U.S. patent application number 10/989624 was filed with the patent office on 2005-09-15 for fluid sample analysis device with sealable sample storage reservoir.
Invention is credited to Dai, Jielin, Tung, Hsiaoho Edward, Wu, Yuzhang, Yang, Ying.
Application Number | 20050202568 10/989624 |
Document ID | / |
Family ID | 34619465 |
Filed Date | 2005-09-15 |
United States Patent
Application |
20050202568 |
Kind Code |
A1 |
Tung, Hsiaoho Edward ; et
al. |
September 15, 2005 |
Fluid sample analysis device with sealable sample storage
reservoir
Abstract
The present invention is directed to devices and methods for
determining the presence of analyte in a fluid sample. The devices
utilize a sample collection well, an expression plate for
expressing sample into the sample collection well, a plunger that
drives a seal, and a test compartment containing test elements. The
devices also contain a reservoir for preserving an aliquot of
sample for later confirmation testing. When the plunger is lowered
into the sample collection well, an aliquot of sample is sealed in
the reservoir. In one embodiment the plunger is lowered as a cap is
applied to the device. The devices are useful for detecting the
presence of analyte in a wide variety of fluid samples, such as
saliva. The invention also provides methods of using the devices,
and kits containing the devices.
Inventors: |
Tung, Hsiaoho Edward; (San
Diego, CA) ; Wu, Yuzhang; (Hangzhou, CN) ;
Dai, Jielin; (Hangzhou, CN) ; Yang, Ying;
(Hangzhou, CN) |
Correspondence
Address: |
AZURE INSTITUTE
INTELLECTUAL PROPERTY DEPT.
4108 SORRENTO VALLEY BOULEVARD
SAN DIEGO
CA
92124
US
|
Family ID: |
34619465 |
Appl. No.: |
10/989624 |
Filed: |
November 15, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60520437 |
Nov 14, 2003 |
|
|
|
Current U.S.
Class: |
436/169 ;
422/400 |
Current CPC
Class: |
B01L 3/5023 20130101;
B01L 2300/0825 20130101; B01L 2400/0644 20130101; G01N 33/48714
20130101; B01L 2200/027 20130101; A61B 10/0045 20130101; A61B
10/007 20130101; A61B 10/0051 20130101; B01L 3/5027 20130101; B01L
3/5029 20130101; B01L 2200/0605 20130101; B01L 2400/0406 20130101;
A61B 2010/0077 20130101; A61B 2010/0074 20130101 |
Class at
Publication: |
436/169 ;
422/058; 422/061 |
International
Class: |
G01N 031/22 |
Claims
1. A test device for detecting an analyte suspected of being
present in a fluid sample, comprising: a casing, comprising a port
for a sample collection well; a test compartment containing at
least one test element; a sample collection well situated in the
port and comprising an upper chamber, an expression plate, a lower
chamber, and a sample outlet; a reservoir within or below the lower
chamber for storing fluid sample for confirmation testing; a
plunger comprised within the sample collection well, the plunger
having a raised position and a lower position; a seal that fits
sealably over the reservoir when the plunger is located in the
lower position; a cap for the sample collection well, wherein a
portion of the cap interacts with the plunger to move the plunger
from the raised position to the lower position when the cap is
applied to the sample collection well.
2. The device of claim 1 wherein the plunger further comprises one
or more plunger arms extending upward from the direction of the
base.
3. The device of claim 2 wherein the one or more plunger arms
extend upward inside the sample collection well and beside the
expression plate.
4. The device of claim 3, wherein the portion of the cap interacts
with the plunger arms to move the plunger from the raised position
to the lower position when the cap is applied to the sample
collection well.
5. The device of claim 1 wherein the reservoir is an indentation
located in the base of the sample collection well.
6. The device of claim 1 wherein the cap and the sample well
comprise complementary engaging screw threads.
7. The device of claim 6 wherein when the plunger is in the raised
position the test compartment and lower chamber are in fluid
communication, and when the screw threads are fully engaged the
plunger is in the lower position, and the test compartment and the
lower chamber are not in fluid communication.
8. The device of claim 1 wherein the sample outlet provides for
fluid communication between the lower chamber and the test
compartment.
9. The device of claim 1 wherein the test element is a test
strip.
10. The device of claim 9 wherein the test strip comprises specific
binding molecules immobilized on the test strip.
11. The device of claim 9 wherein the test strip comprises a
chemical test.
12. The device of claim 1 wherein the sample is selected from the
group consisting of a oral fluid, saliva, blood, serum, plasma,
urine, feces, spinal fluid, vaginal swabs, mucus, and tissue.
13. The device of claim 12 wherein the fluid sample is saliva.
14. The test device of claim 1 wherein the analyte of interest is
selected from the group consisting of: a drug, a hormone, a
protein, a nucleic acid molecule, an etiological agent, and a
specific binding pair member.
15. The test device of claim 14, wherein the analyte is a drug, and
the drug is a drug of abuse.
16. A kit comprising: a test device for detecting an analyte
suspected of being present in a fluid sample, comprising: a casing,
comprising a port for a sample collection well; a test compartment
containing at least one test element; a sample collection well,
situated in the port and comprising an upper chamber, an expression
plate, a lower chamber, and a sample outlet; a reservoir within or
below the lower chamber for storing a fluid sample for confirmation
testing; a plunger comprised within the sample collection well, the
plunger having a raised position and a lower position, and having a
seal at the lower end that fits sealably over the indentation when
the plunger is located in the lower position; a cap for the sample
collection well, wherein a portion of the cap interacts with the
plunger to move the plunger from the raised position to the lower
position when the cap is applied to the sample collection well; and
a sample applicator.
17. The kit of claim 16, wherein the sample applicator comprises an
absorbent member and a handle.
18. The kit of claim 17 wherein the absorbent member is a sponge or
a foam.
19. The kit of claim 17 wherein the absorbent member is treated
with a solution that stimulates salivation in a test subject.
20. The kit of claim 17 further comprising instructions for using
the device to determine the presence of an analyte in saliva.
21. A method of detecting an analyte suspected of being present in
a liquid sample, comprising applying a liquid sample suspected of
containing the analyte to a sample applicator; applying the liquid
sample to a test device by wringing the sample applicator into the
test device, where the test device comprises: a casing, comprising
a port for a sample collection well a test compartment containing
at least one test element; a sample collection well, situated in
the port and comprising an upper chamber, an expression plate, a
lower chamber, and a sample outlet; a reservoir within or below the
lower chamber for storing a fluid sample for confirmation testing;
a plunger comprised within the sample collection well, the plunger
having a raised position and a lower position, and having a seal at
the lower end that fits sealably over the reservoir when the
plunger is located in the lower position; a cap for the sample
collection well, wherein a portion of the cap interacts with the
plunger to move the plunger from the raised position to the lower
position when the cap is applied to the sample collection well; and
determining if the analyte is present in the sample.
22. The method of claim 21 wherein sample is applied to the sample
applicator by placing the sample applicator into the mouth of a
test subject.
23. The method of claim 21 wherein the sample applicator is filled
with saliva.
24. The method of claim 23 wherein liquid sample is applied to the
test device by pressing the sample applicator against the
expression plate of the device, and wringing the sample applicator
out so that liquid sample flows into the bottom chamber of the
sample collection well.
25. The method of claim 21 wherein the cap and the sample
collection well comprise complementary engaging screw threads.
26. The method of claim 25 further comprising fully engaging the
screw threads of the cap and sample collection well, and thereby
lowering the plunger to the lower position and sealing an aliquot
of sample in the reservoir.
27. The method of claim 21 further comprising placing the cap on
the sample collection well, lowering the plunger to the lower
position, and sealing an aliquot of sample in the reservoir.
28. The method of claim 21 wherein the test element is a test
strip.
29. The method of claim 28 wherein the test strip contains reagents
for detecting the presence of a drug of abuse.
Description
[0001] This application claims priority to U.S. provisional patent
application Ser. No. 60/520,437, filed Nov. 14, 2003, which is
hereby incorporated by reference in its entirety, including all
Tables, Figures and claims.
FIELD OF THE INVENTION
[0002] The present invention is directed to devices for the
collection and rapid analysis of fluids for analytes of
interest.
BACKGROUND OF THE INVENTION
[0003] The following Background of the Invention is intended to aid
the reader in understanding the invention and is not admitted to be
prior art.
[0004] Illicit drug use is an established and growing problem in
our society. In 2003, the US Department of Health and Human
Services found that an estimated 19.5 million Americans or 8.2
percent of the population aged 12 or older, were current illicit
drug users. Current illicit drug use means use of an illicit drug
during the month prior to the US Department of Health and Human
Services survey interview. Marijuana was found to be the most
commonly used illicit drug, with a rate of 6.2 percent (14.6
million). An estimated 2.3 million persons (1.0 percent) were
current cocaine users, 604,000 of whom used crack. Hallucinogens
were used by 1.0 million persons, and there were an estimated
119,000 current heroin users.
[0005] To combat and monitor this problem, drug testing has become
standard procedure in a variety of settings, such as employment,
school, sports, law enforcement, and the like. To facilitate this
effort, a drug-testing industry has emerged. This industry provides
a variety of drug testing products. A typical product is a urine
collection cup incorporating analysis tests. These devices can be
complicated and difficult or messy to use, or they may pose special
problems of sample adulteration by the subject trying to hide their
recent drug abuse. In addition, urine samples cannot be collected
in certain situations, such as on the road side or in public.
[0006] There is therefore a need for better methods and apparatuses
for performing sample collection and testing.
SUMMARY OF THE INVENTION
[0007] The present invention is directed to devices for collecting
liquid samples and simultaneously testing the sample for the
presence of an analyte of interest or a physical property. In one
embodiment the devices are for detecting analytes of interest in
body fluids, such as oral fluid or saliva. The devices have a
casing which contains a port for positioning of a sample collection
well. The sample collection well has an upper chamber, an
expression plate, a lower chamber, and a sample outlet providing
fluid communication with a test compartment. A test compartment
containing at least one test element is also provided with the
device. In one embodiment the seal is located on the lower end of
the plunger. When the plunger is moved from the raised position to
the lower position, a reservoir located in fluid communication with
the lower chamber of the sample collection well is sealed, thereby
preserving a fluid sample for confirmation testing. After the
plunger is in the lower position, the reservoir is no longer in
fluid communication with the reservoir. The device also contains a
cap, a portion of which interacts with the plunger to force the
plunger from the raised position into the lower position. In
embodiments where a screw cap is used, the plunger is lowered by
screwing on the cap, a portion of which interacts with the plunger
or a piece connected thereto, and forces the plunger into the lower
position. The device also contains a plunger having a raised
position and a lower position, and a seal. Kits containing the
devices, and methods of using the devices are also provided.
[0008] In a first aspect, the present invention provides a test
device for detecting an analyte suspected of being present in a
fluid sample. The test device has a casing having a port for a
sample collection well. The device also contains a test compartment
containing at least one test element. The device also has a sample
collection well, situated in the port and having an upper chamber,
an expression plate, a lower chamber, and a sample outlet. A sample
reservoir is present within or below the lower chamber for storing
a fluid sample for confirmation testing. A plunger is present
within the sample collection well, and has a raised position and a
lower position. The device contains a sealing member that fits
sealably over the sample reservoir when the plunger is located in
the lower position. In one embodiment the seal is located at the
lower end of the plunger. The device also has a cap for the sample
collection well, where a portion of the cap interacts with the
plunger to move the plunger from the raised position to the lower
position when the cap is applied to the sample collection well.
[0009] The term "sample reservoir" refers to a sealable area of the
apparatus in which fluid sample is stored and preserved from drying
out or from accidental contamination. The fluid sample can be
stored for confirmatory testing at a later time. In one embodiment
the sample reservoir is an indentation, which can be located in the
lower chamber of the sample collection well (e.g., on the bottom of
the sample collection well). The term "fluid communication" refers
to the ability for liquid to flow and be transmitted between two
areas. Thus, the collection well and the test compartment are in
fluid communication when fluid is able to flow from the collection
well and through the sample outlet and into the test compartment.
"Port" refers to the portion of the casing where the sample
collection well interfaces with the casing, and can be placed into
fluid communication with the test compartment. The sample
collection well can be inserted into the port as a separate part,
or the sample collection well and casing can be manufactured as a
single part. The sample collection well itself can be made of one
part, or assembled from sub-parts. By "fits sealably" is meant that
the sealing member prevents fluid from entering or leaving the
sample reservoir after the seal is formed, or from evaporating from
the sample reservoir. In one embodiment the sealing member contacts
the floor of the lower compartment. In one embodiment the seal is
an O-ring and makes contact with the floor of the lower chamber
around the entire circumference of the reservoir, thereby sealing
the reservoir. In one embodiment the plunger in the lower position
also closes the sample outlet and prevents fluid contained in the
test compartment from re-entering the lower chamber.
[0010] The "sample collection well" is where fluid sample is
gathered in preparation for analysis. In one embodiment the sample
collection well is generally cylindrical in its shape, but in other
embodiments it can assume any shape consistent with its function.
The sample collection well can have upper and lower chambers. In
one embodiment the upper chamber is the area above the expression
plate, and the lower chamber is the area below the expression
plate. An "expression plate" refers to a surface where a sample
applicator filled with fluid sample can be squeezed or crushed
against to express sample from the applicator. The expression plate
can have openings or holes to allow the passage of expressed fluid
sample to the sample collection well. The expression plate can be
located within the sample collection well, but can also be placed
in another location where expressed sample will flow to the
collection well. In one embodiment the expression plate is located
in the sample collection well and divides the upper and lower
chambers, and has one or more holes or openings through which fluid
sample can flow from the upper chamber to the lower chamber. When
the sample applicator is pressed against the expression plate,
sample flows through the opening in the expression plate, and into
the lower chamber. The term "plunger" refers to a part of the
device that moves through a portion of the device to bring two
parts into contact and perform a function in the operation of the
device. In one embodiment the plunger moves within a circular or
cylindrical part of the device, and resembles a piston. In one
embodiment the plunger moves through the sample collection
well.
[0011] In one embodiment the plunger has one or more plunger arms
extending upward. In one embodiment the one or more plunger arms
extend upward inside the sample collection well and beside the
expression plate. In another embodiment, the bottom of the cap
interacts with the plunger arms to move the plunger from the raised
position to the lower position when the cap is applied to the
sample collection well. The sample reservoir can be located at the
base of the sample collection well. In one embodiment, the cap and
the sample well have complementary engaging screw threads.
Furthermore, when the plunger is in the raised position the test
compartment and lower chamber of the sample collection well are in
fluid communication, and when the screw threads are fully engaged
the plunger is in the lower position, and the test compartment and
the lower chamber are not in fluid communication. By "fully
engaging" screw threads is meant that the cap has been turned onto
the sample collection well and the complementary screw threads
engaged to the extent that the cap is hand tight. The sample outlet
provides for fluid communication between the lower chamber and the
test compartment.
[0012] The "test element" can be any element that provides a
detectable result. In some embodiments the test element is a test
strip. In some embodiments the test strip has specific binding
molecules immobilized on the test strip and reagents for performing
an immunoassay, but in other embodiments the test strip has a
chemical test, but can also have reagents necessary to conduct any
suitable test that provides a detectable result. In one embodiment
the test element contains reagents for detecting the presence of a
drug of abuse.
[0013] The sample can be any fluid sample. Examples of fluid
samples include oral fluid, saliva, blood, serum, plasma, urine,
feces, spinal fluid, vaginal swabs, mucus, and tissue. "Saliva"
refers to the excretions of the salivary glands. "Oral fluid" is
any fluid present in the buccal cavity. Where the analyte to be
detected is a drug of abuse, the saliva of the test subject will
contain sufficiently high concentrations of the drug for testing if
the test subject has recently ingested the drug.
[0014] The analyte can be any analyte for which a test element is
available, or can be developed. Examples of analytes of interest
include a drug (such as a drug of abuse), a hormone, a protein, a
peptide, a nucleic acid molecule, an etiological agent, and a
specific binding pair member. A "drug of abuse" (DOA) is a drug
that is taken for non-medicinal reasons (usually for mind-altering
effects). The abuse of such drugs can lead to physical and mental
damage and (with some substances) dependence, addiction and even
death. Examples of DOAs include cocaine; amphetamines (e.g., black
beauties, white bennies, dextroamphetamines, dexies, beans);
methamphetamines (crank, meth, crystal, speed); barbiturates
(Valium.RTM., Roche Pharmaceuticals, Nutley, N.J.); sedatives (i.e.
sleep-aids); lysergic acid diethylamide (LSD); depressants
(downers, goofballs, barbs, blue devils, yellow jackets, ludes);
tricyclic antidepressants (TCA, e.g., imipramine, amitriptyline and
doxepin); phencyclidine (PCP); tetrahydrocannabinol (THC, pot,
dope, hash, weed, etc.); and opiates (e.g., morphine, opium,
codeine, heroin, oxycodone).
[0015] In another aspect, the present invention provides kits
including a test device of the invention, and a sample applicator.
The sample applicator can have an absorbent member and a handle.
The absorbent member can be a sponge, a foam, or any material
suitable for absorbing fluids. In one embodiment the absorbent
member is treated with a solution that stimulates salivation in a
test subject. The kit can also include instructions for using the
device. In one embodiment the instructions are for using the device
to determine the presence of an analyte in oral fluid or
saliva.
[0016] In another aspect the present invention provides methods for
detecting an analyte suspected of being present in a liquid sample.
The methods involve applying a liquid sample suspected of
containing the analyte to a sample applicator, and applying the
liquid sample to a test device of the invention by wringing the
sample applicator into the test device, and determining if the
analyte is present in the sample. The methods can also include the
step of moving the plunger to the lower position to seal an aliquot
of fluid sample in the reservoir. In one embodiment, the sample is
applied to the sample applicator by placing the sample applicator
into the mouth of a test subject, whereby the sample applicator is
filled with the saliva of the test subject. The liquid sample can
be applied to the test device by pressing the sample applicator
against the expression plate of the device, and wringing or
squeezing the sample applicator out so that liquid sample flows
into the sample collection well.
[0017] The methods can also include fully engaging the screw
threads of the cap and sample collection well, and thereby lowering
the plunger to the lower position and sealing an aliquot of sample
in the reservoir. In another embodiment, the method includes the
step of placing the cap on the sample collection well and thereby
lowering the plunger to the lower position and sealing an aliquot
of sample in the reservoir.
[0018] The present invention includes a variety of other useful
aspects, which are detailed herein. These aspects of the invention
can be achieved by using the articles of manufacture and
compositions of matter described herein. With reference to the
present disclosure, it will be further recognized that various
aspects of the present invention can be combined to make desirable
embodiments of the invention. In addition, a variety of other
aspects and embodiments of the present invention are described
herein.
[0019] The summary of the invention described above is not limiting
and other features and advantages of the invention will be apparent
from the following detailed description, as well as from the
claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIG. 1 provides a perspective view of one embodiment of the
present invention.
[0021] FIG. 2 provides an exploded view of the device of FIG.
1.
[0022] FIG. 3 provides another exploded view of the device of FIG.
1.
[0023] FIG. 4 show all six sides of the device of FIG. 1.
[0024] FIG. 5 shows top, side, cut-away and perspective views of
the sample application well 120.
[0025] FIG. 6 provides an exterior view and a cut-away view of the
device of FIG. 1, illustrating the state of the device prior to
use. Downward pointing arrows illustrate the future path of
expressed fluid into the lower chamber 330.
[0026] FIG. 7 provides an exterior view and a cut-away view of the
device of FIG. 1, illustrating the state of the device during the
expression of the sample 710 from the absorbent member 160.
[0027] FIG. 8 an exterior view and a cut-away view of the device of
FIG. 1, illustrating the state of the device prior to sealing the
lower chamber 330.
[0028] FIG. 9 an exterior view and a cut-away view of the device of
FIG. 1, illustrating the state of the device after the device has
been capped.
DETAILED DESCRIPTION
[0029] In the following detailed description, reference is made to
the accompanying drawings that form a part hereof, and in which is
shown by way of illustration specific embodiments in which the
invention may be practiced. It is understood that other embodiments
may be utilized and structural changes may be made without
departing from the scope of the present invention.
[0030] One aspect of the present invention is a test device for
testing a fluid sample for the presence of an analytes. The devices
also allow a quantity of sample to be easily stored for
confirmatory testing later in a reservoir on the device. If
desired, a different principle of testing can be used in the
confirmatory test. The confirmation sample is therefore safely
stored from contamination. The confirmatory sample is easily
sequestered during normal assay procedures, and without any
additional steps that need to be taken. In one embodiment, when the
user caps the device, a confirmation sample is automatically
sequestered in a reservoir for future testing as the application of
the cap lowers a seal over the reservoir.
[0031] FIGS. 1 though 9 illustrate one embodiment of the present
invention, a test device 100 for detecting an analyte suspected of
being present in a fluid sample. As shown in FIGS. 1 through 3, the
test device has a casing 110 and a sample collection well 120 (see
FIG. 5). The casing is composed of a top 240 and a base 245. The
casing has a port 150, into which the sample collection well
interfaces with the casing and the test compartment (630, FIG. 6).
The test compartment contains at least one test element 280, such
as a test strip. In this embodiment, the top of the casing has a
window 160 through which the test results on the test strips can be
viewed. The sample collection well is situated in the port and has
an upper chamber 130, an expression plate 320, a lower chamber 330,
and a sample outlet 270, which provides fluid communication between
the sample collection well and the test compartment. In one
embodiment, the fluid communication is provided when the plunger is
in the raised position, and no fluid communication occurs when the
plunger is in the lower position.
[0032] The expression plate has one or more openings 420 through
which fluid can flow. The expression plate can also have an opening
sized and shaped so that fluid can be removed from the lower
chamber by a pipette, syringe or other convenient means. In this
embodiment the expression plate is located in the sample collection
well, dividing the upper chamber from the lower chamber. But in
other embodiments the placement of the expression plate can
vary.
[0033] A reservoir 250 is located within or below the lower chamber
and can store a fluid sample for confirmation testing. In certain
embodiments, the reservoir is in vertical alignment with the port.
In one embodiment the reservoir is an indentation (shown here) in
the lower surface of the sample collection well. In other
embodiments the reservoir can be a chamber or other storage area
receiving fluid sample from the sample collection well. In the
embodiment illustrated the reservoir is located at the bottom of
the sample collection well, in other embodiments it can be located
in the lower end of the sample collection well, or even in another
location.
[0034] The sample collection well also has a plunger 220 having
both raised and lowered positions within the sample collection
chamber (see FIGS. 6 through 9). In one embodiment the plunger has
a seal 230 attached to its lower end. When the plunger is in the
raised position, the lower chamber and the test compartment are in
fluid communication with each other through the sample outlet, and
fluid may flow freely from the lower chamber of the sample
collection well and into the test compartment, through the sample
outlet (see FIGS. 7 and 8). When the plunger is in the lower
position, the seal fits over the reservoir (or opening thereto),
and has a contact point 910 with the reservoir, and seals the lower
chamber from the reservoir. Furthermore, when the plunger is in the
lower position, the lower chamber is also sealed from the test
compartment (FIG. 9) by the closing of the sample outlet. When the
lower chamber is sealed from the test compartment, the lower
chamber and the test compartment are no longer in fluid
communication with each other and fluid does not flow from the
lower chamber into the test compartment. In other embodiments, the
seal can be present as a separate piece that is moved by movement
of the plunger. For example, the seal can be present at the bottom
of the sample collection cup. In one embodiment the seal can be an
O-ring present around the aperture into the reservoir, and closed
by the plunger being lowered into it. In another embodiment the
seal can be a separate piece existing above the aperture of the
reservoir, and pressed by the plunger to form the seal around the
reservoir when the plunger is moved to the lower position.
[0035] In another embodiment, the test device also has a cap 210
for the sample collection well. In one embodiment, the cap and the
sample well have complementary engaging screw threads. In the
embodiment shown, the cap is adapted so that a portion of the cap
310 interacts with the plunger to move the plunger from the raised
position to the lowered position when the cap is applied to the
sample collection well. The interaction can be physical contact
between the parts, where contact with the cap transfers force to
the plunger and causes the plunger to move to the lower position.
In one embodiment the bottom of the cap interacts with the plunger
to apply the force as the cap is screwed onto the sample collection
well. When the cap is screwed onto the sample collection well, the
screw threads are fully engaged and the plunger has moved to the
lower position, and the test compartment and the lower chamber are
no longer in fluid communication. Additionally, the sample outlet
provides for fluid communication between the lower chamber and the
test compartment when the sample outlet is open. While a screw cap
is used in some embodiments, other types of caps can also be used.
For example, the cap can snap onto the sample collection well and
thereby press down the plunger. The cap could also fit into the
sample collection well in the style of a cork and therefore be
wedged into the sample collection well, meaning that it is held in
the well by the expansive forces of the cap. Any format that serves
the purpose of applying force to the plunger while sealing the
opening of the sample collection well is suitable.
[0036] In a further embodiment, the plunger has one or more plunger
arms 140 which extend upward from the direction of the base of the
plunger. As illustrated in FIG. 4, the plunger arms may also extend
upward inside the sample collection well and beside or through the
expression plate. In the embodiment shown, slots 410 have been
provided in the expression plate to accommodate the plunger arms. A
portion of the cap (e.g., the bottom of the cap) interacts with the
plunger arms to move the plunger from the raised position to the
lowered position when the cap is applied to the sample collection
well. As previously discussed, when the cap is screwed onto the
device, the reservoir is sealed, and the sample outlet is closed
such that the lower chamber and the test compartment no are longer
in fluid communication.
[0037] Sample Applicator
[0038] A sample applicator may be supplied with the device of the
present invention. In general, sample applicators consist of an
absorbent member 160 and a handle 180. The absorbent member can be
made of medical grade sponge or foam material commonly used in the
art. But many other materials are available for use as an absorbent
member, such as cotton or paper, or any material having suitable
absorbent capacity. The handle is generally rigid, to facilitate
manipulation of the absorbent member. The handle may be made of any
material commonly employed in the art, such as plastic, wood, metal
or cardboard. In one embodiment the handle has a rim 170 to which
the absorbent member is attached.
[0039] In some embodiments of the present invention, the upper
chamber of the sample application well may have vertical ribs 430
(FIG. 4). The applicator can be adapted so that its rim locks under
the ribs when the applicator has been sufficiently pressed against
the expression plate and then twisted to fit under the ribs. This
may ensure that the absorbent member of the applicator has been
sufficiently squeezed to express as much sample contained therein
as possible.
[0040] Test Strips
[0041] A variety of test components can be incorporated into the
present invention, and many varieties of test components are known
in the art. This discussion provides only a brief overview of some
embodiments. One type of test component is a test strip. Analyte
test strips are test components provided in a variety of formats,
such as immunoassay or chemical test format, for detecting analytes
of interest in a sample, such as a drug of abuse or a metabolite
suggestive of health status. Test components or test strips can be
provided in either noncompetitive or competitive assay formats. In
some formats, the test strips have a bibulous material having a
sample application zone, a reagent zone and a test result zone. The
sample is applied to the sample application zone and flows into the
reagent zone by capillary action. In the reagent zone, the sample
dissolves and mixes with reagents necessary for detection of the
analyte (if it is present in the sample). The sample, now carrying
the reagents, continues to flow to the test results zone.
Additional reagents are immobilized in the test results zone, such
as a specific binding molecule for the analyte. These reagents
react with and bind the analyte (if present) or one of the first
reagents from the reagent zone.
[0042] Normally, in noncompetitive formats, a signal is produced if
the sample contains the analyte, and no signal is produced if the
analyte is not present. In competitive formats, a signal may be
produced if no analyte is present, and no signal if analyte is
present. Of course how the results are interpreted depends on the
design of the assay, and persons of ordinary skill in the art are
familiar with test strip designs.
[0043] When the test element is a test strip, it may be made of
bibulous or non-bibulous material. A test strip can include more
than one material, which are then in fluid communication. One
material of a test strip may be overlaid on another material of the
test strip, such as for example, filter paper overlaid on
nitrocellulose. Alternatively or in addition, a test strip may
include a region comprising one or more materials followed by a
region comprising one or more different materials. In this case,
the regions are in fluid communication and may or may not partially
overlap one another. The material or materials of the test strip
can be bound to a support or solid surface such as a supporting
sheet of plastic, to increase its handling strength.
[0044] In embodiments where the analyte is detected by a signal
producing system, such as by one or more enzymes that specifically
react with the analyte, one or more components of the signal
producing system can be bound to the analyte detection zone of the
test strip material in the same manner as specific binding members
are bound to the test strip material, as described above.
Alternatively or in addition, components of the signal producing
system that are included in the sample application zone, the
reagent zone, or the analyte detection zone of the test strip, or
that are included throughout the test strip, may be impregnated
into one or more materials of the test strip. This can be achieved
either by surface application of solutions of such components or by
immersion of the one or more test strip materials into solutions of
such components. Following one or more applications or one or more
immersions, the test strip material is dried. Alternatively or in
addition, components of the signal producing system that are
included in the sample application zone, the reagent zone, or the
analyte detection zone of the test strip, or that are included
throughout the test strip, may be applied to the surface of one or
more test strip materials of the test strip as was described for
labeled reagents.
[0045] The zones can be arranged in many formats, for example,
sample application zone, one or more reagent zones, one or more
test results determination zones, one or more control zones, one or
more adulteration zones, and fluid absorbing zone. If the test
results determination zone includes a control zone, preferably it
follows the analyte detection zone of the test result determination
zone. All of these zones, or combinations thereof, can be provided
in a single strip of a single material. Alternatively, the zones
are made of different materials and are linked together in fluid
communication. For example, the different zones can be in direct or
indirect fluid communication. In this instance, the different zones
can be jointed end-to-end to be in fluid communication, overlapped
to be in fluid communication, or be communicated by another member,
such a joining material, which is preferably bibulous such as
filter paper, fiberglass or nitrocellulose. In using a joining
material, a joining material may communicate fluid from end-to-end
joined zones or materials including such zones, end-to-end joined
zones or materials including such zones that are not in fluid
communication, or join zones or materials that include such zones
that are overlapped (such as but not limited to from top to bottom)
but not in fluid communication.
[0046] When and if a test strip includes an adulteration control
zone, the adulteration control zone can be placed before or after
the results determination zone. When a control zone is present in
the results determination zone on such a test strip, then the
adulteration control zone is preferably before the control zone,
but that need not be the case. In the embodiment of the present
invention where a test strip is a control test strip for the
determination of an adulteration analyte and/or a control, then the
adulteration control zone can be placed before or after the control
zone, but is preferably before the control zone. The adulteration
zone provides a signal if there is present in the sample an
adulterant being tested for to determine if an attempt has been
made to defeat the purpose of the assay by the test subject.
[0047] Any analyte can be tested for utilizing the present
invention and a suitable test element. In particular, the present
invention can be utilized for the detection of a drug of abuse in
saliva or oral fluid. Additional examples of analytes to be tested
for include but are not limited to creatinine, bilirubin, nitrite,
protein (nonspecific), hormones (e.g. human chorionic gonadotropin,
luteinizing hormone, follicle stimulating hormone, etc.), blood,
leukocytes, sugar, heavy metals or toxins, bacterial components
(e.g. proteins or sugars specific to a particular type of bacteria,
such as E. coli0157:H7, S. aureus, Salmonella, C. perfringens,
Campylobacter, L. monocytogenes, V. parahaemolyticus, or B. cereus)
and physical characteristics of the urine sample, such as pH and
specific gravity. Any other clinical urine chemistry analyte that
can be adapted to a lateral flow test format may also be
incorporated into the present device.
[0048] Types of Samples
[0049] Any sample type can be tested with the device of the present
invention including liquids of biological origin (e.g., body fluids
and clinical samples). Liquid samples may be derived from solid or
semi-solid samples, including feces, biological tissue, and food
samples. Such solid or semi-solid samples can be converted into a
liquid sample by any suitable method, for example by mixing,
chopping, macerating, incubating, dissolving or enzymatically
digesting solid samples in a suitable liquid (e.g., water,
phosphate-buffered saline, or other buffers). "Biological samples"
include samples derived from living animals, plants, and food,
including for example urine, saliva, blood and blood components,
cerebrospinal fluid, vaginal swabs, semen, feces, sweat, exudates,
tissue, organs, tumors, tissue and organ culture, cell cultures and
conditioned media therefrom, whether from humans or animals. A
preferred biological sample is urine. Food samples include samples
from processed food components or final products, meat, cheese,
wine, milk and drinking water. Plant samples include those derived
from any plant, plant tissue, plant cell cultures and conditioned
media therefrom. "Environmental samples" are those derived from the
environment (e.g., a water sample from a lake or other body of
water, effluent samples, soil samples, ground water, ocean water,
and runoff water. Sewage and related wastes can also be included as
environmental samples.
[0050] Methods of Use
[0051] Another aspect of the present invention is a method of
detecting an analyte suspected of being present in a liquid sample,
as describe above. One embodiment is shown in FIG. 6. Note the
position of the sample applicator in the top view and the section
view below. In use, the applicator is fitted within the upper
chamber of the sample well and comes to rest against the expression
plate. At this point the plunger, with its attached seal, is in its
raised position. The lower chamber is in fluid communication with
the test compartment because fluid entering the lower compartment
can flow through the sample outlet and into the test
compartment.
[0052] In some embodiments of the present invention, a small piece
of wicking paper 620 is placed between the sample application zone
of the test strips and the sample outlet. This facilitates sample
flow from the sample collection well through the sample outlet and
to the test strips. Any type of bibulous material that supports
capillary flow can be used as the wicking paper. For example, a
small piece of glass fiber paper treated with buffer and detergent
to make it hydrophilic can be used, or polyester fiber, also
treated to make it more hydrophilic.
[0053] The wicking paper can be used to adjust the characteristics
of the sample before it is loaded onto the test strip. For example,
saliva might contain an antibody that cross-reacts with one of the
anti-drug antibodies (if the presence of a drug is being tested
for). Thus, an antibody (a scavenger antibody) which reacts with
the saliva antibody, and thereby inactivates it, can be affixed to
the wicking paper. When saliva is extremely viscous, therefore
slowing the wicking of the sample through the test strips, buffers,
detergents and proteases can be included in the wicking paper to
denature and cleave the proteins in the saliva, thereby rendering
it less viscous.
[0054] In one embodiment of the present invention, the sample is
applied to the sample applicator by placing the sample applicator
into the mouth of a test subject, where the absorbent member
becomes filled with saliva. The applicator can also be placed into
a beaker or tube of previously collected sample, until the
absorbent member is saturated. If a sample was previously collected
and is stored in another container, such as a tube or cup with a
lid, it is also acceptable to pipette a small amount of sample,
similar to the amount absorbed by an absorbent member, into the
sample well. In certain embodiments, about 100 ul to about 250 ul
of sample can be pipetted into the sample well. But the amount of
fluid sample applied to the sample collection well can be any
appropriate amount such as, for example, from about 250-500 ul, or
from about 500-750 ul, or about 1 ml. "About" means plus or minus
10%.
[0055] FIG. 7 illustrates liquid sample applied to the test device
by pressing the sample applicator against the expression plate of
the device, and wringing the sample applicator out so that liquid
sample flows into the bottom chamber of the sample collection well.
Note in this embodiment that the applicator has been pressed down
and twisted so that the rim of the applicator locks under the
flanges 430. The expressed sample 710 has passed through the
orifice in the expression plate and has collected in the lower
chamber. The plunger and seal are still in the raised position. The
wicking paper is in contact with the expressed sample that has
passed through the sample outlet and sample is wicked to the test
strips by the wicking paper beginning the assay.
[0056] In a further embodiment, the cap and the sample collection
well have complementary engaging screw threads (see FIGS. 8 and 9).
These embodiments include the step of fully engaging the screw
threads of the cap and sample collection well, and thereby lowering
the plunger to the lower position and sealing an aliquot of sample
in the reservoir (which is an indentation at the bottom of the
lower chamber in this embodiment). In other embodiments, the method
includes the step of placing the cap on the sample collection well
(e.g., by snapping or pressing it on) and thereby lowering the
plunger to the lower position and sealing an aliquot of sample in
the indentation. FIG. 8 shows the beginning of putting the cap on
the test device. The sample applicator has been removed and thrown
away. The plunger and seal are still in the raised position, but
the tops of the arms on the plunger are touching the bottom surface
of the cap. Also, the wicking paper and the test compartment are
still in fluid communication with the lower chamber.
[0057] Next, the cap is screwed onto the collection well and the
screw threads are completely engaged. As shown in FIG. 9, the cap
has pushed on the arms of the plunger, forcing the plunger and its
attached seal into the lowered position. Note that the seal makes
contact with the indentation (see point 910). When this happens,
the sample remaining in the lower chamber is sealed off from the
test compartment. Additionally, the test compartment is no longer
in fluid communication with the rest of the device, especially the
lower chamber.
[0058] Test Kits
[0059] Test kits of the invention can be packaged in a variety of
formats, depending upon the customer's needs. For example, a
facility that conducts large numbers of pre-employment drug
screenings may prefer boxes of 1 set of instructions plus 20 vacuum
packed set of devices and applicators. On the other hand, another
user may prefer boxed kits that contain only one device, one sample
collector, and one set of instructions. Any suitable packaging
materials can be used. Test kits may be packaged in a box, or may
be wrapped in protective material such as cellophane. Test kits may
also be provided with a test device (and applicator) provided in
the same or separate sealed pouches, which may or may not then be
provided in box or other packaging.
EXAMPLE 1
Pre-Employment Drug Screening
[0060] The devices of the invention can be utilized in a variety of
contexts, for example, for pre-employment drug screening. The
person to be tested provides a sample of oral fluid by placing the
sample applicator into his or her mouth, and allowing it to remain
in the mouth for about 5 minutes. In embodiments for pre-employment
drug screening the device contains test strips for several common
drugs of abuse, in this embodiment cocaine, methamphetamine,
phencyclidine, THC, morphine, and amphetamines. These test strips
utilize a competitive immunoassay format where labeled specific
binding molecules (antibodies in this embodiment) for each drug
being tested are present on the label zone (or reagent zone) of the
test strip. The test lines contain the antigen being tested for. If
analyte is present in the sample it is bound by labeled specific
binding molecules in the label zone, thereby preventing the labeled
antibody from binding to the test line. Thus, no signal occurs on
the test line when analyte is present. Conversely, when no antigen
is present in the saliva, the labeled antibodies bind to the test
line providing the signal on the test line.
[0061] After receiving the filled or soaked sample applicator, the
testing technician inserts it into the sample collection well of
the device and presses the applicator down into the expression
plate and then twists it, to lock the rim of the applicator under a
pair a flanges (provided in this embodiment). Saliva is thereby
expressed from the absorbent foam of the sample applicator and
flows through holes in the expression plate and into the lower
chamber of the sample collection well. Since the plunger is in the
first position, sample also flows through the sample outlet and
into the test compartment. When sample flows into the lower chamber
of the sample collection well, it comes into contact with wicking
paper extending into the lower chamber and flows out the sample
outlet and to the test strips, thereby initiating the assays. When
all of the sample is loaded, the applicator is discarded, and the
cap is screwed onto the sample application well. When the cap is
screwed onto the device, the force applied by the cap pushes the
plunger into the lower position. As the plunger moves into the
lower position, the seal is lowered around the reservoir and an
aliquot of fluid sample is sequestered in the reservoir. When the
plunger is lowered, the sample outlet is also closed, stopping the
flow of any additional sample to the test compartment. After about
3-5 minutes, the control indicia are provided indicating that the
assay is complete. A signal is provided at the test lines for each
drug being tested for, indicating that no drugs of abuse are
present in the saliva sample (this assay is in a competitive
format). If a positive result is determined, the device may be sent
to a confirmatory laboratory so that the aliquot of sample
preserved in the reservoir can be tested to confirm the result.
[0062] The invention illustratively described herein may be
practiced in the absence of any element or elements, limitation or
limitations that are not specifically disclosed herein. The terms
and expressions which have been employed are used as terms of
description and not of limitation, and there is no intention that
in the use of such terms and expressions of excluding any
equivalents of the features shown and described or portions
thereof, but it is recognized that various modifications are
possible within the scope of the invention claimed. Thus, it should
be understood that although the present invention has been
specifically disclosed by various embodiments and optional
features, modification and variation of the concepts herein
disclosed may be resorted to by those skilled in the art, and that
such modifications and variations are considered to be within the
scope of this invention as defined by the appended claims.
[0063] The contents of the articles, patents, and patent
applications, and all other documents and electronically available
information mentioned or cited herein, are hereby incorporated by
reference in their entirety to the same extent as if each
individual publication was specifically and individually indicated
to be incorporated by reference. Applicants reserve the right to
physically incorporate into this application any and all materials
and information from any such articles, patents, patent
applications, or other documents.
* * * * *