U.S. patent application number 14/893388 was filed with the patent office on 2016-03-31 for two part assembly.
The applicant listed for this patent is RAPID DIAGNOSTEK. Invention is credited to James Russell Webster.
Application Number | 20160091506 14/893388 |
Document ID | / |
Family ID | 51934362 |
Filed Date | 2016-03-31 |
United States Patent
Application |
20160091506 |
Kind Code |
A1 |
Webster; James Russell |
March 31, 2016 |
TWO PART ASSEMBLY
Abstract
A device that includes a first portion, the first portion
including at least one fluid channel; a fluid actuator; and an
introducer; a second portion, the second portion including at least
one well, the well containing at least one material, wherein one of
the first or second portion is moveable with respect to the other,
wherein the introducer is configured to obtain at least a portion
of the material from the at least one well and deliver it to the
fluid channel, and wherein the fluid actuator is configured to move
at least a portion of the material in the fluid channel.
Inventors: |
Webster; James Russell;
(Minnetonka, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RAPID DIAGNOSTEK |
Plymouth |
MN |
US |
|
|
Family ID: |
51934362 |
Appl. No.: |
14/893388 |
Filed: |
May 23, 2014 |
PCT Filed: |
May 23, 2014 |
PCT NO: |
PCT/US14/39400 |
371 Date: |
November 23, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61826845 |
May 23, 2013 |
|
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|
Current U.S.
Class: |
435/5 ; 422/68.1;
422/69; 435/287.1; 435/287.2; 435/29; 435/7.1; 435/7.92;
436/501 |
Current CPC
Class: |
G01N 2291/012 20130101;
G01N 2291/0256 20130101; B01L 2200/027 20130101; B01L 2400/0644
20130101; G01N 29/036 20130101; G01N 2333/59 20130101; G01N 29/022
20130101; G01N 2291/0255 20130101; B01L 2400/065 20130101; B01L
2300/0816 20130101; B01L 3/502738 20130101; B01L 2300/0867
20130101; G01N 33/54386 20130101; B01L 2400/0487 20130101; G01N
29/222 20130101; G01N 33/78 20130101; G01N 2291/0426 20130101 |
International
Class: |
G01N 33/78 20060101
G01N033/78; G01N 33/543 20060101 G01N033/543 |
Claims
1. A device comprising: a first portion, the first portion
comprising: at least one fluid channel; a fluid actuators; and an
introducer; a second portion, the second portion comprising: at
least one well, the well containing at least one material, wherein
one of the first or second portion is moveable with respect to the
other, wherein the introducer is configured to obtain at least a
portion of the material from the at least one well and deliver it
to the fluid channel, and wherein the fluid actuator is configured
to move at least a portion of the material in the fluid
channel.
2. The device according to claim 1, wherein the second portion
moves respect to the first portion.
3. (canceled)
4. The device according to claim 1, wherein there are at least two
wells with a first well comprising a buffer composition and a
second well comprising a reagent composition.
5. (canceled)
6. (canceled)
7. The device according to claim 1, wherein the fluid actuator
comprises a port in fluid communication with the fluid channel.
8. The device according to claim 7, wherein the port is configured
to be in fluid communication with a pump that is external to the
device.
9. The device according to claim 1, wherein the first portion
further comprises a sensor within the fluid channel.
10. (canceled)
11. The device according to claim 1, wherein the fluid channel is
configured to be in fluid communication with a sample introduction
pathway and the sample introduction pathway comprises a sample
introduction chamber.
12. (canceled)
13. The device according to claim 11, wherein the sample
introduction pathway is configured to obtain a sample from the
sample introduction chamber and place it in fluid communication
with the fluid channel.
14. (canceled)
15. The device according to claim 11, wherein the second portion
comprises at least one empty well and the sample introduction
pathway obtains the sample from the sample introduction chamber and
places it in the empty well.
16. The device according to claim 1, wherein the first portion
comprises a plurality of wells and the introducer can randomly
access any of the plurality of wells.
17. (canceled)
18. The device according to claim 9, wherein the sensor is a thin
film bulk acoustic resonance (TFBAR) sensor.
19. A system comprising: a device comprising: a first portion, the
first portion comprising: at least one fluid channel; a fluid
actuator; an introducer; and a sensor; a second portion, the second
portion comprising: at least one well, the well containing at least
one material, wherein one of the first or second portion is
moveable with respect to the other, wherein the introducer is
configured to obtain at least a portion of the material from the at
least one well and deliver it to the fluid channel, and wherein the
fluid actuator is configured to move at least a portion of the
material in the fluid channel; and an external instrument,the
external instrument configured to attain a signal from the
sensor.
20. The system according to claim 19, wherein the external
instrument is further configured to be in fluid communication with
the fluid actuator of the first portion of the sensor assembly.
21. The system according to claim 19, wherein the external
instrument comprises at least one pump.
22. (canceled)
23. (canceled)
24. (canceled)
25. A method comprising: providing a device comprising: a first
portion, the first portion comprising: at least one fluid channel;
a fluid actuator; an introducer; and a sensor; and a second
portion, the second portion comprising: at least one well, the well
containing at least one material, and a sample well, wherein one of
the first or second portions is moveable with respect to the other
wherein the introducer is configured to obtain at least a portion
of the material from the at least one well and deliver it to the
fluid channel, and wherein the fluid actuator is configured to move
at least a portion of the material in the fluid channel; placing a
sample in the sample well; obtaining at least a portion of the at
least one material from the at least one well and depositing it in
the fluidic pathway; obtaining at least a portion of the sample
from the sample well and depositing it in the fluidic pathway;
actuating fluid in the fluidic pathway so tin least a portion of
the sample and the at least one material reach the sensor;
monitoring at least one signal from the sensor; and depositing at
least some of the sample, at least one material, or some
combination thereof in the second portion of the device.
26. The method according to claim 25, wherein the sample is placed
in the sample well via the sample introduction pathway.
27. The method according to claim 26, wherein the device further
comprises a sample introduction chamber and the sample introduction
pathway obtains the sample from the sample introduction chamber and
deposits it in the sample well.
28. (canceled)
29. (canceled)
30. The method according to claim, 25 further comprising mixing the
at least one composition and the sample by placing at least a
portion of the sample and the composition in a well of the second
portion and further comprising obtaining the portion of the sample
and the composition from the well and actuating it in the fluidic
pathway, and repeating placing the portion of the sample and the
material in the well at least two times in order to effectuate
mixing.
31. The method according to claim 25, wherein the step of actuating
fluid in the fluidic pathway so that at least a portion of the
mixed sample and the material reach the sensor comprises reversing
the direction of flow at least once.
32. (canceled)
33. A device according to claim 1, wherein the fluid channel does
not include valves.
34.-56. (canceled)
Description
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional
Patent Application No. 61/826,845, filed on May 23, 2013.
BACKGROUND
[0002] There are numerous instruments and measurement techniques
for diagnostic testing of materials related to medical, veterinary
medical, environmental, biohazard, bioterrorism, agricultural
commodity, and food safety. Diagnostic testing traditionally
requires long response times to obtain meaningful data, involves
expensive remote or cumbersome laboratory equipment, requires large
sample size, utilizes multiple reagents, demands highly trained
users, and can involve significant direct and indirect costs. For
example, in both the human and veterinary diagnostic markets, most
tests require that a sample be collected from a patient and then
sent to a laboratory, where the results are not available for
several hours or days. As a result, the caregiver must wait to
treat the patient.
[0003] Point of use (or point of care when discussing human or
veterinary medicine) solutions for diagnostic testing and analysis,
although capable of solving most of the noted drawbacks, remain
somewhat limited. Even some of the point of use solutions that are
available are limited in sensitivity and reproducibility compared
to in laboratory testing. There is also often significant direct
costs to a user as there can be separate systems for each point of
use test that is available.
SUMMARY
[0004] Disclosed herein are devices that includes a first portion,
the first portion including at least one fluidic pathway; a fluid
actuator; and an introducer; a second portion, the second portion
including at least one well, the well containing at least one
material, wherein one of the first or second portion is moveable
with respect to the other, the introducer is configured to obtain
at least a portion of the material from the at least one well and
deliver it to the fluidic pathway, and the fluid actuator is
configured to move at least a portion of the material in the
fluidic pathway.
[0005] Also disclosed are systems that include an assembly, the
assembly including a first portion, the first portion including at
least one fluidic pathway; a fluid actuator; an introducer; and a
sensor positioned within the fluidic pathway; a second portion, the
second portion including at least one well, the well containing at
least one material, wherein one of the first or second portion is
moveable with respect to the other, the introducer is configured to
obtain at least a portion of the material from the at least one
well and deliver it to the fluidic pathway, and the fluid actuator
is configured to move at least a portion of the material in the
fluidic pathway; and an external instrument, the external
instrument configured to attain a signal from the sensor.
[0006] Also disclosed are methods that include steps of providing a
first device, the first device including a first portion, the first
portion including at least one fluidic pathway; a fluid actuator;
an introducer; and a sensor positioned within the fluidic pathway;
a second portion, the second portion including at least one well
containing at least one material; a sample well; and an empty well,
wherein one of the first or second portion is moveable with respect
to the other, the introducer is configured to obtain at least a
portion of the material from the at least one well and deliver it
to the fluidic pathway, and the fluid actuator is configured to
move at least a portion of the material in the fluidic pathway;
placing a sample in the sample well; obtaining at least a portion
of the at least one composition from the at least one well and
depositing it in the fluidic pathway; obtaining at least a portion
of the sample from the sample well and depositing it in the fluidic
pathway; actuating fluid in the fluidic pathway so that at least a
portion of the sample and the at least one composition reach the
sensor; monitoring at least one signal from the sensor; and
depositing at least some of the sample, at least one composition,
or some combination thereof in the empty well.
[0007] These and various other features will be apparent from a
reading of the following detailed description and related
drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a schematic diagram illustrating an illustrative
sensor assembly.
[0009] FIGS. 2A and 2B are schematic diagrams illustrating the
operational principles of embodiments of thin film bulk acoustic
resonator (TFBAR) sensing devices.
[0010] FIG. 3 is a perspective view of a portion of a sensor
configured within a disclosed first portion.
[0011] FIGS. 4A and 4B are a top down view (FIG. 4A) and a cross
section view (FIG. 4B) of a disclosed sensor assembly.
[0012] FIGS. 5A, 5B, and 5C are an exploded view (FIG. 5A) and
perspective views of a sensor assembly with the second portion at a
first point with respect to the first portion (FIG. 5B) and at a
second point with respect to the first portion (FIG. 5C).
[0013] FIG. 6 is a photograph of an illustrative sensor assembly
used to carry out Example 2A.
[0014] FIGS. 7A, 7B, 7C, 7D, 7E, 7F, and 7G are an exploded view
(FIG. 7A), a cross sectional view of a portion including the
introducer (FIG. 7B), a perspective view of a portion including the
sensor (FIG. 7C), a bottom view of a portion (FIG. 7D), a
perspective view of a cross section of a portion including the
sensor (FIG. 7E), a bottom view of the entire (FIG. 7F)
illustrative assembled sensor assembly, and a top view of the
entire (FIG. 7G) illustrative assembled sensor assembly.
[0015] FIG. 8 shows a cross section of an illustrative channel that
includes an associated sensor and electrical connection board.
[0016] FIGS. 9A to 9C depict various views of an illustrative
specific embodiment of a disclosed assembly.
[0017] The drawings are not necessarily to scale. Like numbers used
in the figures refer to like components, steps and the like.
However, it will be understood that the use of a number to refer to
a component in a given figure is not intended to limit the
component in another figure labeled with the same number. In
addition, the use of different numbers to refer to components is
not intended to indicate that the different numbered components
cannot be the same or similar.
DETAILED DESCRIPTION
[0018] In the following detailed description several specific
embodiments of compounds, compositions, products and methods are
disclosed. It is to be understood that other embodiments are
contemplated and may be made without departing from the scope or
spirit of the present disclosure. The following detailed
description, therefore, is not to be taken in a limiting sense.
[0019] All scientific and technical terms used herein have meanings
commonly used in the art unless otherwise specified. The
definitions provided herein are to facilitate understanding of
certain terms used frequently herein and are not meant to limit the
scope of the present disclosure.
[0020] As used in this specification and the appended claims, the
singular forms "a", "an", and "the" encompass embodiments having
plural referents, unless the content clearly dictates
otherwise.
[0021] As used in this specification and the appended claims, the
term "or" is generally employed in its sense including "and/or"
unless the content clearly dictates otherwise. The term "and/or"
means one or all of the listed elements or a combination of any two
or more of the listed elements.
[0022] As used herein, "have", "having", "include", "including",
"comprise", "comprising" or the like are used in their open ended
sense, and generally mean "including, but not limited to". It will
be understood that "consisting essentially of", "consisting of",
and the like are subsumed in "comprising" and the like. As used
herein, "consisting essentially of," as it relates to a
composition, product, method or the like, means that the components
of the composition, product, method or the like are limited to the
enumerated components and any other components that do not
materially affect the basic and novel characteristic(s) of the
composition, product, method or the like.
[0023] The words "preferred" and "preferably" refer to embodiments
of the invention that may afford certain benefits, under certain
circumstances. However, other embodiments may also be preferred,
under the same or other circumstances. Furthermore, the recitation
of one or more preferred embodiments does not imply that other
embodiments are not useful, and is not intended to exclude other
embodiments from the scope of the disclosure, including the
claims.
[0024] Also herein, the recitations of numerical ranges by
endpoints include all numbers subsumed within that range (e.g., 1
to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc. or 10 or less
includes 10, 9.4, 7.6, 5, 4.3, 2.9, 1.62, 0.3, etc.). Where a range
of values is "up to" a particular value, that value is included
within the range.
[0025] Any direction referred to herein, such as "top," "bottom,"
"left," "right," "upper," "lower," and other directions and
orientations are described herein for clarity in reference to the
figures and are not to be limiting of an actual device or system or
use of the device or system. Devices or systems as described herein
may be used in a number of directions and orientations.
[0026] Disclosed devices can accommodate a large breadth of testing
protocols without requiring the platform to be entirely redesigned.
Disclosed devices may also provide for the use of the same
configuration for different protocols, meaning that only the
materials would need to be different to afford different protocols
to be undertaken with the devices. This along with the option of
not including valves in portions of the consumable device can make
the devices very cost effective to manufacture. The devices may
also offer enhanced performance through mixing because of the two
way flow that is afforded by the devices. The two way flow can also
allow spent sample and reagents to be re-deposited in the wells
from which they came, thereby making the sensor assembly a
contained system with respect to sample and reagents.
[0027] Assembly
[0028] Disclosed herein is an assembly. In some embodiments,
assemblies can include a first portion and a second portion. The
first and second portions can be configured to be assembled
together to form an assembly. The first and second portions can be
assembled together by a manufacturer, an assembler, an end-user, or
any combination thereof. The assembly of the two portions can be
facilitated by the shape of the two portions, components of at
least one of the two portions that are designed to facilitate
assembly, or some combination thereof. The two portions can be made
of the same material(s) or different materials. In some embodiments
the first portion and the second portion can be made of different
materials, which because of the different purposes of the two
portions, may be useful. The two portions of the assembly can be
manufactured separately, in the same or different facilities;
and/or can be packaged and/or sold separately or together.
[0029] At least one of the first and second portions is moveable
with respect to the other. This implies that after the first and
second portion are assembled to form the assembly, one portion is
moveable with respect to the other. The portion that is moveable
with respect to the other can be moveable in one or more directions
or dimensions. Movement of one portion with respect to the other
may offer advantages in that wells in the second portion (discussed
below) can be randomly accessed by the first portion. The ability
to randomly access the wells in the second portion can allow a
large breadth of protocols to be accomplished without altering the
configuration of the assembly itself. Other possible advantages
provided by the movability of one portion with respect to the other
portion are discussed throughout this disclosure.
[0030] FIG. 1 illustrates an illustrative embodiment of an
assembly. This illustrative assembly 100 includes a first portion
110 and a second portion 120. This particular illustrative assembly
100 is configured to be assembled in a way that positions the
second portion 120 below the first portion 110 in the z direction.
In some embodiments, the second portion 120 is moveable with
respect to the first portion 110. The second portion being moveable
with respect to the first portion can imply that the second portion
can move in at least one dimension (x, y, or z) with respect to the
first portion, which is stationary. In some embodiments, the second
portion can move along a straight line with respect to the first
portion (for example, along the x dimension). The embodiment
depicted in FIG. 1 shows such movement, with the second portion 120
moving in the x direction (as indicated by the arrow designated m).
In some embodiments, the second portion can move along a straight
line with respect to the first portion (for example along the x
dimension) and can move up and down with respect to the first
portion (for example along the z dimension). Such movement could be
seen in the assembly 100 if the second portion 120 also moved in
the z dimension.
[0031] In some embodiments, the second portion can move around a
fixed point with respect to the first portion (for example in a
plane defined by the x and y dimensions). The embodiment depicted
in FIG. 4 could have such movement, with the second portion 420
moving in a circular direction (as indicated by the arc designated
m.sub.a) around a fixed point with respect to the first portion
410. This movement could be described as rotational movement. In
some embodiments, the second portion can move around a fixed point
with respect to the first portion (for example in a plane defined
by the x and y dimension) and can move up and down with respect to
the first portion (for example along the z dimension). Such
movement could be seen in the assembly 400 if the second portion
420 also moved in the z dimension.
[0032] First Portion
[0033] The first portion can include at least one fluidic pathway,
a fluid actuator, and an introducer.
[0034] Fluidic pathways can also be described as including a fluid
channel. The illustrative first portion 110 illustrated in FIG. 1
includes a fluid channel 112, a fluid actuator 114, and an
introducer 116. Generally, the fluid channel 112, the fluid
actuator 114, and the introducer 116 are in fluid communication
with one another. It can also be described that the fluid actuator
114, the introducer 116, and the fluid channel 112 are within, on,
or are part of the fluidic pathway.
[0035] The fluidic pathway can have various configurations, and the
examples depicted herein serve only as illustrative configurations.
In some embodiments, the fluidic pathway does not include portions
of the device that obtain the sample. In some embodiments, the
fluidic pathway begins after a sample is contained in a well of the
second portion. The fluidic pathway can be described as a transit
path for fluids in the assembly. The fluidic pathway need not be
fluidly connected at all times. For example, the fluidic pathway
can include a portion of the device that can be (based may be moved
into or out of the fluid pathway, by for example moving one portion
with respect to another portion. The fluidic pathway can also be
described as including any portion of the device accessible by the
introducer, any portion of the device fluidly connected with any
portion of the device accessible by the introducer, or some
combination thereof. The fluidic pathway need not include only an
actual volume that is connected. In some embodiments, a fluidic
pathway can be entirely housed on a first portion, entirely housed
on a second portion, or at least one portion of a fluidic pathway
can exist on a first and at least one portion of a fluidic pathway
can exist on a second portion. In some embodiments, a fluidic
pathway can be one that is connected at all times and in some
embodiments, one or more than one portion of a fluidic pathway can
be at some times disconnected from the remainder of the fluidic
pathway. In some embodiments, a fluidic pathway can include a fluid
channel. In some embodiments, such a fluid channel can be a volume
that is connected at all times. In some embodiments, such a fluid
channel can be entirely housed on the first portion of an assembly.
In some embodiments, such a fluid channel can be entirely housed on
the first portion of an assembly can be a volume that is statically
connected at all times. A fluid channel can refer to a physical
channel on a first portion of an assembly.
[0036] In some embodiments, the fluidic pathway does not include
valves. In some embodiments, the fluid channel does not include
valves. In some embodiments, fluid can flow in either direction in
the fluidic pathway (or in the fluid channel) even though there are
no valves. Bi-directional flow is possible, even though there may
be no valves in the fluidic pathway (or the fluid channel) because
of the ability to randomly access wells (for example an empty well)
in the second portion. More specifically, two directional flow can
be accomplished by depositing liquid (in some embodiments all the
liquid) in the fluidic pathway (or the fluid channel) in an empty
well on the second portion by flowing the fluid in a first
direction and then retrieving that liquid from that well and
directing it in the fluidic pathway by flowing the fluid in a
second direction (opposite to the first direction). Accomplishing
two way flow without the use of any valves can make disclosed
assemblies more cost effective to manufacture and less prone to
issues that may accompany the use of valves.
[0037] Fluidic pathways (and therefore fluid channels that are part
of a fluidic pathway) can have access to a sample introduction
pathway as well. The sample introduction pathway and the fluidic
pathway need not be entirely located on or in the same portion. The
sample introduction pathway can include one or more than one
component that can function to get a sample into a well. The sample
introduction pathway can be described as a transit path for the
sample before it is in a well. The sample introduction pathway need
not be fluidly connected at all times. For example, the sample
introduction pathway can include a portion of the device that can
be (based on for example movement of one portion with respect to
the other portion) moved into or out of the sample introduction
pathway.
[0038] The sample introduction pathway can include, for example a
sample introduction chamber and one or more than one component to
get a sample from the sample introduction chamber to a well (on the
second portion, discussed below). In some embodiments the sample
introduction pathway can include one or more than one irreversible
valve. A valve or valves that may be in the sample introduction
pathway can also be described as not including moving parts. In
some embodiments the sample introduction chamber can be located on
or in the first portion. The sample introduction pathway can for
example include a valve(s), a filter(s), or some combination
thereof. In some embodiments the sample introduction pathway can
utilize the introducer portion of the first portion. In some
embodiments the sample can be moved from a sample introduction
chamber to a sample well on the second portion.
[0039] In some embodiments, a sample introduction pathway can be
configured to introduce sample directly into a fluidic pathway or a
fluid channel that is part of a fluidic pathway. In such
embodiments, the sample introduction pathway would be configured to
deposit a sample into the fluidic pathway without first depositing
it into a sample well. Such configurations could be especially
useful or applicable to instances where the sample size is
relatively small. In some embodiments, such configurations could be
utilized for sample sizes of not greater than 100 .mu.L, for
example. An example of such a sample could include a quantity of
blood obtained via a finger prick.
[0040] FIG. 1 shows a fluid channel 112 that is part of the fluidic
pathway. The fluid channel 112 can be formed (i.e., top, bottom and
sides) from more than one component or piece of the first portion.
In some embodiments, the fluid channel 112 does not contain any
fluid valves. Illustrative fluid channels can be described by their
volumes, either by their total volumes or by the volume both before
and after the sensor. In some embodiments, illustrative fluid
channels can have volumes of 10 .mu.L to 1000 .mu.L in the region
before the sensor and 10 .mu.L to 1000 .mu.L in the region after
the sensor. In some embodiments, illustrative fluid channels can
have volumes of 50 .mu.L to 250 .mu.L in the region before the
sensor and 50 .mu.L to 250 .mu.L in the region after the sensor. In
some embodiments, illustrative fluid channels can have volumes of
75 .mu.L to 200 .mu.L in the region before the sensor and 75 .mu.L
to 200 .mu.L in the region after the sensor. In some embodiments,
illustrative fluid channels can have volumes of 100 .mu.L to 175
.mu.L in the region before the sensor and 100 .mu.L to 175 .mu.L in
the region after the sensor. It should also be understood that the
volumes before and after the sensor need not be the same.
[0041] The first portion also includes a fluid actuator 114.
Although fluid actuator 114 is depicted as being at one end of the
fluid channel 112, it should be understood that a fluid actuator
could be located at any point along the fluid channel 112, could be
located at multiple points along the fluid channel 112, and/or
could have multiple components at multiple points along the fluid
channel 112. The fluid actuator 114 functions to move fluid along
the fluid channel 112. It can also be described that the fluid
actuator 114 functions to move fluid along, into, out of, within
(or any combination thereof) the fluid channel 112.
[0042] The fluid actuator 114 can be as simple as a port or as
complex as a pump or diaphragm. In some embodiments, the fluid
actuator 114 can be a port at the end of the fluid channel 112 (for
example such as that depicted in FIG. 1) that is in fluid
communication with a pump located external to the first portion. In
some embodiments, the fluid actuator 114 is a port that is in fluid
communication with a pump that is located on or within an external
instrument that is configured to control and/or manipulate the
sensor assembly. In some embodiments, the fluid actuator 114 can be
a port that is in fluid communication with an entire fluidic
control system. Illustrative fluidic control systems can include a
pump(s), diaphragm(s), valve(s), further fluid channel(s),
reservoir(s), or some combination thereof. In some embodiments, at
least portions of the illustrative fluidic control system can be
located on or within an external instrument, the first portion of
the sensor assembly, the second portion of the sensor assembly, or
some combination thereof. In some embodiments, the fluid actuator
114 can include a diaphragm that is in fluid communication with
some portion of a fluidic control system.
[0043] The first portion also includes an introducer 116. The
introducer 116 is on, within, or fluidly attached to the fluid
channel 112 and functions to access the wells of the second portion
(discussed below). The function of the introducer 116 can also be
described as being configured to obtain at least a portion of the
contents of at least one well on the second portion. The introducer
116 can be described as being able to both puncture sealed wells of
the second portion and access and obtain at least a portion of the
material in the well. The introducer 116 can be actuated by an
external instrument in order to access the wells. Such actuation
can include movement in one or more than one dimension. For
example, in the example depicted in FIG. 1, movement of the
introducer 116 in the z direction could afford access to at least
one well on the second portion.
[0044] In some embodiments, the introducer 116 can also be
configured to introduce air into a well it has accessed. This may
allow the introducer 116 to more reliably obtain material from the
wells. This optional function of the introducer 116 can be realized
by the particular design of the tip of the introducer, by
puncturing the seal to the well at two (instead of one) points
simultaneously, at different times in a specified order, or by
combinations thereof. In some embodiments, the introducer 116 can
be similar in shape and configuration to a pipette tip.
[0045] The introducer 116 can also be configured to both extract
material from a well of the second portion and introduce material
into a well of the second portion. In such embodiments, the
external instrument, in some embodiments through control of a pump
for example, can control whether the introducer 116 is extracting
or introducing material from or into the well. Introducing material
into a well can allow for storage of materials, while not requiring
a user to have concerns about liquids spilling out of a used sensor
assembly. Introducing material into a well can also provide a
method of mixing. Introducing material into a well can also provide
a method of storing an intermediate composition while another step
of a protocol is being carried out.
[0046] In some embodiments, the first portion 110 can also include
a sensor 118. A sensor in a first portion can be any type of
sensor, for example it could be an optical sensor (using for
example chemiluminescence or fluorescence), an electrochemical
sensor, or a resonant sensor. In some embodiments, the sensor 118
can include at least one thin film resonator sensor, such as a thin
film bulk acoustic resonator (TFBAR) sensor. A TFBAR sensor
includes a piezoelectric layer, or piezoelectric substrate, and
input and output transducer. TFBAR sensors are small sensors making
the technology particularly suitable for use in handheld or
portable devices.
[0047] FIGS. 2A and 2B, general operating principles of a
bulk-acoustic wave piezoelectric resonator 20 used as a sensor to
detect an analyte are shown. The resonator 20 typically includes a
planar layer of piezoelectric material bounded on opposite sides by
two respective metal layers which form the electrodes of the
resonator. The two surfaces of the resonator are free to undergo
vibrational movement when the resonator is driven by a signal
within the resonance band of the resonator. When the resonator is
used as a sensor, at least one of its surfaces is adapted to
provide binding sites for the material being detected. The binding
of the material on the surface of the resonator alters the resonant
characteristics of the resonator, and the changes in the resonant
characteristics are detected and interpreted to provide
quantitative information regarding the material being detected.
[0048] By way of example, such quantitative information may be
obtained by detecting a change in the insertion phase shift of the
resonator caused by the binding of the material being detected on
the surface of the resonator. Such sensors differ from those that
operate the resonator as an oscillator and monitor changes in the
oscillation frequency. Rather such sensors insert the resonator in
the path of a signal of a pre-selected frequency and monitor the
variation of the insertion phase shift caused by the binding of the
material being detected on the resonator surface.
[0049] In more detail, FIG. 2A shows the resonator 20 before the
material being detected is bound to its surface 26. The depicted
resonator 20 is electrically coupled to a signal source 22, which
provides an input electrical signal 21 having a frequency f within
the resonance band of the resonator. The input electrical signal is
coupled to the resonator 20 and transmitted through the resonator
to provide an output electrical signal 23. The output electrical
signal 23 is at the same frequency as the input signal 21, but
differs in phase from the input signal by a phase shift
.DELTA..PHI..sub.1, which depends on the piezoelectric properties
and physical dimensions of the resonator. The output signal 23 is
coupled to a phase detector 24 which provides a phase signal
related to the insertion phase shift.
[0050] FIG. 2B shows the sensing resonator 20 with the material
being detected bound on its surface 26. The same input signal is
coupled to the resonator 20. Because the resonant characteristics
of the resonator are altered by the binding of the material as a
perturbation, the insertion phase shift of the output signal 25 is
changed to .DELTA..PHI..sub.2. The change in insertion phase shift
caused by the binding of the material is detected by the phase
detector 24. The measured phase shift change is related to the
amount of the material bound on the surface of the resonator.
[0051] In an alternative to measuring the insertion phase of the
resonator, a directional coupler is added between the signal source
and the resonator with the opposite electrode grounded. The phase
detector is configured to measure the phase shift of the reflection
coefficient as a result of material binding to the resonator
surface.
[0052] Additional details regarding sensor devices and systems that
may employ TFRs are described in, for example, U.S. Pat. No.
5,932,953 issued Aug. 3, 1999 to Drees et al., which patent is
hereby incorporated herein by reference in its entirety to the
extent that it does not conflict with the disclosure presented
herein. Additionally, the sensor can utilize amplification schemes
such as that disclosed in PCT Application No. PCT/US14/27743 filed
on Mar. 14, 2014 entitled: Thin Film Bulk Acoustic Resonator With
Signal Enhancement, the disclosure of which is incorporated herein
by reference in its entirety to the extent that it does not
conflict with the disclosure presented herein.
[0053] As discussed above, the binding sites for the material being
detected can be utilized in combination with a resonant sensor. The
binding sites for the material being detected could also be
utilized with other types of sensors (examples of which were
mentioned above and may include optical sensors such as
chemiluminescent or fluorescent sensors and electrochemical
sensors). In some embodiments the binding sites for the material
being detected could also be utilized without an associated sensor
in the fluidic pathway. In such embodiments, the fluidic pathway
could be characterized as including a binding region (instead of a
sensor that may include binding sites for the analyte of interest).
The binding region could be configured with the binding sites being
a material immobilized thereon. The immobilized material could be
any material capable of interacting with an analyte of interest in
such a way that would allow the analyte of interest to be analyzed.
The immobilized material could include any component that
selectively binds to the analyte of interest. By way of example,
the immobilized material may be selected from the group consisting
of nucleic acids, nucleotide, nucleoside, nucleic acids analogues
such as PNA and LNA molecules, proteins, peptides, antibodies
including IgA, IgG, IgM, IgE, lectins, enzymes, enzymes cofactors,
enzyme substrates, enzymes inhibitors, receptors, ligands, kinases,
Protein A, Poly U, Poly A, Poly lysine, triazine dye, boronic acid,
thiol, heparin, polysaccharides, coomassie blue, azure A,
metal-binding peptides, sugar, carbohydrate, chelating agents,
prokaryotic cells and eukaryotic cells.
[0054] In some embodiments, the sensor 118 can be within or form
part of the fluidic pathway. More specifically, in some
embodiments, the sensor 118 can be within or form part of the fluid
channel. For example, a portion of the fluidic pathway can be
configured to exist within or form part of the fluidic pathway so
that fluid in the fluidic pathway flows over the sensor. In some
embodiments, the fluid in the fluidic pathway can travel completely
around the sensor, and in other embodiments, the fluid in the
fluidic pathway can travel around less than all surfaces of the
sensor. In some embodiments, the fluid in the fluidic pathway can
travel across the active region of the sensor. In some embodiments,
the fluid in the fluidic pathway can flow over the piezoelectric
layer of the sensor, which is coated with binding sites for an
analyte of interest.
[0055] In some embodiments, the sensor can be part of a sensor
board. Illustrative sensor boards can include a hole, slot or pass
through that allows the sensor to be part of the fluidic pathway.
For example, the sensor or more specifically at least the
piezoelectric layer of the sensor can be positioned within or over
a slot or void in a sensor board. A specific example of such a
configuration can be seen in FIG. 3. FIG. 3 shows a sensor board
305 that includes a sensor 310, the sensor can have characteristics
such as those discussed above and includes a piezoelectric layer.
Within the sensor board is a hole, void, or slot 315. The sensor
310 is positioned so that at least the piezoelectric layer of the
sensor is within or positioned over the slot 315. The slot 315 is
in fluid communication with the fluidic pathway. More specifically,
a first sensor port 320 is fluidly connected to a first portion of
the slot 315 and a second sensor port 322 is fluidly connected to a
second portion of the slot 315. The first and second sensor ports
320 and 322 are part of the fluidic pathway present in a first
portion of the sensor assembly. The configuration of the slot 315
and the piezoelectric layer of the sensor 310 with respect to the
first and second sensor ports 320 and 322 render the piezoelectric
layer of the sensor 310 part of the fluidic pathway or place it
within the fluidic pathway. It should also be noted that other
elements, such as for example, adhesives, films, etc. can be
utilized in combination with the first and second ports 320 and
322, the sensor 310 and the slot 315 in order to form the fluidic
pathway with the piezoelectric layer of the sensor 310 as part of
or within the fluidic pathway.
[0056] FIG. 8 depicts an illustrative configuration of a sensor and
a sensor board. The illustrative device 800 can include a sensor
801 and a board 803. The board 803 can also be referred to as an
electrical connection board. The board 803 can be part of a
flexible circuit board. The flexible circuit board can also be
referred to as a printed circuit board (PCB). The flexible circuit
board can include additional structures, components, devices, or
some combination thereof not specifically discussed herein. The
board 803 can be described as having a first surface 806 and an
opposing second surface 804. Board 803 can also be characterized as
having a thickness, given as thickness.sub.board in FIG. 8. The
board 803 also includes a slot 802.
[0057] The sensor 801 can be any type of sensor. In some
embodiments the sensor 801 can be an optical sensor (for example a
chemiluminescent sensor or a fluorescent sensor) or a resonant
sensor, for example. In some embodiments the sensor 801 can be a
resonant sensor, such as a thin film bulk acoustic resonator
(TFBAR) sensor. In some embodiments the sensor 801 can be in TFBAR
sensor such as those discussed above. The sensor 801 is generally
positioned on the board 803. The sensor 801 is positioned on the
first surface 806 of the board. The sensor 801 spans the slot 802
of the board 803.
[0058] The illustrative device 800 also includes at least one, and
in this embodiment two offsets 805.
[0059] The at least one offset 805 can be described as being
positioned between the sensor 801 and the first surface 806 of the
board 803. FIG. 8 shows that the offset 805 can be described by the
height or thickness thereof, height.sub.offset.
[0060] The device 800 depicted in FIG. 8 also includes a sensor
opposing member 811. The sensor opposing member 811 is positioned
adjacent the second surface 804 of the board 803. The sensor
opposing member 811, like the sensor 801 spans the slot 802 of the
board 803. The sensor opposing member 811 can include numerous
types of material. In some embodiments the sensor opposing member
811 can include polymeric materials. In some embodiments the sensor
opposing member 811 can be described as flexible, and in some
embodiments the sensor opposing member 811 can be described as
rigid. In some embodiments the sensor opposing member 811 can
include an adhesive property. In some embodiments the sensor
opposing member 811 can include a polymeric material in combination
with an adhesive material. In some embodiments the sensor opposing
member 811 can be a pressure sensitive adhesive material.
Illustrative pressure sensitive adhesive materials can include a
polymeric film having an adhesive material coated on at least a
portion thereof. Illustrative materials for the sensor opposing
member 811 may be chosen based at least in part on the chemical
nature thereof. For example the material could be chosen because it
is relatively inert, it has relatively low levels of protein
binding, or some combination thereof. As seen in FIG. 8, the
combination of the board 803, the sensor 801, the offset 805, and
the sensor opposing member 811 form a channel 813. The channel 813
in FIG. 8 is shown as dashed. The channel 813 may be part of or
maybe contained within the fluidic pathway discussed above. More
particularly the channel 813 may be part of or may be contained
within the analysis channel of the fluidic pathway discussed
above.
[0061] The height of the channel 813, given as height.sub.channel
is the sum of height.sub.offset and thickness.sub.board. In some
embodiments height.sub.channel can be as small as 0.003 inches
(about 0.07 millimeters (mm)) and in some embodiments as small as
0.008 inches (about 0.2 mm). In some embodiments height.sub.channel
can be as large as 0.020 inches (about 0.5 mm), in some embodiments
as large as 0.015 inches (about 0.4 mm), or in some embodiments as
large as 0.012 inches (about 0.3 mm). A channel 813 that has a
smaller height may be able to provide that a test could be run in a
shorter period of time. The height of the channel 813 can affect
the analysis time based at least in part on the linear velocity of
the material going through the channel. The linear velocity of the
solution relatively close to the surface where binding is to occur
could be considered the most relevant factor. Because of the
parabolic laminar flow profile, given the same average linear
velocity, a shallower channel height will provide faster reaction
times than a taller channel (up to the kinetic limit of the binding
event). As the linear velocity increases the time necessary for an
analysis that utilizes binding of two materials becomes less
dependent on diffusion and more dependent on reaction kinetics.
Because the diffusion is generally the rate limiting step, having a
test that is more dependent on reaction kinetics provides a faster
test. In some embodiments the channel 813 can be configured to
provide a linear velocity therethrough that can be at least 0.1
mm/second, and in some embodiments at least 0.2 mm/second. In some
embodiments the channel 813 can be configured to provide a linear
velocity therethrough that can be not greater than 100 mm/second,
in some embodiments not greater than 80 mm/second, and in some
embodiments not greater than 20 mm/second.
[0062] The sensor 801 is electrically connected to the board 803.
This allows the sensor 801 to be electronically monitored,
controlled or some combination thereof via a device that could be
electrically connected to the board 803. In the illustrative
embodiment depicted in FIG. 8, the sensor 801 is electrically
connected to the board 803 by the at least one offset 805. In the
particular illustrative embodiment depicted in FIG. 8 two offsets
805 are included. In this particular embodiment, the offsets 805
can include electrically conductive material. For example the
offsets 805 may be electrically conductive adhesive, or an
electrically conductive metal or alloy (for example solder). In
some embodiments the offsets 805 may be solder. In such embodiments
the offsets 805 may be encapsulated with a secondary material. The
secondary material may be chosen to, for example provides further
structural stability to the channel, insulates the offsets 805, or
some combination thereof. In some embodiments the secondary
material may include an electrically insulating polymeric material,
for example underfill.
[0063] In some embodiments the at least one offset 805 functions
only as part of the channel 813 and is not electrically connect the
sensor 801 to the board 803. In such embodiments, a separate
structure can be utilized to electrically connect the sensor 801 to
the board 803. For example, wire bonds may be utilized to
electrically connect the sensor 801 to the board 803.
[0064] Second Portion
[0065] Disclosed assemblies also include a second portion. The
second portion can include at least one well. FIG. 1 depicts an
illustrative second portion 120 that includes a plurality of wells
122. Disclosed second portions of the assembly can include any
number of wells. In some embodiments, a second portion can include
at least one (1), at least three (3), or at least five (5) wells.
In some embodiments, a second portion can include nine (9) wells
with one being a sample well.
[0066] The wells within a second portion can be configured to
contain the same or different volumes. In some embodiments, the
wells can be of a size to contain at least 10 .mu.L. In some
embodiments, the wells can be of a size to contain from 50 .mu.L to
150 .mu.L, for example. In some embodiments, the wells can be of a
size to contain about 100 .mu.L for example. In some embodiments,
the wells can have a total volume that is more than the quantity
which they are designed to hold. For example, a well can have a
total volume that is 200 .mu.L in order to house a volume of 100
.mu.L. The wells can have various configurations, including for
example corners, flat bottoms, and round bottoms. The wells can
have various shapes, for example, they can be cylindrical, or
spherical, hexagonal, or otherwise.
[0067] Wells within a second portion can contain various materials
or can be empty. In some embodiments, a second portion can include
at least one well that is empty. In some embodiments a second
portion can include at least one sample well. The sample well can
generally be empty before the assembly is used. The sample well in
such embodiments can be utilized to hold at least a portion of the
sample transferred from a sample introduction chamber via the
sample introduction pathway. In some embodiments, the sample well
can include one or more than one materials, which the sample will
be combined with upon introduction into the sample well.
[0068] Materials contained within wells can be liquid or solid.
Materials contained within wells can also be referred to as
reagents, diluents, wash solutions, buffer solutions, or other such
terms. In some embodiments, material within a well can be a single
material that is a liquid at room temperature, a solution
containing more than one material, or a dispersion containing one
material dispersed in another. In some embodiments, material within
a well can be a solid. The material within an individual well can
be independently selected with respect to materials in other wells.
In some embodiments, the materials within a well are selected to
carry out a particular testing protocol.
[0069] The second portion can also include a seal. Generally, the
seal functions to contain the materials within the wells. In some
embodiments, the seal can be a unitary element, while in some
embodiments, the seal can be made up of more than one element. For
example, with reference to FIG. 1, in some embodiments, a single
element could cover all of the wells 122. While in some other
embodiments, each well 122 could be covered by an individual
element, with all of the elements making up the seal. An exemplary
seal is illustrated in FIGS. 4A and 4B. FIGS. 4A and 4B shows the
seal 430 which is illustrated as the dashed line that covers the
entire surface of the second portion 420. In other embodiments, not
depicted herein, only the wells 422 of the second portion 420 could
be covered with individual elements, the entirety of which can be
considered as making up the seal.
[0070] The seal can be made of any material that can function to
maintain the contents of the wells within the wells, but also allow
the introducer 416 (in FIGS. 4A and 4B) access to the materials in
the wells. Illustrative materials can include, for example, a foil,
such as a metallic foil which can be sealed to the second portion
(or portions thereof) via an adhesive or heat sealing; plastic
films; or other such materials. In some embodiments, the seal is
made of a metallic foil and covers the entirety of the second
portion.
[0071] The second portion can also include a way of introducing a
sample either directly or indirectly from a user. For example, in
some embodiments, a second portion can include an empty well, whose
seal can be pierced (if it is sealed) by a portion of a disclosed
assembly or a user to introduce a sample to be tested by the sensor
assembly. This well can be referred to as the sample well. In some
embodiments, the sample well is not covered by the seal. In some
embodiments where the sample is introduced directly to the second
portion by a user it can be added to the sample well via a syringe,
a pipette, or other similar instruments. In some embodiments, the
sample can be added to a sample well via, for example a sample
introduction pathway.
[0072] External Instrument
[0073] Disclosed assemblies can be utilized in combination with an
external instrument. Illustrative external instruments can be bench
top type and sized instruments, small hand-held type and sized
instruments, or anything in between for example. In some
embodiments, the external instrument can be a hand-held type
instrument that is configured and designed for disclosed assemblies
to be controlled and interrogated thereby. In some embodiments, the
hand-held type external instrument can be configured to work with
multiple assemblies (in some embodiments, assemblies that differ
based on containing at least one different material in one well)
that are designed for running multiple different analyses.
[0074] Such external instruments can be configured to control
various features of the assembly. For example, an external
instrument can be configured to be in fluid communication with the
fluid actuator of the first portion of the assembly. The external
instrument can then control fluid flow within the fluidic pathway.
The external instrument can include a pump (or pumps), such as a
syringe pump, piston pump, a screw pump, a peristaltic pump, a
diaphragm pump, a solenoid pump, or similar devices. The external
instrument can also include one or more other fluid path
components, for example valves, couplers, etc. The external
instrument can also include a control assembly for controlling the
pump(s), valves, and other fluid path components. The external
instrument can also be configured to control the movement of one of
the portions of the assembly with respect to the other portion. The
external instrument can include mechanisms for actuating one of the
portions with respect to the other (for example the second portion
with respect to the first portion) and control circuitry for
controlling the mechanisms for actuating, for example. The external
instrument can also include an electrical connection(s) for the
sensor, hardware and software for monitoring the sensor, or
combinations thereof.
[0075] It should also be noted that in some embodiments, the
components noted above as being located within the external
instrument: pump(s), other fluidic pathway components, control
assemblies for controlling the fluidic pathway, control assemblies
for controlling the movement of one portion with respect to the
other portion, electrical connection(s); other components not
discussed herein; or any combination thereof, can be located within
the sensor assembly, for example within or on the first
portion.
[0076] Disclosed fluidic pathways can allow for two way flow of
material within the fluidic pathway. Two way flow may be enabled
and/or enhanced by a number of features of the sensor assembly
and/or the external instrument. For example, a pump within the
external instrument can either be bi-directional or two pumps can
be included. For example, the ability to randomly access the wells
in the second portion can allow material to be accessed and
returned. For example, an empty well can afford additional optional
volume within the fluidic pathway (via access by the introducer)
for permanent or temporary storage of material. For example, the
fluidic pathway may have sufficient volume on both sides of the
sensor to allow flow of the material across the sensor in both
directions.
[0077] Two way flow can enable mixing of various materials. For
example, the sample can be aspirated from the sample well (flow
away from the second portion), the second portion can be moved with
respect to the first portion to place a different well beneath the
introducer, and then the sample can be delivered to the well (flow
towards the second portion). Two way flow can also accomplish
thorough mixing of one material (or solution) with another material
(or solution). This could be accomplished, for example, by
aspirating the contents of a well out of the well and then
returning it to the well. The act of returning the contents to the
well from the introducer will effectuate mixing. There are numerous
other examples of instances where two way flow could be
advantageous, for example for diluting, reacting etc. Two way flow
can also be advantageous for allowing the sample to interact with
the sensor. For example, the sample (once it has been diluted, for
example and/or filtered, reacted, etc.) can be moved across the
sensor in a first direction and then flow can be reversed so the
sample is moved across the sensor in the opposite direction. Two
way flow can also allow limited sample volumes to be run across the
sensor at fast flow rates for an extended period of time.
[0078] Disclosed herein are methods of mixing. Disclosed methods
can utilize assemblies such as those discussed above. Disclosed
methods can include a step of placing a sample in a sample
introduction chamber. The sample introduction chamber can be on the
first portion or the second portion. In some embodiments, the
sample introduction chamber is on the first portion and this step
transfers the sample from the sample introduction chamber on the
first portion to a sample well (which may or may not be empty
before use) on the second portion. In some embodiments, this step
can be accomplished by using a sample introduction pathway as
described above.
[0079] A next step in illustrative methods includes obtaining at
least a portion of a material from a well on the second portion and
depositing that material in the fluidic pathway. This step can be
accomplished by using the introducer. The introducer can be
controlled, via an external instrument for example, to access the
well containing the material and deposit it in the fluidic pathway.
The material obtained in this step may depend at least in part on
the particular analysis being accomplished.
[0080] A next step in illustrative methods includes obtaining at
least a portion of the sample from the sample well on the second
portion and depositing that material in the fluidic pathway. This
step can be accomplished by using the introducer. The introducer
can be controlled, via an external instrument for example, to
access the sample well and deposit it in the fluidic pathway. It
should be noted that this step need not transfer all of the sample
from the sample well into the fluidic pathway.
[0081] A next step in illustrative methods includes actuating fluid
in the fluidic pathway. The fluid in the fluidic pathway is
actuated in order to mix the sample with the material from the
well. More specifically, the step can be accomplished by placing at
least a portion of the sample and the material from the well in a
third well on the second portion. This third well may be empty
before the sample and the material is placed therein. The act of
placing the material and the sample in the third well will afford
mixing of the sample and the material.
[0082] Optionally after the sample and the material are placed in
the third well, the mixed composition (containing the sample and
the material upon mixing) can be taken up from the third well.
Re-depositing this material back in the third well (for example)
can effectuate mixing. The steps of obtaining the composition and
re-depositing it back in the well can be repeated any number of
times. In some embodiments it can be repeated twice. In some
embodiments it can be repeated at least two times.
[0083] A next step in illustrative methods includes actuating fluid
in the fluidic pathway so that fluid reaches the sensor. This step
can be accomplished via the fluid actuator on the first portion.
More specifically, this step could be accomplished by a pump, for
example located on an external instrument in fluid communication
with the fluid actuator on the first portion. A next step includes
monitoring at least one signal from the sensor. This step can be
accomplished via an external instrument as discussed above. In some
embodiments the step of actuating the fluid in the fluidic pathway
so that the fluid reaches the sensor can be accomplished by
reversing the direction of flow in the fluidic pathway at least
once. In some embodiments the direction of flow can be reversed at
least two times.
[0084] A next step in the illustrative methods includes depositing
at least some of the fluid in the fluidic pathway into the second
portion of the assembly. More specifically, at least some of the
fluid from the fluidic pathway could be placed in a well in the
second portion of the assembly. In such embodiments the well that
is utilized may be one that was empty before the method was carried
out, one that originally contained a material, or the sample
well.
[0085] Disclosed assemblies can offer the advantage of being able
to randomly access the wells within the second portion. Random
access of the wells may be enabled and/or enhanced by the ability
to move one of first or second portion with respect to the other.
This allows the introducer to access any of the wells at any time.
More specifically, the ability to randomly access the wells may be
enabled and/or enhanced by at least two dimensional movement of one
portion with respect to the other portion. In some examples, the
ability to randomly access the wells may be enabled and/or enhanced
by three dimensional movement of one portion with respect to the
other portion. An example of this can be seen in FIGS. 4A and 4B,
which shows movement of the second portion with respect to the
first portion in the x, y, and z directions. This particular
embodiment moves the second portion around a fixed point and also
moves it up and down in the z direction.
[0086] Random access to the wells can enable access to any material
present in the second portion at any time, not in a sequential
manner for example. This can afford more flexibility in the variety
of analyses that could be undertaken with the disclosed assemblies.
Disclosed assemblies can therefore accommodate a large breadth of
protocols and eliminate technological hurdles that existed in
previous consumable designs. Previously utilized devices could be
quite complex when multiple sample steps were integrated into the
devices. Furthermore, slight changes in the protocol could
potentially require a complete re-design of previously utilized
devices. The ability to randomly access the wells provides a device
that can overcome these and other drawbacks of previously utilized
devices by providing an assembly that can accommodate variably
different protocol configurations while simultaneously removing
somewhat cumbersome constraints on the protocols being used.
[0087] Random access to wells can also offer different methods of
mixing materials by adding a material to a well from another well,
mixing in the well and then removing the mixed solution. Random
access to wells can also allow the material to be returned to an
already accessed well, an intentionally empty well, or both. This
can afford an assembly that can function to contain all liquid
material once the test is complete. Such a characteristic could be
relevant from a safety and/or cleanliness standpoint.
[0088] As noted above, the second portion, which is entirely
separate from the first portion until the assembly is put together,
includes all of the materials necessary to run a protocol. In some
embodiments, the second portion can include all non-bound materials
(e.g., the binding material present in the fluidic pathway)
necessary to run a protocol. In some embodiments, the first portion
does not include any reagents or materials that are not bound to a
surface. Because all of the non-bound materials are located on the
second portion, the assembly can offer an analysis platform that
may be relatively easy to utilize and/or modify for numerous
different analyses. For example, if a different protocol is
desired, the second portion merely needs to have the appropriate
materials contained within the wells. The control assemblies for
movement of one portion with respect to the other and the fluidic
pathway (whether within an external instrument, the first portion,
or some combination thereof) can then be configured to run the
protocol with the different materials (reagents) being accessed
from the second portion. Manufacturing efficiencies could be gained
by being able to manufacture the first portion including the sensor
without the need to load any materials (such as liquids, for
example) on or into the first portion.
[0089] In some embodiments, an entirely different protocol can be
undertaken using disclosed assemblies merely by changing one or
more materials within the wells of the second portion. This can
make such disclosed assemblies more commercially viable because the
manufacture of the first portion need not change at all for
different analyses. Furthermore, the manufacture of the second
portion need not change either, different materials simply need be
deposited into the wells during the manufacture process. Because
different molds, dies, fixtures, etc., would not need to be made to
extend the assembly to different protocols, disclosed assemblies
could be commercially more successful for use as a multiple
platform analysis system. The ability to run a number of different
protocols using virtually the same assembly, can make systems that
include disclosed assemblies and external instruments equivalent in
function to large automated systems that would likely be much more
expensive for an end user. Likewise the "porting" of assays from
such large automated systems to the disclosed assemblies could
potentially be relatively straight forward.
[0090] In some embodiments, the assembly can be considered to be a
consumable. A "consumable" as utilized herein implies that the
particular component will be discarded after use. The more
inexpensive a consumable assembly is to manufacture, the more
likely it is to be commercially successful. In some embodiments,
disclosed assemblies do not include any valves within the fluidic
pathway. This can make them less expensive to manufacture, when
compared with fluidic pathways including valves. Disclosed
valve-less assemblies could therefore be more apt to be
commercially successful because of lower costs of manufacture and
higher reliability.
[0091] Systems
[0092] Disclosed assemblies can be used in combination with another
instrument, for example external instruments. As such, systems are
disclosed utilizing disclosed assemblies and external instruments.
Characteristics of both the assemblies and systems that were
described above are also applicable to instances in which they are
contained within a system. Disclosed systems can be assembled,
configured or used by an end user, for example.
[0093] Methods
[0094] Disclosed devices (assemblies) and systems can be utilized
to carry out various disclosed methods. An illustrative method can
include a number of steps. For example, disclosed methods can
include a step or steps of placing a sample in the sample
introduction chamber. Any suitable method for sample collection and
introduction can be utilized. Suitable methods for collection and
introduction may change based on the type of sample and the target
analyte to be detected.
[0095] Disclosed methods can also include steps of obtaining
materials (either reagents originally contained in the wells or
sample deposited into the sample introduction chamber) from one or
more wells. Generally, such steps can be carried out by moving the
first or second portion with respect to the other and moving fluid
into or within the fluidic pathway, or combinations thereof. More
specifically, such steps could be accomplished by moving a second
portion (for example) with respect to a first one (e.g., in two
dimensions for example x and y or rotationally) to align the
correct well with the introducer and then move the second portion
(for example) with respect to the first portion in a third
dimension (for example z) to pierce a seal (if present) and obtain
material from the well. Such steps can be controlled by a control
assembly (and related circuitry and hardware as necessary) in the
external instrument, for example.
[0096] Disclosed methods can also include a step (or steps) of
actuating fluid in the fluidic pathway. Such steps could include,
for example moving fluid into or out of wells, moving fluid back
and forth in the fluidic pathway, moving fluid across (one or both
ways) the sensor, or combinations thereof. Such steps can be
controlled by a control assembly (and related circuitry and
hardware as necessary) in the external instrument, for example.
[0097] Disclosed methods can also include a step (or steps) of
monitoring a least one signal from a sensor. The signal to be
sensed would depend at least in part on the type of sensor. The
signal to be sensed in embodiments where the sensor is a resonant
sensor can include, for example frequency, phase, frequency change,
phase change, or any combination thereof. Other signals, not
discussed herein, can also be monitored. The signal to be sensed in
embodiments where the sensor is an optical sensor can include, for
example voltage (from an image sensor for example) or current (from
a photodiode). In embodiments where the sensor is an
electrochemical sensor, the signal can be current, potential, or
both, for example. Such steps can be controlled by a control
assembly (and related circuitry and hardware as necessary) in the
external instrument, for example.
[0098] Disclosed methods can also include a step (or steps) of
depositing material into a well. In some embodiments, material can
be deposited into a well that was previously empty, or a well that
previously had material therein. Such a step can be enabled and/or
allowed by the ability to utilize two way flow in the fluidic
pathway and to randomly access the wells on the second portion.
Depositing material into a well can allow the system to be one that
keeps the sample (which could be considered dangerous) contained
after the analysis has been carried out. This allows the user to
dispose of the entire cartridge, simultaneously disposing of the
spent sample and any reagents that were utilized. Such steps can be
controlled by a control assembly (and related circuitry and
hardware as necessary) in the external instrument, for example.
[0099] Uses
[0100] The devices, systems, and methods described herein may be
employed to detect a target analyte in a sample. The devices may
find use in numerous chemical, environmental, food safety, or
medial applications. By way of example, a sample to be tested may
be, or may be derived from blood, serum, plasma, cerebrospinal
fluid, saliva, urine, and the like. Other test compositions that
are not fluid compositions may be dissolved or suspended in an
appropriate solution or solvent for analysis.
[0101] Non-limiting examples of target analytes include nucleic
acids, proteins, peptides, antibodies, enzymes, carbohydrates,
chemical compounds, or infectious species such as bacteria, fungi,
protozoa, viruses, pesticides and the like. In certain
applications, the target analyte is capable of binding more than
one molecular recognition component.
[0102] The present disclosure is illustrated by the following
examples. It is to be understood that the particular examples,
assumptions, modeling, and procedures are to be interpreted broadly
in accordance with the scope and spirit of the disclosure as set
forth herein.
EXAMPLES
Example 1
Sensor Assembly Including Linear Second Portion
[0103] An example of a specific disclosed embodiment is shown in
FIG. 5A. The sensor assembly 500 includes a second portion 502 that
includes six (6) wells (exemplified by well 504). In this
particular embodiments, the second portion 502 is has a linear
configuration. The remaining components shown in FIG. 5A make up
the first portion 506 of the sensor assembly. Although not entirely
visible in FIG. 5A, the cartridge 508, which is the external
housing of the first portion 506, includes a fluidic pathway
therein. The fluidic pathway terminates at one end at the
introducer 510, which in this particular embodiment can function
both as a tool to puncture the seals on the wells 504 and a pipette
tip to access and aspirate materials from the wells. Also included
within the first portion is the sensor 512. The sensor can be as
described above and includes a piezoelectric layer that forms part
of the fluidic pathway. The sensor 512 in this embodiment is housed
on a sensor board, which includes a slot there through to enable
the piezoelectric layer of the sensor to form part of the fluidic
pathway. This particular illustrative sensor assembly is
constructed using two die cut adhesive (in this particular example
pressure sensitive adhesive) forms 514a and 514b.
[0104] FIG. 5B shows the sensor assembly in an assembled form. As
seen there, the second portion is completely inserted into a
specifically designed track in the first portion and the wells 504
are ready to be accessed by the introducer 510. FIG. 5C shows the
sensor assembly after the second portion 502 has been moved in a
linear fashion so that the first well 504a (which is an arbitrary
definition) of the second portion 502 can be accessed by the
introducer 510.
[0105] The particular embodiment of a sensor assembly illustrated
in FIGS. 5A, 5B, and 5C can be constructed using die cut adhesives
and rapid cure UV-glue assembly that minimizes temperature rise.
The channel height of the fluidic pathway above the sensor is
defined by the thickness of the circuit board that the sensor is
mounted to and the final distance below the board the sensor sits
due to solder bump reflow. In some embodiments, the board thickness
can be from 0.007''-0.008'' and the sensor can typically sit
0.002'' below the board surface. In such embodiments, the fluidic
channel would be 0.009''-0.010'' in height above the sensor
surface. This height along with the channel width cutout in the
board (referred to above as the slot) determines the linear
velocity of the sample that flows across the sensor surface for a
given flow rate. For detection of direct binding on a mass sensor,
this linear velocity and channel height above the sensor determines
the height of the depletion layer above the reaction surface for a
given set of reaction kinetics. If the depletion layer is large,
diffusion will limit the reaction rate and reaction kinetics cannot
be accurately determined. As the linear velocity is increased, the
depletion layer decreases and reaction kinetics can be accurately
obtained. In point-of-care immunoassays for example, capture times
are desired to be as fast as possible, therefore maintaining
reaction rates at or near their kinetic limits is advantageous to
minimize assay times even when not directly measuring mass binding
such as in enzyme amplified systems.
Example 2A
Use of Example 1 Sensor Assembly in a Two-Step Enzyme-Linked
Immunoassay for TSH
[0106] A two-step enzyme-linked immunoassay was carried out as
follows using a sensor assembly as disclosed in FIG. 6. As seen in
FIG. 6, the first portion 606 includes a fluidic pathway 620 and a
sensor 612, and an introducer (not readily visible in FIG. 6). The
fluidic pathway 620 seen in the first portion 606 had approximate
volumes of 150 .mu.L before and after the sensor in the fluidic
pathway. The second portion 602 includes eight (8) wells,
exemplified by well 604. In such an embodiment, the second portion
602 can be a commercially available eight (8) well strip with no
seal that is available, for example from VWR International LLC
(Radnor, Pa.) or Greiner Bio-One (Monroe, N.C.).
[0107] The two-step enzyme-linked immunoassay was to determine
human thyroid stimulating hormone (TSH) in a human serum sample.
The sensor was spotted with an anti-human TSH monoclonal antibody
on the test resonator. The reference was spotted with a suitable
isotype control antibody. The sensor was incubated overnight at
4.degree. C. and 70% relative humidity (RH). The sensor was then
rinsed, blocked for 30 minutes in a 1% bovine serum albumin (BSA)
solution in phosphate buffered saline (PBS) buffer pH 7.2, rinsed,
dried and coated with a 2% solution of sucrose. The sensor was then
assembled into the first portion.
[0108] In the second portion, the reagent strip, well 1 contained
100 .mu.L of sensor re-hydration buffer, well 2 contained 100 .mu.L
of a mixture of human serum and secondary antibody enzyme conjugate
(Alkaline phosphatase), wells 3 to 5 contained 100 .mu.L of wash
buffer and well 6 contained 100 .mu.L of enzyme substrate (i.e.
5-bromo-4-chloro-3'-indolyphospate p-toluidine salt/nitro-blue
tetrazolium chloride (BCIP/NBT)).
[0109] The first portion and second portion were placed into an
external instrument. The external instrument indexed the second
portion so that well 1 was below the introducer (the pipette tip).
The instrument then actuated the reagent strip up to aspirate 80
.mu.L of re-hydration buffer from well 1 into the first portion.
The instrument then moved the re-hydration buffer over the sensor
to remove the protein stabilizer from the sensor surface. The
re-hydration buffer was then returned to well 1 of the second
portion.
[0110] Next the instrument indexed the reagent strip so that well 2
was below the pipette tip. The reagent strip was then actuated up
and 80 .mu.L of serum conjugate mixture was aspirated into the
first portion. The instrument then pumped the serum conjugate
mixture across the sensor for a fixed reaction time between 1 and
10 minutes, in this example about four (4) minutes. At the
completion of the reaction the mixture was then returned to well 2.
The instrument then indexed the reagent strip so that well 3 was
below the pipette tip and 80 .mu.L of wash buffer was moved across
the sensor for 30 seconds and returned to well 3. The wash sequence
was then repeated for wells 4 and 5. Well 6 was then indexed below
the pipette tip and 80 .mu.L of substrate solution was moved across
the sensor for a time between 30 and 120 seconds, in this example
about 120 seconds, and then returned to well 6. Sensor response was
read by the instrument throughout the procedure to monitor direct
binding of the diluted sample to the sensor as well as measure the
enzymatic precipitation on the sensor surface.
Example 2B
Use of Example 1 Sensor Assembly in a Two-Step Enzyme-Linked
Immunoassay for TSH with Mixing
[0111] The protocol from Example 2A can be carried out and if
desired, the sample can be loaded into a well. Material to dilute
the sample can be provided in a well, and upon dilution mixing can
be effectuated by pipetting the mixture in and out of the well
after the sample was added to the diluent (or vice versa). The
mixture can be aspirated in and out the well from one (1) to about
six (6) times.
Example 3
Sensor Assembly Including Circular Second Portion
[0112] FIG. 7A shows an exploded view of an illustration of a
specific embodiment of a sensor assembly that includes a circular
second portion. The sensor assembly 700 includes a first portion
702 and a second portion 704. The first portion 702 includes a
channel 706 and a sensor 708 on a sensor board 710. Although not
necessarily easily visible in FIG. 7A, the sensor board 710
includes a slot in which at least the piezoelectric layer of the
sensor 708 sits. The first portion 702 also includes three
different adhesive films 712a, 712b, and 712c. The adhesive films
712a, 712b, and 712c along with the channel 706 and at least a
portion of the sensor board 710 and sensor 708 form the fluidic
pathway. This particular illustrative sensor assembly also includes
a waste wick 714, which is within or in fluid communication with
the fluidic pathway. The waste wick 714 can function to contain
overflow fluid from the fluidic channel. This particular
illustrative sensor assembly also includes at least one, and in
this embodiment two hydrophobic vents 716. The hydrophobic vents
716 function to provide a liquid stop for use in metering and to
prevent liquid ingress into the instrument when using an external
pump.
[0113] The second portion 704 is circular and is configured to be
rotated around a central point. The second portion 704 includes
eight (8) wells (illustrated by well 718). The wells 718 in this
illustrative embodiment have a teardrop shape. Shapes such as a
teardrop shape may provide an advantageous use of space, but it
should also be noted that other shapes, such as circular shapes for
example could also be suitable. It should also be noted that there
are portions of the housing of the second portion that do not
include wells. The portion without a well can be utilized in order
to have a position for the introducer upon assembly of the first
and second portion. It is noted that the empty well for the
introducer to be placed in upon initial assembly cannot be the
sample introduction well, because it has to be accessible for
introduction of the sample. It should also be noted that this
function could be served by an additional empty well (instead of a
void). In this particular embodiment, the wells are sealed with one
portion or piece of material, a seal 720. In this illustrative
embodiment, the seal 720 is made of a metal foil. This particular
embodiment of the seal 720 includes two openings that are
positioned over the voids. These openings can allow advantageous
assembly with introducer placement. This particular embodiment of a
sensor assembly also includes a gasket layer 722. The gasket layer
722 can be made of any material that is somewhat compliant (to
allow for a gasket type of function), and in some embodiments, the
gasket material does not absorb a sufficient amount of liquid. The
gasket layer 722 can be advantageous because it can function to
seal the wells once they have been punctured by the introducer. In
some embodiments, the gasket layer 722 can be attached to (via
adhesive for example), or formed integrally with the seal 720.
[0114] FIG. 7B shows a perspective of a cross section of the sensor
assembly when the first portion 702 and the second portion 704 are
assembled together to form the sensor assembly. In this figure, the
introducer 724 is within the well 718, and has punctured the seal
720. Also visible in this figure is the fluidic pathway 726. FIG.
7C shows a view of the sensor board 710 sitting within the first
portion. As seen from this figure, the fluidic pathway includes the
sensor 708 via the slot 728 through a first sensor port 730 and a
second sensor port 732. FIG. 7D shows a bottom view of the
illustrative first portion 702. This view shows the sensor board
710 and a hole 734 to access the sample well. Also seen in this
figure are various elements that can assist in seating the second
portion correctly with respect to the first portion when the sensor
assembly is assembled. FIG. 7E shows a cross section view of the
portion of the first portion at the region of the sensor/fluidic
pathway region. The illustration in FIG. 7E shows the sensor 708,
the sensor board 710, the first sensor port 730, the second sensor
port 732, and the overall fluidic pathway 726. FIG. 7F shows a
bottom view of the sensor assembly 700 when the first 702 and
second 704 portions are assembled together. FIG. 7G shows a top
view of the sensor assembly 700 illustrating the first 702 portion
and the fluidic pathway 712; and the second portion with only a
well 718 visible in this view.
[0115] FIGS. 9A to 9C depict an illustrative embodiment of a
disclosed assembly. FIG. 9A shows a perspective view of the top of
the assembly 900. Visible in this view is a sample introduction
chamber 902 and a fluidic pathway 904. As seen from this view, an
assembly 900 may be housed in or be configured to have various
shapes and sizes. The various shapes and sizes may be chosen, at
least in part based on manufacturability, overall usability, size,
cost, other factors not discussed herein, or combinations thereof.
The sample introduction chamber 902 may be configured so that it
can interface with a syringe, a pipette or a disposable dropper for
example as is seen in this illustrative embodiment.
[0116] FIG. 9B shows a blown up view of a disclosed assembly in an
unassembled fashion. The assembly in FIG. 9B can include a top
cover 906. The top cover 906 can be made of any useful material,
for example some type of plastic including for example a
polyethylene (PET) substrate having a pressure sensitive adhesive
thereon. In some embodiments, the top cover 906 may form part of
one or more volumes within the fluidic pathway. An illustrative
assembly may also include a first portion 908. The illustrative
first portion 908 can include at least a fluidic pathway 904 (or
part thereof), an introducer (not visible in these figures) and a
fluid actuator 910. The illustrative assembly also includes, on or
in the first portion 908 a sensor 912 housed on an electrical
connection board 914. The electrical connection board 914 may, but
need not be configured to connect to an external instrument (not
shown herein) in a fashion disclosed in commonly assigned and
concurrently filed PCT application entitled Interconnect Device and
Module Using Same having attorney docket number 468.00060201 and
naming John Tischer as inventor. The electrical connection board
914 is electrically connected to an external instrument (not shown)
via an electrical port 940. The electrical port 940 is configured
to interface with an opposite but corresponding portion of the
external instrument that makes electrical connection with the
electrical connections on the electrical connection board 914. This
view also shows the sensor 912 that would be within the fluidic
pathway once the components are put back together. Also seen in
this view is a sensor opposing member 938. The sensor opposing
member 938 forms part of the sensor channel along with the sensor
912.
[0117] The illustrative assembly disclosed in FIG. 9B may also
include a second portion 920. The illustrative second portion may
include nine (9) wells with well 922 indicated as an example
thereof. The second portion 920 may also include a seal 924. The
seal 924 may be configured to cover at least some of the wells in
the second portion. In some embodiments, the seal 924 is configured
to cover at least those wells that contain one or more
materials.
[0118] FIG. 9C is a view of the topside of an illustrative first
portion of an assembly with various portions removed (for the sake
of clarity) and drawn to show features present on both the top and
the bottom. Seen therein is the fluid actuator 910. In this
illustrative embodiment, the fluid actuator 910 is a port that is
configured to connect to fluidly connect with a pump of an external
instrument once the assembly is operably disposed within the
external instrument. FIG. 9C also shows the region 915 where the
electrical connection board having the sensor would be located
electrically connected thereto.
[0119] Also shown in FIG. 9C is the fluid channel 930 and the
sample introduction pathway 932. The sample introduction pathway
932 obtains a sample from the sample introduction chamber 902
transfers it through the sample introduction pathway 932 and
deposits it into a well (not shown in FIG. 9C) at sample
introduction pathway exit 934. From there, the sample goes into a
well and the introducer (not shown in FIG. 9C) transfers the sample
into the fluid channel entry 936. The sample is then modulated in
the fluid channel 930 (additional material can be added to the
sample, the sample and additional material can be mixed, the sample
and additional material can be transferred back into a well on the
second portion, or any combination thereof) by action of the fluid
actuator 910 and eventually flows over the sensor 912 that makes up
part of the fluid channel 930. Analytes of interest can then bind
to the binding region on or within the sensor 912 modifying
something about the sensor. The sensor 912 can communicate with an
external instrument (not shown in FIG. 9C) in order to send
information about the analyte of interest within the sample.
[0120] Thus, embodiments of two part sensor assemblies are
disclosed. The implementations described above and other
implementations are within the scope of the following claims. One
skilled in the art will appreciate that the present disclosure can
be practiced with embodiments other than those disclosed. The
disclosed embodiments are presented for purposes of illustration
and not limitation.
* * * * *