Liquid Biological Sample Test Cartridge

Abstract

A liquid biological sample test cartridge is disclosed. The cartridge can include a tray. The cartridge can also include a chemical reaction pad supported by the tray. The cartridge can further include a chemical reaction pad cover disposed over the chemical reaction pad and coupled to the tray. The chemical reaction pad cover can have a sample opening to facilitate depositing a liquid biological sample at a predetermined location on the chemical reaction pad. In addition, the cartridge can include an outer cover operable to at least partially form an enclosure about the chemical reaction pad.

Description

RELATED APPLICATION

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

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

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:

FIG. 1 is a schematic illustration of a biological test system in accordance with an example of the present disclosure.

FIGS. 2A and 2B are schematic illustrations of a liquid biological sample test cartridge in accordance with an example of the present disclosure.

FIG. 3A is a top isometric view of a biological test system in accordance with an example of the present disclosure.

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.

FIG. 4 is a schematic illustration of the biological test system of FIGS. 3A and 3B.

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.

FIG. 5B is a bottom isometric view of the heating device of FIG. 5A, in accordance with an example of the present disclosure.

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.

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.

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.

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.

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.

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.

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.

FIG. 9C is a bottom isometric view of the tray of FIG. 9A, in accordance with an example of the present disclosure.

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.

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.

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.

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.

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.

FIG. 13A is a top view of the chemical reaction pad of FIG. 9B, in accordance with an example of the present disclosure.

FIG. 13B is a side view of the chemical reaction pad of FIG. 13A, in accordance with an example of the present disclosure.

FIG. 14A is a top view of a chemical reaction pad in accordance with an example of the present disclosure.

FIG. 14B is a side view of the chemical reaction pad of FIG. 14A, in accordance with an example of the present disclosure.

FIG. 15 is a top view of a chemical reaction pad in accordance with an example of the present disclosure.

FIG. 16 is a top view of a chemical reaction pad in accordance with an example of the present disclosure.

FIG. 17 is a top view of a chemical reaction pad in accordance with an example of the present disclosure.

FIG. 18 is a top view of a chemical reaction pad in accordance with an example of the present disclosure.

FIG. 19 is a top view of a chemical reaction pad in accordance with an example of the present disclosure.

FIG. 20 is a schematic illustration of a chemical reaction pad in accordance with an example of the present disclosure.

FIGS. 21A-21C capillary channel cross-sectional shapes in accordance with several examples of the present disclosure.

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.

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.

FIG. 24 is a top isometric view of a liquid biological sample test cartridge in accordance with an example of the present disclosure.

FIG. 25 is a schematic illustration of a liquid biological sample test kit in accordance with an example of the present disclosure.

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

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.

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.

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.

In one aspect, a liquid biological sample test cartridge is disclosed that can include a tray. The cartridge can also include a chemical reaction pad supported by the tray. The cartridge can further include a chemical reaction pad cover disposed over the chemical reaction pad and coupled to the tray. The chemical reaction pad cover can have a sample opening to facilitate depositing a liquid biological sample at a predetermined location on the chemical reaction pad. In addition, the cartridge can include an outer cover operable to at least partially form an enclosure about the chemical reaction pad.

In one aspect, a liquid biological sample test cartridge is disclosed that can include a tray. The cartridge can also include a chemical reaction pad supported by the tray. The cartridge can further include a chemical reaction pad cover disposed over the chemical reaction pad and coupled to the tray. The chemical reaction pad cover can have a sample opening to facilitate depositing a liquid biological sample at a predetermined location on the chemical reaction pad. The chemical reaction pad cover can also have a capillary channel in fluid communication with the sample opening to distribute the liquid biological sample along the chemical reaction pad. The cartridge can also include an outer cover operable to form an enclosure about the chemical reaction pad. The cartridge can further include a tray base coupled to the tray. The tray base can be operable to interface with the outer cover to form the enclosure about the chemical reaction pad. The tray base can have a seal operable with the outer cover to seal the enclosure about the chemical reaction pad. Additionally, the cartridge can include a handle coupled to the tray base to facilitate grasping the test cartridge by a user.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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.

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_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_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_offset. The offset temperature T_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_offset can be applied to the measured T_IR temperature to produce a calculated T_assay temperature, which is the temperature of the biological sample 301. This T_assay temperature is compared to the set point temperature T_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_assay and T_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_cart, completing the control loop.

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_assay and T_set) to decrease at a magnitude equal to the desired temperature increase ramp rate.

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_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 tumed 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.

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.

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.).

In one aspect, illustrated in FIGS. 3B and 5C, 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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 colorimetric 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).

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.

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.

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 perspective 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.

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.

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.

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.

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.).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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. 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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. Numerous modifications and alternative arrangements may be devised without departing from the spirit and scope of the described technology.

Claims

1. A liquid biological sample test cartridge, comprising:

a tray;

a chemical reaction pad supported by the tray;

a chemical reaction pad cover disposed over the chemical reaction pad and coupled to the tray, the chemical reaction pad cover having a sample opening to facilitate depositing a liquid biological sample at a predetermined location on the chemical reaction pad; and

an outer cover operable to at least partially form an enclosure about the chemical reaction pad.

2. The test cartridge of claim 1, wherein the chemical reaction pad comprises at least one of a cellulose material, a paper material, or a fiber material.

3. The test cartridge of claim 1, wherein the chemical reaction pad cover is at least partially optically transparent or translucent to facilitate optical inspection of the chemical reaction pad to determine a test result.

4. The test cartridge of claim 1, wherein the chemical reaction pad cover comprises one or more optically transparent or translucent windows.

5. The test cartridge of claim 1, wherein the chemical reaction pad cover comprises a capillary channel in fluid communication with the sample opening to distribute the liquid biological sample along the chemical reaction pad.

6. The test cartridge of claim 5, wherein the capillary channel comprises at least one of a linear configuration, a cross-configuration, or an X configuration.

7. The test cartridge of claim 1, wherein the sample opening is a plurality of sample openings.

8. The test cartridge of claim 1, wherein the outer cover is at least partially optically transparent or translucent to facilitate optical inspection of the chemical reaction pad to determine a test result.

9. The test cartridge of claim 1, wherein the outer cover comprises one or more optically transparent or translucent windows.

10. The test cartridge of claim 1, further comprising a tray base coupled to the tray, wherein the tray base is configured to interface with the outer cover to form the enclosure about the chemical reaction pad.

11. The test cartridge of claim 10, wherein the tray base comprises a seal operable with the outer cover to seal the enclosure about the chemical reaction pad.

12. The test cartridge of claim 10, further comprising a handle coupled to the tray base to facilitate grasping the test cartridge by a user.

13. The test cartridge of claim 12, wherein the tray base is coupled to the tray via a reduced cross-sectional area portion to reduce conductive heat transfer from the tray to the handle.

14. The test cartridge of claim 10, wherein at least one of the seal or the handle comprises an elastomeric material.

15. The test cartridge of claim 10, further comprising a latch operable to facilitate latching the outer cover to the tray base.

16. The test cartridge of claim 1, wherein the outer cover comprises at least one of a key or a keyway operable to facilitate proper alignment of the test cartridge with a heating device.

17. The test cartridge of claim 1, wherein the outer cover is operable with the tray to form the enclosure about the chemical reaction pad.

18. The test cartridge of claim 17, wherein the outer cover is pivotally coupled to the tray.

19. The test cartridge of claim 17, further comprising a seal operable with the tray and the outer cover to seal the enclosure about the chemical reaction pad.

20. The test cartridge of claim 1, further comprising a handle coupled to the tray to facilitate grasping the test cartridge by a user.

21. The test cartridge of claim 1, further comprising a seal operable with the outer cover to seal the enclosure about the chemical reaction pad.

22. A liquid biological sample test cartridge, comprising:

a tray;

a chemical reaction pad supported by the tray;

a chemical reaction pad cover disposed over the chemical reaction pad and coupled to the tray, the chemical reaction pad cover having a sample opening to facilitate depositing a liquid biological sample at a predetermined location on the chemical reaction pad, and a capillary channel in fluid communication with the sample opening to distribute the liquid biological sample along the chemical reaction pad;

an outer cover operable to form an enclosure about the chemical reaction pad;

a tray base coupled to the tray, the tray base being operable to interface with the outer cover to form the enclosure about the chemical reaction pad, the tray base having a seal operable with the outer cover to seal the enclosure about the chemical reaction pad; and

a handle coupled to the tray base to facilitate grasping the test cartridge by a user.

23. A liquid biological sample test kit, comprising:

a pouch; and

the liquid biological sample test cartridge of claim 1 sealed within the pouch.

24. A method for facilitating testing of a liquid biological sample, comprising:

supporting a chemical reaction pad with a tray;

disposing a chemical reaction pad cover over the chemical reaction pad and coupling the chemical reaction pad cover to the tray;

facilitating depositing a liquid biological sample at a predetermined location on the chemical reaction pad; and

providing an outer cover operable to at least partially form an enclosure about the chemical reaction pad.

25. The method of claim 24, wherein facilitating depositing a liquid biological sample at a predetermined location on the chemical reaction pad comprises providing a sample opening in the chemical reaction pad cover.

26. The method of claim 25, wherein facilitating depositing a liquid biological sample at a predetermined location on the chemical reaction pad further comprises providing a capillary channel in fluid communication with the sample opening to distribute the liquid biological sample along the chemical reaction pad.

27. The method of claim 24, further comprising facilitating sealing the enclosure about the chemical reaction pad.

28. The method of claim 27, wherein facilitating sealing the enclosure about the chemical reaction pad comprises providing a seal operable with the outer cover.