Biochemical reaction temperature regulator having a liquid-gas phase change material

Abstract

In particular, temperature control devices and temperature control systems configured to regulate the temperature of chemical reactions, such as biochemical reactions, are disclosed. The temperature control device includes a film arranged and configured to form a sealed pouch. The sealed pouch encloses a phase change material (e.g., a solvent prepared to have a desired boiling point) that can optionally be held by a solid support. The temperature control devices described herein can be combined with a heat source and a reaction chamber, such as a reaction chamber coupled to a reaction chip or card, for the purpose of forming a temperature control system.

Description

Technical Field

[0001] Background Art

[0001] Certain chemical reactions must be carried out within a specified temperature range in order to be accurate and / or effective. Specifically, biochemical reactions and reactions related to biological materials may be sensitive to temperature changes. In some cases, when the temperature fluctuates, the biological sample itself may denature or be damaged. Furthermore, depending on the process being carried out, the technique itself may be temperature-dependent, and its efficiency and effectiveness may decrease when exposed to excessive temperature fluctuations.

[0002]

[0002] As one example, a loop-mediated isothermal amplification (LAMP) assay has been developed to realize a diagnostic test that is a low-cost alternative to the polymerase chain reaction (PCR) technique. One specific variant form of the LAMP technique is reverse transcription loop-mediated isothermal amplification (RT-LAMP).

[0003]

[0003] Both the LAMP or RT-LAMP reactions usually have to be carried out at a temperature of about 60 degrees Celsius to about 70 degrees Celsius. When carried out in a laboratory, the temperature can be monitored and can be relatively easily controlled. However, outside the laboratory, such as in a home or field test, it may be difficult or impossible to monitor the temperature. In these equipment environments, temperature changes are common and can be harmful to accurate diagnostic tests.

[0004] In short, it is often necessary to adjust the temperature of a chemical reaction, but in some cases, it is not possible under certain conditions. Although methods intended to be used outside the laboratory equipment environment have been further developed, temperature control has become a major issue in the control of accurate tests and assays. Therefore, there has been a long-standing and continuous demand for efficient, low-cost, and high-performance means for adjusting the temperature of chemical reactions, particularly biochemical reactions such as LAMP and RT-LAMP.

Summary of the Invention

Means for Solving the Problems

[0005]

[0005] The present disclosure relates to a temperature control device, a temperature control system, and related methods. The embodiments described herein solve one or more technical problems related to adjusting the temperature of chemical reactions and particularly biochemical reactions. For example, when using LAMP or RT-LAMP to amplify a nucleic acid sequence, the temperature is preferably maintained at about 60 degrees Celsius to about 70 degrees Celsius. The temperature control device described herein is intended to create a temperature control system for effectively adjusting the temperature during the execution of the reaction and can be used together with one or more biochemical reaction chambers, such as one or more LAMP or RT-LAMP reaction chambers, a heat source.

[0006]

[0006] An exemplary temperature control device includes a film arranged and configured to form a sealed port. The sealed port encloses a phase change material (e.g., a solvent prepared to have a desired boiling point) that can optionally be held by a solid carrier. The solid carrier is configured to fit into the port and can be beneficially assist in distributing the phase change material to minimize the formation of hot spots or cold spots during the use of the temperature control device. The temperature control device described herein can be combined with a heat source and a reaction chamber for the purpose of forming a temperature control system.

[0007]

[0007] In some embodiments, the reaction chamber is a LAMP or RT-LAMP reaction chamber, such as a LAMP or RT-LAMP "card" or "chip" that is useful for remote assays (i.e., outside of a laboratory). In some embodiments, the heat source is an electric heater or an exothermic reaction device. During use, the temperature regulating device may be disposed between the heat source and the reaction chamber. When the heat source is activated, the heat source will heat the temperature regulating device, including a phase change material within the temperature regulating device (optionally held by a solid carrier). In the simplest explanation, when the temperature reaches the boiling point of the phase change material, a liquid to gas phase transition occurs. This can cause the temperature regulating device to begin to expand. While the phase change material undergoes a phase change, the temperature within the sealed port will be maintained at the boiling point, and thus, can beneficially buffer temperature fluctuations inherent in the heat source. The overall composition of the contents inside the temperature regulator port determines the thermal conductivity of the path between the heat source and the reaction chamber.

[0008]

[0008] When in contact with the reaction chamber, the temperature regulating device functions to maintain the reaction chamber at a temperature substantially close to the boiling temperature of the phase change material contained in the temperature regulating device. This is particularly common when using a heat source suitable for remote applications, such that even when the heat source provides inconsistent or fluctuating heat, the temperature regulating device functions as a buffer between the heat source and the reaction chamber to provide the reaction chamber with a substantially consistent temperature as long as the heat source maintains a state higher than the minimum temperature acceptable for the assay.

[0009]

[0009] The liquid-gas transition inside the temperature regulator determines its reaction to the temperature applied from the heat source. The solvent can evaporate at a temperature lower than its boiling point at a specific atmospheric pressure, and multiple solvents can be used to adjust the gas-liquid phase change response to a predetermined temperature. Various embodiments can utilize the preparation of various phase change materials, which is determined by the desired regulation temperature, and the desired regulation temperature can be determined based on the specific chemical reaction to be implemented.

[0010]

[0010] This summary is provided to introduce a selection of concepts in a simplified form that will be further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an indication of the scope of the claimed subject matter.

[0011]

[0011] From the following description of the embodiments in conjunction with the accompanying drawings and the appended claims, each forming a part of this specification, various objects, features, properties, and advantages of the present invention will become apparent and more readily recognized. In the drawings, like reference numerals may be used to indicate corresponding or similar parts in the various figures, and the various elements depicted are not necessarily drawn to scale.

Brief Description of the Drawings

[0012]

Figure 1A

[0012] It is a diagram showing an example of a temperature regulation device.

Figure 1B

Figure 1C

[0013] It is a phase change diagram showing a phase change system of a binary solvent composed of methanol and ethanol.

Figure 2

[0014] Figure 2A is a diagram showing an example of a solid carrier inserted into a pouch to form a temperature control device, and Figure 2B is a diagram showing an example of a solid carrier inserted into a pouch to form a temperature control device.

Figure 3

[0015] It is a side view showing a temperature control device in a heating / expanded state.

Figure 4

[0016] Figure 4A is a diagram showing an exemplary temperature control system including the temperature control device of FIGS. 1 - 3, a heat source, and a reaction chamber, which shows an exploded view of the system, and Figure 4B is a diagram showing an exemplary temperature control system including the temperature control device of FIGS. 1 - 3, a heat source, and a reaction chamber, which shows the assembled system.

Figure 5

[0017] It is an experimental result showing the effective use of the temperature control device of FIGS. 1 - 3 for regulating the heat generated by an electric heater.

Figure 6

[0018] It is an experimental result showing the effective use of the temperature control device of FIGS. 1 - 3 for regulating the heat generated by an exothermic reaction device.

Figure 7

[0019] It is a temperature reaction plot comparing multiple temperature control devices using various preparations of phase change materials.

Figure 8

[0020] Figure 8A is a temperature reaction curve of a temperature control device containing denatured alcohol, and Figure 8B is a temperature reaction curve of a temperature control device containing methanol.

Figure 9

[0021] It is a plot of the temperature over time of an integrated biochemical reaction device having a temperature control system, showing that the temperature control system being tested effectively regulates the temperature within the target temperature range over a long period of time.

DETAILED DESCRIPTION OF THE INVENTION

[0013] Preface

[0022] The embodiments described herein can solve one or more of the problems associated with the temperature regulation of biochemical reactions discussed above. The embodiments described herein are particularly useful for low-cost and / or remote applications where power and / or standard laboratory equipment are not readily available or economically feasible.

[0014]

[0023] As will be described in more detail later, temperature regulation devices, and temperature regulation systems incorporating such devices, can be used to regulate temperature in a variety of applications such as temperature-sensitive biochemical reactions. One example of a temperature-sensitive biochemical reaction is the LAMP or RT-LAMP reaction. Such reactions typically have a target temperature between about 60 degrees Celsius and about 70 degrees Celsius.

[0015]

[0024] The disclosed temperature regulation devices can further be utilized in other isothermal amplification reactions such as rolling circle amplification (RCA). RCA typically has a target temperature between about 30 degrees Celsius and about 45 degrees Celsius, although in some cases, RCA can be performed at even lower temperatures.

[0016]

[0025] In a laboratory equipment environment, temperature can be easily regulated. However, when performing LAMP or RT-LAMP-based assays or other biochemical reactions, it can become difficult to regulate temperature in a home or field equipment environment. As used herein, a "remote" equipment environment means any environment where finely controlled laboratory-grade temperature regulation is not available and / or not convenient. Examples include home equipment environments, field equipment environments, outdoor equipment environments, equipment environments where power supply is not readily available, temporary short-term clinic equipment environments, mobile medical units, or even medical facilities where the feasibility of realizing biochemical reactions using laboratory-grade temperature regulation is reduced due to cost constraints or operator training constraints.

[0017]

[0026] As discussed above, certain biochemical reactions require a specified temperature range in order to be effectively carried out. For example, when using LAMP or RT-LAMP, the temperature is preferably maintained at about 60 degrees Celsius to about 70 degrees Celsius. The temperature regulation device used herein is for the purpose of creating a temperature regulation system for effectively regulating the temperature during the execution of the reaction, and can be used together with one or more biochemical reaction chambers, such as one or more LAMP or RT-LAMP reaction chambers, and a heat source.

[0018] Exemplary temperature regulation device

[0027] Figures 1A and 1B show an embodiment of a temperature regulation device 100, and Figure 1B schematically shows a cross-sectional view for explaining the internal components of the device 100. The shown temperature regulation device 100 includes a film 102 and a solid support 106.

[0019]

[0028] The film 102 can include (for example, biaxially oriented polyethylene terephthalate (BoPET) known under the trade name MYLAR) polyethylene terephthalate, polypropylene, nylon, polyethylene, and / or polypropylene, and in addition or alternatively, can include other materials known in the art suitable for film applications. For example, the film 102 can be made of, in addition or alternatively, other polyester materials and / or other polymer materials suitable as films for temperature regulation devices. The film 102 can be metallized. The metallized film includes a thin metal coating that is usually aluminum, but other metals such as nickel and / or chromium can also be utilized.

[0020]

[0029] While most embodiments are described herein as "films", it will be understood that in addition or alternatively, other embodiments can utilize other structures that can provide sufficient structural integrity to contain the solvent and sufficient heat transfer ability to heat adjacent reaction chambers.

[0021]

[0030] Solid carrier 106 can be formed of a suitable fabric such as polybroadcloth, a polyester / cotton blend fabric, and / or other fabric materials capable of holding a phase change material of the solvent. In some embodiments, in addition or alternatively, solid carrier 106 can include solid materials (e.g., non-fabric), such as, for example, absorbent beads, granular materials, sponge materials, paper or other cellulose materials, fibrous materials, fiber bundles, or combinations thereof. Although solid carrier 106 is presently preferred, other embodiments can exclude solid carrier 106 and can simply include a phase change material added directly to the internal cavity of film 102.

[0022]

[0031] When included, solid carrier 106 can be sized to substantially conform to the planar surface area of the internal cavity of device 100. For example, solid carrier 106 can be sized to be equal to at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, or at least 95% (or a range using any two of the above as endpoints) of the planar surface area of the internal cavity of device 100.

[0023]

[0032] The "planar surface area" of the internal cavity is the projected area of the internal cavity from the perspective of a plan view (i.e., the perspective shown in FIG. 1B). That is, the planar surface area is equal to the length of the internal cavity multiplied by the width of the internal cavity (i.e., the two longest dimensions of the internal cavity). Further, the planar surface area is also the effective surface area by which the reaction chamber receives heat during use.

[0024]

[0033] As shown in FIG. 1B, the film 102 can form a pouch, in which the edges are sealed using a heat seal 104. In other embodiments, additionally or alternatively, the pouch can be sealed using an adhesive, thread, staple, stitching, folding, and / or other suitable methods for forming the pouch from the film.

[0025]

[0034] The illustrated embodiment shows four edges included in the heat seal 104. Other embodiments can have different configurations. For example, the film piece can be folded or formed as circular, thereby forming one or more “edges” of the pouch that do not require a heat seal 104.

[0026]

[0035] The solid support 106 can be immersed in or wetted with a phase change material. The phase change material can include, for example, an inorganic solvent and / or an organic solvent. Suitable solvents include methanol, n - hexane, cyclohexane, ethanol, ethyl acetate, isopropanol, tert - butanol, benzene, tetrahydrofuran, other solvents, or combinations thereof.

[0027]

[0036] Generally, a solvent is suitable when it has relatively minimal toxicity and has a boiling point that is at or slightly higher than the target temperature of the intended reaction. Solvent mixtures are also utilized, particularly when the solvents being mixed have comparable boiling points. When using a solvent mixture, one or more of the solvents in the mixture can have a boiling point outside the target range of the intended reaction, but the overall temperature - regulating effect of the mixture can still be effective in maintaining the reaction within the target temperature range.

[0028]

[0037] The phase change material can be selected based on the desired temperature to be regulated by the system and the boiling point of the phase change material. In presently preferred embodiments, the phase change material includes methanol, ethanol, isopropanol, or some combination thereof. Some preparations of denatured alcohol include ethanol in combination with, for example, small amounts of methanol (e.g., from 1 wt% to 15 wt%) and / or isopropanol (e.g., from 1 wt% to 15 wt%). Some embodiments can include mixtures of methanol and denatured alcohol, such as in a methanol to denatured alcohol ratio of from 0.5:1 to 2:1, from 0.75:1 to 1.5:1, or 1:1, or a range of ratios having as endpoints any two of the above values.

[0029]

[0038] FIG. 1C is a phase transition diagram of an ethanol / methanol mixture as an example of a solvent mixture that can be utilized in temperature regulation device 100. As shown, when using ethanol, the liquid-to-gas transition occurs at the boiling point of ethanol, which is plotted just above 78 degrees Celsius here. As more methanol is added (an increase in the mole fraction of methanol is shown along the X-axis), the liquid-to-gas transition occurs at a progressively lower temperature and a vapor-liquid equilibrium region appears. When using pure methanol, the transition occurs just above 64 degrees Celsius, the boiling temperature of methanol. This example shows that the solvent mixture can be prepared to adjust the temperature to be regulated if required for a particular assay.

[0030]

[0039] In LAMP or RT-LAMP, the reaction is preferably run at a temperature of from about 60 to about 70 degrees Celsius. Methanol has a boiling point of about 65 degrees Celsius. As a result, methanol undergoes a liquid-to-gas phase change and thus boils at about 65 degrees Celsius. Thus, during the phase change, the temperature regulation device regulates / maintains the temperature of the RT-LAMP reaction at about 65 degrees Celsius. Ethanol and isopropanol have higher boiling points (about 78 degrees Celsius and about 82 degrees Celsius, respectively), but can still be utilized in at least some applications for effective temperature regulation within the target LAMP / RT-LAMP range of 60 degrees Celsius to 70 degrees Celsius.

[0031]

[0040] During use, due to inherent heat transfer losses, the temperature of the reaction tends to be slightly lower than the temperature within the temperature control device. Thus, in some implementations, the phase change material can be prepared to have a boiling point slightly higher than the target temperature of the intended reaction. For example, the phase change material can be prepared to have a boiling point that is 0.1 degrees Celsius, 0.5 degrees Celsius, 1 degree Celsius, 2.5 degrees Celsius, 5 degrees Celsius, 7.5 degrees Celsius, 10 degrees Celsius, 12.5 degrees Celsius, or 15 degrees Celsius (or within a range using any combination of the foregoing as endpoints) higher than the target reaction temperature. This intentional offset can account for such heat transfer effects and bring the reaction temperature closer to the intended target temperature.

[0032]

[0041] In other embodiments, the temperature control device may need to be adjusted at other temperatures. For example, some biochemical reactions may have a target temperature that is about 20 degrees Celsius, 30 degrees Celsius, 40 degrees Celsius, 50 degrees Celsius, 60 degrees Celsius, 70 degrees Celsius, 80 degrees Celsius, 90 degrees Celsius, or even closer to 100 degrees Celsius, or another value within a range defined by any two of the foregoing temperatures, and the phase change material can be selected accordingly.

[0033]

[0042] The amount of phase change material added to the solid support 106 can vary. For example, the temperature control device 100 can include about 0.01 mL, 0.05 mL, 0.1 mL, 0.15 mL, 0.2 mL, 0.25 mL, 0.5 mL, 0.75 mL, 1.0 mL, 1.25 mL, 1.5 mL, 1.75 mL, 2.0 mL, 2.25 mL, or 2.5 mL of phase change material, or any value within a range defined by any two of the foregoing volumes.

[0034]

[0043] Furthermore, the amount of the phase change material can vary depending on the overall size of the temperature control device. For example, the temperature control device can have a planar surface area of from about 10 square centimeters to about 100 square centimeters, from about 20 square centimeters to about 80 square centimeters, or from about 30 square centimeters to about 60 square centimeters (e.g., from the surface contacting the reaction chamber). Certain embodiments can be in the range of, for example, from about 0.5 square centimeters to about 10 square centimeters or from about 5 square centimeters to about 25 square centimeters. The temperature control device can be sized to have a planar surface area within a range using any two of the above values in this paragraph as endpoints. The volume of the phase change material described above can be applied to a temperature control device of equivalent size and can be scaled accordingly for devices of other sizes.

[0035]

[0044] Thus, the temperature control device 100 has a phase change material volume to planar surface area ratio of from about 0.5 μL / cm 2 to about 225 μL / cm 2 , from about 1 μL / cm 2 to about 200 μL / cm 2 , from about 2.5 μL / cm 2 to about 175 μL / cm 2 , from about 5 μL / cm 2 to about 150 μL / cm 2 , from about 25 μL / cm 2 to about 125 μL / cm 2 , or from about 50 μL / cm 2 to about 100 μL / cm 2 and so on, or within a range using any two of the above values as endpoints, and can include a phase change material volume to planar surface area ratio of from about 0.05 μL / cm 2 to about 250 μL / cm 2 .

[0036]

[0045] Figures 2A and 2B show examples of solid carriers 106 inserted into a pouch formed by film 102. Phase change material can be added to the solid carrier 106 before or after the solid carrier 106 is placed in the pouch. The pouch can be completely sealed after the placement of the solid carrier 106.

[0037]

[0046] In some embodiments, the solid carrier 106 is formed to have a rectangular shape. In other embodiments, the solid carrier 106 can be formed to have an elliptical shape, a circular shape, a triangular shape, or other suitable shapes. The shape of the solid carrier 106 will most likely correspond to the general shape of the pouch, but the solid carrier 106 and the pouch do not necessarily have to have the same shape.

[0038]

[0047] In some embodiments, the solid carrier 106 can have a length of about 10 mm, 20 mm, 30 mm, 50 mm, 70 m, 80 mm, 90 mm, or 100 mm, or any value within the range defined by any two of the above lengths. In these embodiments, the solid carrier 106 can have a width of about 30 mm, 40 mm, 50 mm, 60 mm, 80 mm, 90 mm, 100 mm, 110 mm, or 120 mm, or any value within the range defined by any two of the above widths.

[0039]

[0048] Figure 3 shows a side view of an exemplary temperature control device 100 formed of film 102 having an inflated pouch 108. When the phase change material is heated to its boiling point or above, the phase change material undergoes a liquid-gas phase change. When the phase change occurs and the substance changes to the gas phase, the gas will occupy a larger space, and as a result, the pouch 108 can be inflated.

[0040]

[0049] The magnitude of the pouch expansion shown in FIG. 3 is exemplary, and it will be understood that other implementations may involve different levels of expansion during use. For example, at least some applications may involve expansion magnitudes of from about 1 mm to 5 mm, from about 2 mm to 10 mm, or from about 5 mm to 25 mm, or within a range defined by any two of the above values. The magnitude of the expansion means the difference in the height of the pouch before heating and during or after heating.

[0041] Exemplary temperature control system

[0050] FIG. 4A shows an exploded view of an exemplary temperature control system 200 that includes a temperature control device 100, a heat source 210, and a reaction chamber 220. In some embodiments, the heat source 210 includes an electric heater. However, in many embodiments, the heat source 210 includes a heat source that does not require electricity to provide heat, such as a heat source that relies on an exothermic reaction to generate heat. Exemplary exothermic reaction devices include oxygen-reactive devices (e.g., devices based on the reaction of ambient air with iron and / or zinc), water-reactive devices (e.g., devices based on the reaction of water and sodium chloride with magnesium and iron), and crystallization / nucleation-based devices (e.g., supersaturated sodium acetate devices).

[0042]

[0051] The reaction chamber 220 can be a biochemical reaction chamber, such as an isothermal nucleic acid amplification chamber, including a LAMP amplification chamber, an RT-LAMP amplification chamber, or other reaction chambers that require temperature control. The reaction chamber 220 can be included as part of a "chip" or "card" that is useful for remote facility environments.

[0043]

[0052] FIG. 4B shows an example of the assembled temperature control system 200. Some embodiments can include adding one or more insulating layers disposed around the components of the system 200. The insulating layer can include, for example, insulating foams (e.g., expanded polystyrene), mineral wool, fiberglass materials, cellulose materials, insulating fabrics, other suitable insulating materials, and combinations thereof.

[0044]

[0053] The temperature control device 100 can be disposed between the heat source 210 and the reaction chamber 220. The heat source 210 and / or the reaction chamber 220 can be attached to the temperature control device 100 using an adhesive (e.g., glue or tape) and / or mechanical fixation (e.g., clamping the components together). In the example shown, the temperature control device 100 is somewhat expanded, which implicitly indicates that at least a portion of the phase change material is undergoing a phase change from liquid to gas.

Example

[0045] Example 1

[0054] A temperature control device was created using a metallized MYLAR film heat-sealed on three sides to form a partially sealed pouch. A rectangular piece of fabric made of poly broadcloth and a polyester / cotton blend, having dimensions of 50 mm × 80 mm, was placed inside the pouch, and 1 mL of methanol was added to the fabric piece. Then, air evaporated from the pouch and the fourth side was heat-sealed, thereby creating a completely sealed pouch.

[0046]

[0055] In this experiment, two different heat sources were used: an electric heater and a "90C" oxygen-reactive pouch available from Exothermix (College Station, Texas).

[0047]

[0056] The temperature control system tested included a resistive electronic heater attached to the temperature control device. The temperatures of (1) the electronic heater and (2) the temperature control device (on the opposite side of the electronic heater) were measured over a 70-minute duration. The results of this test are plotted in FIG. 5.

[0048]

[0057] When the electronic heater exceeds a temperature of about 65 degrees Celsius, even if the electronic heater reaches 80 to 90 degrees Celsius, the temperature control device begins to adjust / maintain the temperature at about 63 degrees Celsius. When the electronic heater is less than about 65 degrees, the temperature control device has the same temperature as the electronic heater.

[0049] Example 2

[0058] In a second experiment, a temperature control device similar to that of Example 1 was coupled to a "90C" oxygen-reactive pouch available from Exothermix (College Station, Texas). The temperature of the temperature control device (on the side opposite the oxygen-reactive pouch) was measured over multiple trials for a duration of 13 to 25 minutes.

[0050]

[0059] After an initial test trial, four additional trials were conducted, with one trial measuring the temperature of only the heat source without the temperature control device to be attached, while the other three trials measured the temperature of the temperature control device coupled to the heat source. The results are plotted in Figure 6.

[0051]

[0060] As shown, the "90C" oxygen-reactive pouch reached a temperature just slightly above 85 degrees Celsius. When coupled to the temperature control device, the temperature was effectively adjusted to just slightly above about 60 degrees Celsius in all three of these trials.

[0052] Example 3

[0061] Multiple temperature control devices were constructed to test various phase change materials. The test was conducted by placing the temperature control device between two aluminum plates. The bottom plate was heated using a resistive element. The temperatures of both the top plate and the bottom plate were monitored using a thermistor. The results are shown in Figure 7.

[0053]

[0062] In Figure 7, "air" means that liquid phase change substances are excluded, "H2O" means water, "MeOH100" means 100 μL of methanol, "MeOH150" means 150 μL of methanol, "MxT_150" means denatured alcohol (ethanol having 1 wt% to 15 wt% of methanol and isopropanol respectively), and "1:1" means a 1:1 mixture of methanol and denatured alcohol.

[0054]

[0063] As shown, "air" and "H2O" did not achieve any temperature regulation at the tested temperatures. Devices using methanol were effective, but the slightly higher regulated temperatures presented by the "MxT" and "1:1" embodiments may be suitable for certain applications.

[0055] Example 4

[0064] Figures 8A and 8B show the temperature response curves of MxT (denatured alcohol) and MeOH150 including a temperature regulation device, each using a test setup similar to that of Example 3. The "setpoint" was determined as the regulated temperature when the heater temperature was between 70 degrees Celsius and 90 degrees Celsius, and is shown by bars in the figure.

[0056]

[0065] As shown, the denatured alcohol embodiment presented a more suitable higher temperature setpoint range. That is, a larger portion of the setpoint range was within the target range of 60 degrees Celsius to 70 degrees Celsius. However, the methanol embodiment was able to "exclude" excessive temperatures (e.g., temperatures above about 70 degrees Celsius) better. Therefore, a temperature regulation device having denatured alcohol as the phase change substance may be suitable for applications where the setpoint is most important, while a temperature regulation device having methanol as the phase change substance may be suitable for applications where excluding excessive temperatures is most important. A mixture of denatured alcohol and methanol or a mixture of ethanol and methanol can beneficially balance both goals.

[0057]

[0066] For the purpose of effectively regulating temperature to chemically analyze specifications over the expected ambient temperature range that an integrated device will face during use, the characteristics of the complete phase change of the mixture, including the effects from both boiling and evaporation, can perform the work.

[0058] Example 5

[0067] A temperature regulation system was constructed and tested. Each temperature regulation system included an oxygen-reactive pouch (available from Exothermix (College Station, Texas)), a temperature regulation device containing 150 μL of "MxT" denatured alcohol as a phase change material, and a microfluidic card, which were stacked in this order. The system was covered with insulating foam except for cutouts for the card portion and for oxygen ingress.

[0059]

[0068] The temperature was measured over time on the card in a controlled ambient environment at 20 degrees Celsius. The results are shown in Figure 9. As shown, the system was able to beneficially regulate the temperature within the target range of 60 to 70 degrees Celsius from approximately the 5-minute mark to approximately the 40-minute mark. It is expected that by further optimization, longer temperature regulation times can also be achieved.

[0060] Additional Terms and Definitions

[0069] While specific embodiments of the present disclosure have been described in detail with reference to specific configurations, parameters, components, elements, etc., this description is illustrative and should not be construed as limiting the scope of the claimed invention.

[0061]

[0070] Furthermore, in any given element of the components of the described embodiments, any alternative of the alternatives that may be described for this element or component can generally be used individually or in combination with each other, unless otherwise implied or specifically stated.

[0062]

[0071] In addition, unless otherwise specified, numbers representing amounts, configurations, distances, or other measurements used in this specification and the claims are to be understood as optionally modified by the term "about" or its synonyms. When terms such as "about", "approximately", or "substantially" are used with an amount, value, or condition, it can be interpreted to mean an amount, value, or condition that deviates by less than 20%, less than 10%, less than 5%, less than 1%, less than 0.1%, or less than 0.01% from the recited amount, value, or condition. At least, and also not intending to limit the application of the doctrine of equivalents to the claims, each numerical parameter should be construed in light of the significant digits recited and by applying ordinary rounding techniques.

[0063]

[0072] Any headings and subheadings used in this specification are for organization purposes only and are not intended to be used to limit the scope of this description or the claims.

[0064]

[0073] Furthermore, as used in this specification and the appended claims, the singular forms "a", "an", and "the" do not exclude a plurality of objects unless the context clearly dictates otherwise. Thus, for example, embodiments referring to a single object (e.g., "a small device") can also include two or more such objects.

[0065]

[0074] Embodiments disclosed herein should be understood as comprising / including the disclosed components, and thus can also include additional components not explicitly described. Optionally, embodiments disclosed herein substantially do not have or completely do not have components not specifically described. That is, the components not disclosed can optionally be completely excluded or substantially excluded from the disclosed embodiments. For example, phase change materials (including solvents), solid carriers, and / or film materials not specifically described herein can optionally be completely excluded or substantially excluded.

[0066]

[0075] Embodiments that "substantially exclude" or "substantially do not have" components can include a small amount and / or a non-functional amount of the components. For example, a component that is "substantially excluded" can be included in an amount of 2% or less, 1% or less, 0.1% or less, or 0.01% or less of the weight of the relevant component (e.g., of the total weight of the phase change material or solid carrier).

[0067]

[0076] A configuration that "completely excludes" or "completely does not have" a component does not include an amount of the component that is detectable (i.e., does not include an amount exceeding any inherent background signal associated with the test equipment) when analyzed using standard coating composition analysis techniques such as chromatography (e.g., thin-layer chromatography (TLC), gas chromatography (GC), liquid chromatography (LC)) or spectroscopy (e.g., Fourier transform infrared (FTIR) spectroscopy).

[0068]

[0077] Furthermore, it will be recognized that embodiments described herein can further include one or more distinct embodiments' characteristics and / or features (e.g., inclusions, components, members, elements, parts, and / or portions), and are not necessarily limited only to the features explicitly described for a particular embodiment. Thus, the various features of a given embodiment can be combined with and / or incorporated into other embodiments of the present disclosure. Accordingly, the disclosure of a particular feature associated with a specific embodiment of the present disclosure should not be construed as limiting the application or inclusion of the above feature in this particular embodiment. Rather, it will be recognized that other embodiments can also include such features.

Claims

1. A temperature control device for regulating the temperature during a biochemical reaction, comprising: a film material arranged and configured to form a pouch; a solid support disposed within the internal cavity of the pouch; a phase change material disposed within the internal cavity of the pouch, the phase change material being prepared such that at least a portion thereof undergoes a phase change from liquid to gas during the execution of the biochemical reaction.

2. The temperature control device according to claim 1, wherein the film comprises a polyester film.

3. The temperature control device according to claim 2, wherein the film comprises biaxially oriented polyethylene terephthalate (BoPET).

4. The temperature control device according to claim 1, wherein the phase change material comprises a solvent.

5. The temperature control device according to claim 4, wherein the solvent comprises methanol, ethanol, isopropanol, or a combination thereof.

6. The temperature control device according to claim 4, wherein the solvent has a boiling point between about 20°C and about 80°C.

7. The temperature control device according to claim 4, wherein the solvent comprises a solvent mixture.

8. The temperature control device according to claim 1, wherein the solid support comprises a fabric material.

9. The temperature control device according to claim 1, comprising from about 0.25 mL to 2.0 mL of the phase change material.

10. The temperature control device according to claim 1, wherein the pouch is heat-sealed.

11. The temperature control device according to claim 1, wherein the solid support is sized to substantially conform to the planar surface area of the internal cavity.

12. The temperature control device according to claim 1, having a planar surface area of from about 10 square centimeters to about 100 square centimeters.

13. From about 2.5 μL / cm ２ to about 250 μL / cm ２ The temperature control device according to claim 1, having a phase change material volume to planar surface area ratio of

14. A temperature control system comprising: the temperature control device of claim 1; a heat source coupled to a first side of the temperature control device; and a reaction chamber coupled to a second side of the temperature control device and configured to perform a biochemical reaction.

15. The temperature control system according to claim 14, wherein the heat source comprises an exothermic reaction device.

16. The temperature control system according to claim 15, wherein the exothermic reaction device is an oxygen-reactive device.

17. The temperature control system according to claim 14, wherein the reaction chamber is configured to perform an isothermal nucleic acid amplification reaction.

18. The temperature control system according to claim 17, wherein the isothermal nucleic acid amplification reaction is LAMP or RT-LAMP.

19. A method for controlling the temperature of a biochemical reaction, comprising: providing a temperature control system, the temperature control system comprising: (i) a film material arranged and configured to form a pouch, a solid carrier disposed in the internal cavity of the pouch, and a phase change material disposed in the internal cavity of the pouch, a temperature control device comprising; (ii) a heat source coupled to a first side of the temperature control device, and (iii) a reaction chamber coupled to a second side of the temperature control device and configured to perform a biochemical reaction, including the steps of: activating the heat source to generate heat, whereby the phase change material of the temperature control device undergoes a phase change from liquid to gas; performing the biochemical reaction while the heat source generates heat and while the phase change material undergoes a phase change.

20. The method according to claim 19, wherein the biochemical reaction comprises an isothermal nucleic acid amplification reaction.

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