated, such as, e.g., pipetting, spraying,
printing, or wicking.
[0195] It should also be understood for any of the embodiments
herein that a coating in the channel may extend along the entire
path of the channel. Optionally, the coating may cover a majority
but not all of the channel. Optionally, some embodiments may not
cover the channel in the areas nearest the entry opening to
minimize the risk of cross-contamination, wherein coating material
from one channel migrates into nearby channels by way of the
channels all being in contact with the target sample fluid at the
same time and thus having a connecting fluid pathway.
[0196] Although embodiments herein are shown with two separate
channels in the sample collection device, it should be understood
that some embodiments may use more than two separate channels.
Optionally, some embodiments may use less than two fully separate
channels. Some embodiments may only use one separate channel.
Optionally, some embodiments may use an inverted Y-channel that
starts initially as one channel and then splits into two or more
channels. Any of these concepts may be adapted for use with other
embodiments described herein.
[0197] Collection Device with Self-Supporting Collection
Channels
[0198] FIGS. 5A-5B provide another example of a sample collection
device 500 provided in accordance with an embodiment described
herein. The sample collection device may include a collection
device body 520, support 530, and base 540. In some instances, a
cap may be optionally provided. The collection device body may
contain one or more collection channels 522a, 522b defined by
collection tubes, which may be capable of receiving sample. A base
may have one or more optical indicator 542a, 542b that may provide
a visual indication of whether sample has reached one or more
vessel housed in the base. A support may have one or more optical
indicator 532a, 532b that may provide a visual indication of
whether sample has reached or passed through a portion of the
channels.
[0199] A collection device body 520 of a sample collection device
may contain at least a portion of one or more tubes with channels
522a, 522b therein. Optionally, the device collection body 520 may
also define channels that couple to channels 522a, 522b defined by
the tubes. In some embodiments, a portion of the channels may
extend beyond the collection device body. The channels may extend
beyond one end or two ends of the collection device body.
[0200] The collection device body 520 may be connected to a support
530. The support may contain a portion of one or more channels
therein. The collection device body may be permanently affixed to
the support or may be removable with respect to the support. In
some instances, the collection device body and the support may be
formed of a single integral piece. Alternatively, the collection
device body and support may be formed from separate pieces.
[0201] During the operation of the device the collection device
body 520 and support 530 may move relative to one another. In some
instances, a portion of the body 520 may be insertable within the
support 530 and/or a portion of the support may be insertable
within the body. The body may be capable of moving relative to the
support. In some instances, a sample collection device may have a
longitudinal axis extending along the length of the sample
collection device. The body and/or support may move relative to one
another in the direction of the longitudinal axis. The body and/or
support may be capable of moving a limited distance relative to one
another. The body and/or support may move co-axially without
rotational motion. Alternatively, rotational motion may be
provided.
[0202] The collection device body 520 may be formed from an
optically transmissive material. For example, the collection device
body may be formed from a transparent or translucent material.
Alternatively, the body may be formed from an opaque material. The
support 530 may be formed from an optically opaque, translucent, or
transparent material. The support may or may not have the same
optical characteristics of the collection device body. The support
may be formed from a different material as the collection device
body, or from the same material as the collection device body.
There may be variations and alternatives to the embodiments
described herein and that no single embodiment should be construed
to encompass the entire invention.
[0203] The collection device body, support, and/or base may have
any shape or size. In some examples, the collection device body,
support, and/or base may have a circular, elliptical, triangular,
quadrilateral (e.g., square, rectangular, trapezoidal), pentagonal,
hexagonal, octagonal, or any other cross-sectional shape. The
cross-sectional shape may remain the same or may vary along the
length. The cross-sectional shape may be the same for the body,
support, and base, or may vary. In some instances, the collection
device body, support, and/or base may have a cross-sectional area
of less than or equal to about 10 cm2, 7 cm2, 5 cm2, 4 cm2, 3 cm2,
2.5 cm2, 2 cm2, 1.5 cm2, 1 cm2, 0.8 cm2, 0.5 cm2, 0.3 cm2, or 0.1
cm2. The cross-sectional area may vary or may remain the same along
the length. The cross-sectional size may be the same for the
collection body, support, and/or base, or may vary. The collection
device body, support, and/or base may have a length of less than or
equal to about 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm,
5 cm, 4 cm, 3 cm, 2 cm, 1 cm, 0.5 cm, or 0.1 cm. The collection
device body may have a greater or lesser length than support or
base, or an equal length to the support, or base.
[0204] The channels 522a, 522b may be supported by the device body
520 and/or the support 530. In some instances, the entire length of
the tubes or the channels therein may be encompassed within the
combination of the device body and the support. Alternatively, the
channels may extend beyond the device body and/or support as seen
in FIG. 5. In some instances, the channels may extend beyond one
end of the device body/support combination, or beyond both ends. In
some instances, a portion of the channels may be within the device
body and a portion of the channels may be within the support. The
position of the channels may be affixed by the device body and/or
the support. In some instances, the channels may be affixed to
device body and/or not move relative to the device body. The
channels may be movable relative to the support. In some instances,
a plurality of channels may be provided. At least a portion of the
channels may be substantially parallel to one another. The channels
may be parallel to one another and/or a longitudinal axis extending
along a length of the sample collection device. Alternatively, no
portion of the channels need be parallel to one another. In some
instances, at least a portion of the channels are not parallel to
one another. The channels may be slightly bent. Optionally, they
may be straight, but aligned to be closer to one another as they
near the sample collection point. It should be understood that the
tubes defining the channels 522a and 522b may be made of optically
transparent, transmissive, or other material sufficient to provide
a detectable change that sample has reached a desired fill level in
at least one channel. Optionally, the detectable change can be used
to detect when both channels reach at least the desired fill
level.
[0205] A base 540 may be provided within the sample collection
device. The base may be connected to the support 530. In some
instances, a portion of the base 540 may insertable within the
support 530 and/or a portion of the support may be insertable
within the base. The base may be fixed relative to the support or
may be movable relative to the support. The base may be provided at
an end of the support opposite an end of the support connected to
the body. The base may be formed as a separate piece from the
support. The base may be separable from the support. Alternatively,
the base may be affixed to the support and/or formed as an integral
piece with the support.
[0206] A base 540 may house one or more vessel therein. The vessels
may be in fluidic communication with the channels and/or may be
brought into fluidic communication with the channels. An end of a
channel may be within the vessel or may be brought within the
vessel. A base may have one or more optical indicator 542a, 542b
that may provide a visual indication of whether sample has reached
one or more vessel housed in the base. In some embodiments, the
optical indicators may be optical windows that may enable a user to
see into the base. The optical window may be formed from a
transparent and/or translucent material. Alternatively, the optical
window may be an opening without any material therein. The optical
window may enable a user to directly view a vessel within the base.
The vessel within the base may be formed from a transparent and/or
translucent material that may enable a user to see if a sample has
reached the vessel of the base. For example, if blood is
transported along the channel to the vessels, the vessels may show
the blood therein. In other embodiments, the optical indicators may
include other features that may indicate the vessel has been
filled. For example, one or more sensor may be provided within the
base or vessel that may determine whether a sufficient amount of
sample has been provided within the vessel. The sensor may provide
a signal to an optical indicator on the base that may indicator
whether the sample has been provided to the vessel and/or the
amount of sample that has been provided to the vessel. For example,
the optical indicator may include a display, such as an LCD
display, light display (e.g., LED display), plasma screen display
that may provide an indication that the vessels have been
sufficiently filled. In alternative embodiments, an optical
indicator need not be provided, but alternative indicators may be
provided, such as but not limited to, an audio indicator,
temperature controlled indicator, or other device that may indicate
by a detectable signal, such as one detectable by a user, when the
vessels have been filed.
[0207] A support 530 may have one or more optical indicator 532a,
532b that may provide a visual indication of whether sample has
reached or pass through a portion of a channel housed by the
support. In some embodiments, the optical indicators may be optical
windows that may enable a user to see into the support. The optical
window may be formed from a transparent and/or translucent
material. Alternatively, the optical window may be an opening
without any material therein. The optical window may enable a user
to directly view a portion of a channel within the support. The
channels may be formed from a transparent and/or translucent
material that may enable a user to see if a sample has reached the
portion of the channel underlying the optical window. In other
embodiments, the optical indicators may include other features that
may indicate the sample has passed through a portion of the
channel, such as sensors described elsewhere herein.
[0208] Referring now to FIGS. 6A-6B, additional views of a sample
collection device 500 are provided in accordance with one
embodiment described herein.
[0209] In some embodiments, a portion of the tubes containing
channels 522a, 522b may extend beyond the collection device body
520. The portion of the channels that extend beyond may include
portions of the channels that are configured to receive a sample
from the subject. In one example, the channels may have a first end
523a, 523b that may be a sample receiving end of the channels.
[0210] The channels may optionally be defined by a rigid material.
Alternatively, the channels may be defined by a flexible material
or may have flexible components. The channels may or may not be
designed to bend or curve. The channels may or may not be
substantially parallel to one another. In some instances, the first
ends of the channels may be some distance apart when in a relaxed
state. The first ends of the channels may remain that distance
apart during operation of the device. Alternatively, the first ends
of the channels may be brought closer together. For example, the
first ends of the channels may be squeezed together. Each open end
of the channels may separately receive a sample. The sample may be
received sequentially. The sample may be from the same subject.
Alternatively, the channels may be capable of receiving the same
sample simultaneously.
[0211] The channels 522a, 522b may include one or more features or
characteristics mentioned elsewhere herein. At least a portion of
the channels may be substantially parallel to one another.
Alternatively, the channels may be at angles relative to one
another. In some embodiments, the channels may have a first end
that may be at a sample receiving end 526 of the sample collection
device. The first end of a channel may be an open end capable of
receiving a sample. In some embodiments, the ends of each of the
channels may be provided at the sample receiving end of the sample
collection device. One, two, or more channels may have a first end
at the sample receiving end of the sample collection device.
[0212] In some embodiments, the device body 520 may be movable
relative to the support 530. A portion of the device body may be
insertable within the support or vice versa. In one example, the
device body may have a lip 527 and an interior portion 529. The lip
may have a greater cross-sectional area than the interior portion.
The interior portion may be capable of being inserted into the
support. The lip may act as a stop to prevent the entire body from
being inserted into the support. The lip may rest on a shoulder of
the support.
[0213] FIGS. 7A-7B shows partial cutaway views of an example of a
sample collection device 700 provided in accordance with an
embodiment described herein. The sample collection device in an
extended state, prior to bringing the channels 722a, 722b into
fluid communication with one or more vessels 746a, 746b housed
within a base 740 of the device. The sample collection device may
include a body 720, support 730, and base 740. The body and/or
support may support and/or encompass at least a portion of one, two
or more channels. The base may support and/or encompass one, two or
more vessels. There may be variations and alternatives to the
embodiments described herein and that no single embodiment should
be construed to encompass the entire invention.
[0214] In one embodiment, a body 720 and/or support 730 may support
one or more channels 722a, 722b in a sample collection device. In
one example, two channels are provided, though descriptions
relating to a two-channel embodiment may apply to any number of
channels including but not limited to 1, 3, 4, 5, 6 or more
channels. Each of the channels may have a first end 723a, 723b that
may be a sample receiving end of the device. The first ends of the
respective channels may be open. The channels may be open to
ambient air. When the first ends of the channels contact a fluid,
such as blood, the fluid may be drawn into the channels. Fluid may
be drawn in via capillary action, or any other of the techniques
described elsewhere herein. The fluid may travel along the length
of the channels to the respective second ends of the channels. The
channels may be fluidically segregated from one another. For
example, a fluid may enter a first channel 722a via a first end
723a, pass through the length of the channel, and exit the first
channel at the second end. Similarly, fluid may enter a second
channel 722b via a first end 723b, pass through the length of the
channel, and exit the second channel at the second end. The first
and second channels may be fluidically segregated so that fluid
from the first channel does not pass into the second channel and
vice versa. In some embodiments, the fluid may pass to the second
ends of the channels without exiting initially.
[0215] The channels 722a, 722b may have a parallel configuration.
For example, the first ends 723a, 723b of the channels may be about
the same distance apart as the second ends of the channels. The
first ends of the channels may or may not be in contact with one
another.
[0216] A support 730 may have one or more optical indicators, such
as optical windows 732a, 732b. The optical windows may be
positioned over the channels 722a, 722b. In some instances, the
optical windows may be positioned over portions of the channels. A
single window may provide a view to a single channel portion or to
multiple channel portions. In one example, the same number of
optical windows may be provided as channels. Each optical window
may correspond to a respective channel. Both the optical window and
channels may be formed of an optically transmissive material that
may permit a user to view whether a sample has reached and/or
passed through the underlying portion of the channel from outside
the sample collection device. Such determination may be useful in
determining when to compress the sample collection device.
[0217] A base 740 may be connected to a support 730 of the sample
collection device. The base may or may not directly contact the
support. The base may be fixed relative to the support during use
of the device. In some instances, the base may be removable from
the support. A portion of the base may be insertable into the
support and/or vice versa. In some embodiments, the base may slide
out from the support in a longitudinal direction relative to the
support. In some instances, the base may slide co-axially with the
support without rotating. In some instances, a base may rotate
while moving relative to the support.
[0218] The base 740 may be capable of supporting one or more
vessels 746a, 746b. The base may have a housing that may at least
partially surround the one or more vessels. In some instances, the
vessels may be completely surrounded when the base is engaged with
a support 730. The height of the base may extend beyond the height
of the vessels. Alternatively, the height of the base may extend to
the same degree or less than the height of the vessels. The base
may have one or more indentation, protrusion, groove, or shaped
feature to accept the vessels. The base may be formed with a shape
that is complementary to the shape of the vessels. For example, the
base may have one or more tube shaped indentation into which tube
shaped vessels may snugly fit. The vessels may friction-fit into
the base. The vessels may be maintained in an upright position
relative to the base. There may be variations and alternatives to
the embodiments described herein and that no single embodiment
should be construed to encompass the entire invention.
[0219] The same number of vessels may be provided as the number of
channels. For example, if N channels are provided, then N vessels
may be provided, wherein N is a positive whole number (e.g., 1, 2,
3, 4, 5, 6, 7, 8, or more). Each channel may correspond to a
respective vessel. In one example, a sample collection device may
have a first channel and a second channel, as well as a respective
first vessel and second vessel. A first channel 722a may be in or
may be configured to be brought into fluid communication with a
first vessel 746a, and a second channel 722b may be in or may be
configured to be brought into fluid communication with a second
vessel 746b.
[0220] In some embodiments, each vessel may have a body 749a, 749b
and a cap 748a, 748b. The vessels may have any features or
characteristics as described elsewhere herein.
[0221] A base 740 may have one or more optical indicators, such as
optical windows 742a, 742b. The optical windows may be positioned
over the vessels 746a, 746b. In some instances, the optical windows
may be positioned over the vessel bodies. A single window may
provide a view to a single vessel or to multiple vessels. In one
example, the same number of optical windows may be provided as
vessels. Each optical window may correspond to a respective vessel.
Both the optical window and vessels may be formed of an optically
transmissive material that may permit a user to view whether a
sample has reached the vessel from outside the sample collection
device. Such visual assessment may be useful in determining when
the sample has reached the vessels, and when the base can be
removed from the sample collection device.
[0222] One or more engagement assemblies may be provided. The
engagement assembly may include a channel holder 750 and/or a
force-exerting component, such as a spring 752 or elastic. In one
embodiment, the holder 750 may keep the adaptor channel 754 affixed
to the support. As will be described elsewhere herein, the adaptor
channel 754 may be formed integrally with the collection channel or
may be a discrete element that may be a stand-alone piece, part of
the collection channel, or part of the vessel. In one embodiment,
the holder 750 may prevent the adaptor channel 754 from sliding
relative to the support. The holder 750 may optionally provide a
support upon which a force-exerting component, such as a spring,
may rest.
[0223] In one example, the engagement assemblies may include a
spring 752 which may exert a force so that the body 720 is at an
extended state, when the spring is at its natural state. When the
body is at its extended state, space may be provided between the
vessels 746a, 746b and the engagement assemblies. When a body is in
its extended state, the interior portion 729 of the body may be
exposed and/or uncovered by the support 730. In some instances,
when the body is in its extended state, the second ends of the
channels 722a, 722b may or may not contact the caps of the vessels.
The second ends of the channels may be in a position where they are
not in fluid communication with the interiors of the vessels. There
may be variations and alternatives to the embodiments described
herein and that no single embodiment should be construed to
encompass the entire invention.
[0224] A sample collection device may have any number of engagement
assemblies. For example, the same number of engagement assemblies
may be provided as number of channels. Each channel may have an
engagement assembly. For example, if a first channel and a second
channel are provided, a first engagement assembly may be provided
for the first channel, and a second engagement assembly may be
provided for the second channel. The same number of engagement
assemblies and vessels may be provided.
[0225] FIGS. 8A-8B provide an example of a sample collection device
800 having channels 822a, 822b that are in fluid communication with
the interior of vessels 846a, 846b within the device. The sample
collection device may include a body 820, support 830, and base
840. The body and/or support may support and/or encompass at least
a portion of one, two or more channels. The channels may extend
beyond an end of the body. The base may support and/or encompass
one, two or more vessels.
[0226] In one embodiment, a body 820 and/or support 830 may support
one or more channels 822a, 822b in a sample collection device. For
example, a first channel and second channel may be provided. Each
of the channels may have a first end 823a, 823b that may be
provided at a sample receiving end of the device that may extend
beyond the body. The first ends of the respective channels may be
open. The channels may be open to ambient air. The channels may be
rigid or may be flexible. In some embodiments, the channels may
have a length that may permit them to be bent into contact with one
another. When the first ends of the channels contact a fluid, such
as blood, the fluid may be drawn into the channels. Each channel
end may be separately contacted to a fluid, which is drawn into the
respective channel. This may involve angling the sample collection
device so that only one opening into the channel is in contact with
the sample fluid at any one time. Alternatively, all channels may
be simultaneously contacted to the same sample which is
simultaneously drawn into the respective channels. Alternatively,
multiple but not all channels may be simultaneously contacted to
the same sample which is then simultaneously drawn into the
respective channels. The fluid may be drawn in via capillary
action, or any other of the techniques described elsewhere herein.
The fluid may travel along the length of the channels to the
respective second ends of the channels. In some embodiments, the
fluid may reach the second ends of the channels via capillary
action or other techniques described herein. In other embodiments,
the fluid need not reach the second ends of the channels. The
channels may be fluidically segregated from one another.
[0227] In some embodiments, the fluid may pass to the second ends
of the channels without exiting when the channels are not in fluid
communication with the interiors of the vessels 846a, 846b. For
example, the fluid may be drawn into the channel via capillary
action, which may cause the fluid to flow to or near the end of the
channel without causing the fluid to exit the channel.
[0228] The body 820 may be movable relative to the support 830
during use of the device. In some embodiments, the body may slide
in a longitudinal direction relative to the support. In one
example, the body may have (i) an extended position where the
channels are not in fluid communication with the interior of the
vessels, and (ii) a compressed position where the channels are in
fluid communication with the interior of the vessels. A sample
collection device may be initially provided in an extended state,
as shown in FIG. 7. After the sample has been collected and flown
through the length of the channel, a user may push the body in to
provide the sample collection device in its compressed state, as
shown in FIG. 8. In some instances, when the body is in an extended
state, an interior portion of the body is exposed. When the body is
in a compressed state, the interior portion of the body may be
covered by the support. A lip of the body may contact the support.
Once the body has been pushed in, the body may naturally remain
pushed in, or may spring back out to an extended state, once the
pushing force is removed. In some instances, a body may be pulled
out to an extended state, or may be pulled out completely to
provide access to vessels therein. Optionally, in some assemblies,
removal of the body will not provide access to the vessels.
[0229] A base 840 may be connected to a support 830 of the sample
collection device. The base 840 may be capable of supporting one or
more vessels 846a, 846b. The base may have a housing that may at
least partially surround the one or more vessels. In some
instances, the vessels may be completely surrounded when the base
is engaged with a support 830. The base may have one or more
indentation, protrusion, groove, or shaped feature to accept the
vessels. The base may be formed with a shape that is complementary
to the shape of the vessels. The vessels may be maintained in an
upright position relative to the base.
[0230] The same number of vessels may be provided as the number of
channels. Each channel may correspond to a respective vessel. In
one example, a sample collection device may have a first channel
and a second channel, as well as a respective first vessel and
second vessel. A first channel 822a may be in or may be configured
to be brought into fluid communication with a first vessel 846a,
and a second channel 822b may be in or may be configured to be
brought into fluid communication with a second vessel 846b. The
first channel may initially not be in fluid communication with a
first vessel and the second channel may initially not be in fluid
communication with the second vessel. The first and second channels
may be brought into fluid communication with the interiors of the
first and second vessels respectively when the body is pushed in
relative to the support. The first and second channels may be
brought into fluid communication with the first and second vessels
simultaneously. Alternatively, they need not be brought into fluid
communication simultaneously. The timing of the fluid communication
may depend on the height of the vessel and/or the length of the
channel. The timing of the fluid communication may depend on the
relative distances between the second end of the channel and the
vessel.
[0231] In some embodiments, each vessel may have a body 849a, 849b
and a cap 848a, 848b. The vessel body may have a tubular shape. In
some instances, the vessel body may have a cylindrical portion. The
bottom of the vessel may be flat, tapered, rounded, or any
combination thereof. The vessels may comprise an open end and a
closed end. The open end may be a top end of the vessel, which may
be at the end of the vessel closer to one or more channel. The
closed end may be a bottom end of the vessel, which may be at the
end of the vessel further from one or more channel. There may be
variations and alternatives to the embodiments described herein and
that no single embodiment should be construed to encompass the
entire invention.
[0232] A support 830 may have one or more optical indicators, such
as optical windows 832a, 832b. The optical windows may be
positioned over portions of the channels 822a, 822b. The optical
windows may provide an indicator of whether a sample has reached
and/or passed through the portion of the channels shown by the
optical windows. This may be useful to assess whether the sample
has flowed sufficiently for the user to push the body into the
sample collection device. In some instances, it may be desirable
for the sample to reach the second end of the channels, or to near
the second end of the channels, before causing the channels to
enter into fluid communication with the vessels. In some instances,
the sample may need to reach a certain portion of the channel
before pushing the body in to bring the channels into fluid
communication with the vessels. The certain portion of the channel
may underlie the optical windows.
[0233] A base 840 may have one or more optical indicators, such as
optical windows 842a, 842b. The optical windows may be positioned
over the vessels 846a, 846b. In some instances, the optical windows
may be positioned over the vessel bodies. The optical windows may
provide an indicator of whether a sample has entered the vessels.
The optical windows may show how much sample has filled the
vessels. This may be useful to assess whether a sufficient amount
of sample has entered the vessels. In some instances, it may be
desirable for a particular amount of sample to enter the vessels
before removing the vessels from fluid communication with the
channels. A predetermined volume of sample in the vessels may be
desired before removing a base of the device, thereby bringing the
vessels out of fluid communication with the channels.
[0234] The vessels and/or interfaces with the channels may have any
characteristic or feature, such as those described elsewhere
herein. In some instances, a second end of the channel may
penetrate a cap of the vessel, thereby bringing the channel into
fluid communication with the vessel. In some instances, the channel
may be withdrawn from the vessel, and the cap of the vessel may
form a fluid-tight seal, thereby permitting a fluid-tight
environment within the vessel when the channel is brought out of
fluid communication with the vessel.
[0235] One or more engagement assembly may be provided. The
engagement assembly may include a channel holder and/or a
force-exerting component, such as a spring or elastic. The holder
may keep the channel affixed to the body. The holder may prevent
the channel from sliding relative to the body. The holder may
optionally provide a support upon which a force-exerting component,
such as a spring, may rest.
[0236] In one example, the engagement assemblies may include a
spring which may exert a force so that the body is at its extended
state, when the spring is at its natural state. When the body is at
its extended state, space may be provided between the vessels 846a,
846b and the bottom portion of the sample body 820. The second ends
of the channels may be in a position where they are not in fluid
communication with the interiors of the vessels.
[0237] When the body is pressed in, the spring 852 may be
compressed (see also FIGS. 9A-9C). The second ends of the channels
may penetrate the caps of the vessels. The second ends of the
channels may enter the interior of the vessel. In some instances, a
force may be provided to drive the fluid from the channels into the
vessels. For example, a pressure differential may be generated
between the first and second ends of the channels. A positive
pressure may be provided at the first end 823a, 823b of the
channels and/or a negative pressure may be provided at the second
end of the channels. The positive pressure may be positive relative
to the pressure at the second end of the channel, and/or ambient
air. The negative pressure may be negative relative to the pressure
at the first end of the channel and/or ambient air. In one example,
the vessels 846a and 846b may each have a vacuum therein. When the
second end of a channel penetrates a vessel, the negative pressure
within the vessel may suck the sample into the vessel. In
alternative embodiments, the sample may enter the vessel driven by
capillary forces, gravity, or any other motive force. Optionally,
there may be single or multiple combinations of forces to fill the
vessel with fluid.
[0238] In some instances, different types of motive forces may be
used to draw the sample into the channel, and from the channel into
the vessel. For example, a capillary force may draw the sample into
a channel, and a pressure differential may drive the sample from
the channel into the vessel. Any combinations of motive forces may
be used to draw sample into the channel and into the vessel.
[0239] Some time may elapse after a sample has been introduced to a
channel for traveling along the length of the channel. A user may
introduce a sample to the sample collection device and may wait for
the sample to travel the length of the channel. One or more optical
indicator along the length of the channel may be provided, which
may indicate whether the sample has reached the end of the channel.
In other embodiments, the user may wait a predetermined amount of
time before pushing in the body. The body may be pushed in after
the user has determined the sample has traveled a sufficient length
of the channel and/or a sufficient amount of time has passed since
the sample was introduced. The body may have a flat surface which
may be easy for the user to push. In some instances, the flat
surface may have a cross-sectional area that may be sufficient for
a user's fingers to press down on the body. After the body is
pushed in, the channels may be brought into fluid communication
with the vessels, and sample may flow from the channel into the
vessels. An optical indicator may be provided so that a user may
know when the vessels have been filled.
[0240] Once the vessels have been filled, they may be transferred
to a desired location, using systems and methods described
elsewhere herein. As previously described, the entire sample
collection device may be transferred. In other embodiments, the
base portion may be removable from the rest of the device. In one
example, the base may be removed from the sample collection device,
and the vessels may be transferred along with the base.
Alternatively, the base may be removed from the sample collection
device to provide access to the vessels, and the vessels may be
removed from the device and transmitted
[0241] Referring now to FIGS. 9A-9C, examples of a sample
collection device 900 and method of use will now be described. In
one nonlimiting example, the device may have a body 920, support
930, and base 940. The body 920, support 930, and base 940 may be
movable relative to one another. In some instances, the various
components of the devices may be movable during different stages of
use. Examples of stages of use may include when the device is in an
extended state, compressed state, and separated state.
[0242] FIG. 9A shows an example of the device 900 in an extended
state. The body 920 may be extended relative to the support.
Channels 922a, 922b configured to transport a sample may be affixed
to the body. A first end of a channel may extend out from the body
and/or the rest of the sample collection device. A second end of
the channel may be within and/or encompassed by a portion of the
sample collection device. The channel may be fluidically isolated
from a respective vessel housed by the base 940. The support 930
may be positioned between the body and base. The support may at
least partially encompass a portion of the channel. In some
instances, the support may encompass the second end of the
channel.
[0243] When in an extended state, the device may have an extended
length. The length of the device may be from the bottom of the base
to the first end of the channels. Alternatively, the length of the
device may be measured from the bottom of the base to the top of
the body.
[0244] As seen in FIG. 9A, the device 900 may be in an extended
state when the sample is introduced to the device. For example, a
sample may be contacted by at least a first end of a channel. The
sample may be drawn into the channel via capillary action or any
other technique or motive force described herein. The forces may
act alone or in combination to draw sample into the device. The
device 900 may remain in an extended state while the sample is
traversing the channel. The sample may fill the entire length of
the channel, a portion of the length of the channel, or at least a
minimum portion to meet a desired sample acquisition volume.
[0245] FIG. 9B shows an example of the device 900 in a compressed
state. The body 920 may be compressed relative to the support. The
channels 922a, 922b may be affixed to the body. The channels may be
fluidic communication with their respective vessels. When the
device is brought into a compressed state, a first channel may be
brought into fluid communication with an interior of a first
vessel, and a second channel may be brought into fluid
communication with an interior of a second vessel.
[0246] By way of nonlimiting example, a user may push the body 920
toward the support 930 (or vice versa) to bring the device into a
compressed state. The relative motion between parts may involve
movement of both pieces. Optionally, movement may involve moving
only one of them. In the present example, the body 920 may be
pushed all the way to the support 930 so that no interior portion
of the body is exposed and/or a lip of the body contacts the
support. Any stop mechanism may be used that may be engaged when
the device is completely compressed. Alternatively, the body may
only be partially pushed. For example, a portion of the interior
portion of the body may be exposed. The support may be positioned
between the body and base. The support may at least partially
encompass a portion of the channel. In some instances, the second
end of the channel may extend beyond the support of the device.
[0247] When in a compressed state, it should be understood that the
device 900 may have a compressed length. The length of the device
900 may be from the bottom of the base to the first end of the
channels. Alternatively, the length of the device may be measured
from the bottom of the base to the top of the body. The compressed
length of the device may be less than the extended length of the
device. In some embodiments, the compressed length of the device
may be at least about 0.1 cm, 0.5 cm, 1.0 cm, 1.5 cm, 2.0 cm, 2.5
cm, 3.0 cm, 3.5 cm, 4.0 cm, or 5.0 less than the extended length of
the device. The compressed length of the device may be less than or
equal to about 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97% or 99%
of the extended length of the device.
[0248] One or more engagement assemblies may be provided with the
device 900. The engagement assembly may include a channel holder
950 and/or a force-exerting component, such as a spring 952 or
elastic. The holder 950 may keep the adaptor channel 954 affixed to
the support. As will be described elsewhere herein, the adaptor
channel 954 may be formed integrally with the collection channel or
may be a discrete element that may be a stand-alone piece, part of
the collection channel, or part of the vessel. In one embodiment,
the holder 950 may prevent the adaptor channel 954 from sliding
relative to the support. The holder 950 may optionally provide a
support upon which a force-exerting component, such as a spring,
may rest. The force-exerting component, such as a spring may be in
a compressed state when the device is in a compressed state. The
spring may exert a force on the body of the device when the device
is in a compressed state.
[0249] The device may be in a compressed state when the sample is
transferred from the channels to the respective vessels. In some
examples, the transfer may occur via pressure differential between
the channels and the interiors of the vessels, when they are
brought into fluidic communication. For example, a second end of
the channel may be brought into fluidic communication with the
interior of the vessel. The vessel may have a vacuum and/or
negative pressure therein. The sample may be sucked into the vessel
when the channel is brought into fluidic communication with the
vacu-vessel. The device may remain in a compressed state while the
sample is being transferred to the vessel. The sample may fill the
entire vessel or a portion of the vessel. The entirety of the
sample (and/or greater than 90%, 95%, 97%, 98%, 99%, 99.5% or 99.9%
of the sample) from the channels may be transferred to the vessels.
Alternatively, only a portion of the sample from the channels may
be transferred to the vessels.
[0250] Referring now to FIG. 9C, an example of a device 900 in a
separated state will now be described. The base 940 may be
separated from the rest of the device 900. The body 920 may be
extended or compressed relative to the support 930. In one example,
the extended state may be the natural state, so that when the force
is no longer exerted on the body by the user, the body may extend
back to the extended state. The channels 922a, 922b may be affixed
to the body.
[0251] When the device 900 is in a separated state, the base 940
may be separated from the support 930 of the device. The channels
922a, 922b may be removed from fluidic communication with their
respective vessels 946a, 946b. When the device 900 is brought into
the separated state, a first channel may be brought out of fluid
communication with an interior of a first vessel, and a second
channel may be brought out of fluid communication with an interior
of a second vessel. This may occur sequentially or simultaneously.
When the channels are removed from the vessels, the vessels may
assume a sealed state to prevent undesired material from entering
the vessels. In some embodiments, the vessels may be fluid-tight
after removal of the channels. Optionally, the vessels may be
gas-tight after removal of the channels.
[0252] A user may separate the base 940 from the support 930 to
bring the device into a separated state to remove the vessels
therein. In some embodiments, the base may be separated from the
support or vice versa. Separating the base from the support may
expose the vessels 946a, 946b that are supported by the base. The
vessels may be press-fit or otherwise held within the base. The
vessels 946a, 946b may be removable from the base. By way of
non-limiting example, removing the vessels 946a, 946b allows them
to be placed with other vessels in a climate controlled transport
container for transport to a receiving site such as but not limited
to an analysis site. Optionally, the vessels 946a, 946b may be
removed to allow for pre-treatment such as but not limited to
centrifugation prior to being sent on for processing at a receiving
site such as but not limited to an analysis site. Alternatively,
the vessels 946a, 946b may remain with the base.
[0253] FIGS. 10A-10B provide additional views of a sample
collection device 1000 in a separated state. When in a separated
state, the base 1040 may be separated (partially or completely)
from the support 1030 and/or body 1020 of the device. This allows
for the removal of the vessels 1046a and 1046b through the end of
base 1040 previously not externally exposed when the device 1000
was not in a separate state.
[0254] When the device is in a separated state, one or more
channels 1022a, 1022b may be fluidically isolated from one or more
vessels 1046a, 1046b housed by the base 1040. The vessels may be
fluidically sealed from their environment. The vessels may contain
sample therein, that had been transported through the collection
channels, reached a minimum fill level, and then substantially
fully deposited into the respective vessels. The base 1040 may
include one or more optical indicator 1046a, 1046b. The optical
indicator may show a portion of the vessels therein such that the
device 1000 is not moved into the separate state until a minimum
fill level has been reached in the vessels. By way of non-limiting
example, the vessels may have an optically transmissive material
that may permit a user to view the sample within the vessels from
outside the base.
[0255] In some embodiments, the base 1040 may encompass at least a
portion of the vessels. The base may have a hollow interior and
walls surrounding the hollow interior. The base may have one or
more shaped feature that may support the vessels. The vessels may
be provided within the hollow interior. The walls may surround the
vessel. The base may have an open top though which the vessels may
be exposed. The vessels may or may not be removed through the open
top.
Collection Device with Multiple Collection Channels
[0256] Referring now to FIGS. 11A-11F, a still further embodiment
as described herein will now be described. This embodiment provides
a bodily fluid sample collection device 1100 for use in collecting
a fluid sample that may be pooled or otherwise formed on a surface,
such as but not limited to the skin or other target area of a
subject. Although this embodiment shows a device body which defines
at least two collection channels of different volumes therein, it
should be understood that devices with fewer or greater numbers of
collection channels are not excluded. Embodiments where the same
collection volume is used for one or more the channels are also not
excluded. There may be variations and alternatives to the
embodiments described herein and that no single embodiment should
be construed to encompass the entire invention.
[0257] FIG. 11A shows a perspective view of one embodiment of a
bodily fluid sample collection device 1100 with a distal end 1102
configured to engage a fluid sample on a surface. In this
embodiment, the distal end 1102 may have a configuration designed
to better engage a droplet or pool of bodily fluid or sample formed
on a surface. Some embodiments, in addition to a desired shape, may
also have surface treatments at the distal end 1102, such as but
not limited to, chemical treatments, texturing, surface features,
or coatings to encourage fluid flow towards the one or more
openings 1104 and 1106 on the distal end 1102 leading to the
channels in the device 1100.
[0258] As seen in FIG. 11A, this embodiment of the sample
collection device 1100 has two openings 1104 and 1106 for receiving
the sample fluid. It should be understood that some embodiments may
have more than two openings at the distal end. Some embodiments may
only have one opening at the distal end. Optionally, some
embodiments may have additional openings along a side or other
surfaces leading away from the distal end 1102 of the device 1100.
The openings 1104 and 1106 may have any cross-sectional shape. In
some non-limiting examples, the openings may have a circular,
elliptical, triangular, quadrilateral (e.g., square, rectangular,
trapezoidal), pentagonal, hexagonal, octagonal, or any other
cross-sectional shape. The cross-sectional shape may remain the
same or may vary along the length of the collection device body. In
some instances, the openings may have a cross-sectional area of
less than or equal to about 2 mm.sup.2 1.5 mm.sup.2, 1 mm.sup.2,
0.8 mm.sup.2, 0.5 mm.sup.2, 0.3 mm.sup.2, or 0.1 mm.sup.2. Some
embodiments have the opening be the same shape. Others may use
different shapes for the one or more openings.
[0259] The sample fill portion 1120 which may be the body of the
sample collection device 1100 may be formed from a transparent
and/or translucent material that may enable a user to see if a
sample has entered sample collection channel(s) (see FIG. 11B) in
the sample fill portion 1120. In some embodiments, the entire
sample fill portion 1120 is transparent or translucent.
Alternatively, some embodiments may only have all areas over the
channel or only select portions of the channel or sample fill
portion 1120 be transparent or translucent to allow a user to
visualize the filling of sample into the sample collection device
1100. Optionally, the sample fill portion is made of an opaque
material but has an opening or a window to allow for visualization
of fill level therein. The device 1100 may further include one or
more visualization windows 1112 and 1114 to allow a user to see
when a desired fill level has been reached. The visualization
window may be formed from a transparent and/or translucent
material. Alternatively, the visualization window may be an opening
without any material therein. Additional visualization windows can
also be used to determine of all of the fluid in the collection
channels have been emptied into the vessels 1146a and 1146b (see
FIG. 11B).
[0260] FIG. 11A also shows that some embodiments of support 1130
may have optical windows 1132 and 1134 which are positioned to show
fill levels in the vessels 1146a and 1146b to show if the vessels
in base 1140 have been moved into position to receive sample fluid.
Optionally, the windows 1132 and 1134 may be cutouts that act as
guides for the snap feature of based in order to define the start
and end positions during activation. It should be understood that
the base can be configured to hold one or more sample vessels. By
way of example and not limitation, the entire base 1140 can be
removed from the sample collection device before or after sample
fill. The base 1140 can be used as holder to retain the sample
vessels therein during transport, and in such an embodiment, the
base 1140 along with the sample vessels would be loaded into a
shipping tray or other holder for transport. Alternatively, some
embodiments may remove the sample vessels from the base 1140 and
then transport the vessels without the base 1140 holding them.
[0261] FIG. 11B shows a cross-sectional view along section lines
B-B of the embodiment shown in FIG. 11C. FIG. 11B shows the
channels 1126 and 1128 in the portion 1120. The sample fill portion
1120 may be formed from two or more pieces which join together to
define the portion 1120. Some may define the channels in one piece
and then have another piece which mates to the first piece to
define an opposing or top wall surface of the channel. In terms of
manufacturing, this allows one piece to have channels molded or
otherwise formed into the body and the opposing piece will mate to
act as a cover for the channels or may also include portions of the
channel too. The channels 1126 and 1128 may be formed only in
portion 1120 or may also extend into support 1130 that has features
to connect with the vessels held in base or carrier 1140. Some
embodiments may integrally form portions 1120 and 1130 together.
Support 1130 may also be configured to hold adapter channel 1150
which will fluidically connect the channels 1126 and 1128 with
their respective vessels 1146a and 1146b.
[0262] Although these embodiments herein are described using two
channels and two vessels, it should be understood that other
numbers of channels and vessels are not excluded. Some embodiments
may have more channels than vessels, wherein some channels will
couple to the same vessel. Some embodiments may have more vessels
than channels, in which case multiple vessels may operably couple
to the same channel.
[0263] As seen in FIG. 11B, the channels 1126 and 1128 may be of
different sizes. This allows for different fluid volumes to be
collected in each channel before they are simultaneously
transferred into the vessels 1146a and 1146b. Optionally, some
embodiments may have the channels 1126 and 1128 sized to contain
the same volume of fluid. In some embodiments, the fluid pathway of
the channels 1126 and 1128 are shaped and/or angled so that
openings near the distal end 1102 are closer together than proximal
ends, which may be further apart to align them for entry into the
vessels 1146a and 1146b. There may be variations and alternatives
to the embodiments described herein and that no single embodiment
should be construed to encompass the entire invention.
[0264] FIG. 11B also shows that some embodiments may use needles
for the adapter channels 1150 and 1152 in the body 1130 which are
in communication with the channels 1126 and 1128. The needles each
has a channel to allow for fluid to pass therethrough from the
collection channels 1126 and 1128 to the ends of the needles. As
seen in FIG. 11B, the vessels 1146a and 1146b in the base 1140 are
slidable relative to the support 1130 as indicated by arrow 1156.
Relative motion between support 1130 and base 1140 can close the
gap 1154. Closing the gap 1154 brings the adapter channels 1150
into the cap 1148a of the vessel 1146a until there is fluid
communication between the interior of vessel 1146a and the
collection channel 1126. At that time, motive force in the form
will then move fluid in the channel 1126 into the vessel 1146a.
[0265] By way of example and not limitation, any combinations of
motive forces may be used to draw sample into the vessel. Some
embodiment may use pull from vacuum in the vessels 1146a to draw
sample into the vessel. Some may use pushing force from external
pressure to move fluid into the vessel. Some embodiments may use
both. Some may rely on capillary and/or gravity. In some
embodiments, the motive force(s) used to draw sample into the
channel is different from motive force(s) used to draw sample into
the vessel. In some alternative embodiments, the motive force(s)
may be the same for each stage. In some embodiments, the motive
force(s) are applied sequentially or at defined time periods. By
way of non-limiting example, motive force(s) to draw sample into
the vessel is not applied until the at least one channel has reach
a minimum fill level. Optionally, motive force(s) to draw sample
into the vessel is not applied until the at least two channels have
each reach a minimum fill level for that channel. Optionally,
motive force(s) to draw sample into the vessel is not applied until
all channels have each reach a minimum fill level for that channel.
In some embodiments, the motive force(s) are applied
simultaneously. This features recited may be applicable to any of
the embodiments herein.
[0266] Referring now to FIG. 11E, an enlarged cross-sectional view
of the device 1100 is shown. This embodiment shows that the support
1130 has a lip portion 1136 sized to extend over the adapter
channels 1150 and 1152 in an amount sufficient to prevent a user
from inserting a finger into the gap 1154 and piercing the finger
on one of the needle.
[0267] Additionally, as shown in FIGS. 11B and 11E, the present
embodiment has at least two channels in the sample collection
device 1100. This allows for each of the channels 1128 and 1126 to
each introduce a different material into the sample. By way of
non-limiting example, if the sample is whole blood, one channel can
introduce heparin into the blood while another channel introduces
ethylenediaminetetraacetic acid (EDTA). Not only do these
anti-coagulants prevent premature clogging of the channels during
fill, but also introduce anti-coagulant into the whole blood in
preparation for transport in the vessels 1146a and 1146b.
Optionally, the channel(s) may also be plasma coated in addition to
or in place of the anti-coagulants. The plasma coating can reduce
the flow resistance of the body fluid sample in the channels. Such
a coating can be applied in patterns such as but not limited to
strips, rings, or other patterns along with any other coating(s) to
be used in the channels.
[0268] Optionally, there is sufficient quantity of anti-coagulant
in the respective channel such that the sample fluid will contain a
desired level of anti-coagulant in the sample fluid after only a
single pass of the fluid through the channel. In traditional blood
vials, the blood sample does not contain anti-coagulant until it
enters the vial and once in the vial, the technician typically
repeatedly tilts, shakes, and/or agitates the vial to enable mixing
of anti-coagulant in the vials. In the present embodiment, the
sample fluid will contain anti-coagulant prior to entering the
sample vessel and it will do so without having to repeatedly tilt
or agitate the sample collection device. In the embodiment herein,
a single pass provides enough time and sufficient concentration of
additive such as anti-coagulant into the sample fluid. In one
embodiment, an EDTA channel has a volume of 54 uL coated by 200
mg/mL EDTA; a channel for Heparin has a volume of about 22 uL
coated by 250 units/mL Heparin. In another embodiment, the EDTA
channel has a volume of 70 uL coated by 300 mg/mL EDTA; the channel
for Heparin has a volume of about 30 uL and is coated by 250
units/mL Heparin. By way of non-limiting example, a channel of
volume from 50 to 70 uL can be coated by EDTA in the range from
about 200 to 300 mg/mL EDTA. Optionally, a channel of volume from
70 to 100 uL can be coated by EDTA in the range from about 300 to
450 mg/mL EDTA. Optionally, a channel of volume from 20 to 30 uL
can be coated by Heparin in the range from 250 units/mL Heparin. By
way of example, the material may be solution coated onto the target
surface for less than 1 hour and then dried overnight. There may be
variations and alternatives to the embodiments described herein and
that no single embodiment should be construed to encompass the
entire invention.
[0269] Referring now to FIG. 11G, a still further embodiment will
now be described. The embodiment of FIG. 11G shows that at a distal
end 1202 of the sample collection device 1200, instead of having
one opening 1204 for each of the channels, the sample collection
device 1200 merges two or more of the channels into a single
channel. The embodiment of FIG. 11G shows that there is common
channel portion prior to the split of the common channel into to a
plurality of separate channels. As will be described below in FIG.
11I, optionally, there may be back flow preventer such as but not
limited to a vent positioned along the separate channel to reduce
the possibility of drawing sample from one channel into another
channel during filling and/or extraction of sample from the
channels into the sample vessel(s).
[0270] As seen in FIG. 11H, this use of common flow paths can
result in a reduced number of openings on the exterior of the
sample collection device 1200, which may make it align the opening
1204 to engage the bodily fluid sample. It may also increase the
capillary force for drawing bodily fluid sample into the sample
collection device 1200 by having more capillaries pulling on the
same channel where the bodily fluid sample enters the collection
device.
[0271] Referring now to FIG. 11I, a cross-sectional view of select
components of a sample collection device will now be described.
FIG. 11I shows that the sample collection device can have two
channels 1182 and 1184 that have a common portion 1186 leading
towards an inlet opening on the device. In some embodiments, the
common portion 1186 is a continuation of one of the channels 1182
or 1184 in terms of size, shape, and/or orientation. Optionally,
the common portion 1186 is not of the same size, shape, and/or
orientation of any of the channels 1182, 1184, or any other channel
that may be in fluid communication with the common portion 1186.
FIG. 11I shows that in one non-limiting example, there may be a
step at the interface 1188 between the channel 1182 and 1184. This
interface 1188 may be configured to ensure flow into both of the
channels so that they will both reach a full fill. In one
embodiment, the interface 1188 has a size greater than the channel
1182 leading away from the interface 1188. Although other sizes are
not excluded, this interface 1188 of greater size may ensure that
sufficient flow will enter the channel 1182, which in the present
embodiment, has a smaller diameter and reduced volume relative to
the channel 1184. There may be variations and alternatives to the
embodiments described herein and that no single embodiment should
be construed to encompass the entire invention.
[0272] FIG. 11I also shows that there may be vents 1190 and 1192
that can be used to prevent cross-flow between channels,
particularly when sample is being transferred into the sample
vessels. In one embodiment, the vents 1190 and 1192 are open at all
times. In another embodiment, the vents 1190 and 1192 may be open
only at select times, such as but not limited to after the channels
1182 and 1184 are filled or substantially filled. Some embodiments
may use a dissolvable material the plugs the vents 1190 and 1192
until they are in contact with sample fluid. Optionally, some
embodiments may use a slidable covers one or more of the vents 1190
and 1192 such that they are only opened at times selected by the
user. In one embodiment, the covers are linked to the sample
vessels such that movement of the sample vessels to move into fluid
communication with the channels will also open one or more vents
1190 and 1192 to reduce the risk of cross-flow between channels.
Optionally, other anti-crossflow mechanisms such as but not limited
to valves, gates, or plugs can also be used to prevent fluid
transfer between channels 1190 and 1192.
[0273] FIG. 11I also shows that there may be anti-leakage devices
1194 positioned over the adapters 1150 and 1152. In this
embodiment, the anti-leakage devices 1194 are frits which may be
slidably moved from a first position where they prevent sample from
leaking out from the adapters 1150 and 1152 to a second position
wherein they allow the adapters to deliver fluid into the sample
vessels. In one non-limiting example, the anti-leakage devices 1194
will slide when they are engaged by the sample vessels or the
housing that holds the sample vessels. The movement of the sample
vessels or the housing in this non-limiting example shows that the
movement of those elements will also cause movement of the
anti-leakage devices 1194.
[0274] Referring now FIG. 11J, yet another embodiment of a sample
collection device 1160 will now be described. This embodiment of
the sample collection device 1160 shows that the device 1160 has a
sample entry location 1204 that leads to a plurality of channels
1162 and 1164 in the device 1160. Although FIG. 11J show that the
channels 1162 and 1164 may have different shapes and/or sizes, some
embodiments may be configured to have the same volumes and/or
shapes. It should also be understood that the sample entry location
1204 can be on the surface of the device 1160, or optionally, it
can be part of a tip, nozzle, stub, or other protrusion that
extends from the body of the device 1160. This protrusion may be in
the same plane and aligned parallel with the body of the device or
optionally, it may be angled so that the axis of the protrusion
intersects the plane of the device 1160.
[0275] FIG. 11J further shows that for some embodiments, there may
be sample flow features 1166 and 1168 to draw or otherwise
preferentially direct sample in a desired direction. In some
embodiments, the features 1166 and 1168 are guides that operate to
decrease channel dimension in at least one axis, such as but not
limited to width or height, and thus increase capillary action
through those areas of reduced dimension. In one non-limiting
example, these flow features 1166 and 1168 can assist fluid flow
through the channel areas positioned near the anti-crossflow
features 1170 during sample entry into the channels. In one
embodiment, the flow features 1166 and 1168 are sized so as to
preferentially improve flow in the inbound direction when flow is
drawn primarily by capillary action. Outbound flow, in one
scenario, is not based on capillary force but on vacuum pulling
force (such as from an adjacent channel), and these flow features
1166 and 1168 of the present embodiment are not configured to
provide assistance under those vacuum, non-capillary flow
conditions. Thus, some but not all embodiments of flow features
1166 and 1168 are configured to assist under at least one type of
flow condition but not certain other flow condition(s). Optionally,
some embodiments may use other techniques alone or in combination
with the guides, such as but not limited to, shaped features,
hydrophobic material(s), hydrophilic material(s), or other
techniques to push/pull samples towards a desired location.
[0276] FIG. 11J also shows that in the one or more embodiments
herein, there may be angled side wall features 1167 that conically
or otherwise narrow the cross-sectional area of the channel in a
manner that funnels sample to minimize the amount of sample that
may be retained in the channel and not collected. FIG. 11J also
shows that there may be locating feature(s) 1169 to facilitate
joining of parts together in a define location and orientation
during manufacturing.
[0277] FIG. 11K shows a side view of this embodiment of the sample
collection device 1160. The side view of the device 1160 shows that
there are embodiments where there are one or more anti-crossflow
features 1170 such as but not limited to vents to minimize
undesired crossflow of sample between the channels 1162 and 1164,
particularly once a desired fill level has been reached in the
respective channels. The anti-crossflow features 1170 and 1172 can
prevent crossflow due to the break in fluid pathway created by the
vents. The crossflow issue presents itself most commonly when the
vessels in the holder 1140 are engaged and provide an additional
motive force to pull the sample from the channels into the vessels.
This "pulling" effect may inadvertently draw sample from one
channel to an adjacent channel. To minimize crossflow, forces
associated with pulling sample from the channel into the vessel
will pull from the vent and not fluid in an adjacent channel, thus
minimizing undesired comingling of sample.
[0278] FIG. 11K also shows that in some embodiments herein, there
may be common portions 1130 and 1140 which can be adapted for use
with different sample fill portions 1120. Some may use different
capillary fill portions 1120. Some embodiments may use fill
portions that use different types of capture techniques, such as
but not limited to, samples acquired from venous draws, arterial
draws, or other sample drawn from an interior location or target
site of the subject.
[0279] Referring now to FIG. 11L, one embodiment of the sample flow
features 1166 and 1168 are shown. This cross-sectional view of
sample collection portion with the channels 1162 and 1164 and the
sample flow features 1166 and 1168 near the common inlet pathway
1165 shows that the features are desired in one embodiment near
where the sample is entering the channels. FIG. 11L also shows, for
channels of different volumes, it can be desirable to position the
inlet 1165 closer to the channel 1164 that has the larger volume,
as seen by the asymmetric location of inlet 1165. It can also be
seen that in some embodiments, location(s) of the sample flow
features 1166 and 1168 can also be selected to control filling
rate, filling volume, or the like in the sample collection device
1160. It should be understood that one or more of features
described can be adapted for use with other embodiments herein.
[0280] Referring now to FIG. 11M, channels 1162 and 1164 with
sample anti-crossflow features are shown. In one embodiment, the
sample anti-crossflow features are vents 1170 and 1172 located on
at least one surface of the channels 1162 and 1164. In one
nonlimiting example, these sample anti-crossflow features are
located near any sample flow features 1166 and 1168 in the device.
In one embodiment, these anti-crossflow features are configured to
prevent flow between channels. These anti-crossflow features can be
located near the maximum fill locations of each of the channels
such that as the channel is at or near its maximum sample capacity,
the anti-crossflow features 1170 and 1172 are positioned to prevent
overfilled sample from causing sample that has been treated in one
channel from entering another channel and undesirably mixing
samples from two channels together.
[0281] FIG. 11N shows a perspective view of the sample collection
device 1160 with sample fill indicators 1112 and 1114. In one
embodiment, these indicators 1112 and 1114 are openings or
transparent portions of the device 1160 that allows for observation
of at least one portion of the channel(s) 1162 or 1164. When sample
is visible in at least one of the indicators 1112 and 1114, it
provides a cue to the user to then take another action such as but
not limited to engaging the sample vessels in the holder 1140. In
some embodiments, there is only one sample fill indicator which is
a proxy for sufficient fill of sample in two or more of the
channels. In some embodiments, the action to engage the sample
vessels is only taken when indicated by indicators 1112 and 1114.
In some embodiments, the action to engage the sample vessels is
only taken when indicated by only one of the indicators.
[0282] Referring now to FIGS. 11O, 11P, and 11Q, cross-section at
various locations along one embodiment of the device 1160 in FIG.
11J are shown. FIG. 11O shows a cross-section showing the sample
flow features 1166 and 1168. The anti-crossflow features 1170 and
1172 are also shown. Engagement features 1174 can also be provided
to enable mating of pieces together to form the device 1160.
[0283] FIG. 11P shows that the adapter channels 1150 and 1152 are
positioned to extend into or at least be in fluid communication
with the sample channels 1162 and 1164. Optionally, some
embodiments may have multi-lumen adapter channels 1150 or 1152.
Optionally, some embodiments may have multiple adapter channels per
sample channel, wherein such additional channels may be parallel
to, angled, wrapped, or otherwise oriented relatively to each
other.
[0284] FIG. 11Q shows that in some embodiments, the vessel holder
1140 can be shaped asymmetrically (in the cross-sectional plane) or
otherwise shaped to enable only one orientation that the holder
1140 can be received in the device 1160. This can be particularly
desirable when it is desired to direct sample from a certain
channel into a selected vessel. If the holder 1140 can be inserted
in various orientations, the sample from one channel may end up in
the wrong vessel. Optionally, other features such as alignment
features, slots, visual cues, texture cues, and/or the like may be
used to encourage a preferred orientation of sample vessels in the
device.
Integrated Tissue Penetrating Member
[0285] Referring now to FIG. 11R, yet another embodiment of a
sample collection device will now be described. This sample
collection device 1210 comprises features similar to that shown in
FIG. 11G, except that it further includes a tissue penetrating
member 1212 that is mounted to the sample collection device 1210.
An actuation mechanism 1214 such as but not limited to a spring
actuator can be used to launch the tissue penetrating member. FIG.
11R shows the actuation mechanism 1214 in a resting state and that
it can be a spring that can be compressed to launch a tissue
penetrating member 1212 towards target tissue. The tissue
penetrating member 1212 can be housed inside a housing 1216 (shown
in phantom). In one embodiment, the housing 1216 comprises a
portion that can be peeled back, pierced, released or otherwise
opened to allow the tissue penetrating member 1212 to exit the
housing but also maintain sterility of the tissue penetrating
member 1212 prior to its use. In some embodiments, the portion may
be a foil, a cap, a polymer layer, or the like. There may be
variations and alternatives to the embodiments described herein and
that no single embodiment should be construed to encompass the
entire invention.
[0286] In one embodiment, the tissue penetrating member 1212 path
can be controlled along both the "normal" (i.e., forward direction
of the tissue penetrating member) and "orthogonal" (i.e.,
perpendicular to main motion vector) of the trajectory. Some
embodiments may have not have a hard stop or bang stop at the
deepest point of penetration (i.e., return point), which is the
main cause for spontaneous pain. Some embodiments may use a
cushion, a cam pathway, or other non-hardstop mechanism to prevent
pain associated with the shockwave of a sudden stop. Such a
shockwave is detrimental even if the tissue penetrating member
successfully avoids hitting nerves near the wound location as the
shockwave can activate such nerves even if direct contact was
avoided. Optionally, some embodiments may have the tissue
penetrating member follow a non jitter path, to prevent a rough
wound channel (residual pain). This may be achieved in some
embodiments through tighter tolerance in any guide pathway used
with tissue penetrating member or a pin associated with the tissue
penetrating member. This may be a non-jitter path when penetrating
the tissue. Optionally, this may be a non-jitter path for the
tissue penetrating member both outside the tissue and when it is
inside the tissue. This can reduce overall motion "wobble" of the
tissue penetrating member that may cause residual pain,
long-lasting trauma, and scarring.
[0287] Some embodiments may have a controlled outbound speed to
prevent slow and delayed wound closure and after bleeding. By way
of nonlimiting example, the controlled outbound speed of the tissue
penetrating member can be controlled by mechanical mechanisms such
as but not limited cams or higher friction materials.
[0288] Some embodiments may also include anti-bouncing mechanisms
to prevent unintended re-lancings that can be associated with an
uncontrolled tissue penetrating member that rebounds into the
tissue after initial wound creation. Some embodiments herein may
have "parking" mechanisms or lock-out mechanisms that will engage
the tissue penetrating member or its attachments to prevent
re-entry of the tissue penetrating member once it has retracted out
of the tissue or some other desired distance.
[0289] The abruptness with which the lancet comes to a stop in the
skin at maximum depth, before it starts its outbound motion and
returning to its starting position, is an inherent issue of this
design. With the lancet at its deepest point of penetration, the
greatest amount of force is applied to the skin. The drive
mechanism simply bounces off the end of the device like a ball
bounces back from the floor. The lancet, coming to an abrupt stop
at the end point of its inbound motion, sends a shockwave into the
skin, causing many pain receptors in the vicinity of the lancet to
fire, even though they are not directly struck. This amplifies
spontaneous pain substantially.
[0290] As mentioned, instead of simple spring actuated tissue
penetrating members, some embodiments may use mechanical cam
actuation. Devices with cam-actuation design can minimize "hard
stopping" of the tissue penetrating member. A cam mechanism is
usually spring driven and generally offers a better guided
actuation. The trajectory of the tissue penetrating member is
tightly controlled through a guided path of the tissue penetrating
member holder via a pin riding in a cam. The cam mechanism allows
for a predetermined speed profile with a softer return and distinct
speed control for the tissue penetrating member outbound
trajectory. This mechanism also effectively avoids a bounce back of
the lancet into the skin when the mechanism reaches its motion end
point. In addition, the mechanical oscillation (or jitter/wobble)
of the lance path in both directions is reduced when fired in air.
Some embodiments herein may also minimize any mechanical wobble of
the drive mechanism (e.g., due to uneven or rough cam slots) to
prevent transfer of such drive mechanism wobble directly into the
tissue because of its "forced motion profile."
[0291] Optionally, some embodiments may use electronic actuation
through an electronically controlled drive mechanism. This
technology uses a miniaturized electronic motor (e.g., voice coil,
solenoid) coupled with a very accurate position sensor, moving the
tissue penetrating member into and out of the skin with precisely
controlled motion and velocity. Following rapid entry, the device
decelerates the tissue penetrating member to an exact, preset depth
to return smoothly, without jitter, and relatively slowly. This
allows quick wound closure and avoids long-term trauma. With this
device, the force required to penetrate the lancet into the skin is
controlled while the tissue penetrating member is progressing. The
benefit of tightly controlling the tissue penetrating member
actuation "profile" is a reproducible painless lancing that yields
a sufficient and consistent blood sample for testing.
[0292] In terms of puncture site creation for blood sample
extraction, it may be desirable to elect the appropriate puncture
site on one of the patient's fingers (ring or middle) on their
non-dominant hand. The puncture sites may be on the sides of the
tips of the fingers. In one nonlimiting example, it may be
desirable to hold the hand warmer strip against the patient's
selected finger for 15 seconds. Optionally, some may warm the
patient's finger(s) from 10 to 60 seconds. Others may warm for
longer. The warming will increase blood flow to the target site. To
prepare the target site, it may be desirable to wipe the side tip
of the selected finger or surface of the subject with an alcohol
wipe or similar cleaning agent, being sure to wipe the selected
puncture site. In some embodiments, it is desirable to wait until
the skin is completely dry. Typically, one does not dry with gauze
or blow air on the fingertip to accelerate drying.
[0293] After a puncture has been formed, hold the finger downward,
below the patient's waist, in order to allow blood to flow. Massage
the finger lightly from base to tip until a blood drop has formed.
Carefully fill the blood collection device by touching the tip of
the device to the bead of blood on the finger. Make sure the device
is completely filled. Once the blood collection device is filled,
press the bleeding area of the finger against the gauze pad on the
table. Transfer the blood sample into the collection vessels. Place
a bandage over the finger. Place the vessels with the sample into
the shipping box inside the refrigerator. Discard all supplies in
the biohazard sharps vessel. All supplies are single-use only.
[0294] If enough blood is not obtained from the first puncture,
carefully place the blood collection device on the table surface,
ensuring that the device remains horizontal. Place a bandage over
the finger that was punctured. Select the appropriate puncture site
on a different finger on the patient's same hand. If the ring
finger was punctured first, choose a new puncture site on the
middle finger, and vice versa. Hold the hand warmer strip against
the patient's selected finger for 60 seconds. Optionally, some may
warm the patient's finger(s) from 30 to 90 seconds. This will
increase blood flow to the finger. These techniques for blood
collection using a sample collection device such as any of those
herein can enable sufficient sample collection of capillary blood
for use in laboratory testing at Clinical Laboratory Improvement
Amendments (CLIA) certified facility and/or standards.
[0295] Referring now to FIG. 11S, yet another embodiment of a
sample collection device 1220 will now be described. In this
embodiment, the tissue penetrating member 1222 may be mounted at an
angled relative to the sample collection device 1220. This angled
configuration allows for tissue penetrating member to create a
wound at a location that aligns with sample acquisition opening(s)
1103 and 1105. Although a standard spring-launched actuator is
shown as the drive mechanism 1224 for the tissue penetrating member
1222, it should be understood that cam and/or electrical drive
systems may also be used in place of or in combination with the
spring launcher. When the drive mechanism 1224 is a spring, the
spring can be compressed to move the tissue penetrating member 1222
to a launch position and the released to penetrate into the target
tissue. FIG. 11S shows the tissue penetrating member 1222 in a
resting position. Although the figures show a spring for the drive
mechanism 1224, it should be understood that other drive mechanism
suitable for use in launching a tissue penetrating member to create
a healable wound on a subject are not excluded. There may be
variations and alternatives to the embodiments described herein and
that no single embodiment should be construed to encompass the
entire invention.
[0296] A housing 1226, similar to that described for housing 1216,
may be formed around the tissue penetrating member 1222. Although
FIG. 11S shows two tissue penetrating members 1222 mounted on the
sample collection device, it should be understood that devices with
more or fewer tissue penetrating members are not excluded. For
example, some embodiments may have only one tissue penetrating
member 1222 mounted to the sample collection device 1220. There may
be variations and alternatives to the embodiments described herein
and that no single embodiment should be construed to encompass the
entire invention.
[0297] Referring now to FIG. 11T, another embodiment of a sample
collection device 1230 will now be described. This embodiment shows
that the tissue penetrating member 1232 is contained within the
sample collection device 1230 and as seen in FIG. 11T, it is
actually co-axially aligned with the central axis of the sample
collection device. This positions the tissue penetrating member
1232 to extend outward from the sample collection device 1230 at a
location close to where openings 1103 and 1105 are positioned on
the sample collection device 1230. Of course, devices having more
or fewer openings are not excluded and the embodiment of FIG. 11T
is exemplary and non-limiting. FIG. 11T shows that in one
embodiment of the sample collection device, a firing button 1234
may be mounted on the sample collection device 1230. Optionally,
some embodiments may have the shaped front end 1236 function as the
actuation button, wherein upon pressing the tissue against the
front end 1236 to a certain depth and/or certain pressure, the
tissue penetrating member will be actuated.
[0298] Once fired, the tissue penetrating member 1232 moves as
indicated by arrow 1233. In some embodiments, the tissue
penetrating member 1232 is fully contained inside the sample
collection device 1230 prior to actuation. Some embodiments may
have a visual indicator 1235 on the device 1230 to help guide the
user on where the tissue penetrating member 1232 will exit the
device and where approximately the wound will be formed.
[0299] In this non-limiting example, the entire device 1230 may be
in a sterile pouch or package that is only opened before the device
1230 is used. In this manner, sterile conditions are maintained for
the tissue penetrating member and the collection device prior to
use. This external sterile pouch or package is also applicable to
any of the other embodiments herein. FIG. 11L also shows that a
shaped front end 1236 (shown in phantom) that can be integrally
formed or separately attached to the sample collection device 1230.
This shaped front end 1236 can provide suction to draw sample fluid
into the sample collection device 1230. Optionally, the shaped
front end 1236 can be used to stretch the target tissue and/or
force it into the shaped front end to apply pressure to increase
sample fluid yield from wound formed by the tissue penetrating
member 1232. It should be understood that any of the embodiments
herein can be adapted to have a shaped front end 1236. Optionally,
the shaped front end may have select hydrophobic area(s) to direct
sample fluid to towards one or more collection areas on the front
end. Optionally, the shaped front end may have select hydrophilic
area(s) to direct sample fluid to towards one or more collection
areas on the front end.
[0300] Referring now to FIG. 11U, yet another embodiment of a
sample collection device will now be described. This embodiment is
similar to that of FIG. 11T except that, instead of single tissue
penetrating member such as a lancet, the embodiment of FIG. 11T
uses a plurality of tissue penetrating members 1242. In one
embodiment, these tissue penetrating members are microneedles 1242
that are of reduced diameter as compared to traditional lancets. A
plurality of microneedles 1242 can be simultaneously actuated for
device 1240 and create multiple wound sites on the tissue. The
spacing of the microneedles 1242 can result in more capillary loops
being pierced and more channels being available for blood to reach
the tissue surface. This also allows for a more "square"
penetration profile as compared to a lancet which has a pointed tip
and a tapered profile. This may enable the microneedles 1242 to
engage more capillary loops over a larger area without penetrating
too deep into deeper tissue layers that are more densely populated
with nerve endings.
[0301] Referring now to FIGS. 11V and 11W, a still further
embodiment of a sample collection device will now be described. In
the embodiment shown in these figures, the sample collection device
1100 may be mounted angled to a dedicated wound creation device
1250 that has a tissue penetrating member 1252 configured to extend
outward from the device 1250. The sample collection device 1100,
which may optionally be configured to have a shaped front end 1236
(with or without an opening to accommodate the tissue penetrating
member 1252), can be removably mounted to the wound creation device
1250. Optionally, the sample collection device 1100 may be flat
mounted to the device 1250. Optionally, there may be a shaped
cut-out on device 1250 for press-fit holding the sample collection
device 1100. It should be understood that other techniques for
removably mounting the sample collection device 1100 are not
excluded. This de-coupling of the collection device and the wound
creation device allows for the use of a more sophisticated,
possible non-disposable wound creation device 1250 that can create
a more controlled, reduced-pain wound creation experience.
[0302] FIG. 11W shows that the sample collection device 1100 can be
aligned to be more or less horizontal to be neutral with regards to
gravity effects on the sample collection. Other mounting
configurations of device 1100 to would creation device 1250 are not
excluded.
[0303] Referring now to FIGS. 11X to 11Z, still further embodiments
of various sample collection devices will now be described. FIG.
11X shows a sample collection device 1240 where a shaped front end
1236 may be used with the device 1240. This shaped front end 1236
is similar to that previously described. A vacuum source 1270 can
be used to assist in drawing bodily fluid sample into the device
1240. The vacuum source 1270 may be linked to the body of device
1240 and/or to the shaped front end 1236. It should be understood
that any of the embodiments described in this disclosure can be
adapted for use with a sample acquisition assist device such as but
not limited to a vacuum source 1270.
[0304] FIG. 11Y shows yet another embodiment of a sample collection
device. This embodiment uses a pipette system having a tip 1280 for
collecting sample fluid. The tip may include a coaxially mounted
tissue penetrating member 1282. Optionally, a side mount or angled
tissue penetrating member 1284 is shown to create the wound at the
target site. The pipette system with tip 1280 can apply vacuum to
pull sample fluid from the subject. Optionally, a shaped front end
1236 may be used with the tip 1280 to assist in skin stretching or
tissue reshaping at the target site.
[0305] FIG. 11Z shows that some embodiments may use a diaphragm
1291 linked actuation mechanism to create a vacuum for drawing
blood sample. This linkage allows for the diaphragm to create a
vacuum on the return stroke of the tissue penetrating member 1292
from the target site. In one embodiment, the tissue penetrating
members 1292 are microneedles. The actuation of the tissue
penetrating members as indicated by arrows 1294 launches the tissue
penetrating members 1292 and on the return path, creates the vacuum
due to the motion of the diaphragm linked to the motion of the
tissue penetrating member 1292. One or more vessels 1296 can be
coupled to hold fluid collected by the device 1290. Some
embodiments may have only one vessel 1296. Some embodiments may
have one set of vessels 1296. Some embodiments may have multiple
sets of vessels 1296. Some embodiments may be mounted externally on
device 1290. Some embodiments may be mounted internally in device
1290. There may be variations and alternatives to the embodiments
described herein and that no single embodiment should be construed
to encompass the entire invention.
Vertical Outflow Restrictors
[0306] FIG. 11E also more clearly shows that there are sleeves 1156
around the adapter 1150 and 1152. Although only shown in FIGS.
11A-11F, it should be understood that sleeves with or without vents
may be configured for use with any of the embodiments contemplated
herein. As seen in the embodiment of FIG. 11E, the channels may be
defined by needles. These sleeves 1156 prevent premature flow of
fluid sample out from the adapter channels 1150 and 1152 before the
vessels 1146a and 1146b engage the needles. Because of the low
volumes of sample fluid being acquired, preventing premature flow
reduces the amount of fluid loss associated with transfer of fluid
from the channels to the vessels. In one embodiment, the sleeves
1156 can minimize that fluid loss by providing a sleeve that is
liquid tight, but not air tight. If the sleeve were airtight, it
may prevent the capillary action of the channels from working
properly. Optionally, some embodiments may locate vents near the
base of the needle, away from the tip, such that the sleeve can
contain the sample at locations away from the vents.
[0307] FIG. 11F shows that in an exemplary embodiment, the sleeve
1156 is configured to have an opening 1158 through the sleeve. This
provides an improved embodiment over traditional sleeves which are
typically loosely fitted over a needle. Because of the loose fit,
in traditional sleeves, there is sleeve space in the tip and in
side wall space between the needle and the sleeve within which
fluid sample can accumulate. Although a sleeve of this design can
help prevent greater loss of fluid by restricting the loss to a
defined amount as compared to a needle without a sleeve which can
lose fluid continuously, the fluid accumulating in the sleeve area
along the tip and side wall is still lost and not collected by the
vessels 1146a or 1146b. The sleeve 1156 may also include a narrowed
area 1176 to facilitate engagement of the sleeve against the device
providing fluid communication with the channels 1126 and 1128, such
as but not limited to the needle, probe, tube, channel, or other
adapter channel 1150.
[0308] In the embodiment of FIG. 11F, the opening 1158 is sized
based on calculations which are sufficient to withstand fluid
pressure associated with the flow from the capillary action of the
channels in sample fill portion 1120. This forces allows the
opening 1158 to be there to vent air from the channel but also
prevent fluid from exiting the sleeve until the vessels 1146a and
1146b are pushed to engage the adapter channels 1150 and 1152.
Because of the vent effect created by the opening 1158, the side
wall and other areas of the sleeve can be made to much more tightly
engage the needle than in traditional sleeves. This reduces the gap
space between the needle and the sleeve and thus minimizes the
amount of fluid that can be lost as compared to sleeves without a
vent hole which have a much greater gap space due to the looseness
of the fit. Additionally, the opening 1158 can also be sized such
once fluid reaches the opening, that it provides enough resistance
so that flow out from the channel or needle is also stopped so that
here is minimal fluid loss in any gap between the sleeve and the
needle tip.
[0309] The calculations for sizing the opening are as shown in FIG.
12. The desire is to balance the forces such that there is
sufficient leak-prevention force associated with the hydrophobic
material defining the vent to contain outflow of sample fluid
outside of the sleeve. In FIG. 12, the side walls of the sleeve
1156 may be in direct contact with the needle or in some
embodiments, there may be a gap along the sidewall with the sleeve.
In one embodiment, the sleeve 1156 comprises a hydrophobic material
such as but not limited to thermoplastic elastomer (TPE), butyl
rubber, silicone, or other hydrophobic material. In one embodiment,
the thickness of the sleeve will also determine the length of the
side walls of the opening or vent 1158 in the sleeve 1156.
[0310] The opening 1158 may be located at one or more positions
along the sleeve 1156. Some may have it as shown in FIG. 12.
Alternatively, some embodiments may have the opening 1158 on a side
wall of the sleeve. Other locations are not excluded. Optionally,
the sleeve 1156 may have multiple openings through the sleeve, but
configured such that fluid does not exit from the sleeve and
resistance from the openings is sufficient to prevent additional
outflow from the channel until the vessels 1146a or 1146b are
engaged and in fluid communication with the channels.
[0311] With regards to how the device 1100 is used to collect a
sample, in one technique, the sample collection device 1100 is held
to engage the target bodily fluid and is held in place until a
desired fill level is reached. During this time, the device 1100
may be held horizontally to minimize gravitational force that would
need to be overcome if the device 1100 were held more vertically.
After a fill level is reached, the device 1100 may either be
disengaged from the target fluid and then vessels 1146a and 1146b
engaged to draw collected fluid into the vessels. Optionally, the
device 1100 may be left in contact with the target fluid and the
vessels engaged into fluid contact with the channels so that the
fill will draw fluid in the channel and perhaps also any additional
sample fluid that remains at the target site. This may ensure that
enough bodily fluid is drawn into the vessels.
[0312] After filling the vessels 1146a and 1146b, they may be
prepared for shipment. Optionally, they may be sent for
pre-treatment before being shipped. Some embodiments of the vessels
1146a and 1146b include a material in the vessel of a density such
that after a pre-treatment such as centrifugation, the material due
to its selected density will separate one portion of the
centrifuged sample from another portion of the centrifuged sample
in the same vessel.
[0313] The vessel 1146a or 1146b may have a vacuum and/or negative
pressure therein. The sample may be drawn into the vessel when the
channel is brought into fluidic communication with the vacu-vessel.
Optionally, the vessel may take the form of a test tube-like device
in the nature of those marketed under the trademark "Vacutainer" by
Becton-Dickinson Company of East Rutherford, N.J. The device may
remain in a compressed state with the base 1140 closing gap 1154
while the sample is being transferred to the vessel. The sample may
fill the entire vessel or a portion of the vessel. The entirety of
the sample (and/or greater than 90%, 95%, 97%, 98%, 99%, 99.5% or
99.9% of the sample) from the channels may be transferred to the
vessels. Alternatively, only a portion of the sample from the
channels may be transferred to the vessels.
[0314] In one embodiment as described herein, a two-stage filling
of the sample fluid into the sample collection device 1100 allows
for i) metered collection of the sample fluid to ensure that a
sufficient amount is obtained in a collection channel that is
treated to prevent premature clotting and then ii) an efficient
manner of transferring a high percentage of the sample fluid into
the vessel. This low loss filling of vessel from pre-fill channels
to meter a minimum amount of sample fluid into the vessel 1146
provides for multiple advantages, particularly when dealing with
collecting small volumes of sample fluid. Pre-filling the channels
to a desired level ensures sufficient volume is present in the
vessel to perform the desired testing on the sample fluid.
[0315] As described herein, the entire device including the sample
fill portion 1120, support 1130, and base 1140 are entirely
transparent or translucent to allow for visualization of the
components therein. Optionally, only one of the sample fill portion
1120, support 1130, and base 1140 are fully transparent or
translucent. Optionally, only select portions of sample fill
portion 1120, support 1130, or base 1140 are transparent or
translucent. The user may then more accurately determine when to
perform various procedures based on progression of sample fluid
filling and engagement of the sample vessels to the channels in
sample fill portion 1120. Air bubbles in the collection channel may
be visible during filling and if they are seen, a user may adjust
the position of the sample collection device 1100 to better engage
the target sample fluid to minimize air being drawn into the
channels. It will also allow the user to know when to breakaway or
disengage pieces such as the base or vessel holder 1140 when
filling is completed.
[0316] It should be understood that other methods can be used to
prevent outward sample flow from the adapter channels 1150 and 1152
if the device is held at a non-horizontal angle such as but not
limited to downwardly in a vertical manner. In one embodiment, a
frit 1194 can be used with needles with a central bore that are
used as the adapter channels 1150 and 1152. The frits can be in the
body of sample collection device or on the collection vessels. In
some embodiments, the frits comprise of a material such as but not
limited to PTFE. Optionally, some embodiments may use tape/adhesive
over the needles that are functioning as the adapter channels 1150
and 1152. In one embodiment, the tape and/or adhesive may be used
to cover the needle openings to prevent premature discharge of
sample. Optionally, some embodiments may have adapter channels 1150
and 1152 having hydrophobic surface to prevent controlled outflow
from the adapter channel openings leading toward the sample
vessels. In some embodiments, the adapter channels 1150 and 1152
are needles with hydrophobic material only on the interior surfaces
near an exit. Optionally, the hydrophobic material is only on the
exterior needle surfaces near an exit. Optionally, the hydrophobic
material is on interior and exterior needle surfaces. Optionally,
another method of preventing downward flow is increasing the
surface area of the capillaries by varying the cross-section. By
way of non-limiting example, some embodiments may introduce teeth-
or finger-like structures within the capillary in order increase
surface are in the cross-section of the capillary. Optionally, some
embodiments may include fins oriented toward and/or against the
fluid flow within the capillary in order increase surface are in
the cross-section of the capillary. There may be variations and
alternatives to the embodiments described herein and that no single
embodiment should be construed to encompass the entire
invention.
One Sample Collector Location to Multiple Channels
[0317] Referring now to FIGS. 13A-13B, yet another embodiment as
described herein will now be described. FIG. 13A shows a top down
view of a sample fill portion 1320 with a single collection
location 1322 such as but not limited to a collection well where
two channels 1324 and 1326 meet to draw fluid away from the single
collection location 1322. Optionally, some embodiments may use an
Y-split channel configuration wherein only a single channel lead
away from the collection location 1322 and then splits into
channels 1324 and 1326 after having been a single common channel
leading away from the collection location 1322. Members providing
fluid communication to the channels 1324 and 1326, such as but not
limited to a needle, probe, tube, channel, hollow elongate member,
or other structure, may be coupled to one end of the sample fill
portion 1320.
[0318] FIG. 13B shows a side-cross-sectional view, wherein the
collection location 1322 is shown and in fluidic communication with
channel 1326 which is in turn in fluid communication with an
adapter channel 1352 such as but not limited to a fluid
communication member. Some embodiments, the fluid communication
member may have sufficient stiffness and a sufficiently penetrating
tip to pierce a septum, cap, or other structure of the vessel. Some
may have the adapter channel 1352, 1150, or the like to be a
non-coring structure so as not to leave behind a hole that will not
seal in the septum, cap, or other structure of the vessel.
[0319] As seen in FIG. 13B, sample fluid may be applied or dropped
into the collection location 1322 as indicated by droplet D.
Optionally, some may directly apply or directly contact the
collection location 1322 to apply the sample fluid. Although the
embodiments herein are shown to use only a single collection
location 1322, it should be understood that other embodiments where
multiple channels couple to a common sample collection point are
envisioned. By way of nonlimiting example, one embodiment of a
collection device may have two collection locations 1322, each with
its own set of channels leading away from its respective collection
location. Some embodiments may combine common collection point
channels shown in FIGS. 13A-B with channels that are separate such
as shown in FIGS. 11A-11F. Other combinations of common collection
location structure with other structures with separate channels are
not excluded.
[0320] FIG. 13B also shows that this embodiment may include one or
more tissue penetrating members 1327 configured to extend outward
from the collection location 1322. In one embodiment, this enables
the user to place target tissue simultaneously over the collection
location 1322 and the wound creation location for fluid sample
acquisition. Optionally, a trigger 1323 can be positioned to launch
the tissue penetrating member. Optionally, the trigger is built
into a tissue interface of the device to enable launch of the
device when the target tissue is contacted and/or when sufficient
pressure or contact is in place. This overlap of these two
locations allows for simplified protocol for users to follow for
successful sample acquisition. The tissue penetration member(s)
1327 may be actuated by one or more actuation techniques such as
but not limited to spring actuated, spring/cam actuated,
electronically actuated, or single or multiple combinations of the
foregoing. It should be understood that other assist methods such
as but not limited to vacuum sources, tissue stretching devices,
tissue engagement nose pieces, or the like may be used alone or in
combination with any of the foregoing for improved sample
acquisition.
[0321] Referring now to FIG. 13C, a still further embodiment of a
sample collection device will now be described. This embodiment
shows a cartridge 1400 with a sample collection device 1402
integrated therein. There is a collection location 1322 and one or
more sample openings 1325 and 1329 where sample collection at
location 1322 can then be accessed such as but not limited to
handling by a pipette tip (not shown). The sample from droplet D
will travel along pathway 1326 as indicated by arrow towards the
openings 1325 and 1329, where the sample in the opening and any in
the pathways 1324 and/or 1326 leading towards their respective
openings 1325 and 1329 are drawn into the pipette P. As indicated
by arrows near the pipette P, the pipette P is movable in at least
one axis to enable transport of sample fluid to the desired
location(s). In this embodiment, the cartridge 1400 can have a
plurality of holding vessels 1410 for reagents, wash fluids, mixing
area, incubation areas, or the like. Optionally, some embodiments
of the cartridge 1400 may not include any holding vessels or
optionally, only one or two types of holding vessels. Optionally,
in some embodiments, the holding vessels may be pipette tips.
Optionally, in some embodiments, the holding vessels are pipette
tips that are treated to contain reagent(s) on the tip surface
(typically the interior tip surface although other surfaces are not
excluded). Optionally, some embodiments of the cartridge 1400 may
include only the sample collection device 1402 without the tissue
penetrating member or vice versa.
[0322] Referring now to FIG. 13D, a side cross-sectional view of
the embodiment of FIG. 13C is shown. Optionally, a tissue
penetrating member 1327 may be included for use with creating the
wound for the sample fluid to be collected at location 1322.
[0323] FIG. 14 shows that the sample fill portion 1320 may be
joined with support 1330 and 1340 to form the sample collection
device 1300. There may be a visualization window 1312 to see if
sample fluid has reached a desired fill level. A force-exerting
component, such as a spring 1356 or elastic may be included. The
channel holder may keep the channel affixed to the support. In one
embodiment, the holder may prevent the channel from sliding
relative to the support. It may use a press fit, mechanical
fastening, adhesive, or other attachment technique to couple to the
channel. The holder may optionally provide a support upon which a
force-exerting component, such as a spring, may rest.
[0324] In one example, the engagement assemblies may include a
spring 1356 which may exert a force so that the base 1340 is at an
extended state, when the spring is at its natural state. When the
base is at its extended state, space may be provided between the
vessels 1346a, 1346b and the engagement assemblies. In some
instances, when the base 1340 is in its extended state, the second
ends of the channels may or may not contact the caps of the
vessels. The second ends of the fluid communication members 1352
may be in a position where they are not in fluid communication with
the interiors of the vessels.
[0325] Bringing the support 1330 and the base 1340 together will
bring the channels 1324 and 1326 into fluid communication with the
vessels 1346a and 1346b when the members 1352 penetrate through the
cap on the vessels and thus draw sample fluid into the vessels
1346a and 1346b.
[0326] The vessel 1346a or 1346b may have a vacuum and/or negative
pressure therein. The sample may be drawn into the vessel when the
channel is brought into fluidic communication with the vacu-vessel.
The device may remain in a compressed state with the base 1340
positioned so that vessels are in fluid communication with the
channels 1326 and 1328 when the sample fluid is being transferred
to the vessels. The sample may fill the entire vessel or a portion
of the vessel. The entirety of the sample (and/or greater than 90%,
95%, 97%, 98%, 99%, 99.5% or 99.9% of the sample) from the channels
may be transferred to the vessels. Alternatively, only a portion of
the sample from the channels may be transferred to the vessels.
[0327] As seen in FIG. 15, in one embodiment as described herein, a
two-stage filling of the sample fluid into the sample collection
device 1300 allows for i) metered collection of the sample fluid to
ensure that a sufficient amount is obtained in a collection channel
that is treated to prevent premature dotting and then ii) an
efficient manner of transferring a high percentage of the sample
fluid into the vessel. This low loss filling of vessel from
pre-fill channels to meter a minimum amount of sample fluid into
the vessel 1346 provides for multiple advantages, particularly when
dealing with collecting small volumes of sample fluid. Pre-filling
the channels to a desired level ensures sufficient volume is
present in the vessel to perform the desired testing on the sample
fluid.
[0328] Referring now to FIGS. 16 and 17, still further embodiments
will now be described. FIG. 16 shows a blood collection device 1300
with a secondary collection area 1324 around the collection
location 1322. The secondary collection area 1324 can be used to
direct any overflow, spilled, or mis-directed fluid sample towards
the collection location 1322.
[0329] FIG. 17 further shows that the vessels 1346a and 1346b may
each have an identifier associated with the vessels 1346a and
1346b. FIG. 17 shows that in one nonlimiting example, the
identifier 1600 and 1602 may be at least one of: a barcode (e.g.,
1-D, 2-D, or 3-D), quick response (QR) code, image, shape, word,
number, alphanumeric string, color, or any combination thereof, or
any type of visual identifier. Others may use identifiers that are
not in the visible spectrum. Others may use RFID tags, RF
identifiers, IR emitting tags, or other markers that do not rely on
identification through signals sent through the visual
spectrum.
[0330] Identifiers 1600 and 1602 may be used to identify sample
and/or types of sample in a sample collection device. There may be
one or more identifiers per vessel. Some may also use identifiers
on the vessel holders. Identifiers may identity the sample
collection device, one or more individual vessels within the
device, or components of the device. In some instances, the sample
collection device, a portion of the sample collection device,
and/or the vessels may be transported. In one example, the sample
collection device, portion of the sample collection device may be
transported via a delivery service, or any other service described
elsewhere herein. The sample may be delivered to perform one or
more test on the sample.
[0331] The sample identity and/or the identity of the individual
who provided the sample could be tracked. Information associated
with the individual or individuals (e.g., name, contact
information, social security number, birth date, insurance
information, billing information, medical history) and other
information of who provided the sample may be included. In some
instances, the type of sample (e.g., whole blood, plasma, urine,
etc.) may be tracked. The types of reagents that the sample will
have encountered (e.g., anticoagulants, labels, etc.) could also be
tracked. Additional information about the sample collection, such
as date and/or time of collection, circumstances under which sample
was collected, types of tests to be run on the sample, insurance
information, medical records information, or any other type of
information may be considered.
[0332] Identifiers may assist with tracking such information. The
identifiers may be associated with such information. Such
information may be stored off-board the sample collection device,
on-board the sample collection device, or any combination thereof.
In some instances, the information may be stored on one or more
external devices, such as servers, computers, databases, or any
other device having a memory. In some instances, the information
may be stored on a cloud computing infrastructure. One or more
resources that store the information may be distributed over the
cloud. In some instances, a peer-to-peer infrastructure may be
provided. The information may be stored in the identifier itself,
or may be associated with the identifier elsewhere, or any
combination thereof.
[0333] An identifier may provide unique identification, or may
provide a high likelihood of providing unique identification. In
some instances, the identifier may have a visible component. The
identifier may be optically detectable. In some instances, the
identifier may be discernible using visible light. In some
examples, the identifier may be a barcode (e.g., 1-D, 2-D, or 3-D),
quick response (QR) code, image, shape, word, number, alphanumeric
string, color, or any combination thereof, or any type of visual
identifier.
[0334] In other embodiments, the identifier may be optically
detectable via any other sort of radiation. For example, the
identifier may be detectable via infrared, ultraviolet, or any
other type of wavelength of the electromagnetic spectrum. The
identifier may utilize luminescence, such as fluorescence,
chemiluminescence, bioluminescence, or any other type of optical
emission. In some instances, the identifier may be a radio
transmitter and/or receiver. The identifier may be a radiofrequency
identification (RFID) tag. The identifier may be any type of
wireless transmitter and/or receiver. The identifier may send one
or more electrical signal. In some instances, GPS or other
location-related signals may be utilized with the identifier.
[0335] An identifier may include an audio component, or acoustic
component. The identifier may emit a sound that may be discernible
to uniquely identify the identified component.
[0336] The identifier may be detectable via an optical detection
device. For example, a bar code scanner may be capable of reading
the identifier. In another example, a camera (e.g., for still or
video images) or other image capture device may be capable of
capturing an image of the identifier and analyzing the image to
determine the identification.
[0337] FIGS. 16 and 17 show examples of identifiers provided for
use with a sample collection device 1300 in accordance with an
embodiment described herein. In one example, a sample collection
device may include a base 1340 which may support and/or contain one
or more vessels 1346a, 1346b. Sample may be provided to the sample
collection device. The sample may be provided to the sample
collection device via an inlet 1322. The sample may travel to one
or more vessels 1346a, 1346b within the device.
[0338] One or more identifier 1600, 1602 may be provided on the
sample collection device. In some embodiments, identifiers may be
positioned on a base 1340 of the sample collection device. The
identifiers may be positioned on a bottom surface of the base, side
surface of the base, or any other portion of the base. In one
example, the base may have a flat bottom surface. The identifiers
may be on the flat bottom surface of the base. One or more
indentation may be provided in the base. The identifier may be
located within the indentation. The indentations may be on the
bottom or side surface of the base. In some embodiments, the base
may include one or more protrusion. The identifier may be located
on the protrusion. In some instances, the identifiers may be
provided on an exterior surface of the base. The identifiers may
alternatively be positioned on an interior surface of the base. The
identifiers may be detected from outside the sample collection
device.
[0339] In some embodiments, the identifiers may be provided on the
vessels 1346a, 1346b. The identifiers may be on an exterior surface
of the vessels or an interior surface of the vessels. The
identifiers may be detectable from outside the vessels. In some
embodiments, the identifiers may be provided on a bottom surface of
the vessels.
[0340] In one example, the base may include an optically
transmissive portion. The optically transmissive portion may be on
a bottom of the base or a side of the base. For example, a
transparent or translucent window may be provided. In another
example, the optically transmissive portion may be a hole without
requiring a window. The optically transmissive portion may permit a
portion inside the base to be visible. The identifiers may be
provided on an exterior surface of the base on the optically
transmissive portion, an interior surface of the base but may be
visible through the optically transmissive portion, or on an
exterior or interior surface of the vessel but may be visible
through the optically transmissive portion. In some instances, the
identifier may be provided on an interior surface of the vessel,
but the vessel may be optically transmissive so that the identifier
is viewable through the vessel and/or optically transmissive
portion.
[0341] The identifier may be a QR code or other optical identifier
that may be optically visible from outside the sample collection
device. A QR code may be visible through an optical window or hole
at the bottom of the base of the sample collection device. The QR
code may be provided on the sample collection device base or on a
portion of the vessel visible through the base. An image capturing
device, such as a camera or scanner may be provided externally to
the sample collection device, and may be capable of reading the QR
code.
[0342] A single or a plurality of QR codes or other identifiers may
be provided on a sample collection device. In some instances, each
vessel may have at least one identifier, such as a QR code
associated with it. In one example, at least one window may be
provided in a base per vessel, and each window may permit a user to
view a QR code or other identifier. For example, two vessels 1346a,
1346b may be housed within a base 1340, each of which has an
associated identifier 1600, 1602 discernible from outside the
sample collection device.
[0343] The base 1340 may be separable from the support 1330 or
other portions of the sample collection device. The identifier(s)
may be separated from the rest of the sample collection device
along with the base.
[0344] In some embodiments, the identifiers may be provided with
vessels housed by the base. Separating the base from the rest of
the sample collection device may cause the vessels to be separated
from the rest of the sample collection device. The vessels may
remain within the base or may be removed from the base. The
identifiers may remain with the vessels even if they are removed
from the base. Alternatively, the identifiers may remain with the
base even if vessels are removed. In some instances, both the base
and vessels may have identifiers so that the vessels and bases may
be individually tracked and/or matched even when separated.
[0345] In some instances, any number of vessels may be provided
within the sample collection device. The sample vessels may be
capable of receiving sample received from a subject. Each sample
vessel may have a unique identifier. The unique identifier may be
associated with any information relating to the sample, subject,
device, or component of the device.
[0346] In some instances, each identifier for each vessel may be
unique. In other embodiments, the identifier on the vessel need not
be unique, but may be unique for the device, for the subject, or
for the type of sample.
[0347] A sample collection device may receive a sample from a
subject. The subject may directly contact the sample collection
device or provide the sample to the device. The sample may travel
through the device to one or more vessels within the device. In
some instances, the sample may be treated prior to reaching the
vessels. One or more coating or substance may be provided within a
sample collection unit and/or channel that may convey the sample to
the vessels. Alternatively, no treatment is provided to the sample
prior to reaching the vessel. In some embodiments, the sample may
or may not be treated within the vessel. In some instances, a
plurality of different types of treatments may be provided to a
sample before or when the sample reaches the vessel. The treatments
may be provided in a preselected order. For example, a first
treatment desired first, and may be provided upstream of a second
treatment. In some instances, the sample is not treated at any
point.
[0348] In some embodiments, the sample may be a blood sample. A
first vessel may receive whole blood and a second vessel may
receive blood plasma. Anticoagulants may be provided along the
fluid path and/or in the vessels.
[0349] Once the sample has been provided to the vessels and the
vessels have been sealed, the vessels may be sent to a separate
location for sample analysis. The separate location may be a
laboratory. The separate location may be a remote facility relative
to the sample collection site. The entire sample collection device
may be sent to the separate location. One or more identifiers may
be provided on the sample collection device and may be useful for
identifying the sample collection device and/or vessels therein.
Alternatively, the base 1340 may be removed from the sample
collection device and may be sent to the separate location with the
vessels therein. One or more identifiers may be provided on the
base and may be useful for identifying the base and/or vessels
therein. In some instances, vessels may be removed from the base
and may be sent to the separate location. One or more identifier
may be provided on each vessel, and may be useful for identifying
the vessels.
[0350] The identifiers may be read by any suitable technique. By
way of example and not limitation, in some instances, the
identifiers are read using an optical detector, such as an image
capture device or barcode scanner. In one example, an image capture
device may capture an image of a QR code. Information relating to
the vessel may be tracked. For example, when a vessel arrives at a
location, the identifier may be scanned, and record of the arrival
of the vessel may be kept. The progress and/or location of the
vessel may be updated actively and/or passively. In some instances,
the identifier may need to be scanned intentionally in order to
determine the location of the vessel. In other examples, the
identifier may actively emit a signal that may be picked up by
signal readers. For example, as an identifier travels through a
building, signal readers may track the location of the
identifier.
[0351] In some instances, reading the identifier may permit a user
to access additional information associated with the identifier.
For example, the user may capture an image of the identifier using
a device. The device or another device may display information
about the sample, subject, device, component of the device, or any
other information described elsewhere herein. Information about
tests to be conducted and/or test results may be included. The user
may perform subsequent tests or actions with the sample based on
information associated with the identifier. For example, the user
may direct the vessel to the appropriate location for a test. In
some instances, the vessel may be directed to an appropriate
location and/or have appropriate sample processing (e.g., sample
prep, assay, detection, analysis) performed on the contents of the
vessel in an automated fashion without requiring human
intervention.
[0352] Information relating to sample processing may be collected
and associated with the identifier. For example, if a vessel has an
identifier and sample processing has been performed on the contents
of the vessel, one or more signals produced in response to the
sample processing may be stored and/or associated with the
identifier. Such updates may be made in an automated fashion
without requiring human intervention. Alternatively, a user may
initiate the storing of information or may manually enter
information. Thus, medical records relating to a subject may be
aggregated in an automated fashion. The identifiers may be useful
for indexing and/or accessing information related to the
subject.
Sample Vessels
[0353] FIGS. 18A-18B show one nonlimiting example of a sample
vessel 1800 that may be utilized with a sample collection device in
accordance with an embodiment described herein. In some instances,
the sample vessels may be supported by the sample collection
device. Optionally, the sample vessels may be encompassed or
surrounded by a portion of the sample collection device. In one
example, the sample collection device may have a first
configuration where the sample vessels are completely enclosed. A
second configuration may be provided where the sample collection
device may be opened and at least a portion of the sample vessels
may be exposed. In some examples, the sample vessels may be
supported and/or at least partially enclosed by a holder of the
sample collection device. The holder may be separable from the rest
of the sample collection device, thereby providing access to the
sample vessels therein.
[0354] In the case of bodily fluid collection, the sample fluid may
be extracted from the patient using a sample collection device such
as but not limited to that described in U.S. Patent Application
Ser. No. 61/697,797 filed Sep. 6, 2012 and U.S. Patent Application
Ser. No. 61/798,873 filed Mar. 15, 2013, both of which are fully
incorporated herein by reference for all purposes. In the
non-limiting example of blood samples, some embodiments may collect
the blood sample through collection of capillary blood from the
subject. This may occur by way of a wound, a penetration site, or
other access site to capillary blood from the subject. Optionally,
blood could also be collected by venipuncture or other puncture of
a blood vessel to obtain blood sample for loading into the sample
vessel(s). For example, the blood could be collected by a device
configured for collection of a small volume of blood by
venipuncture. Such a device, for example, may include a hollow
needle fluidically connected with or capable of being fluidically
connected with a vessel having a small interior volume. The vessel
having a small interior volume may have an interior volume, for
example, of equal to or no more than 5 ml 4 ml, 3 ml, 2 ml, 1 ml,
750 .mu.l, 500 .mu.l, 400 .mu.l, 300 .mu.l, 200 .mu.l, 100 .mu.l,
90 .mu.l, 80 .mu.l, 70 .mu.l, 60 .mu.l, 50 .mu.l, 40 .mu.l, 30
.mu.l, 20 .mu.l, 10 .mu.l, or 5 .mu.l. Other types of devices and
techniques used to collect bodily fluid are not excluded.
[0355] A bodily fluid may be drawn from a subject and provided to a
device in a variety of ways, including but not limited to,
fingerstick, lancing, injection, pumping, swabbing, pipetting,
venous draw, venipuncture, and/or any other technique described
elsewhere herein. In some embodiments, the sample may be collected
from the subject's breath. The bodily fluid may be provided using a
bodily fluid collector. A bodily fluid collector may include a
lancet, capillary, tube, pipette, syringe, needle, microneedle,
pump, or any other collector described elsewhere herein. In some
embodiments, the sample may be a tissue sample which may be
provided from the subject. The sample may be removed from the
subject or may have been cast off by the subject.
[0356] In one embodiment, a lancet punctures the skin of a subject
and withdraws a sample using, for example, gravity, capillary
action, aspiration, pressure differential or vacuum force. The
lancet, or any other bodily fluid collector, may be part of the
device, part of a cartridge of the device, part of a system, or a
standalone component. Where needed, the lancet or any other bodily
fluid collector may be activated by a variety of mechanical,
electrical, electromechanical, or any other known activation
mechanism or any combination of such methods.
[0357] In one example, a subject's finger (or other portion of the
subject's body) may be punctured to yield a bodily fluid. The
bodily fluid may be collected using a capillary tube, pipette,
swab, drop, or any other mechanism known in the art. The capillary
tube or pipette may be separate from the device and/or a cartridge
of the device that may be inserted within or attached to a device,
or may be a part of a device and/or cartridge. In another
embodiment where no active mechanism is required, a subject can
simply provide a bodily fluid to the device and/or cartridge, as
for example, with a saliva sample.
[0358] A bodily fluid may be drawn from a subject and provided to a
device in a variety of ways, including but not limited to,
fingerstick, lancing, injection, and/or pipetting. The bodily fluid
may be collected using venous or non-venous methods. The bodily
fluid may be provided using a bodily fluid collector. A bodily
fluid collector may include a lancet, capillary, tube, pipette,
syringe, venous draw, or any other collector described elsewhere
herein. In one embodiment, a lancet punctures the skin and
withdraws a sample using, for example, gravity, capillary action,
aspiration, or vacuum force. The lancet may be part of the device,
part of the cartridge of the device, part of a system, or a
standalone component. Where needed, the lancet may be activated by
a variety of mechanical, electrical, electromechanical, or any
other known activation mechanism or any combination of such
methods. In one example, a subject's finger (or other portion of
the subject's body) may be punctured to yield a bodily fluid.
Examples of other portions of the subject's body may include, but
are not limited to, the subject's hand, wrist, arm, torso, leg,
foot, or neck. The bodily fluid may be collected using a capillary
tube, pipette, or any other mechanism known in the art. The
capillary tube or pipette may be separate from the device and/or
cartridge, or may be a part of a device and/or cartridge. In
another embodiment where no active mechanism is required, a subject
can simply provide a bodily fluid to the device and/or cartridge,
as for example, could occur with a saliva sample. The collected
fluid can be placed within the device. A bodily fluid collector may
be attached to the device, removably attachable to the device, or
may be provided separately from the device.
[0359] Sample obtained from a subject may be stored in a sample
vessel 1800. In one embodiment described herein, the sample vessel
1800 comprises a body 1810 and a cap 1820. In some instances, at
least portions of the sample vessel body may be formed from a
transparent or translucent material. The sample vessel body may
permit a sample provided within the sample vessel body to be
visible when viewed from outside the sample vessel. The sample
vessel body may be optically transmissive. The sample vessel body
may be formed of a material that may permit electromagnetic
radiation to pass through. In some instances, the sample vessel
body may be formed of a material that may permit selected
wavelengths of electromagnetic radiation to pass through while not
permitting other non-selected wavelengths of electromagnetic
radiation to pass through. In some instances a portion or all of
the body may be formed of a material that is opaque along selected
wavelengths of electromagnetic radiation, such as wavelengths for
visible light. Optionally, some portions of the sample vessel body
may be shaped to provide a certain optical path length. Optionally,
some portions of the sample vessel body may be shaped to provide a
flat surface (exterior and/or interior) or other structure to allow
for analysis of sample while it is in the sample vessel.
[0360] In one embodiment, an open end and a closed end may be
provided on a sample vessel body 1810. The open end may be a top
end 1812 of the sample vessel 1800, which may be at the end which
may be configured to engage with a cap. The closed end may be a
bottom end 1814 of the sample vessel, which may be at the end of
the sample vessel opposite the cap. In alternative embodiments, a
bottom end may also be an open end that may be closable with a
floor. In some embodiments, the cross-sectional area and/or shape
of the top end and the bottom end may be substantially the same.
Alternatively, the cross-sectional area of the top end may be
larger than the cross-sectional area of the bottom end, or vice
versa. There may be variations and alternatives to the embodiments
described herein and that no single embodiment should be construed
to encompass the entire invention.
[0361] In one embodiment, a sample vessel body may have an interior
surface and an exterior surface. The surfaces of the sample vessel
body may be smooth, rough, textured, faceted, shiny, dull, contain
grooves, contain ridges, or have any other feature. The surface of
the sample vessel body may be treated to provide a desired optical
property. The interior surfaces and exterior surfaces may have the
same properties or may be different. For example, an exterior
surface may be smooth while the interior surface is rough.
[0362] Optionally, the sample vessel body may have a tubular shape.
In some instances, the sample vessel body may have a cylindrical
portion. In some instances, the sample vessel may have a circular
cross-sectional shape. Alternatively, the sample vessel may have
any other cross-sectional shape which may include elliptical,
triangular, quadrilateral (e.g., square, rectangular, trapezoidal,
parallelogram), pentagonal, hexagonal, heptagonal, octagonal, or
any other shape. The cross-sectional shape of the sample vessel may
or may not have a convex and/or concave shape. The cross-sectional
shape of the sample vessel may remain the same along the length of
the sample vessel, or may vary. The sample vessel may have a
prismatic shape along the length of the body. The prism may have a
cross-sectional shape as those described herein.
[0363] Optionally, the bottom 1814 of the sample vessel may be
flat, tapered, rounded, or any combination thereof. In some
instances, the sample vessel may have a hemispherical bottom. In
other embodiments, the sample vessel may have a rounded bottom with
a flat portion. The sample vessel may or may not be capable of
standing on a flat surface on its own.
[0364] In one embodiment, the sample vessels 1800 may be sized to
contain a small fluid sample. In some embodiments, the sample
vessels may be configured to contain no more than about 5 ml, 4 ml,
3 ml, 2 ml, 1.5 mL, 1 mL, 900 uL, 800 uL, 700 uL, 600 uL, 500 uL,
400 uL, 300 uL, 250 uL, 200 uL, 150 uL, 100 uL, 80 uL, 50 uL, 30
uL, 25 uL, 20 uL, 10 uL, 7 uL, 5 uL, 3 uL, 2 uL, 1 uL, 750 nL, 500
nL, 250 nL, 200 nL, 150 nL, 100 nL, 50 nL, 10 nL, 5 nL, 1 nL, 500
pL, 300 pL, 100 pL, 50 pL, 10 pL, 5 pL, or 1 pL. By way of
non-limiting example, the sample vessels may have the information
storage units thereon such as discussed for FIGS. 1F and 1G. In one
non-limiting example, the sample vessels 100 may hold the small
volume of sample fluid in liquid form without the use of a wicking
material, mesh, solid matrix, or the like to hold the sample fluid
during transport. This allows the sample fluid to be substantially
removed in liquid form from the sample vessel without loss of
sample or sample integrity due to liquid being absorbed by the
wicking or other material.
[0365] Optionally, the sample vessels 1800 may be configured to
contain no more than several drops of blood, a drop of blood, or no
more than a portion of a drop of blood. For example, the sample
vessel may have an interior volume of no greater than the amount of
fluid sample it is configured to contain. Having a small volume
sample vessel may advantageously permit storage and/or transport of
a large number of sample vessels within a small volume. This may
reduce resources used to store and/or transport the sample vessels.
For example, less storage space may be required. Additionally, less
cost and/or fuel may be used to transport the sample vessels. For
the same amount of exertion, a larger number of sample vessels may
be transported.
[0366] In some embodiments, the sample vessel 1800 may have a small
length. For example, the sample vessel length may be no greater
than 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.7
cm, 1.5 cm, 1.3 cm, 1.1 cm, 1 cm, 0.9 cm, 0.8 cm, 0.7 cm, 0.6 cm,
0.5 cm, 0.4 cm, 0.3 cm, 0.2 cm, 0.1 cm, 700 um, 500 m, 300 um, 100
um, 70 um, 50 um, 30 um, 10 um, 7 um, 5 um, 30 um, or 1 um. In some
instances, the greatest dimension of the sample vessel (e.g.,
length, width, or diameter) may be no greater than 8 cm, 7 cm, 6
cm, 5 cm, 4 cm, 3.5 cm, 3 cm, 2.5 cm, 2 cm, 1.7 cm, 1.5 cm, 1.3 cm,
1.1 cm, 1 cm, 0.9 cm, 0.8 cm, 0.7 cm, 0.6 cm, 0.5 cm, 0.4 cm, 0.3
cm, 0.2 cm, 0.1 cm, 700 um, 500 m, 300 um, 100 um, 70 um, 50 um, 30
um, 10 um, 7 um, 5 um, 30 um, or 1 um.
[0367] The sample vessel 1800 may have any cross-sectional area.
The cross-sectional area may be no greater than about 16 cm.sup.2,
8 cm.sup.2, 7 cm.sup.2, 6 cm.sup.2, 5 cm.sup.2, 4 cm.sup.2, 3.5
cm.sup.2, 3 cm.sup.2, 2.5 cm.sup.2, 2 cm.sup.2, 1.5 cm.sup.2, 1
cm.sup.2, 0.9 cm.sup.2, 0.8 cm.sup.2, 0.7 cm.sup.2, 0.6 cm.sup.2,
0.5 cm.sup.2, 0.4 cm.sup.2, 0.3 cm.sup.2, 0.2 cm.sup.2, 0.1
cm.sup.2, 0.07 cm.sup.2, 0.05 cm.sup.2, 0.03 cm.sup.2, 0.02
cm.sup.2, 0.01 cm.sup.2, 0.5 cm.sup.2, 0.3 cm.sup.2, or 0.1
cm.sup.2. The cross-sectional area may remain the same or may vary
along the length of the sample vessel.
[0368] The sample vessel 1800 may have any thickness. The thickness
may remain the same along the length of the sample vessel or may
vary. In some instances, the thickness may be selected and/or may
vary in order to provide a desired optical property. In some
instances, the thickness may be no greater than 5 mm, 3 mm, 2 mm, 1
mm, 700 um, 500 um, 300 um, 200 um, 150 um, 100 um, 70 um, 50 um,
30 um, 10 um, 7 um, 5 um, 3 um, 1 um, 700 nm, 500 nm, 300 nm or 100
nm.
[0369] In one embodiment, the sample vessel 1800 may have a shape
conducive to enabling centrifugation of small volume blood samples.
This allows the collected sample in the sample vessels to be taken
directly to a centrifuge without having to further transfer the
sample fluid to yet another sample vessel that is used in the
centrifuge device.
[0370] Optionally, the sample vessels may contain a cap 1820. The
cap 1820 may be configured to fit over an open end of the sample
vessel. The cap may block the open end of the sample vessel. The
cap may fluidically seal the sample vessel. The cap may form a
fluid-tight seal with the sample vessel body. For example, the cap
may be gas and/or liquid impermeable. Alternatively, the cap may
permit certain gases and/or liquids to pass through. In some
instances, the cap may be gas permeable while being liquid
impermeable. The cap may be impermeable to the sample. For example,
the cap may be impermeable to whole blood, serum or plasma.
[0371] Optionally, the cap may be configured to engage with the
sample vessel body in any manner. For example, the cap may be
press-fit with the sample vessel body. A friction fit and/or
interference fit may permit the cap to stay on the body. In other
examples, a locking mechanism may be provided, such as a sliding
mechanism, clamp, fastener, or other technique. In some instances,
the cap and/or the sample vessel body may be threaded to permit a
screw-type engagement. In other examples, adhesives, welding,
soldering, or brazing may be utilized to connect the cap to the
sample vessel body. The cap may be removably attached to the sample
vessel body. Alternatively, the cap may be permanently affixed to
the sample vessel body.
[0372] In some instances, a portion of the cap may fit into a
portion of the sample vessel body. The cap may form a stopper with
the sample vessel body. In some instances, a portion of the sample
vessel body may fit into a portion of the cap. The plug may include
a lip or shelf that may hang over a portion of the sample vessel
body. The lip or shelf may prevent the cap from sliding into the
sample vessel body. In some instances, a portion of a cap may
overlie a top and/or side of the sample vessel body. Optionally,
some embodiments may include an additional part in the vessel
assembly such as cap holder. In one embodiment, the purpose of the
cap holder is to maintain a tight seal between the cap and sample
vessel. In one embodiment, the cap holder engages an attachment,
lip, indentation, or other attachment location on the outside of
the sample vessel to hold the cap in position. Optionally, some
embodiments can combine the function of both the cap and the cap
holder into one component.
[0373] In some embodiments, the sample vessel body may be formed of
a rigid material. For example, the sample vessel body may be formed
of a polymer, such as polypropylene, polystyrene, or acrylic. In
alternate embodiments, the sample vessel body may be semi-rigid or
flexible. The sample vessel body may be formed from a single
integral piece. Alternatively, multiple pieces may be used. The
multiple pieces may be formed from the same material or from
different materials.
[0374] Optionally, the sample vessel cap may be formed of an
elastomeric material, or any other material described elsewhere
herein. In some instances, the cap may be formed from a rubber,
polymer, or any other material that may be flexible and/or
compressible. Alternatively, the cap may be semi-rigid or rigid.
The sample vessel cap may be formed from a high friction material.
The sample vessel cap may be capable of being friction-fit to
engage with the sample vessel body. When the sample vessel cap is
engaged with the sample vessel body, a fluid-tight seal may be
formed. The interior of the sample vessel body may be fluidically
isolated from the ambient air. In some instances, at least one of
the cap and/or portion of the sample vessel body contacting the cap
may be formed from a high friction and/or compressible
material.
[0375] In one embodiment, the cap 1820 may be a needle and/or a
cannula-penetrable self-sealing gas-proof closure in sealing
engagement in the open end of the sample vessel so as to maintain a
vacuum and/or a close atmosphere inside the sample vessel. In some
embodiments, the interior of the sample vessel is only at a partial
vacuum and not at a full vacuum. Excessive vacuum can damage formed
blood components in the sample fluid. By way of non-limiting
example, the partial vacuum is in the range of about 50 to 60% of a
full vacuum. Optionally, the partial vacuum does not exceed about
60% of a full vacuum. Optionally, the partial vacuum does not
exceed about 50% of a full vacuum. Optionally, the partial vacuum
does not exceed about 40% of a full vacuum. By way of non-limiting
example, the partial vacuum is in the range of about 10% to about
90% of a full vacuum, or between about 20% to about 70%, or between
about 30% to about 60% of a full vacuum. By way of non-limiting
example, the partial vacuum is in the range of about 10% to about
60% of a full vacuum, or between about 20% to about 50%, or between
about 30% to about 50% of a full vacuum. In this manner, a reduced
amount of force is exerted on the bodily fluid sample to minimize
issues with regards to sample integrity. Optionally, after sample
transfer, the atmosphere is at ambient pressure. Optionally, after
sample transfer, the atmosphere is at some partial vacuum.
Optionally, only one of the plurality of sample vessels is at
partial vacuum, while others are at higher vacuum levels or at full
vacuum.
[0376] In some embodiments, the cap 1820 may be a closure device
having one end interior of the sample vessel and another end
exterior of the sample vessel, wherein the end interior having a
surface in continuous sealing contact with the sample vessel, the
end interior having an annular sleeve extending from the surface
toward the closed end, the annular sleeve having a first notch
extending through a wall of the annular sleeve and juxtaposed
against the sample vessel. In one embodiment, the closure has an
indented ring formed about the first notch of the end interior and
the indented ring engaging a hump of the tubular sample vessel.
[0377] Optionally, the sample vessel cap may be formed from a
single integral piece. Alternatively, multiple pieces may be used.
The multiple pieces may be formed from the same material or from
different materials. The cap material may be the same as or
different from the sample vessel body material. In one example, the
sample vessel body may be formed from an optically transmissive
material while the cap is formed from an opaque material.
[0378] Optionally, the cap 1820 may be removably engaged with the
body. A portion of the cap may be insertable into the body. The cap
may include a lip which may rest on top of the body. The lip is not
inserted into the body. In this non-limiting example, the lip may
prevent the cap from being entirely inserted into the body. The lip
may form a continuous flange around the cap. In some instances, a
portion of the lip may overlap or overlie a portion of the body. A
portion of the body may be insertable into a portion of the
cap.
[0379] Optionally, the portion of the cap that may be insertable
into the body may have a rounded bottom. Alternatively, the portion
may be flat, tapered, curved, contoured, or have any other shape.
The cap may be shaped to be easily insertable into the body.
[0380] In some instances, a depression may be provided at the top
of the cap. The depression may follow the portion of the cap that
is inserted into the body. In some instances, a hollow or
depression may be provided in the cap. The depression may be
capable of accepting a portion of a channel that may be used to
deliver a sample to the sample vessel. The depression may assist
with guiding the channel to a desired portion of the cap. In one
example, the channel may be positioned within the depression prior
to bringing the channel and interior of the sample vessel into
fluid communication.
[0381] Optionally, the channel and cap may be pressed together so
that the channel penetrates the cap and enters the interior of the
sample vessel, thereby bringing the channel and interior of the
sample vessel into fluid communication. In some instances, the cap
may have a slit through which the channel passes. Alternatively,
the channel may poke through uninterrupted cap material. The
channel may be withdrawn from the sample vessel, thereby bringing
the channel and sample vessel out of fluid communication. The cap
may be capable of resealing when the channel is removed. For the
example, the cap may be formed of a self-healing material. In some
instances, the cap may have a slit that may close up when the
channel is removed, thereby forming a fluid tight seal.
[0382] In some embodiments, the body may include one or more flange
or other surface feature. Examples of surface features may include
flanges, bumps, protrusions, grooves, ridges, threads, holes,
facets, or any other surface feature. The flange and/or other
surface feature may circumscribe the body. The flange and/or
surface feature may be located at or near the top of the body. The
flange and/or other surface feature may be located at the top half,
top third, top quarter, top fifth, top sixth, top eighth, or top
tenth of the body. The surface features may be useful for support
of the sample vessel within a sample collection device. The surface
features may be useful for removing the sample vessel from the
sample collection device and/or positioning the sample vessel
within the sample collection device. The flange and/or other
surface feature may or may not engage with the cap.
[0383] Optionally, the cap may have any dimension relative to the
sample vessel body. In some instances, the cap and/or body may have
similar cross-sectional areas. The cap may have the same or a
substantially similar cross-sectional area and/or shape as the top
of the body. In some instances, the cap may have a lesser length
than the body. For example, the cap may have a length that may be
less than 60%, 50%, 40%, 30%, 25%, 20%, 15%, 10%, 7%, 5%, 3% or 1%
of the length of the body.
[0384] Referring now to FIGS. 18C to 18E, a still further
embodiment of sample vessel 1800 may include a cap holder 1830 that
fits over the cap to hold the cap in place. By way of non-limiting
example, the cap holder 1830 may also include an opening in the cap
holder 1830 that allows for a member such as an adapter to slide
through and penetrate the cap 1820. FIG. 18C shows the parts in an
exploded view.
[0385] FIG. 18D shows a cross-section view showing one embodiment
wherein the sample vessel body 1810 having a cap 1820 covered by a
cap holder 1830. As seen in FIG. 18D, the cap holder 1830 has a
locking feature 1832 for securing the cap holder 1830 to the sample
vessel body 1810 and/or the cap 1820. In one embodiment, the
locking feature 1832 comprises an interior ridge which will engage
one or more of the ridges 1812 and 1814 on the sample vessel body
1810. FIG. 18E shows a side view of the cap holder 1830 coupled to
the sample vessel body 1810.
[0386] In some instances, a surface (interior and/or exterior) of
the sample vessel may be coated and/or treated with a material. For
example, an interior surface of the sample vessel may be coated
with fixatives, antibodies, optical coatings, anticoagulant, sample
additives and/or preservatives. These may be the same or different
from any material coatings in the channels. In one non-limiting
example, the coating may be but are not limited to
polytetrafluoroethylene, poly-xylene, polysorbate surfactant (e.g.
polysorbate 20) or other material as a treatment for surfaces to
reduce the surface tension.
[0387] In embodiments, sample vessels may contain a blood clotting
activator (e.g. thrombin, silica particles, glass particles), an
antiglycolytic agent (e.g. sodium floride), or a gel to facilitate
the separation of blood cells from plasma. In examples, sample
vessels may contain sodium polyanethol sulfonate (SPS), acid
citrate dextrose additives, perchloric acid, or sodium citrate.
Some embodiments may include at least one material from each of the
above groupings. Optionally, it should also be understood that
other additives or materials are not excluded, particularly if the
additives do not interfere with each other in terms of
functionality.
[0388] Optionally, the coating is applied on all interior surfaces
of the sample vessel. Optionally, some embodiments may apply the
coating in a pattern covering only select areas in the sample
vessel. Some embodiments may only cover upper interior regions of
the sample vessel. Optionally, some may cover only lower interior
regions of the sample vessel. Optionally, some may cover strips,
lanes, or other geometric patterns of the interior regions of the
sample vessel. Optionally, some embodiments may also coat the
surfaces of the cap, plug, or cover that is used with the sample
vessel. Some embodiments may have the surfaces where sample enters
the sample vessel to be coated to provide for a smooth transfer of
sample away from the entry area and towards a destination site such
as but not limited to a bottom portion of the vessel.
[0389] Optionally, the coating may be a wet or dry coating. Some
embodiments may have at least one dry coating and at least one wet
coating. In some instances one or more reagents may be coated and
dried on the interior surface of the sample vessel. The coating may
alternatively be provided in a moist environment or may be a gel.
Some embodiments may include a separator gel in the sample vessel
to keep select portions of the sample away from other portions of
the sample. Some embodiments may include serum separator gel or
plasma separator gel such as but not limited to polyester-based
separator gels available from Becton Dickinson.
[0390] Optionally, one or more solid substrates may be provided
within the sample vessel. For example, one or more beads or
particles may be provided within the sample vessel. The beads
and/or particles may be coated with reagents or any other substance
described herein. The beads and/or particles may be capable of
dissolving in the presence of the sample. The beads and/or
particles may be formed from one or more reagents or may be useful
for treating the sample. A reagent may be provided in a gaseous
form within the sample vessel. The sample vessel may be sealed. The
sample vessel may remain sealed before the sample is introduced
into the sample vessel, after the sample has been introduced to the
sample vessel, and/or while the sample is being introduced into the
sample vessel. In one embodiment, the sample vessels may have
smooth surfaces and/or round bottoms. This is helpful to minimize
the stress on the blood sample, especially during centrifugation.
Of course, in alternative embodiments, other shapes of the bottom
of the sample vessel are not excluded.
[0391] In embodiments, a bodily fluid sample in a sealed sample
vessel may retain dissolved gases in the bodily fluid sample, such
that sample stored in the sealed sample vessel retains a dissolved
gas composition similar to or the same as that of bodily fluid
sample freshly extracted from a subject's body or of a freshly
prepared from a different sample (e.g. plasma freshly prepared from
whole blood). In embodiments, a bodily fluid sample in a sealed
sample vessel may retain at least 99%, 98%, 95%, 90%, 80%, 70%,
60%, 50%, 40%, 30%, or 20% of a dissolved gas over 10 minute, 20
minute, 30 minute, 45 minute, 1 hour, 2 hour, 4 hour, 6 hour, 8
hour, 12 hour, 16 hour, 24 hour, 48 hour, or 72 hour time period.
In such embodiments, typically, the time period starts at the time
of depositing a sample into a sample vessel or the time of sealing
the sample vessel. To facilitate the preservation of dissolved
gases in a bodily fluid sample, the sample may be stored in a
sealed sample vessel at a selected temperature, such as, for
example, 20 C, 15 C, 10 C, 4 C, or at a freezing temperature below
0 C. Other temperatures for sample storage are not excluded.
[0392] Similarly, in embodiments, a bodily fluid sample in a sealed
sample vessel may retain analytes in the bodily fluid sample, such
that sample stored in the sealed sample vessel retains an analyte
composition similar to or the same as that of bodily fluid sample
freshly extracted from a subject's body or of a freshly prepared
bodily fluid sample (e.g. plasma freshly prepared from whole
blood). In embodiments, a bodily fluid sample in a sealed sample
vessel may retain at least 99%, 98%, 95%, 90%, 80%, 70%, 60%, 50%,
40%, 30%, or 20% of an analyte over 10 minute, 20 minute, 30
minute, 45 minute, 1 hour, 2 hour, 4 hour, 6 hour, 8 hour, 12 hour,
16 hour, 24 hour, or 48 hour time period. In such embodiments,
typically, the time period starts at the time of depositing a
sample into a sample vessel or the time of sealing the sample
vessel. To facilitate the preservation of one or more analytes in a
bodily fluid sample, the sample may be stored in a sealed sample
vessel at a selected temperature, such as, for example, 20 C, 15 C,
10 C, 4 C, or at a freezing temperature below 0 C. Other
temperatures for sample storage are not excluded. Optionally, a
sample vessel may be centrifuged after a sample is introduced into
the vessel. For example, a sample vessel may be centrifuged within
30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes,
10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour,
2 hours, 4 hours, 8 hours, 24 hours, 2 days, 3 days, 4 days, 5
days, 7 days, or 10 days of introduction of the sample into the
vessel. Centrifuging a sample vessel containing a sample may, for
example, in the case of a whole blood sample, facilitate the
separation of blood cells from plasma, to yield plasma and pelleted
cells. In some circumstances, centrifuging a sample increases the
stability of one or more analytes in blood or plasma.
[0393] FIG. 18F further shows that the sample vessels may each have
at least one information storage unit associated with the sample
vessels. Optionally, some embodiments may have one information
storage unit convey information about a plurality of sample
vessels, particularly (but not exclusively) in cases where the
sample vessels all contain sample from the same subject. Such an
information storage unit could be on the carrier that holds the
multiple sample vessels, instead of being on the sample vessels
themselves.
[0394] FIG. 18F shows a bottom-up view of an underside of one of
the sample vessels that in one nonlimiting example, the information
storage unit 1860 may be at least one of: a barcode (e.g., 1-D,
2-D, or 3-D), quick response (QR) code, image, shape, word, number,
alphanumeric string, color, or any combination thereof, or any type
of visual information storage unit. Others may use information
storage units that are not in the visible spectrum. Others may use
RFID tags, RF information storage units, IR emitting tags, or other
markers that do not rely on identification through signals sent
through the visual spectrum. Of course, the information storage
unit 1860 may also be positioned to be on a top end surface of the
sample vessel. FIG. 18G shows that, optionally, an information
storage unit 1860 may also be included on a side surface of the
sample vessel. This may be in addition to or in place of the top or
bottom positioned information storage unit(s) 1860.
[0395] In one non-limiting example, information storage unit 1860
may be used to identify sample and/or types of sample in a sample
collection device. Optionally, there may be one or more information
storage units per sample vessel. Some may also use information
storage units on the sample vessel holders. Information storage
units may identify the sample collection device, one or more
individual sample vessels within the device, or components of the
device. In some instances, the sample collection device, a portion
of the sample collection device, and/or the sample vessels may be
transported. In one example, the sample collection device or a
portion of the sample collection device, may be transported via a
delivery service, or any other service described elsewhere herein.
The sample vessel may be delivered so that one or more tests may be
performed on the sample.
[0396] Optionally, the sample identity and/or the identity of the
individual who provided the sample could be tracked. By way of
non-limiting example, information associated with the individual or
individuals (e.g., name, contact information, social security
number, birth date, insurance information, billing information,
medical history) and other information of who provided the sample
may be included. In some instances, the type of sample (e.g., whole
blood, plasma, urine, etc.) may be tracked. Optionally, the types
of reagents that the sample will have encountered (e.g.,
anticoagulants, labels, etc.) could also be tracked. Additional
information about the sample collection, such as date and/or time
of collection, circumstances under which sample was collected,
types of tests to be run on the sample, setting(s) for the tests,
test protocols, insurance information, medical records information,
or any other type of information may be considered.
[0397] In at least one or more embodiments described herein,
information storage units may assist with tracking such
information. The information storage units may be associated with
such information. Such information may be stored off-board the
sample collection device, on-board the sample collection device, or
any combination thereof. In some instances, the information may be
stored on one or more external devices, such as servers, computers,
databases, or any other device having a memory. In some instances,
the information may be stored on a cloud computing infrastructure.
One or more resources that store the information may be distributed
over the cloud, through the internet from a remote server, wireless
to a remote computer processor, or the like. In some instances, a
peer-to-peer infrastructure may be provided. The information may be
stored in the information storage unit itself, or may be associated
with the information storage unit elsewhere, or any combination
thereof.
[0398] Optionally, an information storage unit may provide unique
identification, or may provide a high likelihood of providing
unique identification. In some instances, the information storage
unit may have a visible component. The information storage unit may
be optically detectable. In some instances, the information storage
unit may be discernible using visible light. In some examples, the
information storage unit may be a barcode (e.g., 1-D, 2-D, or 3-D),
quick response (QR) code, image, shape, word, number, alphanumeric
string, color, or any combination thereof, or any type of visual
information storage unit.
[0399] In other embodiments, the information storage unit may be
optically detectable via any other sort of radiation. For example,
the information storage unit may be detectable via infrared,
ultraviolet, or any other type of wavelength of the electromagnetic
spectrum. The information storage unit may utilize luminescence,
such as fluorescence, chemiluminescence, bioluminescence, or any
other type of optical emission. In some instances, the information
storage unit may be a radio transmitter and/or receiver. The
information storage unit may be a radiofrequency identification
(RFID) tag. The information storage unit may be any type of
wireless transmitter and/or receiver. The information storage unit
may send one or more electrical signal. In some instances, GPS or
other location-related signals may be utilized with the information
storage unit.
[0400] Optionally, an information storage unit may be and/or
include an audio component or acoustic component. The information
storage unit may emit a sound that may be discernible to uniquely
identify the identified component.
[0401] Optionally, the information storage unit may be detectable
via an optical detection device. For example, a bar code scanner
may be capable of reading the information storage unit. In another
example, a camera (e.g., for still or video images) or other image
capture device may be capable of capturing an image of the
information storage unit and analyzing the image to determine the
identification.
[0402] Optionally, the information storage units may be on the
holder of the sample vessel(s). One or more indentation may be
provided in the holder. The information storage unit may be located
within the indentation. The indentations may be on the bottom or
side surface of the holder. In some embodiments, the holder may
include one or more protrusion. The information storage unit may be
located on the protrusion. In some instances, the information
storage units may be provided on an exterior surface of the holder.
The information storage units may alternatively be positioned on an
interior surface of the holder. The information storage units may
be detected from outside the sample collection device.
[0403] In some embodiments, the information storage units may be on
an exterior surface of the sample vessels or an interior surface of
the sample vessels. The information storage units may be detectable
from outside the sample vessels. In some embodiments, the
information storage units may be provided on a bottom surface of
the sample vessels.
[0404] In one non-limiting example, the holder may include an
optically transmissive portion. The optically transmissive portion
may be on a bottom of the holder or a side of the holder. For
example, a transparent or translucent window may be provided. In
another example, the optically transmissive portion may be a hole
without requiring a window. The optically transmissive portion may
permit a portion inside the holder to be visible. The information
storage units may be provided on an exterior surface of the holder
on the optically transmissive portion, an interior surface of the
holder but may be visible through the optically transmissive
portion, or on an exterior or interior surface of the sample vessel
but may be visible through the optically transmissive portion. In
some instances, the information storage unit may be provided on an
interior surface of the sample vessel, but the sample vessel may be
optically transmissive so that the information storage unit is
viewable through the sample vessel and/or optically transmissive
portion.
[0405] Optionally, the information storage unit may be a QR code,
bar code, or other optical information storage unit that may be
optically visible, such as but not limited to being visible from
outside the sample collection device. A QR code may be visible
through an optical window, hole, or the like at the bottom of the
holder of the sample collection device. The QR code may be provided
on the sample collection device holder or on a portion of the
sample vessel visible through the holder. An image capturing
device, such as a camera or scanner may be provided external to the
sample vessels or the transport container, and may be capable of
reading the QR code.
[0406] In some embodiments, a single or a plurality of QR codes or
other information storage units may be provided on a sample
collection device. In some instances, each sample vessel may have
at least one information storage unit, such as a QR code associated
with it. In one example, at least one window may be provided in a
holder per sample vessel, and each window may permit a user to view
a QR code or other information storage unit. For example, two
sample vessels may be housed within a holder, each of the sample
vessels having an associated information storage unit discernible
from outside the holder.
[0407] In some embodiments, the information storage units may be
provided with sample vessels housed by the holder. Separating the
holder from the rest of the sample collection device may cause the
sample vessels to be separated from the rest of the sample
collection device. The sample vessels may remain within the holder
or may be removed from the holder. The information storage units
may remain with the sample vessels even if they are removed from
the holder. Alternatively, the information storage units may remain
with the holder even if sample vessels are removed. In some
instances, both the holder and sample vessels may have information
storage units so that the sample vessels and holders may be
individually tracked and/or matched even when separated.
[0408] In some instances, any number of sample vessels may be
provided within the sample collection device. Some embodiments may
connect all of these sample vessels to the sample collection device
all at once. Optionally, the sample vessels may be coupled in a
sequential or other non-simultaneous manner. The sample vessels may
be capable of receiving sample received from a subject. Each sample
vessel may optionally have a unique information storage unit. The
unique information storage unit may be associated with any
information relating to the sample, subject, device, or component
of the device.
[0409] In some instances, each information storage unit for each
sample vessel may be unique or contain unique information. In other
embodiments, the information storage unit on the sample vessel need
not be unique. Optionally, some embodiments may have information
unique for the device, for the subject, and/or for the type of
sample. In some embodiments, the information on the information
storage unit may be used to associate several sample vessels with
the same subject or the same information.
[0410] In some embodiments, the information storage unit is
attached to or otherwise associated (physically or by non-physical
association such as database pointer or linkage) with the sample
vessel or groups of sample vessels at the collection appointment.
If associated by group, the association can be based on all being
from the same user or other factor as set forth herein. Optionally,
some embodiments may have information storage units already on the
sample vessels or groups of sample vessels. In one non-limiting
example, the information storage unit provides identifier
information that is then associated with the subject at or near the
time of sample collection. In this example, the information on the
information storage unit remains the same but is then linked to the
subject. In another embodiment, the information on the information
storage unit is changed to include information about the subject.
Optionally, some embodiments may have both, wherein some
information is changed and some is not (but may be then associated
with the subject or other information about the collection event
such as time date or the like).
[0411] Referring now to FIGS. 19A to 19C, various embodiments of a
front end of a sample collection device will now be described. FIG.
19A shows on view of a front end of the sample collection device
with openings 1103 and 1105 for their respective channels. In the
present embodiment, the openings 1103 and 1105 are placed in close
proximity to each other with the divider wall 1910 between the
openings 1103 and 1105. In one non-limiting example, the thickness
of divider wall 1910 is set to be the minimum thickness that can be
reliably formed through a manufacturing process used to form the
sample collection device. In one embodiment, wall thickness should
be about 1-10 mm. In some embodiments, instead of being side by
side, the openings 1103 and 1105 may be in a top-bottom
configuration, diagonal configuration, or other configuration where
the two openings are in close proximity to one another.
[0412] Referring now to FIG. 19B, this embodiment shows the
openings 1910 and 1912 configured to be coaxial, relative to one
another. This coaxial configuration of openings 1910 and 1912
allows for greater overlap between the two openings.
[0413] Referring now to FIG. 19C, this embodiment is similar to
that of FIG. 19B except that instead of square shaped openings,
these openings 1920 and 1922 are round. It should be understood
that any variety of shapes may be used including but not limited to
circular, elliptical, triangular, quadrilateral (e.g., square,
rectangular, trapezoidal), pentagonal, hexagonal, octagonal, or any
other cross-sectional shape. Of course, it should be understood
that different shapes can be used for each opening and that a
collection device need not have the same cross-sectional shape for
all openings. Some embodiments may have a one cross-sectional shape
for the opening but have a different cross-sectional shape for
channel downstream from the opening.
Single Channel Sample Collection Device
[0414] Referring now to FIGS. 20A-20B, although the embodiments
herein are typically described as sample collection devices with
two separate channels, it should be understood that some
embodiments may use a single entry channel 2010. This single entry
channel 2010 may or may not be coated. Suitable coatings include
but not are limited to an anti-coagulant, plasma, or other
materials.
[0415] FIG. 20A shows that in this embodiment of sample collection
device 2000, a tissue penetrating member 2112 can be mounted
coaxially within the single entry pathway 2010. This allows the
wound at the target tissue to be formed in a manner that will be
aligned with the single entry pathway 2010. The tissue penetrating
member 2012 can be activated by one of a variety of techniques such
as but not limited to actuation upon pressing a trigger, actuation
upon contact of the device front end with the target tissue, or by
pressure once the device is pressed against the target tissue with
sufficient pressure. After actuation, the tissue penetrating member
2012 can remain in the single entry pathway 2010. Optionally, the
tissue penetrating member 2012 may retract out of the single entry
pathway 2010.
[0416] The sample fluid entering the sample collection device 2000
may split into two or more separate pathways 2014 and 2016 from the
single entry pathway 2010. This enables the sample fluid to be
split into at least two portions from a sample collected from a
single point of contact. The two portions may optionally be held in
two separate holding chambers 2018 and 2020. These chambers may
each have one or more adapter channels 2022 and 2024 to transfer
the sample fluid to the vessels such as but not limited to vessels
1146a and 1146b. It should be understood that the holding chambers
2018 and 2020 and/or the vessels 1146a and 1146b may contain
anti-coagulant therein to prepare the sample fluid for
processing.
[0417] Referring now to FIG. 20B, this embodiment shows that the
single entry pathway 2010 with a tissue penetrating member 2012
therein that, after actuation, is configured to remain in whole or
in part within the single entry pathway 2010. It should be
understood that this embodiment may use a solid penetrating member
or one that is hollow, with a lumen therein.
[0418] Referring now to FIG. 21, yet another embodiment of a sample
collection device 2030 will now be described. This embodiment shows
a reduced length single entry pathway 2032 with a tissue
penetrating member 2012 configured to extend outward from the
pathway 2032. After actuation, the tissue penetrating member 2012
may be in the pathway 2032 or optionally, retracted to not be in
the pathway 2032. The sample fluid entering the sample collection
device 2030 may split into two or more separate pathways 2034 and
2036 from the single entry pathway 2032. This enables the sample
fluid to be split into at least two portions from a sample
collected from a single point of contact. This embodiment shows
that the pathways 2034 and 2036 remain in capillary channel
configuration and do not enlarge to become chambers such as the
embodiments of FIGS. 20A-20B. It should be understood that any of
the embodiments herein may include one or more fill indicators for
the collection pathways and/or the vessels on the devices so that
users can know when sufficient fill levels have been reached.
[0419] It should also be understood that due to the small sample
volume collected with vessels such as but not limited to vessels
1146a and 1146b, the "pull" from reduced pressure, such as but not
limited to vacuum pressure, in the vessels is minimally or not
transferred into the body of subject in a manner that may collapse
or detrimentally reshape the blood vessel or other lumen from which
sample fluid is being collected. For example, pediatric and
geriatric patients typically have small and/or weak veins that can
collapse when traditional, large volume vacutainers are used, due
the higher vacuum forces associated with drawing larger sample
volumes into those traditional vessels. In at least one embodiment
of the device, it will not have this problem because it will not
impart a vacuum (suction) force on the vein. In one embodiment, the
amount of vacuum force draws no more than 120 uL of sample fluid
into the vessel 1146a. Optionally, the amount of vacuum force draws
no more than 100 uL into the vessel 1146a. Optionally, the amount
of vacuum force draws no more than 80 uL into the vessel 1146a.
Optionally, the amount of vacuum force draws no more than 60 uL
into the vessel 1146a. Optionally, the amount of vacuum force draws
no more than 40 uL into the vessel 1146a. Optionally, the amount of
vacuum force draws no more than 20 uL into the vessel 1146a. In one
embodiment, this type of draw is performed without the use of a
syringe and based primarily on pulling force from the vessels and
any force from the fluid exiting the subject. Optionally, the
shaped pathway through the device to draw sample that has reached
an interior of the device can assist in reducing force transfer
from the vessels 1146a and 1146b to the subject's blood vessel or
other body lumen. Some embodiments may use about three-quarter
vacuum or less in the small volume vessels listed above to minimize
hemolysis of the sample and to prevent collapsing of blood vessel
in the subject. Some embodiments may use about half vacuum or less
in the small volume vessels listed above to minimize hemolysis of
the sample and to prevent collapsing of blood vessel in the
subject. Some embodiments may use about one quarter vacuum or less
in the small volume vessels listed above to minimize hemolysis of
the sample and to prevent collapsing of blood vessel in the
subject. Vacuum herein is full vacuum, relative to atmospheric
pressure.
[0420] It should also be understood that, in one embodiment, the
chamber cross-sectional area in the device is greater than the
cross-sectional diameter of the needle and/or flexible tubing used
for drawing the bodily fluid from the subject. This further assists
in reducing the force transfer to the subject. The vacuum pull from
the vessels are drawing most immediately on liquid sample in the
device, not directly on sample in the needle which is more
proximate to the subject. The longer pathway, buffered by the
larger volume chamber in the collection device dampens the pull on
the blood vessel in the subject. Additionally, the initial peak
force pull is substantially less in a small volume vessel versus a
larger volume vessel that is also under vacuum. The duration of the
"pull" is also longer to enable the larger amount of sample to
enter the vessel. In a smaller volume, a significant portion of the
sample to be collected is already in the device and there is less
that is drawn from the subject that is not already in the device
prior to beginning the sample pull.
[0421] Referring now to FIG. 22, yet another embodiment of a sample
collection device will now be described. This embodiment shows a
collection device 2100 that has a connector 2102 such as but not
limited to Luer connector that allows for connection to a variety
of sample acquisition devices such as a tissue penetrating member,
needle, or the like. Some Luer connectors may use a press-fit to
engage other connectors while some embodiments of the connector
2102 may include threads to facilitate engagement. FIG. 22 shows
that in this current embodiment, a butterfly needle 2104 is coupled
to a fluid connection pathway 2106 such as but not limited to a
flexible tube that leads to a connector 2108 to connect the sample
acquisition features to the sample collection device 2100. The
flexible tubing 2106 allows the needle portion 2104 to be located
away from but still operably fluidly coupled to the sample
collection device 2100. This allows for greater flexibility in
terms of positioning of the needle 2104 to acquire sample fluid
without having to also move the sample collection device 2100.
Optionally, some embodiments may directly couple the tissue
penetrating member to the device 2100 without the use of flexible
tubing.
[0422] At least some or all of the embodiments can have a fill
indicator such as but not limited to a view window or opening that
shows when sample is present inside the collection device and thus
indicate that it is acceptable to engage the sample vessel(s).
Optionally, embodiments that do not have a fill indicator are not
excluded. Some embodiments may optionally include one or more
vents, such as but not limited to a port, to allow air escape as
the channels in the collection device are filled with sample. In
most embodiments, the filled sample vessel(s) may be disconnected
from the sample collection device after a desired fill level is
reached. Optionally, additional sample vessel(s) can be engaged to
the sample collection device to collect additional amounts of
bodily fluid sample. Optionally, the interior conditions of the
sample vessels are such that the vessels has a reduced pressure
configure to draw in only a pre-determined amount of sample
fluid.
[0423] FIG. 23 shows an exploded view of one embodiment of the
sample collection device 2100. In this non-limiting example, the
portion 1130 may be configured to hold the vessel holder 1140 and
the portion with sampling device holder 2160. The device 2100 may
include an anti-leakage device 2162 that can engage the open ends
of the adapter channels 2022 and 2024 to minimize sample loss
through the open ends until the vessels in holder 1140 are engaged
to draw sample in any vessel(s) therein. In the current embodiment,
the anti-leakage device 2162 covers at least two adapter channels
2022 and 2024 and is configured to be movable. The present
embodiment of anti-leakage device 2162 is sized so that it can be
moved to uncover the openings on adapter channels 2022 and 2024
while still allowing the adapter channels 2022 and 2024 to engage
the vessel(s) in the holder 1140.
[0424] Referring now to FIGS. 24 and 25, one embodiment of the
sampling device holder 2160 is shown in more detail. FIG. 24 shows
the sampling device holder 2160 as an assembled unit. FIG. 25 shows
an exploded view of the sampling device holder 2160 with a first
portion 2164 and a second portion 2166. The adapter channels 2022
and 2024 are also show as being removable from the second portion
2166. Although this embodiment of the sampling device holder 2160
is shown as two separate portions, it should be understood that
some alternative embodiments can configure the sample device holder
2160 as a single unitary unit. Optionally, some embodiments may
configure to have more than two portions that are assembled
together to form the holder 2160. Optionally, some embodiments may
create separate portions along a longitudinal axis 2165 or other
axis of the holder 2160, instead of along a lateral axis of holder
2160 this is shown by the separation in FIG. 25.
[0425] Referring now to FIGS. 26 through 28, various
cross-sectional views of embodiments of the sample device holder
2160 and the device 2100 are shown. FIG. 26 shows a cross-sectional
view of the portions 2164 and 2166. Although not being bound by any
particular theory, the use of the separation portions 2164 and 2166
can be selected simplify manufacturing, particularly for forming
the various internal channels and chambers in the holder 2160. For
example, at least one wall 2167 of the chamber can be formed in the
first portion 2164 while complementary walls 2168 of the chamber
can be formed in the second portion 2166. FIG. 27 shows a top-down
end view of the portion 2166 with the wall 2168 visible from the
end view.
[0426] Referring now to FIG. 28, a cross-sectional view of the
assembled device 2100 will now be described. This FIG. 28 shows
that sample entering the device through the connector 2102 will
enter the common chamber 2170 before leading to the adapter
channels 2022 and 2024. From the adapter channels 2022 and 2024,
movement of the holder 1140 in the direction indicated by arrow
2172 will operably fluidically couple the vessels 1146a and 1146b
to the adapter channels 2022 and 2024, moving sample from the
channels into the vessels. In the present embodiment, there is
sufficient space 2174 to allow for movement of the vessels 1146a
and 1146b to have the adapter channels 2022 and 2024 penetrate the
caps of the vessels 1146a and 1146b so that the adapter channels
2022 and 2024 are in fluid communication with the interior of the
vessels 1146a and 1146b. Although only two vessel and adapter
channel sets are shown in the figures, it should be understood that
other configuration with more or less sets of vessels and adapter
channels can be configured for use with a device such as that shown
in FIG. 28.
[0427] Modular Sample Collection Device
[0428] Referring now to FIGS. 29A-29C, although the embodiments
herein typically describe sample collection device as having an
adapter channel for connecting the sample collection channels with
the vessels, it should be understood that embodiments without such
configurations are not excluded.
[0429] By way of non-limiting example in FIG. 29A, as previously
suggested herein, some embodiments may be without a discrete,
separate adapter channel. Herein the collection channel 2422 may
connect directly to the vessel 2446 by way of relative motion
between one or both of those elements as indicated by the arrow
2449.
[0430] By way of non-limiting example in FIG. 29B, one or more
adapter channels 2454 may be discrete elements not initially in
direct fluid communication with either the collection channel 2422
or the vessels 2446. Herein the collection channel 2422 may connect
to the vessel 2446 by way of relative motion between one or more of
the collection channel, the adapter channel(s) 2454, or the vessel
2446 (sequentially or simultaneously) to create a fluid pathway
from the collection channels through the one or more adapter
channels into the vessels.
[0431] By way of non-limiting example in FIG. 29C, one or more
adapter channels 2454 may be elements initially in contact with the
vessels 2446. The adapter channels 2454 may not be directly in
communication with the interior or the vessels. Herein the
collection channel 2400 may connect to the vessel by way of
relative motion between one or more of those elements (sequentially
or simultaneously) to create a fluid pathway from the collection
channels through the one or more adapter channels into the vessels.
Some embodiments may have a septum, sleeve, sleeve with vent, or
cover 2455 over the end of the collection channel which will be
engaged by the adapter channel. The engagement of the various
elements may also move the adapter channel 2454 into the interior
of the vessel 2446, as initially, the adapter channel 2454 may not
be in fluid communication with the interior. Some embodiments
herein may have more than adapter channel and some embodiments may
use adapter channels with pointed ends on both ends of the channel.
There may be variations and alternatives to the embodiments
described herein and that no single embodiment should be construed
to encompass the entire invention.
[0432] It should be understood that any of the embodiments herein
could be modified to include the features recited in the
description for FIGS. 29A-29C.
Sample Processing
[0433] Referring now to FIG. 30, one embodiment of bodily fluid
sample collection and transport system will now be described. FIG.
30 shows a bodily fluid sample B on a skin surface S of the
subject. In the non-limiting example of FIG. 30, the bodily fluid
sample B can be collected by one of a variety of devices. By way of
non-limiting example, collection device 1530 may be but is not
limited to those described in U.S. Patent Application Ser. No.
61/697,797 filed Sep. 6, 2012, which is fully incorporated herein
by reference for all purposes. In the present embodiment, the
bodily fluid sample B is collected by one or more capillary
channels and then directed into sample vessels 1540. By way of
non-limiting example, at least one of the sample vessels 1540 may
have an interior that is initially under a partial vacuum that is
used to draw bodily fluid sample into the sample vessel 1540. Some
embodiments may simultaneously draw sample from the sample
collection device into the sample vessels 1540 from the same or
different collection channels in the sample collection device.
Optionally, some embodiments may simultaneous draw sample into the
sample vessels
[0434] In the present embodiment after the bodily fluid sample is
inside the sample vessels 1540, the sample vessels 1540 in their
holder 1542 (or optionally, removed from their holder 1542) are
loaded into the transport container 1500. In this embodiment, there
may be one or more slots sized for the sample vessel holder 1542 or
slots for the sample vessels in the transport container 1500. By
way of non-limiting example, they may hold the sample vessels in an
arrayed configuration and oriented to be vertical or some other
pre-determined orientation. It should be understood that some
embodiments of the sample vessels 1540 are configured so that they
hold different amount of sample in each of the vessels. By way of
non-limiting example, this can be controlled based on the amount of
vacuum force in each of the sample vessels, the amount of sample
collected in the sample collection channel(s) of the collection
device, and/or other factors. Optionally, different pre-treatments
such as but not limited to different anti-coagulants or the like
can also be present in the sample vessels.
[0435] As seen in FIG. 30, the sample vessels 1540 are collecting
sample at a first location such as but not limited to a sample
collection site. By way of non-limiting example, the bodily fluid
samples are then transported in the transport container 1500 to a
second location such as but not limited to a receiving site such as
but not limited to an analysis site. The method of transport may be
by courier, postal delivery, or other shipping technique. In many
embodiments, the transport may be implemented by having a yet
another vessel that holds the transport container therein. In one
embodiment, the sample collection site may be a point-of-care.
Optionally, the sample collection site is a point-of-service.
Optionally, the sample collection site is remote from the sample
analysis site.
[0436] Although the present embodiment of FIG. 30 shows the
collection of bodily fluid sample from a surface of the subject,
other alternative embodiments may use collection techniques for
collecting sample from other areas of the subject, such as by
venipuncture, to fill the sample vessel(s) 1540. Such other
collection techniques are not excluded for use as alternative to or
in conjunction with surface collection. Surface collection may be
on exterior surfaces of the subject. Optionally, some embodiments
may collect from accessible surfaces on the interior of the
subject. Presence of bodily fluid sample B on these surfaces may be
naturally occurring or may occur through wound creation or other
techniques to make the bodily fluid surface accessible.
[0437] Referring now to FIG. 31, yet another embodiment is
described herein wherein bodily fluid sample can be collected from
an interior of the subject versus collecting sample that is pooled
on a surface of the subject. This embodiment of FIG. 31 shows a
collection device 1550 with a hypodermic needle 1552 that is
configured to collect bodily fluid sample such as but not limited
to venous blood. In one embodiment, the bodily fluid sample may
fill a chamber 1554 in the device 1550 at which time sample
vessel(s) 1540 may be engaged to draw the sample into the
respective vessel(s). Optionally, some embodiments may not have a
chamber 1554 but instead have very little void space other than
channel(s), pathway(s), or tube(s) used to direct sample from the
needle 1552 to the sample vessel(s) 1540. For bodily fluid samples
such as blood, the pressure from within the blood vessel is such
that the blood sample can fill the chamber 1554 without much if any
assistance from the collection device. Such embodiments may
optionally include one or more vents, such as but not limited to a
port, to allow air escape as the channels in the collection device
are filled with sample. Optionally, some embodiments may have,
instead of tubing connection to a needle, a direct needle attach to
the collection device 1550, similar to that shown in FIG. 44 where
the needle is rigidly or substantially rigidly connected to the
collection device. Some embodiments may have a removable
connection, a releasable connection, a Luer connection, a threaded
connection, or other needle connection technique that may be
developed in the future.
[0438] At least some or all of the embodiments can have a fill
indicator such as but not limited to a view window or opening that
shows when sample is present inside the collection device and thus
indicate that it is acceptable to engage the sample vessel(s) 1540.
Optionally, embodiments that do not have a fill indicator are not
excluded. The filled sample vessel(s) 1540 may be disconnected from
the sample collection device after a desired fill level is reached.
Optionally, additional sample vessel(s) 1540 can be engaged to the
sample collection device 1550 (or 1530) to collect additional
amounts of bodily fluid sample.
Point of Service System
[0439] Referring now to FIG. 32, it should be understood that the
processes described herein may be performed using automated
techniques. The automated processing may be used in an integrated,
automated system. In some embodiments, this may be in a single
instrument having a plurality of functional components therein and
surrounded by a common housing. The processing techniques and
methods for sedimentation measure can be pre-set. Optionally, that
may be based on protocols or procedures that may be dynamically
changed as desired in the manner described in U.S. patent
application Ser. Nos. 13/355,458 and 13/244,947, both fully
incorporated herein by reference for all purposes.
[0440] In one non-limiting example as shown in FIG. 32, an
integrated instrument 2500 may be provided with a programmable
processor 2502 which can be used to control a plurality of
components of the instrument. For example, in one embodiment, the
processor 2502 may control a single or multiple pipette system 2504
that is movable X-Y and Z directions as indicated by arrows 2506
and 2508. The same or different processor may also control other
components 2512, 2514, or 2516 in the instrument. In one
embodiment, tone of the components 2512, 2514, or 2516 comprises a
centrifuge.
[0441] As seen in FIG. 32, control by the processor 2502 may allow
the pipette system 2504 to acquire blood sample from cartridge 2510
and move the sample to one of the components 2512, 2514, or 2516.
Such movement may involve dispensing the sample into a removable
vessel in the cartridge 2510 and then transporting the removable
vessel to one of the components 2512, 2514, or 2516. Optionally,
blood sample is dispensed directly into a vessel already mounted on
one of the components 2512, 2514, or 2516. In one non-limiting
example, one of these components 2512, 2514, or 2516 may be a
centrifuge with an imaging configuration to allow for both
illumination and visualization of sample in the vessel. Other
components 2512, 2514, or 2516 perform other analysis, assay, or
detection functions.
[0442] All of the foregoing may be integrated within a single
housing 2520 and configured for bench top or small footprint floor
mounting. In one example, a small footprint floor mounted system
may occupy a floor area of about 4 m.sup.2 or less. In one example,
a small footprint floor mounted system may occupy a floor area of
about 3 m.sup.2 or less. In one example, a small footprint floor
mounted system may occupy a floor area of about 2 m.sup.2 or less.
In one example, a small footprint floor mounted system may occupy a
floor area of about 1 m.sup.2 or less. In some embodiments, the
instrument footprint may be less than or equal to about 4 m.sup.2,
3 m.sup.2, 2.5 m.sup.2, 2 m.sup.2, 1.5 m.sup.2, 1 m.sup.2, 0.75
m.sup.2, 0.5 m.sup.2, 0.3 m.sup.2, 0.2 m.sup.2, 0.1 m.sup.2, 0.08
m.sup.2, 0.05 m.sup.2, 0.03 m.sup.2, 100 cm.sup.2, 80 cm.sup.2, 70
cm.sup.2, 60 cm.sup.2, 50 cm.sup.2, 40 cm.sup.2, 30 cm.sup.2, 20
cm.sup.2, 15 cm.sup.2, or 10 cm.sup.2. Some suitable systems in a
point-of-service setting are described in U.S. patent application
Ser. Nos. 13/355,458 and 13/244,947, both fully incorporated herein
by reference for all purposes. The present embodiments may be
configured for use with any of the modules or systems described in
those patent applications.
[0443] Referring now to FIGS. 33 to 37, a still further embodiment
of a sample collection device will now be described. As seen in
FIGS. 33 and 34, at least one embodiment shows a sample collection
region 2600 that has a capillary channel region and then a lower
flow resistance region 2610 that increases the cross-sectional area
of the channel to provide for lower flow resistance and increased
flow rates. In at least one embodiment, this lower flow resistance
region 2610 is still a capillary channel, but one with lower flow
resistance. Optionally, other embodiments may increase the size
wherein the sample flows therein but not under capillary action.
The increased size of the channel can also be used to store sample
therein. By way of non-limiting example, this storage can be
temporary during collection, longer term such as for transport from
collection site to refrigeration, from collection site to receiving
site, other location to location transport, or other purpose. One
embodiment can be configured to have caps that go on both ends of
the device so that sample is contained therein without need for
transferring to vessels 1146a and 1146b.
[0444] Because the joint between regions 2600 and 2610 can be
located across the mid-line 2620, this can also reduce the amount
of bonding material used to join the items together. It should be
understood that embodiments can have channels 2612 and 2614 be of
the same cross-sectional size and/or be configured to contain the
same or substantially same volume in the channel. Optionally, the
channels 2612 and 2614 can be configured to hold different volumes.
The same may be true for the channels as they continue into region
2610. Optionally, some embodiments may have different sizes when in
region 2610 while have the same in region 2600 or vice versa. Other
configurations of sizes are not excluded. Although the channels
here are shown as linear, it should be understood that for any of
embodiments disclosed herein, some embodiments may have curved or
other non-straight portion of the channel(s).
[0445] The other parts are similar to those previously described
herein with regards to the vessels 1146a and 1146b, adapter
channels, frits, holders 130, etc. . . . . Wicking of both channels
at the junction (both fill times<6-secs) has been improved (step
removed) and blood got in to the channel easily and passed the
junction area without need for tilting. The parts may be made of
PMMA, PET, PETG, etc. . . . . In this embodiment, this can provide
a 7.5.times. faster fill relative to a capillary channel of one
cross-sectional size because the increase in size of channel in
region 2610 will allow for easier flow into this region.
[0446] The flow resistance decreases to the fourth power in region
2610 based on changes in channel size as seen in the formula:
M . = .pi. .rho. g 32 .mu. [ .sigma. .rho. D 3 L + H 4 D 4 L ]
##EQU00001##
[0447] It should be understood that once a desired amount of sample
is in the channel(s), some embodiments may be configured so that
the sample can be manipulated to be moved into a storage vessel. By
way of non-limiting example, this movement of sample can be by way
of a pull force, a push force, or both. In one embodiment, pull
force may be provided by a vessel that has vacuum therein, a vessel
with a plunger or other movable surface that moves to increase
volume and draw sample therein, or an active vacuum force. In one
embodiment, push force can be pressure from air or other gas
provided from behind a bolus or other fluid grouping. In
embodiment, compressed gas, pressure from a cap with a seal around
the device being slid over the collection device, a syringe coupled
to one end and apply gas pressure, or other force can be exerted to
urge gas forward. Force being provided may be different from the
motive force used to collect the sample in the channel(s).
Optionally, some embodiments may use, different motive force per
channel. Optionally, some may use a different motive force in
region 2600 relative to zone 2610.
[0448] While the teachings has been described and illustrated with
reference to certain particular embodiments thereof, those skilled
in the art will appreciate that various adaptations, changes,
modifications, substitutions, deletions, or additions of procedures
and protocols may be made without departing from the spirit and
scope of the invention. For example, with any of the above
embodiments, it should be understood that the fluid sample may be
whole blood, diluted blood, interstitial fluid, sample collected
directly from the patient, sample that is on a surface, sample
after some pre-treatment, or the like. Those of skill in the art
will understand that alternative embodiments may have more than one
vessel that may be sequentially operably coupled to the needle or
opening of the channel to draw fluid in the vessel. Optionally,
some embodiments may have the vessels configured to operably couple
to the channels simultaneously. Some embodiments may integrate a
lancing device or other wound creation device with the sample
collection device to bring targeted sample fluid to a tissue
surface and then collect the sample fluid, all using a single
device. By way of nonlimiting example, a spring actuated,
mechanically actuated, and/or electromechanically actuated tissue
penetrating member may be mounted to have a penetrating tip exiting
near an end of the sample collection device near sample collection
channel openings so that the wound site that is created will also
be along the same end of the device as the collection openings.
Optionally, an integrated device may have collection openings on
one surface and tissue penetrating elements along another surface
of the device. In any of the embodiments disclosed herein, the
first opening of the collection channel may have a blunt shape,
which is configured to not readily puncture human skin.
[0449] Additionally, the use of heat patches on the finger or other
target tissue can increase blood flow to the target area and thus
increase the speed with which sufficient blood or other bodily
fluid can be drawn from the subject. The heating is used to bring
the target tissue to about 40 C to 50 C. Optionally, the heat
brings target tissue to a temperature range of about 44 to 47
C.
[0450] Furthermore, those of skill in the art will recognize that
any of the embodiments as described herein can be applied to
collection of sample fluid from humans, animals, or other subjects.
Some embodiments as described herein may also be suitable for
collection of non-biological fluid samples. Some embodiment may use
vessels that are not removable from the carrier. Some may have the
fluid sample, after being metered in the sample collection portion,
be directed by the second motive force to a cartridge that is then
placed into an analyte or other analysis device. Optionally, it
should be understood although many embodiments show the vessels in
the carriers, embodiments where the vessels are bare or not mounted
in carrier are not excluded. Some embodiments may have the vessels
that are separate from the device and are only brought into fluid
communication once the channels have reached minimum fill levels.
For example, the vessels may be held in a different location and
are only brought into contact by a technician once sufficient
amount of blood or sample fluid is in the sample collection device.
At that time, the vessels may be brought into fluid communication
simultaneously or sequentially to one or more of the channels of
the sample collection device.
[0451] Additionally, concentrations, amounts, and other numerical
data may be presented herein in a range format. It is to be
understood that such range format is used merely for convenience
and brevity and should be interpreted flexibly to include not only
the numerical values explicitly recited as the limits of the range,
but also to include all the individual numerical values or
sub-ranges encompassed within that range as if each numerical value
and sub-range is explicitly recited. For example, a size range of
about 1 nm to about 200 nm should be interpreted to include not
only the explicitly recited limits of about 1 nm and about 200 nm,
but also to include individual sizes such as 2 nm, 3 nm, 4 nm, and
sub-ranges such as 10 nm to 50 nm, 20 nm to 100 nm, etc . . . .
Transport Container
[0452] Referring now to FIGS. 38A-38B, an exploded perspective view
is shown of one non-limiting example of a transport container 3200
provided in accordance with one embodiment described herein. It
should be understood that the transport container 3200 may be
configured to have one or more features of any other transport
container described elsewhere herein. By way of non-limiting
example, the transport container 3200 may be useful for
transporting one or more sample vessels therein. In some
embodiments, the transport container 3200 provides a thermally
controlled interior area to minimize undesired thermal
decomposition of the sample during transport to another location,
such as but not limited to an analysis facility. It should be
understood that the transport container may be placed inside one or
more other vessels during transport.
[0453] In one embodiment, the sample vessels may be provided from a
sample collection device that collected the bodily fluid sample. By
way of non-limiting example, the sample vessels may contain sample
therein in liquid form. In most embodiments, liquid form also
includes embodiments that are suspensions.
[0454] By way of non-limiting example, the transport container 3200
may have any dimension. In some instances, the transport container
3200 may have a total volume of less than or equal to about 1
m.sup.3, 0.5 m.sup.3, 0.1 m.sup.3, 0.05 m.sup.3, 0.01 m.sup.3, 1000
cm.sup.3, 500 cm.sup.3, 300 cm.sup.3, 200 cm.sup.3, 150 cm.sup.3,
100 cm.sup.3, 70 cm.sup.3, 50 cm.sup.3, 30 cm.sup.3, 20 cm.sup.3,
15 cm.sup.3, 10 cm.sup.3, 7 cm.sup.3, 5 cm.sup.3, 3 cm.sup.3, 2
cm.sup.3, 1.5 cm.sup.3, 1 cm.sup.3, 700 mm.sup.3, 500 mm.sup.3, 300
mm.sup.3, 100 mm.sup.3, 50 mm.sup.3, 30 mm.sup.3, 10 mm.sup.3, 5
mm.sup.3, or 1 mm.sup.3. The footprint and/or a largest
cross-sectional area of the transport container may be less than or
equal to about 1 m.sup.2, 0.5 m.sup.2, 0.1 m.sup.2, 0.05 m.sup.2,
100 cm.sup.2, 70 cm.sup.2, 50 cm.sup.2, 30 cm.sup.2, 20 cm.sup.2,
15 cm.sup.2, 10 cm.sup.2, 7 cm.sup.2, 5 cm.sup.2, 3 cm.sup.2, 2
cm.sup.2, 1.5 cm.sup.2, 1 cm.sup.2, 70 mm.sup.2, 50 mm.sup.2, 30
mm.sup.2, 10 mm.sup.2, 5 mm.sup.2, or 1 mm.sup.2. In some
instances, the transport container may have a dimension (e.g.,
height, width, length, diagonal, or circumference) of less than or
equal to about 1 m, 75 cm, 50 cm, 30 cm, 25 cm, 20 cm, 15 cm, 12
cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1 cm,
0.7 cm, 0.5 cm, 0.3 cm, or 1 mm. In some instances, the largest
dimension of the transport container may be no greater than about 1
m, 75 cm, 50 cm, 30 cm, 25 cm, 20 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8
cm, 7 cm, 6 cm, 5 cm, 4 cm, 3 cm, 2 cm, 1 cm, 0.7 cm, 0.5 cm, 0.3
cm, or 1 mm.
[0455] Optionally, the transport container may be lightweight. In
some embodiments, the transport container may weigh less than or
equal to about 10 kg, 5, kg, 4 kg, 3 kg, 2 kg, 1.5 kg, 1 kg, 0.7
kg, 0.5 kg, 0.3 kg. 100 g, 70 g, 50 g, 30 g, 20 g, 15 g, 10 g, 7 g,
5 g, 3 g, 2 g, 1 g, 500 mg, 300 mg, 200 mg, 100 mg, 70 mg, 50 mg,
30 mg, 10 mg, 5 mg, or 1 mg, with or without the sample vessels
having sample therein.
[0456] As seen in FIGS. 38A and 38B, one embodiment of the
transport container may have a top cover 3210, a housing for a
thermal regulating device 3220, one or more insert trays for the
transport containers 3230a, 3230b, and a bottom plate 3240.
[0457] In one embodiment, the top cover 3210 has a substantially
flat shape although other shapes are not excluded. The top cover
3210 may cover a thermal regulating device such as but not limited
to heater or cooler contained in the transport container. The top
cover may or may not have the same footprint as a housing 3220 for
the thermal regulating device. A cooler, heater, or other thermal
regulating device 3220 may be provided within the transport
container 3200. Optionally, the device 3220 may be active or
passive units. The thermal regulating device may keep the sample
vessels within the transport container 3200 at a desired
temperature or below a predetermined threshold temperature.
Optionally, the thermal regulating device may be any temperature
control unit known in the art. Optionally, the thermal regulating
device may be capable of heating and/or cooling. Optionally, the
thermal regulating device may be a thermoelectric cooler.
Optionally, the thermal regulating device may be encased between
the top cover and the housing for the cooler.
[0458] Optionally, the top cover and the housing may or may not
form an airtight seal. The top cover and/or housing may be formed
from a material with a desired thermal conductivity. For example,
the housing 3220 may have a selectable thermal conductivity. In one
embodiment, the housing may include an embedded phase change
material (PCM) within the box material, so the temperature is
substantially uniform throughout. PCM holds a very good temperature
profile. It is desirable not to have supercooling of the sample,
such as that associated with ice, which may create a negative drop
to -5.degree. C. PCM can be configured to control to temperature
ranges above freezing. By way of nonlimiting example, thermal
conductivity may be in the range between about 100-250 W/m/K
(watts/meter/Kelvin). Optionally, each sample vessel will come into
contact with the PCM. Some embodiments may have one PCM for each
layer. The PCM material may be flow molded into the transport
container material. Optionally, there may be a chamber for the PCM
material. Optionally, gaps in the tray may be filled with PCM. The
PCM can provide a passive thermal control technique.
[0459] Optionally, the PCM may be incorporated into the injection
molding material. In such an embodiment, the entire vessel may be a
cooling medium. This can also prevent leakage of PCM from chambers
in the transport container. Transport container size can also
shrink when the PCM is directly integrated into the transport
container material. Energy density is greater since storage
capacity per mass is increased. Mixing plastics with PCM material
can be configured to have both strength and cooling. By way of
non-limiting example, 30% of the material may be PCM and the
remainder is plastic for rigidity. By way of non-limiting example,
between 20% to 40% of the material may be PCM while the remainder
is another material such as but not limited to plastic for
mechanical rigidity. Some embodiments may use a blow-molded outer
that is filled with PCM or other material. Inner could be formed
with a different technique as it is may not be critical for the
interior to be cosmetically appealing. Optionally, cast molding or
other lower temperature molding process could also be used in place
of or in combination with injection molding of the PCM integrated
transport container material. Embedded PCM could also be in the
trays. Some embodiments could be a tray that is much more thermally
conductive to achieve even, uniform cooling profile. Optionally,
the PCM material is contained in a chamber inside the chassis of
the transport container, wherein the wall of the chamber may be
thinner than wall thickness of other areas of the shipping box
chassis.
[0460] In one embodiment, the transport container 3200 may also
have each of the trays 3230a and 3230b configured so that any
information storage units on the sample vessels are easily readable
without having to remove the sample vessels from the trays 3230a
and 3230b. In one example, the holders have openings at the bottom
that allow information storage units on the bottom to be visualized
while the sample vessels are still in the trays 3230a and
3230b.
[0461] FIG. 39 shows a plurality of views of the transport
container 3200. Some show that the sample vessel holders in the
trays 3230a or 3230b may have open bottoms such that any
information storage unit, such as but limited to a barcode or other
information storage unit, can be read from underneath or other
orientation that does not require that sample vessels be removed
from the transport container 3200. Optionally, only certain
portions of the transport container 3200 such as but not limited to
a layer, a tray, or the like is removed to obtain the desired
information. Optionally, bar codes or other information storage
units can be accessed through one or more openings in the tray.
That allows for bar code scanning of very small transport
container. Optionally, one could scan rows of sample vessels
individually or can scan entire tray all at once. Optionally, a
user can see all sample vessel holders. Optionally, a computer
vision system can also scan to see if a step such as centrifugation
was completed. This can be at either end of the shipping process.
The computer vision system can visualize the sample vessel and
determine if the sample there is in a form that confirms that a
desired step was completed. If it detects an error, the system can
inform the user or the system of the issue and/or re-perform the
missing and/or incorrectly performed step. Optionally, the holders
may have closed bottoms and information may be on the sides or
other surfaces of the transport container 3200.
[0462] In some embodiments, the shapes of the holders may also be
designed to follow the contours of the sample vessels 3134 therein
to increase surface area contact and improve thermal control of the
sample vessels. Optionally, thermal control of the sample vessels
may occur through thermal transfer with tray and/or the PCM, but
not in direct contact with the PCM. Optionally, some sample vessels
3134 could also be in direct contact with the vessel and/or the
PCM. The openings for the sample vessels and/or the holders may be
in linear rows, in a honeycomb pattern, or be in another
pattern.
[0463] Referring now to FIGS. 40A and 40B, a transport container
3200 is shown fully assembled. FIG. 40B shows a plurality of sample
vessels 3134 such as those associated with the sample collection
device. The sample vessels 3134 can all be from sample associated
with one subject in which case an information storage unit
associated with tray 3230a can be used to provide information about
this group of samples. Optionally, individual sample vessels may
still each have an information storage unit that is the same as
that of the tray 3230a or they may each be unique. Some embodiments
may insert sample vessels from multiple subjects into the same tray
3230a. Optionally, some may only partially fill each tray. Some may
fill each opening in the tray, but not every sample vessel will
have sample therein (i.e. some may be empty sample vessels inserted
to provide uniform thermal profile). These stackable trays 3230a
may have closure devices that use elements such as but not limited
to magnets, mechanical latches, or other coupling mechanisms to
couple trays together. In some embodiments, magnets may be used to
engage the tray holding the sample vessels to enable ease of
opening during automation of loading and unloading. Optionally, the
user cannot remove the tray from the transport container.
Optionally, the user cannot remove the tray from the transport
container without the use of a tool to release the tray. Some
embodiments have a keying mechanism (magnetic or other technique).
In this manner, the patient service center can put sample in but
cannot take it out. Optionally, some embodiments can have shaped
openings selected so that one cannot put the sample vessels and/or
their holders in the wrong way to prevent user error.
[0464] In one embodiment, the loading and/or unloading may occur in
a temperature regulated room or chamber to maintain samples in a
desired temperature range. In one embodiment, it is desirable to
have a temperature range between about 1.degree. to 10.degree. C.
Optionally, it is desirable to have the temperature range between
about 2.degree. to 8.degree. C. Optionally, it is desirable to have
a temperature range between about 4.degree. to 5.degree. C.
Optionally, the materials of the trays 230a and 230b may be used to
provide thermally controlled atmosphere for the sample vessels.
Some use convection to control thermal profile inside the transport
container 200.
[0465] FIG. 40B also shows that in this particular embodiment,
there may be a groove 3232 for an o-ring or other seal that can
provide a tight connection between layers of the transport
container. The system may also include closure mechanisms 3234 such
as but not limited magnetic closure devices to maintain the
stackable insert tray in the desired position. It should also be
understood that some embodiments may have through-holes 3236 for
wiring sensor(s) to detect conditions experienced the stackable
insert tray during shipment.
[0466] FIG. 40C shows various perspective views of the embodiment
of FIGS. 40A and 40B when the various components such the stackable
trays and the lids are joined together to form the transport
container 3200. As seen in FIG. 40C, the transport container may be
comprised of multiple layers of sample vessels or trays having
sample vessels. Optionally, some embodiments may have only a single
layer of sample vessels. Some embodiments may use actively cooling
or thermal control in one or more layers of the transport container
3200. By way of non-limiting example, one embodiment may have a
thermo-electric cooler in the top layer. Optionally, some
embodiments may use a combination of active and passive thermal
control. By way of non-limiting example, one embodiment may have a
thermal mass such as but not limited to a phase change material
(PCM) that is already at a desired temperature. An active thermal
control unit may be included to keep the PCM in the desired
temperature range. Optionally, some embodiments may use only a
thermal mass such as but not limited to a PCM to maintain
temperature in a desired range.
Transport Container with Removable Tray
[0467] Referring now to FIG. 41, yet another embodiment of a
transport container will now be described. FIG. 41 shows a
transport container 3300 having a thermally-controlled interior
3302 that houses a tray 3304 that can hold a plurality of sample
vessels 3306 in an array configuration, wherein each of the vessels
3306 holds a majority of its sample in a free-flowing, non-wicked
form and wherein there is about 1 ml or less of sample fluid in
each of the vessels. Optionally, there is about 2 ml or less of
sample fluid in each of the vessels. Optionally, there is about 3
ml or less of sample fluid in each of the vessels. In one
non-limiting example, the vessels are arranged such that there are
at least two vessels in each transport container with sample fluid
from the same subject, wherein at least a first sample includes a
first anticoagulant and a second sample includes a second
anticoagulant in the matrix.
[0468] Although FIG. 41 shows the sample vessels 3306 are held in
an array configuration, other predetermined configurations are not
excluded. Some may place the sample vessels into hinged, swinging,
or other retaining mechanism in the tray that may allow for motion
in one or two degrees of freedom. Some embodiments may place the
sample vessels into a device that has first configuration during
loading and then assumes a second configuration to retain the
sample vessels during transport. Some embodiments may place the
sample vessels into a material that has first material property
during loading and then assumes a second property such as but not
limited to hardening to retain the sample vessels during
transport.
[0469] In some embodiments, the sample vessels are in holders 3310
and the tray 3304 defines openings and/or cavities sized to fit the
holders 3310 and not the sample vessels. By way of non-limiting
example, the holders 3310 can be used to keep associated vessels
3306 physically together while in the tray 3304. Some embodiments
have the holders 3310 directly contacting the tray 3304 so that the
vessels are protected from direct contact with the tray 3304. In
one non-limiting example, the tray can hold at least 100 vessels,
or optionally, at least 50 holders each having two vessels.
[0470] Referring still to FIG. 41, this embodiment of transport
container 3300 may have some retaining mechanism 3320 such as but
not limited to clips, magnetic areas, or the like to hold the tray
3306. The retaining mechanism 3320 may be configured to hold the
tray 3304 in a manner releasable when desired. Optionally, the
retaining mechanism 3320 may be configured to hold the tray 3304 in
an un-releasable manner. In the embodiment shown in FIG. 41, the
retaining mechanism 3320 is shown as magnetic and/or metallic
members in tray 3304 that are attracted to metal and/or magnetic
members in the transport container 3300. When the transport
container 3300 arrives at a processing facility, the tray 3304 may
be configured to be removed from the transport container 3300. This
can occur by use of one or more techniques including but not
limited to using strong magnets to engage the magnetic and/or
metallic members in tray 3304. Some embodiments may use grippers,
hooks, or other mechanical mechanisms to remove the tray 3304 from
the transport container 3300. Some embodiments may use a
combination of techniques to remove the tray 3304. It should also
be understood that some embodiments may opt to remove the vessels
3306 and/or the holders 3310 while the tray 3304 remains in the
transport container 3300. Some techniques may perform at two or
more of the foregoing techniques.
[0471] It should also be understood that the transport container
3300 may itself be a cooling device, comprising a thermal control
material such as but not limited to ice, a PCM, or the like. Other
embodiments may directly integrate the thermal control material
into the material used to form the transport container 3300. As
seen in FIG. 41, some embodiments of the transport container 3300
may have a substantial void space 3324 in which one or more the
thermal control material is housed or integrated therein.
[0472] Referring still to FIG. 41, the transport container 3300 may
also include openings 3330 for attachment of hinges or other
connection devices for covers or connections to other layers of the
transport container 3300. For ease of illustration, the cover
and/or connections to the cover or other layer are not shown in
FIG. 41. Although some embodiments may only use a single layer, it
should be understood that multi-layer embodiments are not
excluded.
[0473] Referring now to FIG. 42, an exploded perspective view of
yet another embodiment of a transport container 3400 will now be
described. The embodiment of FIG. 42 is designed to hold a tray
3402 in the transport container interior 3404. The exploded
perspective view shows a plurality of vessels 3406 in holders 3410
in a tray 3402. The tray 3402 may be configured to have some or all
portions of the retention mechanism 3420 similar to retention
mechanisms 3320 in the tray 3402. It should also be understood that
the tray 3402 may have one or more cutouts, protrusions, or
features to allow the tray 3402 to be inserted into the interior in
a limited number of pre-determined orientations. Some embodiments
may be configured to only enable one orientation of the tray in the
vessel. Some embodiments may be configured to only enable two
possible orientations of the tray in the vessel.
[0474] FIG. 42 shows that in one embodiment, the transport
container 3400 may be formed from two separate pieces 3430 and
3432. Optionally, some embodiment may be formed from three or more
pieces. Optionally, some embodiment may be a single piece. The
pieces 3430 and 3432 can have openings that filled by plugs 3434
and 3436. The interior 3438 of the transport container 3400 can
retain a thermal control material such as but not limited to ice, a
phase change material, or the like. Other embodiments may directly
integrate the thermal control material into the material used to
form the transport container 3400.
[0475] In one instance, the interior 3433 of the piece 3432 can be
filled with a thermal control material such as but not limited to a
PCM. Optionally, one embodiment could use an active thermal control
material such as but not limited to a thermoelectric cooler to cool
the interior.
[0476] Referring now to FIG. 43, yet another embodiment of the
transport container 3500 will now be described. FIG. 43 shows that
the transport container 3500 may include a lid 3502 for covering
the features and/or sample vessels therein. In some embodiments,
the lid 3502 may contain thermal insulating material. Optionally,
the lid 3502 may include a thermal control unit to assist in
keeping the interior of the transport container 3500 within a
desired temperature range. Optionally, some embodiments may
configure lid 3502 to be a thermally conductive material that can
be useful in keeping the interior of the transport container 3500
within a desired temperature range through thermal transfer from an
external thermal control source. By way of non-limiting example,
the thermal control source may be a cooling source, a heating
source, a thermoelectric heat exchanger, or other thermal control
device. It should also be understood that similar thermal control
source such as but not limited to a PCM or an active cooling device
can also be included in the void space 3514 below the layer
3516.
[0477] It should be understood that the features 3512 for retaining
holders 3310, 3410, or other shaped holders for the vessels may be
in a piece separate from the transport container or they can be
integrally formed inside of the transport container. Optionally,
the features 3512 can be part of a tray such as the trays 3302 and
3402 shown in FIGS. 41 and 42. Such a tray can be fixed or
removable from the transport container 3500. Retaining mechanisms
3520 may also be incorporated into the tray to allow it to be held
in place during transport.
Sample Collection and Transport
[0478] In embodiments, provided herein are systems and methods for
collection or transport of small volumes of bodily fluid
sample.
[0479] In embodiments, a sample vessel containing a small volume of
bodily fluid sample may be transported. The sample and sample
vessel may have any of the respective characteristics described
elsewhere herein. In embodiments, a sample vessel may contain less
than or equal to 5 ml, 3 ml, 4 ml, 2 ml, 1.5 ml, 1 ml, 750 .mu.l,
500 .mu.l, 400 .mu.l, 300 .mu.l, 200 .mu.l, 150 .mu.l, 100 .mu.l,
75 .mu.l, 50 .mu.l, 40 .mu.l, 30 .mu.l, 20 .mu.l, 10 .mu.l, or 5
.mu.l bodily fluid sample. In embodiments, a sample vessel may have
an interior volume of less than or equal to 5 ml, 3 ml, 4 ml, 2 ml,
1.5 ml, 1 ml, 750 .mu.l, 500 .mu.l, 400 .mu.l, 300 .mu.l, 200
.mu.l, 150 .mu.l, 100 .mu.l, 75 .mu.l, 50 .mu.l, 40 .mu.l, 30
.mu.l, 20 .mu.l, 10 .mu.l, or 5 .mu.l. In embodiments, a sample
vessel may have an interior volume of less than or equal to 5 ml, 4
ml, 3 ml, 2 ml, 1.5 ml, 1 ml, 750 .mu.l, 500 .mu.l, 400 .mu.l, 300
.mu.l, 200 .mu.l, 150 .mu.l, 100 .mu.l, 75 .mu.l, 50 .mu.l, 40
.mu.l, 30 .mu.l, 20 .mu.l, 10 .mu.l, or 5 .mu.l, and may contain
bodily fluid sample which fills at least 10%, 20%, 30%, 40%, 50%,
60%, 70%, 80%, 90%, 95%, 98%, 99%, or 100% of the interior volume
of the vessel. In embodiments, the sample vessel may be sealed, for
example, with a cap, lid, or membrane. Any of the vessel interior
dimensions or sample dimensions described herein may apply to the
interior dimensions of a sealed sample vessel, or to the dimensions
of a sample therein, respectively. In embodiments, a sealed sample
vessel may have an interior volume of less than or equal to 5 ml, 4
ml, 3 ml, 2 ml, 1.5 ml, 1 ml, 750 .mu.l, 500 .mu.l, 400 .mu.l, 300
.mu.l, 200 .mu.l, 150 .mu.l, 100 .mu.l, 75 .mu.l, 50 .mu.l, 40
.mu.l, 30 .mu.l, 20 .mu.l, 10 .mu.l, or 5 .mu.l, and it may contain
bodily fluid sample which fills at least 10%, 20%, 30%, 40%, 50%,
60%, 70%, 80%, 90%, 95%, 98%, 99%, or 100% the interior volume of
the vessel, such that less than or equal to 2 ml, 1.5 ml, 1 ml, 750
.mu.l, 500 .mu.l, 400 .mu.l, 300 .mu.l, 200 .mu.l, 150 .mu.l, 100
.mu.l, 75 .mu.l, 50 .mu.l, 40 .mu.l, 30 .mu.l, 20 .mu.l, 10 .mu.l,
5 .mu.l, 4 .mu.l, 3 .mu.l, 2 .mu.l, or 1 .mu.l of air is present in
the interior volume of the sealed vessel. Thus, for example, a
sealed sample vessel may have an interior volume of less than or
equal to 300 .mu.l and it may contain bodily fluid sample which
fills at least 90% of the interior volume of the vessel, such that
less than or equal to 30 ul of air is present in the interior
volume of the sealed vessel. In another example, a sealed sample
vessel may have an interior volume of less than or equal to 500
.mu.l and it may contain bodily fluid sample which fills at least
80% of the interior volume of the vessel, such that less than or
equal to 100 ul of air is present in the interior volume of the
sealed vessel. In another example, a sealed sample vessel may have
an interior volume of less than or equal to 150 .mu.l and it may
contain bodily fluid sample which fills at least 98% of the
interior volume of the vessel, such that less than or equal to 3
.mu.l of air is present in the interior volume of the sealed
vessel.
[0480] In embodiments, sample vessels containing a sample may also
contain an anticoagulant. The anticoagulant may be dissolved in the
sample or otherwise present in the vessel (e.g. dried on one or
more interior surfaces of the vessel or in solid form at the bottom
of the vessel). A sample vessel containing a sample may have a
"total anticoagulant content", wherein the total anticoagulant
content is the total amount of anticoagulant present in the
interior volume of the vessel, and includes anticoagulant dissolved
in the sample (if any), as well as anticoagulant in the vessel
which is not dissolved in the sample (if any). In embodiments, a
sample vessel containing a sample may contain no more than 1 ml
sample and have a total anticoagulant content of no more than 3 mg
EDTA, may contain no more than 750 .mu.l sample and have a total
anticoagulant content of no more than 2.3 mg EDTA, may contain no
more than 500 .mu.l sample and have a total anticoagulant content
of no more than 1.5 mg EDTA, may contain no more than 400 .mu.l
sample and have a total anticoagulant content of no more than 1.2
mg EDTA, may contain no more than 300 .mu.l sample and have a total
anticoagulant content of no more than 0.9 mg EDTA, may contain no
more than 200 .mu.l sample and have a total anticoagulant content
of no more than 0.6 mg EDTA, may contain no more than 150 .mu.l
sample and have a total anticoagulant content of no more than 0.45
mg EDTA, may contain no more than 100 .mu.l sample and have a total
anticoagulant content of no more than 0.3 mg EDTA, may contain no
more than 75 .mu.l sample and have a total anticoagulant content of
no more than 0.23 mg EDTA, may contain no more than 50 .mu.l sample
and have a total anticoagulant content of no more than 0.15 mg
EDTA, may contain no more than 40 .mu.l sample and have a total
anticoagulant content of no more than 0.12 mg EDTA, may contain no
more than 30 .mu.l sample and have a total anticoagulant content of
no more than 0.09 mg EDTA, may contain no more than 20 .mu.l sample
and have a total anticoagulant content of no more than 0.06 mg
EDTA, may contain no more than 10 .mu.l sample and have a total
anticoagulant content of no more than 0.03 mg EDTA, or may contain
no more than 5 .mu.l sample and have a total anticoagulant content
of no more than 0.015 mg EDTA. In embodiments, a sample vessel
containing a sample may contain no more than 1 ml sample and have a
total anticoagulant content of no more than 2 mg EDTA, may contain
no more than 750 .mu.l sample and have a total anticoagulant
content of no more than 1.5 mg EDTA, may contain no more than 500
.mu.l sample and have a total anticoagulant content of no more than
1 mg EDTA, may contain no more than 400 .mu.l sample and have a
total anticoagulant content of no more than 0.8 mg EDTA, may
contain no more than 300 .mu.l sample and have a total
anticoagulant content of no more than 0.6 mg EDTA, may contain no
more than 200 .mu.l sample and have a total anticoagulant content
of no more than 0.4 mg EDTA, may contain no more than 150 .mu.l
sample and have a total anticoagulant content of no more than 0.3
mg EDTA, may contain no more than 100 .mu.l sample and have a total
anticoagulant content of no more than 0.2 mg EDTA, may contain no
more than 75 .mu.l sample and have a total anticoagulant content of
no more than 0.15 mg EDTA, may contain no more than 50 .mu.l sample
and have a total anticoagulant content of no more than 0.1 mg EDTA,
may contain no more than 40 .mu.l sample and have a total
anticoagulant content of no more than 0.08 mg EDTA, may contain no
more than 30 .mu.l sample and have a total anticoagulant content of
no more than 0.06 mg EDTA, may contain no more than 20 .mu.l sample
and have a total anticoagulant content of no more than 0.04 mg
EDTA, may contain no more than 10 .mu.l sample and have a total
anticoagulant content of no more than 0.02 mg EDTA, or may contain
no more than 5 .mu.l sample and have a total anticoagulant content
of no more than 0.01 mg EDTA. In embodiments, a sample vessel
containing a sample may contain no more than 1 ml sample and have a
total anticoagulant content of no more than 30 US Pharmacopeia
(USP) units heparin, may contain no more than 750 .mu.l sample and
have a total anticoagulant content of no more than 23 USP units
heparin, may contain no more than 500 .mu.l sample and have a total
anticoagulant content of no more than 15 USP units heparin, may
contain no more than 400 .mu.l sample and have a total
anticoagulant content of no more than 12 USP units heparin, may
contain no more than 300 .mu.l sample and have a total
anticoagulant content of no more than 9 USP units heparin, may
contain no more than 200 .mu.l sample and have a total
anticoagulant content of no more than 6 USP units heparin, may
contain no more than 150 .mu.l sample and have a total
anticoagulant content of no more than 4.5 USP units heparin, may
contain no more than 100 .mu.l sample and have a total
anticoagulant content of no more than 3 USP units heparin, may
contain no more than 75 .mu.l sample and have a total anticoagulant
content of no more than 2.3 USP units heparin, may contain no more
than 50 .mu.l sample and have a total anticoagulant content of no
more than 1.5 USP units heparin, may contain no more than 40 .mu.l
sample and have a total anticoagulant content of no more than 1.2
USP units heparin, may contain no more than 30 .mu.l sample and
have a total anticoagulant content of no more than 0.9 USP units
heparin, may contain no more than 20 .mu.l sample and have a total
anticoagulant content of no more than 0.6 USP units heparin, may
contain no more than 10 .mu.l sample and have a total anticoagulant
content of no more than 0.3 USP units heparin, or may contain no
more than 5 .mu.l sample and have a total anticoagulant content of
no more than 0.15 USP units heparin. In embodiments, a sample
vessel containing a sample may contain no more than 1 ml sample and
have a total anticoagulant content of no more than 15 USP units
heparin, may contain no more than 750 .mu.l sample and have a total
anticoagulant content of no more than 11 USP units heparin, may
contain no more than 500 .mu.l sample and have a total
anticoagulant content of no more than 7.5 USP units heparin, may
contain no more than 400 .mu.l sample and have a total
anticoagulant content of no more than 6 USP units heparin, may
contain no more than 300 .mu.l sample and have a total
anticoagulant content of no more than 4.5 USP units heparin, may
contain no more than 200 .mu.l sample and have a total
anticoagulant content of no more than 3 USP units heparin, may
contain no more than 150 .mu.l sample and have a total
anticoagulant content of no more than 2.3 USP units heparin, may
contain no more than 100 .mu.l sample and have a total
anticoagulant content of no more than 1.5 USP units heparin, may
contain no more than 75 .mu.l sample and have a total anticoagulant
content of no more than 1.2 USP units heparin, may contain no more
than 50 .mu.l sample and have a total anticoagulant content of no
more than 0.75 USP units heparin, may contain no more than 40 .mu.l
sample and have a total anticoagulant content of no more than 0.6
USP units heparin, may contain no more than 30 .mu.l sample and
have a total anticoagulant content of no more than 0.45 USP units
heparin, may contain no more than 20 .mu.l sample and have a total
anticoagulant content of no more than 0.3 USP units heparin, may
contain no more than 10 .mu.l sample and have a total anticoagulant
content of no more than 0.15 USP units heparin, or may contain no
more than 5 .mu.l sample and have a total anticoagulant content of
no more than 0.08 USP units heparin.
[0481] In embodiments, two or more sample vessels containing sample
from a single subject may be obtained or transported. When two or
more sample vessels containing sample from a single subject are
obtained or transported, the two or more sample vessels may be
stored or transported in a vessel that does or does not contain
samples from other subjects. In embodiments, at least 2, 3, 4, 5,
6, 7, 8, 9, or 10 sample vessels containing sample from a single
subject may be obtained or transported. In embodiments, no more
than 2, 3, 4, 5, 6, 7, 8, 9, or 10 sample vessels containing sample
from a single subject may be obtained or transported. In
embodiments, at least 2, 3, 4, 5, 6, 7, 8, or 9 sample vessels and
no more than 3, 4, 5, 6, 7, 8, 9, or 10 sample vessels containing
sample from a single subject may be obtained or transported. In
embodiments involving two or more sample vessels containing sample
from the same subject, the sample in each sample vessel may be
obtained from a subject at the same or at different times. In some
embodiments involving two or more sample vessels containing sample
from the same subject, the sample in each sample vessel may be from
the same location or source site on the subject. For example, two
sample vessels containing whole blood from the same subject may be
obtained, in which both sample vessels contain whole blood from the
same fingerstick site. In other embodiments involving two or more
sample vessels containing sample from the same subject, the sample
in each sample vessel be from a different location/source site on
the subject. For example, two sample vessels containing whole blood
from the same subject may be obtained, in which one sample vessel
contains whole blood from a first fingerstick site (e.g. on a first
digit) and a second sample vessel contains whole blood from a
second fingerstick site (e.g. on a second digit). In embodiments
involving two or more sample vessels containing sample from a
single subject, the two or more sample vessels may contain
different types of anticoagulants or other blood additives. For
example, a first sample vessel may contain whole blood with EDTA
and a second sample vessel may contain whole blood with heparin,
wherein the samples are from the same subject. In another example,
a first and second sample vessel may contain whole blood with EDTA
and a third sample vessel may contain whole blood with heparin,
wherein the samples are from the same subject. In another example,
a first sample vessel may contain whole blood with EDTA, a second
sample vessel may contain whole blood with heparin, and a third
sample vessel may contain whole blood with sodium citrate, wherein
the samples are from the same subject. In embodiments involving two
or more sample vessels containing sample from a single subject, the
two or more sample vessels may contain different types of sample
from the subject. For example, a first sample vessel may contain
whole blood and a second sample vessel may contain plasma from the
same subject. In another example, a first sample vessel may contain
whole blood and a second sample vessel may contain urine from the
same subject. In another example, a first and second sample vessel
may contain whole blood and a third sample vessel may contain
saliva from the same subject.
[0482] In systems and methods provided herein, a total volume of
bodily fluid sample may be obtained from a subject. The total
volume of bodily fluid sample may be transferred into a single
sample vessel, or into two or more sample vessels. For example, a
total volume of 500 microliters of bodily fluid sample may be
obtained from a subject, and it may be transferred into a single
sample vessel, wherein the single sample vessel has a maximum
interior volume of 600 microliters. In another example, a total
volume of 500 microliters of bodily fluid sample may be obtained
from a subject, and it may be transferred into a two sample
vessels, wherein each sample vessel has a maximum interior volume
of 300 microliters. In another example, a total volume of 500
microliters of bodily fluid sample may be obtained from a subject,
and it may be transferred into a two sample vessels, wherein one
sample vessel has a maximum interior volume of 400 microliters and
one sample vessel has a maximum interior volume of 100 microliters.
In systems and methods provided herein, a total volume of bodily
fluid sample of less than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5
ml, 1 ml, 750 .mu.l, 500 .mu.l, 400 .mu.l, 300 .mu.l, 200 .mu.l,
150 .mu.l, 100 .mu.l, 75 .mu.l, 50 .mu.l, 40 .mu.l, 30 .mu.l, 20
.mu.l, 10 .mu.l, 5 .mu.l or 1 .mu.l may be obtained from a subject.
The total volume of bodily fluid sample from the subject may be
divided between 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more sample
vessels, as described elsewhere herein. When a total volume of a
bodily fluid sample from a subject is divided between two or more
sample vessels, portions of the total volume of bodily fluid sample
in some or all of the different sample vessels may contain
different anticoagulants or other additives. For example, a total
volume of 500 microliters of bodily fluid sample may be obtained
from a subject, and it may be transferred into a two sample
vessels, wherein one sample vessel contains 250 microliters of the
bodily fluid sample mixed with EDTA, and one sample vessel contains
250 microliters of the bodily fluid sample mixed with heparin.
Typically, as used herein, a total volume of bodily fluid sample
refers to a single type of bodily fluid sample--e.g. whole blood or
urine or saliva, etc.
[0483] In embodiments, a sample vessel containing whole blood may
be centrifuged before it is stored or shipped, such that the whole
blood is separated into plasma and pelleted cells in the sample
vessel before it is shipped. In other embodiments, a sample vessel
containing whole blood is not centrifuged before it is stored or
shipped.
[0484] In some embodiments of systems and methods provided herein,
a bodily fluid sample may be dried after it is collected and before
it is transported. In embodiments, a dried sample may later be
reconstituted into liquid form, such as at a time of analysis or
processing of the sample.
[0485] In embodiments of systems and methods provided herein, a
sample vessel may be transported from a first location to a second
location. A first location may be a location where a sample is
collected from a subject, and a second location may be a location
where one or more steps are performed for processing or analyzing
the sample. The sample and sample vessel may have any of the
respective characteristics described elsewhere herein. For example,
the sample may be in a liquid, non-matrixed, non-wicked form. The
sample vessel may be transported in a transport container as
described herein or other structure. For example in some optional
embodiments, a sample vessel may be transported in a bag, pouch,
envelope, box, capsule, or other structure. In embodiments, the
first location and the second location may be within the same room,
building, campus, or collection of buildings. In embodiments, a
first location and second location may be separated by at least 1
meter, 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1
kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20
kilometers, 30 kilometers, 50 kilometers, 100 kilometers, or 500
kilometers. In embodiments, a first location and second location
may be separated by no more than 5 meters, 10 meters, 50 meters,
100 meters, 500 meters, 1 kilometer, 5 kilometers, 10 kilometers,
15 kilometers, 20 kilometers, 30 kilometers, 50 kilometers, 100
kilometers, 500 kilometers, or 1000 kilometers. In embodiments, a
first location and second location may be separated by at least 1
meter, 5 meters, 10 meters, 50 meters, 100 meters, 500 meters, 1
kilometer, 5 kilometers, 10 kilometers, 15 kilometers, 20
kilometers, 30 kilometers, 50 kilometers, 100 kilometers, or 500
kilometers and no more than 5 meters, 10 meters, 50 meters, 100
meters, 500 meters, 1 kilometer, 5 kilometers, 10 kilometers, 15
kilometers, 20 kilometers, 30 kilometers, 50 kilometers, 100
kilometers, 500 kilometers, or 1000 kilometers. In embodiments in
which a first location is a location where a sample is obtained
from a subject, a sample vessel may be transported from a first
location to a second location within 48 hours, 36 hours, 24 hours,
12 hours, 8 hours, 6 hours, 4 hours, 3 hours, 2 hours, 1 hour, 45
minutes, 30 minutes, 15 minutes, 10 minutes, 5 minutes, 1 minute,
or 30 seconds of collection of the sample from the subject.
[0486] As used herein, a "sample receiving site" is a place where a
transported sample may be received, and wherein one or more steps
may be performed with the sample. For example, a sample which
arrives at a sample receiving site may be processed, analyzed, or
handled at the sample receiving site, for example, as part of a
test or assay with the sample. A sample may be transported, for
example, in any vessel or device as described herein. In
embodiments, a sample receiving site may contain one or more sample
processing devices, which may be used for processing or analyzing
the sample. A sample processing device may be as described in, for
example, U.S. patent application Ser. No. 13/244,947 filed Sep. 26,
2011, or as in any other document incorporated by reference
elsewhere herein. During the transport of a sample from a sample
collection site to a sample receiving site, the sample may pass
through any number of locations. In embodiments, a first location
may be a sample collection site and a second location may be a
sample receiving site.
[0487] Referring now to FIG. 44, one embodiment of bodily fluid
sample collection and transport will now be described. FIG. 44
shows a bodily fluid sample B on a skin surface S of the subject.
In the non-limiting example of FIG. 44, the bodily fluid sample B
can be collected by one of a variety of devices. By way of
non-limiting example, collection device 3530 may be but is not
limited to those described in U.S. Patent Application Ser. No.
61/697,797 filed Sep. 6, 2012, which is fully incorporated herein
by reference for all purposes. In the present embodiment, the
bodily fluid sample B is collected by one or more capillary
channels and then directed into sample vessels 3540. By way of
non-limiting example, at least one of the sample vessels 3540 may
have an interior that is initially under a partial vacuum that is
used to draw bodily fluid sample into the sample vessel 3540. Some
embodiments may simultaneously draw sample from the sample
collection device into the sample vessels 3540 from the same or
different collection channels in the sample collection device.
Optionally, some embodiments may simultaneous draw sample into the
sample vessels
[0488] In the present embodiment after the bodily fluid sample is
inside the sample vessels 3540, the sample vessels 3540 in their
holder 3542 (or optionally, removed from their holder 3542) are
loaded into the transport container 3500. In this embodiment, there
may be one or more slots sized for the sample vessel holder 3542 or
slots for the sample vessels in the transport container 3500. By
way of non-limiting example, they may hold the sample vessels in an
arrayed configuration and oriented to be vertical or some other
pre-determined orientation. It should be understood that some
embodiments of the sample vessels 3540 are configured so that they
hold different amount of sample in each of the vessels. By way of
non-limiting example, this can be controlled based on the amount of
vacuum force in each of the sample vessels, the amount of sample
collected in the sample collection channel(s) of the collection
device, and/or other factors. Optionally, different pre-treatments
such as but not limited to different anti-coagulants or the like
can also be present in the sample vessels.
[0489] As seen in FIG. 44, the sample vessels 3540 are collecting
sample at a first location such as but not limited to a sample
collection site. By way of non-limiting example, the bodily fluid
samples are then transported in the transport container 3500 to a
second location such as but not limited to a receiving site such as
but not limited to an analysis site. The method of transport may be
by courier, postal delivery, or other shipping technique. In many
embodiments, the transport may be implemented by having a yet
another container that holds the transport container therein. In
one embodiment, the sample collection site may be a point-of-care.
Optionally, the sample collection site is a point-of-service.
Optionally, the sample collection site is remote from the sample
analysis site.
[0490] Although the present embodiment of FIG. 44 shows the
collection of bodily fluid sample from a surface of the subject,
other alternative embodiments may use collection techniques for
collecting sample from other areas of the subject, such as by
venipuncture, to fill the sample vessel(s) 3540. Such other
collection techniques are not excluded for use as alternative to or
in conjunction with surface collection. Surface collection may be
on exterior surfaces of the subject. Optionally, some embodiments
may collect from accessible surfaces on the interior of the
subject. Presence of bodily fluid sample B on these surfaces may be
naturally occurring or may occur through wound creation or other
techniques to make the bodily fluid surface accessible.
[0491] Referring now to FIG. 45, yet another embodiment is
described herein wherein bodily fluid sample can be collected from
an interior of the subject versus collecting sample that is pooled
on a surface of the subject. This embodiment of FIG. 45 shows a
collection device 3550 with a hypodermic needle 3552 that is
configured to collect bodily fluid sample such as but not limited
to venous blood. In one embodiment, the bodily fluid sample may
fill a chamber 3554 in the device 3550 at which time sample
vessel(s) 3540 may be engaged to draw the sample into the
respective vessel(s). Optionally, some embodiments may not have a
chamber 3554 but instead have very little void space other than
channel(s), pathway(s), or tube(s) used to direct sample from the
needle 3552 to the sample vessel(s) 3540. For bodily fluid samples
such as blood, the pressure from within the blood vessel is such
that the blood sample can fill the chamber 554 without much if any
assistance from the collection device. Such embodiments may
optionally include one or more vents, such as but not limited to a
port, to allow air escape as the channels in the collection device
are filled with sample.
[0492] At least some or all of the embodiments can have a fill
indicator such as but not limited to a view window or opening that
shows when sample is present inside the collection device and thus
indicate that it is acceptable to engage the sample vessel(s) 3540.
Optionally, embodiments that do not have a fill indicator are not
excluded. The filled sample vessel(s) 3540 may be disconnected from
the sample collection device after a desired fill level is reached.
Optionally, additional sample vessel(s) 3540 can be engaged to the
sample collection device 3550 (or 530) to collect additional
amounts of bodily fluid sample.
[0493] FIG. 46 shows a still further embodiment of a sample
collection device 3570. This embodiment described herein has a
tissue penetrating portion 3572 such as but not limited to a
hypodermic needle with a handling portion 3574. The handling
portion 3574 can facilitate positioning of the tissue penetrating
portion 3572 to more accurately enter the patient to a desired
depth and location. In the present embodiment, the sample
collection vessel(s) 3540 are in a carrier 3576 that is not in
direct physical contact with the tissue penetration portion 3572. A
fluid connection pathway 3578 such as but not limited to a flexible
tube can be used to connect the tissue penetrating portion 3572
with the sample collection vessel(s) 3540. Some embodiments have
the sample vessel(s) 3540 configured to be slidable to only be in
fluid communication with the tissue penetrating portion 3572 upon
control of the user. At least some or all of the embodiments can
have a fill indicator such as but not limited to a view window or
opening that shows when sample is present inside the collection
device and thus indicate that it is acceptable to engage the sample
vessel(s) 3540. Optionally, embodiments that do not have a fill
indicator are not excluded. Some embodiments may optionally include
one or more vents, such as but not limited to a port, to allow air
escape as the channels in the collection device are filled with
sample. In most embodiments, the filled sample vessel(s) 3540 may
be disconnected from the sample collection device after a desired
fill level is reached. Optionally, additional sample vessel(s) 3540
can be engaged to the sample collection device 3570 to collect
additional amounts of bodily fluid sample.
Sample Processing
[0494] Referring now to FIG. 47, a system view is shown of the
transport container 3500 having its contents unloaded after
arriving at a destination location by unloading assembly 3600. In
one embodiment, after the lid 3502 is positioned in an open
position, the sample vessels in the vessel 3500 can be removed from
therein. By way of non-limiting example, the removal may occur by
removing an entire tray of the sample vessels, removing holders of
multiple sample vessels from the tray, and/or by removing the
sample vessels individually. Some embodiments may use a robotically
controlled structure 3602 that can move vertically as indicated by
arrow 3604 and/or horizontally as indicated by arrow 3606 along a
gantry 3608 to remove sample vessels from the transport container
3500. A programmable process 3610 can be used to control the
position of the structure 3602 that is used to manipulate the
sample vessels. In one embodiment, the structure 3602 includes a
magnet for engaging the retention mechanisms to remove the tray
from the structure 3602. Other embodiments using robotic arms
and/or other types of programmable manipulators can be configured
for use herein and are not excluded.
[0495] In embodiments, upon the arrival of a sample vessel
containing a sample at a location for processing or analysis of the
sample, the sample may be removed from the sample vessel. The
sample vessel may processed (e.g. shaken, rotated, mixed, or
centrifuged) before the sample is removed from the sample vessel.
Sample may be removed from the sample vessel by any appropriate
mechanism, such as aspiration (e.g. by a fluid handling system or
pipette), pouring, or mechanical force (e.g. by forcing the sample
from the vessel by reducing the dimensions of the interior region
of the sample vessel). In embodiments, upon the removal of the
sample from the sample vessel, little or no sample remains behind
in the vessel (e.g. as mechanical/transfer loss). For example,
after the removal of sample from the vessel, less than or equal to
50 .mu.l, 40 .mu.l, 30 .mu.l, 20 .mu.l, 15 .mu.l, 10 .mu.l, 5
.mu.l, 4 .mu.l, 3 .mu.l, 2 .mu.l, 1 .mu.l, or 0 .mu.l of sample may
remain in the sample vessel.
[0496] By way of non-limiting example, the samples in the sample
vessels can then be processed using systems such as that described
in U.S. patent application Ser. No. 13/244,947 filed Sep. 26, 2011,
fully incorporated herein by reference for all purposes. The
analysis system can be configured in a CLIA compliant manner as
described in U.S. patent application Ser. No. 13/244,946 filed Sep.
26, 2011, fully incorporated herein by reference for all purposes.
In embodiments, a sample transported according to systems or
methods provided herein may be divided into two or more smaller
portions upon arrival at location for processing or analysis, and
various assays may be performed with the sample. For example, in
embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or
50 assays may be performed with a sample transported according to
systems or methods provided herein. The assays may include assays
of different types (e.g. to assay for protein, nucleic acid, or
cells), and use one or more detection methods (e.g. cytometry,
luminescence, or spectrophotometer-based). In embodiments, two or
more sample vessels containing sample from a single subject may be
transported, wherein the two or more sample vessels contain at
least two different anticoagulants mixed with the sample (e.g. one
sample vessel contains EDTA-sample and one sample vessel contains
heparin-sample). Sample from the EDTA-sample vessel may then be
used for one or more assays that are heparin-sensitive or
EDTA-insensitive. Similarly, sample from the heparin-sample vessel
may then be used for one or more assays that are EDTA-sensitive or
heparin-insensitive. In embodiments, a sample transported according
to systems and methods provided herein may be divided into two or
more portions upon arrival at a destination, and analyzed on 1, 2,
3, 4, 5, 6, 7, 8, 9, 10 or more different sample analyzers.
[0497] Referring now to FIGS. 49 to 51, it should be understood
that at least any two of the tests on the list (FIGS. 49 to 51) can
be performed using a sample from a subject prepared or transported
according to a system or method provided herein. For example, at
least two tests on the list may be performed using a bodily fluid
sample from a subject, wherein the total volume of bodily fluid
sample used to perform the test is no more than 300 microliters,
and the total volume of bodily fluid sample from the subject is
transported in liquid form a sample vessel having an interior
volume of 400 microliters or less. In another example, at least two
tests on the list may be performed using a bodily fluid sample from
a subject, wherein the total volume of bodily fluid sample used to
perform the tests is no more than 300 microliters, and the total
volume of bodily fluid sample from the subject is transported in
liquid form in a first sample vessel and a second sample vessel,
each vessel having an interior volume of 200 microliters or less,
the first sample vessel containing bodily fluid sample mixed with a
first anticoagulant and the second sample vessel containing bodily
fluid sample mixed with a second anticoagulant. In embodiments, at
least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30,
35, 40, 50, or 60 of the tests on the list (FIGS. 49 to 51) may be
performed using a bodily fluid sample from a subject having a total
volume of no greater than or equal to 5 ml, 4 ml, 3 ml, 2 ml, 1.5
ml, 1 ml, 750 .mu.l, 500 .mu.l, 400 .mu.l, 300 .mu.l, 200 .mu.l,
150 .mu.l, 100 .mu.l, 75 .mu.l, 50 .mu.l, 40 .mu.l, 30 .mu.l, 20
.mu.l, 10 .mu.l, 5 .mu.l or 1 .mu.l. The total volume of the bodily
fluid sample may be stored or transported from a collection site to
an analysis or processing location in a single sample vessel, or it
may be divided between 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 20, 25, or more sample vessels. When the total volume of a
bodily fluid sample from a single subject is divided into two or
more sample vessels, the sample portions in some or each of the
sample vessels may contain a different anticoagulant or other
additive. In an example, no more than a total volume of 300
microliters of bodily fluid sample from a subject may be used for
performing two or more of the tests, wherein at least one portion
of the no more than 300 microliter sample is mixed with first
anti-coagulant and a second portion of the no more than 300
microliter sample is mixed with a second anti-coagulant different
from the first. Optionally, each portion of the no more than 300
microliter sample is in its own sample vessel. Optionally, two or
more of the tests may be performed, wherein all of the no more than
300 microliter sample is transported in a single vessel and
contains a single anti-coagulant. Optionally, at least any three of
the tests on that list can be conducted using no more than a total
volume of 300 microliters of blood from a subject for all of the
tests. Optionally, at least any five of the tests on that list can
be conducted using no more than a total volume of 300 microliters
of blood from a subject for all of the tests. Optionally, at least
any seven of the tests on that list can be conducted using no more
than a total volume of 300 microliters of blood from a subject for
all of the tests. Optionally, at least any ten of the tests on that
list can be conducted using no more than a total volume of 300
microliters of blood from a subject for all of the tests.
Optionally, at least any fifteen of the tests on that list can be
conducted using no more than a total volume of 300 microliters of
blood from a subject for all of the tests. Optionally, at least any
twenty of the tests on that list can be conducted using no more
than a total volume of 300 microliters of blood from a subject for
all of the tests. For any of the above, in at least some
embodiments, at least one portion is of a first anti-coagulant and
a second portion is of a second anti-coagulant different from the
first.
[0498] Referring now to FIG. 52, yet another embodiment is shown of
a device for bodily fluid sample collection. FIG. 52 shows a bodily
fluid sample B on the subject being collected by a collection
device 3710. As seen in FIG. 52, the collection device 3710 may
include a collection portion 3712 such as but not limited to
capillary tube or other collection structure. The collection
portion 3712 draws fluid therein, eventually directing it towards
an inner cavity 3714 of the device 3710. After the collection
portion 3712 has collected a desired amount, the entire device 3710
can be oriented as shown in FIG. 52 so that gravity can then draw
the sample into the cavity 3714. After all the sample B has been
moved into the cavity 3714, the collection portion 3712 can be
removed from device 3710. In one embodiment, the cap and the
collection portion 3712 is removed and replaced with a closed cap
3718. In one non-limiting example, the cap 3718 can be one without
any openings thereon. Optionally, some may have a septa or other
closable opening in the cap, wherein the collection portion 3712
can be removed without having to replace the cap with a new one of
a different configuration.
Modular Sample Collection Device
[0499] Referring now to FIGS. 53A-53C, although the embodiments
herein typically describe sample collection device as having an
adapter portion 3750 for connecting the sample collection portion
3740 with the sample storage vessels 3760, it should be understood
that embodiments without such configurations are not excluded.
[0500] By way of non-limiting example in FIG. 53A, one or more
adapter portion 3750 may be discrete elements not initially in
direct fluid communication with either the collection portion 3740
or the sample storage vessels 3760. Herein the collection portion
3740 may connect to the vessel 3760 by way of relative motion
between one or more of the collection portion, the adapter portion
3750, or the vessel(s) 3760 (sequentially or simultaneously) to
create a fluid pathway from the collection channels through the one
or more adapter channels into the vessels.
[0501] By way of non-limiting example in FIG. 53B, as previously
suggested herein, some embodiments may be without a discrete,
separate adapter portion 3750. Herein the collection portion 3740
may connect directly to the vessel 3760 by way of relative motion
between one or both of those elements as indicated by the arrow
3770. As seen in FIG. 53B, there may be a fluid flow feature 3780
that with relative motion between one or both of those elements as
indicated by the arrow 3782. In one non-limiting example, this
fluid flow feature 3780 can be a cap that engages one end of the
collection portion 3740 to encourage fluid flow in to the vessel
3760. Optionally, the fluid flow feature 3780 may be a cap that has
a front surface shaped to engage the collection portion 3740.
Optionally, the fluid flow feature 3780 may be a plunger, a rod,
and/or other device to encourage flow towards the sample storage
vessel 3760. Optionally, the fluid flow feature 3780 is not fully
engaged until the sample collection portion 3740 is ready to engage
the vessel 3760. Optionally, some embodiments may be configured so
that the flow from collection portion 3740 to sample storage vessel
3760 is without the use of the fluid flow feature 3780, but is
instead based on a different motive force, such as but not limited
to gravity, vacuum suction, or blowing force provided at the
appropriate end of the collection portion 3740.
[0502] By way of non-limiting example in FIG. 53C, one or more
embodiment may use the collection portion 3740 as the storage
vessel. Some embodiments may simply cap both ends with caps 3790
and 3792 once the desired fill level is reached. As seen in Figure
in FIG. 53C, the caps 3790 and 3792 can hold the fluid therein,
even when the portion 3740 is in a vertical orientation.
[0503] There may be variations and alternatives to the embodiments
described herein and that no single embodiment should be construed
to encompass the entire invention. For example, there can be two or
more capillary tubes in the collection portion 3740. Optionally,
they can be each formed as discrete tubes or channels. Optionally,
some may have a common initial portion but separate exits ports
such as but not limited to a Y configuration. It should be
understood that any of the embodiments herein could be modified to
include the features recited in the description for FIGS.
53A-53C.
[0504] Referring now to FIG. 54, after a sample vessel 3800 arrives
at a desired processing destination, the sample in the vessel 3800
can be appropriately prepared. In one embodiment, the vessel 3800
is similar to that of vessel 3710. As seen in FIG. 54, the sample
can be processed to aliquot one portion into a processing device
such as but not limited to an inlet on a cartridge 3802 and to
another inlet on another cartridge 3804. In one embodiment, both of
the cartridges 3802 are microfluidic discs that process sample for
blood chemistry testing such as but not limited to Comprehensive
Metabolic Panel (ALB, ALP, ALT, AST, BUN, Ca, Cl-, CRE, GLU, K+,
Na+, TBIL, tCO2, TP), Basic Metabolic Panel (BUN, Ca, CRE, eGFR,
GLU, Cl-, K+, Na+, tCO2) Lipid Panel (CHOL, HDL, CHOL/HDL, LDL,
TRIG, VLDL, nHDLc); Lipid Panel Plus (tCHOL, HDL, CHOL/HDL Ratio,
LDL, TRIG, VLDL, GLU, ALT, AST, nHDLc); Liver Panel Plus (ALB, ALP,
ALT, AST, AMY, TBIL, TP, GGT); Electrolyte Panel (Cl-, K+, Na+,
tCO2); General Chemistry (ALB, ALP, ALT, AMY, AST, BUN, Ca, CRE,
eGFR, GGT, GLU, TBIL, TP, UA); General Chemistry 6 (ALT, AST, CRE,
eGFR, GLU, BUN, GGT) Renal Function Panel (ALB, BUN, Ca, CRE, eGFR,
GLU, Cl-, K+, Na+, tCO2 PHOS); Metlyte (Cl-, K+, Na+, tCO2, BUN,
CK, CRE, eGFR, GLU); Kidney Function (BUN, CRE, eGFR; Hepatic
Function Panel (ALB, ALP, ALT, AST, DBIL, TBIL, TP); Basic
Metabolic Panel (BUN, Ca, CRE, eGFR, GLU, Cl-, K+, Na+, tCO2, Mg,
LDH); MetLyte Plus CRP (Cl-, K+, Na+, tCO2, BUN, CK, CRE, eGFR,
GLU, CRP); BioChemistry Panel Plus (ALB, ALP, ALT, AMY, AST, BUN,
Ca, CRE, eGFR, CRP, GGT, GLU, TP, UA); MetLac (ALB, BUN, Ca, Cl-,
CRE, GLU, K+, LAC, Mg, Na+, Phos, tCO2). It should be understood
that other fluid handling technologies that may be developed in the
future can also be adapted for use in at least one of the
embodiments herein. In some embodiments, the sample can be
delivered to a general chemistry microfluidic/centrifugal
cartridge(s) 3802 (and/or 3804) using tubing to carry the fluid to
a destination such as but not limited to fluid receiving port on
the cartridge. At least one or more other cartridges, such as but
not limited to an open-fluid movement type cartridge as described
in the applications incorporated by reference herein, can also be
used to improve the types of testing available. Although at least
two destination cartridges are shown, it should be understood that
embodiment with more than two are not excluded (as shown by the
additional cartridge shown in phantom). Fluid transport may be by
way of pipette, by fluidic tubing, microfluidics, or by other fluid
handling technologies that may be developed in the future.
[0505] Referring now to FIG. 55A, it should be understood that some
embodiments can use a sample handling system with pipette(s) or the
like the extract the sample in a tubeless manner from the vessel
3800. Although pipette(s) are described in this embodiment, it
should be understood that other fluid handling technologies that
may be developed in the future can also be adapted for use in at
least one of the embodiments herein. FIG. 55A shows that an
automated system can be used to aliquot the sample. It should also
be understood that in some embodiments, prior to, during, or after
aliquoting, there can be sample dilution to increase the liquid
volume of the sample. This can be beneficial for various purposes.
FIG. 55A also shows that in some embodiments, the sample can be
delivered to a general chemistry microfluidic/centrifugal
cartridge(s) 3802 (and/or 3804). At least one or more other
cartridges, such as but not limited to an open-fluid movement type
cartridge as described in the applications incorporated by
reference herein, can also be used to improve the types of testing
available. Although at least two destination cartridges are shown,
it should be understood that embodiment with more than two are not
excluded (as shown by the additional cartridge shown in phantom).
Fluid transport may be by way of pipette, by fluidic tubing,
microfluidics, or by other fluid handling technologies that may be
developed in the future. Some embodiments may use the same
techniques to move sample to the cartridges or other
destination(s), or optionally, some may use a combination of one or
more of the techniques to move the sample. By way of example and
not limitation, testing may involve using other detection
techniques such as but not limited to ELISA, nucleic acid
amplification, microscopy, spectrophotometry, electrochemistry
and/or other detection techniques to augment the types of analysis
that can be done, in addition to the general chemistry testing
using the cartridge 3802. Optionally, it should be understood that
more than one cartridge 3802 and/or individual unit cartridge 3806
can be used herein with the system of aliquoting from the vessel
3800.
[0506] Referring now to FIG. 55B, a still further embodiment is
shown wherein a vessel 3800 is shown having a sample fluid therein.
In one example, the sample fluid therein may be "neat" or
undiluted. Optionally, some embodiments may be configured so that
sample may have been pre-processed at the collection site and/or at
the receiving site to dilute the sample and/or provide certain
chemical material into the sample. As seen in FIG. 55B, a fluid
handling system may use a pipette 3602 to aliquot sample from
vessel 3800 to one or more other vessels 3810, 3812, and/or 3814.
By way of non-limiting example, these vessels 3810, 3812, or 3814
may be the same vessel as that of vessel 3800. Optionally, they may
be different type of vessel. Based on bar code or other information
about the sample, the processor programmed to determine at least a
desired sample dilution for a sample and at least a desired number
of aliquot(s). In this non-limiting example, the aliquots are each
transported to one sample processing unit 3820, 3822, and 3824.
These may all be the same type of processing unit, each may be a
type different from the other, or some may be the same and some
different. In at least one non-limiting example, the sample
processing unit can be single sample processor or a batch processor
that can handle a plurality of sample simultaneously.
[0507] FIG. 55C shows a still further embodiment wherein a sample
is collected at a collection site and then transported to a second
site while sample remains in liquid form. FIG. 55C shows that a
plurality of vessels having sample can be collected from a single
wound on the subject. This allows the subject to provide multiple
samples that can be treated by different types of chemicals in each
of the vessels. FIG. 55C shows a courier that can transport a
transport container that may include samples from only one subject
or multiple samples from multiple subjects to a receiving site.
Although a human courier is shown, it should be understood that
robotic transports, drones, or other transport techniques, systems,
or devices that may be developed in the future are not excluded
(including but not limited to transport of "virtual" version(s) of
the sample). In this non-limiting example, the receiving site may
load one or more vessels 1504 from the transport container into a
cartridge having independently movable reagent units and/or assay
units. This cartridge can then be loaded into one or more
processing modules 701 to 707. These units may be identical
modules. Optionally, at least one of the modules is different from
the others. Similar to FIG. 55B, some embodiments may include a
processor 3830 that may coordinate dilution and/or aliquoting of
sample from vessel 1504 (based on vessel ID or other associated
information) prior to loading the vessel 1504 or other vessel(s)
that contain the sample and/or pre-diluted sample into the
cartridge. In at least one embodiment herein, each of the modules
can receive at least one cartridge and at least one sample vessel.
Optionally, more than one sample vessel can be placed in each
cartridge. Optionally, the sample vessels may contain different
types of sample so that cartridge can have more than one type of
sample loaded into it. Optionally, some embodiments may have
modules with at least one receiving area for a cartridge and at
least one receiving area for a sample.
[0508] Optionally, some embodiments may have only one location for
receiving a cartridge which then also contains at least one sample.
In this manner, a user has decreased risk of having to load
separate items into the module. Once loaded, at least one
embodiment herein is configured so that there is no more user
manipulation of the sample once it is inserted in the module. This
non-limiting example can be used minimize error associated with
human factors once the sample is being processed in the module.
[0509] It should also be understood that some embodiments may
handle a plurality of sample simultaneously using centrifugal or
other force to bring the sample down to a settled level inside the
sample vessels. In one non-limiting example, this can be achieved
by way of a tray centrifuge such as but not limited to a 384 well
plate centrifuge.
[0510] FIG. 55C shows a system 700 having a plurality of modules
701-706 and a cytometry station 707, in accordance with an
embodiment of the invention. The plurality of modules include a
first module 701, second module 702, third module 703, fourth
module 704, fifth module 705 and sixth module 706.
[0511] The cytometry station 707 is operatively coupled to each of
the plurality of modules 701-706 by way of a sample handling system
708. The sample handling system 708 may include a pipette, such as
a positive displacement, air displacement or suction-type pipette,
as described herein.
[0512] The cytometry station 707 includes a cytometer for
performing cytometry on a sample, as described above and in other
embodiments of the invention. The cytometry station 707 may perform
cytometry on a sample while one or more of the modules 701-706
perform other preparation and/or assaying procedure on another
sample. In some situations, the cytometry station 707 performs
cytometry on a sample after the sample has undergone sample
preparation in one or more of the modules 701-706.
[0513] The system 700 includes a support structure 709 having a
plurality of bays (or mounting stations). The plurality of bays is
for docking the modules 701-706 to the support structure 709. The
support structure 709, as illustrated, is a rack.
[0514] Each module is secured to rack 709 with the aid of an
attachment member. In an embodiment, an attachment member is a hook
fastened to either the module or the bay. In such a case, the hook
is configured to slide into a receptacle of either the module or
the bay. In another embodiment, an attachment member includes a
fastener, such as a screw fastener. In another embodiment, an
attachment member is formed of a magnetic material. In such a case,
the module and bay may include magnetic materials of opposite
polarities so as to provide an attractive force to secure the
module to the bay. In another embodiment, the attachment member
includes one or more tracks or rails in the bay. In such a case, a
module includes one or more structures for mating with the one or
more tracks or rails, thereby securing the module to the rack 709.
Optionally, power may be provided by the rails.
[0515] An example of a structure that may permit a module to mate
with a rack may include one or more pins. In some cases, modules
receive power directly from the rack. In some cases, a module may
be a power source like a lithium ion, or fuel cell powered battery
that powers the device internally. In an example, the modules are
configured to mate with the rack with the aid of rails, and power
for the modules comes directly from the rails. In another example,
the modules mate with the rack with the aid of attachment members
(rails, pins, hooks, fasteners), but power is provided to the
modules wirelessly, such as inductively (i.e., inductive coupling).
In some embodiments, a module mating with a rack need not require
pins. For example, an inductive electrical communication may be
provided between the module and rack or other support. In some
instances, wireless communications may be used, such as with the
aid of ZigBee communications or other communication protocols or
protocols that may be developed in the future.
[0516] Each module may be removable from the rack 709. In some
situations, one module is replaceable with a like, similar or
different module. In an embodiment, a module is removed from the
rack 709 by sliding the module out of the rack. In another
embodiment, a module is removed from the rack 709 by twisting or
turning the module such that an attachment member of the module
disengages from the rack 709. Removing a module from the rack 709
may terminate any electrical connectivity between the module and
the rack 709.
[0517] In an embodiment, a module is attached to the rack by
sliding the module into the bay. In another embodiment, a module is
attached to the rack by twisting or turning the module such that an
attachment member of the module engages the rack 709. Attaching a
module to the rack 709 may establish an electrical connection
between the module and the rack. The electrical connection may be
for providing power to the module or to the rack or to the device
from the module and/or providing a communications bus between the
module and one or more other modules or a controller of the system
700.
[0518] Each bay of the rack may be occupied or unoccupied. As
illustrated, all bays of the rack 709 are occupied with a module.
In some situations, however, one or more of the bays of the rack
709 are not occupied by a module. In an example, the first module
701 has been removed from the rack. The system 700 in such a case
may operate without the removed module.
[0519] In some situations, a bay may be configured to accept a
subset of the types of modules the system 700 is configured to use.
For example, a bay may be configured to accept a module capable of
running an agglutination assay but not a cytometry assay. In such a
case, the module may be "specialized" for agglutination.
Agglutination may be measured in a variety of ways. Measuring the
time-dependent change in turbidity of the sample is one method. One
can achieve this by illuminating the sample with light and
measuring the reflected light at 90 degrees with an optical sensor,
such as a photodiode or camera. Over time, the measured light would
increase as more light is scattered by the sample. Measuring the
time dependent change in transmittance is another example. In the
latter case, this can be achieved by illuminating the sample in a
vessel and measuring the light that passes through the sample with
an optical sensor, such as a photodiode or a camera. Over time, as
the sample agglutinates, the measured light may reduce or increase
(depending, for example, on whether the agglutinated material
remains in suspension or settles out of suspension). In other
situations, a bay may be configured to accept all types of modules
that the system 700 is configured to use, ranging from detection
stations to the supporting electrical systems.
[0520] Each of the modules may be configured to function (or
perform) independently from the other modules. In an example, the
first module 701 is configured to perform independently from the
second 702, third 703, fourth 704, fifth 705 and sixth 706 modules.
In other situations, a module is configured to perform with one or
more other modules. In such a case, the modules may enable parallel
processing of one or more samples. In an example, while the first
module 701 prepares a sample, the second module 702 assays the same
or different sample. This may enable a minimization or elimination
of downtime among the modules.
[0521] The support structure (or rack) 709 may have a server type
configuration. In some situations, various dimensions of the rack
are standardized. In an example, spacing between the modules
701-706 is standardized as multiples of at least about 0.5 inches,
or 1 inch, or 2 inches, or 3 inches, or 4 inches, or 5 inches, or 6
inches, or 7 inches, or 8 inches, or 9 inches, or 10 inches, or 11
inches, or 12 inches.
[0522] The rack 709 may support the weight of one or more of the
modules 701-706. Additionally, the rack 709 has a center of gravity
that is selected such that the module 701 (top) is mounted on the
rack 709 without generating a moment arm that may cause the rack
709 to spin or fall over. In some situations, the center of gravity
of the rack 709 is disposed between the vertical midpoint of the
rack and a base of the rack, the vertical midpoint being 50% from
the base of the rack 709 and a top of the rack. In an embodiment,
the center of gravity of the rack 709, as measured along a vertical
axis away from the base of the rack 709, is disposed at least about
0.1%, or 1%, or 10%, or 20%, or 30%, or 40%, or 50%, or 60%, or
70%, or 80%, or 90%, or 100% of the height of the rack as measured
from the base of the rack 709.
[0523] A rack may have multiple bays (or mounting stations)
configured to accept one or more modules. In an example, the rack
709 has six mounting stations for permitting each of the modules
701-706 to mount the rack. In some situations, the bays are on the
same side of the rack. In other situations, the bays are on
alternating sides of the rack.
[0524] In some embodiments, the system 700 includes an electrical
connectivity component for electrically connecting the modules
701-706 to one another. The electrical connectivity component may
be a bus, such as a system bus. In some situations, the electrical
connectivity component also enables the modules 701-706 to
communicate with each other and/or a controller of the system
700.
[0525] In some embodiments, the system 700 includes a controller
(not shown) for facilitating processing of samples with the aid of
one or more of the modules 701-706. In an embodiment, the
controller facilitates parallel processing of the samples in the
modules 701-706. In an example, the controller directs the sample
handling system 708 to provide a sample in the first module 701 and
second module 702 to run different assays on the sample at the same
time. In another example, the controller directs the sample
handling system 708 to provide a sample in one of the modules
701-706 and also provide the sample (such as a portion of a finite
volume of the sample) to the cytometry station 707 so that
cytometry and one or more other sample preparation procedures
and/or assays are done on the sample in parallel. In such fashion,
the system minimizes, if not eliminates, downtime among the modules
701-706 and the cytometry station 707.
[0526] Each individual module of the plurality of modules may
include a sample handling system for providing samples to and
removing samples from various processing and assaying modules of
the individual module. In addition, each module may include various
sample processing and/or assaying modules, in addition to other
components for facilitating processing and/or assaying of a sample
with the aid of the module. The sample handling system of each
module may be separate from the sample handling system 708 of the
system 700. That is, the sample handling system 708 transfers
samples to and from the modules 701-706, whereas the sample
handling system of each module transfers samples to and from
various sample processing and/or assaying modules included within
each module.
[0527] In the illustrated example of FIG. 55C, the sixth module 706
includes a sample handling system 710 including a suction-type
pipette 711 and positive displacement pipette 712. The sixth module
706 includes a centrifuge 713, a spectrophotometer 714, a nucleic
acid assay (such as a polymerase chain reaction (PCR) assay)
station 715 and PMT 716. An example of the spectrophotometer 714 is
shown in FIG. 55C (see below). The sixth module 706 further
includes a cartridge 717 for holding a plurality of tips for
facilitating sample transfer to and from each processing or
assaying module of the sixth module.
[0528] In an embodiment, the suction type pipette 711 includes 1 or
more, or 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6
or more, or 7 or more, or 8 or more, or 9 or more, or 10 or more,
or 15 or more, or 20 or more, or 30 or more, or 40 or more, or 50
or more heads. In an example, the suction type pipette 711 is an
8-head pipette with eight heads. The suction type pipette 711 may
be as described in other embodiments of the invention.
[0529] In some embodiments, the positive displacement pipette 712
has a coefficient of variation less than or equal to about 20%,
15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.3%, or
0.1% or less. The coefficient of variation is determined according
to .quadrature..quadrature..quadrature., wherein `.quadrature.` is
the standard deviation and `.quadrature.` .quadrature. is the mean
across sample measurements.
[0530] In an embodiment, all modules are identical to one another.
In another embodiment, at least some of the modules are different
from one another. In an example, the first, second, third, fourth,
fifth, and sixth modules 701-706 include a positive displacement
pipette and suction-type pipette and various assays, such as a
nucleic acid assay and spectrophotometer. In another example, at
least one of the modules 701-706 may have assays and/or sample
preparation stations that are different from the other modules. In
an example, the first module 701 includes an agglutination assay
but not a nucleic acid amplification assay, and the second module
702 includes a nucleic acid assay but not an agglutination assay.
Modules may not include any assays.
[0531] In the illustrated example of FIG. 55C, the modules 701-706
include the same assays and sample preparation (or manipulation)
stations. However, in other embodiments, each module includes any
number and combination of assays and processing stations described
herein.
[0532] The modules may be stacked vertically or horizontally with
respect to one another. Two modules are oriented vertically in
relation to one another if they are oriented along a plane that is
parallel, substantially parallel, or nearly parallel to the
gravitational acceleration vector. Two modules are oriented
horizontally in relation to one another if they are oriented along
a plane orthogonal, substantially orthogonal, or nearly orthogonal
to the gravitational acceleration vector.
[0533] In an embodiment, the modules are stacked vertically, i.e.,
one module on top of another module. In the illustrated example of
FIG. 55C, the rack 709 is oriented such that the modules 701-706
are disposed vertically in relation to one another. However, in
other situations the modules are disposed horizontally in relation
to one another. In such a case, the rack 709 may be oriented such
that the modules 701-706 may be situated horizontally alongside one
another.
[0534] In yet another embodiment of a system 730 is shown with a
plurality of modules 701 to 704. This embodiment shows a horizontal
configuration wherein the modules 701 to 704 are mounted to a
support structure 732 on which a transport device 734 can move
along the X, Y, and/or optionally Z axis to move elements such as
but not limited sample vessels, tips, cuvettes, or the like within
a module and/or between modules. By way of non-limiting example,
the modules 701-704 are oriented horizontally in relation to one
another if they are oriented along a plane orthogonal,
substantially orthogonal, or nearly orthogonal to the gravitational
acceleration vector.
[0535] It should be understood that, like the embodiment of FIG.
55C, modules 701-704 may all be modules that are identical to one
another. In another embodiment, at least some of the modules are
different from one another. In an example, the first, second,
third, and/or fourth modules 701-704 may be replaced by one or more
other modules that can occupy the location of the module being
replaced. The other modules may optionally provide different
functionality such as but not limited to a replacing one of the
modules 701-704 with one or more cytometry modules 707,
communications modules, storage modules, sample preparation
modules, slide preparation modules, tissue preparation modules, or
the like. For example, one of the modules 701-704 may be replaced
with one or more modules that provide a different hardware
configuration such as but not limited to provide a thermal
controlled storage chamber for incubation, storage between testing,
and/or storage after testing. Optionally, the module replacing one
or more of the modules 701-704 can provide a non-assay related
functionality, such as but not limited to additional
telecommunication equipment for the system 730, additional imaging
or user interface equipment, or additional power source such as but
not limited to batteries, fuel cells, or the like. Optionally, the
module replacing one or more of the modules 701-704 may provide
storage for additional disposables and/or reagents or fluids. It
should be understood that although some embodiments show only four
modules mounted on the support structure, other embodiments having
fewer or more modules are not excluded from this horizontal
mounting configuration. It should also be understood that
configurations may also be run with not every bay or slot occupied
by a module, particularly in any scenario wherein one or more types
of modules draw more power that other modules. In such a
configuration, power otherwise directed to an empty bay can be used
by the module that may draw more power than the others.
[0536] It should be understood that, like the embodiment of FIG.
55C, modules 701-706 may all be modules that are identical to one
another. In another embodiment, at least some of the modules are
different from one another. In an example, the first, second,
third, and/or fourth modules 701-706 may be replaced by one or more
other modules that can occupy the location of the module being
replaced. The other modules may optionally provide different
functionality such as but not limited to a replacing one of the
modules 701-706 with one or more cytometry modules 707,
communications modules, storage modules, sample preparation
modules, slide preparation modules, tissue preparation modules, or
the like.
[0537] It should be understood that although some embodiments show
only six modules mounted on the support structure, other
embodiments having fewer or more modules are not excluded from this
horizontal and vertical mounting configuration. It should also be
understood that configurations may also be run with not every bay
or slot occupied by a module, particularly in any scenario wherein
one or more types of modules draw more power that other modules. In
such a configuration, power otherwise directed to an empty bay can
be used by the module that may draw more power than the others.
[0538] Some embodiments may provide a system with a plurality of
modules 701, 702, 703, 704, 706, and 707. Such an embodiment may
have an additional module that can with one or more modules that
provide a different hardware configuration such as but not limited
to provide a thermal controlled storage chamber for incubation,
storage between testing, or storage after testing. Optionally, the
module replacing one or more of the modules 701-704 can provide a
non-assay related functionality, such as but not limited to
additional telecommunication equipment for the system, additional
imaging or user interface equipment, or additional power source
such as but not limited to batteries, fuel cells, or the like.
Optionally, the module replacing one or more of the modules 701-707
may provide storage for additional disposables and/or reagents or
fluids.
[0539] It should be understood that although FIG. 55C shows seven
modules mounted on the support structure, other embodiments having
fewer or more modules are not excluded from this mounting
configuration. It should also be understood that configurations may
also be run with not every bay or slot occupied by a module,
particularly in any scenario wherein one or more types of modules
draw more power that other modules. In such a configuration, power
otherwise directed to an empty bay can be used by the module that
may draw more power than the others.
[0540] In some embodiments, the modules 701-706 are in
communication with one another and/or a controller of the system
700 by way of a communications bus ("bus"), which may include
electronic circuitry and components for facilitating communication
among the modules and/or the controller. The communications bus
includes a subsystem that transfers data between the modules and/or
controller of the system 700. A bus may bring various components of
the system 700 in communication with a central processing unit
(CPU), memory (e.g., internal memory, system cache) and storage
location (e.g., hard disk) of the system 700.
[0541] A communications bus may include parallel electrical wires
with multiple connections, or any physical arrangement that
provides logical functionality as a parallel electrical bus. A
communications bus may include both parallel and bit-serial
connections, and can be wired in either a multidrop (i.e.,
electrical parallel) or daisy chain topology, or connected by
switched hubs. In an embodiment, a communications bus may be a
first generation bus, second generation bus or third generation
bus. The communications bus permits communication between each of
the modules and other modules and/or the controller. In some
situations, the communications bus enables communication among a
plurality of systems, such as a plurality of systems similar or
identical to the system 700.
[0542] The system 700 may include one or more of a serial bus,
parallel bus, or self-repairable bus. A bus may include a master
scheduler that control data traffic, such as traffic to and from
modules (e.g., modules 701-706), controller, and/or other systems.
A bus may include an external bus, which connects external devices
and systems to a main system board (e.g., motherboard), and an
internal bus, which connects internal components of a system to the
system board. An internal bus connects internal components to one
or more central processing units (CPUs) and internal memory.
[0543] In some embodiments, the communication bus may be a wireless
bus. The commuincations bus may be a Firewire (IEEE 1394), USB
(1.0, 2.0, 3.0, or others), Thunderbolt, or other protocols
(current or developed in the future).
[0544] In some embodiments, the system 700 includes one or more
buses selected from the group consisting of Media Bus, Computer
Automated Measurement and Control (CAMAC) bus, industry standard
architecture (ISA) bus, USB bus, Firewire, Thunderbolt, extended
ISA (EISA) bus, low pin count bus, MBus, MicroChannel bus,
Multibus, NuBus or IEEE 1196, OPTi local bus, peripheral component
interconnect (PCI) bus, Parallel Advanced Technology Attachment
(ATA) bus, Q-Bus, S-100 bus (or IEEE 696), SBus (or IEEE 1496),
SS-50 bus, STEbus, STD bus (for STD-80 [8-bit] and STD32
[16-/32-bit]), Unibus, VESA local bus, VMEbus, PC/104 bus, PC/104
Plus bus, PC/104 Express bus, PCI-104 bus, PCIe-104 bus, 1-Wire
bus, HyperTransport bus, Inter-Integrated Circuit (I2C) bus, PCI
Express (or PCIe) bus, Serial ATA (SATA) bus, Serial Peripheral
Interface bus, UNI/O bus, SMBus, 2-wire or 3-wire interface,
self-repairable elastic interface buses and variants and/or
combinations thereof.
[0545] In some situations, the system 700 includes a Serial
Peripheral Interface (SPI), which is an interface between one or
more microprocessors and peripheral elements or I/O components
(e.g., modules 701-706) of the system 700. The SPI can be used to
attach 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6 or
more, or 7 or more, or 8 or more, or 9 or more, or 10 or more or 50
or more or 100 or more SPI compatible I/O components to a
microprocessor or a plurality of microprocessors. In other
instances, the system 700 includes RS-485 or other standards.
[0546] In an embodiment, an SPI is provided having an SPI bridge
having a parallel and/or series topology. Such a bridge allows
selection of one of many SPI components on an SPI I/O bus without
the proliferation of chip selects. This is accomplished by the
application of appropriate control signals, described below, to
allow daisy chaining the device or chip selects for the devices on
the SPI bus. It does however retain parallel data paths so that
there is no Daisy Chaining of data to be transferred between SPI
components and a microprocessor.
[0547] In some embodiments, an SPI bridge component is provided
between a microprocessor and a plurality of SPI I/O components
which are connected in a parallel and/or series (or serial)
topology. The SPI bridge component enables parallel SPI using MISO
and MOSI lines and serial (daisy chain) local chip select
connection to other slaves (CSL/). In an embodiment, SPI bridge
components provided herein resolve any issues associated with
multiple chip selects for multiple slaves. In another embodiment,
SPI bridge components provided herein support four, eight, sixteen,
thirty two, sixty four or more individual chip selects for four SPI
enabled devices (CS1/-CS4/). In another embodiment, SPI bridge
components provided herein enable four times cascading with
external address line setting (ADR0-ADR1). In some situations, SPI
bridge components provided herein provide the ability to control up
to eight, sixteen, thirty two, sixty four or more general output
bits for control or data. SPI bridge components provided herein in
some cases enable the control of up to eight, sixteen, thirty two,
sixty four or more general input bits for control or data, and may
be used for device identification to the master and/or diagnostics
communication to the master.
[0548] One embodiment may use an SPI bridge scheme having master
and parallel-series SPI slave bridges, in accordance with an
embodiment of the invention. The SPI bus is augmented by the
addition of a local chip select (CSL/), module select (MOD_SEL) and
select data in (DIN_SEL) into a SPI bridge to allow the addition of
various system features, including essential and non-essential
system features, such as cascading of multiple slave devices,
virtual daisy chaining of device chip selects to keep the
module-to-module signal count at an acceptable level, the support
for module identification and diagnostics, and communication to
non-SPI elements on modules while maintaining compatibility with
embedded SPI complaint slave components. FIG. 41B shows an example
of an SPI bridge, in accordance with an embodiment of the
invention. The SPI bridge includes internal SPI control logic, a
control register (8 bit, as shown), and various input and output
pins.
[0549] Each slave bridge is connected to a master (also "SPI
master" and "master bridge" herein) in a parallel-series
configuration. The MOSI pin of each slave bridge is connected to
the MOSI pin of the master bridge, and the MOSI pins of the slave
bridges are connected to one another. Similarly, the MISO pin of
each slave bridge is connected to the MISO pin of the master
bridge, and the MISO pins of the slave bridges are connected to one
another.
[0550] Each slave bridge may be a module (e.g., one of the modules
701-706 of FIG. 55C) or a component in a module. In an example, the
First Slave Bridge is the first module 701, the Second Slave Bridge
is the second module 702, and so on. In another example, the First
Slave Bridge is a component of a module.
[0551] At least one non-limiting example may use a module component
diagram with interconnected module pins and various components of a
master bridge and slave bridge, in accordance with an embodiment of
the invention. Slave bridges may be connected to a master bridge,
in accordance with an embodiment of the invention. The MISO pin of
each slave bridge is in electrical communication with a MOSI pin of
the master bridge. The MOSI pin of each slave bridge is in
electrical communication with a MISO pin of the master bridge. The
DIN_SEL pin of the first slave bridge (left) is in electrical
communication with the MOSI pin of the first slave bridge. The
DOUT_SEL pin of the first slave bridge is in electrical
communication with the DIN_SEL of the second slave (right).
Additional slave bridges may be connected as the second slave by
bringing the DIN_SEL pins of each additional slave bridge in
electrical communication with a DOUT_SEL pin of a previous slave
bridge. In such fashion, the slave bridge are connected in a
parallel-series configuration.
[0552] In some embodiments, CLK pulses directed to connected
SPI-Bridges capture the state of DIN_SEL Bits shifted into the
Bridges at the assertion of the Module Select Line (MOD_SEL). The
number of DIN_SEL bits corresponds to the number of modules
connected together on a parallel-series SPI-Link. In an example, if
the two modules are connected in a parallel-series configuration
(e.g. RS486), the number of DIN_SEL is equal to two.
[0553] In an embodiment, SPI-Bridges which latch a `1` during the
module selection sequence become the `selected module` set to
receive 8 bit control word during a following element selection
sequence. Each SPI-Bridge may access up to 4 cascaded SPI Slave
devices. Additionally, each SPI-Bridge may have an 8-Bit GP Receive
port and 8-Bit GP Transmit Port. An `element selection` sequence
writes an 8 bit word into the `selected module` SPI-Bridge control
register to enable subsequent transactions with specific SPI
devices or to read or write data via the SPI-Bridge GPIO port.
[0554] In an embodiment, element selection takes place by assertion
of the local chip select line (CSL/) then clocking the first byte
of MOSI transferred data word into the control register. In some
cases, the format of the control register is CS4 CS3 CS2 CS1 AD1
AD0 R/W N. In another embodiment, the second byte is transmit or
receive data. When CSL/is de-asserted, the cycle is complete.
[0555] In an SPI transaction, following the element selection
sequence, subsequent SPI slave data transactions commence. The SPI
CS/(which may be referred to as SS/) is routed to one of 4 possible
bridged devices, per the true state of either CS4, CS3, CS2 or CS1.
Jumper bits AD0, ADlare compared to AD0, AD1 of the control
register allow up to four SPI-Bridges on a module.
[0556] One embodiment shows a device having a plurality of modules
mounted on a SPI link of a communications bus of the device, in
accordance with an embodiment of the invention. Three modules are
illustrated, namely Module 1, Module 2 and Module 3. Each module
includes one or more SPI bridges for bringing various components of
a module in electrical connection with the SPI link, including a
master controller (including one or more CPU's) in electrical
communication with the SPI link. Module 1 includes a plurality of
SPI slaves in electrical communication with each of SPI Bridge 00,
SPI Bridge 01, SPI Bridge 10 and SPI Bridge 11. In addition, each
module includes a Receive Data controller, Transmit Data controller
and Module ID jumpers.
[0557] In other embodiments, the modules 701-706 are configured to
communicate with one another and/or one or more controllers of the
system 700 with the aid of a wireless communications bus (or
interface). In an example, the modules 701-706 communicate with one
another with the aid of a wireless communications interface. In
another example, one or more of the modules 701-706 communicate
with a controller of the system 700 with the aid of a wireless
communications bus. In some cases, communication among the modules
701-706 and/or one or more controllers of the system is solely by
way of a wireless communications bus. This may advantageously
preclude the need for wired interfaces in the bays for accepting
the modules 701-706. In other cases, the system 700 includes a
wired interface that works in conjunction with a wireless interface
of the system 700.
[0558] Although the system 700, as illustrated, has a single rack,
a system, such as the system 700, may have multiple racks. In some
embodiments, a system has at most 1, or 2, or 3, or 4, or 5, or 6,
or 7, or 8, or 9, or 10, or 20, or 30, or 40, or 50, or 100, or
1000, or 10,000 racks. In an embodiment, the system has a plurality
of racks disposed in a side-by-side configuration.
[0559] In some embodiments, a user provides a sample to a system
having one or more modules, such as the system 700 of FIG. 55C. The
user provides the sample to a sample collection module of the
system. In an embodiment, the sample collection module includes one
or more of a lancet, needle, microneedle, venous draw, scalpel,
cup, swab, wash, bucket, basket, kit, permeable matrix, or any
other sample collection mechanism or method described elsewhere
herein. Next, the system directs the sample from the sample
collection module to one or more processing modules (e.g., modules
701-706) for sample preparation, assaying and/or detection. In an
embodiment, the sample is directed from the collection module to
the one or more processing modules with the aid of a sample
handling system, such as a pipette. Next, the sample is processed
in the one or more modules. In some situations, the sample is
assayed in the one or more modules and subsequently put through one
or more detection routines.
[0560] In some embodiments, following processing in the one or more
modules, the system communicates the results to a user or a system
(e.g., server) in communication with the system. Other systems or
users may then access the results to aid in treating or diagnosing
a subject.
[0561] In an embodiment, the system is configured for two-way
communication with other systems, such as similar or like systems
(e.g., a rack, such as that described in the context of FIG. 55C)
or other computers systems, including servers.
[0562] Devices and methods provided herein, by enabling parallel
processing, may advantageously decrease the energy or carbon
footprint of point of service systems. In some situations, systems,
such as the system 700 of FIG. 55C, has a footprint that is at most
10%, or 15%, or 20%, or 25%, or 30%, or 35%, or 40%, or 45%, or
50%, or 55%, or 60%, or 65%, or 70%, or 75%, or 80%, or 85%, or
90%, or 95%, or 99% that of other point of service systems.
[0563] In some embodiments, methods are provided for detecting
analytes. In an embodiment, a processing routine includes detecting
the presence or absence of an analyte. The processing routine is
facilitated with the aid of systems and devices provided herein. In
some situations, analytes are associated with biological processes,
physiological processes, environmental conditions, sample
conditions, disorders, or stages of disorders, such as one or more
of autoimmune disease, obesity, hypertension, diabetes, neuronal
and/or muscular degenerative diseases, cardiac diseases, and
endocrine diseases.
[0564] In some situations, a device processes one sample at a time.
However, systems provided herein are configured for multiplexing
sample processing. In an embodiment, a device processes multiple
samples at a time, or with overlapping times. In an example, a user
provides a sample to a device having a plurality of modules, such
as the system 700 of FIG. 55C. The device then processes the sample
with the aid of one or more modules of the device. In another
example, a user provides multiple samples to a device having a
plurality of modules. The device then processes the samples at the
same time with the aid of the plurality of modules by processing a
first sample in a first module while processing a second sample in
second module.
[0565] The system may process the same type of sample or different
types of samples. In an embodiment, the system processes one or
more portions of the same sample at the same time. This may be
useful if various assaying and/or detection protocols on the same
sample are desired. In another embodiment, the system processes
different types of samples at the same time. In an example, the
system processes a blood and urine sample concurrently in either
different modules of the system or a single module having
processing stations for processing the blood and urine samples.
[0566] In some embodiments, a method for processing a sample with
the aid of a point of service system, such as the system 700 of
FIG. 55C, comprises accepting testing criteria or parameters and
determining a test order or schedule based on the criteria. The
testing criteria is accepted from a user, a system in communication
with the point of service system, or a server. The criteria are
selectable based on a desired or predetermined effect, such as
minimizing time, cost, component use, steps, and/or energy. The
point of service system processes the sample per the test order or
schedule. In some situations, a feedback loop (coupled with
sensors) enables the point of service system to monitor the
progress of sample processing and maintain or alter the test order
or schedule. In an example, if the system detects that processing
is taking longer than the predetermined amount of time set forth in
the schedule, the system speeds up processing or adjusts any
parallel processes, such as sample processing in another module of
the system. The feedback loop permits real-time or pseudo-real time
(e.g., cached) monitoring. In some situations, the feedback loop
may provide permit reflex testing, which may cause subsequent
tests, assays, preparation steps, and/or other processes to be
initiated after starting or completing another test and/or assay or
sensing one or more parameter. Such subsequent tests, assays,
preparation steps, and/or other processes may be initiated
automatically without any human intervention. Optionally, reflex
testing is performed in response to an assay result. Namely by way
of non-limiting example, if a reflex test is ordered, a cartridge
is pre-loaded with reagents for assay A and assay B. Assay A is the
primary test, and assay B is the reflexed test. If the result of
assay A is meets a predefined criteria initiating the reflex test,
then assay B is run with the same sample in the device. The device
protocol is planned to account for the possibility of running the
reflex test. Some or all protocol steps of assay B can be performed
before the results for assay A are complete. For example, sample
preparation can be completed in advance on the device. It is
possible also to run a reflex test with a second sample from the
patient. In some embodiments, devices and systems provided herein
may contain components such that multiple different assays and
assay types may be reflex tested with the same device. In some
embodiments, multiple tests of clinical significance may be
performed in a single device provided herein as part of a reflex
testing protocol, where the performance of the same tests with
known systems and methods requires two or more separate devices.
Accordingly, systems and devices provided herein may permit, for
example, reflex testing which is faster and requires less sample
than known systems and methods. In addition, in some embodiments,
for reflex testing with a device provided herein, it is not
necessary to know in advance which reflexed tested will be
performed.
[0567] In some embodiments, the point of service system may stick
to a pre-determined test order or schedule based on initial
parameters and/or desired effects. In other embodiments, the
schedule and/or test order may be modified on the fly. The schedule
and/or test order may be modified based on one or more detected
conditions, one or more additional processes to run, one or more
processes to no longer run, one or more processes to modify, one or
more resource/component utilization modifications, one or more
detected error or alert condition, one or more unavailability of a
resource and/or component, one or more subsequent input or sample
provided by a user, external data, or any other reason.
[0568] In some examples, one or more additional samples may be
provided to a device after one or more initial samples are provided
to the device. The additional samples may be from the same subject
or different subjects. The additional samples may be the same type
of sample as the initial sample or different types of samples
(e.g., blood, tissue). The additional samples may be provided prior
to, concurrently with, and/or subsequent to processing the one or
more initial samples on the device. The same and/or different tests
or desired criteria may be provided for the additional samples, as
opposed to one another and/or the initial samples. The additional
samples may be processed in sequence and/or in parallel with the
initial samples. The additional samples may use one or more of the
same components as the initial samples, or may use different
components. The additional samples may or may not be requested in
view of one or more detected condition of the initial samples.
[0569] In some embodiments, the system accepts a sample with the
aid of a sample collection module, such as a lancet, scalpel, or
fluid collection vessel. The system then loads or accesses a
protocol for performing one or more processing routines from a
plurality of potential processing routines. In an example, the
system loads a centrifugation protocol and cytometry protocol. In
some embodiments, the protocol may be loaded from an external
device to a sample processing device. Alternatively, the protocol
may already be on the sample processing device. The protocol may be
generated based on one or more desired criteria and/or processing
routines. In one example, generating a protocol may include
generating a list of one or more subtasks for each of the input
processes. In some embodiments, each subtask is to be performed by
a single component of the one or more devices. Generating a
protocol may also include generating the order of the list, the
timing and/or allocating one or more resources.
[0570] In an embodiment, a protocol provides processing details or
specifications that are specific to a sample or a component in the
sample. For instance, a centrifugation protocol may include
rotational velocity and processing time that is suited to a
predetermined sample density, which enables density-dependent
separation of a sample from other material that may be present with
a desirable component of the sample.
[0571] A protocol is included in the system, such as in a protocol
repository of the system, or retrieved from another system, such as
a database, in communication with the system. In an embodiment, the
system is in one-way communication with a database server that
provides protocols to the system upon request from the system for
one or more processing protocols. In another embodiment, the system
is in two-way communication with a database server, which enables
the system to upload user-specific processing routines to the
database server for future use by the user or other users that may
have use for the user-specific processing routines.
[0572] Referring now to FIGS. 56A and 56B, the transport container
4000 may be configured to contain therein a plurality of bodily
fluid samples from a plurality of subjects such as patients. In
some embodiments there are multiple vessels of sample from each
subject. Optionally, at least two of the samples from the same
subject have had different chemical pre-treatment, such as but not
limited to different anti-coagulant in each vessel. Optionally,
some embodiments may use a vessel that has two or more separate
chambers, wherein each chamber is configured to hold a portion of
the fluid sample separate from fluid sample in another chamber.
Some embodiments may include samples from a subject in single
chamber vessels and/or multi-chamber vessels.
[0573] As seen in FIGS. 56A and 56B, various views of one
embodiment of the transport container 4000 wherein the lid 4010 has
a least a mesa portion 4012 that is sized to fit into a recess 4020
on the bottom of the transport container 4000 as seen in FIG. 57A
so that the vessels 4000 may be stackable. The transport container
4000 may have any of the features described herein for other
embodiments of transport containers described herein.
[0574] FIG. 57B shows that there may be a tray 4030 in the
transport container 4000 that is fixed and/or removable from the
transport container 4000. In one embodiment, the tray 4030 is held
in place by a fixture device such as but not limited to magnetic or
metal portions 4032 that align with metal or magnetic portions in
the chassis of the transport container 4000 to form a magnetic
connection. In some embodiments, the length-to-width aspect ratio
is in the range of about to 128:86 to 127:85. Optionally, the
length-to-width aspect ratio is in the range of about to 130:90 to
120:80. Optionally, the length of the tray is in the range of about
to 130 mm to 120 mm and the width is in the range of about 90 mm to
80 mm. In some embodiments, the height or thickness of the tray is
in the range of about 14 to 20 mm. The aspect ratio and/or size is
configured to hold a tray that is sized to fit a slot, recess, or
other holder on a plate centrifuge. In this manner, the entire tray
4030 can be centrifuged to prepare a plurality of the samples
therein.
[0575] As seen in FIGS. 57B and 58B, the tray 4030 has a plurality
of slots 4034, wherein the slots 4034 are sized to hold at least
one of the sample storage vessels. At least one portion 4040 of the
slot 4034 has a first shape and at least a second portion 4042
having a second shape different from the first shape, wherein the
shapes are keyed in a manner that the sample vessel can only be
inserted into the slot 4034 in a desired orientation. As seen in
FIG. 58B, one end is semi-circular while the other is
asymmetrically shaped. The tray 4030 can also be shaped to have cut
outs 4036 or other shapes so that the tray 4030 can only be
inserted in one orientation into the transport container 4000. It
should also be understood that the tray 4030 can be held in the
tray so that a user cannot remove it using their fingers from the
vessel 4000 without the use of a tool or other tray extraction
device. This minimizes the risk of user tampering. The tray 4030
can be configured to be held in the transport container 4000 even
when the transport container 4000 is upside down and can resist the
pull of earth gravity.
[0576] FIGS. 59A and 59B show yet another embodiment wherein there
a plurality of slots 4100 in a tray 4102. The tray has a different
aspect ratio (closer to square) and has a plurality of shaped slots
in the tray to hold the sample vessels.
[0577] Referring now to FIG. 60, at least one embodiment of a
sample sorting system will now be described. In this non-limiting
example, a frame 5000 such as but not limited to a tray from a
shipping container is provided. The number of sample containers
(not shown for ease of illustration) that may fit into the slots
5002 of the frame 5000 may be sorted based on one or more criteria.
The sample containers may be sorted as indicated by the arrows to
frames 5010 that may be of a different size or form factor than the
frame 5000. The frame 5010 may be configured to be sized to fit
certain equipment such as but not limited to standard plates of 96
well or other standard plate sizes. As seen in FIG. 60, by having
at least one sort process from the frame 5000 that arrive from
shipping to the frames 5010 that may be used for sample processing,
the shipping frame 5000 is not constrained by any particular
equipment format. Optionally, even some embodiments may use the
same form-factor frames for shipping and processing, there may
still be at least one sorting step to group sample containers based
on one or more factors such as but not limited the types of common
processing to be performed on the sample, type of sample, other
common denominator, or other factor. It should be understood that
some embodiments may use centrifuge equipment that can centrifuge
an entire frame 5000 or 5010. In this manner, a plurality of
samples can be processed at once. Some embodiments may centrifuge
before sorting, after sorting, or during sorting. Entire frames may
be centrifuged or only certain sample containers. Centrifugation of
an entire frame allows from simultaneous processing of many of the
sample containers at once, which can be particularly helpful if all
of the sample containers are sorted such that those with a certain
anti-coagulant or other pre-treatment will be pre-processed in the
same manner.
[0578] Optionally, some embodiments may scan all barcodes on the
sample containers while they are in shipping frame 5000.
Optionally, some may scan or read bar codes, RFID, or other sample
container identifier both before and after the sort. Optionally,
some may perform a scan after the sort. Some may not sort based on
bar code or other information storage unit on the sample container,
but based on some other information such as but not limited to
color of the container or other information provided through
non-bar code methods. Some embodiments may scan all of the slots in
the frame 5000 singly, line by line, rastering, in groups, or all
at once. A user interface maybe provide to let an operator know if
the system detects a barcode or information storage unit but fails
to get an accurate read. The system, in one non-limiting example,
may prevent the operator from moving on to the sort step until all
detected sample containers have had their information properly
read.
[0579] A pick-and-place robot or other transport device can be used
to perform the sort. Sample containers may be moved singly or in
groups. Some embodiments may move entire frames 5010 to new
stations where the entire set of sample containers may be imaged,
centrifuged, or otherwise processed. There may be register marks or
other positioning guides on the frames to assist in positioning
during these whole frame movements. Some embodiments may also begin
un-capped or otherwise accessing the sample inside the containers
while they are frames 5000 or 5010 to begin sample preparation. It
should be understood that some embodiments may also image each of
the containers individually by removing them from frames 5010 or
5000 as desired. It should also be understood that some embodiments
may have cascading sets of these sorting stations where samples
from frames are sorted from one frame to yet another frame,
carrier, or other grouping apparatus. Some embodiments may aliquot
sample from the sample containers, may dilute them (single or
serially), may begin to transport sample to different shaped or
sized sample vessels more suited for other equipment that will
process the samples. They may also be taken to various other sample
processing stations, with sample handling robots or devices to
handle this transportation.
[0580] In at least some embodiments, a medical provider (or their
staff when appropriate) can be the sample collector, test result
recipient, and/or both. For example, in one embodiment, a
healthcare professional such as but not limited to a dentist can
collect a sample as part of or separate from a dental procedure.
Optionally, some embodiments may have the sample collected from
suctioned blood and/or saliva from the subject's dental procedure.
The collected sample can be processed in the dental office and/or
shipped to a receiving location that receives a plurality of
samples for processing.
[0581] In embodiments, a bodily fluid sample used in a system,
device, or method provided herein may be diluted. In embodiments, a
bodily fluid sample may be diluted before it is transported from a
first location to a second location. In embodiments, a bodily fluid
sample may be diluted after it is transported from a first location
to a second location. In embodiments, a bodily fluid sample may be
diluted both before and after it is transported from a first
location to a second location. In embodiments, the bodily fluid
sample may be diluted after it is transported from a first location
to a second location and before it is used for performing one or
more steps of a laboratory test at the second location. An original
bodily fluid sample may be diluted, for example, at least 2, 3, 4,
5, 6, 7, 8, 9, 10, 15, 20, 50, 100, 200, 300, 400, 500, 1000,
5,000, 10,000, 50,000, or 100,000-fold. As used herein, an "n-fold"
dilution refers to a ratio by which an original sample is
diluted--e.g. an original sample which is diluted 5-fold contains,
after dilution, original sample at 1/5 of its original
concentration (i.e. the diluted sample contains sample at 1/5 of
the concentration of sample in the original sample); similarly, an
original sample which is diluted 500-fold contains, after dilution,
original sample at 1/500 of its original concentration. Thus, for
example, if an original sample contains 5 mg protein/microliter,
and it is diluted 2-fold, the diluted sample contains 2.5 mg
protein/microliter. A bodily fluid sample may be divided into any
number of portions, and the various portions may be diluted to
varying degrees of dilution, such that an original bodily fluid
sample may be processed to yield multiple diluted samples, each
having a different degree of dilution. Thus, for example, an
original bodily fluid sample may be divided into 5 portions, with
one portion being diluted 8-fold, another portion being diluted
12-fold, another portion being diluted 3-fold, another portion
being diluted 400-fold, and another portion being diluted
2,000-fold. Dilution of a sample may be performed serially or in a
single step. For a single-step dilution, a selected quantity of
sample may be mixed with a selected quantity of diluent, in order
to achieve a desired dilution of the sample. For a serial dilution,
two or more separate sequential dilutions of the sample may be
performed in order to achieve a desired dilution of the sample. For
example, a first dilution of the sample may be performed, and a
portion of that first dilution may be used as the input material
for a second dilution, to yield a sample at a selected dilution
level.
[0582] For dilutions described herein, an "original sample" or the
like refers to the sample that is used at the start of a given
dilution process. Thus, while an "original sample" may be a sample
that is directly obtained from a subject (e.g. whole blood), it may
also include any other sample (e.g. sample that has been processed
or previously diluted in a separate dilution procedure) that is
used as the starting material for a given dilution procedure.
[0583] In some embodiments, a serial dilution of a sample may be
performed as follows. A selected quantity (e.g. volume) of an
original sample may be mixed with a selected quantity of diluent,
to yield a first dilution sample. The first dilution sample (and
any subsequent dilution samples) will have: i) a sample dilution
factor (e.g. the amount by which the original sample is diluted in
the first dilution sample) and ii) an initial quantity (e.g. the
total quantity of the first dilution sample present after combining
the selected quantity of original sample and selected quantity of
diluent). For example, 10 microliters of an original sample may be
mixed with 40 microliters of diluent, to yield a first dilution
sample having a 5-fold sample dilution factor (as compared with the
original sample) and an initial quantity of 50 microliters. Next, a
selected quantity of the first dilution sample may be mixed with a
selected quantity of diluent, to yield a second dilution sample.
For example, 5 microliters of the first dilution sample may be
mixed with 95 microliters of diluent, to yield a second dilution
sample having an 100-fold dilution factor (as compared with the
original sample) and an initial quantity of 100 microliters. For
each of the above dilution steps, the original sample, dilution
sample(s), and diluent may be stored or mixed in fluidically
isolated vessels. Sequential dilutions may continue in the
preceding manner for as many steps as needed to reach a selected
sample dilution level/dilution factor. In embodiments, a sample may
be diluted as described in, for example, U.S. patent application
Ser. No. 13/769,820, filed Feb. 18, 2013, or any other document
incorporated by reference elsewhere herein.
[0584] As used herein, a reagent that is, or may be used as, a
"diluent" is one which is, e.g., useful for increasing the volume
of a sample, or portion of a sample, or is useful for the
preparation of a liquid formulation, such as a formulation
reconstituted after lyophilization, or for adding to a sample,
solution, or material for any other reason. In embodiments, a
diluent may be buffered (e.g., to have a pH near pH 7, or near pH
7.4, or other desired pH), and may be pharmaceutically acceptable
(safe and non-toxic for administration to a human). A diluent
typically does not react with, or bind to, an analyte in a sample.
Water may be a diluent, as may be an aqueous saline solution, a
buffered solution, a solution containing a surfactant, or any other
solution. Exemplary diluents include sterile water, bacteriostatic
water for injection (BWFI), a pH buffered solution (e.g.
phosphate-buffered saline), sterile saline solution, Ringer's
solution or dextrose solution. In embodiments, diluents can include
aqueous solutions of salts or buffers.
[0585] In embodiments, a bodily fluid sample or portion thereof
which has been, for example, collected from a subject, processed,
or transported according to a system or method provided herein may
be divided into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25,
30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000 or
more different portions. For descriptions of division of a sample
into multiple portions provided herein, an "original sample" or the
like refers to the sample that is used at the start of a given
sample division process. Thus, while an "original sample" may be,
for example, a sample that was directly obtained from a subject
(e.g. whole blood), it may also include any other sample (e.g.
sample that has been processed or previously divided in a separate
sample division procedure) that is used as the starting material
for a given sample division procedure. In embodiments, an "original
sample" may be subject to both sample division and dilution steps;
in such circumstances, reference to the "original sample" refers to
a starting material that is used for the combination sample
dilution/sample division procedure. When a sample is divided into
different portions, the different portions may contain different
amounts of the original sample. For instance, if an original sample
having of volume of 100 microliters is divided into 5 portions, one
portion may contain 50 microliters original sample, another portion
may contain 25 microliters original sample, another portion may
contain 15 microliters original sample, another portion may contain
8 microliters original sample, and the last portion may contain 2
microliters original sample. Likewise, when a sample is both
diluted and divided into different portions, the different portions
may have different degrees of dilution relative to the original
sample. For example, if an original sample is divided into three
portions, one portion may be diluted 5-fold relative to the
original sample, another portion may be diluted 20-fold relative to
the original sample, and the third portion may be diluted 200-fold
relative to the original sample.
[0586] Thus, in an example, a bodily fluid sample may be collected
from a subject at a first location (e.g. a sample collection site).
The bodily fluid sample as first collected from the subject may be
considered an "original sample". Such an "original sample" may be,
for example, a small quantity (e.g. less than 400, 300, 200, or 100
microliters) of whole blood from the subject. Shortly after or
concurrent with the collection of the "original sample" from the
subject, the "original sample" may be divided into at least a first
portion and a second portion, after which the first portion is
transferred into a first vessel and the second portion is
transferred into a second vessel. In embodiments, the first vessel
may contain a first anticoagulant (e.g. EDTA) and the second vessel
may contain a second anticoagulant (e.g. heparin). The first and
second vessels may be transported according to a system or method
provided herein from the first location to a second location. In
embodiments, at the second location, the sample in one or both of
the vessels or portions thereof may be subject to further
processing or analysis steps. For example, the sample in one or
both of the vessels or portions thereof may be divided into
additional portions, diluted, and/or used for performing one or
more tests.
[0587] In another example, a bodily fluid sample may be shipped in
a vessel from a first location to a second location according to
systems and methods provided herein. The bodily fluid sample in the
vessel may be the entirety of a sample that was collected from a
subject, or a portion thereof. At the second location, at least
some of the bodily fluid sample in the vessel may be removed from
the vessel and used for a sample division and/or dilution
procedure. The sample that is removed from vessel and used for the
sample division and/or dilution procedure may be considered an
"original sample". That original sample may be, for example, whole
blood, plasma, serum, saliva, or urine, and may constitute the
entirety of the sample that was transported in the vessel, or a
portion thereof. That original sample may be divided into any
number of portions; the various portions may have different degrees
of dilution relative to the original sample. For example, the
original sample removed from a transported vessel may have a volume
of less than or equal to 400, 300, 250, 200, 150, 100, 90, 80, 70,
60, 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1
microliter. The original sample removed from a transported vessel
may then be divided into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15,
20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500, 1000, 5,000,
10,000 or more different portions. In embodiments, the different
portions may have different degrees of dilution relative to the
original sample. For example, the different portions may have at
least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100,
200, 300, 400, 500, 1000, or 5,000 different degrees of dilution
relative to the original sample, with the condition that the number
of portions having different degrees of dilution does not exceed
the total number of portions prepared from the original sample. The
different portions may have any type of dilution relative to the
original sample, including, for example, no dilution, at least
2-fold dilution, at least 3-fold dilution, at least 5-fold
dilution, at least 10-fold dilution, at least 20-fold dilution, at
least 50-fold dilution, at least 100-fold dilution, at least
500-fold dilution, at least 1000-fold dilution, at least 5000-fold
dilution, at least 10,000-fold dilution, at least 50,000-fold
dilution, or at least 100,000-fold dilution. In embodiments, one or
more different portions of an original sample may be used for a
laboratory test. In embodiments, one portion of an original sample
may be used for one laboratory test. A portion of an original
sample used for a laboratory test may be a diluted sample.
[0588] In embodiments, an original sample may be a whole blood
sample obtained from a subject. The original sample may be obtained
from a subject's digit. The original sample may have a volume of no
greater than 400, 300, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30,
25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliters. The
original sample may be divided into multiple portions. Division of
the sample into multiple portions may occur before, after, or a
combination of before and after the sample is transported from a
first location to a second location according to a system or method
provided herein. In embodiments, the original sample may be divided
into at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40,
50, 100, 200, 300, 400, 500, 1000, 5,000, 10,000 or more different
portions, and the different portions are used to perform at least
2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200,
300, 400, 500, 1000, 5,000, 10,000 different laboratory tests. The
different portions of the original sample may have diluted original
sample. In embodiments, no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1,
0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.05, or 0.01
microliter of the original sample is used per each laboratory
test.
[0589] In embodiments, an original sample may be plasma or serum
obtained from whole blood sample obtained from a subject. The whole
blood may be obtained from a subject's digit. The whole blood
sample from which the plasma or serum is obtained may have a volume
of no greater than 400, 300, 200, 150, 100, 90, 80, 70, 60, 50, 40,
30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliters. The
plasma or serum original sample may have a volume of no greater
than 300, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15,
10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 microliters. The original sample
may be divided into multiple portions. Division of the sample into
multiple portions may occur before, after, or a combination of
before and after the sample is transported from a first location to
a second location according to a system or method provided herein.
In embodiments, the original sample may be divided into at least 2,
3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300,
400, 500, 1000, 5,000, 10,000 or more different portions, and the
different portions are used to perform at least 2, 3, 4, 5, 6, 7,
8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400, 500,
1000, 5,000, 10,000 different laboratory tests. The different
portions of the original sample may have diluted original
sample.
[0590] In embodiments, the equivalent of no more than 10, 9, 8, 7,
6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1,
0.05, or 0.01 microliter of an original sample is used for a
laboratory test. For example, if an original sample is whole blood,
and the original sample is divided into multiple portions, and at
least one of the portions contains a diluted sample which contains
original sample which has been diluted 100-fold, and 5 microliters
of that diluted sample is used to perform a laboratory test, then
the equivalent of 0.05 microliters of the original sample (e.g.
whole blood) is used for that test (5 microliters.times.1/100
dilution). In another example, an original sample may be whole
blood. That whole blood may be processed to yield plasma [e.g. by
separating the liquid components of the blood from the solid
components of blood (e.g. cells]. A certain volume of plasma may be
obtained from a certain volume of whole blood--e.g. the volume of
plasma that may be obtained from a volume of whole blood may be,
for example, at least or about 30%, 40%, 50%, 60%, or 70% of the
volume of whole blood. Thus, for example, if the volume of plasma
from whole blood is 50%, from 2 ml whole blood, 1 ml plasma may be
obtained. The plasma from whole blood may be further diluted, and
one or more diluted portions of the plasma may be used to perform
one or more laboratory tests. In another example, an original
sample may be whole blood. The whole blood may be processed to
yield plasma, where the volume of plasma from the whole blood is
60% of the whole blood (e.g. from 100 microliters whole blood, 60
microliters plasma is obtained). The plasma may be diluted 10-fold.
2 microliters of the diluted plasma may be used to perform a
laboratory test. Thus, for that laboratory test, the equivalent of
about 0.33 microliters original sample (whole blood) is used to
perform the test (2 microliters.times.1/10 dilution.times.100/60
whole blood/plasma conversion). In another example, an original
sample may be plasma, and the original sample may be divided into
multiple portions, and at least one of the portions contains a
diluted sample which contains original sample which has been
diluted 50-fold, and 4 microliters of that diluted sample is used
to perform a laboratory test, then the equivalent of 0.08
microliters of the original sample (e.g. plasma) is used for that
test (4 microliters.times.1/50 dilution).
[0591] In embodiments, an original sample may be divided into at
least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100,
200, 300, 400, 500, 1000, 5,000, 10,000 or more different portions,
and the different portions may be used to perform at least 2, 3, 4,
5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 100, 200, 300, 400,
500, 1000, 5,000, 10,000 different laboratory tests. In some
embodiments, at least as many portions of sample are prepared as
laboratory tests are performed with portions of a sample (e.g. in
order to perform 10 laboratory tests with an original sample, the
original sample may be divided into at least 10 portions, with at
least 1 portion being used per test). In certain other embodiments,
more than one laboratory test may be performed with a single
sample. For instance, in embodiments, an optical property of a
sample may be measured (e.g. cell count in a blood sample), and
then the same sample may be used to assay for an analyte in the
blood. Thus, in some embodiments, more laboratory tests may be
performed with an original sample than the number of portions which
are prepared from the same original sample (e.g. 10 laboratory
tests may be performed from an original sample which is divided
into only 8 portions).
[0592] When an original sample is divided into multiple portions,
and the multiple portions are used to perform two or more
laboratory tests, the laboratory tests may be of the same type of
laboratory test, or they may be of different types of laboratory
test. For instance, if an original sample is divided into 10
portions, and the 10 portions are each used for a laboratory test,
the laboratory test with each of the portions may be an
immunoassay. In another example, if an original sample is divided
into 5 portions, and the 5 portions are each used for a laboratory
test, the laboratory test with each of the portions may be a
nucleic acid amplification-based test.
[0593] In other situations, when an original sample is divided into
multiple portions, and the multiple portions are used to perform
two or more laboratory tests, at least two of the laboratory tests
may be of different types of laboratory test. For instance, if an
original sample is divided into 5 portions, and the 5 portions are
each used for a laboratory test, 2 of the portions may be used for
an immunoassay (e.g. ELISA) and 3 of the portions may be used for a
nucleic acid amplification-based test.
[0594] A bodily fluid sample or portion thereof transported
according to a system or method provided herein may be used in
various types of laboratory test, such as an immunoassay, nucleic
acid amplification assay, general chemistry assay, or cytometry
assay. In embodiments, a bodily fluid sample or portion thereof
transported according to a system or method provided herein may be
used in any type of assay or laboratory test as described in, for
example, U.S. patent application Ser. No. 13/769,820, filed Feb.
18, 2013, or any other document incorporated by reference elsewhere
herein.
[0595] In some embodiments, a bodily fluid sample or portion
thereof transported according to a system or method provided herein
may be used in an immunoassay. As used herein, an "immunoassay"
refers to any assay which involves probing for an analyte with an
antibody which has affinity for the analyte. Immunoassays may
include, for example, enzyme-linked immunosorbent (ELISA) assays
and may include competitive and non-competitive based-assays. The
term "antibody" as used herein refers to immunoglobulin molecules
and immunologically active portions of immunoglobulin molecules,
i.e., molecules that comprise an antigen-binding unit ("Abu" or
plural "Abus") which specifically binds ("immunoreacts with") an
antigen. Structurally, the simplest naturally occurring antibody
(e.g., IgG) comprises four polypeptide chains, two heavy (H) chains
and two light (L) chains inter-connected by disulfide bonds. The
immunoglobulins represent a large family of molecules that include
several types of molecules, such as IgD, IgG, IgA, IgM and IgE. The
term "immunoglobulin molecule" includes, for example, hybrid
antibodies, or altered antibodies, and fragments thereof.
Antigen-binding unit can be broadly divided into "single-chain"
("Sc") and "non-single-chain" ("Nsc") types based on their
molecular structures.
[0596] Also encompassed within the terms "antibodies" and
"antigen-binding unit" are immunoglobulin molecules and fragments
thereof that may be human, nonhuman (vertebrate or invertebrate
derived), chimeric, or humanized. For a description of the concepts
of chimeric and humanized antibodies see Clark et al., 2000 and
references cited therein (Clark, (2000) Immunol. Today 21:397-402).
In embodiments, "immunoassays" as provided herein may also include
assays in which the analyte to be measured in the assay is an
antibody, and the antibody is probed for with a molecule to which
the antibody has affinity (e.g. a target molecule of the
antibody).
[0597] In some embodiments, a bodily fluid sample or portion
thereof transported according to a system or method provided herein
may be used in a nucleic acid amplification assay. As used herein,
a "nucleic acid amplification assay" refers to an assay in which
the copy number of a target nucleic acid may be increased. Nucleic
acid amplification assays may include both isothermal and
temperature-variable amplification techniques, and include, for
example, techniques such as polymerase chain reaction (PCR) and
loop-mediated isothermal amplification (LAMP). Typically, a nucleic
acid amplification assay includes at least i) a nucleic acid
polymerase, ii) primers which can bind to a target nucleic acid
sequence, and iii) free nucleotides which may be incorporated into
synthesized nucleic acid by a polymerase. Amplification of a target
nucleic acid may be detected in various ways, such as measuring the
fluoresecence or turbidity of a reaction over a period of time.
[0598] In some embodiments, a bodily fluid sample or portion
thereof transported according to a system or method provided herein
may be used in a general chemistry assay. General chemistry assays
may include, for example, assays of a Basic Metabolic Panel
[glucose, calcium, sodium (Na), potassium (K), chloride (Cl), CO2
(carbon dioxide, bicarbonate), creatinine, blood urea nitrogen
(BUN)], assays of an Electrolyte Panel [sodium (Na), potassium (K),
chloride (Cl), CO2 (carbon dioxide, bicarbonate)], assays of a Chem
14 Panel/Comprehensive Metabolic Panel [glucose, calcium, albumin,
total protein, sodium (Na), potassium (K), chloride (Cl), CO2
(carbon dioxide, bicarbonate), creatinine, blood urea nitrogen
(BUN), alkaline phosphatase (ALP), alanine aminotransferase
(ALT/GPT), aspartate aminotransferase (AST/GOT), total bilirubin]
assays of a Lipid Profile/Lipid Panel [LDL cholesterol, HDL
cholesterol, total cholesterol, and triglycerides], assays of a
Liver Panel/Liver Function [alkaline phosphatase (ALP), alanine
aminotransferase (ALT/GPT), aspartate aminotransferase (AST/GOT),
total bilirubin, albumin, total protein, gamma-glutamyl transferase
(GGT), lactate dehydrogenase (LDH), prothrombin time (PT)],
alkaline phosphatase (APase), hemoglobin, VLDL cholesterol,
ethanol, lipase, pH, zinc protoporphyrin, direct bilirubin, blood
typing (ABO, RHD), lead, phosphate, hemagglutination inhibition,
magnesium, iron, iron uptake, fecal occult blood, and others,
individually or in any combination.
[0599] In general chemistry assays provided herein, in some
examples, the level of an analyte in a sample is determined through
one or more assay steps involving a reaction of the analyte of
interest with one or more reagents, leading to a detectable change
in the reaction (e.g. change in the turbidity of the reaction,
generation of luminescence in the reaction, change in the color of
the reaction, etc.). In some examples, a property of a sample is
determined through one or more assay steps involving a reaction of
the sample of interest with one or more reagents, leading to a
detectable change in the reaction (e.g. change in the turbidity of
the reaction, generation of luminescence in the reaction, change in
the color of the reaction, etc.). Typically, as used herein,
"general chemistry" assays do not involve amplification of nucleic
acids, imaging of cells on a microscopy stage, or the determination
of the level of an analyte in solution based on the use of a
labeled antibody/binder to determine the level of an analyte in a
solution. In some embodiments, general chemistry assays are
performed with all reagents in a single vessel--i.e. to perform the
reaction, all necessary reagents are added to a reaction vessel,
and during the course of the assay, materials are not removed from
the reaction or reaction vessel (e.g. there is no washing step; it
is a "mix and read" reaction). General chemistry assays may also
be, for example, colorimetric assays, enzymatic assays,
spectroscopic assays, turbidimetric assays, agglutination assays,
coagulation assays, and/or other types of assays. Many general
chemistry assays may be analyzed by measuring the absorbance of
light at one or more selected wavelengths by the assay reaction
(e.g. with a spectrophotometer). In some embodiments, general
chemistry assays may be analyzed by measuring the turbidity of a
reaction (e.g. with a spectrophotometer). In some embodiments,
general chemistry assays may be analyzed by measuring the
chemiluminescence generated in the reaction (e.g. with a PMT,
photodiode, or other optical sensor). In some embodiments, general
chemistry assays may be performed by calculations, based on
experimental values determined for one or more other analytes in
the same or a related assay. In some embodiments, general chemistry
assays may be analyzed by measuring fluorescence of a reaction
(e.g. with a detection unit containing or connected to i) a light
source of a particular wavelength(s) ("excitation wavelength(s)");
and ii) a sensor configured to detect light emitted at a particular
wavelength(s) ("emission wavelength(s)"). In some embodiments,
general chemistry assays may be analyzed by measuring agglutination
in a reaction (e.g. by measuring the turbidity of the reaction with
a spectrophotometer or by obtaining an image of the reaction with
an optical sensor). In some embodiments, general chemistry assays
may be analyzed by imaging the reaction at one or more time points
(e.g. with a CCD or CMOS optical sensor), followed by image
analysis. Optionally, analysis may involve prothrombin time,
activated partial thromboplastin time (APTT), either of which may
be measured through a method such as but not limited to
turbidimetry. In some embodiments, general chemistry assays may be
analyzed by measuring the viscosity of the reaction (e.g. with a
spectrophotometer, where an increase in viscosity of the reaction
changes the optical properties of the reaction). In some
embodiments, general chemistry assays may be analyzed by measuring
complex formation between two non-antibody reagents (e.g. a metal
ion to a chromophore; such a reaction may be measured with a
spectrophotometer or through colorimetry using another device). In
some embodiments, general chemistry assays may be analyzed by
non-ELISA or cytometry-based methods for assaying cellular antigens
(e.g. hemagglutination assay for blood type, which may be measured,
for example, by turbidity of the reaction). In some embodiments,
general chemistry assays may be analyzed with the aid of
electrochemical sensors (e.g. for carbon dioxide or oxygen).
Additional methods may also be used to analyze general chemistry
assays.
[0600] In some embodiments, a spectrophotometer may be used to
measure a general chemistry assay. In some embodiments, general
chemistry assays may be measured at the end of the assay (an
"end-point" assay) or at two or more times during the course of the
assay (a "time-course" or "kinetic" assay).
[0601] In some embodiments, a bodily fluid sample or portion
thereof transported according to a system or method provided herein
may be used in a cytometry assay. Cytometry assays are typically
used to optically, electrically, or acoustically measure
characteristics of individual cells. For the purposes of this
disclosure, "cells" may encompass non-cellular samples that are
generally of similar sizes to individual cells, including but not
limited to vesicles (such as liposomes), small groups of cells,
virions, bacteria, protozoa, crystals, bodies formed by aggregation
of lipids and/or proteins, and substances bound to small particles
such as beads or microspheres. Such characteristics include but are
not limited to size; shape; granularity; light scattering pattern
(or optical indicatrix); whether the cell membrane is intact;
concentration, morphology and spatio-temporal distribution of
internal cell contents, including but not limited to protein
content, protein modifications, nucleic acid content, nucleic acid
modifications, organelle content, nucleus structure, nucleus
content, internal cell structure, contents of internal vesicles
(including pH), ion concentrations, and presence of other small
molecules such as steroids or drugs; and cell surface (both
cellular membrane and cell wall) markers including proteins,
lipids, carbohydrates, and modifications thereof. By using
appropriate dyes, stains, or other labeling molecules either in
pure form, conjugated with other molecules or immobilized in, or
bound to nano- or micro-particles, cytometry may be used to
determine the presence, quantity, and/or modifications of specific
proteins, nucleic acids, lipids, carbohydrates, or other molecules.
Cytometric analysis may, for example, be by flow cytometry or by
microscopy. Flow cytometry typically uses a mobile liquid medium
that sequentially carries individual cells to an optical,
electrical or acoustic detector. Microscopy typically uses optical
or acoustic means to detect stationary cells, generally by
recording at least one magnified image. In embodiments, a cytometry
assay may involve obtaining images of one or more cells in a
sample. In embodiments, a sample may be provided on or in a
microscope slide or cuvette, which may permit cells in a sample to
settle in a desired configuration for imaging. Images of cells may
be obtained, for example, with a CCD or CMOS-based camera.
[0602] In some embodiments, laboratory test types may be classified
based on how the results of the test are detected. Different types
of laboratory test result detection may include, for example, i)
luminescence detection; ii) fluorescence detection; iii) absorbance
detection; iv) light scattering detection; and v) imaging. Each of
these detection methods are described, for example, in U.S. patent
application Ser. No. 13/769,820, filed Feb. 18, 2013, which is
hereby incorporated in its entirety for all purposes. Briefly,
luminescence may be detected from tests which yield a measurable
light signal. Such reactions may be, for example, chemiluminescent
reactions. In order to detect the result of a luminescent reaction,
a light detector such as a PMT or photodiode may be used to detect
light from an assay unit containing a luminescent reaction.
Fluorescence may be detected, for example, with an optical set up
which includes a light source and a light detector. The light
source may emit light of a particular wavelength(s). An assay unit
containing the test material may be situated in the path of the
light source, such that light of the particular wavelength(s)
reaches the contents of the assay unit ("excitation
wavelength(s)"). The assay unit may contain a molecule of interest
which, at least under some circumstances, absorbs light at the
particular wavelength(s) from the light source, and, subsequently,
releases light of a different wavelength. The light detector may be
configured to detect light released by the molecule of interest
("emission wavelength(s)"). The light source and/or light detector
may include a band-pass filter after the light source or before the
light detector, in order to restrict the wavelength(s) of light
from the light source or reaching the light detector. The light
source may be, for example, a light bulb, a laser or an LED, and
the light detector may be, for example, a PMT or photodiode.
Absorbance may be detected, for example, with an optical set up
which includes a light source and a light detector. The light
source and light detector may be situated in line with each other,
and configured such that an assay unit containing the test material
may be situated between the light source and light detector, such
that some light may pass through the test material to the light
detector and some light may be absorbed. Different amounts of light
may be absorbed by the test material, based on the outcome of the
test. Similarly, transmission of light through the test material
may be determined. For an absorbance/transmission determination
assay, the wavelength(s) of light emitted by the light source may
be same as the wavelength(s) of light detected by the light
detector. The light source may be, for example, a light bulb, a
laser or an LED, and the light detector may be, for example, a PMT
or photodiode. Light scattering may be detected, for example, with
an optical set up which includes a light source and a light
detector. The light source and light detector may be situated at an
angle relative to each other, and configured such that an assay
unit containing the test material may be situated in line with both
the light source and light detector, such that light from the light
source may reach the assay unit and be scattered by test material
in the assay unit, to reach the light detector. Different amounts
of light may be scattered by the test material, based on the
outcome of the test. The light source may be, for example, a light
bulb, a laser or an LED, and the light detector may be, for
example, a PMT or photodiode. Images of a test material may be
obtained, for example, by a detector which includes an image sensor
(e.g. a CCD or CMOS sensor). Typically the image sensor will be
included in a camera. Images of test material may be analyzed, for
example, by automated or manual image analysis, in order to
determine test results. Bodily fluid samples as provided herein may
also be used in laboratory tests which detect results through
non-optical based detection methods (e.g. measurements of
conductivity, radioactivity, or temperature).
[0603] In embodiments, in order to perform an assay/test with a
portion of a bodily fluid sample, the portion of the bodily fluid
sample may be transferred into an assay unit for at least one step
of the assay/test. Assay units may have various form factors, such
as a pipette tip, a tube, or a microscope slide. Steps of an assay
that may occur in an assay unit may include, for example, an
analyte in the sample binding to a binder (e.g. an antibody) for
the analyte, a target nucleic acid in the sample being amplified in
a nucleic acid amplification reaction, a sample coagulating based
on the addition of one or more reagents to the sample, or a sample
adopting a configuration for optical analysis (e.g. cells settling
on a surface of a microscope slide in order to facilitate obtaining
one or more images of the cells). As used herein, the terms "assay"
and "test" may be used interchangeably, unless the context clearly
dictates otherwise.
EXAMPLES
[0604] The following examples are offered for illustrative purposes
only, and are not intended to limit the present disclosure in any
way.
Example 1
[0605] A whole blood sample was obtained from a subject. The whole
blood sample was centrifuged in a vessel, in order to separate the
whole blood into pelleted cells and a plasma supernatant. The
centrifuged vessel was moved to an argon-purged glove box. Plasma
was aspirated from the centrifuged vessel and then aliquoted into 5
separate sample vessels as provided herein, wherein the sample
vessels each had an interior volume of no greater than 100
microliters, wherein no greater than 95 microliters plasma was
aliquoted into each sample vessel, and wherein each of the sample
vessels was of the same size and received the same volume of
plasma. The vessels each had a removable butyl rubber cap. The 5
sample vessels were associated with the labels "0 hour", "1 hour",
"2 hours", "8 hours", and "24 hours". At the respective time period
associated with each sample vessel, the sample in each vessel was
assayed for bicarbonate. The results of the assays are provided
below in Table 1.
TABLE-US-00001 TABLE 1 Time (hours) 0 1 2 8 24 Concentration 32.7
30.4 29.8 31.6 31.1 Bicarbonate (mM)
[0606] As shown in Table 1, the bicarbonate in the sample was
stable for at least 24 hours in a sample vessel provided
herein.
Example 2
[0607] A whole blood sample was obtained from a subject. EDTA was
mixed with the whole blood sample. Eighty microliters of the
EDTA-containing blood was aliquoted into each of 10 sample vessels
as provided herein, wherein each sample vessel had an interior
volume of no greater than 100 microliters, and was of the same
size. The sample vessels were associated with labeled for analysis
as follows: Real-time: Day 1, 2, 3, 4, 5, and 7; Pre-centrifuged:
Day 1, 2, 4, and 7. Each of the "pre-centrifuged" vessels were
centrifuged at the time of aliquoting the sample into the vessel,
to generate plasma and pelleted cells. Each of the "real-time"
vessels was centrifuged on the respective day, to generate plasma
and pelleted cells. After sample was aliquoted into each sample
vessel, it was capped. On the respective day for each vessel,
plasma was removed from the vessel and assayed for blood nitrogen
urea (BUN). The BUN assay results are shown in the graph in FIG.
48. As shown in the graph, BUN remains stable in a sample in a
sample vessel provided herein for at least 7 days, in both whole
blood and plasma samples.
[0608] The publications discussed or cited herein are provided
solely for their disclosure prior to the filing date of the present
application. Nothing herein is to be construed as an admission that
the present invention is not entitled to antedate such publication
by virtue of prior invention. Further, the dates of publication
provided may be different from the actual publication dates which
may need to be independently confirmed. All publications mentioned
herein are incorporated herein by reference to disclose and
describe the structures and/or methods in connection with which the
publications are cited. The following applications are fully
incorporated herein by reference for all purposes: in U.S.
Provisional Patent Application No. 61/435,250, filed Jan. 21, 2011
("SYSTEMS AND METHODS FOR SAMPLE USE MAXIMIZATION"), and U.S.
Patent Publication No. 2009/0088336 ("MODULAR POINT-OF-CARE
DEVICES, SYSTEMS, AND USES THEREOF"). The following applications
are also fully incorporated herein by reference for all purposes:
U.S. Patent Publication 2005/0100937, U.S. Pat. No. 8,380,541; U.S.
Pat. App. Ser. No. 61/766,113, filed Feb. 18, 2013; U.S. patent
application Ser. No. 13/769,798, filed Feb. 18, 2013; U.S. patent
application Ser. No. 13/769,779, filed Feb. 18, 2013; U.S. patent
application Ser. No. 13/769,820, filed Feb. 18, 2013; U.S. patent
application Ser. No. 13/244,947 filed Sep. 26, 2011;
PCT/US2012/57155, filed Sep. 25, 2012; U.S. application Ser. No.
13/244,946, filed Sep. 26, 2011; U.S. patent application Ser. No.
13/244,949, filed Sep. 26, 2011; and U.S. Application Ser. No.
61/673,245, filed Sep. 26, 2011, the disclosures of which patents
and patent applications are all hereby incorporated by reference in
their entireties.
Embodiments
[0609] In one embodiment described herein, a device for collecting
a bodily fluid sample from a subject is provided comprising: at
least two sample collection pathways configured to draw the bodily
fluid sample into the device from a single end of the device in
contact with the subject, thereby separating the fluid sample into
two separate samples; a second portion comprising a plurality of
sample vessels for receiving the bodily fluid sample collected in
the sample collection pathways, the sample vessels operably
engagable to be in fluid communication with the sample collection
pathways, whereupon when fluid communication is established, the
vessels provide a motive force to move a majority of the two
separate samples from the pathways into the vessels.
[0610] In another embodiment described herein, a device for
collecting a bodily fluid sample is provided comprising: a first
portion comprising at least one fluid collection location leading
to at least two sample collection pathways configured to draw the
fluid sample therein via a first type of motive force; a second
portion comprising a plurality of sample vessels for receiving the
bodily fluid sample collected in the sample collection pathways,
the sample vessels operably engagable to be in fluid communication
with the sample collection pathways, whereupon when fluid
communication is established, the vessels provide a second motive
force different from the first motive force to move a majority of
the bodily fluid sample from the pathways into the vessels; wherein
at least one of the sample collection pathways comprises a fill
indicator to indicate when a minimum fill level has been reached
and that at least one of the sample vessels can be engaged to be in
fluid communication with at least one of the sample collection
pathways.
[0611] In another embodiment described herein, a device for
collecting a bodily fluid sample is provided comprising a first
portion comprising at least two sample collection channels
configured to draw the fluid sample into the sample collection
channels via a first type of motive force, wherein one of the
sample collection channels has an interior coating designed to mix
with the fluid sample and another of the sample collection channels
has another interior coating chemically different from said
interior coating; a second portion comprising a plurality of sample
vessels for receiving the bodily fluid sample collected in the
sample collection channels, the sample vessels operably engagable
to be in fluid communication with the collection channels,
whereupon when fluid communication is established, the vessels
provide a second motive force different from the first motive force
to move a majority of the bodily fluid sample from the channels
into the vessels; wherein vessels are arranged such that mixing of
the fluid sample between the vessels does not occur.
[0612] In another embodiment described herein, a device for
collecting a bodily fluid sample is provided comprising: a first
portion comprising a plurality of sample collection channels,
wherein at least two of the channels are configured to
simultaneously draw the fluid sample into each of the at least two
sample collection channels via a first type of motive force; a
second portion comprising a plurality of sample vessels for
receiving the bodily fluid sample collected in the sample
collection channels, wherein the sample vessels have a first
condition where the sample vessels are not in fluid communication
with the sample collection channels, and a second condition where
the sample vessels are operably engagable to be in fluid
communication with the collection channels, whereupon when fluid
communication is established, the vessels provide a second motive
force different from the first motive force to move bodily fluid
sample from the channels into the vessels.
[0613] In another embodiment described herein, a sample collection
device is provided comprising: (a) a collection channel comprising
a first opening and a second opening, and being configured to draw
a bodily fluid sample via capillary action from the first opening
towards the second opening; and (b) a sample vessel for receiving
the bodily fluid sample, the vessel being engagable with the
collection channel, having an interior with a vacuum therein, and
having a cap configured to receive a channel; wherein the second
opening is defined by a portion the collection channel configured
to penetrate the cap of the sample vessel, and to provide a fluid
flow path between the collection channel and the sample vessel, and
the sample vessel has an interior volume no greater than ten times
larger than the interior volume of the collection channel.
[0614] In another embodiment described herein, a sample collection
device is provided comprising: (a) a collection channel comprising
a first opening and a second opening, and being configured to draw
a bodily fluid sample via capillary action from the first opening
towards the second opening; (b) a sample vessel for receiving the
bodily fluid sample, the vessel being engagable with the collection
channel, having an interior with a vacuum therein, and having a cap
configured to receive a channel; and (c) an adaptor channel
configured to provide a fluid flow path between the collection
channel and the sample vessel, having a first opening and a second
opening, the first opening being configured to contact the second
opening of the collection channel, the second opening being
configured to penetrate the cap of the sample vessel.
[0615] In another embodiment described herein, a sample collection
device is provided comprising: (a) a body, containing a collection
channel, the collection channel comprising a first opening and a
second opening, and being configured to draw a bodily fluid via
capillary action from the first opening towards the second opening;
(b) a base, containing a sample vessel for receiving the bodily
fluid sample, the sample vessel being engagable with the collection
channel, having an interior with a vacuum therein, and having a cap
configured to receive a channel; and (c) a support, wherein, the
body and the base are connected to opposite ends of the support,
and are configured to be movable relative to each other, such that
sample collection device is configured to have an extended state
and a compressed state, wherein at least a portion of the base is
closer to the body in the extended state of the device than in the
compressed state, the second opening of the collection channel is
configured to penetrate the cap of the sample vessel, in the
extended state of the device, the second opening of the collection
channel is not in contact with the interior of the sample vessel,
and in the compressed state of the device, the second opening of
the collection channel extends into the interior of the sample
vessel through the cap of the vessel, thereby providing fluidic
communication between the collection channel and the sample
vessel.
[0616] In another embodiment described herein, a sample collection
device is provided comprising: (a) a body, containing a collection
channel, the collection channel comprising a first opening and a
second opening, and being configured to draw a bodily fluid via
capillary action from the first opening towards the second opening;
(b) a base, containing a sample vessel for receiving the bodily
fluid sample, the sample vessel being engagable with the collection
channel, having an interior with a vacuum therein and having a cap
configured to receive a channel; (c) a support, and (d) an adaptor
channel, having a first opening and a second opening, the first
opening being configured to contact the second opening of the
collection channel, and the second opening being configured to
penetrate the cap of the sample vessel, wherein, the body and the
base are connected to opposite ends of the support, and are
configured to be movable relative to each other, such that sample
collection device is configured to have an extended state and a
compressed state, wherein at least a portion of the base is closer
to the body in the extended state of the device than in the
compressed state, in the extended state of the device, the adaptor
channel is not in contact with one or both of the collection
channel and the interior of the sample vessel, and in the
compressed state of the device, the first opening of the adaptor
channel is in contact with the second opening of the collection
channel, and the second opening of the adaptor channel extends into
the interior of the sample vessel through the cap of the vessel,
thereby providing fluidic communication between the collection
channel and the sample vessel.
[0617] In another embodiment described herein, a device for
collecting a fluid sample from a subject is provided comprising:
(a) a body containing a collection channel, the collection channel
comprising a first opening and a second opening, and being
configured to draw a bodily fluid via capillary action from the
first opening towards the second opening; (b) a base, engagable
with the body, wherein the base supports a sample vessel, the
vessel being engagable with the collection channel, having an
interior with a vacuum therein, and having a cap configured to
receive a channel; wherein the second opening of the collection
channel is configured to penetrate the cap of the sample vessel,
and to provide a fluid flow path between the collection channel and
the sample vessel.
[0618] In another embodiment described herein, a device for
collecting a fluid sample from a subject is provided comprising:
(a) a body containing a collection channel, the collection channel
comprising a first opening and a second opening, and being
configured to draw a bodily fluid via capillary action from the
first opening towards the second opening; (b) a base, engagable
with the body, wherein the base supports a sample vessel, the
sample vessel being engagable with the collection channel, having
an interior with a vacuum therein and having a cap configured to
receive a channel; and (c) an adaptor channel, having a first
opening and a second opening, the first opening being configured to
contact the second opening of the collection channel, and the
second opening being configured to penetrate the cap of the sample
vessel.
[0619] It should be understood that one or more of the following
features may be adapted for use with any of the embodiments
described herein. By way of non-limiting example, the body may
comprise of two collection channels. Optionally, the interior of
the collection channel(s) are coated with an anticoagulant.
Optionally, the body comprises a first collection channel and a
second collection channel, and the interior of the first collection
channel is coated with a different anticoagulant than the interior
of the second collection channel. Optionally, the first
anticoagulant is ethylenediaminetetraacetic acid (EDTA) and the
second anticoagulant is different from EDTA. Optionally, the first
anticoagulant is citrate and the second anticoagulant is different
from citrate. Optionally, the first anticoagulant is heparin and
the second anticoagulant is different from heparin. Optionally, one
anticoagulant is heparin and the second anticoagulant is EDTA.
Optionally, one anticoagulant is heparin and the second
anticoagulant is citrate. Optionally, one anticoagulant is citrate
and the second anticoagulant is EDTA. Optionally, the body is
formed from an optically transmissive material. Optionally, the
device includes the same number of sample vessels as collection
channels. Optionally, the device includes the same number of
adaptor channels as collection channels. Optionally, the base
contains an optical indicator that provides a visual indication of
whether the sample has reached the sample vessel in the base.
Optionally, the base is a window that allows a user to see the
vessel in the base. Optionally, the support comprises a spring, and
spring exerts a force so that the device is at the extended state
when the device is at its natural state. Optionally, the second
opening of the collection channel or the adaptor channel is capped
by a sleeve, wherein said sleeve does not prevent movement of
bodily fluid via capillary action from the first opening towards
the second opening. Optionally, the sleeve contains a vent.
Optionally, each collection channel can hold a volume of no greater
than 500 uL. Optionally, each collection channel can hold a volume
of no greater than 200 uL. Optionally, each collection channel can
hold a volume of no greater than 100 uL. Optionally, each
collection channel can hold a volume of no greater than 70 uL.
Optionally, each collection channel can hold a volume of no greater
than 500 uL. Optionally, each collection channel can hold a volume
of no greater than 30 uL. Optionally, the internal circumferential
perimeter of a cross-section of each collection channel is no
greater than 16 mm. Optionally, the internal circumferential
perimeter of a cross-section of each collection channel is no
greater than 8 mm. Optionally, the internal circumferential
perimeter of a cross-section of each collection channel is no
greater than 4 mm. Optionally, the internal circumferential
perimeter is a circumference. Optionally, the device comprises a
first and a second collection channel, and the opening of the first
channel is adjacent to an opening of said second channel, and the
openings are configured to draw blood simultaneously from a single
drop of blood. Optionally, the opening of the first channel and the
opening of the second channel have a center-to-center spacing of
less than or equal to about 5 mm. Optionally, each sample vessel
has an interior volume no greater than twenty times larger than the
interior volume of the collection channel with which it is
engagable. Optionally, each sample vessel has an interior volume no
greater than ten times larger than the interior volume of the
collection channel with which it is engagable. Optionally, each
sample vessel has an interior volume no greater than five times
larger than the interior volume of the collection channel with
which it is engagable. Optionally, each sample vessel has an
interior volume no greater than two times larger than the interior
volume of the collection channel with which it is engagable.
Optionally, establishment of fluidic communication between the
collection channel and the sample vessel results in transfer of at
least 90% of the bodily fluid sample in the collection channel into
the sample vessel.
[0620] It should be understood that one or more of the following
features may be adapted for use with any of the embodiments
described herein. Optionally, establishment of fluidic
communication between the collection channel and the sample vessel
results in transfer of at least 95% of the bodily fluid sample in
the collection channel into the sample vessel. Optionally,
establishment of fluidic communication between of the collection
channel and the sample vessel results in transfer of at least 98%
of the bodily fluid sample in the collection channel into the
sample vessel. Optionally, establishment of fluidic communication
between the collection channel and the sample vessel results in
transfer of the bodily fluid sample into the sample vessel and in
no more than ten uL of bodily fluid sample remaining in the
collection channel. Optionally, establishment of fluidic
communication between the collection channel and the sample vessel
results in transfer of the bodily fluid sample into the sample
vessel and in no more than five uL of bodily fluid sample remaining
in the collection channel. Optionally, engagement of the collection
channel with the sample vessel results in transfer of the bodily
fluid sample into the sample vessel and in no more than 2 uL of
bodily fluid sample remaining in the collection channel.
[0621] In another embodiment described herein, a method is provided
comprising contacting one end of a sample collection device to a
bodily fluid sample to split the sample into at least two portions
by drawing the sample into at least two collection channels of the
sample collection device by way of a first type of motive force;
establishing fluid communication between the sample collection
channels and the sample vessels after a desired amount of sample
fluid has been confirmed to be in at least one of the collection
channels, whereupon the vessels provide a second motive force
different from the first motive force to move each of the portions
of bodily fluid sample into their respective vessels.
[0622] In another embodiment described herein, a method is provided
comprising metering a minimum amount of sample into at least two
channels by using a sample collection device with at least two of
the sample collection channels configured to simultaneously draw
the fluid sample into each of the at least two sample collection
channels via a first type of motive force; after a desired amount
of sample fluid has been confirmed to be in the collection
channels, fluid communication is established between the sample
collection channels and the sample vessels, whereupon the vessels
provide a second motive force different from the first motive force
use to collect the samples to move bodily fluid sample from the
channels into the vessels.
[0623] In another embodiment described herein, a method of
collecting a bodily fluid sample is provided comprising (a)
contacting a bodily fluid sample with a device comprising a
collection channel, the collection channel comprising a first
opening and a second opening, and being configured to draw a bodily
fluid via capillary action from the first opening towards the
second opening, such that the bodily fluid sample fills the
collection channel from the first opening through the second
opening; (b) establishing a fluid flow path between the collection
channel and the interior of a sample vessel, said sample vessel
having an interior volume no greater than ten times larger than the
interior volume of the collection channel and having a vacuum prior
to establishment of the fluid flow path between the collection
channel and the interior of the sample vessel, such that
establishment of the fluid flow path between the collection channel
and the interior of the sample vessel generates a negative pressure
at the second opening of the collection channel, and the fluidic
sample is transferred from the collection channel to the interior
of the sample vessel.
[0624] In another embodiment described herein, a method of
collecting a bodily fluid sample is provided comprising (a)
contacting a bodily fluid sample with any collection device as
described herein, such that the bodily fluid sample fills the
collection channel from the first opening through the second
opening of at least one of the collection channel(s) in the device;
and (b) establishing a fluid flow path between the collection
channel and the interior of the sample vessel, such that
establishing a fluid flow path between the collection channel and
the interior of the sample vessel generates a negative pressure at
the second opening of the collection channel, and the fluidic
sample is transferred from the collection channel to the interior
of the sample vessel.
[0625] It should be understood that one or more of the following
features may be adapted for use with any of the embodiments
described herein. Optionally, the collection channel and the
interior of the sample vessel are not brought into fluid
communication until the bodily fluid reaches the second opening of
the collection channel. Optionally, the device comprises two
collection channels, and the collection channels and the interior
of the sample vessels are not brought into fluidic communication
until the bodily fluid reaches the second opening of both
collection channels. Optionally, the second opening of the
collection channel in the device is configured to penetrate the cap
of the sample vessel, and wherein a fluidic flow path between the
second opening of the collection channel and the sample vessel is
established by providing relative movement between the second
opening of the collection channel and the sample vessel, such that
the second opening of the collection channel penetrates the cap of
the sample vessel. Optionally, the device comprises an adaptor
channel for each collection channel in the device, the adaptor
channel having a first opening and a second opening, the first
opening being configured to contact the second opening of the
collection channel, and the second opening being configured to
penetrate the cap of the sample vessel, and wherein a fluidic flow
path between the collection channel and the sample vessel is
established by providing relative movement between two or more of:
(a) the second opening of the collection channel, (b) the adaptor
channel, and (c) the sample vessel, such that the second opening of
the adaptor channel penetrates the cap of the sample vessel.
[0626] In another embodiment described herein, a method for
collecting a bodily fluid sample from a subject is provided
comprising: (a) bringing a device comprising a first channel and a
second channel into fluidic communication with a bodily fluid from
the subject, each channel having an input opening configured for
fluidic communication with said bodily fluid, each channel having
an output opening downstream of the input opening of each channel,
and each channel being configured to draw a bodily fluid via
capillary action from the input opening towards the output opening;
(b) bringing, through the output opening of each of the first
channel and the second channel, said first channel and said second
channel into fluidic communication with a first vessel and a second
vessel, respectively; and (c) directing said bodily fluid within
each of said first channel and second channel to each of said first
vessel and second vessel with the aid of: (i) negative pressure
relative to ambient pressure in said first vessel or said second
vessel, wherein said negative pressure is sufficient to effect flow
of said bodily fluid through said first channel or said second
channel into its corresponding vessel, or (ii) positive pressure
relative to ambient pressure upstream of said first channel or said
second channel, wherein said positive pressure is sufficient to
effect flow of said whole blood sample through said first channel
or said second channel into its corresponding vessel.
[0627] In another embodiment described herein, a method of
manufacturing a sample collection device is provided comprising
forming one portion of a sample collection device having at least
two channels configured to simultaneously draw the fluid sample
into each of the at least two sample collection channels via a
first type of motive force; forming sample vessels, whereupon the
vessels are configured to be coupled to the sample collection
device to the provide a second motive force different from the
first motive force use to collect the samples to move bodily fluid
sample from the channels into the vessels.
[0628] In another embodiment described herein, computer executable
instructions are provided for performing a method comprising:
forming one portion of a sample collection device having at least
two channels configured to simultaneously draw the fluid sample
into each of the at least two sample collection channels via a
first type of motive force.
[0629] In another embodiment described herein, computer executable
instructions for performing a method comprising: forming sample
vessels, whereupon the vessels are configured to be coupled to the
sample collection device to provide a second motive force different
from the first motive force use to collect the samples to move
bodily fluid sample from the channels into the vessels.
[0630] In yet another embodiment described herein, a device for
collecting a bodily fluid sample from a subject, the device
comprising: means for drawing the bodily fluid sample into the
device from a single end of the device in contact with the subject,
thereby separating the fluid sample into two separate samples;
means for transferring the fluid sample into a plurality of sample
vessels, wherein the vessels provide a motive force to move a
majority of the two separate samples from the pathways into the
vessels.
[0631] While the above is a complete description of the preferred
embodiment as described herein, it is possible to use various
alternatives, modifications and equivalents. Therefore, the scope
of the present invention should be determined not with reference to
the above description but should, instead, be determined with
reference to the appended claims, along with their full scope of
equivalents. Any feature, whether preferred or not, may be combined
with any other feature, whether preferred or not. The appended
claims are not to be interpreted as including means-plus-function
limitations, unless such a limitation is explicitly recited in a
given claim using the phrase "means for." It should be understood
that as used in the description herein and throughout the claims
that follow, the meaning of "a," "an," and "the" includes plural
reference unless the context clearly dictates otherwise. Also, as
used in the description herein and throughout the claims that
follow, the meaning of "in" includes "in" and "on" unless the
context clearly dictates otherwise. Finally, as used in the
description herein and throughout the claims that follow, the
meanings of "and" and "or" include both the conjunctive and
disjunctive and may be used interchangeably unless the context
expressly dictates otherwise. Thus, in contexts where the terms
"and" or "or" are used, usage of such conjunctions do not exclude
an "and/or" meaning unless the context expressly dictates
otherwise. The following US patent applications are incorporated
herein by reference for all purposes: 61/733,886 filed Dec. 5,
2012, 61/875,030 filed Sep. 7, 2013, and 61/875,107 filed Sep. 8,
2013. This document contains material subject to copyright
protection. The copyright owner (Applicant herein) has no objection
to facsimile reproduction of the patent documents and disclosures,
as they appear in the US Patent and Trademark Office patent file or
records, but otherwise reserves all copyright rights whatsoever.
The following notice shall apply: Copyright 2013 Theranos, Inc.
* * * * *