U.S. patent application number 16/100198 was filed with the patent office on 2019-05-09 for reagent storage device for storing a target-specific reagent.
The applicant listed for this patent is Shazi Iqbal, Michael C. L. Vickery. Invention is credited to Shazi Iqbal, Michael C. L. Vickery.
Application Number | 20190134634 16/100198 |
Document ID | / |
Family ID | 66327905 |
Filed Date | 2019-05-09 |
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United States Patent
Application |
20190134634 |
Kind Code |
A1 |
Iqbal; Shazi ; et
al. |
May 9, 2019 |
Reagent Storage Device for Storing a Target-Specific Reagent
Abstract
A target specific PCR component reagent storage device is
configured to enable customization of a universal reagent
cartridge. The reagent storage cartridge may exhibit a generally
tubular geometry and includes a reagent storage section and a
remaining section with a break-off region therebetween. The reagent
section is configured to store a lyophilized, target-specific
reagent therein. The break-off region exhibits a lower structural
integrity than the remainder of the reagent storage device such
that the reagent storage section breaks-off from the remaining
section when the reagent storage section is pressed against a port
in a universal reagent cartridge that includes multiple
predetermined reagents, such that the lyophilized, target-specific
reagent enters the reagent cartridge via the port to customize the
universal reagent cartridge with the target-specific reagent.
Inventors: |
Iqbal; Shazi; (Danville,
CA) ; Vickery; Michael C. L.; (Birmingham,
AL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Iqbal; Shazi
Vickery; Michael C. L. |
Danville
Birmingham |
CA
AL |
US
US |
|
|
Family ID: |
66327905 |
Appl. No.: |
16/100198 |
Filed: |
August 9, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62543352 |
Aug 9, 2017 |
|
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|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 2200/0647 20130101;
B01L 2300/087 20130101; B01L 3/0275 20130101; B01L 2200/02
20130101; B01L 3/527 20130101; C12Q 1/6806 20130101; B01L 2300/021
20130101; C12Q 1/686 20130101; B01L 2200/14 20130101; B01L 2300/046
20130101; G06K 19/06028 20130101; B01L 2300/0832 20130101; B01L
3/52 20130101; B01L 3/545 20130101; B01L 3/502 20130101; B01L
3/50825 20130101; B01L 2200/16 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00; G06K 19/06 20060101 G06K019/06 |
Claims
1-14. (canceled)
15. A reagent storage device, comprising: a tubular member
including opposed first and second open ends; a break-off region
situated a predetermined distance from the first open end, the
break-off region dividing the tubular member into a reagent storage
section between the first open end and the break-off region, and a
remaining section between the break-off region and the second open
end; wherein the reagent storage section is configured to store a
lyophilized, target-specific reagent therein; wherein the break-off
region exhibits a lower structural integrity than the reagent
storage section and the remaining section of the reagent storage
device, such that the reagent storage section breaks-off from the
remaining section at the break-off region when the tubular member
is bent about the break-off region.
16. The reagent storage device of claim 15, wherein the break-off
region of the reagent storage device is configured such that the
reagent storage section breaks-off from the remaining section at
the break-off region when the reagent storage section is pressed
against a port in a universal reagent cartridge that includes a
plurality of predetermined reagents, such that the reagent storage
section with the target-specific reagent therein can enter the
universal reagent cartridge via the port to customize the universal
reagent cartridge with the target-specific reagent.
17. The reagent storage device of claim 16, wherein the
target-specific reagent is a target-specific polymerase chain
reaction (PCR) component.
18. The reagent storage device of claim 15, wherein the tubular
member narrows at the break-off region to provide lower structural
integrity to the break-off region than the reagent storage section
and the remaining section of the reagent storage device.
19. The reagent storage device of claim 15, wherein the tubular
member exhibits a generally conical geometry.
20. The reagent storage device of claim 15, wherein the reagent
storage device exhibits a generally cylindrical geometry with a
fixed diameter between the first and second open ends thereof.
21. The reagent storage device of claim 15, wherein the tubular
member includes a central channel situated between the first and
second open ends thereof.
22. The reagent storage device of claim 15, wherein the first open
end exhibits a narrower diameter than the second open end, the
first open end being designated the narrow end, the second open end
being designated the wide end, wherein the break-off region is
situated closer to the narrow end than to the wide end.
23. The reagent storage device of claim 22, wherein the wide end is
adapted for connection to a reagent suction apparatus to pull
reagent into the narrow end.
24. The reagent storage device of claim 23, wherein the reagent
suction apparatus is a micropipette.
25. The reagent storage device of claim 23, wherein reagent suction
apparatus is a liquid handling system.
26. The reagent storage device of claim 22, wherein the tubular
member includes a collar at the wide end thereof to increase the
structural rigidity of the wide end.
27. The reagent storage device of claim 26, wherein the collar
includes a plurality of castellation elements.
28. The reagent storage device of claim 22, wherein the wide end is
adapted for connection to a water dispensing apparatus to dispense
water into the wide end to rehydrate a lyophilized reagent in the
reagent storage section.
29. The reagent storage device of claim 28, wherein water
dispensing apparatus is a liquid handling system.
30. An identification tab apparatus for use with a reagent storage
device, comprising: an identification member including a first
surface configured to receive a removable identification label, the
removable identification label including a unique identification
code; and a plug member attached to the identification member and
extending away therefrom, the plug member being configured to plug
an open end of a reagent storage device that is adapted to store a
target specific reagent therein.
31. The identification tab apparatus of claim 30, wherein the plug
member includes first and second opposed plug ends, the plug member
including a substantially conical portion.
32. The identification tab apparatus of claim 31, wherein the first
opposed plug end is attached to the identification member and the
second opposed plug end is adapted for insertion into the open end
of the reagent storage device, the substantially conical portion
ending at the second opposed plug end of the plug member.
33. The identification tab apparatus of claim 32, wherein the plug
member further includes a substantially cylindrical portion between
the substantially conical portion and the identification
member.
34. The identification tab apparatus of claim 30, wherein the
unique identification code of the removable identification label
identifies a particular target specific reagent.
35. The identification tab apparatus of claim 30, wherein the
identification member includes a substantially flat surface on
which the removable identification label is situated.
36. The identification tab apparatus of claim 35, wherein the
identification member is substantially planar and substantially
rectangular.
37. A method, comprising: providing a reagent storage device that
includes: a tubular member including opposed first and second open
ends; a break-off region situated a predetermined distance from the
first open end, the break-off region dividing the tubular member
into a reagent storage section between the first open end and the
break-off region, and a remaining section between the break-off
region and the second open end; wherein the reagent storage section
is configured to store a target-specific reagent therein; wherein
the break-off region exhibits a lower structural integrity than the
reagent storage section and the remaining section of the reagent
storage device such that the reagent storage section breaks-off
from the remaining section at the break-off region when the tubular
member is bent about the break-off region; storing a particular
target specific reagent in the reagent storage section of the
reagent storage device; providing an identification tab apparatus
that includes: an identification member including a first surface
configured to receive a removable identification label, the
removable identification label including a unique identification
code; a plug member attached to the identification member and
extending away therefrom, the plug member being configured to plug
an open end of the reagent storage device that stores the
particular target specific reagent therein; and inserting the plug
member of the identification tab apparatus into the second open end
of the reagent storage device, the particular unique identification
code on the identification tab apparatus corresponding to the
particular target specific reagent stored in the reagent storage
section of the reagent storage device.
38. The method of claim 37, further comprising: inserting the
reagent storage section of the reagent storage device into a port
of a universal reagent cartridge, and breaking off the reagent
storage section from the remaining section about the break-off
region such that the reagent storage section with the particular
target specific reagent therein falls into the port of the
universal cartridge.
39. The method of claim 38, further comprising: removing the
removable identification label from the identification member of
the identification tab apparatus; and affixing the removable
identification label to the universal reagent cartridge to identify
the particular target specific reagent now therein.
40. A reagent storage device comprising: a tubular member including
first and second opposed ends; a removable cap situated at the
first opposed end of the tubular member, the first opposed end of
the tubular member being designated the narrow cap end; wherein the
tubular member is configured to store a target-specific reagent
therein, the tubular member exhibiting a tapered geometry that
narrows between the second opposed end and the narrow cap end, such
that after cap removal when the tubular member with the
target-specific reagent therein enters a universal reagent
cartridge that includes a plurality of predetermined reagents
therein, the target-specific reagent customizes the universal
reagent cartridge.
41. The reagent storage device of claim 40, wherein the
target-specific reagent is a target-specific polymerase chain
reaction (PCR) component reagent.
42. The reagent storage device of claim 40, wherein an end of the
removable cap includes a flexible bulbous ejector that ejects the
tubular member from the removable cap.
Description
CROSS REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This patent application claims priority to Provisional U.S.
Patent Application Ser. No. 62/543,352, filed Sep. 9, 2017, by
inventors Shazi S. Iqbal and Michael C. L. Vickery, the disclosure
of which is incorporated herein by reference in its entirety.
BACKGROUND
[0002] The disclosures herein relate generally to molecular
testing, and more specifically to the molecular testing of samples
for diagnostic purposes. The disclosures herein also relate to
fluidic analysis systems that receive cartridges containing
reagents used for sample testing by such fluidic analysis
systems.
BRIEF SUMMARY
[0003] In one embodiment, a method is disclosed for customizing a
universal reagent cartridge with a lyophilized target-specific
reagent, wherein the method includes providing a universal reagent
cartridge including a plurality of chambers populated with
predetermined non-target-specific reagents therein. The method
further includes providing a custom reagent storage device that
stores a lyophilized, target-specific reagent therein, the custom
reagent storage device being configured to be end user insertable
into the universal reagent cartridge to customize the universal
reagent cartridge with the target-specific reagent. In accordance
with the disclosed method, the target-specific reagent may be a
lyophilized, target-specific polymerase chain reaction (PCR)
component. In accordance with one embodiment of the method, the
target-specific reagent is designated for a predetermined target
DNA or RNA gene sequence in a sample. The method may further
include inserting a portion of the custom reagent storage device
into the universal reagent cartridge to customize the universal
reagent cartridge with the target-specific reagent.
[0004] In another embodiment, a reagent storage device is disclosed
that includes a tubular member including opposed first and second
open ends. A break-off region is situated a predetermined distance
from the first open end, the break-off region dividing the tubular
member into a reagent storage section between the first open end
and the break-off region, and a remaining_section between the
break-off region and the second open end. The reagent storage
section is configured to store a lyophilized, target-specific
reagent therein. The break-off region exhibits a lower structural
integrity than the remainder of the reagent storage device such
that the reagent storage section breaks-off from the remaining
section when the reagent storage section is pressed against a port
in a reagent cartridge that includes a plurality of predetermined
reagents. In this manner the lyophilized, target-specific reagent
enters the reagent cartridge via the port to customize the reagent
cartridge with the target-specific reagent.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] The appended drawings illustrate only exemplary embodiments
of the invention and therefore do not limit its scope because the
inventive concepts lend themselves to other equally effective
embodiments.
[0006] FIG. 1A is a representation of a universal cartridge shown
together with different embodiments of a target specific PCR
component storage device including a break-off region.
[0007] FIG. 1B is a representation of the universal cartridge being
opened by a user and is shown together with a foil wrapper that
contains a target specific PCR component storage device
therein.
[0008] FIG. 1C is a representation the universal cartridge being
further opened by a user.
[0009] FIG. 1D is a representation of the opened universal
cartridge adjacent the unopened foil wrapper.
[0010] FIG. 1E depicts the opening of the foil wrapper containing
the target specific PCR component storage device.
[0011] FIG. 1F is a representation of a user moving the target
specific PCR component storage device toward the universal
cartridge.
[0012] FIG. 1G is a representation of the reagent storage section
of the target specific PCR component storage device being placed in
a dedicated port of the universal cartridge.
[0013] FIG. 1H is a representation of the reagent storage section
of the target specific PCR component storage device being placed
further into the dedicated port of the universal cartridge.
[0014] FIG. 1I is a representation of the reagent storage section
of the storage device being snapped off at the break-off
region.
[0015] FIG. 1J is a representation of the remaining section of the
storage device being moved away from the universal cartridge by the
user.
[0016] FIG. 1K depicts a sample buffer being added to the sample
port of the universal cartridge.
[0017] FIG. 1L depicts of a pipette being moved toward the sample
port of the universal cartridge before adding the sample
thereto.
[0018] FIG. 1M depicts the pipette dispensing the sample into the
sample port of the universal cartridge.
[0019] FIG. 1N is a representation of a general purpose computer
executing a test application to receive test information input.
[0020] FIG. 1O depicts a user opening a bay of a test instrument in
preparation for placing the universal cartridge therein.
[0021] FIG. 1P depicts the universal cartridge situated in the open
test bay prior to closure of the test bay and the beginning of the
test.
[0022] FIG. 1Q depicts a user closing the test bay of the test
instrument so that testing can commence.
[0023] FIG. 1R is a representation of the general purpose computer
of FIG. 1N showing test results after executing the test
application.
[0024] FIG. 2A is a perspective view of one embodiment of the
target specific PCR component storage device.
[0025] FIG. 2B is side elevational view of one embodiment of the
target specific PCR component storage device.
[0026] FIG. 2C depicts target specific PCR component storage device
after being separated into two sections at the break-off
region.
[0027] FIG. 3 depicts a standalone reagent storage device.
[0028] FIG. 4A depicts a cap that is mountable on the target
specific PCR component storage device to facilitate handling of the
storage device without contamination.
[0029] FIG. 4B depicts another embodiment of the cap that includes
a bulbous ejector at one end.
[0030] FIG. 4C depicts the cap of FIG. 4B mounted on one end of the
target specific PCR component storage device.
[0031] FIG. 5A is a perspective view of another embodiment of the
target specific PCR component storage device.
[0032] FIG. 5B is a side elevational view of the target specific
PCR component storage device.
[0033] FIG. 5C is another side elevational view of the target
specific PCR component storage device.
[0034] FIG. 5D is a cross section of the side elevational view of
the target specific PCR component storage device of FIG. 5B taken
along section line 5D-5D.
[0035] FIG. 5D' is a cross section of the side elevational view of
the target specific PCR component storage device of FIG. 5B taken
along section line 5D-5D but showing an alternative embodiment.
[0036] FIG. 5E is an end view of the target specific PCR component
storage device as viewed from the narrow end thereof.
[0037] FIG. 5F is an end view of the target specific PCR component
storage device as viewed from the wide end thereof.
[0038] FIG. 6A is representation of the target specific PCR
component storage device installed on a shaft or mandrel of a
liquid handling system prior to drawing the target specific PCR
component liquid reagent into the storage device.
[0039] FIG. 6B is representation of the target specific PCR
component storage device installed on a shaft or mandrel of a
liquid handling system after drawing the target specific PCR
component liquid reagent into the storage device.
[0040] FIG. 7A is a perspective view the disclosed dual purpose tab
that includes both a plug and a planar portion with a barcode ID
label thereon.
[0041] FIG. 7B depicts the tab of FIG. 7A being plugged into the
wide end of the target specific PCR component storage device.
[0042] FIG. 7C depicts one side of the tab of FIG. 7A with the
barcode ID thereon.
[0043] FIG. 7D depicts the side of the tab opposite the barcode ID
side depicted in FIG. 7C.
[0044] FIG. 7E is a right side elevation view of the tab of FIG.
7A.
[0045] FIG. 7F is a left side elevation view of the tab of FIG.
7A
[0046] FIG. 7G is first end view of the tab of FIG. 7A.
[0047] FIG. 7H is second end view of the tab of FIG. 7A.
DETAILED DESCRIPTION
[0048] In one embodiment, a reagent storage device and testing
methodology are disclosed that may be used with a molecular
diagnostic assay instrument to customize the testing of samples by
the instrument.
[0049] Molecular diagnostic assay testing instruments may include
one or more testing bays that receive respective assay cartridges
which contain predetermined reagents and samples for testing
purposes. A particular cartridge may include multiple chambers with
different reagents, as well as a chamber in which the sample to be
tested is inserted. After the user places a cartridge with its
reagents and sample in a testing bay of the instrument, the
instrument processes the sample by using the supplied reagents. For
example, this processing may include DNA and RNA extraction and
purification. The instrument may also perform polymerase chain
reaction (PCR) amplification on the sample to amplify a targeted
DNA or RNA gene sequence. In this manner, the target may be
amplified millions-fold or billions-fold and further be provided
with a fluorescent tag. For example, if the test is to detect a
particular pathogen or disease cancer gene, the test targets DNA
that is specific to that disease. The target DNA is amplified
billions-fold. The instrument then fluorometrically detects the
amplified target using optical readers to detect the targeted
disease, if present. The testing instrument includes the
mechanical, electromechanical, optical, electronic and other
structures needed to process the cartridge. Notably, the testing
instrument includes optical detection apparatus to detect the
presence of a targeted gene sequence.
[0050] Testing instrument manufacturers typically manufacture the
multi-chamber cartridge and preload the chambers of the cartridge
with all of the reagents required for a particular target detection
protocol. In other words, the cartridge is prepackaged with all of
the necessary reagents installed in the cartridge before the
cartridge is shipped to the customer. The cartridge manufacturer
ships the preloaded cartridge to a customer, and the customer
receives the preloaded cartridge in ready-to-use condition to
detect a particular target. The customer adds a sample to the
cartridge wherein the sample will be tested for presence of the
particular target that the manufacturer effectively "programmed"
into the cartridge. The sample may be a blood sample, saliva
sample, sputum sample, i.e. any sample for which detection of the
specific target sequence is desired. As used herein, the term
"customer" may include an "end-user", or more simply, the "user",
i.e. the person actually performing the test.
[0051] In the above described testing system, each cartridge is
dedicated to a specific target for detection. First, the customer
places an order with the manufacturer. The customer order specifies
a particular target sequence to be detected. In response, the
manufacturer prepares a unique cartridge that is populated with
particular reagents for detecting a specific target. This approach
may result in high manufacturing costs because, with each cartridge
effectively being unique, economy of scale is not possible. In this
approach, quality control costs may also be very high. Moreover,
the customer or user is foreclosed from detecting some target other
than the particular target for which the cartridge was built and
dedicated by the manufacturer.
[0052] In accordance with the advanced testing apparatus and
methodology disclosed herein, a "cartridge provider" (for example a
manufacturer), preloads generic reagents in the chambers of a
cartridge. This cartridge will be referred to as a "universal
cartridge". The universal cartridge includes the generic reagents
needed for testing a sample, but does not initially store a target
specific reagent, also referred to as a target specific PCR
component. The universal cartridge includes a port that is
dedicated to receiving the target specific PCR component after the
customer receives the universal cartridge containing the generic
reagents from the manufacturer.
[0053] As an example, a customer desires to test for a particular
target sequence. The customer orders and receives a universal
cartridge from the "cartridge provider", for example the
manufacturer. As described above, the universal cartridge stores
the generic reagents for the general type of test that the customer
desires to conduct. In this particular example, the customer
desires to test for a first target sequence by using a first target
specific PCR component and also desires to test for a second target
sequence by using a second target specific PCR component. The
customer places an order with a "target provider" to provide a
first target specific PCR component and a second target specific
PCR component. The "target provider" stores the ordered first
target specific PCR component in a first reagent storage device.
The "target provider" stores the ordered second target specific PCR
component in a second regent storage device. The "reagent storage
device" may be configured as a plastic tube that stores the target
specific PCR component, as described below in more detail with
respect to the disclosed reagent storage tip.
[0054] The customer receives the first and second reagent storage
devices from the target provider. The customer also orders and
receives multiple universal cartridges from the cartridge provider.
The customer is now fully equipped with the ability to customize a
universal cartridge to detect a particular target. In a first
example, the user may wish to customize the first universal
cartridge with a first target specific PCR component to detect a
particular target sequence. To do so, the customer takes the first
reagent storage device and transfers the contents of the first
reagent storage device to a dedicated port of the first universal
cartridge. This port is dedicated to receiving the target specific
PCR component. The first universal cartridge is now ready for
testing by the testing instrument because the first universal
cartridge is now populated with both the generic reagents needed
for the test as well as the target specific PCR component needed to
target and test the desired target sequence. The customer adds the
sample to be tested into the first universal cartridge, and then
moves the first universal cartridge to an open testing bay of the
molecular testing instrument. The testing instrument performs the
test and provides output to the user to indicate the presence or
absence of the target sequence.
[0055] In a second example, the user may wish to customize the
second universal cartridge with a second target specific PCR
component to test for a different target sequence than the
particular target sequence associated with the first target
specific PCR component of the first test. To do so, the customer
takes the second reagent storage device and transfers the contents
of the second reagent storage device to the dedicated port of the
universal cartridge. The second universal cartridge is now ready to
conduct a test because it is now populated with both the generic
reagents needed for the test as well as the second target specific
PCR component needed to test for the new target sequence. As
before, the user/customer adds the sample to be tested into the
second universal cartridge, and then moves the second universal
cartridge to an open testing bay of the molecular testing
instrument. As before, the testing instrument performs the test and
provides output to indicate the presence or absence of the target
sequence. Those skilled in the art will appreciate that while the 2
examples above are serial tests, these tests may be conducted in
parallel to save time.
[0056] Referring now to FIG. 1A, the customer receives a universal
cartridge 100 from the cartridge provider and a target specific PCR
component from the target provider. Cartridges that are useful as a
universal cartridge when modified as described below are seen in
U.S. Pat. Nos. 8,048,386 and 9,394,086, the disclosures of which
are incorporated herein by reference in their entirety. In FIG. 1A,
the target specific PCR component is stored in a reagent storage
device 200 or a reagent storage device 500. For example, reagent
storage device 200, with the target specific PCR component therein,
is packaged in a sealed foil wrapper 110 for protection. The cap
102 of the universal cartridge 100 is shown as being closed.
[0057] The universal cartridge 100, as received from the "cartridge
provider", already contains the generic reagents for a particular
test type that the customer desires to run on the sample. The
customer may now customize the test to detect a particular target
sequence by adding the customer specified target reagent from
reagent storage device 200 or 500 (after removal from the sealed
foil wrapper 102) to the universal cartridge 100, as discussed in
more detail below. A "target provider" supplies the reagent storage
device 200 or 500 containing the desired target specific PCR
component according to the target sequence order that the customer
sends to the "target provider".
[0058] The customer, i.e. user, opens the cap 102 of universal
cartridge 100 as seen in FIG. 1B and FIG. 1C. Next, the customer
opens foil wrapper 110 to access the reagent storage device 200 or
500 with the selected target specific PCR component therein, as
seen in FIG. 1D and FIG. 1E.
[0059] As seen more clearly in FIG. 1F, universal cartridge 100
includes a dedicated port 104 for receiving the target specific PCR
component. Universal cartridge 100 also includes a sample port 106
that receives a sample under test after the target specific PCR
component is deposited in dedicated port 104. Before depositing the
sample in sample port 106, the customer moves reagent storage
device 300 toward the dedicated target specific PCR component port
104 of universal cartridge 100 as shown in FIG. 1F. In one
embodiment, the reagent storage device may take the form of a
plastic tube, such as reagent storage device 200 of FIG. 2A or
reagent storage device 500 of FIG. 5A. The reagent storage device
may be tubular and/or generally conical in shape. The reagent
storage device tube may be fabricated of plastic material. In one
embodiment, a reagent storage device 200 may be divided into two
sections, namely a reagent storage section 205 and a remaining
section 210, as seen and discussed in more detail with reference to
FIGS. 2A-2B below. However, briefly, the reagent storage section
205 is divided from the remaining section 210 by a score line 215.
The score line 215 is sufficiently deep to allow the reagent
storage section 205 to break-off, i.e. snap off, and separate from,
the remaining section 210 at the score line 215, when the user
applies torque to reagent storage section 120 against the side of
dedicated port 104. The reagent storage section contains the target
specific PCR component in a lyophilized form.
[0060] In more detail, the customer or user inserts the narrow end
of reagent storage device tip 200 into the dedicated target
specific PCR component port 104 in the universal cartridge 100, as
seen in FIG. 1G. As seen in FIG. 1H, the customer bends (i.e.
torques or levers) the reagent storage device against the side of
dedicated port 104. In response to this action, the reagent storage
section 205 breaks off from the remaining section 210 of reagent
storage device 200 at score line 215. Upon separation from the
remaining section 210 which the user is still holding, the reagent
storage section 205 with the target specific PCR component therein
falls into the chamber below the dedicated target specific port 104
of universal cartridge 100. FIG. 1I depicts universal cartridge 100
and remaining section 210 after reagent storage section 205 has
fallen into the chamber below dedicated port 104.
[0061] FIG. 1J depicts the user moving remaining section 210 away
from universal cartridge 100 after the target specific PCR
component is deposited in dedicated port 104. After adding the
target specific PCR component to the target specific port 104 of
the universal cartridge 100, the user or customer may add a sample
buffer to sample port 106 adjacent the front right side of the
cartridge, as seen in FIG. 1K. The customer adds the sample under
test to the sample port 106 as seen in Fig. L and Fig. M.
[0062] As seen in FIG. 1N, the customer or user inputs test run
information into a general-purpose computer 130 that is configured
with a testing application to communicate with a molecular testing
instrument 140 that is depicted in both FIG. 1O and FIG. 1P. The
test run information includes information such as parameters and
conditions for the particular tests to be performed by molecular
testing instrument 140 using the reagents and sample now all
present in the universal cartridge 100. Molecular testing
instruments suitable for conducting tests with the universal
cartridge 100 described herein are seen in U.S. Patent Application
Publications 2014/0098252. and 2017/0021356, the disclosures of
which are incorporated herein by reference in their entirety.
[0063] In more detail and as seen in FIG. 1O, the user opens the
door of a bay of the testing instrument 140. The user places
cartridge 100 into the bay as seen in FIG. 1P. Next, the user
closes the door of the bay of the testing instrument, as seen in
FIG. 1Q. Molecular testing instrument 140, working in cooperation
with general purpose computer 140, provides test results on display
135 for the particular test specified in the input test run
information, as seen in FIG. 1R.
[0064] FIG. 2A is a perspective view, and FIG. 1B is a plan view,
of a first embodiment of the reagent storage device 200 that
employs a score line separator 215 to provide a break-off region to
device 200. This break-off region may also be referred to as a
snap-off region. The break-off region is intentionally structurally
weakened in comparison with the remainder of device 200, so that
when device 200 is bent or torqued, device 200 will break and
separate at the break-off region. Score line 215 is one way to
implement this break-off region so that device 200 is separable,
i.e. breakable, into reagent storage section 205 and remaining
section 210. FIG. 2C depicts reagent storage device 200 after it is
separated at score line 215 into reagent storage section 205 and
remaining section 210.
[0065] Reagent storage device 200 includes a central channel 220
(indicated in dashed lines) situated between the opposed ends of
the device, namely between narrow end 205A of reagent storage
section 205 and wide end 210A of the remaining section 210. The
lyophilized target specific reagent 225 is positioned in the
central channel 220 in reagent storage section 205, as shown. As
stated above, the reagent storage device 200 may exhibit a
generally conical geometry as depicted. Alternatively, the reagent
storage device 200 may have a tubular or substantially cylindrical
geometry, depending on the particular application. The central
channel 220 may likewise exhibit a tubular or substantially
cylindrical geometry as depicted, or exhibit a generally conical
geometry, depending on the particular application.
[0066] FIG. 3 shows a second embodiment of the reagent storage
device as device 300 wherein the reagent storage section 305 is
formed as a standalone unit. This embodiment may be referred to as
the standalone reagent section embodiment. Reagent storage device
300 exhibits a geometry similar to reagent storage section 205 of
FIG. 2C. This embodiment requires no score line. Like the first
embodiment, reagent storage device 300 may be conical, tubular or
cylindrical and its central channel may be conical, tubular or
cylindrical.
[0067] Reagent storage devices 200, 300 and 500 may be formed as a
pipette tip that is insertable into a pipette that transfers the
target specific PCR component into the reagent storage device prior
to lyophilization of the target specific PCR component, i.e.
reagent, in the reagent storage device. In one embodiment, the
reagent storage device exhibits a narrow end closest to the stored
reagent 225 and a wide end farthest from the stored reagent 225. In
another embodiment, both ends of the reagent storage device may
exhibit the same diameter or substantially similar diameters.
[0068] Referring generally to FIG. 4A, the reagent storage device
may employ a 405 cap placed over one of the ends of the tube of the
reagent storage device, such as device 300, of FIG. 3 to enable the
user to pick up the reagent storage device 300 with a gloved hand
via the cap 405 while avoiding contamination of the reagent storage
device 300 by the user. In one embodiment, wherein the reagent
storage device exhibits a narrow end and a wide end, the cap 405 is
placed over the narrow end. Alternatively, the cap 405 is placed
over the wide end. If the reagent storage device exhibits same size
ends, i.e. same diameter opposed ends, the cap is placed over
either opposed end to facilitate transfer of the reagent storage
device to the dedicated target specific port in the universal
cartridge 100 while avoiding contamination.
[0069] Cap 405 of FIG. 4A includes at least one open end that is
placed over one of the ends of the reagent storage device 300. In
the embodiment depicted, cap 405 is a sleeve of flexible plastic
material that includes two open in FIG. 4A. Either end of this dual
open-ended cap may be placed over an end of reagent storage device
300. The user slightly squeezes the flexible cap 405 sufficiently
to hold an end of the reagent storage device 300 therein. The user,
now grasping the reagent storage device 300 via the cap 405, moves
the reagent storage device 300 over the dedicated port 104 in
universal cartridge 100. The user reduces the squeezing action on
cap 405 to allow the reagent storage device 300 to fall into the
chamber below the dedicated port 104. Subsequently, the lyophilized
target specific PCR component may be rehydrated and testing is
conducted in the testing instrument. Alternatively, rehydration may
be performed at an earlier time.
[0070] In another embodiment shown in FIG. 4B and FIG. 4C, an
improved cap 415 includes a flexible bulbous ejector 420 that
facilitates the user in ejecting the reagent storage device 300
from cap 415 when the user desires to place the reagent storage
device 300 in the dedicated port 104 of universal cartridge 100. In
this embodiment, improved cap 415 is still sleeve-like in that it
fits over an end of the reagent storage device 300, but one end of
cap 415 is closed. For example, as seen in FIGS. 4B and 4C, the
closed end of the cap 415 may include a flexible bulbous ejector
420 that the user squeezes to push the end of the reagent storage
device out of cap 415 and into the dedicated port 104 of cartridge
100. FIG. 4C shows cap 415 installed on one end of the reagent
storage device 300. Cap 415 may be installed on an open end of the
sleeve-shaped cylindrical reagent storage device 300 described
above or an open end of a conically-shaped reagent storage device.
In actual practice, if a conically-shaped reagent storage device is
employed, cap 415 is installed on the narrow end of the reagent
storage device. Alternatively, cap 415 may be installed on the wide
end of the reagent storage device. Alternatively, instead of the
cap described above, the reagent storage device 300 may include a
small handle that the user may grasp while moving the reagent
storage device 300 to the dedicated port 104 of the universal
cartridge 100.
[0071] FIG. 5A shows a perspective view of the preferred embodiment
of the reagent storage device as device 500. Reagent storage device
500 may also be referred to as a "tip". Device 500 includes a
break-off region 515 at which device 500 intentionally breaks when
device 500 is inserted into dedicated port 104 of universal
cartridge 100 and is bent or torqued in the manner described above.
Breaking, i.e. snapping off, device 500 at break-off region 515
separates device 100 into 2 structures, namely reagent storage
section 505 and remaining section 510. Reagent storage device 500
is fabricated of a moldable plastic material such as high purity
polypropylene, medical grade polystyrene, or polydimethylsiloxane
(PDMS) silicones, for example. Reagent storage device 500 is
fabricated to be transparent, translucent or opaque, as desired. In
any case, target specific PCR component 525 is drawn to be visible
in FIG. 5A although it is situated in central channel 520 which is
interior to device 500.
[0072] In this embodiment, the geometry of device 500 is generally
conical from wide end 510A to narrow end 505A. In other words,
reagent storage section 505 is generally conical and exhibits an
increasing diameter as distance increases from narrow end 505A. In
this particular embodiment, remaining section 510 includes
subsections 510B and 510C, each of which are generally conical as
shown. More particularly, middle subsection 510B is conical and
exhibits generally increasing diameter from break-off region 515 to
wide-end subsection 510C. Device 500 includes a collar 530 at wide
end 510A as shown. Collar 530 includes castellation elements 532
that increase the rigidity of collar 530 and wide end 510A to
facilitate the reliable mounting of wide end 510A to a mandrel or
shaft of a liquid handling system or alternatively to a
micropipette. When reagent storage device 500 is so mounted, the
target specific PCR component 525 can be drawn up into narrow end
505A before freezing and lyophilization. Reagent storage device 500
may also be so mounted to dispense water into wide end 510A to
rehydrate target specific PCR component 525 before dispensing the
rehydrated target specific PCR component 525 into dedicated port
104 of universal cartridge 100.
[0073] As seen in FIGS. 5B and 5C, device 500 is molded in two
pieces, namely top portion 500A and bottom portion 500B as
evidenced by mold lines 542 and 544. After molding, top portion
500A and bottom portion 500B may be fused together using heat and
pressure.
[0074] Break-off region 515 is formed in top portion 500A and
bottom portion 500B during the molding process. At break-off region
515, reagent storage device 500 is intentionally structurally
weakened in comparison with the structural integrity of the
remainder of the device. In this manner, when reagent storage
section 505 is inserted in dedicated port 104 and bent against the
interior of port 104, reagent storage section 505 breaks away from
remaining section 510. Consequently, reagent storage section 505
with the user selected target specific PCR component 525 therein
falls into dedicated port 104. This completes the "programming" of
universal cartridge 100 for use in a test that targets a sequence
corresponding to the particular target specific PCR component
525.
[0075] FIG. 5D shows a cross-section of reagent storage device 500
taken along section line 5D-5D of FIG. 5B. More particularly, FIG.
5D shows a break-off region that is implemented as a V-shaped
groove 517 in the exterior surface of device 500. FIG. 5D' shows a
break-off region that is implemented as a V-shaped groove 517 in
the exterior surface of device 500 and a coaxial V-shaped groove in
the interior surface of device 500, i.e. a coaxial V-shaped groove
in central channel 520. In alternative embodiments, groove's 517
and 519 may exhibit other geometries, such as U-shaped for example,
as long as the selected geometry provides break-off region 515 with
sufficient structural weakness that it breaks when bent or torqued
in dedicated port 104 as described above. Selecting a geometry that
generally narrows the thickness of the tubular member that forms
device 500 at break-off region 515 can provide the desired
break-off or snap-off feature to device 500.
[0076] FIG. 5E is an end view of reagent storage device 500 as
viewed from narrow end 505A. FIG. 5E shows mainly the exterior of
device 500. FIG. 5F is an end view of reagent storage device 500 as
viewed from wide end 510A. FIG. 5F shows mainly the interior of
device 500.
[0077] FIG. 6A shows a simplified liquid handling system (LHS) 600
that includes multiple shafts 605 or mandrels on which reagent
storage device 500 may be mounted to draw a reagent, namely the
target specific PCR component, into device 500 for storage. When so
mounted, LHS 600 may alternatively dispense liquid into reagent
storage device 500 to rehydrate a lyophilized target specific PCR
component stored within device 500 prior to dispensing into the
dedicated port 104 of universal cartridge 100, as described above.
Reagent storage device 500 may alternately be coupled to a
micropipette (not shown) for these same purposes.
[0078] Specifically, FIG. 6A shows LHS 600 configured with reagent
storage device 500 situated on a shaft 605 or mandrel such that LHS
600 can draw the target specific PCR component reagent 525 (in
liquid form) from reservoir 610 into reagent storage section 505.
FIG. 6B shows LHS 600 after successfully drawing reagent 525 into
reagent storage section 505. Reagent 525 within reagent storage
section 505 of may now be frozen and lyophilized by using
appropriate refrigeration and lyophilization apparatus.
[0079] FIG. 7A shows a dual-purpose tab 700 that includes a plug
portion 705 that is dimensioned to fit into and plug, i.e. seal,
wide end 510A of target specific reagent storage device 500. As
depicted, plug portion 705 is generally conical. In one embodiment,
dual-purpose tab 700 also includes a planar tab portion 710 with
opposed sides 710A and 710B.
[0080] FIG. 7B shows dual purpose tab 700 with plug portion 705
situated in the central channel of reagent storage device 500 at
the wide end 510A thereof. Side 710B of tab 700 includes a
removably attached identification label 715, for example a barcode
label, that uniquely identifies the particular target specific PCR
component 525 in reagent storage device 500. Identification label
715 may be adhesively attached to side 710B of tab portion 710.
Identification label 715 is placed on tab portion 710 after LHS 600
draws the target specific PCR component 525 into reagent storage
device 500 and target specific PCR component 525 is frozen and
lyophilized, as per the discussion of LHS 600 with reference to
FIGS. 6A and 6B above. Tab 700 thus provides both a unique
identifier and a convenient way for the user to hold the target
specific PCR component reagent storage device 500.
[0081] FIG. 7C and FIG. 7D respectively provide front and back
views of tab 700. FIG. 7E and FIG. 7F respectively provide right
side and left side elevational views of tab 700. FIG. 7G and FIG.
7H respectively provide first and second end views of tab 700.
[0082] The customer or user may use tab 700 in two different ways
when tab 700 is installed in the wide end 510A of reagent storage
device 500, as depicted in FIG. 7B. In a first use, the user can
remove tab 700 from reagent storage device 500 (with the
lyophilized target specific PCR component reagent therein) and
reinsert device 500 on shaft 605 of the liquid handling system 600
of FIG. 6A. LHS 600, via its shaft 605, may draw water or buffer up
from a reservoir in fluidic communication with reagent storage
section 505 at narrow end 505A. The drawn fluid rehydrates the
lyophilized target specific PCR component 525. The rehydrated
target specific PCR component 525 in reagent storage device 500 may
now be dispensed into dedicated port 104 of universal cartridge
100. This dispensing action may be performed using the break-off
region method described above in detail. As an alternative to
employing LHS 600 for rehydration, the user may install device 500
in a micropipette to perform rehydration prior to dispensing the
rehydrated target specific PCR component 525 into dedicated port
104 of universal cartridge 100 using the above-described break-off
region method.
[0083] In a second use of tab 700, the user may opt to leave tab
700 installed in wide end 510A of reagent storage device 500. In
this user scenario, the user inserts the reagent storage section
505 into dedicated port 104 of universal cartridge 100 and uses the
break-off region dispensing method described above. Reagent storage
section 505 thus snaps or breaks off, and the target specific PCR
component reagent 525 in reagent storage section 505 is deposited
in port 104 of universal cartridge 100. After completing this
dispensing action, the user removes the barcode ID label 715 from
tab 700 and affixes barcode label 715 to the top of universal
cartridge 100. In this manner, now that the target specific PCR
component reagent 525 is inside universal cartridge 100, the
relocated barcode label 715 now on cartridge 100 identifies this
particular cartridge as containing the reagent that just dropped
into cartridge 100.
[0084] The varied embodiments described above may exhibit different
respective desirable features. In one embodiment, the disclosed
reagent storage device enables the rapid menu expansion of testing
options for users. As discussed above, universal cartridge 100
stores generic reagents applicable to a number of different tests,
but does not initially store a target specific PCR component
reagent that targets a particular sequence desired by the user for
a particular test. The user is empowered to effectively customize a
test to target a particular sequence. This is achieved uniquely by
dispensing the target specific PCR component stored in the
disclosed reagent storage device which includes the special
break-off region as described above. Users may now conduct
different types of tests with different specimens and targeting
different sequences without the need for a massive and expensive
inventory of cartridges that contain all reagents for all possible
desired tests.
[0085] The universal cartridge stores generic reagents for testing,
but also includes a dedicated port that receives a target specific
PCR component that customizes the test to be performed using the
universal cartridge. In one embodiment, after dispensing the target
specific PCR component into the dedicated port using the
above-described break off region method, when the user moves the
unique barcode label from the tab to the universal cartridge, this
signifies that the universal cartridge is effectively programmed to
perform a dedicated test.
[0086] The terminology used herein is for the purpose of describing
particular embodiments only and is not intended to be limiting of
the invention. As used herein, the singular forms "a", "an" and
"the" are intended to include the plural forms as well, unless the
context clearly indicates otherwise. It will be further understood
that the terms "comprises" and/or "comprising," when used in this
specification, specify the presence of stated features, integers,
steps, operations, elements, and/or components, but do not preclude
the presence or addition of one or more other features, integers,
steps, operations, elements, components, and/or groups thereof.
[0087] The corresponding structures, materials, acts, and
equivalents of all means or step plus function elements in the
claims below are intended to include any structure, material, or
act for performing the function in combination with other claimed
elements as specifically claimed. The description of the present
invention has been presented for purposes of illustration and
description, but is not intended to be exhaustive or limited to the
invention in the form disclosed. Many modifications and variations
will be apparent to those of ordinary skill in the art without
departing from the scope and spirit of the invention. The
embodiment was chosen and described in order to best explain the
principles of the invention and the practical application, and to
enable others of ordinary skill in the art to understand the
invention for various embodiments with various modifications as are
suited to the particular use contemplated.
* * * * *