U.S. patent application number 17/393398 was filed with the patent office on 2022-02-24 for devices and methods for biological assay sample preparation and delivery.
The applicant listed for this patent is Lucira Health, Inc.. Invention is credited to Ivan Krastev Dimov, Ryan C. Griswold, Wei Hsuan Ho, Debkishore Mitra, Frank B. Myers, III, Bruce Richardson, John Robert Waldeisen.
Application Number | 20220057305 17/393398 |
Document ID | / |
Family ID | |
Filed Date | 2022-02-24 |
United States Patent
Application |
20220057305 |
Kind Code |
A1 |
Myers, III; Frank B. ; et
al. |
February 24, 2022 |
Devices and Methods for Biological Assay Sample Preparation and
Delivery
Abstract
Devices and methods for preparing and delivering biological
assay samples are provided herein. Components of such devices
include a sample receiving module within which a biological assay
sample can be prepared and a cap, which when operatively coupled
with the sample receiving module, pressurizes the module. These
devices can be employed for subsequently delivering a biological
assay sample.
Inventors: |
Myers, III; Frank B.;
(Richmond, CA) ; Ho; Wei Hsuan; (Foster City,
CA) ; Mitra; Debkishore; (Fremont, CA) ;
Waldeisen; John Robert; (Berkeley, CA) ; Dimov; Ivan
Krastev; (Union City, CA) ; Griswold; Ryan C.;
(Los Gatos, CA) ; Richardson; Bruce; (Los Gatos,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Lucira Health, Inc. |
Emeryville |
CA |
US |
|
|
Appl. No.: |
17/393398 |
Filed: |
August 3, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16081799 |
Aug 31, 2018 |
11125661 |
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PCT/US17/22304 |
Mar 14, 2017 |
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17393398 |
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62307876 |
Mar 14, 2016 |
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International
Class: |
G01N 1/30 20060101
G01N001/30; B01L 3/00 20060101 B01L003/00; G01N 1/38 20060101
G01N001/38 |
Claims
1. A biological assay sample preparation device, the device
comprising: a. a sample receiving module comprising an outer body
forming a first chamber, an inner body forming a second chamber, a
preparation solution, and a first attachment element; and b. a cap
removably coupleable to the sample receiving module and comprising:
i. a pressurizing component; and ii. a second attachment element
operatively coupleable with the first attachment element, wherein
the pressurizing component extends into and pressurizes the sample
receiving module upon operative coupling of the first attachment
element to the second attachment element wherein the outer body
comprises a piercing member, wherein the inner body comprises a
breakable seal and is movable within the outer body, and wherein
operatively coupling the first attachment element to the second
attachment element comprises moving the inner body within the outer
body to break the breakable seal and place the first and second
chambers in fluidic communication.
2. The device according to claim 1, wherein the fluid container is
adapted to receive one or more portions of a sample.
3. The device according to claim 1, wherein the preparation
solution is a nucleic acid amplification preparation solution.
4. The device according to claim 1, wherein the cap comprises a
receptacle configured to receive an end of the sample receiving
module therein when the cap is coupled to the sample receiving
module.
5. The device according to claim 4, wherein the pressurizing
component is disposed within the receptacle or integral with the
cap.
6. (canceled)
7. The device according to claim 1, wherein the device is a
hand-held device.
8. The device according to claim 1, wherein the fluid container has
a volume of 50 cm.sup.3 or less.
9. The device according to claim 1, wherein the sample collector
comprises a swab.
10. The device according to claim 1, wherein the first attachment
element comprises a thread and the second attachment element
comprises a reciprocating groove for slidably receiving the thread
therein.
11. The device according to claim 1, wherein the pressurizing
component pressurizes the sample receiving module to a peak
pressure ranging from 10000 Pa to 30000 Pa.
12. The device according to claim 1, wherein the pressurizing
element extends from an interior surface of the cap.
13. The device according to claim 1, wherein the pressurizing
element is cylindrical.
14-16. (canceled)
17. The device according to claim 1, wherein the sample receiving
module comprises an actuable valve configured to discharge fluid
from the fluid container therethrough when actuated.
18. The device according to claim 17, wherein the first attachment
element is at a first end of the sample receiving module and the
valve is at a second end of the sample receiving module opposite
the first end.
19-20. (canceled)
21. The device according to claim 17, wherein the device further
comprises a filter configured to filter a sample fluid prior to
discharging the sample fluid through the valve.
22-25. (canceled)
26. The device according to claim 1, wherein the outer body
comprises a staging reagent.
27. The device according to claim 26, wherein the staging reagent
is a lyophilized lysing reagent.
28-29. (canceled)
30. A method of delivering a biological assay sample, the method
comprising: a. collecting a biological sample with a sample
collector; b. inserting the sample collector into a sample
receiving module of a sample preparation device, wherein inserting
the sample collector comprises exposing the biological sample to a
preparation solution to produce a prepared biological assay sample;
c. operatively coupling a cap of the sample preparation device to
the sample receiving module and thereby pressurizing the sample
receiving module; and d. delivering the prepared biological assay
sample by depressurizing the sample receiving module by flowing at
least a portion of the prepared biological assay sample out of the
sample receiving module.
31-52. (canceled)
53. A biological assay sample preparation device, the device
comprising: a. a cap comprising a first chamber, a plunger
comprising a piercing member, and a seal; and b. a sample receiving
module which is operatively coupleable to the cap and comprises a
second chamber, wherein when the sample receiving module is
operatively coupled to the cap, advancing the plunger pierces the
seal with the piercing member and places the first chamber in
fluidic communication with the second chamber.
54. (canceled)
55. A method of preparing a biological assay sample, the method
comprising: a. operatively coupling a cap and a sample receiving
module of a biological assay sample preparation device, wherein the
cap comprises a seal and a plunger comprising a piercing member;
and b. advancing the plunger to pierce the seal with the piercing
member and thereby placing the first chamber in fluidic
communication with the second chamber and preparing the biological
assay sample.
56-60. (canceled)
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 16/081,799, filed on August 31, 2018, now U.S. Pat. No.
11,125,661, issued Sep. 21, 2021, which is a 35 U.S.C. 371 national
stage filing of International Application No. PCT/US2017/022304,
filed on Mar. 14, 2017, which claims priority from U.S. Provisional
Patent Application No. 62/307,876 filed on Mar. 14, 2016, which are
hereby incorporated by reference in their entireties.
INTRODUCTION
[0002] Biological assays sometimes require one or more fluids to be
mixed, moved, separated and/or otherwise processed. Some biological
assay devices and methods employ passive media control techniques
such as capillary action for moving such fluids. Other methods and
devices use active media control techniques which include
propelling one or more fluids into, through and/or out of devices.
Active media control techniques, in some instances, involve
employing one or more pumps, such as electrically driven pumps, to
create a fluid flow.
SUMMARY
[0003] Devices and methods for preparing and delivering biological
assay samples are provided herein. Components of such devices
include a sample receiving module within which a biological assay
sample can be prepared and a cap, which when operatively coupled
with the sample receiving module, pressurizes the module. These
devices can be employed for subsequently delivering a biological
assay sample.
[0004] Embodiments of the disclosed devices include a sample
receiving module having a fluid container for receiving one or more
portions of a sample collector therein, a preparation solution,
such as a nucleic acid amplification preparation solution, and a
first attachment element. Such devices can also include a cap, such
as a cap which is removably coupleable to the sample receiving
module and which includes a pressurizing component, and a second
attachment element operatively coupleable with the first attachment
element. In some versions of the devices, the pressurizing
component extends into and pressurizes the sample receiving module
for expelling fluid therefrom when the first attachment element is
operatively coupled to the second attachment element. In some
versions, the first attachment element is a thread and the second
attachment element is a reciprocating groove for slidably receiving
the thread therein. According to various aspects, the second
attachment element extends concentrically around the pressurizing
component.
[0005] In various aspects of the devices, a cap includes a
receptacle configured to receive an end of the sample receiving
module therein when the cap is coupled to the sample receiving
module. The pressurizing component can extend from an interior
surface of the cap and/or be disposed within the receptacle and/or
can be integral with the cap. Also, in some aspects, the
pressurizing component pressurizes the sample receiving module to a
pressure ranging from 10 Pa to 30000 Pa.
[0006] Where desired, the disclosed devices can be hand-held and/or
can include a fluid container having a volume of 50 cm.sup.3 or
less. In some versions, the device includes a sample collector,
such as a sample collector including a swab configured for
collecting a biological sample.
[0007] In some embodiments, the pressurizing component is shaped
substantially as a cylinder and/or the cap is shaped as a cylinder.
In various embodiments, the sample receiving module is shaped as a
cylinder having a diameter of 5 cm or less and having a height of
20 cm or less. Also, in some versions, the fluid container has a
volume ranging from 1.0 cm.sup.3 to 1.5 cm.sup.3 and/or can contain
from 1.0 cm.sup.3 to 1.5 cm.sup.3 of fluid therein.
[0008] In some instances, the sample receiving module includes a
reversibly actuable valve configured to discharge fluid from the
fluid container therethrough when actuated. In some aspects, the
first attachment element is at a first end of the sample receiving
module and the valve is at a second end of the sample receiving
module opposite the first end. A device can also include one or
more breakable seal, e.g., a seal including a foil sheet, for
sealing the valve. A device can also include one or more
re-sealable valve, e.g., a re-sealable puncture seal, e.g., a
rubber septum, for sealing the valve. Such a valve may be
incorporated in the device at the same location but instead of a
breakable seal. A device can also include one or more filter for
filtering fluid discharging through the valve. A filter can be
configured to filter a sample fluid prior to discharging the sample
fluid through the valve. As used herein the phrase "sample fluid"
refers to fluid comprising sample that optionally can include any
one or more reagents mixed with the sample within the sample
preparation device.
[0009] Where appropriate, the sample receiving module includes an
outer body forming a first chamber, and/or the fluid container
includes a breakable seal and an inner body forming a second
chamber, wherein the inner body is actuable within the outer body.
In some versions, the outer body includes one or more piercing
member. In some aspects, the inner body actuates within the outer
body when the cap is coupled to the sample receiving module to
break the seal with the piercing member and place the first and
second chambers in fluidic communication. According to some
aspects, the outer body and/or inner body includes a staging
reagent, e.g., a lyophilized lysing reagent.
[0010] The subject devices also include biological assay sample
preparation devices such as devices including a cap having a first
chamber, a plunger including a piercing member, and a seal. Such
devices can also include a sample receiving module, e.g., a sample
receiving module configured to receive a biological sample
collector therein, which is operatively coupleable to the cap and
includes a second chamber. In some aspects, when the sample
receiving module is operatively coupled to the cap, advancing the
plunger pierces the seal with the piercing member and places the
first chamber in fluidic communication with the second chamber.
[0011] As noted above, the subject disclosure is also drawn to
methods of delivering a biological assay sample. The methods can
include collecting a biological sample with a sample collector
and/or inserting the sample collector into a sample receiving
module of a sample preparation device. In some versions, inserting
the sample collector includes exposing the biological sample to a
preparation solution, e.g., a nucleic acid amplification
preparation solution, to produce a prepared biological assay
sample, e.g., a prepared nucleic acid amplification sample. The
methods, in some aspects also include operatively coupling a cap of
the sample preparation device to the sample receiving module and
thereby pressurizing the sample receiving module. Additionally,
where desired, the methods include delivering the prepared
biological assay sample by depressurizing the sample receiving
module by flowing at least a portion of the prepared biological
assay sample out of the sample receiving module.
[0012] In some instances, a cap includes a pressurizing component
and operatively coupling the cap involves inserting the
pressurizing component into the sample receiving module.
Pressurizing the sample receiving module can include pressurizing
the module to a pressure ranging from 100 Pa to 30000 Pa.
[0013] According to some aspects, operatively coupling a cap of the
sample preparation device to the sample receiving module includes
inserting an end of the sample receiving module into the cap. In
some embodiments, operatively coupling a cap of the sample
preparation device to the sample receiving module includes screwing
the sample receiving module to the cap. In some embodiments, the
sample receiving module and the cap are irreversibly engageable.
For example, in some versions, when the cap is screwed back on, a
user can screw it all the way down to a visually recognizable
marker, e.g., a line, on the outside of the sample receiving
module, at which point the cap will irreversibly engage by locking
and will no longer re-open. Irreversibly engaging the components
can also generate a clicking sound to notify a user of the
irreversible engagement.
[0014] In some versions of the methods, the cap is operatively
coupled to a first end of the sample preparation device and the
sample receiving module includes a reversibly actuable valve at a
second end of the sample preparation device opposite the first end.
In some instances, the device further includes a breakable seal for
sealing the valve and depressurizing the sample receiving module
includes breaking the seal. In some versions, the methods also
include filtering fluid discharging from the sample receiving
module with a filter of a device.
[0015] According to various embodiments, the sample receiving
module includes an outer body forming a first chamber, and wherein
the fluid container includes a breakable seal and an inner body
forming a second chamber, wherein the inner body is actuable within
the outer body. In some aspects, operatively coupling a cap of the
sample preparation device to the sample receiving module includes
actuating the inner body within the outer body to break the seal
and place the first and second chambers in fluidic communication.
Also, where desired, the outer body includes a piercing member
which breaks the seal when the inner body is actuated within the
outer body. In addition, in some of the subject methods, the outer
body and/or inner body includes a staging reagent and placing the
first and second chambers in fluidic communication includes mixing
the preparation solution and the staging reagent.
[0016] In some versions of the methods wherein the sample receiving
module includes a first attachment element and the cap includes a
second attachment element, operatively coupling a cap of the sample
preparation device to the sample receiving module includes mateably
connecting the first and second attachment elements. Also, in some
aspects wherein the sample receiving module includes a breakable
seal over an opening, inserting the sample collector into a sample
receiving module of a sample preparation device includes breaking
the seal and inserting at least a portion of the sample collector
through the opening.
[0017] The subject methods also include methods of preparing one or
more biological assay sample. Such methods can include operatively
coupling a cap and a sample receiving module of a biological assay
sample preparation device, wherein the cap includes a seal and a
plunger including a piercing member. Such methods also, according
to some embodiments, include advancing the plunger to pierce the
seal with the piercing member and thereby placing the first chamber
in fluidic communication with the second chamber and preparing the
biological assay sample. Such methods can also include a step of
inserting a biological sample collector into the sample receiving
module.
[0018] Where desired, a plunger includes a first end and a second
end opposite the first end and including the piercing member, and
advancing the plunger includes exerting force on a first end of the
plunger toward the second end. Also, in some versions, advancing
the plunger includes screwing the cap to the sample receiving
module.
[0019] In various embodiments, wherein the first chamber includes a
preparation solution, the second chamber includes a staging
reagent, placing the first chamber in fluidic communication with
the second chamber mixes the preparation solution and the staging
reagent. Also, in some versions, delivering the prepared biological
assay sample includes actuating a reversibly actuable valve of the
sample preparation device and flowing at least a portion of the
prepared biological assay out of the sample receiving module
through the valve.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0020] FIG. 1 provides a partial cross sectional view of a device
according to embodiments of the subject disclosure.
[0021] FIG. 2 provides a partial cross sectional view of a device
according to embodiments of the present disclosure.
[0022] FIGS. 3A and 3B provide side views of devices according to
embodiments of the subject disclosure. FIG. 3A provides a partial
cross sectional view of disclosed devices.
[0023] FIG. 4 provides side views of a device according to
embodiments of the present disclosure.
[0024] FIGS. 5A and 5B provide side views of devices according to
embodiments of the subject disclosure. FIGS. 5A and 5B each
includes a cross sectional view of disclosed devices.
[0025] FIGS. 6A-6C provide side cross sectional views of devices
according to embodiments of the present disclosure.
[0026] FIGS. 7A-7D provide side cross sectional views of device
aspects according to embodiments of the subject disclosure.
[0027] FIGS. 8A-8D provide side cross sectional views of devices
according to embodiments of the subject disclosure.
[0028] FIGS. 9A-9D provide side cross sectional views of devices
according to embodiments of the subject disclosure.
[0029] FIG. 10 provides a partial cross sectional view of a device
according to embodiments of the present disclosure.
[0030] FIG. 11 provides a partial cross sectional view of a device
according to some embodiments of the subject disclosure.
[0031] FIG. 12 provides a partial cross sectional view of a device
according to embodiments of the present disclosure.
[0032] FIG. 13 provides perspective and partial cross sectional
views of devices according to embodiments of the disclosure.
[0033] FIG. 14 provides perspective views of devices according to
various embodiments of the subject disclosure.
[0034] FIG. 15 provides a cross sectional view of a device
according to embodiments of the present disclosure.
[0035] FIG. 16 provides pressure generated in a sample preparation
device upon pressurization by the application and rotation of a
cap, e.g., screw cap, to the top of the device according to
embodiments of the subject disclosure.
DETAILED DESCRIPTION
[0036] Devices and methods for preparing and delivering biological
assay samples are provided herein. Components of such devices
include a sample receiving module within which a biological assay
sample can be prepared and a cap, which when operatively coupled
with the sample receiving module, pressurizes the module. These
devices can be employed for subsequently delivering a biological
assay sample.
[0037] Before the present invention is described in greater detail,
it is to be understood that this invention is not limited to
particular embodiments described, as such can, of course, vary. It
is also to be understood that the terminology used herein is for
the purpose of describing particular embodiments only, and is not
intended to be limiting, since the scope of the present invention
will be limited only by the appended claims.
[0038] Where a range of values is provided, it is understood that
each intervening value, to the tenth of the unit of the lower limit
unless the context clearly dictates otherwise, between the upper
and lower limit of that range and any other stated or intervening
value in that stated range, is encompassed within the invention.
The upper and lower limits of these smaller ranges can
independently be included in the smaller ranges and are also
encompassed within the invention, subject to any specifically
excluded limit in the stated range. Where the stated range includes
one or both of the limits, ranges excluding either or both of those
included limits are also included in the invention.
[0039] Certain ranges can be presented herein with numerical values
being preceded by the term "about." The term "about" is used herein
to provide literal support for the exact number that it precedes,
as well as a number that is near to or approximately the number
that the term precedes. In determining whether a number is near to
or approximately a specifically recited number, the near or
approximating unrecited number can be a number which, in the
context in which it is presented, provides the substantial
equivalent of the specifically recited number.
[0040] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
any methods and materials similar or equivalent to those described
herein can also be used in the practice or testing of the present
invention, representative illustrative methods and materials are
now described.
[0041] All publications and patents cited in this specification are
herein incorporated by reference as if each individual publication
or patent were specifically and individually indicated to be
incorporated by reference and are incorporated herein by reference
to disclose and describe the methods and/or materials in connection
with which the publications are cited. The citation of any
publication is for its disclosure prior to the filing date and
should not 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 can be
different from the actual publication dates which can need to be
independently confirmed.
[0042] It is noted that, as used herein and in the appended claims,
the singular forms "a," "an," and "the" include plural referents
unless the context clearly dictates otherwise. It is further noted
that the claims can be drafted to exclude any optional element. As
such, this statement is intended to serve as antecedent basis for
use of such exclusive terminology as "solely," "only" and the like
in connection with the recitation of claim elements, or use of a
"negative" limitation.
[0043] Additionally, certain embodiments of the disclosed devices
and/or associated methods can be represented by drawings which can
be included in this application. Embodiments of the devices and
their specific spatial characteristics and/or abilities include
those shown or substantially shown in the drawings or which are
reasonably inferable from the drawings. Such characteristics
include, for example, one or more (e.g., one, two, three, four,
five, six, seven, eight, nine, or ten, etc.) of: symmetries about a
plane (e.g., a cross-sectional plane) or axis (e.g., an axis of
symmetry), edges, peripheries, surfaces, specific orientations
(e.g., proximal; distal), and/or numbers (e.g., three surfaces;
four surfaces), or any combinations thereof. Such spatial
characteristics also include, for example, the lack (e.g., specific
absence of) one or more (e.g., one, two, three, four, five, six,
seven, eight, nine, or ten, etc.) of: symmetries about a plane
(e.g., a cross-sectional plane) or axis (e.g., an axis of
symmetry), edges, peripheries, surfaces, specific orientations
(e.g., proximal), and/or numbers (e.g., three surfaces), or any
combinations thereof
[0044] As will be apparent to those of skill in the art upon
reading this disclosure, each of the individual embodiments
described and illustrated herein has discrete components and
features which can be readily separated from or combined with the
features of any of the other several embodiments without departing
from the scope or spirit of the present invention. Any recited
method can be carried out in the order of events recited or in any
other order which is logically possible.
[0045] In further describing the subject invention, subject devices
for use in practicing the subject methods will be discussed in
greater detail, followed by a review of associated methods.
Devices
[0046] Aspects of the subject disclosure include biological assay
sample preparation devices.
[0047] As used herein, a "biological assay" is test on a biological
sample which is performed to evaluate one or more characteristics
of the sample. A biological sample is a sample containing a
quantity of organic material, e.g., one or more organic molecules,
such as one or more nucleic acids e.g., DNA and/or RNA or portions
thereof, which can be taken from a subject. Accordingly, biological
assay sample preparation devices, according to some embodiments,
are devices which prepare a biological sample for analysis with a
biological assay. Also, in some aspects a biological sample is a
nucleic acid amplification sample, which is a sample including one
or more nucleic acids or portions thereof which can be amplified
according to the subject embodiments.
[0048] A biological sample can be collected from a subject and
include one or more cells, such as tissue cells of the subject. As
used herein, the term "tissue" refers to one or more aggregates of
cells in a subject (e.g., a living organism, such as a mammal, such
as a human) that have a similar function and structure or to a
plurality of different types of such aggregates. Tissue can
include, for example, organ tissue, muscle tissue (e.g., cardiac
muscle; smooth muscle; and/or skeletal muscle), connective tissue,
nervous tissue and/or epithelial tissue. Tissue can, in some
versions, include cells from the inside of a subject's cheek and/or
cells in a subject's saliva. A biological sample can also not
include one or more cells. In some embodiments, a biological sample
can include viral particles, free DNA, free RNA, bacteria cells or
cell portions, fungi, spores, prions, or any combination
thereof
[0049] In some versions, and as described further below, a
biological sample is collected from a subject. In certain
embodiments, a subject is a "mammal" or a "mammalian" subject,
where these terms are used broadly to describe organisms which are
within the class mammalia, including the orders carnivore (e.g.,
dogs and cats), rodentia (e.g., mice, guinea pigs, and rats), and
primates (e.g., humans, chimpanzees, and monkeys). In some
embodiments, the subject is a human. The term "humans" can include
human subjects of both genders and at any stage of development
(e.g., fetal, neonates, infant, juvenile, adolescent, and adult),
where in certain embodiments the human subject is a juvenile,
adolescent or adult. While the devices and methods described herein
can be applied in association with a human subject, it is to be
understood that the subject devices and methods can also be applied
in association with other subjects, that is, on "non-human
subjects."
[0050] One embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIG. 1. In various embodiments, the device 100 includes a sample
receiving module 101 including a fluid container 102 for receiving
one or more portions of a sample collector therein, e.g., entirely
therein, a preparation solution 104, and a first attachment element
103. Such a device 100 can also include a cap 105 operatively,
e.g., removably, coupleable to the sample receiving module 101 and
including a pressurizing component 106, and a second attachment
element 107 operatively coupleable with the first attachment
element 103. In some embodiments of the devices, the pressurizing
component 106 extends into and pressurizes the sample receiving
module 101 for expelling fluid therefrom when the first attachment
element 103 is operatively coupled to the second attachment element
107.
[0051] By "operatively coupled," "operatively connected" and
"operatively attached" as used herein, is meant connected in a
specific way that allows the disclosed devices to operate and/or
methods to be carried out effectively in the manner described
herein. For example, operatively coupling can include removably
coupling or fixedly coupling two or more aspects. Operatively
coupling can also include fluidically and/or electrically and/or
mateably and/or adhesively coupling two or more components. Also,
by "removably coupled," as used herein, is meant coupled, e.g.,
physically and/or fluidically and/or electrically coupled, in a
manner wherein the two or more coupled components can be un-coupled
and then re-coupled repeatedly.
[0052] A portion of a biological assay sample preparation device
for use in practicing the subject methods is provided in FIG. 15.
The provided device 1500 portion includes many of the same elements
of the embodiment shown in FIG. 1 including a cap 105 operatively,
e.g., removably, coupled to the sample receiving module 101. Also
provided is a fluid container 102, a first attachment element 103,
and a second attachment element 107 operatively coupled with the
first attachment element 103. As shown, the pressurizing component
106 extends into and pressurizes the sample receiving module 101
for expelling fluid therefrom when the first attachment element 103
is operatively coupled to the second attachment element 107.
[0053] Furthermore, and as is also shown in FIG. 1, the subject
devices can also include one or more valve 108, e.g., a reversibly
actuable valve. The devices can also include a variety of optional
components, any one or combination of which can be included in the
devices, including a filter 109 for filtering one or more fluids
passing through a valve 108, a first seal 110, e.g., a breakable
seal, for sealing an opening at an end of the sample receiving
module 101 also including a valve 108, and/or a second seal 111,
e.g., a breakable seal, for sealing an opening at an end of the
sample receiving module 101 which is operatively coupleable with
the cap 105.
[0054] As noted above, embodiments of the subject devices include a
sample receiving module. Such a module can be configured to receive
one or more portions of a biological sample described herein. Such
a module can also be shaped, or shaped substantially, for example,
as a cylinder and/or can be an elongated cylindrical tube. As used
herein, "substantially" means to a great or significant extent,
such as almost fully or almost entirely.
[0055] In embodiments wherein the sample receiving module is shaped
as a cylinder, it can have a height, e.g., a height from one
surface to an opposite surface, ranging from 1 cm to 50 cm, such as
1 cm to 10 cm, such as 1 cm to 5 cm, inclusive. The sample
receiving module can also have a height of 50 cm or less, such as
30 cm or less, such as 20 cm or less, such as 10 cm or less, such
as 5 cm or less, such as 3 cm or less, such as 1 cm or less. The
sample receiving module can also have a height of 1 cm or more,
such as 3 cm or more, such as 5 cm or more, such as 10 cm or more,
such as 30 cm or more, such as 50 cm or more. Such a sample
receiving module can also have a diameter, e.g., an outer diameter
from an outer surface to an opposite outer surface, ranging from 1
mm to 5 cm, such as 1 mm to 3 cm, such as 1 mm to 1 cm, or 1 cm to
3 cm, each inclusive. Such a sample receiving module can also have
a diameter, e.g., an outer diameter, of 5 cm or less, such as 3 cm
or less, such as 1 cm or less, such as 5 mm or less, such as 3 mm
or less, such as 1 mm or less. A sample receiving module can also
have a diameter, e.g., an outer diameter, of 1 mm or more, such as
3 mm or more, such as 5 mm or more, such as 1 cm or more, such as 3
cm or more, such as 5 cm or more. A sample receiving module can
also define an internal volume configured to receive any of the
samples, and/or sample collectors, and/or preparation solutions
described herein. Such an internal volume can range from, for
example, 1 mm.sup.3 to 500 cm.sup.3, such as from 1 mm.sup.3 to 200
cm.sup.3, such as from 1 mm.sup.3 to 100 cm.sup.3, such as from 1
mm.sup.3 to 10 cm.sup.3, such as from 1 mm.sup.3 to 5 cm.sup.3,
such as from 5 mm.sup.3 to 1 cm.sup.3, or from 1.5 cm.sup.3 to 1
cm.sup.3. A sample receiving module can also define an internal
volume of 1 mm.sup.3 or more, such as 1.5 cm.sup.3 or more, such as
5 cm.sup.3 or more, such as 1 cm.sup.3 or more, such as 5 cm.sup.3
or more, such as 10 cm.sup.3 or more, such as 50 cm.sup.3 or more,
such as 100 cm.sup.3 or more, such as 200 cm.sup.3 or more, such as
300 cm.sup.3 or more. A sample receiving module can also define an
internal volume of 500 cm.sup.3 or less, such as 300 cm.sup.3 or
less, such as 100 cm.sup.3 or less, such as 50 cm.sup.3 or less,
such as 10 cm.sup.3 or less, such as 5 cm.sup.3 or less, such as
1.5 cm.sup.3 or less, such as 1 cm.sup.3 or less or 5 mm.sup.3 or
less.
[0056] A sample receiving module can have a first end, e.g., an
open end having an opening which is sealable by a cap, and a second
end, e.g., a closed end, opposite the first end. A first end can
include a terminal flat surface which is insertable into, e.g.,
entirely insertable into, a cap. A pressurizing component can also
be insertable into the first end of the sample receiving module.
Furthermore, a second end, e.g., a closed end, can include one or
more actuable valves, such as one or more reversibly actuable
valves, such as reversibly actuable depressurization valves.
[0057] In some versions of the subject aspects, the devices include
one or more valves, e.g., reversibly actuable depressurization
valves. Such valves, can be configured to discharge fluid from a
fluid container, e.g., a pressurized fluid container, therethrough
when actuated. Valves according to the subject devices can be
reversibly actuable between a first conformation and a second
conformation. In the first conformation, the valve can provide an
opening therethrough. Fluid, such as air and/or biological sample
and/or a prepared sample and/or preparation solution, or any
combination thereof, can pass through the opening in the valve when
the valve is in the first conformation. In the second conformation,
the valve is sealed and prevents the passage of fluid therethrough.
The valve can be actuated from the first conformation to the second
conformation by rotating the valve or a portion thereof, e.g., a
first portion with respect to a second portion, such as by rotating
the valve 45.degree., or 90.degree. or 180.degree. or 360.degree.
in a first rotational direction. The valve can be actuated from the
second conformation to the first conformation by rotating the valve
or a portion thereof, e.g., a first portion with respect to a
second portion, such as by rotating the valve 45.degree., or
90.degree. or 180.degree. or 360.degree. in a second rotational
direction opposite the first rotational direction. In some
versions, valves according to the subject embodiments are luer
connectors, e.g., male and/or female luer connectors, and are
mateably connectable to other luer connectors, e.g., male and/or
female luer connectors. One or more valve according to the subject
embodiments can be at an end of a sample receiving module opposite
from an end attached to a cap when the sample receiving module is
operatively coupled to the cap. In some versions, one or more valve
according to the subject embodiments can be at an end of a sample
receiving module opposite from an end at which an attachment
element, e.g., a first attachment element, is positioned. Also, one
or more valve according to the subject embodiments can be on a
terminal flat surface of a sample receiving module and in some
versions, can be centered on the surface. One or more valve
according to the subject embodiments can also provide fluidic
communication between a fluid container according to the subject
embodiments and the environment external to the sample receiving
module. The one or more valves can also include a locking element
which provides tactile feedback to a user when the valve is
operatively coupled to another and/or a sample preparation device
is operatively coupled to an analyzing device.
[0058] In various embodiments, the sample receiving modules include
a fluid container for containing one or more fluid, e.g., a liquid
and/or a gas, and/or receiving one or more portions of a sample
collector therein. Such a fluid container can be fluidically
sealable such that, when sealed, fluids such as gasses and/or
liquids cannot pass in or out of the container.
[0059] Sample receiving modules can include an outer surface and an
interior surface defined by the one or more fluid container. Such a
fluid container can extend inwardly from an opening, e.g., a
circular opening, in a single flush and flat surface, e.g., a
circular surface, of a sample receiving module at and end thereof.
A fluid container can be configured to receive therein, e.g.,
entirely therein, one or more portions of a cap, e.g., a
pressurizing component or an end thereof, when the cap is
operatively coupled to the sample receiving module. A cap can also
seal, e.g., fluidically seal, the fluid container of a sample
receiving module when the cap is operatively coupled to the sample
receiving module. A fluid container can be shaped as and/or define
a cavity shape of a cylinder, rectangular box, pyramid, cube, or
any combination thereof.
[0060] In embodiments where the fluid container is shaped as a
cylinder, it can have a height ranging from 1 cm to 50 cm, such as
1 cm to 10 cm, such as 1 cm to 5 cm, inclusive. The fluid container
can also have a height of 50 cm or less, such as 30 cm or less,
such as 10 cm or less, such as 5 cm or less, such as 3 cm or less,
such as 1 cm or less. The fluid container can also have a height of
1 cm or more, such as 3 cm or more, such as 5 cm or more, such as
10 cm or more, such as 30 cm or more, such as 50 cm or more. Such a
fluid container can also have a diameter ranging from 1 mm to 5 cm,
such as 1 mm to 3 cm, such as 1 mm to 1 cm, or 1 cm to 3 cm, each
inclusive. Such a fluid container can also have a diameter of 5 cm
or less, such as 3 cm or less, such as 1 cm or less, such as 5 mm
or less, such as 3 mm or less, such as 1 mm or less. A fluid
container can also have a diameter of 1 mm or more, such as 3 mm or
more, such as 5 mm or more, such as 1 cm or more, such as 3 cm or
more, such as 5 cm or more. A fluid container can also define an
internal volume configured to receive any of the samples, and/or
sample collectors, and/or preparation solutions described herein.
Such an internal volume can range from, for example, 1 mm.sup.3 to
500 cm.sup.3, such as from 1 mm.sup.3 to 200 cm.sup.3, such as from
1 mm.sup.3 to 100 cm.sup.3, such as from 1 mm.sup.3 to 10 cm.sup.3,
such as from 1 mm.sup.3 to 5 cm.sup.3, such as from 5 mm.sup.3 to 1
cm.sup.3, or from 1.5 cm.sup.3 to 1 cm.sup.3. A fluid container can
also define an internal volume of 1 mm.sup.3 or more, such as 5
mm.sup.3 or more, such as 1 cm.sup.3 or more, such as 1.5 cm.sup.3
or more, such as 5 cm.sup.3 or more, such as 10 cm.sup.3 or more,
such as 100 cm.sup.3 or more, such as 200 cm.sup.3 or more, such as
300 cm.sup.3 or more. A fluid container can also define an internal
volume of 500 cm.sup.3 or less, such as 300 cm.sup.3 or less, such
as 100 cm.sup.3 or less, such as 10 cm.sup.3 or less, such as 5
cm.sup.3 or less, such as 1.5 cm.sup.3 or less, such as 1 cm.sup.3
or less or 5 mm.sup.3 or less.
[0061] Embodiments of the subject sample receiving modules include
one or more attachment elements, e.g., first attachment elements.
An attachment element can be configured to operatively couple the
cap with a sample receiving module. Such an element can be disposed
on an exterior surface, e.g., entirely on an exterior surface, of a
sample receiving module or a portion thereof, e.g., a body of a
sample receiving module. An attachment element can specifically
include one or more engagement elements for mateably coupling with
a cap or a portion thereof, e.g., an attachment element. In some
versions, an attachment element of a sample receiving module can
include a screwable thread and/or a thread track or groove, for
screwing to a reciprocating thread or thread track or groove. In
some versions, an attachment element, e.g., a first attachment
element or a second attachment element, includes a thread and
another, e.g., a second or a first, attachment element includes a
reciprocating groove for slidably receiving the thread therein.
Attachment elements according to the subject embodiments can also
include one or more releasing element for releasing one attachment
from another and which can include one or more button and/or lever
and/or switch. Attachment elements, e.g., a first attachment
element, can extend around, e.g., concentrically around, a
pressurizing component of a device when a cap is operatively
coupled with a sample receiving module. Attachment elements, e.g.,
a second attachment element, can also be exclusively outside, e.g.,
on an external surface of, or inside, e.g., on an internal surface
of, a sample receiving module or a portion thereof, e.g., a body.
In other words, all portions of an attachment element can fall
between at least two other portions of the sample receiving module,
e.g., sample receiving module body.
[0062] As noted above, in some aspects of the subject disclosure,
the devices include a preparation solution. In some versions of the
subject disclosure, the preparation solution is a nucleic acid
amplification preparation solution and can include one or more
buffer. A nucleic acid amplification preparation solution is a
solution which prepares a biological sample such that one or more
nucleic acid thereof can be amplified, e.g., amplified
isothermally.
[0063] Also, the phrases "nucleic acid amplification" or
"amplification reaction" refers to methods of amplifying DNA, RNA,
or modified versions thereof. Nucleic acid amplification includes
several techniques, such as an isothermal reaction or a
thermocycled reaction. More specifically, nucleic acid
amplification includes methods such as polymerase chain reaction
(PCR), loop-mediated isothermal amplification (LAMP), strand
displacement amplification (SDA), recombinase polymerase
amplification (RPA), helicase dependent amplification (HDA),
multiple displacement amplification (MDA), rolling circle
amplification (RCA), and nucleic acid sequence-based amplification
(NASBA). The phrase "isothermal amplification" refers to an
amplification method that is performed without changing the
temperature of the amplification reaction. Protons are released
during an amplification reaction: for every deoxynucleotide
triphosphate (dNTP) that is added to a single-stranded DNA template
during an amplification reaction, one proton (Hf) is released.
[0064] A nucleic acid amplification preparation solution can be a
solution that prepares a biological sample for amplification with
an isothermal amplification protocol including: transcription
mediated amplification, strand displacement amplification, nucleic
acid sequence-based amplification, rolling circle amplification,
loop-mediated isothermal amplification, isothermal multiple
displacement amplification, helicase-dependent amplification,
circular helicase-dependent amplification, single primer isothermal
amplification, loop-mediated amplification, or any combination
thereof
[0065] In various embodiments, a preparation solution, such as a
nucleic acid amplification preparation solution, includes one or
more lysing agent, such as one or more detergent. Such a lysing
agent can, for example, include dithiothreitol (DTT), detergents,
e.g., TRITON X-100.TM., TWEEN.RTM., Sodium dodecyl sulfate (SDS),
dichlorodiphenyltrichloroethane (DDT), chaotropic salts, acids
and/or bases, pH buffers, beads, solvents, or any combinations
thereof. Such an agent can lyse cells of a biological sample to
release nucleic acids therefrom. A preparation solution, such as a
nucleic acid amplification preparation solution, can also include
H2O and/or one or more buffer.
[0066] In some versions of the subject disclosure, the devices
include one or more sample collector. A sample collector can be
configured for obtaining and/or retaining a biological sample as
described herein. A sample collector can also be configured for
fitting into and/or being retain within, e.g., entirely within, a
sample receiving module, such as a sample receiving module
operatively coupled to a cap. A sample collector can be retained
within, e.g., entirely within, a sample receiving module, such as a
sample receiving module operatively coupled to a cap while
preparing a sample and/or delivering a prepared sample as described
herein.
[0067] Embodiments of the subject sample collectors can extend
longitudinally from a handle to a sample collection element at an
end opposite the handle. A sample collector can be or include a
swab, such as a cotton swab, configured for collecting and/or
retaining a biological sample. Sample collectors can also be or
include a scraping element for scraping a biological sample source
to obtain the biological sample. A sample collector can also be or
include a container, such as a sealable container for retaining a
biological sample. Sample collectors according to the subject
embodiments also can include one or more syringe, hollow capillary
tube, punch tool, or any combination thereof.
[0068] A sample collector can be substantially shaped, for example,
as a cylinder or a rectangular box. In embodiments where the sample
collector is shaped as a cylinder, it can have a height ranging
from 1 cm to 50 cm, such as 1 cm to 20 cm, such as 1 cm to 10 cm,
such as 1 cm to 5 cm, such as from 1 cm to 3 cm inclusive. The
sample collector can also have a height of 50 cm or less, such as
30 cm or less, such as 20 cm or less, such as 10 cm or less, such
as 5 cm or less, such as 3 cm or less, such as 1 cm or less. The
sample collector can also have a height of 1 cm or more, such as 3
cm or more, such as 5 cm or more, such as 10 cm or more, such as 20
cm or more, such as 30 cm or more, such as 50 cm or more. Such a
sample collector can also have a diameter ranging from 1 mm to 5
cm, such as 1 mm to 3 cm, such as 1 mm to 1 cm, or 1 cm to 3 cm,
each inclusive. Such a sample collector can also have a diameter of
5 cm or less, such as 3 cm or less, such as 1 cm or less, such as 5
mm or less, such as 3 mm or less, such as 1 mm or less. A sample
collector can also have a diameter of 1 mm or more, such as 3 mm or
more, such as 5 mm or more, such as 1 cm or more, such as 3 cm or
more, such as 5 cm or more. Sample collectors can also have or
define a total volume ranging from, for example, 1 mm.sup.3 to 200
cm.sup.3, such as from 1 mm.sup.3 to 100 cm.sup.3, such as from 1
mm.sup.3 to 10 cm.sup.3, such as from 1 mm.sup.3 to 5 cm.sup.3,
such as from 5 mm.sup.3 to 1 cm.sup.3. A sample collector can also
have a volume of 1 mm.sup.3 or more, such as 5 mm.sup.3 or more,
such as 1 cm.sup.3 or more, such as 5 cm.sup.3 or more, such as 10
cm.sup.3 or more, such as 100 cm.sup.3 or more, such as 200
cm.sup.3 or more. Sample collectors can also have a volume of 200
cm.sup.3 or less, such as 100 cm.sup.3 or less, such as 10 cm.sup.3
or less, such as 5 cm.sup.3 or less, such as 1 cm.sup.3 or less or
5 mm.sup.3 or less.
[0069] As noted above, embodiments of the subject devices include a
cap. Such a cap can be configured to operatively couple, e.g.,
reversibly couple and/or sealably couple, to a sample receiving
module. Accordingly, such a cap can be configured for sealing one
or more opening of a sample receiving module. A cap can have a
first end, e.g., an open end having an opening which defines a
receptacle, and a second end, e.g., a closed and/or sealed end,
opposite the first end and defined by a single flat terminal
surface.
[0070] In various embodiments, a cap includes a pressurizing
component and/or a cap body. A pressurizing component can be a
protrusion, e.g., a cylindrical protrusion, extending from a
surface, e.g., an interior surface, of the cap body. A pressurizing
component can be integral with the cap body, e.g., composed of a
single piece of material, or can be operatively coupled, e.g.,
adhesively coupled, thereto. In some versions, a pressurizing
component is composed of the same material as the cap body and in
other versions, the pressurizing component is composed of a
different material than the cap body.
[0071] A pressuring component can include one or more biasing
elements or materials which can be configured to deform from a
first configuration to a second configuration and while in the
second configuration, be biased to return to the first
configuration. As described herein, biasing elements can deform
from a first configuration to a second configuration when a cap is
operatively coupled to a sample receiving module and while in the
second configuration, be biased to return to the first
configuration. A pressuring component can also return to a first
configuration from a first configuration when a fluid is discharged
from a sample receiving module. Biasing elements can exert force on
a fluid in contact with the elements and can thereby pressurize the
fluid.
[0072] A pressuring component according to the subject embodiments
can be flexible. By "flexible," as used herein is meant pliable or
capable of being bent or flexed repeatedly (e.g., bent or flexed
with a force exerted by a human hand or other body part) without
damage (e.g., physical deterioration). A pressuring component can
also include one or more polymeric materials (e.g., materials
having one or more polymers including, for example, plastic and/or
rubber and/or foam) and/or metallic materials, such as metallic
materials forming a spring.
[0073] A pressurizing component can be shaped as a cylinder,
rectangular box, pyramid, cube, or any combination thereof. In
embodiments where the pressurizing component is shaped as a
cylinder, it can have a height ranging from .1 mm to 5 cm, such as
1 mm to 1 cm, such as 1 mm to 5 mm, inclusive. As used herein,
"inclusive" refers to a provided range including each of the listed
numbers. Unless noted otherwise herein, all provided ranges are
inclusive. The pressurizing component can also have a height of 5
cm or less, such as 3 cm or less, such as 1 cm or less, such as 5
mm or less, such as 3 mm or less, such as 1 mm or less. The
pressurizing component can also have a height of 1 mm or more, such
as 3 mm or more, such as 5 mm or more, such as 1 cm or more, such
as 3 cm or more, such as 5 cm or more. Such a pressurizing
component can also have a diameter ranging from 1 mm to 5 cm, such
as 1 mm to 3 cm, such as 1 mm to 1 cm, or 1 cm to 3 cm, each
inclusive. Such a pressurizing component can also have a diameter
of 5 cm or less, such as 3 cm or less, such as 1 cm or less, such
as 5 mm or less, such as 3 mm or less, such as 1 mm or less. A
pressurizing component can also have a diameter of 1 mm or more,
such as 3 mm or more, such as 5 mm or more, such as 1 cm or more,
such as 3 cm or more, such as 5 cm or more.
[0074] In versions where a pressurizing component is shaped as a
rectangular box or a cube, the pressurizing component can have a
length, width, and/or height of 5 cm or less, such as 3 cm or less,
such as 1 cm or less, such as 5 mm or less, such as 3 mm or less,
such as 1 mm or less. A pressurizing component can also have a
length, width, and/or height of 1 mm or more, such as 3 mm or more,
such as 5 mm or more, such as 1 cm or more, such as 3 cm or more,
such as 5 cm or more. A pressurizing component can also have a
length, width, and/or height ranging from 1 mm to 5 cm, such as 1
mm to 3 cm, such as 1 mm to 1 cm, or 1 cm to 3 cm, each
inclusive.
[0075] A pressurizing component can also be configured to extend
into, such as fully into, and/or engage with, e.g., slidably and/or
sealably engage with, a sample receiving module, or a portion
thereof, such as a fluid container or a portion thereof, e.g., an
internal surface defining the fluid container, when a cap is
operatively coupled with the sample receiving module.
[0076] The subject disclosure also provides device embodiments
wherein the pressurizing component extends into, e.g., extends
fully into, and pressurizes the sample receiving module when the
cap is operatively coupled to the sample receiving module, such as
when a first attachment element is operatively coupled to a second
attachment element. The pressure can be applied, for example, for
expelling fluid from the sample receiving module. When desired, the
sample receiving module or a fluid container thereof is sealed when
the pressurizing component is inserted and extends therein.
[0077] The pressurizing component pressurizes the sample receiving
module by exerting force on one or more fluid, e.g., a liquid
and/or gas, within the sample receiving module, such as air and/or
preparation solution. As the pressurizing component extends further
into the sample receiving module, the pressure increases because
the pressurizing component exerts more force on the one or more
fluid. When the pressurizing component is retained in a particular
position within the sample receiving module, the pressure in the
module remains constant when the sample receiving module remains
sealed.
[0078] In various embodiments, the pressurizing component
pressurizes the sample receiving module to a pressure ranging from
50 Pa to 50000 Pa, such as 500 Pa to 50000 Pa, such as 1000 Pa to
50000 Pa, such as 5000 Pa to 50000 Pa, such as 10000 Pa to 30000
Pa, such as 15000 Pa to 25000 Pa, each inclusive. Where desired,
the pressurizing component pressurizes the sample receiving module
to a pressure of 1000000 Pa or less, such as 50000 Pa or less, such
as 30000 Pa or less, such as 10000 Pa or less, such as 5000 Pa or
less, such as 1000 Pa or less, such as 500 Pa or less, such as 50
Pa or less. In some versions, the pressurizing component
pressurizes the sample receiving module to a pressure of 1000000 Pa
or more, 50000 Pa or more, 30000 Pa or more, 10000 Pa or more, or
5000 Pa or more, 1000 Pa or more, 500 Pa or more, or 50 Pa or
more.
[0079] In some embodiments, caps include one or more receptacle
therein. Caps can include an outer surface and an interior surface
defined by the one or more receptacle. Such a receptacle can extend
inwardly from an opening, e.g., a circular opening, in a single
flush and flat surface, e.g., a circular surface, of a cap. A
receptacle can be configured to receive therein, e.g., entirely
therein, one or more portions of a sample receiving module, e.g.,
an end of a sample receiving module and/or one or more portions of
a preparation solution of a sample receiving module and/or one or
more seal of a sample receiving module and/or one or more
attachment elements of a sample receiving module, when the cap is
operatively coupled to the sample receiving module. In some
versions, a terminal end surface of a sample receiving module
contacts and/or is flush against a surface of a cap, such as an
internal surface, e.g., a terminal internal surface, of a cap
receptacle, when the cap is operatively coupled to the sample
receiving module. A cap can also seal, e.g., fluidically seal, a
fluid container of a sample receiving module when the cap is
operatively coupled to the sample receiving module. A receptacle
can be shaped as a cylinder, rectangular box, pyramid, cube, or any
combination thereof.
[0080] In embodiments where the receptacle is shaped as a cylinder,
it can have a height ranging from 0.1 mm to 5 cm, such as 1 mm to 1
cm, such as 1 mm to 5 mm, inclusive. The receptacle can also have a
height of 5 cm or less, such as 3 cm or less, such as 1 cm or less,
such as 5 mm or less, such as 3 mm or less, such as 1 mm or less.
The receptacle can also have a height of 1 mm or more, such as 3 mm
or more, such as 5 mm or more, such as 1 cm or more, such as 3 cm
or more, such as 5 cm or more. Such a receptacle can also have a
diameter ranging from 1 mm to 5 cm, such as 1 mm to 3 cm, such as 1
mm to 1 cm, or 1 cm to 3 cm, each inclusive. Such a receptacle can
also have a diameter of 5 cm or less, such as 3 cm or less, such as
1 cm or less, such as 5 mm or less, such as 3 mm or less, such as 1
mm or less. A receptacle can also have a diameter of 1 mm or more,
such as 3 mm or more, such as 5 mm or more, such as 1 cm or more,
such as 3 cm or more, such as 5 cm or more. A receptacle can also
define an internal volume ranging from 1 mm.sup.3 to 50 cm.sup.3,
from 1 mm.sup.3 to 10 cm.sup.3, from 1 mm.sup.3 to 5 cm.sup.3, such
as from 5 mm.sup.3 to 3 cm.sup.3, such as from 5 mm.sup.3 to 1
cm.sup.3. A receptacle can also define an internal volume of 1
mm.sup.3 or more, such as 5 mm.sup.3 or more, 1 cm.sup.3 or more,
or 10 cm.sup.3 or more. A receptacle can also define an internal
volume of 50 cm.sup.3 or less, such as 10 cm.sup.3 or less, such as
5 cm.sup.3 or less, such as 1 cm.sup.3 or less or 5 mm.sup.3 or
less.
[0081] In some versions of the subject embodiments, a pressurizing
component is disposed within, e.g., entirely within, a receptacle
of a cap. In some embodiments, a pressurizing component can extend
from a circular end surface of a cylindrical receptacle toward an
opposite open end of the cylindrical receptacle.
[0082] Also, in some embodiments, caps include one or more
attachment element. Such an element can be disposed within, e.g.,
entirely within, a receptacle of a cap. Such an element can also be
disposed on an exterior surface of a cap. An attachment element can
be configured to operatively couple the cap with a sample receiving
module. Such an attachment element can specifically include one or
more engagement elements for mateably coupling with a sample
receiving module. In some versions, an attachment element can
include a screwable thread and/or a thread track or groove, for
screwing to a reciprocating thread or thread track or groove.
Attachment elements according to the subject embodiments can also
include one or more releasing element for releasing one attachment
from another and which can include one or more button and/or lever
and/or switch. Attachment elements, e.g., a second attachment
element, can extend around, e.g., concentrically around, a
pressurizing component of a device. Attachment elements, e.g., a
second attachment element, can also be exclusively inside, e.g., on
an internal surface of, a cap or a portion thereof, e.g., a cap
body. In other words, all portions of an attachment element can
fall between at least two other portions of the cap, e.g., cap
body.
[0083] According to the subject embodiments, the sample receiving
modules and/or caps or portions thereof, e.g., pressurizing
components, can each be composed of a variety of materials and can
be composed of the same or different materials. The sample
receiving modules and/or caps or portions thereof can be composed
of polymeric materials (e.g., materials having one or more polymers
including, for example, plastic and/or rubber) and/or metallic
materials. Such materials can have characteristics of flexibility
and/or high strength (e.g., able to withstand significant force,
such as a force exerted on it by use, without breaking and/or
resistant to wear) and/or high fatigue resistance (e.g., able to
retain its physical properties for long periods of time regardless
of the amount of use or environment).
[0084] Materials of interest of which any of the device components
described herein can be composed include, but are not limited to:
polymeric materials, e.g., plastics, such as polytetrafluoroethene
or polytetrafluoroethylene (PFTE), including expanded
polytetrafluoroethylene (e-PFTE), polyester (Dacron.TM.), nylon,
polypropylene, polyethylene, high-density polyethylene (HDPE),
polyurethane, etc., metals and metal alloys, e.g., titanium,
chromium, stainless steel, etc., and the like.
[0085] According to some embodiments, the subject devices and
components thereof, e.g., sample receiving modules and/or caps, are
hand-held devices. As used herein, the term "hand-held" refers to
the characteristic ability of an aspect to be held (e.g., retained,
or easily or comfortably held) in a hand, such as the hand of a
mammal, such as the hand of a human, such as the hand of an adult
male or female human of an average size and/or strength. As such, a
hand-held aspect is an aspect that is sized and/or shaped to be
retained (e.g., easily or comfortably retained) in the hand of a
human. A hand-held aspect can also be an aspect that can be moved
(e.g., easily moved, such as easily moved in a vertical and/or
horizontal direction) by a human (e.g., one or two hands of a
human).
[0086] As noted above, in some versions, the subject devices can
include a variety of optional components, any one or combination of
which can be included in the devices, including a filter for
filtering one or more fluids passing through a valve. The filter
can be a porous membrane and/or a gel and/or a sponge material and
can be selectively permeable. Such a filter can have a porosity
such that it filters cellular components, such as cellular
membranes from a prepared sample when the prepared sample flows
through the filter. The filter can also have a porosity such that
it traps and/or concentrates particles, e.g., bacteria, from a
sample. As such, the subject methods as provided below can include
concentrating one or more particles, e.g., particles in a sample
fluid, by flowing a liquid, e.g., a sample fluid, through the
filter. The filter can also be modified to bind to nucleic acids or
proteins for downstream elution. A filter can have a pore size
ranging from 1 .mu.m to 100 .mu.m, 1 .mu.m to 50 .mu.m, 1 .mu.m to
25 .mu.m, 1 .mu.m to 15 .mu.m, such as 1 .mu.m to 10 .mu.m, such as
1 .mu.m to 5 .mu.m, or 100 .mu.m or less, or 50 .mu.m or less, or
15 .mu.m or less or 10 .mu.m or less or 5 .mu.m or less. A filter
can also be mounted within, e.g., entirely within, a wall of a
sample receiving module and can be at an end of a sample receiving
module opposite an end operatively connectable to a cap. Filters,
according to the subject embodiments, can be part of or positioned
within the one or more valves described herein.
[0087] Embodiments of the disclosed devices also include a first
seal e.g., a breakable seal and/or a frangible seal, for sealing an
opening at an end of the sample receiving module through which
fluid can flow out of the module via the valve. The seal can be
positioned between, such as between in a path of fluid flow when
fluid is flowing out of the sample receiving module, a filter and a
valve, as such components are described herein. A first seal can be
punctured by actuating a valve of a pressurized sample receiving
module. Pressurized fluid from a pressurized sample receiving
module can exert sufficient force on a seal to break it and flow
through the created opening.
[0088] Some embodiments of the disclosed devices also include a
second seal e.g., a breakable seal and/or a frangible seal, for
sealing an opening at an end of the sample receiving module which
operatively couples to a cap. A second seal can provide a fluidic
seal to a fluid container. Such a seal can be broken by exerting
force on it with a sample collector and thus creating an opening in
the seal through which the sample collector or a portion thereof
can be inserted. A second seal can also be broken by operatively
coupling a cap to a sample receiving module. Such an action can
cause a pressurizing component to exert sufficient force on the
seal to puncture it.
[0089] A seal, such as a first and/or second seal, can be a layer
of material, such as a polymeric and/or metallic material as such
materials are described herein. In some versions, a seal is a foil
sheet composed of aluminum and/or other metals. A seal, as
described herein, can have a thickness of 1 mm or less, such as 0.5
mm or less, such as 0.1 mm or less.
[0090] An embodiment of a biological assay sample preparation
device is provided in FIG. 2. As is shown, in some versions, the
device 200 includes a sample receiving module 201 including an
outer body 209 forming a first chamber 210. The sample receiving
module 201 also includes a fluid container 202 for receiving one or
more portions of a sample collector 211 therein, e.g., entirely
therein, a preparation solution 204, and a first attachment element
203. As shown, in some versions, the fluid container 202 includes a
breakable seal 213 and an inner body 214 forming a second chamber
215, wherein the inner body 214 is actuable, e.g., slidable, within
the outer body 209.
[0091] As is shown, the sample collector includes a handle 212 and
a sample collection portion 219. Such a device 200 can also include
a cap 205 operatively, e.g., removably, coupleable to the sample
receiving module 201 and including a pressurizing component 206,
and a second attachment element 207 operatively coupleable with the
first attachment element 203. In some embodiments of the devices,
the pressurizing component 206 extends into and pressurizes the
sample receiving module 201 for expelling fluid therefrom when the
first attachment element 203 is operatively coupled to the second
attachment element 207.
[0092] In some versions, the outer body 209 includes one or more
piercing member 216. Also, in some aspects, the inner body 214
actuates within the outer body 209 when the cap 205 is operatively
coupled to the sample receiving module 201 to break the breakable
seal 213 with the one or more piercing member 216 and place the
first chamber 210 in fluidic communication with the second chamber
215. Such actuation can be in a direction, e.g., a linear direction
along an axis of symmetry of the device, toward the one or more
piercing member 216 and/or valve 218 and/or away from the cap 205.
In some versions, the outer body 209 includes a staging reagent 217
and such actuation places the staging reagent 217 in fluidic
communication with the second chamber 215. In some aspects, the
staging reagent 217 includes one or more lyophilized agents, such
as one or more lyophilized cell lysing reagent, and placing the
staging reagent 217 in fluidic communication hydrates the reagent
with the preparation solution 204 and/or exposes the staging
reagent 217 to the biological sample. Additionally, in some
versions, a cap 205 and/or valve 217 are centered on an axis of
symmetry of the sample receiving module 201 when the module 201 is
operatively coupled to the cap 205.
[0093] As used herein, a reagent or agent is a composition for use
in the subject assays. Reagents or agents can be a liquid
composition which is configured to change, e.g., chemically and/or
physically modify, one or more aspects of a biological sample or an
aspect thereof upon contact with the sample or aspect. Also, as
used herein, staging reagents are reagents that prepare a
biological sample for further processing as described herein. Such
reagents can be lysing agents and can be configured to create a
lysate. In various embodiments, the one or more staging reagents
217 include dichlorodiphenyltrichloroethane (DDT), dithiothreitol
(DTT), detergents, e.g., TRITON X-100.TM., TWEEN.RTM., Sodium
dodecyl sulfate (SDS), chaotropic salts, acids and/or bases, pH
buffers, beads, solvents, or any combinations thereof.
[0094] In some versions of the subject devices, the devices include
one or more plunger. Such a device is shown, for example, in FIGS.
3A, 3B and 4. Specifically, provided in these figures is a
biological assay sample preparation device 300 including a cap 301
and a sample receiving module 302 which is operatively coupleable
to the cap 301. As depicted, the cap 301 can include a first
chamber 303, a plunger 304 including a piercing member 305, and/or
a seal 306. In various embodiments, the first chamber 303 includes
a preparation solution 310, such as any of the solutions described
herein. Also, the sample receiving module 302 can include a second
chamber 307. The second chamber 307 can be configured to receive
and/or retain a sample collector 311 therein. The second chamber
307 can also include solution, such as a preparation solution
and/or water and/or one or more buffer.
[0095] The cap can include a preparation solution 310 in an amount
ranging from 500 .mu.L to 1500 .mu.L, such as from 700 .mu.L to
1000 .mu.L, such as from 700 .mu.L to 900 .mu.L. The cap can
include a preparation solution in an amount of 1500 .mu.L or less,
such as 1000 .mu.L or less, such as 800 .mu.L or less. The cap can
include a preparation solution in an amount of 600 .mu.L or more,
such as 800 .mu.L or more, such as 1000 .mu.L or more. The cap can
include a preparation solution in an amount of 800 .mu.L. Also, in
some embodiments, the preparation solution is a buffer, such as a
cell lysis buffer, and can include one or more detergents.
[0096] In some versions, when the sample receiving module 302 is
operatively coupled to the cap 301, advancing the plunger 304
pierces the seal 306 with the piercing member 305 and places the
first chamber 303 in fluidic communication with the second chamber
307. As is also shown, the plunger can include one or more, e.g.,
two, or four, or more, O-rings 308 for sealably actuating the
plunger 304 within the cap 301 and/or operatively coupling the cap
301 and the sample receiving module 302. The device 300 can also
include one or more actuable valve 309 on the sample receiving
module 302.
[0097] The plunger 304 can also be a manual plunger which actuates
within the first chamber 303 linearly along an axis of symmetry of
the sample receiving module 302 and/or in a direction toward and/or
away from a valve 309 of the device. Such a plunger 304 can be
pushable directly by a user to increase pressure within the second
chamber 307. The plunger 304 is shown in FIG. 4 in an advanced
conformation where the plunger 304 has pushed the preparation
solution 310 from the first chamber 303 into the second chamber
307. As is depicted, the plunger 304 is actuable, e.g., slidably
actuable, within the cap 301 with respect to other portions of the
cap 301, e.g., the cap body or housing, and as such, can move
independently of the other portions. Also, as is shown, the plunger
304 is actuable, e.g., slidably actuable, within the cap 301 after
the cap is first operatively coupled with the sample receiving
module 302. Accordingly, operatively coupling the sample receiving
module 302 and the cap 301 and then actuating the plunger 304 can
be performed as two and separate steps with the subject device
300.
[0098] The user action of pressing the top of the cap 301, once it
is sealed to the sample receiving module 302 forces the plunger 304
to break the seal 306 at the bottom of the cap 301, and exposes the
sample collector 311 to the preparation solution 310. The pressure
required for driving fluid flow is generated by the depression of
the plunger 304 within the cap 301. This user action compresses
fluid, e.g., preparation solution and/or biological sample, and/or
air, inside the cap 301, leading to pressure generation.
Subsequently, a valve 309, e.g., a luer-activated valve, of the
device can be actuated and fluid, e.g., prepared sample and/or
preparation solution and/or air, propelled by the pressure
therethrough and out of the device. Alternatively, a valve 309 of
the device can be replaced by a seal (not shown), e.g., a foil
seal, e.g., a foil heat seal, which can be broken to allow fluid,
e.g., prepared sample and/or preparation solution and/or air,
propelled by the pressure to pass therethrough and out of the
device. In other embodiments, a seal covers valve 309 and is
ruptured by application of pressure or by a puncturing mechanism as
described below.
[0099] The plunger 304 can be configured to reversibly actuate
within the first chamber 303, such as by actuating in a first
direction and/or actuating in a second direction opposite the
first. Advancing the plunger 304 can pressurize the sample
receiving module 302 or portion thereof, e.g., second chamber 307,
to a pressure ranging from 50 Pa to 50000 Pa, 500 Pa to 50000 Pa,
1000 Pa to 50000 Pa, or 5000 Pa to 50000 Pa, such as 10000 Pa to
40000 Pa, such as 15000 Pa to 25000 Pa, each inclusive. Where
desired, the plunger pressurizes the sample receiving module to a
pressure of 1000000 Pa or less, such as 50000 Pa or less, such as
40000 Pa or less, such as 10000 Pa or less, such as 5000 Pa or
less. In some versions, the plunger pressurizes the sample
receiving module to a pressure of 1000000 Pa or more, 50000 Pa or
more, 40000 Pa or more, 10000 Pa or more, or 5000 Pa or more.
[0100] In addition, any of the components of FIGS. 3A, 3B, 4, 5A or
5B, such as the plunger 304, can be composed of any of the
polymeric and/or metallic materials described herein, or any
combinations thereof. Also, the plunger 304 is shown, for example,
in FIG. 4 in an advanced conformation wherein the plunger 304 has
pushed the preparation solution 310 from the first chamber 303 into
the second chamber 307.
[0101] In some versions of the subject devices, such as the device
shown in FIGS. 5A and 5B, the device 500 includes one or more
plunger 503 of a cap 501 which is advanced by operatively coupling,
such as by screwing, the cap 501 to a sample receiving module 502.
More specifically, FIG. 5A provides both side and cross-sectional
side views of the device 500 in a first conformation wherein the
plunger 503 is substantially un-advanced within the device 500.
FIG. 5B provides both side and cross-sectional side views of the
device 500 in a second conformation wherein the plunger 503 is
fully advanced within the device 500.
[0102] Operatively coupling the sample receiving module 502 and the
cap 501 and actuating the plunger 503 can be performed as a single
concerted step with the subject device 500. In other words,
operatively coupling the sample receiving module 502 and the cap
501 also advances the plunger 503 of the device 500, such as
advances the plunger from the first conformation to the second
conformation. Also, as is depicted, the plunger 503 is integral
with at least some portions of the cap, e.g., a housing or exterior
shell. In some versions, the cap 501 includes a stationary body
portion 511 which sealably mates with the sample receiving module
502 and includes a protruding portion which extends into the sample
receiving module 502 when the two are mated. The plunger 503, as
well the portions of the cap other than the stationary body portion
511 are freely actuable, e.g., slidably actuable, with respect to
and can move independently of the stationary body portion 511 when
the plunger actuates. As is shown in FIGS. 5A and 5B, the
stationary body portion 511 remains in a fixed position with
respect to the sample receiving module 502 when the device advances
from the first conformation to the second conformation.
[0103] The cap 501 of device 500 shown in FIGS. 5A and 5B also
includes a first chamber 504, plunger 503, piercing member 505,
and/or seal 506. In various embodiments, the first chamber 504
includes a preparation solution 510, such as any of the solutions
described herein. Also, the sample receiving module 502 can include
a second chamber 507. The second chamber 507 can be configured to
receive and/or retain a sample collector 514 therein. The second
chamber 507 can also include solution, such as a preparation
solution and/or water and/or one or more buffer.
[0104] The cap can include a preparation solution in an amount
ranging from 500 .mu.L to 1500 .mu.L, such as from 700 .mu.L to
1000 .mu.L, such as from 700 .mu.L to 900 .mu.L. The cap can
include a preparation solution in an amount of 1500 .mu.L or less,
such as 1000 .mu.L or less, such as 800 .mu.L or less. The cap can
include a preparation solution in an amount of 600 .mu.L or more,
such as 800 .mu.L or more, such as 1000 .mu.L or more. The cap can
include a preparation solution in an amount of 800 .mu.L. Also, in
some versions, the preparation solution is a buffer, such as a cell
lysis buffer, and can include one or more detergents.
[0105] In some versions, advancing the plunger 503 by operatively
coupling the sample receiving module 502 and the cap 501, such as
by screwing the sample receiving module 502 and the cap 501,
pierces the seal 506 with the piercing member 505 and places the
first chamber 504 in fluidic communication with the second chamber
507. As is also shown, the plunger can include one or more, e.g.,
two, or four, or more, O-rings 508 for sealably actuating the
plunger 304 within the cap 501. The device 500 can also include one
or more actuable valve 509 on the sample receiving module 502.
[0106] The plunger 503 can also actuates within the first chamber
504 linearly along an axis of symmetry of the sample receiving
module 502 and/or in a direction toward and/or away from a valve
509 of the device. Such a plunger 503 can be advance to increase
pressure within the second chamber 507. The plunger 503 is shown in
FIG. 5B in an advanced conformation where the plunger 503 has
pushed the preparation solution 510 from the first chamber 504 into
the second chamber 507.
[0107] The subject sample receiving module 502 can also include one
or more first attachment element 512. Also, a cap 501 can include
one or more second attachment element 513 for operatively, e.g.,
reciprocally, coupling with the first attachment element 512. Such
attachment elements can be configured to operatively couple the cap
501 with the sample receiving module 502. In some versions, and as
shown in FIGS. 5A and 5B, a first and/or second attachment element
of a sample receiving module or a cap can each include a screwable
thread and/or a thread track or groove, for screwing to a
reciprocating thread or thread track or groove. In some versions,
an attachment element, e.g., a first attachment element or a second
attachment element, includes a thread and another, e.g., a second
or a first, attachment element includes a reciprocating groove for
slidably receiving the thread therein.
[0108] The plunger 503 can be configured to reversibly actuate
within the first chamber 504, such as by actuating in a first
direction and/or actuating in a second direction opposite the
first. Advancing the plunger 503 can pressurize the sample
receiving module 502 or portion thereof, e.g., second chamber 507,
to a pressure ranging from 5000 Pa to 50000 Pa, such as 10000 Pa to
40000 Pa, such as 15000 Pa to 25000 Pa, each inclusive. Where
desired, the plunger pressurizes the sample receiving module to a
pressure of 1000000 Pa or less, such as 50000 Pa or less, such as
40000 Pa or less, such as 10000 Pa or less, such as 5000 Pa or
less. In some versions, the plunger pressurizes the sample
receiving module to a pressure of 1000000 Pa or more, 50000 Pa or
more, 40000 Pa or more, 10000 Pa or more, or 5000 Pa or more.
[0109] In various embodiments, a user action of turning the cap
501, after it is sealed to the sample receiving module 502, forces
the plunger 503 to break the seal 506 at the bottom of the cap 501,
and places the preparation solution 510 and the sample collector
514 in fluidic communication and in some embodiments, immerses the
sample collector 514 in the preparation solution 510. According to
some embodiments, the pressure required for driving fluid flow
within device 500 is generated by the actuation of the plunger due
to rotation of the cap 501 with respect to the sample receiving
module 502. Such a user action compresses fluid, e.g., air and/or
preparation solution and/or biological sample, inside the device
500, and causes pressure generation. Such pressure is maintained
while the preparation solution reacts with the biological sample to
produce a prepared sample. Subsequently, a valve 509, e.g., a
luer-activated valve, of the device can be actuated and fluid,
e.g., prepared sample and/or preparation solution and/or air,
propelled by the pressure therethrough and out of the device.
Alternatively, a valve 509 of the device can be replaced by a seal
(not shown), e.g., a foil seal, e.g., a foil heat seal, which can
be broken to allow fluid, e.g., prepared sample and/or preparation
solution and/or air, propelled by the pressure to pass therethrough
and out of the device. Also, in some embodiments, when the sample
receiving module is operatively coupled to the cap, advancing the
plunger pierces the seal with the piercing member and places the
first chamber in fluidic communication with the second chamber.
[0110] An embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIGS. 6A-6C. The provided device 600 includes a sample receiving
module 601 including a fluid container 602 for receiving one or
more portions of a sample collector 611 therein, e.g., entirely
therein, and a first attachment element 603. Such a device 600 can
also include a cap 605 operatively, e.g., removably, coupleable to
the sample receiving module 601 and including a preparation
solution, e.g., a lysis buffer 606, second attachment element 607
operatively coupleable with the first attachment element 603. The
sample receiving module 601, cap 605 and other provided components
can have any of the characteristics or combination of
characteristics of sample receiving modules, caps and/or other
corresponding components described herein.
[0111] In the embodiment shown, operatively coupling the sample
receiving module 601 and the cap 605, as is shown in FIG. 6B, such
as by screwing the sample receiving module 601 and the cap 605,
pierces a seal 604 with a piercing member 608 and places a first
chamber 609 in fluidic communication with a second chamber 610. As
such, operatively coupling the sample receiving module 601 and the
cap 605, such as by screwing the sample receiving module 601 and
the cap 605 together, exposes preparation solution 606 to a sample
on a sample collector 611 and thereby produces a prepared, e.g.,
lysed, sample 612.
[0112] Once the prepared, e.g., lysed, sample 612 is made, the
sample receiving module 601 can be operatively coupled to a
pressurizing module 615. Operatively coupling can be performed by
attaching, such as by screwing, an attachment element 613 of a
sample receiving module 601 and a second attachment element 614 of
a pressurizing module 615. The pressurizing module 615 also
includes a buffer, e.g., a dilution buffer 616. Operatively
coupling the sample receiving module 601 and the pressurizing
module 615, as is shown in FIG. 6C, places the prepared sample 612
in fluidic communication with the dilution buffer 616 so that the
prepared sample 612 is diluted and pressurizes the sample receiving
module. Thereafter, the diluted prepared sample can be delivered
out of the device 600 for further analysis using the pressure
within the device to push the diluted prepared sample out of the
device 600.
[0113] Another embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIGS. 7A-7D. The provided device 700 includes a sample receiving
module 701 including a fluid container 702 for receiving one or
more portions of a sample collector 711 therein, e.g., entirely
therein, and a first attachment element 703. Such a device 700 can
also include a cap 705 operatively, e.g., removably, coupleable to
the sample receiving module 701 and including a preparation
solution, e.g., a lysis buffer 706, second attachment element 707
operatively coupleable with the first attachment element 703.
Operatively coupling the cap 705 and the sample receiving module
701 can pressurize the sample receiving module 701. The sample
receiving module 701 can also include a buffer, e.g., a dilution
buffer 718 in a buffer container 719 therein. The sample receiving
module 701, cap 705 and other provided components can have any of
the characteristics or combination of characteristics of sample
receiving modules, caps and/or other corresponding components
described herein.
[0114] In the embodiment shown, operatively coupling the sample
receiving module 701 and the cap 705, as is shown in FIG. 7B, such
as by screwing the sample receiving module 701 and the cap 705,
pierces a seal 704 with a piercing member 708 and places a first
chamber 709 in fluidic communication with a second chamber 710. As
such, operatively coupling the sample receiving module 701 and the
cap 705, such as by screwing the sample receiving module 701 and
the cap 705 together, exposes preparation solution 706 to a sample
on a sample collector 711 and thereby produces a prepared, e.g.,
lysed, sample 712.
[0115] Once the prepared, e.g., lysed, sample 712 is made, the
sample receiving module 701 can be operatively coupled to, such as
by being lowered onto, a cartridge 715. Such operative coupling can
actuate a fluidic communication element 717 and/or open a valve
716, e.g., poppet valve, of the fluidic communication element 717.
The fluidic communication element 717 can be actuated toward the
cap 705 when the cartridge 715 exerts force on it. Opening the
valve 716 in turn releases the prepared sample 712 into the
dilution buffer 718 in the buffer container 719 and produces a
prepared diluted sample 720. Operatively coupling the sample
receiving module 701 and the cartridge 715, as is shown in FIG. 7D,
delivers the prepared diluted sample 720 out of the sample
receiving module 703 and in to the cartridge.
[0116] One embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIGS. 8A-8D. The provided device 800 includes a sample receiving
module 801 including a fluid container 802 for receiving one or
more portions of a sample collector 811 therein, e.g., entirely
therein. Such a device 800 can also include a cap 805 operatively,
e.g., removably, coupleable to the sample receiving module 801 and
including a preparation solution, e.g., a lysis buffer 806.
[0117] Operatively coupling the cap 805 and the sample receiving
module 801 may not pressurize the sample receiving module 801 but
may place the lysis buffer 806 in fluidic communication with a
sample on the sample collector 811 and thereby produce a prepared,
e.g., lysed, sample 812. The sample receiving module 801, cap 805
and other provided components can have any of the characteristics
or combination of characteristics of sample receiving modules, caps
and/or other corresponding components described herein.
[0118] The device 800 also includes a pressurizing chamber 816
operatively coupled to the sample receiving module 801 and
including a valve 817, e.g., a one-way valve, to provide fluidic
communication therebetween. The pressurizing chamber 816 also
includes a plunger 818, e.g., a manually actuable plunger, which
creates positive and/or negative pressure within the pressurization
chamber 816 when actuated. The pressurizing chamber 816 also
includes a buffer, e.g., a dilution buffer 821. The pressurizing
chamber 816 also includes an expulsion valve 819 for expelling a
diluted prepared sample 820 therefrom upon actuation of the plunger
818.
[0119] The device 800 is configured such that when the cap 805 is
operatively coupled to the sample receiving module 801 to produce a
prepared sample 812, the plunger 818 can be actuated in a first
direction, as is shown in FIG. 8C, to propel the prepared sample
812 from the sample receiving module 801 and into the pressurizing
chamber 816 via valve 817 and thereby produce a diluted prepared
sample 820. The device 800 is also configured such that the plunger
818 can then be actuated in a second direction opposite the first,
as is shown in FIG. 8D, to propel the diluted prepared sample 820
out of the pressurizing chamber 816 via expulsion valve 819.
[0120] Another embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIGS. 9A-9D. The provided device 900 includes a sample receiving
module 901 including a fluid container 902 for receiving one or
more portions of a sample collector 911 therein, e.g., entirely
therein. Such a device 900 can also include a cap 905 operatively,
e.g., removably, coupleable to the sample receiving module 901 and
including a preparation solution, e.g., a lysis buffer 906.
[0121] Operatively coupling the cap 905 and the sample receiving
module 901 may not pressurize the sample receiving module 901 but
may place the lysis buffer 906 in fluidic communication with a
sample on the sample collector 911 and thereby produce a prepared,
e.g., lysed, sample 912. The sample receiving module 901, cap 905
and other provided components can have any of the characteristics
or combination of characteristics of sample receiving modules, caps
and/or other corresponding components described herein.
[0122] The device 900 also includes a pressurizing chamber 916
operatively coupled to the sample receiving module 901 and
including an opening, e.g., a vent 917, to provide fluidic
communication therebetween. The pressurizing chamber 916 also
includes a plunger 918, e.g., a manually actuable plunger, which
creates positive and/or negative pressure within the pressurization
chamber 916 when actuated. The pressurizing chamber 916 also
includes a buffer, e.g., a dilution buffer 921. The pressurizing
chamber 916 also includes an expulsion valve 919 for expelling a
diluted prepared sample 920 therefrom upon actuation of the plunger
918.
[0123] The device 900 is configured such that when the cap 905 is
operatively coupled to the sample receiving module 901 to produce a
prepared sample 912, the plunger 918 can be actuated in a first
direction, as is shown in FIG. 9C, to propel the prepared sample
912 from the sample receiving module 901 and into the pressurizing
chamber 916 via vent 917 and thereby produce a diluted prepared
sample 920. Actuating the plunger 918 in such as direction can
unseal the vent 917. The device 900 is also configured such that
the plunger 918 can then be actuated in a second direction opposite
the first, as is shown in FIG. 9D, to propel the diluted prepared
sample 920 out of the pressurizing chamber 916 via expulsion valve
919. Actuating the plunger 918 in such as direction can seal the
vent 917 and prevent further fluid communication therethrough.
[0124] An embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIG. 10. The provided device 1000 includes a sample receiving
module 1001 including a fluid container 1002 for receiving one or
more portions of a sample collector 1011 therein, e.g., entirely
therein. Such a device 1000 can also include a cap 1005
operatively, e.g., removably, coupleable to the sample receiving
module 1001. The sample receiving module 1001, cap 1005 and other
provided components can have any of the characteristics or
combination of characteristics of sample receiving modules, caps
and/or other corresponding components described herein. Operatively
coupling the cap 1005 and the sample receiving module 1001 may not
pressurize the sample receiving module 1001 but can place a
preparation solution, e.g., a lysis buffer, in fluidic
communication with a sample on the sample collector 1011 and
thereby produce a prepared, e.g., lysed, sample.
[0125] The device 1000 also includes a pressurizing chamber 1016
operatively coupled to the sample receiving module 1001 and
including an opening, e.g., a channel 1017 including one or more
containers, such as containers including one or more buffer, to
provide fluidic communication therebetween. The pressurizing
chamber 1016 can be oriented in parallel to the sample receiving
module 1001, e.g., can both have a central axis of symmetry
oriented in the same direction with respect to that of the other.
The pressurizing chamber 1016 also includes a plunger 1018, e.g., a
manually actuable plunger, which operates by pushing and/or pulling
in a linear direction, and which creates positive and/or negative
pressure within the pressurization chamber 1016 and/or sample
receiving module 1001 when actuated. The pressurizing chamber 1016
also can include a buffer, e.g., a dilution buffer 1021. The sample
receiving module 1001 also includes an expulsion valve 1019 for
expelling a diluted prepared sample therefrom upon actuation of the
plunger 1018.
[0126] The device 1000 is configured such that the plunger 1018 can
be actuated in a first direction, to propel a buffer from channel
1017 into the sample receiving module 1001 and thereby produce a
diluted prepared sample therein and pressurize the sample receiving
module. The diluted prepared sample can then be propelled by the
pressure out of the sample receiving module 1001 via expulsion
valve 1019.
[0127] One embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIG. 11. The provided device 1100 includes many of the same
components as the device shown in FIG. 10. However, the
pressurizing chamber 1016 of the device 1100 of FIG. 11, can be
oriented at an angle to the sample receiving module 1001, e.g., can
both have a central axis of symmetry which intersects the other
and/or is oriented at an angle, e.g., 30.degree. or less,
45.degree. or less, or 50.degree. or less, or an angle ranging from
10.degree. to 90.degree., inclusive, with respect to that of the
other.
[0128] Another embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in
FIG. 12. The provided device 1200 includes many of the same
components as the devices shown in FIGS. 10 and 11. The
pressurizing chamber 1016 can be oriented at an angle to the sample
receiving module 1001, e.g., can both have a central axis of
symmetry which intersects the other and/or is oriented at an angle,
e.g., 30.degree. or less, 45.degree. or less, or 50.degree. or
less, or an angle ranging from 10.degree. to 90.degree., inclusive,
with respect to that of the other. Furthermore, the cap 1005 of the
device 1200 is operatively coupleable to the sample receiving
module 1001 by screwable attachment. Also, the plunger 1018 of the
device 1200 is actuable by screwing it, such as by twisting it,
further into the pressurizing chamber 1016 to pressurize the
pressurizing chamber 1016 and/or the sample receiving module
1001.
[0129] One embodiment of a biological assay sample preparation
device for use in practicing the subject methods is provided in A-D
of FIG. 13. A of FIG. 13 shows the device in a stored configuration
and B of FIG. 13 shows the device in a configuration such that a
sample collector can be inserted therein. The device 1300 includes
a sample receiving module 1301 including a fluid container 1302 for
receiving one or more portions of a sample collector therein, e.g.,
entirely therein. Such a device 1300 can also include a cap 1305
operatively, e.g., removably, coupleable to the sample receiving
module 1301 to pressurize the sample receiving module 1301, as is
shown in C of FIG. 13. The sample receiving module 1301, cap 1305
and other provided components can have any of the characteristics
or combination of characteristics of sample receiving modules, caps
and/or other corresponding components described herein.
[0130] In the embodiment shown, operatively coupling the sample
receiving module 1301 and the cap 1305, as is shown in C of FIG.
13, can expose a preparation solution to a sample on a sample
collector and thereby produces a prepared, e.g., lysed, sample.
Once the prepared, e.g., lysed, sample is made, the sample
receiving module 1301 can be operatively coupled, fluidically
coupled, such as by actuating, such as by rotating the sample
receiving module 1301 about an axis of a coupling component 1317,
via a vent 1316, to a preparation module 1315 of the device 1300.
Operatively coupling can be performed by rotating the sample
receiving module 1301 about an axis of a coupling component 1317
90.degree. or less.
[0131] The preparation module 1315 also can include a buffer, e.g.,
a dilution buffer. Operatively coupling the sample receiving module
1301 and the preparation module 1315, as is shown in D of FIG. 13,
places the prepared sample in fluidic communication with the
dilution buffer so that the prepared sample is diluted in the
preparation module 1315. Thereafter, the diluted prepared sample
can be delivered out of the device 1300 for further analysis using
the pressure within the device to push the diluted prepared sample
out of the device 1300.
[0132] One version of a biological assay sample preparation device
for use in practicing the subject methods is provided in A-F of
FIG. 14. A of FIG. 14 shows the device in a configuration such that
a sample collector can be inserted therein, as indicated by the
arrow. The device 1400 includes a sample receiving module 1401
including a fluid container 1402 for receiving one or more portions
of a sample collector therein, e.g., entirely therein. Such a
device 1400 can also include a cap 1405 operatively, e.g.,
removably, coupleable to the sample receiving module 1401, as is
shown in C of FIG. 14. Such a cap 1405 can also include a
preparation solution, e.g., a lysis buffer 1406, a seal 1421, and a
plunger 1422 including a piercing member 1423. The plunger 1422 can
be actuated by pushing the plunger 1422 to pierce the seal 1421
with the piercing member 1423, provide fluidic communication
between the lysis buffer 1406 and a sample collector in the sample
receiving module 1401, and pressurize the sample receiving module
1401. The sample receiving module 1401, cap 1405 and other provided
components can have any of the characteristics or combination of
characteristics of sample receiving modules, caps and/or other
corresponding components described herein.
[0133] Once the prepared, e.g., lysed, sample is made, the prepared
sample can pass to a sample incubation chamber 1424 via an
actuating valve 1425 which can include a bimetal valve actuator.
Therein, the sample can be incubated and the incubated sample
measured to produce an assay result. The assay result can be
displayed to a user via a display 1426 of the device 1400. The
device 1400 also includes a power source 1426, e.g., one or more
batteries, and a substrate 1427, e.g., a printed circuit board, for
performing the measurement and displaying the result. The device
1400 also includes a housing composed of a top cover 1428 and a
bottom cover 1429 and a bottom plate 1430 and/or gasket 1431
separating the sample receiving module 1401 and the incubation
chamber 1424.
Methods
[0134] The present disclosure includes methods of delivering a
sample, such as a biological assay sample. Delivering a sample can
include moving, e.g., flowing, a sample, such as a prepared
biological assay sample, to a particular location, such as a
location outside a sample delivery device and/or a specific
location intended by a user, such as a sample analysis device or a
portion thereof.
[0135] In some aspects, the subject methods include collecting a
biological sample with a sample collector. Such a sample can
include, for example, human saliva, blood, or a solid tissue such
as buccal tissue. Such a sample can also include bacteria or
spores. Collecting can include contacting, e.g., rubbing and/or
scraping, the sample collector against one or more surfaces of a
subject and/or surfaces of a biological sample of a subject, such
as a liquid, e.g., saliva and/or blood, sample extracted from the
subject. As such, in some versions, collecting includes extracting
one or more biological samples from the subject. In some versions,
collecting the biological sample can include instructing a subject
to produce a biological sample, such as by spitting onto and/or
into a sample collector. Collecting the biological sample can also
include retaining a biological sample or a portion thereof, e.g.,
one or more cells, on the sample collector while, for example
transferring the sample collector to an assay device. In some
instances, a sample collector is a swab and collecting the
biological sample includes swabbing the inside of a subject's mouth
to obtain the biological sample on the collector.
[0136] In some aspects, the methods include inserting a sample
collector into a sample receiving module of a sample preparation
device. Inserting can include moving one or more portions of the
sample collector, e.g., the sample collection portion and/or the
handle, into, such as fully into, a sample receiving module via an
opening in the module. The inserting can include rubbing one or
more portions of the sample collector against an interior wall of
the sample receiving module. In some versions, the methods include
retaining the one or more portions of the sample collector, e.g.,
the sample collection portion and/or the handle, within, such as
fully within, the sample receiving module after insertion. In some
embodiments, the methods include removing the one or more portions
of the sample collector, e.g., the sample collection portion and/or
the handle, from the sample receiving module after insertion. Also,
in some aspects, a sample receiving module includes a seal, e.g., a
breakable and/or frangible seal, such as a foil seal, over an
opening and wherein inserting the sample collector into a sample
receiving module of a sample preparation device includes breaking
the seal, such as breaking the seal by exerting force on it with
the sample collector, and inserting at least a portion of the
sample collector through the opening.
[0137] The subject embodiments, in some versions also include
inserting the sample collector by exposing the biological sample to
a preparation solution within the sample receiving module to
produce a prepared biological assay sample. Such exposure can
include immersing the biological sample and/or sample collector
entirely within the preparation solution. Also, producing the
prepared biological sample can include exposing the preparation
solution to one or more aspects of the biological sample, wherein
such exposure results in a change in the biological sample, e.g.,
cell lysing, such that the modified biological sample can be
further processed and/or analyzed.
[0138] A prepared biological assay sample is a biological assay
sample which has been processed by exposing the sample to a
preparation solution, as described above. Such exposure can prepare
the sample for further analysis and can include lysing cells of the
sample with a lysing agent of the preparation solution and/or
extracting nucleic acids therefrom. Such extracted nucleic acids
can be released into a resulting prepared sample solution. In some
embodiments, the methods include a step of extracting genomic
deoxyribonucleic acid (DNA) from a biological sample. In some
versions, the preparation solution is a nucleic acid amplification
preparation solution and exposure to the solution prepares nucleic
acids of the sample for amplification, e.g., isothermal
amplification. After such exposure, the sample is a prepared
nucleic acid amplification sample.
[0139] In various aspects, the subject methods include operatively
coupling a cap of the sample preparation device to the sample
receiving module and thereby pressurizing the sample receiving
module. Operatively coupling the cap of the sample preparation
device to the sample receiving module can include adhesively,
snapedly, and/or screwably, fastening the cap to the sample
receiving module. Such coupling can also be removable and as such,
reversible and repeatable a plurality of times. Such operative
coupling can also in include sealing the sample receiving module or
apportion thereof, e.g., a fluid container, with the cap.
Operatively coupling the cap and the sample receiving module can
include screwing the cap to the module by rotating the cap with
respect to the module while screwable threads of the two elements
are engaged. Operatively coupling the cap and the sample receiving
module, in some embodiments includes inserting the sample receiving
module or a portion thereof, e.g., an end, into a cap. Operatively
coupling the cap and the sample receiving module, in some
embodiments includes inserting the cap, or a portion thereof, e.g.,
a pressurizing component and/or an end, into, such as fully into,
the sample receiving module or a portion thereof, e.g., a fluid
container.
[0140] In some versions of the methods, the sample receiving module
includes a first attachment element and/or the cap includes a
second attachment element. In such embodiments, operatively
coupling a cap of the sample preparation device to the sample
receiving module includes mateably connecting the first and second
attachment elements, such as screwing the first attachment element,
e.g., a thread, into the second attachment element, e.g., a groove,
by rotating the cap with respect to the sample receiving module
while the attachment elements are engaged.
[0141] Operatively coupling the cap of the sample preparation
device to the sample receiving module also includes pressurizing
the sample receiving module or a portion thereof, e.g., a fluid
container. The pressurizing includes exerting force on one or more
fluid, e.g., a liquid and/or gas, within the sample receiving
module, such as air and/or preparation solution with a pressurizing
component. As the pressurizing component extends further into the
sample receiving module, the pressure increases because the
pressurizing component exerts more force on the one or more fluid.
The methods also include retaining the pressurizing component in a
particular position within the sample receiving module, wherein, in
such a configuration, the pressure in the module remains constant
while the sample receiving module remains sealed.
[0142] In various embodiments, the methods include pressurizing the
sample receiving module to a pressure ranging from 50 Pa to 50000
Pa, such as 500 Pa to 50000 Pa, such as 1000 Pa to 50000 Pa, such
as 5000 Pa to 50000 Pa, such as 10000 Pa to 30000 Pa, such as 15000
Pa to 25000 Pa, each inclusive. Where desired, the pressurizing
component pressurizes the sample receiving module to a pressure of
1000000 Pa or less, such as 50000 Pa or less, such as 30000 Pa or
less, such as 10000 Pa or less, such as 5000 Pa or less, such as
1000 Pa or less, such as 500 Pa or less, such as 50 Pa or less. In
some versions, the pressurizing component pressurizes the sample
receiving module to a pressure of 1000000 Pa or more, 50000 Pa or
more, 30000 Pa or more, 10000 Pa or more, or 5000 Pa or more, 1000
Pa or more, 500 Pa or more, or 50 Pa or more. As used herein, the
term pressure can refer to peak pressure.
[0143] One example of pressurization according to the subject
embodiments is illustrated in FIG. 16. Specifically, FIG. 16
provides a graph illustrating pressure generated in a sample
preparation device upon pressurization by the application and
rotation of a cap, e.g., screw cap, to the top of the device
according to embodiments of the subject disclosure. As is shown,
pressure is linearly related to displacement, and therefore
rotation, of the cap.
[0144] In some aspects, the methods include storing reagents with
long shelf-life at room temperature. Such storage can include
storing stable reagents, e.g., preparation solutions and/or staging
reagents, in liquid form and/or unstable reagents, e.g.,
preparation solutions and/or staging reagents, in dry, e.g.,
lyophilized, form. Storage according to the subject methods can be
performed for a length of time of 1 day or less, such as 1 month or
less, such as 6 months or less, such as 1 year or less and/or one
year or more. The methods also can include sample loading into, for
example a sample analyzing device.
[0145] In various aspects, a solution, e.g., a lysis solution, is
heated. Such heating can be achieved using a heat source such as an
exothermic reaction. Furthermore, in some embodiments, the methods
include adding to contents of a sample receiving module one or more
heating reagents which, when mixed, cause an exothermal reaction.
Such a reaction can, for example, heat a sample for lysis.
Exothermal reactions can generate heat and/or gas. Exothermal
reactions can include the hydration of a mixture composed of
encapsulated and/or non-encapsulated oxides such as calcium oxide
and/or magnesium oxide and dehydrated and/or hydrated zeolite, or
any combinations thereof. Such a process can be coupled with
control of pH of the mixture through compounds such as Citric acid,
or combination exothermic mixes, such as Cao and Mg--Fe. Modulation
can include timed/controlled release from encapsulated reactants
and can include particles with tailored size distribution and
different burn characteristics. Phase change materials (PCM) can be
used to control the heat stability of the reaction. PCMs include,
for example, organics (paraffins, non paraffins and fatty acids)
and inorganics (salt hydrates).
[0146] Also, in some versions, the methods include adding one or
more gas-producing regents, e.g., liquid reagents, that, when
mixed, generate a gas and further pressurize a subject device or a
portion thereof, e.g., a sample receiving module. Such reagents may
be the same or different reagents than those applied in an
exothermic reaction. The gas produced by such reagents may be
applied in propelling at least a portion of the prepared biological
assay sample out of the sample receiving module. In some forms, a
chemical reaction is used to produce gases that can increase
pressure, e.g., pressure which can be applied for driving out a
liquid, inside the module.
[0147] The methods, in some instances, include generating fluid
driving pressure and/or dispensing a prepared sample and/or reagent
and sample mix into an analyzing device with the pressure. Also,
according to various embodiments, a user can pressurize a sample
receiving module on-demand before, during and/or after reagents,
e.g., preparation solutions and/or staging reagents, are exposed to
a biological sample.
[0148] One embodiment of the subject methods is illustrated, for
example, by FIG. 1 and FIG. 15. In various embodiments, a device
according to the methods includes a sample receiving module 101
including a fluid container 102 for receiving one or more portions
of a sample collector therein, e.g., entirely therein, a
preparation solution 104, and a first attachment element 103. Such
a device 100 can also include a cap 105 operatively, e.g.,
removably, coupleable to the sample receiving module 101 and
including a pressurizing component 106, and a second attachment
element 107 operatively coupleable with the first attachment
element 103. As noted above, the methods include operatively
coupling the cap 105 and the sample receiving module 101. Such a
process can be performed by causing a device to go from a
conformation as shown in FIG. 1 or FIG. 2 to a conformation as
shown in FIG. 15. Accordingly, the methods can include inserting a
pressurizing component 106 into, e.g., entirely into, the sample
receiving module 101. The methods can also include expelling fluid
from sample receiving module 101 when the first attachment element
103 is operatively coupled to the second attachment element 107 by,
for example, actuating a valve 108 of the device.
[0149] Furthermore, and as is illustrated, for example, by FIG. 2,
the methods include actuating an inner body 214 within an outer
body 209 when a cap 205 is operatively coupled to a sample
receiving module 201. Operatively coupling the cap includes
exerting force on the inner body 214 with the cap 205 or a portion
thereof, such as a pressurizing component 206, so that the inner
body 214 moves. Such actuating can also include breaking a
breakable seal 213 with the one or more piercing member 216 and
placing the first chamber 210 in fluidic communication with the
second chamber 215. Also, in some versions, the outer body 209
includes a staging reagent 217 and the methods include placing the
staging reagent 217 in fluidic communication with the second
chamber 215. In some aspects, the staging reagent 217 includes one
or more lyophilized agents, such as one or more lyophilized cell
lysing reagent, and placing the staging reagent 217 in fluidic
communication includes hydrating the reagent with the preparation
solution 204 and/or exposing the staging reagent 217 to the
biological sample.
[0150] Embodiments of the subject methods also include delivering a
sample, e.g., a prepared biological assay sample, by depressurizing
the sample receiving module by flowing and/or discharging at least
a portion of the contents of the sample receiving module, such as a
prepared biological assay sample, preparation solution, unprepared
biological sample and/or air, out of the sample receiving module.
Depressurizing includes providing fluidic communication, such as
via a valve, e.g., a reversibly actuable valve, between a fluidic
container of a sample receiving module and an environment, such as
a sample analysis device, outside the sample receiving module. Such
depressurization can include actuating the valve from a sealed
conformation to an unsealed conformation and thereby providing such
fluidic communication via an opening, e.g., a depressurization
opening, therethrough. In various embodiments, an opening such as a
depressurization opening does not allow passage of a gas, such as
air, therethrough. In such embodiments, air is not passed through
the opening while, for example, a liquid is passed through the
opening, the plunger actuates toward the opening and/or the plunger
is not actuated.
[0151] Where desired, a device according to the subject embodiments
includes a breakable and/or frangible seal, such as a foil seal,
for sealing a valve, e.g., a reversibly actuable valve. In such
embodiments, depressurizing the sample receiving module includes
breaking the seal so that a fluid can flow from a first side of the
seal to a second side of the seal opposite the first. Breaking the
seal can include exerting force on it with fluid within the
pressurized container by opening the valve. Also, in some versions,
the subject devices can include a filter for filtering fluid
discharging from the sample receiving module. In such embodiments,
the methods include filtering by flowing one or more fluid, e.g., a
prepared biological assay sample and/or air, through the filter.
Flowing can be achieved by passing the fluid through the material
of the filter, such as through one or more entire surface, e.g., a
top and/or bottom surface of the material. The filtering can be
performed on the fluid, e.g., sample, discharging from a
depressurizing sample receiving module through, for example, a
valve.
[0152] In some aspects of the methods, the sample receiving module
includes an outer body forming a first chamber, and a fluid
container of a sample receiving module includes a breakable seal
and an inner body forming a second chamber which can be sealed at
an end by the breakable seal, wherein the inner body is actuable
within the outer body. In such embodiments, operatively coupling a
cap of the sample preparation device to the sample receiving module
includes actuating, such as by sliding, the inner body within the
outer body to break the seal and place the first and second
chambers in fluidic communication. Operatively coupling, such as by
screwing, a cap of the sample preparation device to the sample
receiving module can include exerting force on the inner body with
the cap or a portion thereof, e.g., the pressurizing component, by
contacting the two components. Actuating the inner body within the
outer body includes moving the inner body in a linear direction
toward a valve of the sample receiving module and/or away from the
cap. In some versions, the outer body includes a piercing member
and actuating the body includes piercing the seal on the inner body
with the piercing member. Also, in various aspects, an outer body
includes a staging reagent, e.g., a lyophilized staging reagent,
and placing the first and second chambers in fluidic communication
includes mixing the preparation solution and/or biological sample
and the staging reagent and/or hydrating the staging reagent.
[0153] Also included in the subject methods are methods for
preparing a biological assay sample including operatively coupling
a cap and a sample receiving module of a biological assay sample
preparation device, wherein the cap includes a seal and a plunger
including a piercing member, e.g., a needle and/or sharpened
cylindrical protrusion. In such methods, operatively coupling can
include inserting, e.g., fully inserting, a portion of a cap, e.g.,
an insertion portion and/or an end, into a sample receiving module
or a portion, e.g., chamber thereof. Such insertion can form a
sealed fluidic connection between chambers of each element. Also,
an insertion portion can be cylindrical and can extend at and end
from and have a smaller diameter than other portions of the cap. An
insertion portion can be at a first end of a cap opposite a second
end, wherein the second end includes a plunger.
[0154] The methods also, in some aspects include advancing the
plunger to pierce the seal with the piercing member and thereby
placing a first chamber in fluidic communication with a second
chamber and preparing a biological assay sample. Such advancing can
include moving, such as by sliding, the plunger in a linear
direction, such as a direction toward a sample receiving module or
a portion thereof, e.g., a valve, and/or a direction along an axis
of symmetry of the plunger and/or the cap and/or the sample
receiving module. The plunger can include a first end and a second
end opposite the first end and including the piercing member, and
wherein advancing the plunger includes exerting force on a first
end of the plunger in a direction toward the second end. Advancing
the plunger can be performed manually by, for example, contacting
and exerting force directly on an end of the plunger, as can be
performed with the device embodiment shown for example, in FIGS. 3A
and 3B and 4. Advancing the plunger can also be performed by,
screwing the cap to the sample receiving module, such as by
twisting the two components with respect to one another while their
respective attachment elements are engaged, as can be performed
with the device embodiment shown for example, in FIGS. 5A and
5B.
[0155] Also, in some versions, the plunger includes a body portion,
e.g., a cylindrical body portion, which is received entirely within
other portions of the cap when the plunger is advanced, and a
contacting portion at an end of the body portion and which can be
contacted by a user directly to advance the plunger. Also, as is
sown, for example in FIGS. 5A and 5B, in some versions, the plunger
is retained entirely within other portions of the cap while it is
advanced.
[0156] In various embodiments of the subject disclosure, a first
chamber, e.g., first chamber of a cap, includes a preparation
solution, and a second chamber, e.g., second chamber of a sample
receiving module, includes a staging reagent. In such embodiments,
the methods can include placing the first chamber in fluidic
communication with the second chamber and mixing the preparation
solution and the staging reagent. Also, in some embodiments of the
methods, delivering the prepared biological assay sample includes
actuating, such as by rotating 45.degree. or less, or 90.degree. or
less, a reversibly actuable valve of the sample preparation device
and flowing at least a portion of the prepared biological assay out
of the sample receiving module through the valve, e.g., through an
opening in the valve.
[0157] Furthermore, and as is representatively shown, for example,
by FIGS. 6A-6C, the methods include using a device 600 composed of
a sample receiving module 601 including a fluid container 602 for
receiving one or more portions of a sample collector 611 therein,
e.g., entirely therein, and a first attachment element 603. The
methods include operatively coupling a cap 605 and the sample
receiving module 601, as is shown in FIG. 6B. The sample receiving
module 601 in turn includes a preparation solution, e.g., a lysis
buffer 606, and a second attachment element 607 operatively
coupleable with the first attachment element 603 when the
components are operatively coupled.
[0158] In some versions, the methods include operatively coupling
the sample receiving module 601 and the cap 605, by screwing the
sample receiving module 601 and the cap 605, and thereby piercing a
seal 604 with a piercing member 608 and placing a first chamber 609
in fluidic communication with a second chamber 610. As such,
operatively coupling the sample receiving module 601 and the cap
605, such as by screwing the sample receiving module 601 and the
cap 605 together, includes exposing a preparation solution 606 to a
sample on a sample collector 611 and thereby producing a prepared,
e.g., lysed, sample 612.
[0159] Once the prepared, e.g., lysed, sample 612 is made, the
methods include operatively coupling the sample receiving module
601 to a pressurizing module 615. Operatively coupling can be
performed by attaching, such as by screwing, an attachment element
613 of a sample receiving module 601 and a second attachment
element 614 of a pressurizing module 615. The pressurizing module
615 also includes a buffer, e.g., a dilution buffer 616.
Operatively coupling the sample receiving module 601 and the
pressurizing module 615, as is shown in FIG. 6C, can include
placing the prepared sample 612 in fluidic communication with the
dilution buffer 616 so that the prepared sample 612 is diluted and
pressurizes the sample receiving module. Such an action can also
pierce a seal 617 with a piercing member 618. Thereafter, the
methods can include delivering the diluted prepared sample out of
the device 600 for further analysis using the pressure within the
device to push the diluted prepared sample out of the device
600.
[0160] As is representatively shown, for example, by FIGS. 7A-7D,
the methods include using a device 700 including a sample receiving
module 701 including a fluid container 702 for receiving one or
more portions of a sample collector 711 therein, e.g., entirely
therein, and a first attachment element 703. Such a device 700 can
also include a cap 705 and the methods can include operatively
coupling the cap 705 to the sample receiving module 701. The cap
705 also can include a preparation solution, e.g., a lysis buffer
706, and a second attachment element 707 operatively coupleable
with the first attachment element 703. Operatively coupling the cap
705 and the sample receiving module 701 also includes pressurizing
the sample receiving module 701. The sample receiving module 701
can also include a buffer, e.g., a dilution buffer 718 in a buffer
container 719 therein.
[0161] In the embodiment shown, operatively coupling the sample
receiving module 701 and the cap 705, as is shown in FIG. 7B, such
as by screwing the sample receiving module 701 and the cap 705,
includes piercing a seal 704 with a piercing member 708 and placing
a first chamber 709 in fluidic communication with a second chamber
710. As such, operatively coupling the sample receiving module 701
and the cap 705, such as by screwing the sample receiving module
701 and the cap 705 together, includes exposing preparation
solution 706 to a sample on a sample collector 711 and thereby
producing a prepared, e.g., lysed, sample 712.
[0162] After the prepared, e.g., lysed, sample 712 is made, the
methods include operatively coupling the sample receiving module
701 to, such as by lowering onto, a cartridge 715. Such operative
coupling can include actuating a fluidic communication element 717
and/or opening a valve 716, e.g., poppet valve, of the fluidic
communication element 717. The methods also include actuating the
fluidic communication element 717 toward the cap 705 by exerting
force on it with the cartridge 715. Opening the valve 716 in turn
includes releasing the prepared sample 712 into the dilution buffer
718 in the buffer container 719 and producing a prepared diluted
sample 720. Operatively coupling the sample receiving module 701
and the cartridge 715, as is shown in FIG. 7D, includes delivering
the prepared diluted sample 720 out of the sample receiving module
703 and into the cartridge.
[0163] In addition, and as is illustrated representatively, for
example, by FIGS. 8A-8D, the methods include using a device 800
including a sample receiving module 801 including a fluid container
802 for receiving one or more portions of a sample collector 811
therein, e.g., entirely therein. Such a device 800 can also include
a cap 805 and the methods can include operatively coupling the cap
805 to the sample receiving module 801. The cap can also include a
preparation solution, e.g., a lysis buffer 806.
[0164] Operatively coupling the cap 805 and the sample receiving
module 801 may not pressurize the sample receiving module 801 but
may include placing the lysis buffer 806 in fluidic communication
with a sample on the sample collector 811 and thereby producing a
prepared, e.g., lysed, sample 812.
[0165] The device 800 also includes a pressurizing chamber 816
operatively coupled to the sample receiving module 801 and
including a valve 817, e.g., a one-way valve, to provide fluidic
communication therebetween. The methods include actuating a plunger
818 to create positive and/or negative pressure within a
pressurization chamber 816. The pressurizing chamber 816 also
includes a buffer, e.g., a dilution buffer 821. The pressurizing
chamber 816 also includes an expulsion valve 819 and the methods
include expelling a diluted prepared sample 820 therefrom by
actuating the plunger 818.
[0166] According to the subject methods, when the cap 805 is
operatively coupled to the sample receiving module 801 to produce a
prepared sample 812, the methods include actuating the plunger 818
in a first direction, as is shown in FIG. 8C, and propelling the
prepared sample 812 from the sample receiving module 801 into the
pressurizing chamber 816 via valve 817 and thereby producing a
diluted prepared sample 820. The plunger 818 can then be actuated
in a second direction opposite the first, as is shown in FIG. 8D,
to thereby propel the diluted prepared sample 820 out of the
pressurizing chamber 816 via expulsion valve 819.
[0167] As is shown representatively, for example, by FIGS. 8A-8D,
the methods include using a device 900 which includes a sample
receiving module 901 including a fluid container 902 for receiving
one or more portions of a sample collector 911 therein, e.g.,
entirely therein. Such a device 900 can also include a cap 905
operatively, e.g., removably, coupleable to the sample receiving
module 901 and including a preparation solution, e.g., a lysis
buffer 906. As such, the methods can include operatively coupling
the cap 905 and the sample receiving module 901.
[0168] Operatively coupling the cap 905 and the sample receiving
module 901 may not pressurize the sample receiving module 901 but
may place the lysis buffer 906 in fluidic communication with a
sample on the sample collector 911 and thereby produce a prepared,
e.g., lysed, sample 912. The sample receiving module 901, cap 905
and other provided components can have any of the characteristics
or combination of characteristics of sample receiving modules, caps
and/or other corresponding components described herein.
[0169] In various instances, the device 900 also includes a
pressurizing chamber 916 and the methods include operatively
coupling the pressurizing chamber 916 to the sample receiving
module 901. The pressurizing chamber 916 also includes a plunger
918, e.g., a manually actuable plunger, which and the methods
include actuating the plunger to create positive and/or negative
pressure within the pressurizing chamber 916.
[0170] The device 900 is configured such that when the cap 905 is
operatively coupled to the sample receiving module 901 to produce a
prepared sample 912, the plunger 918 can be actuated in a first
direction according to the subject methods, as is shown in FIG. 9C,
to propel the prepared sample 912 from the sample receiving module
901 and into the pressurizing chamber 916 via vent 917 and thereby
produce a diluted prepared sample 920. Actuating the plunger 918 in
such as direction can include unsealing a vent 917. The methods
also include actuating the plunger 918 in a second direction
opposite the first, as is shown in FIG. 9D, and propelling the
diluted prepared sample 920 out of the pressurizing chamber 916 via
the valve 919. Actuating the plunger 918 in such as direction can
include sealing the vent 917 and preventing further fluid
communication therethrough.
[0171] As is shown representatively, for example, by FIGS. 10, 11
and 12, the methods include using a device, e.g., device 1000,
1100, and/or 1200, which includes a sample receiving module 1001
including a fluid container 1002 for receiving one or more portions
of a sample collector 1011 therein, e.g., entirely therein. As
such, the methods include inserting such a sample collector
therein. Such a device 1000 can also include a cap 1005
operatively, e.g., removably, coupleable to the sample receiving
module 1001 and the methods include operatively coupling the cap
1005 and the sample receiving module 1001. In some versions,
operatively coupling the cap 1005 and the sample receiving module
1001 includes placing a preparation solution, e.g., a lysis buffer,
in fluidic communication with a sample on the sample collector 1011
and thereby producing a prepared, e.g., lysed, sample.
[0172] The pressurizing chamber 1016 also includes a plunger 1018,
e.g., a manually actuable plunger, and the methods include pushing
and/or pulling the plunger in a linear direction, e.g., along a
central axis of symmetry of a pressurizing chamber and/or sample
receiving module, and thereby creating positive and/or negative
pressure within the pressurization chamber 1016 and/or sample
receiving module 1001. The sample receiving module 1001 also
includes an expulsion valve 1019 and the methods include expelling
a diluted prepared sample therefrom upon actuation of the plunger
1018.
[0173] The methods include actuating the plunger 1018 in a first
direction, to propel a buffer from channel 1017 into the sample
receiving module 1001 and thereby produce a diluted prepared sample
therein and pressurize the sample receiving module. According to
the methods, the diluted prepared sample can then be propelled by
the pressure out of the sample receiving module 1001 via expulsion
valve 1019.
[0174] Also, in some versions of the methods, the methods include
operatively coupling by screwing the cap 1005 to the sample
receiving module 1001. The methods also can include screwing, such
as by twisting, the plunger 1018 to actuate it into the
pressurizing chamber 1016 to pressurize the pressurizing chamber
1016 and/or the sample receiving module 1001.
[0175] As is shown representatively, for example by A-D of FIG. 13,
the methods include using a device 1300. Such methods can include
storing the device 1300 in a stored configuration, such as that
shown in A of FIG. 13. The methods also can include inserting, such
as fully inserting, a sample collector as indicated by the arrow
into a device 1300 in a sample collector receiving configuration as
shown in B of FIG. 13. A device 1300 can also include a cap 1305
and the methods can include operatively, e.g., removably, coupling
the cap 1305 to the sample receiving module 1301 and thereby
pressurizing the sample receiving module 1301, as is shown in C of
FIG. 13.
[0176] Also, operatively coupling the sample receiving module 1301
and the cap 1305, as is shown in C of FIG. 13, can include exposing
a preparation solution to a sample on a sample collector and
thereby producing a prepared, e.g., lysed, sample. Once the
prepared, e.g., lysed, sample is made, the methods include
operatively coupling, such as fluidically coupling, such as by
actuating, such as by rotating, the sample receiving module 1301
about an axis of a coupling component 1317, wherein the operative
coupling is via a vent 1316, to a preparation module 1315 of the
device 1300.
[0177] Operatively coupling the sample receiving module 1301 and
the preparation module 1315, as is shown in D of FIG. 13, can
include placing the prepared sample in fluidic communication with a
dilution buffer so that the prepared sample is diluted in the
preparation module 1315. Thereafter, the methods can include moving
the diluted prepared sample out of the device 1300 for further
analysis using the pressure within the device to push the diluted
prepared sample out of the device 1300.
[0178] As is shown representatively, for example by A-F of FIG. 14,
the methods include using a device 1400 including a sample
receiving module 1401 including a fluid container 1402 for
receiving one or more portions of a sample collector therein, e.g.,
entirely therein. Such a device 1400 can also include a cap 1405
and the methods include operatively, e.g., removably, coupling the
cap 1405 to the sample receiving module 1401, as is shown in C of
FIG. 14. Such a cap 1405 can also include a preparation solution,
e.g., a lysis buffer 1406, a seal 1421, and a plunger 1422
including a piercing member 1423. The methods include actuating the
plunger 1422 by pushing the plunger 1422 to pierce the seal 1421
with the piercing member 1423, providing fluidic communication
between the lysis buffer 1406 and a sample collector in the sample
receiving module 1401, and pressurizing the sample receiving module
1401.
[0179] Once the prepared, e.g., lysed, sample is made, the methods
include flowing the prepared sample to a sample incubation chamber
1424 via an actuating valve 1425 which can include a bimetal valve
actuator. Therein, the sample can be incubated according to the
subject methods and the incubated sample measured to produce an
assay result. The assay result can be displayed to a user via a
display 1426 of the device 1400. Furthermore, F of FIG. 14 provides
a cross sectional view of the device.
Kits
[0180] The embodiments disclosed herein also include kits including
the subject devices and which can be used according to the subject
methods. The subject kits can include two or more, e.g., a
plurality, three or less, four or less, five or less, ten or less,
or fifteen or less, or fifteen or more, sample preparation devices
or components thereof, according to any of the embodiments
described herein, or any combinations thereof.
[0181] The kits can include one or more solutions and/or reagents,
such as any of those described herein, e.g., preparation solutions
and/or staging reagents and/or buffers, which can be stored in the
kits in containers separate from the devices. In addition, the kits
can include any device or other element which can facilitate the
operation of any aspect of the kits. For example, a kit can include
one or more devices for receiving and/or analyzing one or more
characteristics of a sample, e.g., a prepared sample. Kits can also
include packaging, e.g., packaging for shipping the devices without
breaking.
[0182] In certain embodiments, the kits which are disclosed herein
include instructions, such as instructions for using devices. The
instructions for using devices are, in some aspects, recorded on a
suitable recording medium. For example, the instructions can be
printed on a substrate, such as paper or plastic, etc. As such, the
instructions can be present in the kits as a package insert, in the
labeling of the container of the kit or components thereof (i.e.,
associated with the packaging or subpackaging etc.). In other
embodiments, the instructions are present as an electronic storage
data file present on a suitable computer readable storage medium,
e.g., Portable Flash drive, CD-ROM, diskette, etc. The instructions
can take any form, including complete instructions for how to use
the devices or as a website address with which instructions posted
on the world wide web can be accessed.
Utility
[0183] As demonstrated above, the subject devices and methods are
directed to biological sample preparation devices and methods for
preparing and delivering biological assay samples. Reagent storage,
release and/or other manipulation has been performed by storing
reagents in vials that are opened manually by an operator and
manipulated using pipettes to, for example, aliquot, mix and/or
incubate the reagents. Attempts at resolving challenges associated
with reagent storage and/or manipulation such as complexity, large
time requirement, and inconvenience have included, for example,
applying blister packs and dry reagent storage to utilizing fluidic
networks driven by active pressure sources such syringe pumps,
compressors, peristaltic pumps and pressurized canisters. Many of
the attempts have included applying separate structures on a device
and utilizing active components. Such previous attempts have
involved a high degree of complexity and cost which in turn has
provided limited reliability and usability.
[0184] The disclosed subject matter addresses these issues with the
described user-powered integrated device that provides reagent
storage/release and fluid propulsion. As such, the subject
embodiments integrate and thus simplify steps including, for
example, aliquoting, mixing, measuring and/or incubating using the
described self-contained automatic fluidic device. Accordingly, the
subject methods and devices are cheaper, less complex and/or more
accurate than other such devices or methods. Thus, the subject
devices and methods can be applied, for example, to provide
efficient on-demand reagent storage and/or release by using
effective fluid manipulation, including propulsion, of a sample
and/or reagents.
[0185] All publications and patent applications cited in this
specification are herein incorporated by reference as if each
individual publication or patent application were specifically and
individually indicated to be incorporated by reference. The
citation of any publication is for its disclosure prior to the
filing date and should not be construed as an admission that the
present invention is not entitled to antedate such publication by
virtue of prior invention.
[0186] Although the foregoing invention has been described in some
detail by way of illustration and example for purposes of clarity
of understanding, it is readily apparent to those of ordinary skill
in the art in light of the teachings of this invention that certain
changes and modifications can be made thereto without departing
from the spirit or scope of the appended claims.
* * * * *