Microfluidic chip and reaction system

Abstract

The present disclosure provides a microfluidic chip and a reaction system, wherein the microfluidic chip comprises: a substrate substrate; a microcavity-defining layer arranged on the substrate substrate and defining a plurality of microreaction chambers; a cover plate provided on a side of the microcavity-defining layer facing away from the substrate substrate; a heating layer provided between the substrate substrate or the cover plate and the microcavity-defining layer to heat the plurality of microreaction chambers; wherein the side of the substrate substrate and the cover plate furthest from the heating layer has a first surface facing the heating layer and a second surface facing away from the heating layer, the second surface having an area larger than the area of ​​the first surface.

Description

Technical field

[0001] The present disclosure relates to the field of biological testing and specifically to a microfluidic chip and a reaction system. State of the art

[0002] The polymerase chain reaction (PCR) is a molecular biology technique for the amplification of specific DNA fragments, allowing minute amounts of deoxyribonucleic acid (DNA) to be replicated on such a massive scale that their quantity is greatly increased. Unlike conventional PCR technology, digital PCR (dPCR) dilutes the nucleic acid sample to such an extent that the number of target molecules (i.e., DNA templates) in each reaction unit is less than or equal to one. Separate PCR amplification of the target molecules is then performed in each reaction unit, and the fluorescence signals from each unit are statistically analyzed after amplification to achieve an absolute quantitative determination of the single-molecule DNA.Since dPCR offers the advantages of high sensitivity, high specificity, high detection throughput and accurate quantification, it is widely used in clinical diagnosis, gene instability analysis, single-cell gene expression, microbiological environmental testing and prenatal diagnosis. Disclosure of the invention

[0003] The present disclosure provides a microfluidic chip and a reaction system.

[0004] In a first aspect, the present disclosure provides a microfluidic chip, comprising: a substrate base; a microcavity-defining layer that is provided on the substrate and defines a plurality of microreaction chambers; a cover plate that is provided on a side of the microcavity-forming layer facing away from the substrate; a heating layer provided between the substrate base or cover plate and the microcavity-defining layer to heat the majority of microreaction chambers; wherein the surface of the substrate and the cover plate that is away from the heating layer serves as a heat dissipation plate, having a first surface facing the heating layer and a second surface facing away from the heating layer, the second surface having an area larger than the area of ​​an orthographic projection of the heat dissipation plate on the plane in which the heating layer is located.

[0005] In some embodiments, the second surface has a plurality of recesses, wherein the orthographic projection of the plurality of microreaction chambers on the substrate overlaps with the orthographic projection of at least two of the recesses on the substrate.

[0006] In some embodiments, each of the plurality of recesses extends in a first direction and the plurality of recesses are spaced apart from each other in a second direction.

[0007] In some embodiments, the recesses in the second direction have a size between 0.2 mm and 0.4 mm; wherein the recesses have a depth between 0.1 mm and 0.3 mm, and wherein the distance between any two adjacent recesses is between 0.8 mm and 1.2 mm.

[0008] In some embodiments, the plurality of recesses comprises a plurality of first recesses and a plurality of second recesses, wherein an orthographic projection of the plurality of first recesses onto the microcavity-defining layer lies in a central region of the microcavity-defining layer; wherein the plurality of second recesses surrounds the region in which the plurality of first recesses is located, and wherein the plurality of first recesses has a distribution density that is greater than the distribution density of the plurality of second recesses.

[0009] In some embodiments, each of the plurality of first recesses extends in a first direction, wherein the plurality of first recesses are spaced apart in a second direction, the first direction intersecting the second direction; wherein each of the plurality of second recesses extends in a third direction, wherein on each side of an area in which the plurality of first recesses are located several second recesses are provided, wherein the multiple second recesses located on the same side are spaced apart from each other in a fourth direction, wherein the third direction intersects the fourth direction.

[0010] In some embodiments, the size of the first recesses in the second direction is approximately equal to the size of the second recesses in the fourth direction; wherein the depth of the first recesses is approximately equal to the depth of the second recesses; and wherein the distance between adjacent first recesses is less than the distance between adjacent second recesses.

[0011] In some embodiments, the distance between adjacent first recesses is 0.4 to 0.9 times the distance between adjacent second recesses.

[0012] In some embodiments, the size of the first recesses in the second direction and the size of the second recesses in the fourth direction are both between 0.2 mm and 0.4 mm; wherein the depth of the first recesses and the depth of the second recesses are both between 0.1 mm and 0.3 mm, wherein the distance between adjacent first recesses is between 0.4 mm and 0.6 mm, and the distance between adjacent second recesses is between 0.8 mm and 1.2 mm.

[0013] In some embodiments, the heating layer comprises a plurality of heating electrodes connected in series, wherein an orthographic projection of the plurality of microreaction chambers on the substrate overlaps with an orthographic projection of at least two of the heating electrodes on the substrate.

[0014] In some embodiments, each of the plurality of heating electrodes extends in a fifth direction, wherein the plurality of heating electrodes are spaced apart from each other in a sixth direction, the fifth direction intersecting the sixth direction.

[0015] In some embodiments, the size of the multiple heating electrodes in the sixth direction is approximately the same, with the distance between each pair of adjacent heating electrodes being approximately the same.

[0016] In some embodiments, the distance between any two adjacent heating electrodes is between 0.8 mm and 1.2 mm, with the size of each heating electrode in the sixth direction being between 0.4 mm and 0.6 mm.

[0017] In some embodiments, the plurality of heating electrodes comprises a plurality of first heating electrodes and a plurality of second heating electrodes, wherein the second heating electrodes are arranged on both sides of the plurality of first heating electrodes in the sixth direction; wherein the first heating electrodes comprise: a first sub-electrode and a second sub-electrode connected to each other, wherein the first sub-electrode is provided on both sides in the fifth direction with the second sub-electrode, wherein the orthographic projection of the first sub-electrode on the second surface is located in a central region of the second surface; where the resistance of the first subelectrode per unit length is lower than the resistance of the second subelectrode per unit length.

[0018] In some embodiments, a cross-sectional area of ​​the first sub-electrode in a direction perpendicular to the fifth direction is larger than a cross-sectional area of ​​the second sub-electrode in a direction perpendicular to the fifth direction.

[0019] In some embodiments, the first subelectrode has a larger size in the sixth direction than the second subelectrode in the sixth direction.

[0020] In some embodiments, the size of the first subelectrode in the sixth direction is 1.5 to 3 times the size of the second subelectrode in the sixth direction.

[0021] In some embodiments, the size of the first subelectrode in the sixth direction is between 0.8 mm and 1.2 mm, with the size of the second subelectrode in the sixth direction being between 0.4 mm and 0.6 mm.

[0022] In some embodiments, the distance between adjacent first lower electrodes 311 is between 0.4 mm and 0.6 mm; wherein the distance between adjacent second lower electrodes is between 0.8 mm and 1.2 mm, wherein the distance between adjacent second heating electrodes is between 0.8 mm and 1.2 mm.

[0023] In some embodiments, the size of the first sub-electrode in the fifth direction is 1 / 4 to 1 / 2 the size of the first heating electrode in the fifth direction.

[0024] In some embodiments, an orthographic projection of the majority of heating electrodes on the second surface surrounds the central area of ​​the second surface.

[0025] In some embodiments, the heating layer further comprises a first drive electrode and a second drive electrode, wherein the plurality of heating electrodes are connected in series between the first drive electrode and the second drive electrode.

[0026] In some embodiments, the heating electrodes are made of a transparent material.

[0027] In some embodiments, the microfluidic chip further comprises a bonding layer, wherein the bonding layer is located between the cover plate and the substrate and encloses a receiving space together with the cover plate and the microcavity-defining layer, wherein the microreaction chambers are located in the receiving space.

[0028] In some embodiments, the microfluidic chip further comprises a hydrophilic layer, wherein the hydrophilic layer covers at least the side wall and the bottom wall of each of the plurality of microreaction chambers.

[0029] In some embodiments, the microfluidic chip also includes a hydrophobic layer; wherein the heating layer is located on a surface of the substrate that faces the cover plate, and the hydrophobic layer is arranged on a surface of the cover plate that faces the substrate; or wherein the heating layer is located on a surface of the cover plate facing the substrate, and the hydrophobic layer is arranged on a side of the heating layer facing the microcavity-defining layer.

[0030] In some embodiments, the microfluidic chip further comprises a sample inlet and a sample outlet, wherein both the sample inlet and the sample outlet penetrate the cover plate and the hydrophobic layer.

[0031] In some embodiments, both the first and second substrates comprise a glass substrate.

[0032] In some embodiments, the heating layer is located on a surface of the cover plate that faces the microcavity-defining layer, wherein the substrate and the microcavity-defining layer are formed as a single-piece structure.

[0033] In a second aspect, the present disclosure provides a reaction system that includes a microfluidic chip as described above. Brief explanation of the drawings

[0034] The drawings serve to further understand the present disclosure and are part of the description. They are used in conjunction with the following embodiments to illustrate the present disclosure, but do not constitute a limitation of the present disclosure. In the drawings: Fig. Figure 1 shows a schematic structural representation of a microfluidic chip provided in some embodiments of the present disclosure. Fig. Figure 2A shows a schematic structural representation of a microfluidic chip, which is provided in some further embodiments of the present disclosure. Fig. Figure 2B shows a schematic structural representation of a microfluidic chip, which is provided in some other embodiments of the present disclosure. Fig. Figure 3 shows a plan view of a heating layer, which is provided in some embodiments of the present disclosure. Fig. Figure 4 shows a plan view of a heating layer, which is provided in some other embodiments of the present disclosure. Fig. Figure 5 shows a plan view of a heating layer, which is provided in some other embodiments of the present disclosure. Fig. Figure 6 shows a three-dimensional view of a distribution of recesses on the second surface, which is provided in some embodiments of the present disclosure. Fig. Figure 7 shows a plan view of the distribution of recesses on the second surface, which is provided in some embodiments of the present disclosure. Fig. Figure 8 shows a plan view of a distribution of recesses on the second surface, which is provided by other embodiments of the present disclosure. Fig. Figure 9 shows a schematic block diagram of a reaction system provided in some embodiments of the present disclosure. Designs

[0035] To clarify the purpose, technical solutions, and advantages of the embodiments of this disclosure, the technical solutions of the embodiments of this disclosure are described below in detail and in conjunction with the drawings of the embodiments of this disclosure. Obviously, the described embodiments relate only to some and not all of the embodiments of this disclosure. Starting from the embodiments in this disclosure, all other embodiments that a person skilled in the art arrives at without inventive effort also fall within the scope of protection of this disclosure.

[0036] Unless otherwise defined, technical or scientific terms used in this disclosure have the ordinary meaning understood by a person skilled in the art in the field to which this disclosure belongs. The terms "first," "second," and the like, used in this disclosure, do not imply any order, number, or importance, but merely serve to distinguish between different components. Likewise, words such as "a," "an," or "the," and similar words do not signify any numerical limitation, but rather that at least one component is present. Words such as "comprise" or "include" mean that the element or object that is the subject includes the element or object enumerated as the object and its equivalents, but do not exclude other elements or objects.Words like "connected" or "attached" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Words like "above," "below," "left," "right," etc., are used only to indicate relative positions. If the absolute position of what is being described changes, the relative position can also change accordingly.

[0037] During a PCR reaction, the double-stranded structure of the DNA fragment is denatured at high temperature to form a single-stranded structure. The primer and the single-stranded structure are then joined together at low temperature according to the principle of complementary base pairing. The elongation of the base bond occurs at the optimal temperature for DNA polymerase. The process described above is the temperature cycle of denaturation-heating-stretching. DNA fragments can be replicated in large quantities through multiple temperature cycles of denaturation-heating-stretching.

[0038] To achieve the aforementioned temperature cycling processes, it is typically necessary to use a series of external devices to heat a microfluidic chip, making the devices bulky, complex to operate, and expensive. To improve integration, a temperature control layer, such as a heating layer and a heat dissipation layer, can be integrated into the microfluidic chip. In some examples, the microfluidic chip comprises a microcavity-defining layer with multiple microreaction chambers, a heating layer, and a heat dissipation layer, with the heat dissipation layer located on the side of the heating layer furthest from the microcavity-defining layer. In such a case, when a sample cools in the microreaction chambers, heat must be dissipated from the heating layer before the sample cools, resulting in reduced testing efficiency.

[0039] Fig. Figure 1 shows a schematic structural representation of a microfluidic chip provided in some embodiments of the present disclosure, Fig. Figure 2A shows a schematic structural representation of a microfluidic chip, which is provided in some further embodiments of the present disclosure. Fig. Figure 2B shows a schematic structural representation of a microfluidic chip provided in some other embodiments of the present disclosure. As in Fig. As shown in Figures 1 to 2B, the microfluidic chip comprises: a substrate base 10, a microcavity-defining layer 40, a cover plate 20 and a heating layer 30.

[0040] The microcavity-defining layer 40 is located on the substrate 10 and defines a plurality of microreaction chambers 41. Alternatively, the microfluidic chip can be used to perform a polymerase chain reaction (e.g., a digital polymerase chain reaction) and for a subsequent testing procedure. The microreaction chambers 41 can be used to hold the reaction system solution.

[0041] The cover plate 20 is arranged opposite the substrate base 10 and is located on a side of the microcavity-defining layer 40 facing away from the substrate base 10.

[0042] The heating layer 30 is positioned between the substrate base 10 or the cover plate 20 and the microcavity-defining layer 40 to heat the multiple microreaction chambers 41, thereby heating a reaction system solution within the microreaction chambers 41 so that it can undergo an amplification reaction. The heating layer 30 can be made of an electrically conductive material to dissipate heat when an electric current is applied.

[0043] The surface of the substrate 10 and the cover plate 20 that is furthest from the heating layer 30 serves as a heat dissipation plate with a first surface S1 and a second surface S2, wherein the first surface S1 faces the heating layer 30 and the second surface S2 faces away from the heating layer 30, the second surface S2 serving as a heat dissipation area whose area is larger than the area of ​​an orthographic projection of the heat dissipation plate on the plane in which the heating layer 30 is located, so that when the cooling fluid is blown onto the second surface S2, the heat dissipation effect on the solution inside the microreaction chambers 41 is improved.

[0044] For example, as in Fig. As shown in Figure 1, the heating layer 30 is located between the substrate base 10 and the microcavity-defining layer 40, and the lower surface of the cover plate 20 in Fig. 1 is the first surface S1, the upper surface of the cover plate 20 is the second surface S2, and the area of ​​the upper surface of the cover plate 20 is larger than the area of ​​the orthographic projection of the cover plate 20 on the plane on which the heating layer 30 is located. Fig. 1 is the plane in which the heating layer 30 is located, the upper surface of the substrate 10. If the lower surface of the cover plate 20 is a plane, the area of ​​the orthographic projection of the cover plate 20 onto the plane in which the heating layer 30 is located is the area of ​​the lower surface of the cover plate 20. For example, as in Fig. As shown in Figure 2A, the heating layer 30 is located between the substrate base 10 and the microcavity-defining layer 40, and the substrate base 10 is in Fig. 2A serves as a heat dissipation plate, and its upper surface is the first surface S1, the lower surface of the substrate 10 is the second surface S2, and the area of ​​the lower surface of the substrate 10 is larger than the area of ​​the orthographic projection of the substrate 10 on the plane in which the heating layer 30 is located. Fig. 2A is the plane in which the heating layer 30 is located, the lower surface of the cover plate 20. If the upper surface of the substrate 10 is a plane, the area of ​​the orthographic projection of the substrate 10 onto the plane in which the heating layer 30 is located is the area of ​​the upper surface of the substrate 10. In other words, the second surface S2 (the heat dissipation surface) has a larger area to improve the heat dissipation effect. Furthermore, the second surface S2 and the heating layer 30 are located on opposite sides of the microcavity-defining layer 40. In this case, when the second surface S2 dissipates heat, it does not have to dissipate heat from the heating layer 30. The heating layer 30 is also not affected by the temperature of the heat dissipation surface when heated, thus improving the heating efficiency.

[0045] The microfluidic chip in the embodiments of the present disclosure is described below, with the heating layer 30 located between the substrate 10 and the microcavity-defining layer 40 as an example.

[0046] Both the substrate 10 and the cover plate 20 can be made of glass. Of course, both can also be made of other suitable materials. There are no restrictions in this regard in the embodiments described in this disclosure. The shapes of the substrate 10 and the cover plate 20 can be rectangular or other suitable shapes. The embodiments described in this disclosure do not restrict this. Furthermore, the cover plate 20 can have the same shape and size as the substrate 10.

[0047] As in Fig. As shown in Figure 1, the microcavity-defining layer 40 is arranged on the substrate 10 and defines a plurality of microreaction chambers 41. Adjacent microreaction chambers 41 are at least partially separated from one another (e.g., by partitions). Each microreaction chamber 41 comprises a side wall 41a and a bottom wall 41b. The microreaction chambers 41 can be configured as microreaction recesses, depressions, or the like, as long as they have a space that can accommodate the reaction system solution, and the embodiments of this disclosure do not impose any restrictions in this respect. For example, the depth of the microreaction recesses or depressions can be about 10 µm or other appropriate values.

[0048] Alternatively, the shapes of the several microreaction chambers 41 can be the same, and the three-dimensional shape of each of the microreaction chambers 41 is, for example, an approximately frustoconical body, i.e., approximately trapezoidal in section in a direction perpendicular to the substrate 10 and approximately circular in section parallel to the substrate 10. Of course, it is also possible that at least some of the microreaction chambers 41 have a different shape.

[0049] It should be noted that in the embodiments described in this disclosure, the shapes of the microreaction chambers 41 are not limited and can be designed according to actual needs. For example, the shape of each microreaction chamber 41 can also be cylindrical, cuboid, polygonal prism, spherical, ellipsoidal, or any other suitable shape. For example, the microreaction chambers 41 can have a cross-sectional shape of an ellipse, triangle, polygon, irregular shape, etc., in a plane parallel to the substrate 10, and a cross-sectional shape of a square, circle, parallelogram, rectangle, etc., in a direction perpendicular to the substrate 10.

[0050] Alternatively, the multiple microreaction chambers 41 are uniformly distributed in the microcavity-defining layer 40. For example, the multiple microreaction chambers 41 are arranged in an array, resulting in a more regular and clearer fluorescence image obtained during optical inspection of the microfluidic chip in a later stage, thus enabling fast and accurate test results. Of course, the embodiments described in this disclosure are not limited to this, and the multiple microreaction chambers 41 can also be unevenly distributed or arranged otherwise; the embodiments described in this disclosure do not constitute a limitation in this respect.

[0051] Furthermore, in the embodiments described in this disclosure, the size and number of the microreaction chambers 41 can be based on actual requirements, and the size and number of the microreaction chambers 41 depend on the size of the microcavity-defining layer 40. In cases where the size of the microreaction chambers 41 is fixed, the size of the microcavity-defining layer 40, the substrate 10, and the cover plate 20 will be larger as the number of microreaction chambers 41 increases. For example, in the current manufacturing process, the number of microreaction chambers 41 can reach hundreds of thousands or even millions on an area of ​​a few tens of square centimeters, with the microfluidic chip exhibiting a large sensing flow.

[0052] Alternatively, the material of the microcavity-defining layer 40 can be photoresist, which can be formed by rotational coating on the substrate 10. The photoresist is structured such that a microcavity-defining layer 40 with a plurality of microreaction chambers 41 can be obtained.

[0053] In some embodiments, such as in Fig. As shown in Figure 1, the heating layer 30 is provided on the substrate base 10 and is located between the substrate base 10 and the microcavity-defining layer 40. The heating layer 30 is configured to emit heat when energized, thereby heating the reaction system solution within the microreaction chambers 41.

[0054] Fig. Figure 3 shows a plan view of a heating layer, which is provided in some embodiments of the present disclosure. As in Fig. As shown in Figure 3, the heating layer 30 can comprise a first drive electrode 30c and a second drive electrode 30d, and further comprise a plurality of heating electrodes 30a connected in series between the first drive electrode 30c and the second drive electrode 30d. The orthographic projection of the multiple microreaction chambers 41 onto the substrate 10 overlaps with the orthographic projection of the at least two heating electrodes 30a onto the substrate 10 to facilitate effective heating of the multiple microreaction chambers 41 by the heating layer 30.For example, the orthographic projection of the area containing the multiple microreaction chambers 41 on the substrate 10 is located within the orthographic projection of the area containing the multiple heating electrodes 30a on the substrate 10, in order to facilitate sufficient heating of the multiple microreaction chambers 41 by the heating layer 30. For example, the orthographic projection of the area containing the multiple heating electrodes 30a on the substrate 10 can be the same as, or slightly larger than, the orthographic projection of the area containing the multiple microreaction chambers 41 on the substrate 10.

[0055] It is noted that the area containing the multiple microreaction chambers 41 is a continuous area that can be considered the smallest area capable of enclosing all the microreaction chambers 41. Likewise, the area containing the multiple heating electrodes 30a is also a continuous area that can be considered the smallest area capable of enclosing all the heating electrodes 30a. Fig. 3 is, for example, the area where the multiple heating electrodes 30a are located, the area surrounded by the dashed box M.

[0056] When the microreaction chambers 41 need to be heated, different voltage signals are provided to the first control electrode 30c and the second control electrode 30d by a drive device, thereby forming a current path between the first control electrode 30c and the second control electrode 30d, so that a current flows through each heating electrode 30a, thereby releasing heat.

[0057] Compared to a parallel circuit, in a series circuit of several heating electrodes 30a, the current at each heating electrode 30a is the same, and the heating efficiency of the heating electrodes 30a depends on the resistance. Therefore, if it is necessary to adjust the heating efficiency of the heating electrodes 30a for different areas of the microcavity-defining layer 40, only the resistance needs to be adjusted, and the adjustment procedure is simpler. Furthermore, for the same machining error, the heating power error of a series circuit is much smaller than that of a parallel circuit.In Table 1, in the case of several heating electrodes 30a connected in series, if the target resistance of each heating electrode 30a is 20 Ω and the resistance produced by the actual machining is 21 Ω, the power actually produced by the several heating electrodes 30a connected in series is 7.20 W, and the difference to the target power (6.85 W) is relatively small; in the case of several heating electrodes 30a connected in parallel, if the target resistance of each heating electrode 30a is 20 Ω and the resistance produced by the actual machining is 21 Ω, the power actually produced by the several heating electrodes 30a connected in series is 27.43 W, and the difference to the target power (28.8 W) is relatively large. Table 1 Spannung: 24V Leistung der Parallelschaltung (W) Leistung der Reihenschaltung (W) Widerstand 1 20 Ω 28,8 6,85 Widerstand 2 21 Ω 27,43 7,20 Leistungsdifferenz 1,37 0,35

[0058] In some embodiments, such as in Fig. As shown in Figure 3, each heating electrode 30a is elongated, its orthographic projection on the first surface S1 extends in a fifth direction, and the multiple heating electrodes 30a are spaced apart from each other in a sixth direction, with the fifth direction intersecting the sixth direction. For example, the fifth direction is perpendicular to the sixth direction.

[0059] It should be noted that the elongated shape of the heating electrodes 30a means that the maximum size of a heating electrode 30a in the fifth direction is larger than the maximum size of this heating electrode 30a in the sixth direction. For example, the heating electrodes 30a are rectangular; or the heating electrodes 30a are wavy, i.e., the left and right side edges of the heating electrodes 30a are wavy; or the heating electrodes 30a are trapezoidal, i.e., the left and right side edges of the heating electrodes 30a are not perpendicular to the bottom side edges; and of course, the heating electrodes 30a can have other shapes.

[0060] As in Fig. As shown in Figure 3, the majority of the heating electrodes 30a are connected to form an electrode chain, with at least two of the heating electrodes 30a being connected to each other by a connecting section 30b. For example, if the multiple heating electrodes 30a extend in the same direction and are arranged one after the other in a direction intersecting the direction of extension, each pair of adjacent heating electrodes 30a is connected to each other by a connecting section 30b. The connecting section 30b can be made of the same material as the heating electrodes 30a, which simplifies the manufacturing process.

[0061] In some embodiments, such as in Fig. As shown in Figure 3, the different heating electrodes 30a can have the same resistance. For example, the orthographic projection of each heating electrode 30a on the first surface S1 is rectangular, different heating electrodes 30a have approximately the same dimensions in the sixth direction, and the distance between any two adjacent heating electrodes 30a is approximately the same.

[0062] It should be noted that the distance between two adjacent heating electrodes 30a means the smallest distance between the two adjacent heating electrodes 30a, more precisely, the distance between the edges of the two adjacent heating electrodes that are closest to each other. In embodiments of the present disclosure, the expression that several values ​​are "approximately equal" means that the difference between any two values ​​is less than a certain range, e.g., less than 5% or 10%. Of course, "approximately equal" can also mean that these values ​​are exactly equal.

[0063] In one example, the distance between any two adjacent heating electrodes 30a, arranged in the same direction, is between 0.8 mm and 1.2 mm. For example, the distance between any two adjacent heating electrodes 30a is 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, or 1.2 mm. Each heating electrode 30a has a size between 0.4 mm and 0.6 mm in the sixth direction. For example, each heating electrode 30a has a size of 0.4 mm, 0.5 mm, or 0.6 mm in the sixth direction.

[0064] Fig. Figure 4 shows a plan view of a heating layer, which is provided in some other embodiments of the present disclosure. The in Fig. 4 heating layer 30 shown, similar to the one in Fig. The heating layer 30 shown in Figure 3 comprises a first drive electrode 30c, a second drive electrode 30d, and a plurality of heating electrodes 30a connected in series between them, each of which has an elongated shape whose orthographic projection on the first surface S1 extends in the fifth direction, and the plurality of heating electrodes 30a are spaced apart from each other in the sixth direction, and any two adjacent heating electrodes 30a are connected via a connecting section 30b. The difference between the one shown in Figure 3 is Fig. 4 and Fig. The heating layer 30 shown in section 3 consists in the fact that in Fig. 4 the plurality of heating electrodes 30a comprises: a plurality of first heating electrodes 31 and a plurality of second heating electrodes 32, wherein several first heating electrodes 31 are provided on both sides in the sixth direction with a second heating electrode 32. For example, several first heating electrodes 31 are provided on both sides in the sixth direction with several second heating electrodes 32. It should be noted that in Fig. 4 only three second heating electrodes 32 are schematically shown, which are provided on both sides of the several first heating electrodes 31, but the embodiments of the present disclosure do not provide for any limitation in this respect, and the number of second heating electrodes 32 can be determined according to the actual needs.

[0065] If the heat dissipated at the individual positions of the heating layer 30 is identical, a heat concentration occurs in the central region of the microcavity-defining layer 40, leading to uneven heating of the microcavity-defining layer 40. To improve the uniformity of the heating of the microcavity-defining layer 40, the heating effect of the heating layer 30 can be reduced to the central region of the microcavity-defining layer 40, which can be achieved by adjusting the resistance of the first heating electrodes 31.

[0066] As in Fig. As shown in Figure 4, a first heating electrode 31 comprises a first subelectrode 311 and a second subelectrode 312 connected to each other, the first subelectrode 311 being provided with the second subelectrode 312 on both sides in the fifth direction, wherein an orthographic projection of the first subelectrode 311 onto the microcavity-defining layer 40 is located in the central region of the microcavity-defining layer 40. That is, the region Q in which the first subelectrodes 311 of the multiple first heating electrodes 31 are located is opposite the central region of the microcavity-defining layer 40. The resistance of the first subelectrode 311 per unit length is lower than the resistance of the second subelectrode 312 per unit length.It should be noted that the "middle area" is a predetermined-sized region located in the central part of the microcavity-defining layer 40, the size of which can be determined according to the actual situation. For example, if the heat dissipated at each position of the heating layer 30 is identical, the area in the microcavity-defining layer 40 that heats up faster is considered the middle area. It should also be noted that the "unit of length" refers to a unit of length in the fifth direction, which can be 1 µm or 1 mm. That is, in the fifth direction, the resistance of the first subelectrode 311 is lower within a length of 1 µm (or 1 mm) than the resistance of the second subelectrode 312 within a length of 1 µm (or 1 mm). This setting improves the uniformity of the heating of the microcavity-defining layer 40.

[0067] In some embodiments, the ratio of the length of the first sub-electrode 311 (i.e., the size of the first sub-electrode 311 in the fifth direction) to the length of the first heating electrode 31 (i.e., the size of the first heating electrode 31 in the fifth direction) can be determined according to the size of the central region. In some examples, the length of the first sub-electrode 311 is 1 / 4 to 1 / 2 the length of the first heating electrode 31. For example, the length of the first sub-electrode 311 is 1 / 4, 1 / 3, or 1 / 2 the length of the first heating electrode 31. In some embodiments, the length of the first heating electrode 31 and the length of the second heating electrode 32 can be approximately equal.

[0068] In some embodiments, the first subelectrode 311 and the second subelectrode 312 are made of the same material to simplify the manufacturing process. In this case, it is possible to adjust the cross-sectional area of ​​the first subelectrode 311 in the direction perpendicular to the fifth direction to be larger than the cross-sectional area of ​​the second subelectrode 312 in the direction perpendicular to the fifth direction, so that the resistance of the first subelectrode 311 per unit length is lower than the resistance of the second subelectrode 312 per unit length.

[0069] In some embodiments, the thicknesses of the first subelectrode 311 and the second subelectrode 312 are set to be equal, and the size of the first subelectrode 311 in the sixth direction is larger than the size of the second subelectrode 312 in the sixth direction, so that the first subelectrode 311 and the second subelectrode 312 meet the above resistance requirements and the manufacturing process is facilitated.

[0070] For example, the first subelectrode 311, the second subelectrode 312, and the second heating electrode 32 all have a rectangular orthographic projection on the first surface S1. The size of the first subelectrode 311 in the sixth direction is 1.5 to 3 times the size of the second subelectrode 312 in the sixth direction. For example, the size of the first subelectrode 311 in the sixth direction is 1.5 times, 1.8 times, 2 times, 2.5 times, or 3 times the size of the second subelectrode 312 in the sixth direction.

[0071] For example, the size of the first subelectrode 311 in the sixth direction is between 0.8 mm and 1.2 mm. For example, the size of the first subelectrode 311 in the sixth direction is 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, or 1.2 mm. For example, the size of the second subelectrode 312 in the sixth direction is between 0.4 mm and 0.6 mm. For example, the size of the first subelectrode 312 in the sixth direction is 0.4 mm, 0.45 mm, 0.5 mm, 0.55 mm, or 0.6 mm.

[0072] For example, the distance between adjacent first sub-electrodes 311 is between 0.4 mm and 0.6 mm. For example, the distance between adjacent first sub-electrodes 311 is 0.4 mm, 0.45 mm, 0.5 mm, 0.55 mm, or 0.6 mm. For example, the distance between adjacent second sub-electrodes 312 is between 0.8 mm and 1.2 mm. For example, the distance between adjacent second sub-electrodes 312 is 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, or 1.2 mm. For example, the distance between adjacent second heating electrodes 32 is between 0.8 mm and 1.2 mm. For example, the distance between adjacent second heating electrodes 32 is 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, or 1.2 mm.

[0073] Fig. Figure 5 shows a plan view of a heating layer, which is provided in some other embodiments of the present disclosure. The in Fig. Heating layer 30 shown in section 5, similar to the one in Fig. The heating layer 30 shown in Figure 3 comprises a first drive electrode 30c, a second drive electrode 30d, and a plurality of heating electrodes 30a connected in series between them, each of which may have an elongated shape. The plurality of heating electrodes 30a are connected via a connecting section 30b to form an electrode chain. The difference between the one shown in Figure 30c is that the heating layer 30c is connected in series with the heating layer 30d. The heating layer 30c is connected in series with the heating layer 30d. The heating layer 30a is connected via a connecting section 30b to form an electrode chain. The difference between the heating layer 30c shown in Figure 30c is that the heating layer 30a is connected in series with the heating layer 30d. The heating layer 30c is connected in series with the heating layer 30d. The heating layer 30a shown in Figure 30c is connected in series with the heating layer 30d. The heating layer 30a Fig. 5 and Fig. The heating layer 30 shown in section 3 consists in the fact that in Fig. 5. An orthographic projection of the majority of heating electrodes 30a onto the microcavity-defining layer 40 surrounds the central region of the microcavity-defining layer 40. This setting allows the heating power in the central part of the heating layer 30 to also be reduced, thus increasing the uniformity of the heating of the microcavity-defining layer 40.

[0074] For example, as in Fig. As shown in Figure 5, the plurality of heating electrodes 30a comprises: a plurality of third heating electrodes 33, a plurality of fourth heating electrodes 34, a plurality of fifth heating electrodes 35, and a plurality of sixth heating electrodes 36. The plurality of third heating electrodes 33 and the plurality of fourth heating electrodes 34 are all spaced apart from each other in the X direction. The plurality of fifth heating electrodes 30a and the plurality of sixth heating electrodes 30a are all spaced apart from each other in the Y direction. Each fifth heating electrode 30a and each sixth heating electrode 30a extends in the X direction, and each third heating electrode 30a and each fourth heating electrode 30a extends in the Y direction.The orthographic projections of the third heating electrode 30a, the fourth heating electrode 30a, the fifth heating electrode 30a and the sixth heating electrode 30a on the microcavity-defining layer 40 are each located on different sides of the central area.

[0075] In the Fig. In the embodiments shown in Figures 3 to 5, the orthographic projection of each heating electrode 30a on the first surface S1 can be rectangular, but the embodiments of the present disclosure are not limited to this. For example, the orthographic projection of part of the heating electrodes 30a on the first surface S1 is arc-shaped.

[0076] In the embodiments described in this disclosure, the heating electrode 30a can be manufactured using an electrically conductive material with a higher resistivity, so that this heating electrode 30a generates more heat when a smaller electrical signal is applied, thus improving the energy conversion rate. The heating electrode 30a can, for example, be made of a transparent electrically conductive material such as indium tin oxide (ITO), tin oxide, and the like, since these transparent electrically conductive materials not only have a higher resistivity than metallic materials but are also transparent, which allows for heating and facilitates subsequent optical inspection. Of course, the embodiments described in this disclosure are not limited to these. The heating electrode 30a can also be manufactured using other suitable materials, such as metal, etc., can be manufactured. The embodiments described in this disclosure do not impose any limitations in this regard.

[0077] Furthermore, the first drive electrode 30c and the second drive electrode 30d can have a square shape with larger dimensions, allowing for convenient connection to probes or electrodes in the drive device. This provides a large contact area and ensures stable reception of electrical signals. In this way, the microfluidic chip can be plug-and-play, easy to use, and simple to handle. The first drive electrode 30c and the second drive electrode 30d can be made of a metallic material to improve their electrical conductivity, which is advantageous for the drive device when providing a drive signal to the heating layer 30.

[0078] Furthermore, the positions of the first drive electrode 30c and the second drive electrode 30d relative to the plurality of heating electrodes 30a can be adjusted according to actual needs, and the present disclosure does not impose any restrictions in this regard. For example, as described in Fig. As shown in Figures 3 to 5, the first drive electrode 30c and the second drive electrode 30d are each arranged on opposite sides of the plurality of heating electrodes 30a. Of course, the second drive electrode 30d and the second drive electrode 30d can also be arranged on the same side of the plurality of heating electrodes 30a.

[0079] Further with reference to Fig. 1. When the heating layer 30 is arranged on the substrate 10, the microfluidic chip can further comprise an insulating layer 70, wherein the insulating layer 70 is arranged between the heating layer 30 and the microcavity-defining layer 40. The insulating layer 70 serves to protect the heating electrodes 30a, to prevent erosion of the heating electrodes 30a by water vapor, to slow down the aging of the heating electrodes, and can serve to flatten them. The insulating layer 70 can, for example, consist of an inorganic or an organic insulating material. The material of the insulating layer 70 can, for example, comprise silicon oxide or silicon nitride.

[0080] It should be noted that the insulating layer 70 is provided with through holes at positions corresponding to the first drive electrode 30c and the second drive electrode 30d, thereby exposing at least part of the first drive electrode 30c and at least part of the second drive electrode 30d in order to ensure the electrical connection of the first drive electrode 30c and the second drive electrode 30d with the drive device.

[0081] Further referring to Fig. 1 The microfluidic chip further comprises a hydrophilic layer 51, wherein the hydrophilic layer 51 covers at least the side wall 41a and the bottom wall 41b of each of the microreaction chambers 41, and wherein the hydrophilic layer 51 exhibits hydrophilic and oleophobic properties. The hydrophilic layer 51 can, for example, also cover the area between the microreaction chambers 41. Since the hydrophilic layer 51 is provided on the surfaces of the microreaction chambers 41 (i.e., side wall 41a and bottom wall 41b) and thereby increases the hydrophilicity of the microreaction chambers 41, the reaction system solution can automatically and gradually penetrate each of the microreaction chambers 41 based on the capillary phenomenon in the absence of an external driving force exerted on the reaction system solution, thus realizing automatic sample introduction and sample filling.

[0082] The material of the hydrophilic layer 51 is, for example, a silicon oxide or silicon oxynitride that has been subjected to a surface alkali treatment, wherein the surface alkali treatment is understood to mean the use of an alkali solution with which the part of the silicon oxide or silicon oxynitride covering the side wall 41a and the bottom wall 41b of a microreaction chamber 41 is impregnated for surface modification in order to form a hydrophilic layer 51.

[0083] Further regarding Fig. The microfluidic chip further comprises a bonding layer 60, a sample inlet 21, and a sample outlet 22. The bonding layer 60 is located between the substrate base 10 and the cover plate 20, for example, at an edge of the microfluidic chip. The bonding layer 60 consists of a thermosetting adhesive or a photosensitive adhesive with a spacer. The bonding layer 60, together with the cover plate 20 and the microcavity-defining layer 40, encloses a receiving space, and the microreaction chambers 41 are arranged within the receiving space. The receiving space is a cavity in the microfluidic chip. During use of the microfluidic chip, the receiving space is filled with a continuous phase (e.g., mineral oil), and the reaction system solution enters each microreaction chamber 41 as a discrete phase.

[0084] The sample inlet 21 and the sample outlet 22 both penetrate the cover plate 20 and are connected to the receiving chamber. The sample inlet 21 and the sample outlet 22 can be located on opposite sides of the majority of microreaction chambers 41. The reaction system solution can be injected into the sample inlet 21 via a microsyringe pump or a pipette gun and then pipetted into the respective microreaction chamber 41. Reaction system solutions that do not reach the microreaction chambers 41 are drained from the microfluidic chip via the sample outlet 22.

[0085] In addition, in some examples the microcavity-defining layer 40 can also define a sample inlet and a sample outlet channel (not shown in the figures), both of which are connected to the recording space.

[0086] For example, the sample inlet channel is also connected to sample inlet channel 21, so that liquid can flow from sample inlet 21 into the receiving chamber via the sample inlet channel. The sample outlet channel is also connected to sample outlet 22, so that liquid can flow out of the chip from the receiving chamber via the sample outlet channel and sample outlet 22. For example, the sample inlet and sample outlet channels can have any shape, such as straight, folded, or curved, which may be based on actual needs, and the embodiments of this disclosure are not limited thereto. It should be noted that in other examples, the sample inlet and sample outlet channels can also be omitted, with sample inlet 21 and sample outlet 22 being provided directly at the boundaries of the receiving chamber.

[0087] With continued reference to Fig. 1. The microfluidic chip can also include a hydrophobic layer 52 provided on a surface of the cover plate 20 facing the substrate 10. The hydrophobic layer 52 has hydrophobic and lipophilic properties, and by providing a hydrophobic layer 52, it is possible to facilitate the entry of the reaction system solution into each microreaction chamber 41. The material of the hydrophobic layer 52 is, for example, a silicon nitride modified by plasma treatment. Of course, the embodiments of the present disclosure are not limited thereto, and the hydrophobic layer 52 can also consist of resin or another suitable inorganic or organic material, as long as the hydrophobic layer 52 is hydrophobic on the side facing the microcavity-defining layer 40. The hydrophobic layer 52 can, for example, be produced directly from a hydrophobic material.As another example, the hydrophobic layer 52 can be made from a material that is not hydrophobic, in which case the surface of the hydrophobic layer 52 on the side facing the microcavity-defining layer 40 must be made hydrophobic in order for the hydrophobic layer 52 to become hydrophobic.

[0088] In the embodiments described in this disclosure, the hydrophilic layer 51 and the hydrophobic layer 52 can interact to adjust the surface contact angle of the liquid droplets of the reaction system solution such that the microfluidic chip achieves a pipetting sample entry and an oil seal. For example, in this microfluidic chip, the hydrophobicity of the outer surface of the microreaction chambers 41 is enhanced by the hydrophobic layer 52, while the hydrophilicity of the inner surface of the microreaction chambers 41 is good, allowing the reaction system solution to penetrate the interior of the microreaction chambers 41 from the outside. Consequently, the interaction of the hydrophilic layer 51 and the hydrophobic layer 52 makes it easier for the reaction system solution to enter each of the microreaction chambers 41.

[0089] It should be noted that both the sample inlet 21 and the sample outlet 22 penetrate the hydrophobic layer 52.

[0090] In the Fig. In the microfluidic chip shown in Figure 1, the cover plate 20 serves as a heat dissipation plate with a first surface S1 facing the heating layer 30 and a second surface S2 facing away from the heating layer 30, and the second surface S2 serves as a heat dissipation area that is larger than the area of ​​an orthographic projection of the cover plate 20 on the plane in which the heating layer 30 is located, thereby improving the heat dissipation effect.

[0091] In some embodiments, the second surface S2 is provided with a plurality of recesses Va, so that the second surface S2 has a larger area, which in turn improves the heat dissipation effect. Furthermore, if the heat-dissipating fluid comes into contact with a grooved surface, heat exchange is facilitated compared to a flat surface, which further improves the heat dissipation effect. It is understood that if the second surface S2 has recesses Va, the area of ​​the second surface S2 is the sum of the area of ​​the inner wall of each recess Va and the portion that does not form a recess Va.

[0092] The orthographic projection of the multiple microreaction chambers 41 on the substrate 10 overlaps with the orthographic projection of the at least two heating electrodes 30a on the substrate 10 to facilitate effective heat dissipation from the multiple microreaction chambers 41 through the recesses Va. For example, the orthographic projection of the area containing the multiple microreaction chambers 41 on the substrate 10 lies within the orthographic projection of the area containing the multiple recesses Va on the substrate 10 to facilitate sufficient heat dissipation from the multiple microreaction chambers 41 through the recesses Va.For example, the orthographic projection of the area containing the multiple recesses Va on the substrate 10 may be the same as or slightly larger than the orthographic projection of the area containing the multiple microreaction chambers 41 on the substrate 10.

[0093] It is noted that the area containing the multiple recesses Va is a continuous area that can be considered the smallest area capable of enclosing all recesses Va. Likewise, the area containing the multiple recesses Va is also a continuous area that can be considered the smallest area capable of enclosing all recesses Va.

[0094] Fig. Figure 6 shows a three-dimensional view of a distribution of recesses on the second surface, which is provided in some embodiments of the present disclosure, and Fig. Figure 7 shows a plan view of the distribution of recesses on the second surface, which is provided in some embodiments of the present disclosure. As in Fig. 6 and Fig. As shown in Figure 7, each of the multiple recesses Va extends in a first direction, and the multiple recesses Va are spaced apart from each other in a second direction, with the first direction intersecting the second direction, e.g. perpendicular to the second direction.

[0095] The fact that the recesses Va extend in a first direction means that the orthographic projection of the recesses Va on a first plane tends to extend substantially in the first direction. The present disclosure does not specifically restrict the shape of the recesses Va. For example, the cross-section of the recesses Va perpendicular to the fifth direction is rectangular, or approximately trapezoidal, or arcuate; and the orthographic projection of the recesses Va on the first surface S1 is rectangular or approximately rectangular.

[0096] For example, in Fig. 6 and Fig. 7. The majority of the recesses Va have the same length, the same width, and the same depth. Fig. 6 and Fig. 7. The length of the recesses Va refers to a dimension of the recesses Va in a first direction, and the width of the recesses Va refers to a dimension of the recesses Va in a second direction. For example, the length of each recess Va can be between 0.2 mm and 0.4 mm. For example, the width of each recess Va is 0.2 mm, 0.3 mm, or 0.4 mm. For example, the depth of each recess Va is between 0.1 mm and 0.3 mm. For example, each recess Va has a depth of 0.1 mm, 0.2 mm, or 0.3 mm. Each of the recesses Va can penetrate a second plane in the first direction; that is, the length of the recesses Va can be the same with respect to the second plane in the first direction.

[0097] As in Fig. 6 and Fig. As shown in Figure 7, in some embodiments the multiple recesses Va are evenly distributed, i.e., the distance between any two adjacent recesses Va is the same. For example, the distance between any two adjacent recesses Va is between 0.8 mm and 1.2 mm. For instance, the distance between any two adjacent recesses Va is 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, or 1.2 mm. The distance between two adjacent recesses Va is the shortest distance between two adjacent recesses Va.

[0098] Fig. Figure 8 shows a plan view of a distribution of recesses on the second surface, which is provided by other embodiments of the present disclosure. As in Fig. As shown in Figure 8, the majority of cutouts Va is unevenly distributed. More precisely, the majority of cutouts Va comprises a majority of first cutouts Va1 and a majority of second cutouts Va2, and the majority of first cutouts Va1 lies within a region M defined by the dashed box in Figure 8. Fig. Figure 8 shows that the orthographic projection of the majority of first depressions Va1 lies opposite the central region of the microcavity-defining layer 40, meaning that the orthographic projection of the majority of first depressions Va1 is located in the central region of the microcavity-defining layer 40. In contrast, the orthographic projection of the majority of second depressions Va2 surrounds the central region of the microcavity-defining layer 40. The distribution density of the majority of first depressions Va1 is greater than the distribution density of the majority of second depressions Va2.

[0099] It is understood that when a cooling fluid impacts a flat surface, the heat dissipation effect will be weaker in the central area of ​​the surface than at the edges. In the Fig. In the embodiment shown in Figure 8, the several first recesses Va1 are surrounded by the several second recesses Va2, and the distribution density of the first recesses Va1 is greater than the distribution density of the second recesses Va2 in order to improve the heat dissipation effect in the area where the first recesses Va1 are located and thus to make the cooling effect at the individual points of the microcavity-defining layer 40 tend to be uniform.

[0100] In embodiments of the present disclosure, the shapes of the first recesses Va1 and the second recesses Va2 are not specifically limited. As in Fig. As shown in Figure 8, for example, each of the multiple first recesses Va1 extends in the first direction, and the multiple first recesses Va1 are spaced apart from each other in the second direction, with the first direction intersecting the second direction, e.g., perpendicular to the second direction. It should be noted that the statement that the first recesses Va1 extend in the first direction means that the first recesses Va1 essentially tend to extend in the first direction, and that their maximum size in the first direction is larger than their maximum size in the second direction, but does not mean that the first recesses Va1 are necessarily straight. The orthographic projection of the first recesses Va1 on the first plane may, for example, be rectangular, trapezoidal, or even have irregular shapes, such as arcuate, wavy, etc.Furthermore, the cross-section of the first recesses Va1 in the direction perpendicular to the first direction can be rectangular, approximately trapezoidal or arc-shaped, the present disclosure making no restrictions in this regard.

[0101] On each side of the area containing the multiple first recesses Va1, multiple second recesses Va2 are provided, each extending in a third direction. Multiple second recesses Va2 on the same side are spaced apart in a fourth direction, and the third direction intersects the fourth direction. For example, the third direction is perpendicular to the fourth direction. It should be noted that the phrase "the second recesses Va2 extend in the third direction" means that the second recesses Va2 essentially tend to extend in the third direction and that their maximum size in the third direction is greater than their maximum size in the fourth direction, but it does not mean that the second recesses Va2 are necessarily straight.The orthographic projection of the second recesses Va2 on the first plane can, for example, be rectangular, trapezoidal, or have irregular shapes, such as arcuate, wavy, etc. Furthermore, the cross-section of the second recesses Va2 in the direction perpendicular to the third direction can be rectangular, approximately trapezoidal, or arcuate, and the present disclosure does not impose any restrictions in this regard.

[0102] In one example, as in Fig. As shown in Figure 8, the direction of extension of the first recesses Va1 is the same as the direction of extension of the second recesses Va2, and the arrangement direction of the multiple first recesses Va1 is the same as the arrangement direction of the multiple second recesses Va2, i.e., the third direction is the same as the first direction, and the second direction is the same as the fourth direction. It should be noted that the embodiments of this disclosure are not limited to these. For example, the direction of extension of the first recesses Va1 and the direction of extension of the second recesses Va2 can also intersect.

[0103] In some embodiments, the size of the first recesses Va1 is approximately equal to the width of the second recesses Va2. It should be noted that the width of the first recesses Va1 / second recesses Va2 is the size of the first recesses Va1 / second recesses Va2 in the direction perpendicular to their extent. For the in Fig. In the case shown in Figure 8, if the first recesses Va1 extend in the first direction, then the width of the first recesses Va1 is the size of the first recesses Va1 in the second direction; if the second recesses Va2 extend in the third direction, then the width of the second recesses Va2 is the size of the second recesses Va2 in the fourth direction.

[0104] For example, the width of the first recess Va1 and the width of the second recess Va2 are both in the range of 0.2 mm to 0.4 mm. For instance, the width of the first recess Va1 and the width of the second recess Va2 could both be 0.2 mm, 0.3 mm, or 0.4 mm. Of course, the widths of the first recess Va1 and the second recess Va2 can also be different.

[0105] In some embodiments, the depth of the first recesses Va1 is approximately equal to the depth of the second recesses Va2. For example, the depth of the first recesses Va1 and the depth of the second recesses Va2 are both in the range of 0.1 mm to 0.3 mm. For instance, the depth of the first recesses Va1 and the depth of the second recesses Va2 are both 0.1 mm, or 0.2 mm, or 0.3 mm.

[0106] In some embodiments, the distance between adjacent first recesses Va1 is less than the distance between adjacent second recesses Va2. For example, the distance between adjacent first recesses Va1 is 0.4 to 0.9 times the distance between adjacent second recesses Va2. For example, the distance between adjacent first recesses Va1 is 0.4, 0.5, 0.6, 0.7, 0.8, or 0.9 times the distance between adjacent second recesses Va2.

[0107] For example, the distance between adjacent first recesses Va1 is between 0.4 mm and 0.6 mm. For example, the distance between adjacent first recesses Va1 is 0.4 mm, 0.5 mm, or 0.6 mm. For example, the distance between adjacent second recesses Va2 is between 0.8 mm and 1.2 mm. For example, the distance between adjacent second recesses Va2 is 0.8 mm, 0.9 mm, 1.0 mm, 1.1 mm, or 1.2 mm.

[0108] It should be noted that the in Fig. The embodiment shown in Figure 8 is an example where the orthographic projections of both the first recesses Va1 and the second recesses Va2 on the first surface S1 are rectangular. In practice, the first recesses Va1 and the second recesses Va2 can be adjusted to other shapes as needed. For example, the first recesses Va1 can be cylindrical, frustoconical, or similar, and each of the second recesses Va2 surrounds the multiple first recesses Va1, with the multiple second recesses Va2 being successively nested.

[0109] It should also be noted that in the microfluidic chip, the various arrangement possibilities of the heating layer 30 and the various arrangement possibilities of the recesses Va can be combined. For example, if the majority of recesses Va are arranged according to the in Fig. As shown in the 7 arrangement, the heating layer 30 can be arranged according to one of the instructions in Fig. Arrangements 3 to 5 are provided for; if the majority of the recesses Va are in accordance with the Fig. As shown in section 8, the heating layer 30 can also be arranged according to one of the instructions in Fig. The arrangements shown in 3 to 5 are provided for.

[0110] Furthermore, it should be noted that the above embodiments each represent an example in which the heating layer 30 is arranged on the substrate 10 and the recesses Va are arranged on the cover plate 20. In other embodiments, the positions of the heating layer 30 and the recesses Va can be changed. For example, in the embodiment described in Fig. In the embodiment shown in 2A, the heating layer 30 is provided on the cover plate 20 and the recesses Va are provided on the substrate base 10.

[0111] The in Fig. The microfluidic chip shown in Figure 2A is similar to the one in Figure 2A. Fig. 1 microfluidic chip shown, with the difference that in Fig. 2A the heating layer 30 is arranged on a surface of the cover plate 20 facing the substrate 10, and the substrate 10 has a plurality of recesses Va on a surface of the substrate 10 facing away from the cover plate 20. In this case, no insulating layer can be arranged between the substrate 10 and the microcavity-defining layer 40, and furthermore, the heating layer 30 lies between the hydrophobic layer 52 and the cover plate 20.

[0112] It should be noted that, although the positions of the heating layer 30 and the recesses Va in Fig. 2A of those in Fig. 1. The specific structures of the heating layer 30 and the recesses Va can still be constructed with reference to the structures described in the above embodiments, which will not be discussed in more detail here.

[0113] It should also be noted that in the Fig. 1 and Fig. In the microfluidic chip shown in Figure 2A, the substrate 10 and the microcavity-defining layer 40 are made of different materials, while in other embodiments the substrate 10 and the microcavity-defining layer 40 may be made of the same material.

[0114] The in Fig. The microfluidic chip shown in Figure 2B is similar to the one in Figure 2B. Fig. 2A shows a microfluidic chip, with the only difference being that in Fig. 2B the substrate base 10 and the microcavity-defining layer 40 are made of the same material. For example, both consist of organic materials or both of inorganic materials. In this case, the substrate base 10 and the microcavity-defining layer 40 are formed as a single-piece structure, which is more conducive to heat dissipation from the microreaction chambers 41.

[0115] The present disclosure also provides a reaction system comprising a microfluidic chip as described in each embodiment of the present disclosure. The reaction system can improve the heating efficiency and heat transfer efficiency of most microreaction chambers, thereby improving testing efficiency. Furthermore, at least some embodiments can also improve the uniformity of heating and cooling for most microreaction chambers.

[0116] Fig. Figure 9 shows a schematic block diagram of a reaction system provided in some embodiments of the present disclosure. As in Fig. As shown in Figure 9, the reaction system comprises a drive device 200 and a microfluidic chip 100, wherein the drive device 200 is electrically connected to the microfluidic chip 100 to provide an electrical signal to the microfluidic chip 100. For example, the drive device 200 applies an electrical signal to the aforementioned microfluidic chip 100, causing the heating layer to dissipate heat and thereby controlling the temperature in the microreaction chambers so that the reaction system solution housed in the microreaction chambers carries out the amplification reaction at a suitable temperature.

[0117] The drive device 200 can use universal or special hardware, software or firmware, etc., and can, for example, also include a central processing unit (CPU), an embedded processor, a programmable logic controller (PLC), etc., and the embodiments of the present disclosure do not constitute any limitations in this respect.

[0118] It should be noted that in the embodiments of the present disclosure, the reaction system may also include other components, such as a temperature sensor, an optical unit, a cooling unit, a communication unit, a power supply and the like, and the embodiments of the present disclosure are not limited thereto.

[0119] It is understood that the above embodiments are merely exemplary embodiments for the purpose of illustrating the principles of the present disclosure, which is not limited to them. Various variants and improvements are possible for the person skilled in the art without departing from the spirit and content of the present disclosure, which is also considered to be the scope of protection of the present disclosure.

Claims

[1] Microfluidic chip comprising: a substrate base; a microcavity-defining layer provided on the substrate support and defining a plurality of microreaction chambers; a cover plate provided on a side of the microcavity-forming layer facing away from the substrate support; a heating layer provided between the substrate support or the cover plate and the microcavity-defining layer for heating the plurality of microreaction chambers; wherein the one of the substrate base and the cover plate that is remote from the heating layer serves as a heat dissipation plate having a first surface facing the heating layer and a second surface facing away from the heating layer, the second surface having an area that is larger than the area of ​​an orthographic projection of the heat dissipation plate on the plane in which the heating layer is located. [2] The microfluidic chip of claim 1, wherein the second surface has a plurality of recesses, wherein the orthographic projection of the plurality of microreaction chambers on the substrate base overlaps with the orthographic projection of at least two of the recesses on the substrate base. [3] The microfluidic chip of claim 2, wherein each of the plurality of recesses extends in a first direction and the plurality of recesses are spaced apart from each other in a second direction. [4] The microfluidic chip according to claim 3, wherein the recesses in the second direction have a size between 0.2 mm and 0.4 mm; wherein the recesses have a depth between 0.1 mm and 0.3 mm, and wherein the distance between any two adjacent recesses is between 0.8 mm and 1.2 mm. [5] The microfluidic chip of claim 2, wherein the plurality of recesses comprises a plurality of first recesses and a plurality of second recesses, wherein an orthographic projection of the plurality of first recesses on the microcavity-defining layer is located in a central region of the microcavity-defining layer; wherein the plurality of second recesses surround the region in which the plurality of first recesses are located, and wherein the plurality of first recesses have a distribution density that is greater than the distribution density of the plurality of second recesses. [6] The microfluidic chip of claim 5, wherein each of the plurality of first recesses extends in a first direction, the plurality of first recesses being spaced apart in a second direction, the first direction crossing the second direction; wherein each of the plurality of second recesses extends in a third direction, a plurality of second recesses being provided on each side of a region in which the plurality of first recesses are located, the plurality of second recesses located on the same side being spaced apart from each other in a fourth direction, the third direction crossing the fourth direction. [7] The microfluidic chip of claim 6, wherein the size of the first recesses in the second direction is approximately the same as the size of the second recesses in the fourth direction; wherein the depth of the first recesses is approximately the same as the depth of the second recesses; and wherein the distance between adjacent first recesses is smaller than the distance between adjacent second recesses. [8] The microfluidic chip of claim 7, wherein the distance between adjacent first recesses is 0.4 to 0.9 times the distance between adjacent second recesses. [9] The microfluidic chip of claim 7, wherein the size of the first recesses in the second direction and the size of the second recesses in the fourth direction are both between 0.2 mm and 0.4 mm; wherein the depth of the first recesses and the depth of the second recesses are both between 0.1 mm and 0.3 mm, wherein the distance between adjacent first recesses is between 0.4 mm and 0.6 mm, and the distance between adjacent second recesses is between 0.8 mm and 1.2 mm. [10] The microfluidic chip of any one of claims 1 to 9, wherein the heating layer comprises a plurality of heating electrodes connected in series, wherein an orthographic projection of the plurality of microreaction chambers on the substrate base overlaps with an orthographic projection of at least two of the heating electrodes on the substrate base. [11] The microfluidic chip of claim 10, wherein each of the plurality of heating electrodes extends in a fifth direction, the plurality of heating electrodes being spaced apart from each other in a sixth direction, the fifth direction intersecting the sixth direction. [12] The microfluidic chip of claim 11, wherein the size of the plurality of heating electrodes in the sixth direction is approximately the same, wherein the distance between any two adjacent heating electrodes is approximately the same. [13] The microfluidic chip of claim 12, wherein the distance between any two adjacent heating electrodes is between 0.8 mm and 1.2 mm, wherein the size of each heating electrode in the sixth direction is between 0.4 mm and 0.6 mm. [14] The microfluidic chip according to claim 11, wherein the plurality of heating electrodes comprises a plurality of first heating electrodes and a plurality of second heating electrodes, the second heating electrodes being arranged on both sides of the plurality of first heating electrodes in the sixth direction; wherein the first heating electrodes comprise: a first sub-electrode and a second sub-electrode connected to each other, the first sub-electrode being provided with the second sub-electrode on both sides in the fifth direction, the orthographic projection of the first sub-electrode on the second surface being located in a central region of the second surface; wherein the resistance of the first sub-electrode per unit length is lower than the resistance of the second sub-electrode per unit length. [15] The microfluidic chip according to claim 14, wherein a sectional area of ​​the first sub-electrode in a direction perpendicular to the fifth direction is larger than a sectional area of ​​the second sub-electrode in a direction perpendicular to the fifth direction. [16] The microfluidic chip of claim 14, wherein the first sub-electrode has a larger size in the sixth direction than the second sub-electrode in the sixth direction. [17] The microfluidic chip according to claim 16, wherein the size of the first sub-electrode in the sixth direction is 1.5 to 3 times the size of the second sub-electrode in the sixth direction. [18] The microfluidic chip of claim 16, wherein the size of the first sub-electrode in the sixth direction is between 0.8 mm and 1.2 mm, wherein the size of the second sub-electrode in the sixth direction is between 0.4 mm and 0.6 mm. [19] The microfluidic chip of claim 14, wherein the distance between adjacent first sub-electrodes is between 0.4 mm and 0.6 mm; wherein the distance between adjacent second sub-electrodes is between 0.8 mm and 1.2 mm, wherein the distance between adjacent second heating electrodes is between 0.8 mm and 1.2 mm. [20] The microfluidic chip according to claim 14, wherein the size of the first sub-electrode in the fifth direction is 1 / 4 to 1 / 2 the size of the first heating electrode in the fifth direction. [21] The microfluidic chip of claim 10, wherein an orthographic projection of the plurality of heating electrodes on the second surface surrounds the central region of the second surface. [22] The microfluidic chip of any one of claims 10 to 21, wherein the heating layer further comprises a first drive electrode and a second drive electrode, wherein the plurality of heating electrodes are connected in series between the first drive electrode and the second drive electrode. [23] A microfluidic chip according to any one of claims 10 to 22, wherein the heating electrodes are made of a transparent material. [24] Microfluidic chip according to one of claims 1 to 23, wherein the microfluidic chip further comprises a bonding layer, wherein the bonding layer lies between the cover plate and the substrate base and encloses a receiving space with the cover plate and the microcavity-defining layer, wherein the microreaction chambers are located in the receiving space. [25] The microfluidic chip of any one of claims 1 to 24, wherein the microfluidic chip further comprises a hydrophilic layer, the hydrophilic layer covering at least the side wall and the bottom wall of each of the plurality of microreaction chambers. [26] A microfluidic chip according to any one of claims 1 to 25, wherein the microfluidic chip further comprises a hydrophobic layer; wherein the heating layer is located on a surface of the substrate base facing the cover plate, and the hydrophobic layer is arranged on a surface of the cover plate facing the substrate base; or wherein the heating layer is located on a surface of the cover plate facing the substrate support, and the hydrophobic layer is arranged on a side of the heating layer facing the microcavity-defining layer. [27] The microfluidic chip of claim 26, wherein the microfluidic chip further comprises a sample inlet and a sample outlet, wherein the sample inlet and the sample outlet both penetrate the cover plate and the hydrophobic layer. [28] A microfluidic chip according to any one of claims 1 to 27, wherein both the first substrate and the second substrate comprise a glass substrate. [29] A microfluidic chip according to any one of claims 1 to 27, wherein the heating layer is located on a surface of the cover plate facing the microcavity-defining layer, wherein the substrate support and the microcavity-defining layer are formed as a one-piece structure. [30] Reaction system comprising a microfluidic chip according to any one of claims 1 to 29

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