Thermal cycling method and system

Abstract

The present invention provides a method, device, etc., for thermal cycling of a microfluidic cartridge, comprising a permeable heat sink and / or a flexible heat spreader for sealing one or more channels on the microfluidic cartridge. [Solution] A device for thermally cycling a microfluidic cartridge, The system comprises a microfluidic cartridge in contact with a light-absorbing material, a first heat sink in contact with the microfluidic cartridge, a second heat sink adjacent to the first heat sink, one or more light sources adjacent to the first heat sink, and a temperature sensor for detecting temperature changes of the microfluidic cartridge. The first heatsink is located within the second heatsink. The device is a device that alternately heats and cools the microfluidic cartridge.

Description

Technical Field

[0001]

[0001] Priority and Incorporation by Reference

[0002]

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 106,254, filed October 27, 2020, the disclosure of which is hereby incorporated by reference in its entirety.

[0003]

[0003] Field of Disclosure

[0004]

[0004] The present disclosure relates to rapid thermal cycling, such as provided in applications including amplification of genetic material. The present disclosure further relates to microfluidic chips for use in rapid thermal cycling systems.

Background Art

[0005]

[0005] Background

[0006]

[0006] In PCR and other reactions, the thermal gradient of the target region is an important physical property for the function of the device. It is desirable for the overall heating region gradient to be within a very small range so that the entire solution is heated uniformly and PCR or other reactions occur simultaneously everywhere in the reaction vessel. A constant temperature is even more important in digital reactions such as dPCR. This is because non-uniform heating can affect performance or limit where the PCR reaction occurs in different regions of the cartridge, which is less of a problem in other reactions such as qPCR. When using an optical method to heat a microfluidic device, very fast heating can be achieved, but a transparent optical path from the light source to the cartridge is required, limiting the applicability of conventional cooling methods such as the application of an aluminum heat sink.

[0007]

[0007] This application seeks to provide alternative means to enable constant and uniform heating and cooling.

[0008]

[0008] Furthermore, when performing PCR and other reactions requiring thermal cycling in microfluidic devices, including digital PCR, sealing or closing the channels is usually an essential requirement. To obtain good thermal cycling performance, the microchannels must be properly closed. To do this, the fabrication process, especially for joining the cartridge components, is key. One example of such joining is the process of joining the channel substrate and the sealing substrate, as shown in (Figure 1). Typically, methods such as thermal bonding, solvent bonding, adhesive bonding, and laser welding are used. However, each method has its advantages and disadvantages, and the difficulty of joining depends greatly on the materials used. Some materials, such as PMMA, can be joined more easily than others, such as cyclic olefin polymers (COP). If the microfluidic channels are not adequately sealed, delamination and bubble formation may occur (Figure 1), which may adversely affect the reactions taking place in the channels.

[0009]

[0009] Accordingly, this disclosure also seeks to provide alternative means that enable improved sealing of microfluidic channels. [Overview of the project]

[0010]

[0010] This disclosure relates to methods and systems for thermal cycling, including for use in reactions such as PCR. To achieve rapid PCR / thermal cycling, a combination of features is provided that includes an optical method in which a high-power LED irradiates a light-absorbing material to convert light into heat, thereby enabling rapid heating. For rapid cooling, an air-cooling method may be used.

[0011]

[0011] These and other embodiments, purposes, features, and advantages of the present disclosure will become apparent when the following detailed description relating to exemplary embodiments of the present disclosure is read in conjunction with the accompanying drawings and the provided claims. [Brief explanation of the drawing]

[0012]

[0012] The accompanying drawings incorporated herein and forming a part of this specification illustrate various embodiments, objects, features, and advantages of the present disclosure.

[0013] [Figure 1]

[0013] FIG. 1 is a diagram showing air bubbles trapped in a microfluidic cartridge during manufacture.

[0014] [Figure 2]

[0014] FIG. 2 is a diagram showing one embodiment of sealing a microfluidic channel using a heat spreader.

[0015] [Figure 3]

[0015] FIG. 3 is a conceptual diagram of the arrangement of components in one embodiment.

[0016] [Figure 4]

[0016] FIG. 4 is a conceptual diagram of the arrangement of components in one embodiment illustrating functionality during heating and cooling.

[0017] [Figure 5AB]

[0017] FIGS. 5A - 5B are diagrams showing alternative arrangements of components.

[0018] [Figure 6AB] 、 [Figure 6CD]

[0018] FIGS. 6A - 6D are diagrams showing alternative arrangements of components.

[0019] [Figure 7AB] 、 [Figure 7CD]

[0019] FIGS. 7A - 7D are diagrams showing the configuration of alternative light sources.

[0020] [Figure 8]

[0020] FIG. 8 is a diagram showing an exemplary thermal cycler in one embodiment.

[0021] [Figure 9]

[0021] Figure 9 is a diagram of a thermal cycler in one embodiment.

[0022] [Figure 10]

[0022] Figure 10 is an exploded view of a thermal cycler in one embodiment.

[0023] [Figure 11]

[0023] Figure 11 is an exploded view of a thermal cycler in one embodiment.

[0024] [Figure 12]

[0024] Figure 12 is a diagram showing the configuration of a multi-LED having infrared temperature detection in one embodiment.

[0025] [Figure 13]

[0025] Figure 13 is a diagram showing ray tracing in sapphire cubes and light guides of two exemplary configurations.

[0026] [Figure 14]

[0026] Figure 14 is a diagram showing the configuration of a gasket of a cartridge and a vacuum sealing system in one embodiment.

[0027] [Figure 15]

[0027] Figure 15 is a graph showing the simulation results of a two-step PCR thermal profile.

[0028] [Figure 16]

[0028] Figure 16 is a result table showing the relationship between simulation (high flux) and experiment (low flux) conditions.

[0029] [Figure 17]

[0029] Figure 17 is a graph showing the experimental results of the heating rate and temperature of the lower thermocouple over time.

[0030] [Figure 18]

[0030] Figure 18 is a graph showing the heating rate and temperature over time at the ends and center of a microfluidic cartridge, in relation to a diagram of a thermal cycler in one embodiment.

[0031] [Figure 19]

[0031] Figure 19 is a graph showing the irradiance of the light guide emission surface of a diffuse surface having a specular film on the transition region.

[0032] [Figure 20]

[0032] Figure 20 is a graph showing the optical uniformity characteristics of a thermal cycle system in one embodiment.

[0033] [Figure 21]

[0033] Figures 21A and 21B are graphs comparing the optical uniformity of a hollow light pipe with that of a thermal cycle system in one embodiment.

[0034] [Figure 22]

[0034] Figure 22 is a graph illustrating the relationship between irradiance, input current, and distance in a thermal cycle system in one embodiment.

[0035] [Figure 23]

[0035] Figure 23 is a block diagram of the thermal models for slow heating with slow cooling and fast heating with slow cooling.

[0036] [Figure 24]

[0036] Figure 24 shows a practical implementation of the thermal cycle system used in the one-dimensional simulation.

[0037] [Figure 25]

[0037] Figure 25 is a graph illustrating the thermal simulation results for various configurations of the thermal cycle system.

[0038] [Figure 26]

[0038] Figure 26 is a graph illustrating the simulation results of the maximum cartridge temperature for various configurations of the thermal cycle system.

[0039] [Figure 27]

[0039] Figure 27 shows two graphs illustrating the heating profile of a thermal cycle configuration in one embodiment using an adhesive with a thickness of 25 μm.

[0040] [Figure 28]

[0040] Figure 28 is a graph showing the superposition of the heating and cooling curves obtained by simulation and the experimental results.

[0041] [Figure 29]

[0041] Figure 29 is a graph illustrating the relationship between temperature and time at various heating and cooling rates.

[0042] [Figure 30]

[0042] Figure 30 shows an infrared thermal image plot of a cartridge in a thermal cycle system in one embodiment, and a specific point in the thermal cycle.

[0043] [Figure 31]

[0043] Figure 31 is a graph showing an overview of the heating and cooling rates and steady-state temperature uniformity of a thermal cycle system in one embodiment.

[0044] [Figure 32]

[0044] Figure 32 is a graph illustrating the relationship between temperature and time during a complete PCR thermal cycle operation using a thermal cycle system in one embodiment.

[0045] [Figure 33]

[0045] Figure 33 shows the simulation results of an infrared image plot of one embodiment having a complete mirror transition.

[0046] [Figure 34]

[0046] Figure 34 shows the simulation results of an infrared image plot of one embodiment having a 3M mirror coating.

[0047] [Figure 35]

[0047] Figure 35 shows the simulation results of an infrared image plot of one embodiment having machined bare aluminum.

[0048] [Figure 36]

[0048] Figure 36 is a simulation graph showing the relationship between the average fluid temperature and time, and the relationship between the maximum cartridge temperature and time, in a thermal cycler in which a heat spreader / light absorber is attached to a microfluidic chip in one embodiment.

[0049]

[0049] Throughout the drawings, unless otherwise noted, the same reference numerals and numerals are used to indicate similar features, elements, components, or parts of the illustrated embodiments. Further, the present disclosure will be described in detail with reference to the drawings, in relation to exemplary embodiments for illustrative purposes. It is intended that changes and modifications may be made to the exemplary embodiments described without departing from the true scope and spirit of the present disclosure as defined by the appended claims. [Modes for carrying out the invention]

[0050]

[0050] This disclosure describes several embodiments, and details known to those skilled in the art rely on patents, patent applications, and other references. Accordingly, wherever patents, patent applications, or other references are cited or repeated herein, it should be understood that they are incorporated herein by reference in their entirety for any purpose other than the proposals described herein.

[0051]

[0051] Efficient thermal cycling of a microfluidic chip requires a configuration that allows for both optimal heating and cooling, as well as sufficient observation of the microfluidic chip. To maintain a transparent optical path and provide an efficient cooling method, this disclosure provides the use of a transmissive heatsink in the infrared (IR) to near-ultraviolet (UV) wavelength range. Such a heatsink also has sufficient thermal conductivity and heat capacity to operate efficiently in removing heat from the microfluidic device. This device, in conjunction with a radiant thermal heating system, provides an efficient and simplified method for both heating and passive cooling of a microfluidic device. In this device, the transmissive heatsink forms a transparent optical path for light from a radiant heat source to travel to the cartridge. The transmissive heatsink has a thermal diffusivity close to that of ceramic or aluminum and can be used as an efficient heatsink.

[0052]

[0052] Accordingly, the present disclosure provides a method and system for passively cooling an optically heated cartridge, enabling the design of such devices to be simplified and miniaturized. Such a design also achieves efficient cooling that improves the thermal cycle rate without significantly affecting the heating rate. The present disclosure also enables combinations of multiple light sources, e.g., LEDs (including arrays of LEDs), lasers, lamps, and the like, to increase the usable heating area or increase the light intensity. In addition, it provides an efficient means for measuring the heating area temperature via an infrared thermometer. Furthermore, the devices and systems in the present disclosure enable the minimization of the cooling gradient across the entire microfluidic chip.

[0053]

[0053] In one embodiment, a device is provided for thermally cycling a microfluidic cartridge, comprising a microfluidic cartridge in contact with a light-absorbing material, a first heat sink in contact with the microfluidic cartridge, a second heat sink adjacent to the first heat sink, one or more light sources adjacent to the first heat sink, and a temperature sensor for detecting temperature changes of the microfluidic cartridge, the device alternately heating and cooling the microfluidic cartridge. In one embodiment, one or more light sources emit light in the infrared to UV wavelength range. In some embodiments, the first heat sink is transparent. In another embodiment, the first heat sink is transparent to light in the infrared to UV wavelength range. In other embodiments, the first heat sink comprises a thermal conductive material. The first heat sink may optionally include sapphire.

[0054]

[0054] In another embodiment, the light absorber converts light into heat. The light absorber may be on or inside the microfluidic cartridge, or may be in thermal communication with the microfluidic cartridge. The light absorber may be incorporated on or inside a part of a device other than the microfluidic cartridge, and when the cartridge is placed inside the device, this material will be in thermal communication with the microfluidic cartridge. The light absorber may be attached to the microfluidic cartridge or other structures within the device using an adhesive. In one embodiment, the light absorber may be attached to a transparent heat sink.

[0055]

[0055] In yet another embodiment, the first permeable heat sink allows light to be transmitted to the microfluidic cartridge through the heat sink during heating. During cooling, the first permeable heat sink can function as a passive heat sink for cooling the microfluidic cartridge. In another embodiment, the second heat sink is equipped with a thermal conductive material and may optionally be made of aluminum.

[0056]

[0056] One or more light sources may be one or more LEDs. In some embodiments, a first transparent heat sink captures light from one or more light sources and transmits it to a microfluidic cartridge.

[0057]

[0057] In another embodiment, the device further comprises a feedback and control unit that communicates with a temperature sensor to provide the initiation, stopping, and temperature control of heating and cooling. Furthermore, the device may further comprise one or more infrared sensors positioned close to the device so that one or more sensors can observe the microfluidic cartridge. Additional or alternative, at least one resistance temperature sensing element may be provided in contact with the surface of the first heat sink that is in contact with the microfluidic cartridge. The resistance temperature detector may be in the form described in U.S. Published Patent Application No. 20120052560, or used in the manner described herein, the disclosure thereof is incorporated herein by reference in whole.

[0058]

[0058] In another embodiment, the microfluidic cartridge may have an open microfluidic channel, and a flexible heat spreader is provided between the open microfluidic channel and the first heat sink. In another embodiment, the first heat sink can be pressurized to contact and deform the flexible heat spreader, so that the flexible heat spreader contacts the microfluidic cartridge and fluidly seals the microfluidic channel.

[0059]

[0059] In another embodiment, a method is provided for thermal cycling a microfluidic cartridge, the method comprising: (i) providing a device comprising a microfluidic cartridge in contact with a heat absorber, a first heat sink in contact with the microfluidic cartridge, a second heat sink adjacent to the first heat sink, one or more light sources adjacent to the first heat sink, and a temperature sensor for detecting temperature changes of the microfluidic cartridge; (ii) heating the microfluidic cartridge by turning on one or more light sources; (iii) cooling the microfluidic cartridge by turning off one or more light sources; and (iv) continuously repeating steps (ii) and (iii) throughout the thermal cycle.

[0060]

[0060] Figure 3 shows a model of such a system or device in one embodiment. A light-absorbing layer 312 having high light absorption in the wavelength range of radiant thermal light is positioned in direct contact with a fluid tank 301, the fluid tank may be a microfluidic cartridge or a microfluidic cartridge assembly formed by combining multiple components and / or held in place. For example, a microfluidic cartridge can be formed using a single-layer body 302 having an open well or channel 303 that is closed by pressurizing the absorption layer 312, a gasket or the like. For example, Figure 2 shows a microfluidic cartridge 201 having a well or channel 203 that is initially open to the environment. After applying a fluid sample to the well or channel 203, a heat spreader 207 can be bonded to the cartridge 201 using a suitable adhesive means 208 (e.g., liquid adhesive, epoxy resin, double-sided tape or the like). When a permeable heat sink 210, such as a sapphire block, is placed against the gasket 207, the gasket deforms to contact the upper surface of the cartridge 201, effectively sealing the well or channel 203. This allows the permeable heat sink 210 to thermally communicate with the heat spreader 207 and the cartridge 201, and as a result, when the radiant heat source 209 is lit, the light can pass through the permeable heat sink 210 to efficiently and uniformly heat the cartridge 201. Such embodiments have been found in the art and directly address the problem of the cartridge 101 described herein (Figure 1), which comprises a lower cover 102 and an upper cover 104 joined at a joint surface 106 with a well or channel 103 in between. Improper sealing of the well or channel 103 can lead to delamination and the formation of bubbles 105, thereby adversely affecting the reaction within the channel.

[0061]

[0061] Referring again to Figure 3, in another embodiment, the cartridge body may be formed of upper and lower layers, which, when bonded together, enclose the well or channel 303. The absorption layer 312 may be part of the cartridge 301, so that typical concerns regarding contact thermal resistance can be ignored, and efficient heating can be achieved with lower power requirements. Alternatively, the absorption layer 312 may be placed on or thermally communicated with the permeable heat sink 310 described herein. The absorption layer 312 may be a black or dark-colored substrate or a heat spreader. In some embodiments, the absorption layer 312 may also function as a gasket. The radiant heat source 309 is located distal to the cartridge 301, such that the permeable heat sink 310 is located between the radiant heat source 309 and the cartridge 301. To heat, the radiant heat source 309 is turned on. To cool the system (including the microfluidic cartridge assembly 301), the radiant heat source 309 can be switched off, allowing the (first) permeable heat sink 310 to become substantially isothermal, thereby passively cooling the system. Figure 3 further outlines the various temperature points and contact thermal resistances of the materials between the permeable heat sink 310 and the fluid sample in the cartridge 301.

[0062]

[0062] Figure 4 illustrates the functionality of the transmissive heatsink 410 during the heating (left) and cooling (right) stages of a thermal cycle in another embodiment. The radiant heat source 409 is positioned so that light from the light source 409 can pass through a light guide having a reflective film or polished surface 414 before entering the light-transmitting heatsink 410. The transmissive heatsink 410 is located within a second heatsink 415. The opposite end of the heatsink 410 is in thermal communication with a sample 416, which may be contained in a microfluidic cartridge or similar. During heating, the radiant heat source 409 is lit, and light (straight arrow) passes through the light guide and the transmissive heatsink 410 before reaching the sample 416 and heating it. During cooling, the heat source 409 is turned off, and the temperature of the sample 416 decreases as heat (wavy arrow) is dissipated from the sample 416 through the transmissive heatsink 410 and the second heatsink 415.

[0063]

[0063] In some embodiments, the transmissive heat sink can be formed using sapphire (Al2O3) or other transmissive materials. Using a transmissive material with a refractive index close to or higher than that of glass (sapphire has a high refractive index of 1.73) as a heat sink has the advantage of being usable as a light pipe or light guide for an incident radiant heat source. This makes it possible to distribute the light profile evenly through internal refraction in some embodiments, including total internal refraction, thereby improving heating uniformity in the target area. Figure 13 shows the simulation results of ray tracing, starting from inside a second heat sink 1315 having an inner surface with a reflective film or polished surface 1314 that functions as a light guide, and then the light ray enters the incident surface 1318 of the transmissive heat sink 1310, passes through the transmissive heat sink, and exits from the exit surface 1319. The only difference between the left and right simulations is the plane as seen through the transmissive heat sink 1310, with the left being a front view and the right being a diagonal view, both illustrating the even distribution of the light profile through internal refraction. This allows for the use of multiple LEDs in combination, concentrating the total radiant flux into a single plane. This also enables heating of a larger cartridge area while maintaining a similar heat flux range and increasing the electric flux density. Figure 12 shows a configuration using multiple LEDs with a translucent heatsink. In some embodiments, translucent materials (such as sapphire) have a higher thermal diffusivity compared to other optical materials, enabling efficient cooling of the system. Other relevant properties of translucent materials used in the first heatsink include good strength, high surface hardness and thermal stability, as well as good light transmittance in the visible to near-infrared light spectrum.

[0064]

[0064] Figures 5A and 5B show another embodiment and provide an alternative configuration for the light-absorbing layer 512. In Figure 5A, the transparent heat sink 510 is located inside the second heat sink 515. The light-absorbing layer 512 is attached to the cartridge 501 such that the light-absorbing layer 512 is located between the cartridge 501 and the transparent heat sink 510. In some embodiments, physical contact can be made between the light-absorbing layer 512 and the transparent heat sink 510. In other embodiments, there is no physical contact between the light-absorbing layer 512 and the transparent heat sink 510, but in all configurations, the transparent heat sink 510 is thermally in communication with the light-absorbing layer 512, and the light-absorbing layer 512 is thermally in communication with the cartridge 501. In Figure 5B, the light-absorbing layer 512 is attached to the transparent heat sink 510 instead. The light-absorbing layer 512 can be in physical contact with the cartridge 501, or, in other embodiments, there is no physical contact between the light-absorbing layer 512 and the cartridge 501. In any configuration, the permeable heat sink 510 is in thermal communication with the light-absorbing layer 512, and the light-absorbing layer 512 is in thermal communication with the cartridge 501.

[0065]

[0065] Figures 6A to 6D show further embodiments having alternative configurations. In Figure 6A, the translucent heatsink 610 is located inside or between the second heatsink 615. As shown in Figure 6A, the single light-absorbing layer 612 can be directly attached to or bonded to the translucent heatsink 610 so that it is positioned between the translucent heatsink 610 and the cartridge 601. Alternatively, as shown in Figure 6B, the multilayer light-absorbing layers 612, 617 can also be directly attached to or bonded to the translucent heatsink 610 so that they are positioned between the translucent heatsink 610 and the cartridge 601. In either of the configurations shown in Figures 6A and 6B, when the cartridge 601 is inserted into an instrument or device comprising a transparent heat sink 610, a second heat sink 615, and one or multiple light-absorbing layers 612, 617, the cartridge 601 can be positioned so as to be in direct contact with the one or multiple light-absorbing layers 612, 617, or so as to be in thermal communication with the one or multiple light-absorbing layers 612, 617, thereby enabling heating and cooling of the cartridge 601 using the processes described herein.

[0066]

[0066] In Figure 6C, the transparent heat sink 610 is located inside or between the second heat sink 615. The single light-absorbing layer 612 can be placed between the transparent heat sink 610 and the cartridge 601, and the adhesive can be placed between the transparent heat sink 610 and the single light-absorbing layer 612, so that the adhesive is attached to or bonded to the transparent heat sink 610 via adhesive 608. Alternatively, as shown in Figure 6D, the multilayer light-absorbing layers 612, 617 can be placed between the transparent heat sink 610 and the cartridge 601, and the multilayer light-absorbing layers 612, 617 can be attached to or bonded to the transparent heat sink 610 via adhesive 608, so that the adhesive is placed between the transparent heat sink 610 and at least one of the multilayer light-absorbing layers 612, 617. Adhesives used in the implementation of this disclosure include liquid adhesives, epoxy resins, double-sided adhesive tapes, and the like.

[0067]

[0067] In each configuration shown in Figures 6A to 6B, when the cartridge 601 is inserted into an instrument or device comprising a transparent heat sink 610, a second heat sink 615, and one or multiple light-absorbing layers 612, 617 (with or without adhesive 608), the cartridge 601 can be positioned so that it is in direct contact with the one or multiple light-absorbing layers 612, 617 and / or is in thermal communication with the one or multiple light-absorbing layers 612, 617, and as a result, heating and cooling of the cartridge 601 can be brought about using the process described herein. Similarly, if an adhesive 608 is used between the permeable heat sink 610 and the single light-absorbing layer 612 or one or more multilayer light-absorbing layers 612, 617, the permeable heat sink 610 is in thermal communication with the single light-absorbing layer 612 and / or the multilayer light-absorbing layers 612, 617, and these light-absorbing layers are in direct contact and / or thermal communication with the cartridge 601, so that heating and cooling can be brought to the cartridge 601 using the processes described herein.

[0068]

[0068] Figures 7A to 7D show different configurations of one or more radiant heat sources 709. In each of Figures 7A to 7D, there is a transmissive heat sink 710 having at least one first surface located at one end and a second surface located at the distal end, where the at least one first surface is one or more incident surfaces 718 and the second surface is an exit surface 719. At least one of the at least one incident surfaces 718, or each alternatively, has at least one radiant heat source 709 directed toward the incident surface 718, so that light can enter the transmissive heat sink 710 from the incident surface 718, pass through the transmissive heat sink 710, and travel to the exit surface 719. The light then exits from the exit surface 719 heats at least one light-absorbing layer and cartridge which are thermally in communication with the transmissive heat sink 710.

[0069]

[0069] In one embodiment, the incident surface 718 and the outgoing surface 719 of the translucent heat sink 710 (the translucent heat sink 710 functions as a light guide) can be any two-dimensional shape, fused from circular to circular, circular to square, square to circular, or another two-dimensional shape. The cross-sectional areas of the incident surface 718 and the outgoing surface 719 may be the same or different. The radiant heat source 709 may comprise a single light source or a set of multiple light sources, and such a single light source or set of multiple light sources may be used with one or more incident surfaces 718. In another embodiment, the incident surface 718 and the outgoing surface 719 may optionally be smoothly polished or have a rough diffuse surface. The incident surface 718 and the outgoing surface 719 may optionally be coated with an anti-reflective coating.

[0070]

[0070] Figure 7A shows a transmissive heat sink 710 having two separate incident surfaces 718 and a single exit surface 719. The incident surfaces 718 and the exit surface 719 are arranged in an inverted "Y" shape with an angle of less than 180° between the two incident surfaces 718. Each of the two incident surfaces 718 has a radiant heat source 709 directed toward the incident surface 718, which may be a single light source or a set of multiple light sources. In Figure 7B, the transmissive heat sink 710 has two separate incident surfaces 718 and a single exit surface 719. The incident surfaces 718 and the exit surface 719 are arranged in an inverted "T" shape with an angle of approximately 180° between the two incident surfaces 718. In such a configuration, the transmissive heat sink 710 may have a structure configured to allow incident light to be reflected toward the exit surface 719, for example, a notch forming an angled surface on the opposite side of each incident surface 718. Each of the two incident surfaces 718 has a radiant heat source 709 directed toward the incident surface 718, which may be a single light source or a set of multiple light sources. Figures 7C and 7D both illustrate a configuration in which at least one incident surface 718 has a different size and / or shape from the exit surface 719. In Figure 7C, the incident surface 718 is shown to have a wider shape or a larger cross-sectional opening than the exit surface 719. In Figure 7D, the opposite configuration is shown, in which the incident surface 718 has a smaller shape or a larger cross-sectional opening than the exit surface 719.

[0071]

[0071] Figure 8 shows one embodiment of the device 832 in this disclosure. The radiant heat source 809 is located on the light source heat sink 827. Above the radiant heat source 809 is a second heat sink 815 having an internal (i.e., central) opening, and a transparent heat sink 810 is positioned inside the opening. The transparent heat sink 810 may be the same length as the second heat sink 815, or it may be longer or shorter than the second heat sink 815, and the transparent heat sink 810 may be positioned so as to be on the same plane, or it may extend beyond the distal end of the second heat sink 815 from the radiant heat source 809. A polymer mounting plate 820 is mounted and / or positioned on top of the device, which is located on the permeable heatsink 810. The microfluidic cartridge 801 is positioned on the polymer mounting plate 820 and is secured to the mounting plate 821 with stepped screws and springs 822 to compress the mounting plate 821 and maintain thermal communication and / or direct contact between the microfluidic cartridge 801 and the permeable heatsink 810.

[0072]

[0072] Figure 9 illustrates another embodiment, illustrating a device 932 in the present disclosure having two second heatsinks 915 that can be positioned opposite each other to enclose a permeable heatsink (shown in Figure 10). A radiant heat source 909 is located on a light source heatsink 927. The two second heatsinks 915 are provided above the radiant heat source 909 and are arranged to be combinable with each other to form an internal opening or space for positioning the permeable heatsink. A fan 926 can be positioned on one or both of the second heatsinks 915 to be useful for rapid cooling of the device. A cartridge 910 is located above the permeable heatsink and the second heatsinks 915 by a cartridge contact plate 925, the cartridge contact plate 925 may optionally comprise a polymer mounting plate and a fixing plate, or may be otherwise configured to firmly maintain direct contact or thermal communication of the cartridge 910 with the permeable heatsink. The vacuum connection port 923 allows a vacuum to be applied to the cartridge contact plate 925 and is useful for providing uniform contact between the cartridge 910 and other components necessary for thermal communication, which may include a permeable heat sink, adhesive, one or more light-absorbing layers, gaskets, and the like.

[0073]

[0073] Figure 10 shows an exploded view of Figure 9, in which one of the second heatsinks 1015 has been removed from the device 1032, making the transparent heatsink 1010 visible. The transparent heatsink 1010 fits into an internal opening or space formed when the two second heatsinks 1015 are joined together using fasteners 1028. The radiant heat source 1009 is located on the light source heatsink 1027, and these are located below the two second heatsinks 1015. A fan 1026 may be placed on one or both of the second heatsinks 1015 to be useful for rapid cooling of the device. The inner surface of the second heat sink 1015, located between the radiant heat source 1009 and the transmissive heat sink 1010, is provided with a reflective film or polished surface 1014. As a result, when the two second heat sinks 1015 are joined together, the inner surface with the reflective film or polished surface 1014 functions as a light guide, directing light from the radiant heat source 1009 to the incident surface of the transmissive heat sink 1010. The cartridge 1001 is positioned above the transmissive heat sink 1010 and the second heat sink 1015 by a cartridge contact plate 1025. A gasket 1024 is located below the cartridge 1001, and a vacuum can be applied to this gasket 1024 via a vacuum connection port 1023. The vacuum is useful for providing uniform contact between the gasket 1024, the cartridge 1001, and any other components necessary for thermal communication with the transmissive heat sink 1010, which may include an adhesive, one or more light-absorbing layers, and the like. In some embodiments, the gasket 1024 can function as a light-absorbing layer and / or a heat spreader.

[0074]

[0074] Figure 14 shows an exemplary configuration of the gasket and vacuum sealing system for cartridge 1401. The cartridge contact plate 1425 receives cartridge 1401, and the gasket 1424 is positioned beneath cartridge 1401 within the cartridge contact plate 1425. The gasket 1424 can be attached to the cartridge contact plate 1425 using adhesive 1408. The light-absorbing layer and / or heat spreader 1412 can be attached to either the underside of the gasket opposite the microfluidic cartridge or to the permeable heat sink 1410. Vacuum can be applied to the vacuum port 1423 to hold the permeable heat sink 1410, the light-absorbing layer and / or heat spreader 1412, the gasket 1424, and cartridge 1401 in direct contact and / or to enhance thermal communication. In alternative embodiments, the light-absorbing layer and / or heat spreader 1412 may be optional, for example, in situations where the gasket 1024 can function as a light-absorbing layer or heat spreader, or it may be positioned elsewhere so that the light-absorbing layer and / or heat spreader 1412 is in direct contact with the cartridge 1401. While continuous direct contact between the components of Figure 14 may be desirable to enhance thermal communication from the permeable heat sink 1410 to the cartridge 1401, such direct contact is unnecessary if thermal communication is achieved.

[0075]

[0075] Figure 11 is another exploded view of Figure 10, illustrating a portion of the device 1132. One of the second heatsinks 1115 is positioned above the radiant heat source 1109 and the light source heatsink 1127. The inner surface of the second heatsink 1115, located between the radiant heat source 1109 and the lower surface (incident surface) of the transmissive heatsink 1110, is provided with a reflective film or polished surface 1114. As a result, when the second heatsinks 1115 are joined together, the inner surface with the reflective film or polished surface 1114 functions as a light guide, directing light from the radiant heat source 1109 to the incident surface of the transmissive heatsink 1110. The second heatsinks 1128 can be fastened together using fasteners 1128. The vacuum connection port 1123 is located on the cartridge contact plate 1125, allowing direct contact or thermal communication of the gasket and / or cartridge with the transmissive heatsink 1110.

[0076]

[0076] Furthermore, one important aspect of this system is the temperature measurement method and the corresponding feedback control loop resulting from the rapid heating and cooling cycle. An efficient means of measuring and controlling the cartridge temperature in a manner that minimizes heat intrusion is important. For example, large thermocouples may hinder efficient thermal contact between the cartridge and the permeable heat sink. Non-contact methods are preferred for temperature sensing. However, most polymers are opaque within the range of a typical infrared thermometer, and the temperature of the upper part of the microfluidic cartridge may differ significantly from the heating zone below. In the proposed system shown in Figure 12, this problem is overcome by the careful design of the permeable heat sink 1210. When one or more radiant heat sources 1209 (e.g., LEDs) are used, a cavity for arranging an infrared thermometer (IR sensor) 1229 can be provided at the bottom of the heat sink. One or more radiant heat sources 1209, the permeable heat sink 1210, and the IR sensor 1229 are surrounded by a second heat sink 1215. The IR sensor 1229 functions as a thermometer and can be observed through the transparent heatsink 1210 (which is transparent in the IR range) to image the heating area of ​​the cartridge 1201, which is most critical to performance. The IR sensor 1229 is fitted with a filter that allows only the IR range of light to pass through, so as not to be affected by the heating light supplied in the visible to UV range. Multiple IR sensors 1229 can also be used to monitor key areas in a similar manner. Adding LEDs 1209 will increase the total power, which will also increase the heating area. The configuration can be extended to use any number of LEDs 1209, and the shape and form of the transparent heatsink 1210 will be modified accordingly. Control systems that may be useful in providing temperature measurement and feedback in this disclosure include, for example, those described in U.S. Published Patent Application No. 20120052560, the entire disclosure of which is incorporated herein by reference.

[0077]

[0077] The Disclosure further provides a system and method for thermal cycling a microfluidic cartridge, wherein a flexible heat spreader is used to seal the channels of the microfluidic cartridge. As shown in Figure 2, the flexible material is placed on the open channels of the microfluidic device and, upon contact with a heat sink or other solid heating / cooling source that pressurizes the flexible material, bends and presses against the open channels, thereby sealing the channels as long as the pressure source remains in place. Therefore, the resulting thermal cycling device or system does not require a bonding process between the cartridge and the sealing substrate.

[0078]

[0078] Flexible heat spreaders, such as those provided herein, can be used in any contact thermal cycling method, whether described herein or known to those skilled in the art. Thus, the use of flexible heat spreaders eliminates the need for joining covers and seals on microfluidic cartridges, and consequently avoids common joining-related problems such as delamination and bubbling. Furthermore, this disclosure provides simplified processes for both thermal cycling and cartridge manufacturing. The cartridge configuration can be simplified based on the elimination of the need for top sealing, resulting in time and cost savings. Suitable materials for use as flexible heat spreaders in this disclosure include graphene and thin-film plastics, but those skilled in the art will understand that there may be further materials that are suitable alternatives. The use of a heat sink, such as the sapphire block described herein, which deforms the flexible heat spreader and provides pressure to seal the channels, also provides the further advantage of bringing thermal uniformity throughout the heat spreader, and consequently, even materials that would not normally be considered heat spreaders can be used. Furthermore, a flexible heat spreader can be used to seal channels on a microfluidic cartridge used in any thermal cycling system, and means are provided for pressurizing and maintaining the flexible heat spreader in the direction of the microfluidic cartridge.

[0079]

[0079] Example

[0080]

[0080] Example 1: Feasibility Experiment

[0081]

[0081] Experiments were conducted to prove the feasibility of this concept. Figure 8 shows the experimental setup. A sapphire cube was obtained and one side was finely polished to diffuse the surface and make it function as a light cube. The outside of the cube was covered with a reflective film to further promote internal reflection of light. The cube was then covered with thermal adhesive and placed on an aluminum heatsink. The purpose of the aluminum heatsink was to act as a guide to direct the light emitted from the LED (circular) into the cube (rectangular). The heatsink was also useful in thermally stabilizing the temperature of the sapphire cube and maintaining it in an isothermal state during heating and cooling. The final setup is illustrated in Figures 9 to 11.

[0082]

[0082] A 1 mm thick microfluidic cartridge was fabricated, having a 50 μm black aluminum lid that functions as a light-absorbing surface. A small thermocouple was placed at the interface between the cartridge and the sapphire cube. The cartridge was then heated by turning on an LED, and when the LED was turned off, the cartridge was passively cooled via the sapphire heatsink. The LED did not operate at 9.38 W / cm² and output a much lower heat flux in the range of 2–4 W / cm². The results for heating / cooling rate and uniformity are shown in Figures 17 and 18, respectively. The maximum heating and cooling rates were approximately 100°C / s (°C / sec). The average heating and cooling rates between 60–80°C were 50°C / sec and 35°C / sec, respectively. Uniformity was observed to be around ±12°C at the denaturation temperature of 95°C, but at the more important annealing temperature of 55°C, it showed ±0.1°C to 2.5°C, which is close to the preferred target range of ±1°C.

[0083]

[0083] Figure 16 summarizes the above experimental results compared with the simulated values ​​(the simulation results for the two-stage PCR thermal profile are shown in Figure 15). Even at low heat flux, the heating rate is still significantly faster than most methods, and the simulation conditions indicate that the heating rate can be further increased through optimization. Furthermore, the use of thermocouples was not ideal because the physical arrangement of the thermocouples affects the contact thermal resistance between the cube and the microfluidic cartridge. As explained in the previous section, non-contact temperature measurement is preferred and can improve heating and cooling rates and uniformity.

[0084]

[0084] Example 2: Optical simulation and measurement

[0085]

[0085] Using modeling, the thermal and optical behavior of the proposed thermal cycle system was predicted. Two different stages were used: one focused on optimizing optical performance and processing power, and the other focused on determining the optimal thermal performance.

[0086]

[0086] To assess the optical effects, the ray tracing behavior of several proposed configurations was modeled using LightTools Illumination (Synopsys), and the results are summarized in Table 1. The total power (W) supplied by the LEDs with a given current was used as the key input. The outputs used for evaluation were the incident power (W), efficiency (incident power / input power), and uniformity normalized to the maximum irradiance at the exit of the light guide. Based on the achievement of total internal reflection (TIR) ​​using this system and several simulated reflectance values, it was found that increasing the reflective finish in the circular-to-square transition region of the entrance improved the overall efficiency by approximately 5%. The diffuse finish at the exit was approximated by defining the exit of the light guide cube as a Lambert scattering surface, resulting in an improvement in uniformity of approximately 2.5%. However, the results were close to the simulation error or noise level of approximately 3%, suggesting that the actual results may have been better than indicated, but this could not be determined due to inherent uncertainties. Figures 19 and 13 show exemplary output irradiance plots and ray paths, respectively, for a specular film on a transition region (R=0.98) with diffuse surface conditions (R=0.2, T=0.8).

[0087]

[0087] Table 1: Overview of simulation using LightTools [Table 1]

[0088]

[0088] After optical simulations revealed that the sapphire plate was the most efficient and had the lowest uniformity when normalized to the maximum irradiance, a 30x30x100mm sapphire cube with a 300-grit polished diffusion outlet surface was created. The cube was formed to match the configuration from the simulation that showed the highest uniformity and was placed inside an aluminum heatsink of the thermal cycling system. Optical uniformity was measured using a CCD beam profiler (Ophir Optics), and the data was evaluated using a beam gauge (Ophir Optics). The results are shown in Figure 20, and the experimental results correlated well with the simulation results. Next, the data from this sapphire cube was compared with the optical uniformity obtained using a hollow light pipe, as shown in Figure 21 (A: hollow light pipe, B: sapphire cube). The uniformity obtained with the sapphire cube was significantly improved compared to that obtained using a hollow light pipe.

[0089]

[0089] The output irradiance of the thermal cycle system using the sapphire cube was also measured using a photodiode power meter (Newport 2936-R, manufactured by Newport Corporation). The measurement results are shown in Figure 22. It was found that both the output irradiance and uniformity were in agreement with the simulated values ​​within approximately 5%.

[0090]

[0090] Example 3: Thermodynamic simulation

[0091]

[0091] A simulation focusing on the thermal evaluation of the system was performed. This was done by modeling the transient conjugate heat transfer behavior using SolidWorks Flow Simulation (Dassault Systèmes) and then performing the simulation. The thermodynamic material properties used are shown in Table 2.

[0092]

[0092] Table 2: Thermodynamic material properties [Table 2]

[0093]

[0093] The modeling focused on extreme cases in the system, such as when the heat spreader or light-absorbing layer 2307 is in direct contact with the sapphire 2310, or when there is a large permeable insulating layer 2331 between the heat spreader or light-absorbing layer 2307 and the sapphire 2310. Figure 23 shows diagrams of these conditions. Under conditions including an insulating layer, it was expected that heating would be very fast but cooling would be slow due to the added insulation. Under conditions including direct contact between the heat spreader or light-absorbing layer and the sapphire, it was expected that cooling would be very fast but heating would be very slow for the same amount of incident power, as heat would be transferred to the sapphire more easily. Therefore, it is necessary to optimize the conditions to determine the optimal thermal circuit for a given input irradiance.

[0094]

[0094] Figure 24 shows the practical model used in the one-dimensional simulation. The input variables were the contact resistance between the cartridge (composed of the upper lid 2404 and the lower lid 2402) (to determine the effect of the vacuum holding force), the thickness of the heat spreader / light absorption layer 2407, and the thickness of the adhesive / insulating layer 2408. Figure 25 summarizes the simulation results. It was found that both heating and cooling improved due to better thermal contact when the contact resistance was low or the vacuum holding force was high. The speed advantage was very small compared to other factors as the heat spreader 2507 became thinner and the thermal mass decreased. The thickness of the insulating layer / adhesive 2508 had the greatest impact on performance. Figure 26 shows the maximum cartridge temperature results for the same series of simulations. The presence of the heat spreader / light absorption layer 2607 on the device resulted in a stable maximum temperature for the cartridge during heating, and it never rose above 100°C.

[0095]

[0095] Example 4: Thermodynamic test

[0096]

[0096] After determining the optimal resistance circuit structure by thermodynamic simulation, several configurations were formed and the results were confirmed. Figures 9 to 11 illustrate the prototype designs used for further testing. Figure 14 shows the design of the vacuum holding system. The soft 30-40A durometer silicone gasket 1424 was found to function best with a compression set of approximately 25-30%.

[0097]

[0097] A heat spreader thickness of 25 μm was selected, and several adhesive thicknesses were applied. Tests were conducted using prototypes to confirm the simulation predictions. As shown in Figure 27, the heating profiles for cases using a thinner (25 μm) acrylic adhesive layer and a 25 μm thick pyrolysis graphite heat spreader (manufactured by Samsung) showed excessively long heating times, even when tested with a higher LED drive current. These results were consistent with the simulation results and indicated that a thin insulating layer was insufficient. Figures 33 to 36 show additional results from the simulation. Figure 33 shows the results of the light irradiance simulation at a perfect mirror transition R=1, Figure 34 shows the results of the light irradiance simulation on a 3M mirror film at a transition R=0.98, and Figure 35 shows the results of the light irradiance simulation on bare aluminum (machined) R=0.90. Figure 36 shows the simulation results of a heat spreader / light absorber attached to a microfluidic chip under various light irradiation conditions, including (A) the relationship between average fluid temperature and time, and (B) the relationship between maximum cartridge temperature and time.

[0098]

[0098] Figure 28 shows the heating profile results of an experiment using a thermal cycler with a 188 μm thick acrylic adhesive and a 25 μm heat spreader (Samsung). A vacuum of 12 psi was applied via a custom cartridge contact plate, and a thin polycarbonate microfluidic cartridge was held on sapphire. The cartridge was filled with 20 μL of deionized water. A high-speed infrared thermocouple array sensor (Omega #OS-PC16-2M-1V, Omega Engineering) with a custom software interface was used to monitor the cartridge temperature. An infrared camera (FLIR A8580 MWIR, Teledyne FLIR) and its associated software (Research IR, Teledyne FLIR) were used to monitor the temperature distribution on the cartridge surface. Figure 28 shows a plot of experimental results and simulation results (thick line), verifying that there was considerable agreement between the simulation values ​​and the experimental values. Furthermore, the fact that the heating and cooling times were as fast as predicted indicates good system performance.

[0099]

[0099] The microfluidic cartridge described above was mounted on a prototype thermal cycler and subjected to a standard PCR temperature cycle. Figures 29 and 30 show the results obtained from the thermal imaging system, which allowed for an objective comparison of the thermal uniformity of the cartridge under various conditions of the thermal cycle. The letter identifiers in Figures 29 and 30 relate the thermal image plot in Figure 30 to the point in time (Figure 29) when the image was obtained during the thermal cycle. Under no conditions was it observed that the uniformity in the 25x25mm target area of ​​the cartridge increased beyond 1.4°C (standard deviation). This result was maintained even at higher denaturation temperatures, indicating good thermal control and stability. Furthermore, it was observed that a uniformity of 0.4°C was possible at lower annealing temperatures where thermal control is most critical. These results were repeated for five cartridges with similar structures.

[0100] Figure 31 shows a graphical overview of the results for all tested cartridges (n=5). The results were averaged over 3 cycles and then averaged again across the 5 tested cartridges. Figure 32 is an exemplary example of these tested cartridges, in which the sample was subjected to 40 cycles of full PCR. For the full PCR cycle, 20 μL of sample was used, and 40 cycles were performed at 95°C (denaturation, no retention) and 55°C (annealing, no retention). The total operating time, including the preheating cycle, was 4.6 minutes. Figure 32 shows the rapid and uniform temperature transitions across the entire cycle achieved using this thermal cycle prototype.

[0101] [Definition] [000101] In the description, specific details are provided so that the disclosed embodiments may be fully understood. In other examples, well-known methods, procedures, components, and circuits are not described in detail to avoid unnecessarily lengthening this disclosure.

[0102] [000102] As used herein, “genetic material” means any nucleic acid, including DNA and RNA. Thus, genetic material may include genes, parts of genes, groups of genes, fragments of many genes, molecules of DNA or RNA, multiple molecules of DNA or RNA, fragments of DNA or RNA molecules, or fragments of many DNA or RNA molecules. Genetic material can refer to anything from small fragments of DNA or RNA to the entire genome of an organism.

[0103] [000103] In this specification, when an element or part is referred to as "on top of," "in contact with," "connected to," or "joined to" another element or part, it may be directly "on top of," "in contact with," "connected to," or "joined to" that other element or part, or there may be an intervening element or part. In contrast, when an element is referred to as "directly on top of," "directly connected to," or "directly joined to" another element or part, there is no intervening element or part. When the terms "and / or" are used, any combination of one or more of the items listed in relation to it is included.

[0104] [000104] In this specification, spatially relative terms such as “under,” “beneath,” “below,” “lower,” “above,” “upper,” “proximal,” and “distal” may be used to facilitate explanation when describing the relationship between one or more elements or features of an element or feature shown in various drawings. However, these spatially relative terms should be understood as being intended to encompass not only the orientation shown in the drawings but also various orientations of the device in use or operation. For example, if the device in the drawing is inverted, elements described as “below” or “beneath” another element or feature will be oriented “above” that other element or feature. Therefore, relative spatial terms such as “below” can encompass both upper and lower orientations. The apparatus may be oriented in other ways (it may be rotated 90 degrees or to other orientations), and the spatially relative descriptive terms used herein shall be interpreted accordingly. Similarly, the relative spatial terms “proximal” and “distal” may be interchangeable where applicable.

[0105] [000105] As used herein, the term “approximately” means, for example, within 10%, within 5%, or less. In some embodiments, the term “approximately” may also mean within the measurement error.

[0106] [000106] In this specification, terms such as first, second, third, etc. may be used to describe various elements, components, areas, parts, and / or sections. These elements, components, areas, parts, and / or sections should be understood not to be limited by these terms. These terms are used merely to distinguish one element, component, area, part, or section from another area, part, or section. Accordingly, the first element, component, area, part, or section discussed below may also be called the second element, component, area, part, or section without departing from the teachings of this specification.

[0107] [000107] The terms used herein are intended solely to describe specific embodiments and are not intended to limit them. In the context describing this disclosure (in particular in the context of the appended claims), the terms “a, an” and “the” and similar demonstrative pronouns shall be construed to include both singular and plural forms unless otherwise indicated herein or unless it is evident from the context. The terms “comprising,” “having,” “includes,” “including,” and “containing” shall be construed to be non-limiting terms (i.e., “includes, but not limited to”) unless otherwise indicated herein. Specifically, when these terms are used herein, they specify the existence of a feature, integer, step, operation, element, and / or component described herein, but do not preclude the existence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof that are not expressly stated. The descriptions of value ranges in this specification are intended merely as abbreviated notation to refer individually to each distinct value falling within that range, unless otherwise indicated herein, and each distinct value is incorporated herein as if it were individually stated. For example, if the range 10–15 is disclosed, then 11, 12, 13, and 14 are also disclosed. All methods described herein may be performed in any appropriate order unless otherwise indicated herein or unless it is evident from the context. The use of any examples or exemplary words presented herein (e.g., “such as”) is intended merely to clarify this disclosure and does not limit the scope of this disclosure unless otherwise stated in the claims. Nothing in this specification should be construed as indicating that any element not described in the claims is essential for performing this disclosure.

[0108] [000108] The methods and configurations of this disclosure can be incorporated in various forms, and only a small number of them are disclosed herein. Variations of those embodiments will be obvious to those skilled in the art by reading the above description. The inventors assume that those skilled in the art will adopt such variations as needed, and that this disclosure is intended to be implemented in ways other than those specifically described herein. Accordingly, this disclosure includes all modifications and equivalents of the subject matter described in the claims appended herein, as permitted by applicable law. Furthermore, unless otherwise indicated herein, or unless it is evident from the context otherwise, any combination of the above elements in all possible variations is incorporated herein.

Claims

1. A device for thermally cycling a microfluidic cartridge, A microfluidic cartridge in contact with a light-absorbing material, A first heat sink in contact with the microfluidic cartridge, A second heatsink adjacent to the first heatsink, One or more light sources adjacent to the first heat sink, The system includes a temperature sensor that detects temperature changes in the microfluidic cartridge, A device for alternately heating and cooling the microfluidic cartridge.

2. The device according to claim 1, wherein the light-absorbing material converts light into heat.

3. The device according to claim 1, wherein the light-absorbing material is located on or inside the microfluidic cartridge.

4. The device according to claim 1, wherein the light-absorbing material is contained on or inside a portion of the device other than the microfluidic cartridge, and when the cartridge is placed inside the device, the material is in thermal communication with the microfluidic cartridge.

5. The device according to claim 1, wherein the first heat sink is permeable.

6. The device according to claim 5, wherein the first heat sink comprises a thermal conductive material.

7. The device according to claim 5, wherein the first heat sink is transparent to light in the wavelength range from infrared to UV.

8. The device according to claim 5, wherein the first transparent heat sink allows light to be transmitted to the microfluidic cartridge via the heat sink during heating.

9. The device according to claim 5, wherein the first permeable heat sink functions as a passive heat sink for cooling the microfluidic cartridge during cooling.

10. The device according to claim 1, wherein the second heat sink comprises a thermal conductive material.

11. The device according to claim 1, wherein the one or more light sources are one or more LEDs.

12. The device according to claim 1, wherein the first heat sink captures the light from one or more light sources and transmits it to the microfluidic cartridge.

13. The device according to claim 1, further comprising a feedback and control unit that communicates with the temperature sensor and provides temperature control for heating and cooling.

14. The device according to claim 1, further comprising one or more infrared sensors positioned in close proximity to the device, wherein the one or more sensors can observe the microfluidic cartridge.

15. The device according to claim 1, further comprising at least one resistance temperature sensing element in contact with the surface of the first heat sink which is in contact with the microfluidic cartridge.

16. The device according to claim 1, wherein the microfluidic cartridge comprises an open microfluidic channel, and a flexible heat spreader is provided between the open microfluidic channel and the first heat sink.

17. The device according to claim 16, wherein the first heat sink is pressurized to contact and deform the flexible heat spreader, and as a result, the flexible heat spreader comes into contact with the microfluidic cartridge and fluidly seals the microfluidic channel.

18. The device according to claim 5, wherein the light-absorbing material is located on the transparent heat sink.

19. A method for thermally cycling a microfluidic cartridge, (i) A microfluidic cartridge in contact with the heat absorber, A first heat sink in contact with the microfluidic cartridge, A second heatsink adjacent to the first heatsink, One or more light sources adjacent to the first heat sink, To provide a device comprising a temperature sensor for detecting temperature changes in the microfluidic cartridge, (ii) Heating the microfluidic cartridge by turning on one or more of the light sources, (iii) Turning off one or more of the light sources to cool the microfluidic cartridge, and (iv) A method comprising performing steps (ii) and (iii) in succession and repeatedly during the thermal cycle.

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