U.S. patent application number 17/576969 was filed with the patent office on 2022-07-21 for heating device for testing a biological sample.
The applicant listed for this patent is Purdue Research Foundation, Raytheon BBN Technologies, Corp.. Invention is credited to Aaron Adler, Avram Bar-Cohen, Bryan Bartley, David Dempster, Paul Dryer, Mike Gavin, Dylan Horvath, Parth Jain, Frank M. LaDuca, Andrew Lowe, Charlie Man, Timothy Quinn, Mohit Verma.
Application Number | 20220228956 17/576969 |
Document ID | / |
Family ID | 1000006211653 |
Filed Date | 2022-07-21 |
United States Patent
Application |
20220228956 |
Kind Code |
A1 |
Horvath; Dylan ; et
al. |
July 21, 2022 |
Heating Device for Testing a Biological Sample
Abstract
A heating device for testing a biological sample is disclosed.
The heating device can include a heat source operable to generate
heat. In addition, the heating device can include a controller in
communication with the heat source and operable to control heat
generation by the heat source to heat a biological sample at less
than or equal to about 2 degrees C./s. Furthermore, a heating
device for testing a biological sample is disclosed that can
include a heat source operable to generate heat to heat a
biological sample. The biological sample can be at least partially
contained within a removable enclosure distinct from the heating
device. Additionally, the heating device can include an enclosure
interface associated with the heat source. The enclosure interface
can be configured to interface with the enclosure such that heat is
transferred from the heat source to the enclosure by
conduction.
Inventors: |
Horvath; Dylan; (Toronto,
CA) ; Man; Charlie; (Toronto, CA) ; Lowe;
Andrew; (Toronto, CA) ; Dempster; David;
(Mississauga, CA) ; Jain; Parth; (Toronto, CA)
; Adler; Aaron; (Towson, MD) ; Bartley; Bryan;
(Arlington, MA) ; Dryer; Paul; (Marshfield,
MA) ; Quinn; Timothy; (Gloucester, MA) ;
Bar-Cohen; Avram; (Bethesda, MD) ; Gavin; Mike;
(Princeton, NJ) ; LaDuca; Frank M.; (Warrensburg,
NY) ; Verma; Mohit; (West Lafayette, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Raytheon BBN Technologies, Corp.
Purdue Research Foundation |
Cambridge
West Lafayette |
MA
IN |
US
US |
|
|
Family ID: |
1000006211653 |
Appl. No.: |
17/576969 |
Filed: |
January 16, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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63138310 |
Jan 15, 2021 |
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63138312 |
Jan 15, 2021 |
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63138314 |
Jan 15, 2021 |
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63138316 |
Jan 15, 2021 |
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63138318 |
Jan 15, 2021 |
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63138320 |
Jan 15, 2021 |
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63138321 |
Jan 15, 2021 |
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63138323 |
Jan 15, 2021 |
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63138337 |
Jan 15, 2021 |
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63138341 |
Jan 15, 2021 |
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63148527 |
Feb 11, 2021 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01K 7/22 20130101; G01N
1/44 20130101; G01K 7/02 20130101 |
International
Class: |
G01N 1/44 20060101
G01N001/44; G01K 7/22 20060101 G01K007/22; G01K 7/02 20060101
G01K007/02 |
Claims
1. A heating device for testing a biological sample, comprising: a
heat source operable to generate heat; and a controller in
communication with the heat source and operable to control heat
generation by the heat source to heat a biological sample at less
than or equal to about 2 degrees C./s.
2. The heating device of claim 1, wherein the controller is
operable to control heat generation by the heat source to heat the
biological sample from about 0.5-1.5 degrees C./s.
3. The heating device of claim 2, wherein the controller is
operable to control heat generation by the heat source to heat the
biological sample from about 0.8-1.2 degrees C./s.
4. The heating device of claim 1, further comprising a timer in
communication with the controller and operable to provide time data
to the controller, wherein the controller controls the heater to
provide heat for a predetermined incubation time period.
5. The heating device of claim 1, further comprising a thermal
sensor in communication with the controller, the thermal sensor
being operable to sense a temperature associated with the
biological sample, wherein the controller controls heat generation
by the heat source based on the temperature.
6. The heating device of claim 5, wherein the thermal sensor
comprises at least one of a contact sensor or a non-contact
sensor.
7. The heating device of claim 5, wherein the thermal sensor
comprises at least one of an optical thermal sensor, an infrared
thermal sensor, a thermocouple, a thermistor, or a resistance
temperature detector (RTD).
8. The heating device of claim 1, wherein the heat source comprises
at least one of a resistance heater, an induction heater, a radiant
heater, a convection heater, a thermoelectric heater, or a heat
spreader.
9. The heating device of claim 1, further comprising a thermal
sensor in communication with the controller, the thermal sensor
being operable to sense a temperature associated with the heat
source.
10. The heating device of claim 1, wherein the biological sample is
at least partially contained within an enclosure, and the heat
source is configured to interface with the enclosure such that heat
is transferred from the heat source to the enclosure by
conduction.
11. The heating device of claim 1, further comprising a chamber
configured to receive the biological sample therein.
12. The heating device of claim 11, wherein the chamber is defined
at least in part by a portion of the heat source.
13. The heating device of claim 11, wherein the heat source is
physically separated from the biological sample such that heat is
transferred from the heat source to the biological sample by at
least one of radiation or convection.
14. The heating device of claim 13, wherein the biological sample
is at least partially contained within an enclosure and heat is
transferred from the heat source to the enclosure by at least one
of radiation or convection.
15. A heating device for testing a biological sample, comprising: a
heat source operable to generate heat to heat a biological sample,
the biological sample being at least partially contained within a
removable enclosure distinct from the heating device; and an
enclosure interface associated with the heat source, wherein the
enclosure interface is configured to interface with the enclosure
such that heat is transferred from the heat source to the enclosure
by conduction.
16. The heating device of claim 15, further comprising a controller
in communication with the heat source and operable to control heat
generation by the heat source to heat a biological sample at less
than or equal to about 2 degrees C./s.
17. The heating device of claim 16, wherein the controller is
operable to control heat generation by the heat source to heat the
biological sample from about 0.5-1.5 degrees C./s.
18. The heating device of claim 17, wherein the controller is
operable to control heat generation by the heat source to heat the
biological sample from about 0.8-1.2 degrees C./s.
19. The heating device of claim 17, further comprising a timer in
communication with the controller and operable to provide time data
to the controller, wherein the controller controls the heater to
provide heat for a predetermined incubation time period.
20. The heating device of claim 16, further comprising a thermal
sensor in communication with the controller, the thermal sensor
being operable to sense a temperature associated with the
biological sample, wherein the controller controls heat generation
by the heat source based on the temperature.
21. The heating device of claim 20, wherein the temperature
associated with the biological sample is a temperature of at least
a portion of the enclosure.
22. The heating device of claim 20, wherein the thermal sensor
comprises at least one of a contact sensor or a non-contact
sensor.
23. The heating device of claim 20, wherein the thermal sensor
comprises at least one of an optical thermal sensor, an infrared
thermal sensor, a thermocouple, a thermistor, or a resistance
temperature detector (RTD).
24. The heating device of claim 15, wherein the heat source
comprises at least one of a resistance heater, an induction heater,
a radiant heater, a convection heater, a thermoelectric heater, or
a heat spreader.
25. The heating device of claim 15, further comprising a thermal
sensor in communication with the controller, the thermal sensor
being operable to sense a temperature associated with the heat
source.
26. The heating device of claim 15, further comprising a base and a
lid rotatably coupled to the base.
27. The heating device of claim 26, further comprising a sensor
associated with at least one of the base or the lid, the sensor
being operable to determine whether the enclosure is present.
28. The heating device of claim 26, further comprising at least one
of a key or a keyway associated with at least one of the base or
the lid, the at least one of the key or the keyway being operable
to facilitate proper alignment of the enclosure with the at least
one of the base or the lid.
29. A tangible and non-transitory computer readable medium
comprising one or more computer software modules configured to
direct one or more processors to: receive temperature data
generated by a thermal sensor, the temperature data associated with
a biological sample; determine a control command for a heat source
based on the temperature data, the heat source being operable to
heat the biological sample, wherein the control command is
configured to heat the biological sample at less than or equal to
about 2 degrees C./s; and communicate the control command to the
heat source.
30. The tangible and non-transitory computer readable medium of
claim 29, wherein the control command is configured to control heat
generation by the heat source to heat the biological sample from
about 0.5-1.5 degrees C./s.
31. The tangible and non-transitory computer readable medium of
claim 30, wherein the control command is configured to control heat
generation by the heat source to heat the biological sample from
about 0.8-1.2 degrees C./s.
32. The tangible and non-transitory computer readable medium of
claim 29, further comprising: receive time data generated by a
timer; determine an expiration of a predetermined incubation time
interval for the biological sample beginning when the temperature
data indicates a temperature value greater than or equal to a
predetermined minimum temperature value; and communicate a
termination command to the heat source to cease heat generation
upon expiration of the incubation period.
33. A method for facilitating testing of a liquid biological
sample, comprising: facilitating heating of a biological sample at
less than or equal to about 2 degrees C./s.
34. The method of claim 33, wherein facilitating heating of the
biological sample comprises obtaining a controller in communication
with a heat source, the controller being operable to control heat
generation by the heat source.
35. The method of claim 34, further comprising obtaining a thermal
sensor in communication with the controller, the thermal sensor
being operable to sense a temperature associated with the
biological sample, wherein the controller controls heat generation
by the heat source based on the temperature.
36. The method of claim 34, further comprising facilitating
termination of heating the biological sample upon expiration of a
predetermined incubation time period.
37. The method of claim 36, wherein facilitating termination of
heating the biological sample upon expiration of a predetermined
incubation time period comprises obtaining a timer in communication
with the controller and operable to provide time data to the
controller, wherein the controller controls the heater to provide
heat for the predetermined incubation time period.
Description
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 63/138,310 filed Jan. 15, 2021, U.S.
Provisional Patent Application Ser. No. 63/138,312 filed Jan. 15,
2021, U.S. Provisional Patent Application Ser. No. 63/138,314 filed
Jan. 15, 2021, U.S. Provisional Patent Application Ser. No.
63/138,316 filed Jan. 15, 2021, U.S. Provisional Patent Application
Ser. No. 63/138,318 filed Jan. 15, 2021, U.S. Provisional Patent
Application Ser. No. 63/138,320 filed Jan. 15, 2021, U.S.
Provisional Patent Application Ser. No. 63/138,321 filed Jan. 15,
2021, U.S. Provisional Patent Application Ser. No. 63/138,323 filed
Jan. 15, 2021, U.S. Provisional Patent Application Ser. No.
63/138,337 filed Jan. 15, 2021, U.S. Provisional Patent Application
Ser. No. 63/138,341 filed Jan. 15, 2021, U.S. Provisional Patent
Application Ser. No. 63/148,527 filed Feb. 11, 2021, the entire
contents of each of which are incorporated herein by reference.
BACKGROUND
[0002] In some forms of pathogen testing (e.g., Loop-Mediated
Isothermal Amplification (LAMP)), a heating process can be utilized
to test a biological sample for the presence of a pathogen (e.g., a
viral pathogen, a bacterial pathogen, a fungal pathogen, or a
protozoa pathogen). Such tests can use a simple visual output test
indicator, such as a color change, to identify the presence or
absence of a pathogen. These tests can be performed with minimal
equipment (e.g., sample collection and preparation tools, a heating
device, etc.) and sample preparation and can therefore be
accessible for use in point of care settings, such as clinics,
emergency rooms, and even on a mobile basis.
BRIEF DESCRIPTION OF THE DRAWINGS
[0003] Features and advantages of the invention will be apparent
from the detailed description which follows, taken in conjunction
with the accompanying drawings, which together illustrate, by way
of example, features of the invention; and, wherein:
[0004] FIG. 1 is a schematic illustration of a biological test
system in accordance with an example of the present disclosure.
[0005] FIGS. 2A and 2B are schematic illustrations of a liquid
biological sample test cartridge in accordance with an example of
the present disclosure.
[0006] FIG. 3A is a top isometric view of a biological test system
in accordance with an example of the present disclosure.
[0007] FIG. 3B is a top isometric view of the biological test
system of FIG. 3A with a lid of a heating device in an open
configuration, in accordance with an example of the present
disclosure.
[0008] FIG. 4 is a schematic illustration of the biological test
system of FIGS. 3A and 3B.
[0009] FIG. 5A is a top isometric view of a heating device of the
biological test system of FIGS. 3A and 3B, in accordance with an
example of the present disclosure.
[0010] FIG. 5B is a bottom isometric view of the heating device of
FIG. 5A, in accordance with an example of the present
disclosure.
[0011] FIG. 5C is a top isometric view of the heating device of
FIG. 5A with a lid in an open configuration, in accordance with an
example of the present disclosure.
[0012] FIG. 6 is a feedback control diagram for controlling heating
a biological sample in the biological test system of FIGS. 3A and
3B, in accordance with an example of the present disclosure.
[0013] FIG. 7 illustrates multiple heating devices as in the
biological test system of FIGS. 3A and 3B coupled to one another,
in accordance with an example of the present disclosure.
[0014] FIG. 8A is a top isometric view of a liquid biological
sample test cartridge of the biological test system of FIGS. 3A and
3B, in accordance with an example of the present disclosure.
[0015] FIG. 8B is a bottom isometric view of the liquid biological
sample test cartridge of FIG. 8A, in accordance with an example of
the present disclosure.
[0016] FIG. 9A is a top isometric view of a tray of the liquid
biological sample test cartridge of FIGS. 8A and 8B, in accordance
with an example of the present disclosure.
[0017] FIG. 9B is a top isometric view of the tray of FIG. 9A
supporting a chemical reaction pad, in accordance with an example
of the present disclosure.
[0018] FIG. 9C is a bottom isometric view of the tray of FIG. 9A,
in accordance with an example of the present disclosure.
[0019] FIG. 10 is a top isometric view of the tray of FIG. 9A with
a chemical reaction pad cover over the chemical reaction pad, in
accordance with an example of the present disclosure.
[0020] FIG. 11A is a top isometric view of the chemical reaction
pad cover of FIG. 10, in accordance with an example of the present
disclosure.
[0021] FIG. 11B is a bottom isometric view of the chemical reaction
pad cover of FIG. 10, in accordance with an example of the present
disclosure.
[0022] FIG. 12A is a top isometric view of an outer cover of the
liquid biological sample test cartridge of FIGS. 8A and 8B, in
accordance with an example of the present disclosure.
[0023] FIG. 12B is a bottom isometric view of the outer cover of
the liquid biological sample test cartridge of FIG. 12A, in
accordance with an example of the present disclosure.
[0024] FIG. 13A is a top view of the chemical reaction pad of FIG.
9B, in accordance with an example of the present disclosure.
[0025] FIG. 13B is a side view of the chemical reaction pad of FIG.
13A, in accordance with an example of the present disclosure.
[0026] FIG. 14A is a top view of a chemical reaction pad in
accordance with an example of the present disclosure.
[0027] FIG. 14B is a side view of the chemical reaction pad of FIG.
14A, in accordance with an example of the present disclosure.
[0028] FIG. 15 is a top view of a chemical reaction pad in
accordance with an example of the present disclosure.
[0029] FIG. 16 is a top view of a chemical reaction pad in
accordance with an example of the present disclosure.
[0030] FIG. 17 is a top view of a chemical reaction pad in
accordance with an example of the present disclosure.
[0031] FIG. 18 is a top view of a chemical reaction pad in
accordance with an example of the present disclosure.
[0032] FIG. 19 is a top view of a chemical reaction pad in
accordance with an example of the present disclosure.
[0033] FIG. 20 is a schematic illustration of a chemical reaction
pad in accordance with an example of the present disclosure.
[0034] FIGS. 21A-21C capillary channel cross-sectional shapes in
accordance with several examples of the present disclosure.
[0035] FIG. 22 illustrates a tray and the chemical reaction pad of
the liquid biological sample test cartridge of FIG. 8A, with the
chemical reaction pad cover omitted for clarity.
[0036] FIG. 23 illustrates a top view of the liquid biological
sample test cartridge of FIG. 8A, showing the chemical reaction pad
visible through the chemical reaction pad cover and the outer
cover.
[0037] FIG. 24 is a top isometric view of a liquid biological
sample test cartridge in accordance with an example of the present
disclosure.
[0038] FIG. 25 is a schematic illustration of a liquid biological
sample test kit in accordance with an example of the present
disclosure.
[0039] Reference will now be made to the exemplary embodiments
illustrated, and specific language will be used herein to describe
the same. It will nevertheless be understood that no limitation of
the scope of the invention is thereby intended.
DETAILED DESCRIPTION
[0040] As used herein, the term "substantially" refers to the
complete or nearly complete extent or degree of an action,
characteristic, property, state, structure, item, or result. For
example, an object that is "substantially" enclosed would mean that
the object is either completely enclosed or nearly completely
enclosed. The exact allowable degree of deviation from absolute
completeness may in some cases depend on the specific context.
However, generally speaking the nearness of completion will be so
as to have the same overall result as if absolute and total
completion were obtained. The use of "substantially" is equally
applicable when used in a negative connotation to refer to the
complete or near complete lack of an action, characteristic,
property, state, structure, item, or result.
[0041] As used herein, "adjacent" refers to the proximity of two
structures or elements. Particularly, elements that are identified
as being "adjacent" may be either abutting or connected. Such
elements may also be near or close to each other without
necessarily contacting each other. The exact degree of proximity
may in some cases depend on the specific context.
[0042] An initial overview of the inventive concepts are provided
below and then specific examples are described in further detail
later. This initial summary is intended to aid readers in
understanding the examples more quickly, but is not intended to
identify key features or essential features of the examples, nor is
it intended to limit the scope of the claimed subject matter.
[0043] In one aspect, a heating device for testing a biological
sample is disclosed that can include a heat source operable to
generate heat. In addition, the heating device can include a
controller in communication with the heat source and operable to
control heat generation by the heat source to heat a biological
sample at less than or equal to about 2 degrees C./s.
[0044] In one aspect, a heating device for testing a biological
sample is disclosed that can include a heat source operable to
generate heat to heat a biological sample. The biological sample
can be at least partially contained within a removable enclosure
distinct from the heating device. Additionally, the heating device
can include an enclosure interface associated with the heat source.
The enclosure interface can be configured to interface with the
enclosure such that heat is transferred from the heat source to the
enclosure by conduction.
[0045] To further describe the present technology, examples are now
provided with reference to the figures. With reference to FIG. 1,
one embodiment of a biological test system 100 is schematically
illustrated. In general, the biological test system 100 can
comprise a biological sample 101 and a heating device 102 for
testing the biological sample 101. In one aspect, the biological
test system 100 can provide for point-of-care (POC) testing of the
biological sample 101 in an in-patient or out-patient hospital
setting, a physician office laboratory, a drive thru clinic, a
pharmacy, a community care setting, etc. In some examples, the
biological sample 101 can be contained within a suitable enclosure
103, such as that provided by a test cartridge as disclosed herein
and discussed in more detail below. The enclosure 103 can serve to
provide a suitable test environment for the biological sample
101.
[0046] The biological sample 101 can be or include any suitable
biological material, such as saliva, mucus, blood, urine, feces,
etc. The heating device 102 can be utilized in any suitable manner
to perform a given type of test on the biological sample 101.
Examples of suitable tests that may be performed using the
biological test system 100 are disclosed in U.S. patent application
Ser. No. ______ (TNW Attorney Docket No. 3721-20.14629), which is
incorporated herein by reference in its entirety.
[0047] In one aspect, Loop-Mediated Isothermal Amplification (LAMP)
can be utilized to perform diagnostic identification of target
nucleotides that reside in a pathogen of interest, which may be
present in the biological sample 101. LAMP is a one-step nucleic
acid amplification method to multiply specific nucleotide
sequences. In addition to use of an isothermal heating process,
which can be executed by the heating device 102, LAMP can use a
simple visual output test indicator, such as a color change.
Reverse-transcription LAMP (RT-LAMP) can be used in order to
identify target nucleotides from RNA, and as such, can be used in a
diagnostic capacity to identify the presence or absence of viral
pathogens. Thus, in cases where the pathogen is a virus, the LAMP
analysis can be an RT-LAMP analysis. In one aspect, the biological
sample 101 can be in the presence of one or more reagents including
one or more target primers, DNA polymerase, and a re-solubilization
agent. In another aspect, the reagents can form a composition
sufficient to carry out a LAMP reaction.
[0048] In one aspect, the target pathogen can comprise a viral
pathogen, a bacterial pathogen, a fungal pathogen, or a protozoa
pathogen. In one aspect, the target pathogen can comprise a viral
pathogen. In one aspect, the viral pathogen can comprise a dsDNA
virus, an ssDNA virus, a dsRNA virus, a positive-strand ssRNA
virus, a negative-strand ssRNA virus, an ssRNA-RT virus, or a
ds-DNA-RT virus. In one aspect, each primer sequence can match a
sequence from a viral target comprising H1N1, H2N2, H3N2,
H1N1pdm09, or SARS-CoV-2.
[0049] In another aspect, the target nucleotide sequence can be
from at least one of a viral pathogen, a bacterial pathogen, a
fungal pathogen, or a protozoan pathogen. In one aspect, the target
nucleotide sequence can be from a viral pathogen. In one aspect,
the viral pathogen can be selected from the group consisting of:
Coronoviridae, Orthomyxoviridae, Paramyxoviridae, Picomaviridae,
Adenoviridae, and Parvoviridae. In another aspect, the viral
pathogen can be selected from the group consisting of: severe acute
respiratory syndrome coronavirus (SARS-CoV-1), severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East
respiratory syndrome (MERS), influenza, and H1N1. In one aspect,
the target nucleotide sequence can be from a severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen.
[0050] With further reference to FIG. 1, the heating device 102 can
include a heat source 110 operable to generate heat. The heat
source 110 can comprise any suitable type of heater or heating
element known in the art, such as at least one of a resistance
heater (e.g., a polymer thick-film (PTF) heating element), an
induction heater, a radiant heater, a convection heater, a chemical
heater (e.g., heat produced by an exothermic chemical reaction), a
thermoelectric heater (e.g., a Peltier device or heater), or a heat
spreader. In one aspect, the heat source 110 can be operable to
provide uniform heating across the biological sample 101. In one
aspect, the heat source 110 can provide for a heating uniformity
within the enclosure 103 that has a variability of less than 1
degree C. The spatial variability of the temperature around the
enclosure 103 should not be greater than about 0.5 degrees C. to
avoid interference with a LAMP reaction. In one example, the heat
source 110 can be physically separated from the biological sample
101 such that heat is transferred from the heat source to the
biological sample by at least one of radiation or convection. In
one aspect, the heating device 102 can include a chamber 111
configured to receive the biological sample 101 therein. In this
case, the chamber 111 and the heater 110 can form an oven. In some
examples, the chamber 111 can be defined at least in part by a
portion of the heat source 110 (e.g., forming at least a portion of
a wall of the chamber 111). In one example, the biological sample
101 can be at least partially contained within the enclosure 103
(e.g., as provided by a test cartridge). In one aspect, the heat
source 110 can be configured to interface with the enclosure 103
such that heat is transferred from the heat source 110 to the
enclosure 103 by conduction. In another aspect, heat can be
transferred from the heat source 110 to the enclosure 103 by at
least one of radiation or convection (e.g., the enclosure 103 or
test cartridge is located in an oven or the chamber 111).
[0051] In some examples, the heating device 102 can include a
controller 112 in communication with the heat source 110. The
controller 112 can be operable to control heat generation by the
heat source 110 to heat the biological sample 101 at a temperature
"ramp rate," which is an increase of temperature as a function of
time, as opposed to a steady state temperature that does not change
appreciably over time. In one aspect, the controller 112 can be
operable to control heat generation by the heat source 110 to heat
the biological sample 101 at a ramp rate of less than or equal to
about 2 degrees C./s. In one aspect, the controller 112 can be
operable to control heat generation by the heat source 110 to heat
the biological sample at a ramp rate from about 0.5-1.5 degrees
C./s. In another aspect, the controller 112 can be operable to
control heat generation by the heat source 110 to heat the
biological sample at a ramp rate from about 0.8-1.2 degrees C./s.
In yet another aspect, the controller 112 can be configured to
control heat generation by the heat source 110 to heat the
biological sample at a target ramp rate less than or equal to about
2 degrees C./s (e.g., about 0.1 degrees C./s) as controlled by a
feedback control loop. For example, the heating device 102 can
include a thermal sensor 113 in communication with the controller
112. The thermal sensor 113 can be operable to sense a temperature
associated with the biological sample 101, and the controller 112
can control heat generation by the heat source 110 based on the
temperature.
[0052] In some examples, an amount of reverse transcriptase can be
provided sufficient to facilitate an RT-LAMP reaction. In one
example, the reverse transcriptase can be activated at about 55
degrees C. and the DNA polymerase can be activated at about 65
degrees C. In one example, the ramp rate can be raised until the
test environment temperature is in a range from about 60 degrees C.
to about 67 degrees C. Consequently, a ramp rate higher than about
0.2 degrees C./s can interfere with the LAMP reaction. In some
examples, when the test environment is increased to about 55
degrees C. (i.e., the temperature at which the reverse
transcriptase can be activated), with a ramp rate of about 0.1
degrees C. from 55 degrees C. to about 65 degrees C., the
biological sample test apparatus can provide invalid results.
Therefore, the ramp rate should be monitored not just in the
testing environment temperature range from about 55 degrees C. to
about 65 degrees C., but also as the biological sample is being
heated to about 55 degrees C.
[0053] The thermal sensor 113 can be or include any suitable type
of sensor known in the art, such as, broadly speaking, at least one
of a contact sensor or a non-contact sensor. In particular,
non-limiting examples of the thermal sensor 113 can include at
least one of an optical thermal sensor, an infrared thermal sensor,
a thermocouple, a thermistor, or a resistance temperature detector
(RTD). In one example, the heating device 102 can include a thermal
sensor 114 in communication with the controller 112 that can be
operable to sense a temperature associated with the heat source
110. In some examples, the thermal sensor 114 can be used to
determine whether a suitable cool-down temperature (e.g., for user
safety) has been reached following completion of a test of the
biological sample 101. The thermal sensor 114 can be of any
suitable type known in the art as discussed above relative to the
thermal sensor 113.
[0054] In one aspect, the heating device 102 can include a timer or
clock 115 in communication with the controller 112. The timer 115
can be operable to provide time data to the controller 112. The
controller 112 can control the heater 110 to provide heat for a
predetermined incubation time period based on data provided by the
timer 115 and, in some examples, data provided by the thermal
sensor 113. The timer 115 can be or include any suitable type of
timer or clock known in the art to provide time information or data
to the controller 112, such as, broadly speaking, at least one of a
hardware clock or a software clock.
[0055] In one aspect, a testing time can be from about 15 minutes
to about 30 minutes for a saliva sample. In another aspect, a
testing time can be from about 30 minutes to about 45 minutes for a
saliva sample. In another aspect, a testing time can be from about
45 minutes to about 60 minutes for a saliva sample. In another
aspect, a testing time can be from about 60 minutes to about 90
minutes for a saliva sample. In another aspect, a testing time can
be from about 20 minutes to about 30 minutes for a nasopharyngeal
sample. In another aspect, a testing time can be from about 30
minutes to about 40 minutes for a nasopharyngeal sample.
[0056] In one aspect, the heat source 110 can be configured to
isothermally heat the enclosure 103 to an internal temperature
sufficient to initiate and sustain a LAMP reaction between a LAMP
reagent mixture and the biological sample 101 for a time used to
generate a test result via the pH-sensitive dye.
[0057] In one aspect, the heat source 110 can be configured to
actively and/or passively cool the enclosure 103. In some examples,
the heat source 110 can comprise a thermoelectric heater (e.g., a
Peltier device or heater), which can also be operable as a cooler
(e.g., a heat pump) to actively cool the enclosure 103 and reduce
the time needed to cool the enclosure 103 sufficient for safe
handling.
[0058] The controller 112 can have any suitable structure and can
include any suitable component known in the art to perform the
function of a controller as disclosed herein. For example, the
controller 112 can include any suitable hardware (e.g., a processor
117, computer memory 118, etc.) and/or software operable to control
operation of the heat source 110 and/or communicate with and
process data from the thermal sensors 113, 114 and/or the timer
115. It should be appreciated by those skilled in the art that the
controller 112 can include a tangible and non-transitory computer
readable medium comprising one or more computer software modules
configured to direct one or more processors to perform the method
steps and functions/operations described herein.
[0059] FIGS. 2A and 2B schematically illustrate an example of a
liquid biological sample test cartridge 204 that can be used with a
heating device as disclosed herein to test a biological sample. The
cartridge 204 can include a tray 220. The cartridge 204 can also
include a chemical reaction pad 221 supported by the tray 220. The
cartridge 204 can further include a chemical reaction pad cover 222
disposed over the chemical reaction pad 221. The chemical reaction
pad cover 222 can be coupled to the tray 220. The chemical reaction
pad cover 222 can have a sample opening 223 to facilitate
depositing a liquid biological sample 201 on the chemical reaction
pad 221 (e.g., at a predetermined location). In addition, the
cartridge 204 can include an outer cover 224 operable to at least
partially form an enclosure 203 (FIG. 2B) about the chemical
reaction pad 221.
[0060] The chemical reaction pad 221 can have any suitable
configuration and composition of materials, which can be selected
based on a type of test to be performed on the biological sample
201. In one aspect, the chemical reaction pad 221 can comprise a
"solid phase medium," which refers to a non-liquid medium. In one
example, the non-liquid medium can be a material with a porous
surface. In another example, the non-liquid medium can be a
material with a fibrous surface. In yet another example, the
non-liquid medium can be paper. A "solid phase medium," "solid
phase base" "solid phase substrate" "solid phase test substrate"
"solid phase testing substrate," "solid phase reaction medium" and
the like can be used interchangeably herein and refer to a
non-liquid medium, device, system, or environment. In some aspects,
the non-liquid medium may be substantially free of liquid or
entirely free of liquid. In one example, the non-liquid medium can
comprise or be a porous material or a material with a porous
surface. In another example, the non-liquid medium can comprise or
be a fibrous material or a material with a fibrous surface. In yet
another example, the non-liquid medium can be a paper.
[0061] There are various materials that the solid-phase reaction
medium can be comprise or include. In one aspect, the solid-phase
reaction medium can comprise one or more of glass fiber, nylon,
cellulose, polysulfone, polyethersulfone, cellulose acetate,
nitrocellulose, hydrophilic polytetrafluoroethylene (PTFE), the
like, or combinations thereof. In another aspect, the solid-phase
reaction medium can be a cellulose-based medium.
[0062] In some examples, the chemical reaction pad 221 can include
a solid-phase reaction medium in combination with a LAMP reagent
mixture and a pH sensitive dye. In some examples, the chemical
reaction pad 221 can include a substrate engaging a solid phase
reaction medium in combination with a dehydrated loop-mediated
isothermal amplification (LAMP) reagent mixture and a dehydrated
pH-sensitive dye. In one aspect, the substrate can comprise an
optically transparent material. In another aspect, the substrate
can engage the solid phase reaction medium via an adhesive. In
another aspect, the adhesive can be substantially optically
transparent. In another aspect, an adhesive layer can be disposed
on a substrate, a reaction layer can be disposed on the adhesive
layer, and a spreading layer can be disposed on the reaction layer.
These and other aspects of a chemical reaction pad as disclosed
herein are discussed in more detail below.
[0063] FIGS. 3A and 3B illustrate a biological test system 300 in
accordance with an example of the present disclosure. A schematic
representation of the biological test system 300 is shown in FIG.
4. The biological test system 300 can include a heating device 302
and a liquid biological sample test cartridge 304, which can be
configured to contain a biological sample 301 for testing. Various
aspects and features of the heating device 302 are shown more
particularly in FIGS. 5A-7. Various aspects and features of the
cartridge 304 are shown more particularly in FIGS. 8A-23.
[0064] The fully assembled cartridge 304 is shown isolated from the
heating device 302 in FIGS. 8A and 8B. In general, as with the
cartridge 204 of FIGS. 2A and 2B, the cartridge 304 can include a
tray 320 (FIGS. 9A-10), a chemical reaction pad 321 upon which the
biological sample 301 can be deposited (FIGS. 9B, 13A, and 13B), a
chemical reaction pad cover 322 (FIGS. 10-11B), and an outer cover
324 (FIGS. 8A, 8B, 12A, and 12B). The outer cover 324 can be
operable to at least partially form an enclosure 303 (FIGS. 8A and
8B) about the biological sample 301.
[0065] The heating device 302 is shown isolated from the cartridge
304 in FIGS. 5A-5C. In general, as with the heating device 102 of
FIG. 1, the heating device 302 can include a heat source 310 (FIG.
4) operable to generate heat to heat the biological sample 301. In
the case of the heating device 302, the biological sample 301 can
be at least partially contained within a removable enclosure (e.g.,
the enclosure 303 provided by the cartridge 304), which is distinct
from the heating device 302. The heating device 302 can include an
enclosure interface 360 associated with the heat source 310. The
enclosure interface 360 can be configured to interface with the
enclosure 303 (e.g., the outer cover 324) such that heat is
transferred from the heat source 310 to the enclosure 303 by
conduction. An outer surface defining the enclosure 303 (e.g., an
outer surface of a bottom wall 355a of the outer cover 324 shown in
FIG. 8B) can be configured to interface with the enclosure
interface 360 or the heat source 310 (e.g., a heater, a heating
element, or related structure, such as a heat spreader) of the
heating device 302. In one aspect, the heat source 310 can be
operable to provide uniform heating across the biological sample
301, such as by evenly heating the bottom wall 355a of the outer
cover 324 via the enclosure interface 360. The heat source 310 can
comprise any suitable type of heater or heating element known in
the art, such as at least one of a resistance heater (e.g., a
polymer thick-film (PTF) heating element), an induction heater, a
radiant heater, a convection heater, a thermoelectric heater (e.g.,
a Peltier device or heater), or a heat spreader. In some examples,
a heat spreader can be separate and distinct from the heat source
310 (e.g., a spatially removed and separate component).
[0066] In one aspect, the heat source 310 can be configured to
actively and/or passively cool the enclosure 303 (e.g., the outer
cover 324). In some examples, the heat source 310 can comprise a
thermoelectric heater (e.g., a Peltier device or heater), which can
also be operable as a cooler (e.g., a heat pump) to actively cool
the enclosure 303 (e.g., the outer cover 324) and reduce the time
needed to cool the enclosure 303 sufficient for safe handling.
[0067] With reference to FIG. 4, the heating device 302 can include
a controller 312 in communication with the heat source 310. In one
aspect the controller 312 can be operable to control heat
generation by the heat source 310 to heat the biological sample at
a ramp rate less than or equal to about 2 degrees C./s. In one
aspect, the controller 312 can be operable to control heat
generation by the heat source 310 to heat the biological sample at
a ramp rate from about 0.5-1.5 degrees C./s. In another aspect, the
controller 312 can be operable to control heat generation by the
heat source 310 to heat the biological sample at a ramp rate from
about 0.8-1.2 degrees C./s. In yet another aspect, the controller
312 can be configured to control heat generation by the heat source
310 to heat the biological sample at a target ramp rate less than
or equal to about 2 degrees C./s (e.g., about 0.1 degrees C./s) as
controlled by a feedback control loop. For example, the heating
device 302 can include a thermal sensor 313 in communication with
the controller 312. The thermal sensor 313 can be operable to sense
a temperature associated with the biological sample 301, and the
controller 312 can control heat generation by the heat source 310
based on the temperature. The temperature associated with the
biological sample 301 can be a temperature of at least a portion of
the enclosure 303 (e.g., a surface of the outer cover 324, such as
an outer surface of a top wall 355b of the outer cover 324).
[0068] The thermal sensor 313 can be or include any suitable type
of sensor known in the art, such as, broadly speaking, at least one
of a contact sensor or a non-contact sensor. In particular,
non-limiting examples of the thermal sensor 313 can include at
least one of an optical thermal sensor, an infrared thermal sensor,
a thermocouple, a thermistor, or a resistance temperature detector
(RTD). In one example, the heating device 302 can include a thermal
sensor 314 in communication with the controller 312 that can be
operable to sense a temperature associated with the heat source
310. In some examples, the thermal sensor 314 can be used to
determine whether a suitable cool-down temperature (e.g., for user
safety) has been reached following completion of a test of the
biological sample 301. The thermal sensor 314 can be of any
suitable type known in the art as discussed above relative to the
thermal sensor 313.
[0069] One example of a feedback control diagram for controlling
heating of the biological sample 301 is shown in FIG. 6. In this
example, the controller 312 can comprise a digital PID
(proportional-integral-derivative) controller and the sensor 313
can comprise a non-contact infrared (IR) sensor, although any
suitable controller and sensor type can be utilized. In FIG. 6,
T.sub.IR is the temperature sensed from the IR sensor, which can
have a viewing angle directed at a center of the cartridge 304
(e.g., a center of a region within the cartridge where the
biological sample 301 is located). The temperature of the top side
of the cartridge 304 (e.g., the outer surface of the top wall 355b
of the outer cover 324) where the T.sub.IR is taken may lag the
temperature of the biological sample 301 within the cartridge 304
during heating. This temperature difference is referred to as
T.sub.offset. The offset temperature T.sub.offset can be determined
through empirical testing and/or thermal modeling to determine the
difference between the IR sensor temperature reading and the actual
temperature of the biological sample or assay. T.sub.offset can be
applied to the measured T.sub.IR temperature to produce a
calculated T.sub.assay temperature, which is the temperature of the
biological sample 301. This T.sub.assay temperature is compared to
the set point temperature T.sub.set, which is the target
temperature of the biological sample 301 and is selected to control
the maximum temperature of the biological sample 301 during the
test. The error produced by taking the difference between
T.sub.assay and T.sub.set is sent to the digital PID controller,
which outputs a heater control on/off duty cycle. Based on this
duty cycle, the heater will produce a corresponding heat which is
applied to the enclosure interface 360. The enclosure interface 360
is in contact with the cartridge 304 (e.g., the outer cover 324),
which contains the biological sample 301. Thus, the cartridge 304
(e.g., the outer surface of the top wall 355b of the outer cover
324) will heat up to a temperature of T.sub.cart, completing the
control loop.
[0070] In some examples, a desired temperature ramp rate may not be
directly controlled by the PID controller. For example, the
integral term of the PID controller may be set to keep the PID
controller at a relatively slow speed, which can result in the
heater ramping at a slow rate that falls within a desired ramp rate
range. In some examples, the PID controller can control a desired
temperature ramp rate by being configured to control the error term
received by the PID controller (i.e., the error produced by taking
the difference between T.sub.assay and T.sub.set) to decrease at a
magnitude equal to the desired temperature increase ramp rate.
[0071] In one aspect, the heating device 302 can include a timer or
clock 315 in communication with the controller 312. The timer 315
can be operable to provide time data to the controller 312. The
timer 315 can be or include any suitable type of timer or clock
known in the art to provide time information or data to the
controller 312, such as, broadly speaking, at least one of a
hardware clock or a software clock. The controller 312 can control
the heater 310 to provide heat for a predetermined incubation time
period based on data provided by the timer 315 and, in some
examples, data provided by the thermal sensor 313. In one example,
once the biological sample 301 reaches the temperature set point
T.sub.set, the timer 315 can start and run for a predetermined time
period. The timer 315 can control how long the biological sample
301 will remain at the set point temperature. In some examples, the
controller 312 can control the heat source 310 to produce a
temperature "spike," where the temperature of the biological sample
301 is increased to a predetermined temperature and maintained at
that temperature for a period of time, as measured by the timer
315. Once this time period has elapsed, the heat source 310 can be
turned off and the system 300 can be allowed to cool down until the
cartridge 304 is at a safe temperature for handling by a user.
[0072] The controller 312 can have any suitable structure and can
include any suitable components known in the art to perform the
function of a controller as disclosed herein. For example, the
controller 312 can include any suitable hardware (e.g., a processor
317, computer memory 318, etc.) and/or software operable to control
operation of the heat source 310 and/or communicate with and
process data from the thermal sensors 313, 314 and/or the timer
315. It should be appreciated by those skilled in the art that the
controller 312 can include a tangible and non-transitory computer
readable medium comprising one or more computer software modules
configured to direct one or more processors to perform the method
steps and operations described herein.
[0073] In some examples, as illustrated in FIG. 3A, the heating
device 302 can include a visual indicator 370, such as one or more
lights or any other suitable visual indicator (e.g., LED lights of
the same or different colors, a display, etc.) to assist the user
in operating the heating device 302 and/or to provide information
to the user (e.g., indicate testing progress and/or provide an
alert when a test has reached conclusion, signal an error or other
malfunction of the heater, indicate that a starting temperature has
been reached, and any other notification or information).
Alternatively, or in addition, the heating device 302 can include a
speaker or other sound generation device (not shown) that can
perform the same functions. In some examples, the heating device
302 can include a user interface 371, such as a button, a knob, a
lever, a touch pad, a touch screen display, or other suitable user
interface known in the art, to provide the user with a certain
degree of control over operation of the heating device 302 (e.g.,
power on/off, begin a test, access/select device
control/configuration menu items, etc.).
[0074] In one aspect, illustrated in FIGS. 3B and 3C, the cartridge
304 and the heating device 302 can be configured to operably
interface with one another to provide and ensure proper heating of
the biological sample. For example, the outer cover 324 can include
at least one of a key or a keyway 358 that interfaces with a
portion of the heating device 302, and that is operable to
facilitate proper alignment and/or orientation of the cartridge 304
with the heating device 302. Similarly, the heating device 302 can
include at least one of a key 368 or a keyway operable to
facilitate proper alignment of the enclosure 303 (e.g., provided by
the cartridge 304) with the heating device 302. In the illustrated
example, the heating device 302 can include a base 361 and a lid
362 rotatably coupled to the base 361 (e.g., at a pivot or hinge
363). The key 368 can be associated with at least one of the base
361 (as in this case) or the lid 362. In some examples, the heating
device 302 can include a sensor 316 associated with at least one of
the base 361 or the lid 362 (as in this case), which can be
operable to determine whether the enclosure 303 (e.g., the
cartridge 304) is present in the heating device 302.
[0075] In one aspect, the enclosure interface 360 (and any
associated heat source 310 and/or related structures or devices)
can be mounted or part of a floating platform to ensure a proper
alignment and interface of the enclosure interface 360 with the
cartridge 304 (e.g., the bottom wall 355a of the outer cover 324).
For example, the enclosure interface 360 and the heat source can be
on or a part of a platform 364, which is suspended by one or more
springs 365. In one aspect, the platform 364 can serve as a heat
spreader and the enclosure interface 360 can be a surface of the
heat spreader. The springs 365 can deflect to accommodate the
presence of the cartridge 304, which can preload the springs 365 to
maintain the enclosure interface 360 and the cartridge 304 in
contact with one another to ensure effective conductive heat
transfer from the enclosure interface 360 to the cartridge 304.
[0076] In one aspect, the heating device 302 can be configured to
maintain the lid 362 in a closed position (e.g., as shown in FIGS.
3A and 4), which can ensure that the enclosure interface 360 and
the cartridge 304 remain in contact with one another during the
test. Any suitable structure of device can be utilized for this
purpose, such as a latch, a clasp, a pin, etc. In one example,
magnets 366a, 366b can be associated with the base 361 and the lid
362, respectively. The magnets 366a, 366b can be configured to
provide a magnetic attraction force that exceeds the force exerted
by the springs 365 to maintain the lid 362 in a closed position
relative to the base 361.
[0077] The heating device 302 can include a power connection port
367 to facilitate connection with a power cord (not shown) to
receive power from an external power source. In some examples, the
heating device 302 can be battery powered as an alternative or in
addition to an external power source option. In some examples, the
heating device 302 can include a battery that is operable to supply
power for the heating device 302.
[0078] In one aspect, as illustrated in FIG. 7, the heating device
302 can be configured to be coupled to other similar heating
devices to provide for distribution of power among several
connected devices so that all connected heating devices can run on
a single power supply cable. In this case, each connected heating
device 302 can include two power connection ports, and a power
coupler 369 can be coupled between adjacent heating devices 302 to
provide for power supply to each connected device. In this way, any
suitable number of heating devices 302 can be "ganged" together to
facilitate performing multiple tests at the same time. A compact
configuration of the power coupler 369 can minimize the space
occupied by the heating devise 302 and associated electrical
couplings on a support surface (e.g., a table).
[0079] With reference to FIGS. 9A-9C, the chemical reaction pad 321
(FIG. 9B) can be supported by the tray 320. Top and side views of
the chemical reaction pad 321 are shown in FIGS. 13A and 13B,
respectively. In general, the tray 320 can be of any suitable
configuration to support the chemical reaction pad 321 while
receiving a biological sample and undergoing a heating and cooling
cycle to test the biological sample. In one aspect, the tray 320
can include a bottom wall 330, end walls 331a, 331b, and, in some
examples, rails or guides 332a, 332b configured to form a
receptacle or pocket 333 at a desired location on the tray 320 and
provide a boundary or barrier to confine the chemical reaction pad
321 at that location. In the illustrated example, the chemical
reaction pad 321 has a narrow or elongated "strip" configuration
and the rails 332a, 332b are spaced apart from one another to
receive the chemical reaction pad 321 between the rails 332a, 332b
at a central location on the tray 320 and prevent substantial
movement of the chemical reaction pad 321 in that location.
Although rails, guides, walls, etc. are illustrated for maintaining
the chemical reaction pad 321 in a desired location on the tray
320, it should be recognized that any structure suitable for this
purpose can be utilized, such as a spike (e.g., that impales the
chemical reaction pad 321), a rounded or semispherical protrusion
(e.g., that presses into or binds the chemical reaction pad 321
with a locally high pressure), a column, a bar, or any other
suitable locating feature. It should also be recognized that the
tray 320 can be configured to position or orient the chemical
reaction pad 321 in any suitable position or orientation (e.g.,
rotated 90 degrees to the orientation in the illustrated example).
The tray 320 can be made of any suitable material, such as a
polymer (e.g., polypropylene, polycarbonate, polystyrene,
polymethyl methacrylate (PMMA), polyethylene, etc.), glass,
etc.
[0080] In one aspect, the chemical reaction pad 321 can have any
suitable configuration. For example, as illustrated in FIG. 13B,
top surfaces of the test sites 350a-d can be raised or elevated
above intervening structures or spacers 351a-c between the test
sites 350a-d, which can serve to separate the test sites 350a-d
from one another. As further illustrated in FIG. 13B, in some
examples, the tops of the test sites 350a-d can each include a
distribution or spreading layer 352a-d, respectively, configured to
facilitate spreading of liquid (e.g., a biological sample, such as
a saliva sample) across the test sites 350a-d. In some examples,
one or more test sites may not have a distribution layer.
[0081] In one aspect, as shown in a chemical reaction pad 321'
FIGS. 14A and 14B, test sites 350a`-d` can be at substantially the
same level as intervening structures or spacers 351a`-c` between
the test sites 350a`-d`. Although the test sites 350a-d and
350a`-d` are illustrated as having rectangular shapes, it should be
recognized that a test site as disclosed herein can have any
suitable configuration, shape, or geometry, such as a circular
shape, a triangular shape, etc.
[0082] Furthermore, it should be recognized that a chemical
reaction pad as disclosed herein can have any suitable number of
test sites. For example, a chemical reaction pad can have one test
site (at 450 in FIG. 15), two test sites (at 550a, 550b in FIG.
16), three test sites (at 650a-c in FIG. 17), four test sites (at
350a-d in FIGS. 13A and 13B; at 350a`-d` in FIGS. 14A and 14B; at
750a-d in FIG. 18; at 850a-d in FIG. 19), or more. In addition,
test sites can be in any suitable arrangement relative to one
another. For example, the test sites can be arranged linearly in a
row (FIGS. 13A-14B, 16, and 17), in a cross-pattern (FIG. 18), in a
grid pattern (FIG. 19), in a circular pattern, or any other
suitable arrangement or pattern.
[0083] In one example, as illustrated in FIG. 20, a chemical
reaction pad (e.g., a solid phase reaction medium) 921 for
conducting a LAMP analysis can comprise a substrate 953, an
adhesive layer 959 disposed on the substrate 953, a reaction layer
973 including test sites, test spots, reaction locations, or
segments 950a-c, and spacers 951a-d disposed on the adhesive layer
959, and a spreading layer 952 disposed on the reaction layer 973.
In one aspect, the test sites 950a-c can include or otherwise hold
reagents including one or more target primers, DNA polymerase, a
re-solubilization agent, etc. In one aspect, the reagents can form
a composition sufficient to carry out a LAMP reaction.
[0084] The spreading layer 952 can facilitate a uniform spreading
of a biological sample throughout different sections of the
solid-phase reaction medium. In another example, the spreading
layer can be less hydrophilic than the solid-phase reaction medium.
Having a spreading layer that is less hydrophilic than the
solid-phase reaction medium can facilitate the uniform spreading of
the biological sample because the biological sample will diffuse
away from the less hydrophilic spreading layer towards the more
hydrophilic solid-phase reaction medium.
[0085] In one aspect, the spacers 951a-d can comprise one or more
of glass fiber, nylon, cellulose, polysulfone, polyethersulfone,
cellulose acetate, nitrocellulose, polystyrene, polyester,
hydrophilic polytetrafluoroethylene (PTFE), or combinations
thereof. In another aspect, the spacers 951a-d can be oriented in
the same plane as the reaction layer 973 and oriented between
segments of the reaction layer 973.
[0086] The spatially discontinuous reaction layer 973 can allow
multiplexing of multiple controls or multiple pathogens. For
example, test site 950a can be a positive control (e.g., test for a
known saliva protein), test site 950b can be negative control
(e.g., test for a colorimetric result without including all of the
reagents used for the LAMP reaction, and test site or reaction
segment 950c can test for the target pathogen.
[0087] The spatially discontinuous test sites or reaction locations
950a-c can also allow for multiplexing of multiple pathogens. For
example, test site 950a can test for influenza, test site 950b can
test for a bacterial infection, and test site 950c can test for a
fungal infection.
[0088] The dimensions of the reaction locations or segments 950a-c
can impact the multiplexing potential. In one aspect, the test
sites 950a-c can have a thickness from about 0.05 mm to about 2 mm.
In another aspect, the test sites 950a-c can have a width from
about 4 mm to about 12 mm and a length from about 4 mm to about 25
mm. In one example, the test sites 950a-c can be spatially
discontinuous. In another example, the test sites 950a-c can have a
surface area to thickness ratio from about 90 to about 600.
[0089] In one example, the chemical reaction pad or solid-phase
reaction medium 921 can be configured to receive a biological fluid
that can flow transversely across the spreading layer 952 and that
can migrate vertically down into the test sites 950a-c of the
reaction layer 973. The test sites 950a-c can contain all the
components used for a RT-LAMP or LAMP reaction to occur. In one
example, the test sites 950a-c can contain a re-solubilization
agent (e.g., a surfactant), enzymes (e.g., DNA polymerase, reverse
transcriptase, DNase inhibitors, or RNase inhibitors), stabilizers
(e.g., blocking agents such as BSA or casein), a colorimetiic
indicator (e.g., a magnesium colorimetric indicator, a pH
colorimetric indicator, or a DNA intercalating colorimetric
indicator), and a buffer (e.g., 20 mM Tris).
[0090] The test sites 950a-c can comprise any suitable material
disclosed herein. In one example, the test sites 950a-c can
comprise one or more of glass fiber, nylon, cellulose, polysulfone,
polyethersulfone, cellulose acetate, nitrocellulose, hydrophilic
PTFE, the like, or combinations thereof. In one aspect, the pore
size of the test sites 950a-c can be from about 1 to about 100
microns. The test sites 950a-c can be optically clean and smooth in
appearance.
[0091] In another aspect, the test sites 950a-c can provide a
uniform end-color in a read zone for accurate and precise signal
output or detection. In one example, a biological sample can slowly
migrate vertically downward into the test sites 950a-c. The
end-color intensity of the test sites 950a-c can be measured by a
user with optical observation and comparison to a color chart or
scale or with a handheld LED meter as percent reflectance units and
converted to copies of RNA or DNA per reaction using a curve set
calibrated against a laboratory reference instrument, or as an
optical image obtaining RGB values or pixel count which can be
calibrated against a laboratory reference instrument. The
concentration of RNA or DNA can be determined by the end-color
intensity at a selected time or by kinetic rate determination.
[0092] As shown in FIG. 10, the chemical reaction pad cover 322 can
be disposed over the chemical reaction pad 321 (hidden from view in
FIG. 10). FIGS. 11A and 11B show top and bottom isometric views,
respectively, of the chemical reaction pad cover 322 isolated from
other components of the cartridge 304. The chemical reaction pad
cover 322 can have a sample opening 323 to facilitate depositing a
liquid biological sample at a predetermined location on the
chemical reaction pad 321 to ensure that biological samples are
consistently and properly deposited for each test performed by a
variety of different users. For example, the chemical reaction pad
cover 322 can include a top portion 340 configured to extend
substantially over the chemical reaction pad 321. The sample
opening 323 can be formed at a suitable (e.g., central) location in
the top portion 340 to facilitate depositing a liquid biological
sample on the chemical reaction pad 321 below the top portion 340.
The sample opening 323 can have any suitable shape, geometry, or
configuration (e.g., a rectangle shape, a circular shape, a slot
configuration, a funnel configuration, etc.) to facilitate
depositing a liquid biological sample at a predetermined location
on the chemical reaction pad 321. In some examples, only a single
sample opening may be included. In other examples, multiple sample
openings can be included, which can allow depositing a liquid
biological sample at multiple locations on the chemical reaction
pad 321. In the illustrated example, the chemical reaction pad 321
includes multiple (e.g., four) test sites 350a-d. Thus, in one
example, the chemical reaction pad cover 322 can include a sample
opening corresponding to each of the four test sites 350a-d. In
such cases, the chemical reaction pad cover 322 may not include a
capillary channel as such a channel may not be needed to adequately
distribute a liquid biological sample across the chemical reaction
pad to the various test sites 350a-d.
[0093] In one aspect, shown in FIGS. 10 and 11A, the chemical
reaction pad cover 322 can include indicia 341 configured to
indicate to a user the location of the sample opening 323. Any
suitable type of indicia can be utilized, such as shapes (e.g., an
arrow, a triangle, a circle, a line, etc.), alphanumeric
characters, a combination of these, etc. The indicia 341 can be of
any suitable type or construction, such as formed into or on the
chemical reaction pad cover 322 (e.g., embossed, molded, stamped,
etc. into or on the top portion 340), printed on the chemical
reaction pad cover 322, etc.
[0094] As shown in FIG. 11B, the chemical reaction pad cover 322
can include a capillary channel 342 in fluid communication with the
sample opening 323 to distribute a liquid biological sample across
or along the chemical reaction pad 321 (e.g., to one or more of the
various test sites 350a-d). The capillary channel 342 can have any
suitable cross-sectional shape or configuration known in the art
for conveying a liquid along an underside of the chemical reaction
pad cover 322 via capillary action and/or surface tension, such as
a U-shape (FIG. 21A), a V-shape (FIG. 21B), a T-shape (FIG. 21C),
etc.
[0095] In one aspect, the capillary channel 342 can have any
suitable pattern or path shape, such as at least one of a linear
configuration, a cross-configuration, or an X configuration, a
circular or curved configuration, which may be configured based on
the pattern, distribution, or location of the underlying test
sites. For example, the chemical reaction pad 321 as illustrated
has a strip configuration with linearly arranged test sites 350a-d.
In this case, the capillary channel 342 can have a linear
configuration to facilitate delivery of a biological sample to one
or more of the various test sites 350a-d. A linear capillary
channel configuration of capillary channels 542, 642 can also be
utilized with the linear arrangement of test sites in the chemical
reaction pad examples shown in FIGS. 16 and 17, respectively. A
capillary channel 742 having a cross-configuration can be utilized
to deliver a biological sample to one or more of the various test
sites of the chemical reaction pad example shown in FIG. 18, which
are arranged in a cross pattern or configuration. A capillary
channel 842 having an X configuration can be utilized to deliver a
biological sample to one or more of the various test sites of the
chemical reaction pad example shown in FIG. 19, which are arranged
in a grid pattern or configuration. A capillary channel with an X
configuration may also be suitable for use with a wide chemical
reaction pad in a strip configuration with linearly arranged test
sites.
[0096] Although various capillary channels are discussed herein, it
should be recognized that a chemical reaction pad cover in
accordance with the present disclosure need not include a capillary
channel, as a liquid biological sample may be adequately
distributed across the chemical reaction pad in some examples
without relying on a capillary channel. For example, a chemical
reaction pad and/or a chemical reaction pad cover may be configured
to facilitate distribution of a liquid biological sample across the
chemical reaction pad even without the aid of a capillary channel
(e.g., a chemical reaction pad may have a distribution layer or
other such material or layer, test sites may be arranged in close
proximity to a sample opening in the chemical reaction pad cover, a
sample opening may be associated with each test site, etc.).
[0097] In one aspect, the chemical reaction pad cover 322 can
include a bottom surface 343 (FIG. 11B) configured to form a top
wall or barrier over the receptacle or pocket 333 of the tray 320
(FIG. 9A) to maintain the chemical reaction pad 321 between the
rails 332a, 332b and prevent substantial movement of the chemical
reaction pad 321 in that location. In some examples, the bottom
surface 343 can be sized to fit between the rails 332a, 332b. In
other examples, the bottom surface 343 can be configured to fit
over the rails 332a, 332b.
[0098] In one aspect, the chemical reaction pad cover 322 can be
coupled to the tray 320. For example, the tray 320 can include
coupling features 334 (e.g., resiliently flexible coupling
protrusions) and the chemical reaction pad cover 322 can include
mating coupling features 344 (e.g., coupling recesses) configured
to engage one another to mechanically secure the chemical reaction
pad cover 322 to the tray 320 in a fixed relationship to properly
locate the sample opening 323 and/or the capillary channel 342 over
a predetermined location of the chemical reaction pad 321 (e.g., in
a middle portion of the pad 321 and/or over one or more test sites
350a-d). The coupling features 334 can have any suitable
configuration and can be at any suitable location, such as
associated with one or more outer walls 335a, 335b of the tray 320.
Similarly, the coupling features 344 can have any suitable
configuration and can be at any suitable location, such as
associated with one or more outer walls 345a, 345b of the chemical
reaction pad cover 322.
[0099] In one aspect, the cartridge 304 can include a handle 325
(FIGS. 8A-10) coupled to the tray 320 to facilitate grasping the
cartridge 304 by a user. The handle 325 can be made of any suitable
material, such as an elastomer (e.g., thermoplastic elastomer
(TPE), thermoplastic polyurethane (TPU), silicone, nitrile
butadiene rubber (Buna-N), styrene-butadiene rubber (SBR), ethylene
propylene diene monomer (EPDM), etc.). In some examples, the
cartridge 304 can include a tray base 326 (FIGS. 9A-10) coupled to
the tray 320. The tray base 326 can provide a structural interface
for coupling with the outer cover 324. The tray base 326 can also
provide a structural support for the handle 325, which can be
coupled to the tray base 326.
[0100] In some examples, the tray base 326 can be coupled to the
tray 320 via a reduced cross-sectional area portion 336 to reduce
or minimize conductive heat transfer from the tray 320 to the
handle 325, which can prevent burns or discomfort of the user when
handling the cartridge 304 immediately following a test of a
biological sample (e.g., when removing the cartridge 304 from the
heating device 302 for interpretation of the test results). The
reduced cross-sectional area portion 336 can have any suitable
configuration that reduces cross-sectional area between the tray
320 and the tray base 326. For example, the reduced cross-sectional
area portion 336 can include beams 337a, 337b that extend between
the tray 320 and the tray base 326 and leave an open space 338
between the tray 320 and the tray base 326. Thus, the open space
338 can provide thermal insulation and limit heat transfer between
the tray 320 and the tray base 326, with a conductive heat transfer
path from the tray 320 to the tray base 326 being through the beams
337a, 337b. The beams 337a, 337b can be configured to provide
adequate structural support between the tray 320 and the tray base
326 in the absence of material in the location that forms the open
space 338.
[0101] The outer cover 324 can define an opening or chamber 354
(FIG. 12B) to receive the chemical reaction pad 322 (and associated
structures, such as the tray 320 and the chemical reaction pad
cover 322). For example, the chamber 354 can be defined at least in
part by one or more walls 355a-e (FIGS. 8A, 8B, 12A, and 12B). An
entrance to the chamber 354 can be defined by a tray base interface
portion 356 configured to interface with the tray base 326. For
example, interior surfaces 357a, 357b (FIG. 12B) of the tray base
interface portion 356 can be configured to interface with the tray
base 326. The tray base 326 can a rim or flange 339 to provide a
backing interface surface for the tray base interface portion 356
with the tray base 326.
[0102] In one aspect, the outer cover 324 can be operable to at
least partially form the enclosure 303 (FIGS. 8A and 8B) about the
chemical reaction pad 322 (and associated structures, such as the
tray 320 and the chemical reaction pad cover 322). In one aspect,
the cartridge 304 can include one or more seals 327a, 327b (FIGS.
9A-10) operable with the outer cover 324 to seal the enclosure 303
about the chemical reaction pad 322. In another aspect, the tray
base 326 can be configured to interface with the outer cover 324 to
form the enclosure 303 about the chemical reaction pad 322. Thus,
in some examples, the tray base 326 can include and/or support the
seals 327a, 327b. The seals 327a, 327b can be configured to
maintain a seal about biological sample material within the
enclosure 303 to ensure test integrity by preventing external
material (e.g., from a previous test) from contaminating the
biological sample within the enclosure 303, as well as maintaining
an environment within the enclosure 303 that prevents the
biological material from drying out during the test. The seals
327a, 327b can also assist in maintaining the integrity of
subsequent tests performed on the same heating device 302 by
preventing biological material from escaping and contaminating the
heating device 302. In addition, the seals 327a, 327b can maintain
safety by ensuring that no biological sample material can escape
and pose a health risk to the user or others. Thus, in some
examples, the seals 327a, 327b can be configured to provide a
hermetic seal. The cartridge 304 can therefore be self-contained
and sealed so that the heating device 302 cannot be contaminated.
This can simplify the design of the heating device 302 because the
heating device 302 does not need to be configured to capture or
contain the biological sample (e.g., contaminants) or be configured
for ease of cleaning.
[0103] In the illustrated example, the seals 327a, 327b can be
configured to interface with the interior surfaces 357a, 357b,
respectively, of the tray base interface portion 356 of the outer
cover 324. In one aspect, the sealing perimeter at this interface
can be minimized in order to minimize the area where leakage can
occur. Although two seals 327a, 327b are shown in the illustrated
example, it should be recognized that any suitable number of seals
can be utilized (e.g., only a single seal or more than two seals).
Utilizing multiple seals (e.g., two seals) can provide redundancy.
Because the biological sample is heated by the heating device 302
in order to perform a test of the biological sample, the increase
in temperature can elevate the pressure inside the enclosure 303.
Therefore, in one aspect, the air volume inside the enclosure 303
can be minimized or reduced to a level that can be safely sealed by
the seals 327a, 327b throughout the heating cycle of the test
procedure.
[0104] The seals 327a, 327b can include any suitable material, such
as an elastomer (e.g., thermoplastic elastomer (TPE), thermoplastic
polyurethane (TPU), silicone, nitrile butadiene rubber (Buna-N),
styrene-butadiene rubber (SBR), ethylene propylene diene monomer
(EPDM), etc.). In one aspect, the seal material can be selected so
as to be hard enough to allow suitable compression to form an
effective seal, but not too soft such that a proper seal cannot be
maintained under the design conditions. In some examples, the seal
material can have a hardness of about 30-60 Shore A durometer. In
some examples, the seals 327a, 327b and the handle 325 can be made
of the same material. The seals 327a, 327b can have any suitable
configuration, such as a gasket, an O-ring, etc. In one aspect, the
seals 327a, 327b can be attached and/or integrally formed with the
underlying structure. For example, the seals 327a, 327b and the
associated tray base 326 structure can be permanently attached
and/or integrally formed with one another. In some examples, the
seals 327a, 327b and the handle 325 can be integrally formed of a
single, unitary component or structure. In cases where the seals
327a, 327b are attached and/or integrally formed with the
underlying structure, the seals 327a, 327b can be overmolded on the
underlying structure, which can molecularly bond the seals to the
underlying structure thereby enhancing the integrity and robustness
of the seals. For example, elastomer seals 327a, 327b can be
overmolded onto an underlying polymer (e.g., polypropylene)
structure, such as that used to form the tray 320 and a structural
frame underlying the tray base 326 and the handle 325.
[0105] In one aspect, the cartridge 304 can include a latch 328
(FIG. 8A) operable to facilitate latching the outer cover 324 to
the tray base 326. For example, the outer cover 324 can include a
first latch portion 329a (e.g., a tab or other suitable protrusion
as shown in FIGS. 8A, 12A, and 12B) and a second latch portion 329b
(e.g., a catch defining a suitable recess as shown in FIGS. 8A, 9A,
9B, and 10) can be associated with the tray base 326. The first and
second latch portions 329a, 329b can interface with and engage one
another to secure the outer cover 324 to the tray base 326. In one
aspect, the latch 328 can maintain the seals 327a, 327b in a
preloaded condition to ensure a proper seal between the outer cover
324 the tray base 326.
[0106] The chemical reaction pad cover 322 and the outer cover 324
can be made of any suitable material, such as a polymer (e.g.,
polypropylene, polycarbonate, polystyrene, polymethyl methacrylate
(PMMA), polyethylene, etc.), glass, etc. In one aspect, at least
one of the chemical reaction pad cover 322 or the outer cover 324
can be at least partially optically transparent or translucent to
facilitate optical inspection of the chemical reaction pad 321 to
determine a test result. In some examples, substantially the entire
chemical reaction pad cover 322 and/or outer cover 324 can be
constructed of optically transparent or translucent material.
[0107] In use, an operator can apply the liquid biological sample
301 to the chemical reaction pad 321, for example, by depositing
the biological sample 301 into the sample opening 323. The tray 320
and the chemical reaction pad 321 are shown in FIG. 22 with the
chemical reaction pad cover 222 omitted for clarity. The biological
sample 301 can then spread across the chemical reaction pad 321 to
the various test sites 350a-d, which can be aided by a spreading
layer and/or the capillary channel 342 in the chemical reaction pad
cover 222. The outer cover 324 can then be placed over the tray
320, the chemical reaction pad 321, and the chemical reaction pad
cover 222 to fully assemble the cartridge 304, as shown in FIGS. 8A
and 8B. With the fully assembled cartridge 304 containing the
biological sample 301, the cartridge 304 can then be placed into
the heating device 302 as shown in FIG. 3B, and then the lid 362
can be closed over the cartridge 304 against the base 361, as shown
in FIG. 3A. A test can be initiated by activating the heating
device 302. At the end of the test, the lid 362 can be opened and
the test cartridge 304 can be removed. The chemical reaction pad
321 can be visually inspected to determine the results of the test
(e.g., as indicated by the color of one or more of the test sites
350a-d), as illustrated in FIG. 23.
[0108] In some examples, as illustrated in FIG. 23, the test sites
350a-d can be visible through the chemical reaction pad cover 222
and the outer cover 324 to facilitate visual inspection of the test
sites 350a-d without the need to remove the covers 324, 322. In one
example, the chemical reaction pad cover 322 and/or the outer cover
324 can be at least partially optically transparent or translucent.
In another example, at least one of the chemical reaction pad cover
322 or the outer cover 324 can include one or more optically
transparent or translucent windows 346 to facilitate optical
inspection of the underlying chemical reaction pad 321 (e.g.,
located over the test sites 350a-d).
[0109] FIG. 24 illustrates a liquid biological sample test
cartridge 1004 in accordance with another example of the present
disclosure. As with other cartridges disclosed herein, the
cartridge 1004 can include a tray 1020, a chemical reaction pad
(hidden from view) supported by the tray 1020, and a chemical
reaction pad cover 1022 disposed over the chemical reaction
pad.
[0110] The chemical reaction pad cover 1022 can be coupled to the
tray 1020. The chemical reaction pad cover 1022 can have a sample
opening 1023 to facilitate depositing a liquid biological sample at
a predetermined location on the chemical reaction pad. In addition,
the cartridge 1004 can include an outer cover 1024 operable to at
least partially form an enclosure about the chemical reaction
pad.
[0111] In the FIG. 24 example, the outer cover 1024 and the tray
1020 can form the enclosure about the chemical reaction pad. For
example, the tray 1020 can be configured as a container and the
outer cover 1024 can be configured as a lid over the container. In
some examples, the outer cover 1024 can be pivotally coupled to the
tray 1020 (e.g., by a living hinge). In one aspect, the cartridge
1004 can include a seal 1027 operable with the tray 1020 and the
outer cover 1024 to seal the enclosure about the chemical reaction
pad. One or more latches 1028a-c can be included to secure the
outer cover 1024 and the tray 1020 to one another and maintain the
enclosure seal.
[0112] In one aspect, as illustrated in FIG. 25, a liquid
biological sample test kit 1105 can comprise a pouch 1106 and a
liquid biological sample test cartridge 1104 as disclosed herein
sealed within the pouch 1106. The cartridge 1104 may or may not be
in a fully assembled condition within the pouch 1106 (e.g., an
outer cover may be separate or uncoupled from other components of
the cartridge 1104).
[0113] In accordance with one aspect of the present disclosure, a
tangible and non-transitory computer readable medium can comprise
one or more computer software modules configured to direct one or
more processors to receive temperature data generated by a thermal
sensor, the temperature data associated with a biological sample,
determine a control command for a heat source based on the
temperature data, the heat source being operable to heat the
biological sample, wherein the control command is configured to
heat the biological sample at less than or equal to about 2 degrees
C./s, and communicate the control command to the heat source.
[0114] In one aspect, the control command can be configured to
control heat generation by the heat source to heat the biological
sample from about 0.5-1.5 degrees C./s. In another aspect, the
control command can be configured to control heat generation by the
heat source to heat the biological sample from about 0.8-1.2
degrees C./s.
[0115] In one aspect, the tangible and non-transitory computer
readable medium can comprise one or more computer software modules
configured to direct one or more processors to receive time data
generated by a timer, determine an expiration of a predetermined
incubation time interval for the biological sample beginning when
the temperature data indicates a temperature value greater than or
equal to a predetermined minimum temperature value, and communicate
a termination command to the heat source to cease heat generation
upon expiration of the incubation period.
[0116] In accordance with one embodiment of the present invention,
a method for facilitating testing of a liquid biological sample is
disclosed. The method can comprise supporting a chemical reaction
pad with a tray. The method can also comprise disposing a chemical
reaction pad cover over the chemical reaction pad and coupling the
chemical reaction pad cover to the tray. The method can further
comprise facilitating depositing a liquid biological sample at a
predetermined location on the chemical reaction pad. Additionally,
the method can comprise providing an outer cover operable to at
least partially form an enclosure about the chemical reaction pad.
It is noted that no specific order is required in this method,
though generally in one embodiment, these method steps can be
carried out sequentially.
[0117] In one aspect of the method, facilitating depositing a
liquid biological sample at a predetermined location on the
chemical reaction pad can comprise providing a sample opening in
the chemical reaction pad cover.
[0118] In one aspect of the method, facilitating depositing a
liquid biological sample at a predetermined location on the
chemical reaction pad can further comprise providing a capillary
channel in fluid communication with the sample opening to
distribute the liquid biological sample along the chemical reaction
pad.
[0119] In one aspect, the method can further comprise facilitating
sealing the enclosure about the chemical reaction pad. In one
aspect, facilitating sealing the enclosure about the chemical
reaction pad can comprise providing a seal operable with the outer
cover.
[0120] In accordance with one embodiment of the present invention,
a method for facilitating testing of a liquid biological sample can
comprise facilitating heating of a biological sample at less than
or equal to about 2 degrees C./s. In one aspect of the method,
facilitating heating of the biological sample can comprise
obtaining a controller in communication with a heat source, the
controller being operable to control heat generation by the heat
source. In one aspect, the method can further comprise obtaining a
thermal sensor in communication with the controller, the thermal
sensor being operable to sense a temperature associated with the
biological sample, wherein the controller controls heat generation
by the heat source based on the temperature. In one aspect, the
method can further comprise facilitating termination of heating the
biological sample upon expiration of a predetermined incubation
time period. In one aspect, facilitating termination of heating the
biological sample upon expiration of a predetermined incubation
time period can comprise obtaining a timer in communication with
the controller and operable to provide time data to the controller,
wherein the controller controls the heater to provide heat for the
predetermined incubation time period. It is noted that no specific
order is required in this method, though generally in one
embodiment, these method steps can be carried out sequentially.
[0121] Reference was made to the examples illustrated in the
drawings and specific language was used herein to describe the
same. It will nevertheless be understood that no limitation of the
scope of the technology is thereby intended. Alterations and
further modifications of the features illustrated herein and
additional applications of the examples as illustrated herein are
to be considered within the scope of the description.
[0122] Although the disclosure may not expressly disclose that some
embodiments or features described herein may be combined with other
embodiments or features described herein, this disclosure should be
read to describe any such combinations that would be practicable by
one of ordinary skill in the art. The user of "or" in this
disclosure should be understood to mean non-exclusive or, i.e.,
"and/or," unless otherwise indicated herein.
[0123] Furthermore, the described features, structures, or
characteristics may be combined in any suitable manner in one or
more examples. In the preceding description, numerous specific
details were provided, such as examples of various configurations
to provide a thorough understanding of examples of the described
technology. It will be recognized, however, that the technology may
be practiced without one or more of the specific details, or with
other methods, components, devices, etc. In other instances,
well-known structures or operations are not shown or described in
detail to avoid obscuring aspects of the technology.
[0124] Although the subject matter has been described in language
specific to structural features and/or operations, it is to be
understood that the subject matter defined in the appended claims
is not necessarily limited to the specific features and operations
described above. Rather, the specific features and acts described
above are disclosed as example forms of implementing the
claims.
[0125] Numerous modifications and alternative arrangements may be
devised without departing from the spirit and scope of the
described technology.
* * * * *