Chip

Abstract

The utility model discloses a chip. The chip comprises a chip assembly, the chip assembly comprises a first half part and a second half part, the second half part and the first half part are arranged in parallel in the width direction of the chip, and the first half part is provided with a first channel; the first half part is provided with a first bottom surface, and a through hole penetrating through the first bottom surface and communicating with the first channel is formed in the first half part; the second half part is provided with a second bottom face flush with the first bottom face, and the second bottom face is a complete plane of a continuous structure. Therefore, a reagent solution can enter the first channel from the through hole and circulate in the first half part of the chip; the bottom surface of the second half part is flush with the bottom surface of the first half part, so that the possibility of abnormity when the first half part and the second half part are adsorbed on the bearing platform in a vacuum manner can be reduced; and the second bottom surface is a complete plane with a continuous structure, so that a reagent solution can be prevented from entering the second half part, and the effect of filling the chip is achieved, so that the chip is adaptive to the bearing platform, and meanwhile, the purpose of small-amount sequencing is achieved.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of gene sequencing, especially a chip. BACKGROUND

[0002] The chip adapted to the sequencing platform is a reaction device that can carry the nucleic acid to be tested and accommodate the solution to provide a reaction environment or a detection environment for the nucleic acid to be tested, also known as a flow cell.

[0003] On the platform (sometimes referred to as a sequencer) for detecting the chip to achieve sequencing based on an optical imaging system, the base sequence order of the nucleic acid to be tested is identified and determined based on the information of the images obtained by imaging the specific positions (positions connected with the nucleic acid molecules to be tested, sometimes also referred to as reaction areas or fluid channels) of the chip. For example, specifically, on the platform for sequencing based on the principle of sequencing by synthesis using nucleotides with optical labels, during sequencing, the sequencer irradiates the labels in the reagent solution and excites the labels to emit optical signals, and then acquires the optical signals, for example, takes pictures to obtain images, and identifies and determines the base sequence order based on the information on the images to achieve the purpose of sequencing.

[0004] In the related art, the chip is divided into a 4-channel chip and an 8-channel chip, the size of the 8-channel chip is larger than that of the 4-channel chip, when a small amount of sequencing is performed using the 8-channel sequencer, only 4 channels are needed, the excess channels in the 8-channel chip will cause waste of the reagent solution, and the 4-channel chip cannot be placed on the carrying device adapted to the 8-channel chip. SUMMARY

[0005] The utility model provides a chip.

[0006] The chip of the present application embodiment comprises a chip assembly, the chip assembly comprises a first half and a second half arranged side by side with the first half along the width direction of the chip, the first half is provided with a first channel;

[0007] The first half has a first bottom surface, and the first half is formed with a through hole penetrating through the first bottom surface and communicating with the first channel; the second half has a second bottom surface flush with the first bottom surface, and the second bottom surface is a complete plane with continuous structure.

[0008] In this way, the reagent solution can enter the first channel from the through hole and circulate in the first half of the chip; the bottom surface of the second half is flush with the bottom surface of the first half, which can reduce the possibility of abnormality when the first half and the second half are vacuum adsorbed on the carrying platform; the second bottom surface is a complete plane with continuous structure, which can prevent the reagent solution from entering the second half and fill the chip, so that the chip can be adapted to the carrying platform while achieving the purpose of small amount of sequencing.

[0009] In some embodiments, the first half and the second half are a split structure.

[0010] In this way, the first half and the second half can be disassembled and maintained respectively, and the maintenance cost of the chip is reduced.

[0011] In some embodiments, the first half includes a first base plate and a first top plate arranged opposite to the first base plate, the first channel is formed between the first base plate and the first top plate, and the first base plate has a first bottom surface and is formed with a through hole.

[0012] In this way, the first channel formed between the first base plate and the first top plate enables the reagent solution to flow in the first half, and the through hole enables the fluid such as the reagent solution to flow into the first channel from the through hole and flow out of the through hole after the reaction.

[0013] In some embodiments, the first half further includes a first connecting layer arranged between the first base plate and the first top plate, the first connecting layer is formed with the first channel, and the first channel penetrates the first connecting layer along the thickness direction of the first connecting layer.

[0014] In this way, the first connecting layer can fixedly connect the first base plate and the first top plate, so that the first base plate and the first top plate form an integral whole, the structural stability of the first half is improved, and the reaction in the first channel is ensured to proceed normally.

[0015] In some embodiments, the second half includes a second base plate and a second top plate arranged opposite to the second base plate, the second base plate has a second bottom surface, and the second channel is formed between the second base plate and the second top plate.

[0016] In this way, the first half and the second half can have the same structure and be assembled in the same way, and the operation is simple.

[0017] In some embodiments, the second half further includes a second connecting layer arranged between the second base plate and the second top plate, the second connecting layer is formed with the second channel, and the second channel penetrates the second connecting layer along the thickness direction of the second connecting layer.

[0018] In this way, the second connecting layer can fixedly connect the second base plate and the second top plate, so that the second base plate and the second top plate form an integral whole, and the structural stability of the second half is improved.

[0019] In some embodiments, the second half includes a second base plate, a second top plate, and a second connecting layer arranged between the second base plate and the second top plate, the second base plate has a second bottom surface, and the second connecting layer is a solid piece of structure.

[0020] Therefore, the chip as a whole has similar structural composition, and no large structural adjustment is needed to adapt to the current sequencing platform, especially the stage structure. More importantly, the chip specification has the size of the sum of the first half and the second half, but only the first half is provided with channels for reagent flow and reaction, that is, the flow channel is arranged in a partial area of the chip, which can meet the demand of a small amount or trace amount of sample on the number of flow channels. In addition, the design can increase the connection area of the connection layer with the first substrate and the second top plate, and improve the structural stability of the second half.

[0021] In some embodiments, the first connection layer and the second connection layer are an integral structure.

[0022] Therefore, the first connection layer and the second connection layer can be processed and produced as a whole, reducing the production cost of the chip assembly.

[0023] In some embodiments, the first top plate and the second top plate are a split structure.

[0024] Therefore, the first top plate and the second top plate can be disassembled and maintained separately, reducing the maintenance cost of the chip.

[0025] In some embodiments, the first substrate and the second substrate are a split structure.

[0026] Therefore, the first substrate and the second substrate can be disassembled and maintained separately, reducing the maintenance cost of the chip.

[0027] In some embodiments, the chip includes a sealing member arranged on the first bottom surface, and the sealing member is provided with a connecting hole in communication with the through hole.

[0028] Therefore, the sealing member can improve the sealing performance of the chip and external components, reducing the probability of reagent solution leakage.

[0029] In some embodiments, the second half is a plate member with an integral structure.

[0030] Therefore, the second half has a simple structure, reducing the production process and assembly process, and reducing the production time and production cost of the chip.

[0031] In some embodiments, the chip includes a frame, the frame is provided with a window, and the first half and the second half are fixed on the frame and at least partially exposed through the window.

[0032] Therefore, the frame can serve as a support structure of the chip, reducing the impact of the outside on the inside of the chip, and improving the stability of the chip.

[0033] In some embodiments, the end of the first channel in the length direction is convergent, and the through hole is communicated with the end of the first channel in the length direction; when the chip is arranged in the second channel, the end of the second channel in the length direction is convergent, and the through hole is communicated with the end of the second channel in the length direction.

[0034] In this way, the reagent solution is facilitated to flow from the end to the first channel, and the reagent solution in the first channel is facilitated to converge to the end.

[0035] In some embodiments, the number of the first channels is plural, and in the two first channels on the outside, the ends of the first channels in the length direction converge to each other; and / or, the number of the second channels is plural, and in the two second channels on the outside, the ends of the second channels in the length direction converge to each other.

[0036] In this way, the positions of the through holes on the outermost sides of the first half and the second half are moved inward, and when the holes are arranged on the stage and communicated with the through holes, the positions of the two holes on the outermost sides can be defined, and the opening area on the stage connected with the through holes can be reduced. When the chip is combined with the stage by vacuum adsorption, the adsorbable area of the chip and the stage can be increased by this way, and the adsorption effect of the stage is improved.

[0037] In some embodiments, the number of the first channels is plural and arranged in pairs, and in a pair of the first channels, the ends of the two first channels in the length direction converge to each other; and / or, the number of the second channels is plural and arranged in pairs, and in a pair of the second channels, the ends of the two second channels in the length direction converge to each other.

[0038] In this way, the multiple first channels are arranged in pairs, which can improve the uniformity of the first channels, thereby facilitating the liquid injection operation.

[0039] In some embodiments, in a pair of the first channels, the two first channels are symmetrically arranged in the length direction; and / or, in a pair of the second channels, the two second channels are symmetrically arranged in the length direction.

[0040] In this way, the paired first channels are symmetrically arranged in the length direction of the first channel, which can make the fluid injection into the first channel more consistent, and is beneficial to obtain a reaction result with better overall stability.

[0041] The additional aspects and advantages of the present application will be in part apparent and in part pointed out hereinafter in the description of the application. BRIEF DESCRIPTION OF DRAWINGS

[0042] The above and / or additional aspects and advantages of the present application will become apparent and be more readily understood from the following description, taken in conjunction with the accompanying drawings, in which:

[0043] Figure 1 is a structural schematic diagram of a chip of the embodiment of the present application;

[0044] Figure 2 is a structural schematic diagram of a chip of the embodiment of the present application;

[0045] Figure 3 is a structural schematic diagram of a chip of the embodiment of the present application;

[0046] Figure 4 is an exploded view of a chip of the embodiment of the present application;

[0047] Figure 5 is an exploded view of a chip of the embodiment of the present application;

[0048] Figure 6 is an exploded view of a chip of the embodiment of the present application;

[0049] Figure 7 is an exploded view of a chip of the embodiment of the present application;

[0050] Figure 8 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0051] Figure 9 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0052] Figure 10 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0053] Figure 11 is a structural schematic diagram of an apparatus for manufacturing a first half of a chip of the embodiment of the present application;

[0054] Figure 12 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0055] Figure 13 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0056] Figure 14 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0057] Figure 15 is a flow chart of a manufacturing method of a chip of the embodiment of the present application;

[0058] Figure 16 is a flow chart of a manufacturing method of a chip of the embodiment of the present application.

[0059] Label explanation: 100, chip assembly; 10, first half; 11, first channel; 111, middle section; 112, first end; 113, second end; 12, first bottom surface; 13, through hole; 14, first base plate; 15, first top plate; 16, first connecting layer; 20, second half; 21, second bottom surface; 22, second base plate; 23, second top plate; 24, second connecting layer; 25, second channel; 200, sealing element; 210, connecting hole; 300, third connecting layer; 310, via hole; 400, frame; 410, window; 500, fourth connecting layer; 1, chip; 2, bearing platform; 3, conveying device; 4, positioning device; 5, pressing device. DETAILED DESCRIPTION

[0060] The embodiments of the present application will be described in detail below, examples of which are shown in the drawings, wherein the same or similar notations represent the same or similar elements or elements having the same or similar functions throughout. The embodiments described below by referring to the drawings are exemplary only, and are used only for explaining the present application, and cannot be understood as a limitation of the present application.

[0061] In the description of the present application, it should be understood that the orientations or positional relationships indicated by the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise" are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the devices or elements indicated must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation of the present application. In addition, the terms "first", "second" are only for the purpose of description, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features limited by "first", "second" can explicitly or implicitly include one or more of the features. In the description of the present application, the meaning of "multiple" is two or more, unless otherwise specifically limited.

[0062] In the description of the present application, it should be noted that, unless otherwise specifically specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected or can communicate with each other; it can be directly connected, or indirectly connected through an intermediate medium; it can be the communication or interaction relationship between two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0063] In the present application, unless otherwise explicitly specified and limited, the first feature is "on" or "under" the second feature can include that the first and second features are in direct contact, or can include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, the first feature is "on", "above" and "on top of" the second feature includes that the first feature is directly above and obliquely above the second feature, or only indicates that the horizontal height of the first feature is higher than that of the second feature. The first feature is "under", "below" and "underneath" the second feature includes that the first feature is directly below and obliquely below the second feature, or only indicates that the horizontal height of the first feature is less than that of the second feature.

[0064] The length direction refers to the direction of the outer edge with relatively long dimension in the outer edge of the part, and the width direction refers to the direction perpendicular to the length direction. For example, in a chip with a whole rectangular shape, the direction of the long side of the rectangular outer edge is the length direction, and the direction of the short side perpendicular to the length direction is the width direction, that is, the direction of the short side is the width direction.

[0065] The following disclosure provides many different embodiments or examples for implementing different structures of the present application. For simplicity of the present application, the components and settings of specific examples are described in the following. Of course, they are only examples, and the purpose is not to limit the present application. In addition, the present application can repeatedly refer to numbers and / or letters in different examples, and such repetition is for the purpose of simplification and clarity, which itself does not indicate the relationship between the various embodiments and / or settings discussed. In addition, the present application provides various specific examples of processes and materials, but those skilled in the art can realize the application of other processes and / or the use of other materials.

[0066] In the present application, the so-called "chip" is a reaction chamber, which has a space for containing liquid, and can be used for fixing the sample to be tested, also known as flow cell, flow tank or flow chamber (Flowcell). In the field of sequencing, the so-called "chip" can also be called sequencing slide, sequencing chip or biochip.

[0067] In the present application, the term "sequencing" refers to sequence determination, which is also called "nucleic acid sequencing" or "gene sequencing", and refers to the determination of the order of bases in a nucleic acid sequence; includes sequencing by synthesis (SBS) and / or sequencing by ligation (SBL); includes DNA sequencing and / or RNA sequencing; includes long fragment sequencing and / or short fragment sequencing, where long and short are relative, such as nucleic acid molecules longer than 1 Kb, 2 Kb, 5 Kb or 10 Kb can be called long fragments, and shorter than 1 Kb or 800 bp can be called short fragments; includes paired-end sequencing, single-end sequencing and / or mate-pair sequencing, etc., where paired-end sequencing or mate-pair sequencing can refer to the reading of any two segments or portions of the same nucleic acid molecule that do not overlap completely.

[0068] The term "sequencing" includes the process of binding nucleotides (including nucleotide analogs) to a template and collecting the corresponding reaction signals. In some sequencing platforms where the binding of nucleotides to a template and the collection of corresponding reaction signals are not synchronized, the determination of the order of multiple nucleotides / bases on a template is generally achieved through multiple sequencing cycles, where a cycle is also called a sequencing round, which can be defined as one base extension of four types of nucleotides / bases, or in other words, as the process of completing the determination of the base type at any given position on the template; for sequencing platforms based on controlled polymerization or ligation reactions, a cycle includes the process of binding four types of nucleotides to the template and collecting the corresponding reaction signals; for platforms based on polymerization reactions, the reaction system includes reaction substrates (nucleotides), polymerase and template, with a pre-set sequence (sequencing primer) bound to the template, based on the principles of base pairing and polymerization reactions, the added reaction substrates (nucleotides) are controllably ligated to the 3' end of the sequencing primer under the catalysis of polymerase, achieving base pairing with the corresponding position on the template; generally, a cycle can include one or more base extensions, for example, four types of nucleotides are added to the reaction system in turn, and base extension and collection of corresponding reaction signals are performed respectively, a cycle includes four base extensions; for another example, four types of nucleotides are added to the reaction system in any combination, such as two-by-two or one-three, two combinations are performed for base extension and collection of corresponding reaction signals respectively, a cycle includes two base extensions; for another example, four types of nucleotides are added to the reaction system simultaneously for base extension and collection of reaction signals, a cycle includes one base extension.

[0069] The sequencing can be performed by a sequencing platform, which can be selected from, but is not limited to, Hiseq / Miseq / Nextseq / Novaseq sequencing platforms of Illumina, IonTorrent platforms of Thermo Fisher / Life Technologies, BGISEQ and MGISEQ / DNBSEQ platforms of Huada, and single molecule sequencing platforms; and the sequencing mode can be selected from single-end sequencing or double-end sequencing.

[0070] The chip provided in the embodiments of the present application can be used in the field of sequencing. Specifically, the chip can play the role of a substrate to carry a nucleic acid template, and can also provide a reaction site for base extension. It should be understood that gene sequencing is one application scenario of the chip, and does not limit the application range of the chip. The chip can also be used in other fields besides sequencing, including but not limited to fields such as chemical molecule detection, protein detection, enzyme detection, etc. Unlike the sequencing application, when the chip is applied in other fields such as chemical molecule detection, protein detection, enzyme detection, etc., the substances carried on the surface of the chip can be chemical molecules, biological molecules, proteins, enzymes, etc. different from nucleic acid molecules, or can be nucleic acid molecules; in addition, the biochemical reactions occurring on the surface of the chip can also be different based on different detection methods.

[0071] Please refer to Figures 1-3 The chip 1 in the embodiments of the present application includes a chip assembly 100, which includes a first half 10 and a second half 20 arranged side by side with the first half 10 along the width direction of the chip 1, and the first half 10 is provided with a first channel 11;

[0072] The first half 10 has a first bottom surface 12, and the first half 10 is formed with a through hole 13 penetrating through the first bottom surface 12 and communicating with the first channel 11; the second half 20 has a second bottom surface 21 flush with the first bottom surface 12, and the second bottom surface 21 is a complete plane with continuous structure.

[0073] In this way, the reagent solution can enter the first channel 11 from the through hole 13 and flow in the first half 10 of the chip 1; the bottom surface of the second half 20 is flush with the bottom surface of the first half 10, which can reduce the possibility of abnormality when the first half 10 and the second half 20 are vacuum adsorbed on the carrying platform; the second bottom surface 21 is a complete plane with continuous structure, which can prevent the reagent solution from entering the second half 20 and fill the chip 1, so that the chip 1 can be adapted to the carrying platform while achieving the purpose of small-scale sequencing.

[0074] Specifically, the chip assembly 100, as the main component of the chip 1, is used to carry the sample to be tested. Taking the sequencing chip 1 as an example, the chip assembly 100 can carry the nucleic acid molecules to be tested, provide a reaction site for the reaction that occurs on the surface of the chip 1, and at the same time provide a channel for the reagent solution to participate in the reaction.

[0075] In this embodiment, the sheet assembly 100 is an assembly formed by stacking multiple sheet-like parts. In this embodiment, stacking means that multiple sheet-like parts have a common contact surface with each other but do not enter each other's bodies, and the contact surfaces of the multiple sheet-like parts are bonded together to form the sheet assembly 100.

[0076] The number of sheet-like parts is greater than or equal to two, meaning that the sheet assembly 100 is formed by stacking at least two sheet-like parts. In different implementations, the number of sheet-like parts can be designed in conjunction with the material and thickness of the sheet assembly 100. When the number of sheet-like parts is two, the two layers of sheet-like parts are stacked to form the sheet assembly 100, which performs the function of the sheet assembly 100 as described above.

[0077] The overall shape of the chip assembly 100 can be set to match the shape of other structures of the chip 1. For example, the overall shape of the chip assembly 100 can be a rectangle, square, rhombus, other polygons, or an irregular shape with an arc-shaped outer perimeter. In some embodiments, in order to match the structural settings of most sequencing platform instruments that accommodate and fix the chip 1, the overall shape of the chip assembly 100 is set to a rectangle.

[0078] The sheet assembly 100 is made of glass to ensure surface flatness. Alternatively, the sheet assembly 100 may be made of at least one of silica, crystal, quartz glass, or plastic, ceramic, PET (polyterephthalic acid), PMMA (polymethyl methacrylate), or any other suitable material. It is understood that at least one of the plurality of sheet-like parts comprising the sheet assembly 100 is made of one of the aforementioned materials. In some embodiments, a sheet-like part is made of one of the aforementioned materials. Exemplarily, the sheet-like part is a silica sheet, a crystal sheet, a quartz glass sheet, etc.

[0079] The first half 10 is provided with at least one first channel 11, which is a channel for the reagent solution to flow in the chip 1. In this embodiment, the first channel 11 can also immobilize the sample to be tested. Taking the sequencing chip 1 as an example, the nucleic acid molecules to be tested are immobilized in the first channel 11, and when the reagent solution flows through the first channel 11, it reacts with the nucleic acid molecules to be tested. Therefore, the first channel 11 also provides a reaction site for the surface reaction of the chip 1.

[0080] The first channel 11 is formed between two adjacent sheet-like parts, and in the area outside the first channel 11, the two adjacent sheet-like parts can be combined, for example, one of the sheet-like parts is provided with a protrusion in the thickness direction to combine with the other sheet-like part, or a layer of material such as channel adhesive can be filled to form the combination. The first channel 11 can be irregularly shaped.

[0081] In some embodiments, the first channel 11 can be identified by coding, which can be placed at either end of the first channel 11 or at both ends of the first channel 11, and the coding types include but are not limited to numerical coding, alphabetical coding, symbolic coding, or a combination thereof.

[0082] Referring to Figure 1 and Figure 3 In some embodiments, the first half 10 and the second half 20 are in a split structure.

[0083] In this way, the first half 10 and the second half 20 can be disassembled and maintained separately, thereby reducing the maintenance cost of the chip 1.

[0084] Specifically, the first half 10 and the second half 20 can be split into two separate parts, and the thicknesses of the first half 10 and the second half 20 are equal, so that the bottom surface and the top surface of the first half 10 and the second half 20 form a consistent plane.

[0085] Referring to Figure 3 and Figure 4 In some embodiments, the first half 10 includes a first base plate 14 and a first top plate 15 arranged opposite to the first base plate 14, the first channel 11 is formed between the first base plate 14 and the first top plate 15, and the first base plate 14 has the first bottom surface 12 and is formed with the through hole 13.

[0086] In this way, the first channel 11 formed between the first base plate 14 and the first top plate 15 allows the reagent solution to flow within the first half 10, and the through hole 13 allows the reagent solution and other fluids to flow into the first channel 11 from the through hole 13 and to flow out of the first channel 11 from the through hole 13 after the reaction.

[0087] Specifically, the material of the first substrate 14 can include at least one of silicon dioxide, crystal, quartz glass, and can also include at least one of plastic, ceramic, PET (polyethylene terephthalate), PMMA (polymethyl methacrylate), and can also be a composite material of at least one of silicon dioxide, crystal, quartz glass and at least one of plastic, ceramic, PET (polyethylene terephthalate), PMMA (polymethyl methacrylate). It can be understood that the first substrate 14 is made of one or more of the above-mentioned materials. In some embodiments, the first substrate 14 is made of one of the above-mentioned materials. For example, the first substrate 14 is a silicon dioxide substrate, a crystal substrate, a quartz glass substrate, etc. Of course, the first substrate 14 can also be formed by stacking a plurality of substrate units made of the same or different materials. In this embodiment, the stacking manner can be sequentially stacked along a direction perpendicular to one surface of the substrate unit, or can be sequentially stacked along a direction parallel to one surface of the substrate unit. For example, the first substrate 14 is a composite substrate including a silicon dioxide substrate unit and a quartz glass layer formed on one side surface of the silicon dioxide substrate unit. When the first substrate 14 includes a plurality of substrate units, the number of substrate units is not strictly limited and can be adjusted according to the desired size, such as thickness, of the first substrate 14.

[0088] In the embodiments of the present application, the shape of the first substrate 14 can be rectangular, square, rhombic, other polygonal, irregular shape with an arc-shaped outer periphery, etc. In some embodiments, in order to match the structure of the instrument for accommodating and fixing the chip 1 in most of the current sequencing platforms, the overall shape of the first substrate 14 is set to be rectangular.

[0089] In the embodiments disclosed in the present application, as shown in Figure 3 and Figure 4 , the first substrate 14 is rectangular, and the first substrate 14 includes through holes 13 arranged at both ends in the length direction and penetrating the first substrate 14 in the thickness direction.

[0090] In the embodiments of the present application, the number of through holes 13 at one end of the first substrate 14 in the length direction corresponds to the number of first channels 11 arranged on the chip 1, and the shape of the through hole 13 is not strictly limited and can be a square hole, a circular hole or other types of holes, which are not specifically limited in the present application. For example, the through hole 13 is a circular hole, and at this time, it is understood that the cross section of the through hole 13 along the planar direction of the first substrate 14 is circular.

[0091] The first top plate 15 can have a shape of a square, a rectangle, a rhombus, a circle, a triangle, or the like. The first top plate 15 can also have an irregular shape. In one embodiment, the first top plate 15 has a rectangular shape. In some embodiments, the first top plate 15 has the same shape as the first base plate 14. In some embodiments, the first top plate 15 has the same shape as the first base plate 14.

[0092] In some embodiments, the first top plate 15 has an area smaller than that of the first base plate 14. For example, in the length and / or width direction of the first half 10, the two ends of the first top plate 15 are recessed towards the middle region, so that the two ends of the first half 10 in the length and / or width direction are left empty relative to the first top plate 15.

[0093] In some embodiments, the first top plate 15 has a thickness smaller than that of the first base plate 14.

[0094] In one embodiment, the first half 10 includes one first top plate 15 which is combined with one surface of the first base plate 14. In another embodiment, the first half 10 includes two first top plates 15 which are combined with two surfaces of the first base plate 14, i.e., the upper and lower surfaces of the first base plate 14 cover the first top plates 15, respectively.

[0095] The first top plate 15 can be made of, for example, glass, silica, crystal, quartz glass, plastic, ceramic, PET (polyethylene terephthalate), PMMA (polymethyl methacrylate), or any other suitable material. It should be understood that at least one of the first base plate 14 and the first top plate 15 is made of a light-transmitting material, including but not limited to glass and crystal.

[0096] In one embodiment, the first base plate 14 and / or the first top plate 15 are made of a light-transmitting material, so that the optical system can collect optical signals generated on the surface of the chip 1. Thus, the types of reactions occurring on the surface of the chip 1, in particular the first half 10, can be extended to the optical application level. As in the sequencing chip 1, when the substrate containing the fluorescent group reacts with the nucleic acid molecules fixed on the surface of the chip 1, in particular the surface of the first half 10, the optical signals generated by the fluorescent group on the surface of the first half 10 are collected by the optical system to identify the reaction site and the type of substrate.

[0097] Of course, it can be understood that the first substrate 14 and the first top plate 15 are both formed of sheet-shaped parts of light-transmitting material, and the first half 10 is subjected to light-shielding treatment on the side that does not need to transmit light. In some embodiments, when the laser emitted by the laser of the sequencing platform irradiates the chip 1 through the lens, it also irradiates the material, such as the adhesive layer, connecting the first substrate 14 and the first top plate 15, and the molecules of the adhesive layer are thus excited to emit fluorescence, which greatly interferes with the identification and detection of the target signal, i.e., the signal from the nucleic acid molecules to be detected in the first channel 11. In order to avoid such interference, the first substrate 14 is subjected to light-shielding treatment. The light-shielding treatment can be achieved in various ways, such as forming a light-shielding coating on the first bottom surface 12 to meet the requirements of the genetic sequencer, especially the single-molecule sequencer, for the fluorescence background characteristics of the chip 1. The first bottom surface 12 is the surface of the first substrate 14 facing away from the first top plate 15.

[0098] In some embodiments, the material of the first substrate 14 and / or the first top plate 15 includes glass. In this way, the glass material of the first substrate 14 and / or the first top plate 15 makes the fluidity of the liquid better, and the liquid is less likely to adhere to the inside of the chip 1, improving the accuracy of detection of the chip 1. Specifically, glass is an amorphous inorganic non-metallic material, which is generally made of various inorganic minerals such as quartz sand, borax, boric acid, barite, barium carbonate, limestone, feldspar, soda ash, etc. as the main raw material, and a small amount of auxiliary raw materials are added. Its main components are silicon dioxide and other oxides.

[0099] Please refer to Figure 4 In some embodiments, the first half 10 further includes a first connecting layer 16 disposed between the first substrate 14 and the first top plate 15, and the first connecting layer 16 is formed with the first channel 11, which penetrates the first connecting layer 16 in the thickness direction of the first connecting layer 16.

[0100] In this way, the first connecting layer 16 can fixedly connect the first substrate 14 and the first top plate 15, so that the first substrate 14 and the first top plate 15 form an integral whole, improving the structural stability of the first half 10 and ensuring the normal progress of the reaction in the first channel 11.

[0101] ​Specifically, the first connecting layer 16 is combined to at least one side surface of the first substrate 14, so that the thickness direction of the first connecting layer 16 is perpendicular to the surface of the first substrate 14. It should be understood that the first connecting layer 16 combined to at least one side surface of the first substrate 14 includes two cases, specifically, as a first case: the first connecting layer 16 is combined to one surface of the first substrate 14, at this time, the sample to be detected is fixed to the surface of the first substrate 14 where the first connecting layer 16 is arranged, more specifically, the sample to be detected is fixed to the region of the surface of the first substrate 14 where the material of the first connecting layer 16 is not combined. As a second case: the first connecting layer 16 is combined to the opposite two surfaces of the first substrate 14, at this time, the two surfaces of the first substrate 14 where the first connecting layer 16 is arranged, specifically, the region of the surface of the first substrate 14 where the material of the first connecting layer 16 is not combined, can be combined with the sample to be detected. This way can sequence the upper and lower surfaces of a chip 1, and even can sequence the two surfaces at the same time.

[0102] In one embodiment, the area of the first connecting layer 16 is smaller than the area of the first substrate 14. As an example, in the length and / or width direction of the first half 10, the two ends of the first connecting layer 16 are recessed to the middle region, so that the first substrate 14 is left empty at the two ends in the length and / or width direction, that is, the first substrate 14 is not combined with the first connecting layer 16 at the two ends in the length and / or width direction. In another embodiment, the first connecting layer 16 is the same in shape and size as the outer edge of the first top plate 15.

[0103] In some embodiments, the material of the first connecting layer 16 can include at least one of the epoxy resin in the epoxy adhesive, the acrylic resin in the acrylic adhesive, the OCA (Optically Clear Adhesive) optical adhesive, the PSA (Pressure Sensitive Adhesive) pressure sensitive adhesive, and the PI (Polyimide) double-sided adhesive. Therefore, the first connecting layer 16 can be combined to at least one side surface of the first substrate 14 by its own bonding performance. Specifically, the first connecting layer 16 can bond the first substrate 14 and the first top plate 15. In this way, the first substrate 14 and the first top plate 15 are connected by bonding, so that the first substrate 14 is fixedly connected with the first top plate 15.

[0104] In some embodiments, the material of the first connecting layer 16 can include other materials forming a surface adhesive layer, such as PE foam double-sided adhesive. In this case, the first connecting layer 16 can be pasted on at least one side surface of the first substrate 14 through the surface adhesive layer. It should be understood that the surface adhesive layer can be provided in the partial area where the first connecting layer 16 is combined with the first substrate 14, or the adhesive material can be provided in all areas where the first connecting layer 16 is combined with the first substrate 14. In an embodiment, the adhesive material is provided in all areas where the first connecting layer 16 is combined with the first substrate 14, which can reduce the risk of reaction reagent solution or solution in different flow channels, thereby reducing the influence on the accuracy of the detection result. In addition, by fully bonding the first connecting layer 16 with the first substrate 14, the infiltration of the reagent solution in the unbonded area can also be reduced, and the loss of the reagent solution can be reduced.

[0105] Please refer to Figure 4 In some embodiments, the second half 20 includes a second substrate 22 having a second bottom surface 21 and a second top plate 23 arranged opposite to the second substrate 22, and a second channel 25 is formed between the second substrate 22 and the second top plate 23.

[0106] In this way, the first half 10 and the second half 20 can have the same structure and be assembled in the same way, which is simple to operate.

[0107] Specifically, the material of the second substrate 22 can include at least one of silica, crystal, and quartz glass, or at least one of plastic, ceramic, PET (polyethylene terephthalate), and PMMA (polymethyl methacrylate), or a composite material generated by at least one of silica, crystal, and quartz glass and at least one of plastic, ceramic, PET (polyethylene terephthalate), and PMMA. It can be understood that the second substrate 22 is made of one or more of the above-mentioned materials. In some embodiments, the second substrate 22 is made of one of the above-mentioned materials. For example, the second substrate 22 is a silica substrate, a crystal substrate, a quartz glass substrate, etc. Of course, the second substrate 22 can also be formed by stacking a plurality of substrate units made of the same or different materials. In this embodiment, the stacking manner can be sequentially stacking along a direction perpendicular to one surface of the substrate unit, or sequentially stacking along a direction parallel to one surface of the substrate unit. For example, the second substrate 22 is a composite substrate including a silica substrate unit and a quartz glass layer formed on one side surface of the silica substrate unit. When the second substrate 22 includes a plurality of substrate units, the number of substrate units is not strictly limited and can be adjusted according to the desired size, such as thickness, of the second substrate 22.

[0108] In this embodiment, the shape of the second substrate 22 can be a rectangle, square, rhombus, other polygons, or an irregular shape with an arc-shaped outer perimeter. In some embodiments, in order to match the structural setup of most sequencing platform instruments that accommodate and fix the chip 1, the overall shape of the second substrate 22 is set to a rectangle.

[0109] The second top plate 23 can be in various regular shapes such as square, rectangle, rhombus, circle, and triangle. Of course, the second top plate 23 can also be irregular in shape. In one embodiment, the second top plate 23 is rectangular. In some embodiments, the shape of the second top plate 23 is the same as the shape of the second substrate 22. In some embodiments, the second top plate 23 has the exact same shape as the second substrate 22.

[0110] In some embodiments, the area of ​​the second top plate 23 is smaller than the area of ​​the second substrate 22. For example, in the length and / or width direction of the second half 20, both ends of the second top plate 23 are recessed towards the middle region, such that the two ends of the second half 20 are left empty relative to the second top plate 23 in the length and / or width direction.

[0111] In some embodiments, the thickness of the second top plate 23 is less than the thickness of the second substrate 22.

[0112] In one embodiment, the second half 20 includes a second top plate 23, which is attached to one surface of the second substrate 22; in another embodiment, the second half 20 includes two second top plates 23, which are respectively attached to two surfaces of the second substrate 22, that is, the upper and lower surfaces of the second substrate 22 respectively cover the second top plate 23.

[0113] The second top plate 23 can be made of materials such as glass, silica, crystal, quartz glass, plastic, ceramic, PET (polyterephthalic acid), PMMA (polymethyl methacrylate), or any other suitable material.

[0114] In some embodiments, the second substrate 22 and / or the second top plate 23 are made of glass. Specifically, glass is an amorphous inorganic non-metallic material, generally made from a variety of inorganic minerals such as quartz sand, borax, boric acid, barite, barium carbonate, limestone, feldspar, soda ash, etc., as the main raw materials, with the addition of a small amount of auxiliary raw materials. Its main components are silicon dioxide and other oxides.

[0115] Please see Figure 4 In some embodiments, the second half 20 further includes a second connecting layer 24 disposed between the second substrate 22 and the second top plate 23. The second connecting layer 24 has a second channel 25 that extends through the second connecting layer 24 along its thickness direction.

[0116] In this way, the second connecting layer 24 can fixedly connect the second substrate 22 and the second top plate 23, so that the second substrate 22 and the second top plate 23 form an integral whole, improving the structural stability of the second half 20.

[0117] Specifically, in one embodiment, the area of the second connecting layer 24 is smaller than the area of the second substrate 22. As an example, in the length and / or width direction of the second half 20, the two ends of the second connecting layer 24 are recessed towards the middle region, so that the second substrate 22 is left empty at both ends in the length and / or width direction, i.e., the second substrate 22 is not combined with the second connecting layer 24 at both ends in the length and / or width direction. In another embodiment, the second connecting layer 24 is the same in shape and size as the outer edge of the second top plate 23.

[0118] In some embodiments, the material of the second connecting layer 24 can include at least one of an epoxy resin in an epoxy adhesive, an acrylic resin in an acrylic adhesive, an OCA (Optically Clear Adhesive), a PSA (Pressure Sensitive Adhesive), a PI (Polyimide) double-sided adhesive, etc. In this way, the second connecting layer 24 can be combined with at least one side surface of the second substrate 22 by its own bonding performance. Specifically, the second connecting layer 24 can bond the second substrate 22 and the second top plate 23. In this way, the second substrate 22 and the second top plate 23 are connected by bonding, so that the second substrate 22 is fixedly connected with the second top plate 23.

[0119] In some embodiments, the material of the second connecting layer 24 can include other materials that form a glue layer on the surface, such as PE foam double-sided adhesive. At this time, the second connecting layer 24 can be pasted on at least one side surface of the second substrate 22 through the glue layer on the surface. It should be understood that the glue layer on the surface can be provided in the part of the area where the second connecting layer 24 is combined with the second substrate 22, or the bonding material can be provided in all areas where the second connecting layer 24 is combined with the second substrate 22.

[0120] In some embodiments, the second channel 25 can be identified by coding, which can be placed at either end of the second channel 25 or at both ends of the second channel 25, and the coding types include but are not limited to numerical coding, alphabetical coding, symbolic coding or a combination thereof. The coding of the second channel 25 can be continuous with the coding of the first channel 11, or can be independent of each other.

[0121] Please refer to Figure 5In some embodiments, the second half 20 comprises a second base plate 22, a second top plate 23, and a second connecting layer 24 disposed between the second base plate 22 and the second top plate 23, the second base plate 22 has a second bottom surface 21, and the second connecting layer 24 is a solid sheet with continuous structure.

[0122] In this way, the chip 1 as a whole has similar structural composition, and no large structural adjustment is needed to adapt to the current sequencing platform, especially to adapt to the stage structure. More importantly, the chip 1 has a size equal to the sum of the first half 10 and the second half 20, but only the first half 10 is provided with channels for reagent flow and reaction, that is, the flow channel is arranged in a partial area of the chip 1, which can meet the demand of a small amount or trace amount of sample for the number of flow channels. In addition, this design can increase the connection area of the connecting layer with the first base plate 14 and the second top plate 23, and improve the structural stability of the second half 20.

[0123] Specifically, the second connecting layer 24 is provided with adhesive material on all surfaces, and the size of the second connecting layer 24 can be less than or equal to the size of the second base plate 22 and the size of the second top plate 23, so that the second base plate 22 and the second top plate 23 can be bonded with all surfaces of the second connecting layer 24.

[0124] In some embodiments, the material of the second connecting layer 24 is the same as that of the first connecting layer 16, except that the second connecting layer 24 does not form a hollow area corresponding to the first channel 11.

[0125] Please refer to Figure 6 In some embodiments, the first connecting layer 16 and the second connecting layer 24 are an integral structure.

[0126] In this way, the first connecting layer 16 and the second connecting layer 24 can be integrally machined and produced, thereby reducing the production cost of the chip assembly 100.

[0127] Specifically, the first connecting layer 16 and the second connecting layer 24 can be integrally formed. In one embodiment, the first connecting layer 16 and the second connecting layer 24 are a split structure, that is, the first connecting layer 16 and the second connecting layer 24 are respectively manufactured, and the first connecting layer 16 and the second connecting layer 24 can have the same structure, that is, the first connecting layer 16 and the second connecting layer 24 are both formed with channels, and the first connecting layer 16 and the second connecting layer 24 can be used interchangeably, or the first connecting layer 16 is formed with the first channel 11, and the second connecting layer 24 is a solid sheet with continuous structure.

[0128] Please refer to Figure 6 In some embodiments, the first top plate 15 and the second top plate 23 are a split structure.

[0129] Therefore, the first top plate 15 and the second top plate 23 can be disassembled and maintained respectively, and the maintenance cost of the chip 1 is reduced.

[0130] Specifically, the first top plate 15 and the second top plate 23 can be made of the same material and have the same size, or the first top plate 15 and the second top plate 23 can be used interchangeably, or the first top plate 15 and the second top plate 23 can have the same structure.

[0131] In some embodiments, the first top plate 15 and the second top plate 23 are integrated structures, that is, integrally formed.

[0132] Referring to Figure 6 In some embodiments, the first substrate 14 and the second substrate 22 are separate structures.

[0133] Therefore, the first substrate 14 and the second substrate 22 can be disassembled and maintained respectively, and the maintenance cost of the chip 1 is reduced.

[0134] Specifically, the first substrate 14 and the second substrate 22 can be made of the same material and have the same size, but the first substrate 14 is formed with a through hole 13 communicating with the first channel 11, and the second substrate 22 is a solid sheet with continuous structure.

[0135] In some embodiments, the first substrate 14 and the second substrate 22 are integrated structures, that is, integrally formed.

[0136] It should be understood that when the second half 20 contains multiple layer structures, one of the layer structures can be integrally designed with part of the first half 10, or each layer structure can be integrally designed with each layer structure of the first half 10.

[0137] Referring to Figure 7 In some embodiments, the second half 20 is a one-piece plate.

[0138] Therefore, the second half 20 has a simple structure, reduces the production and assembly processes, and reduces the production time and cost of the chip 1.

[0139] Specifically, the second half 20 can include any suitable material, such as glass, silicon dioxide, crystal, quartz glass, plastic, ceramic, PET (polyethylene terephthalate), PMMA (polymethyl methacrylate), or any other suitable material.

[0140] The shape of the second half 20 can be square, rectangular, circular, triangular, or any other regular shape. Of course, the second half 20 can also be irregularly shaped. In the present embodiment, the second half 20 is a long rectangle.

[0141] Optionally, the material of the second half 20 may include glass. Glass is an amorphous inorganic non-metallic material, generally made from a variety of inorganic minerals such as quartz sand, borax, boric acid, barite, barium carbonate, limestone, feldspar, and soda ash as the main raw materials, with the addition of a small amount of auxiliary raw materials. Its main components are silicon dioxide and other oxides.

[0142] Please see Figure 3 and Figure 6 In some embodiments, the chip 1 includes a seal 200 disposed on the first bottom surface 12, the seal 200 having a connection hole 210 communicating with the through hole 13.

[0143] Thus, the seal 200 can improve the sealing performance of the connection between the chip 1 and the external components, and reduce the probability of reagent solution leakage.

[0144] Specifically, the seal 200 can be an elastic element, such as rubber. The seal 200 can be fixedly connected to the first bottom surface 12 via a third connecting layer 300. The third connecting layer 300 includes, but is not limited to, water-based adhesive and double-sided adhesive. The shape and size of the third connecting layer 300 can be adapted to the seal 200. A through hole 310 adapted to the connecting hole 210 is formed on the third connecting layer 300. The central axis of the through hole 310 is coaxial with the central axis of the connecting hole 210. The connecting hole 210 can be a cylindrical through hole 13. The connecting hole 210 connects the external component and the through hole 13, allowing the reagent solution to flow from the external component to the first channel 11 and from the first channel 11 to the external component. The central axis of the connecting hole 210 is coaxial with the central axis of the through hole 13. The seal 200 can be cylindrical, with one connecting hole 210 formed on one seal 200, and the seal 200 and the through hole 13 are set one-to-one; the seal 200 can also be cuboid, with multiple connecting holes 210 formed on one seal 200, and the seal 200 and the multiple through holes 13 are set one-to-one.

[0145] Please see Figure 1 and Figure 4 In some embodiments, the chip 1 includes a frame 400, the frame 400 having a window 410, and the first half 10 and the second half 20 are both fixed to the frame 400 and exposed at least partially through the window 410.

[0146] Thus, the frame 400 can serve as a support structure for chip 1, reducing the impact of external forces on the chip 1 and improving the stability of chip 1.

[0147] Specifically, the frame 400 is the outermost layer of the chip 1, which protects the chip 1 and surrounds the chip assembly 100, thereby providing a carrier for the reagent solution. The frame 400 is arranged on the side of the first top plate 15 away from the first base plate 14, which facilitates the taking and placing of the chip assembly 100 and avoids leaving fingerprints or other residues on the surface of the chip 1 when directly contacting the chip assembly 100, thereby affecting the collection of the optical signal generated in the chip 1. Moreover, by setting the structure of the frame 400, the chip 1 can be fixed in a specific area of a test instrument to detect the sample to be tested fixed in the chip 1. For example, the chip 1 is fixed on the chip 1 loading table surface of a sequencing platform to achieve stable sequencing. The frame 400 can be made of resin, and the frame 400 is formed by using an injection molding process, which is low in manufacturing cost and simple in manufacturing process. The first half 10 and the second half 20 can be fixedly connected to the surface of the frame 400 through the fourth connecting layer 500, and the fourth connecting layer 500 includes but is not limited to water glue and double-sided adhesive.

[0148] The window 410 is used for the imaging system to image the first channel 11 through the window 410. The window 410 can be a hollow structure, and the shape of the window 410 includes but is not limited to an oval shape, a rectangular shape, etc.

[0149] At both ends of the frame 400, codes for identifying the channel and / or the chip 1 can be arranged. The position of the codes is not strictly limited and can be flexibly arranged. For example, the code for identifying the channel can be arranged at one end of the frame 400, and the code for identifying the chip 1 can be arranged at the other end of the frame 400.

[0150] Please refer to Figure 2 In some embodiments, the end of the first channel 11 in the length direction is convergent, and the through hole 13 is in communication with the end of the first channel 11 in the length direction. When the chip 1 is provided with the second channel 25, the end of the second channel 25 in the length direction is convergent, and the through hole is in communication with the end of the second channel 25 in the length direction.

[0151] In this way, the reagent solution can flow from the end to the first channel 11, and the reagent solution in the first channel 11 can also converge to the end.

[0152] Specifically, the shape of the first channel 11 can be irregular, for example, the first channel 11 can include a middle section 111, a first end 112 and a second end 113. The first end 112 and the second end 113 are symmetrically arranged at the two ends of the first channel 11 and are both triangular in shape, and the middle section 111 is long and narrow rectangular in shape. Of course, the first end 112 and the second end 113 can also have different shapes, for example, the first end 112 forms an included angle, and the second end 113 forms a rounded corner.

[0153] The first end 112, the middle section 111 and the second end 113 are sequentially arranged along the length direction of the first half 10. The middle section 111 is used for the reagent solution to perform corresponding reactions; the first end 112 can be arranged as a liquid inlet area for the reagent solution to flow into the first channel 11, and the second end 113 can be arranged as a liquid outlet area for the reagent solution to flow out of the first channel 11. Of course, it should be understood that the positions of the first end 112 and the second end 113 can be interchanged, so that the first channel 11 can also be arranged such that the second end 113 is the liquid inlet area for the reagent solution to flow into the first channel 11, and the first end 112 is the liquid outlet area for the reagent solution to flow out of the first channel 11. The shape and size of the second channel 25 can be consistent with those of the first channel 11.

[0154] Referring to Figure 2 In some embodiments, the number of the first channels 11 is multiple, and in the outer two first channels 11, the ends of the first channels 11 in the length direction are gathered towards each other; and / or, the number of the second channels 25 is multiple, and in the outer two second channels 25, the ends of the second channels 25 in the length direction are gathered towards each other.

[0155] In this way, the positions of the outermost through holes 13 of the first half 10 and the second half 20 are moved inward, and when the hole passages communicating with the through holes 13 are arranged on the platform, the positions of the outermost two hole passages can be defined, and the opening area of the platform connected with the through holes 13 is reduced. When the chip 1 is combined with the platform by vacuum adsorption, the adsorbable area of the chip 1 and the platform can be increased in this way, and the adsorption effect of the platform is improved.

[0156] Specifically, the number of the first channels 11 can be 2, 3, 4, 5 or more. In one embodiment, the number of the first channels 11 is 3, and the ends of the first first channel 11 and the third first channel 11 are close to each other.

[0157] The number of the second channels 25 can be 2, 3, 4, 5 or more. In one embodiment, the number of the second channels 25 is 3, and the ends of the first second channel 25 and the third second channel 25 are close to each other.

[0158] The first channels 11 can be multiple in number, and in the outer two first channels 11, the end portions of the first channels 11 in the length direction are gathered in the direction of approaching each other; the second channels 25 can also be multiple in number, and in the outer two second channels 25, the end portions of the second channels 25 in the length direction are gathered in the direction of approaching each other; the first channels 11 and the second channels 25 can also be multiple in number, and in the outer two first channels 11, the end portions of the first channels 11 in the length direction are gathered in the direction of approaching each other, and in the outer two second channels 25, the end portions of the second channels 25 in the length direction are gathered in the direction of approaching each other.

[0159] Please refer to Figure 2 In some embodiments, the first channels 11 are multiple in number and arranged in pairs, and in a pair of first channels 11, the end portions of the two first channels 11 in the length direction are gathered in the direction of approaching each other; and / or, the second channels 25 are multiple in number and arranged in pairs, and in a pair of second channels 25, the end portions of the two second channels 25 in the length direction are gathered in the direction of approaching each other.

[0160] In this way, the multiple first channels 11 are arranged in pairs, which can improve the uniformity of the first channels 11, thereby improving the uniformity of the liquid inlet, making the liquid inlet operation convenient.

[0161] Specifically, the number of the first channels 11 can be 2, 4, 6, 8, or more even numbers. In one embodiment, the number of the first channels 11 is 4, the end portions of the first first channel 11 and the second first channel 11 approach each other, the end portions of the third first channel 11 and the fourth first channel 11 approach each other, and the end portions of the second first channel 11 and the third first channel 11 are away from each other.

[0162] The number of the second channels 25 can be 2, 4, 6, 8, or more even numbers. In one embodiment, the number of the second channels 25 is 4, the end portions of the first second channel 25 and the second second channel 25 approach each other, the end portions of the third second channel 25 and the fourth second channel 25 approach each other, and the end portions of the second second channel 25 and the third second channel 25 are away from each other.

[0163] The first channels 11 can be provided in pairs, and in each pair, the ends of the two first channels 11 in the length direction thereof are gathered towards each other; the second channels 25 can be provided in pairs, and in each pair, the ends of the two second channels 25 in the length direction thereof are gathered towards each other; or the first channels 11 and the second channels 25 can be provided in pairs, and in each pair of first channels 11, the ends of the two first channels 11 in the length direction thereof are gathered towards each other, and in each pair of second channels 25, the ends of the two second channels 25 in the length direction thereof are gathered towards each other.

[0164] Referring to Figure 2 In some embodiments, in each pair of first channels 11, the two first channels 11 are symmetrically arranged along the length direction thereof; and / or in each pair of second channels 25, the two second channels 25 are symmetrically arranged along the length direction thereof.

[0165] In this way, the pairs of first channels 11 are symmetrically arranged along the length direction thereof, which can make the fluid injection into the first channels 11 more consistent, and thus facilitate obtaining a reaction result with better overall stability.

[0166] Specifically, the two first channels 11 are symmetrically arranged along the length direction thereof, which means that the first end 112, the second end 113 and the middle section 111 of the two first channels 11 are symmetrically arranged along the length direction of the first channels 11. In one embodiment, the number of the first channels 11 is four, the first first channel 11 and the second first channel 11 are symmetrically arranged along the length direction of the first channels 11, the third first channel 11 and the fourth first channel 11 are symmetrically arranged along the length direction of the first channels 11, and of course, the second first channel 11 and the third first channel 11 can also be symmetrically arranged along the length direction of the first channels 11.

[0167] The two second channels 25 are symmetrically arranged along the length direction thereof, which means that the first end, the second end and the middle section of the two second channels 25 are symmetrically arranged along the length direction of the second channels 25. In one embodiment, the number of the second channels 25 is four, the first second channel 25 and the second second channel 25 are symmetrically arranged along the length direction of the second channels 25, the third second channel 25 and the fourth second channel 25 are symmetrically arranged along the length direction of the second channels 25, and of course, the second second channel 25 and the third second channel 25 can also be symmetrically arranged along the length direction of the second channels 25.

[0168] The two first channels 11 can be symmetrically arranged along the length direction thereof in the pair of first channels 11, or the two second channels 5 can be symmetrically arranged along the length direction thereof in the pair of second channels 25, or the two first channels 11 can be symmetrically arranged along the length direction thereof in the pair of first channels 11 and the two second channels 5 can be symmetrically arranged along the length direction thereof in the pair of second channels 25.

[0169] Referring to Figure 8 The manufacturing method of the chip 1 in the embodiments of the present application includes:

[0170] S100, providing a frame 400;

[0171] S200, arranging the first half 10 and the second half 20 of the chip assembly 100 on the frame 400 in parallel along the width direction of the chip 1.

[0172] In this way, the first half 10 and the second half 20 can be arranged on the frame 400 by the above steps to form the chip 1.

[0173] Specifically, the frame 400 can be formed by injection molding using a resin material, and the first half 10 and the second half 20 can be fixedly connected to the surface of the frame 400 through the fourth connecting layer 500. The first half 10 can be fixed on the frame 400 first, and then the second half 20 can be fixed on the frame 400. Alternatively, the second half 20 can be fixed on the frame 400 first, and then the first half 10 can be fixed on the frame 400. Alternatively, the first half 10 and the second half 20 can be fixed on the frame 400 at the same time.

[0174] Referring to Figure 9 In some embodiments, the first half 10 is implemented by the following steps:

[0175] S10, providing a first substrate 14, a first connecting layer 16 and a first top plate 15;

[0176] S20, arranging the first connecting layer 16 between the first substrate 14 and the first top plate 15, and connecting the first connecting layer 16 to the first substrate 14 and the first top plate 15.

[0177] In this way, the first connecting layer 16 can connect and fix the first substrate 14 and the first top plate 15 to form the first half 10.

[0178] Specifically, the first connecting layer 16 can be connected to the first substrate 14 first, and then the first top plate 15 can be connected to the first connecting layer 16. Alternatively, the first connecting layer 16 can be connected to the first top plate first, and then the first substrate 14 can be connected to the first connecting layer 16.

[0179] Referring to Figure 10 andFigure 11 In some embodiments, a first connecting layer 16 is arranged between the first substrate 14 and the first top plate 15 (step S20), including:

[0180] S21, the first substrate 14 is arranged on the carrying platform 2;

[0181] S22, the first connecting layer 16 is arranged on the conveying device 3;

[0182] S23, the carrying platform 2 and the conveying device 3 are driven to move relative to each other, so that the carrying platform 2 and the conveying device 3 are close to each other, and the first connecting layer 16 and the first substrate 14 are close to each other;

[0183] S24, the positioning device 4 is used to assist the positioning of the first substrate 14 and the first connecting layer 16;

[0184] S25, the pressing device 5 is controlled to press the first connecting layer 16 and the first substrate 14;

[0185] S26, the first top plate 15 is attached to the side of the first connecting layer 16 away from the first substrate 14.

[0186] In this way, by driving the conveying device 3 and the carrying platform 2 to move relative to each other, and using the positioning device 4 to assist the accurate positioning of the first substrate 14 and the first connecting layer 16, the attachment precision of the first connecting layer 16 and the first substrate 14 after being pressed by the pressing device 5 is improved, thereby reducing defects of the first substrate 14 and the first connecting layer 16.

[0187] Specifically, in step S21, the carrying platform 2 can provide support for the first substrate 14, and the carrying platform 2 is provided with a mounting position, and the carrying platform 2 can form a negative pressure to adsorb the first substrate 14 on the mounting position. The surface shape of the carrying platform 2 is not strictly limited, and the carrying platform 2 can be approximately rectangular plate-shaped structure, for example.

[0188] In step S22, the conveying device 3 is provided with a mounting position, and the conveying device 3 can form a negative pressure to adsorb the first connecting layer 16 on the mounting position.

[0189] In step S23, the conveying device 3 can move or rotate to convey the first connecting layer 16 from a feeding position away from the carrying platform 2 to an attachment position close to the carrying platform 2. The distance between the conveying device 3 and the carrying platform 2 can be adjusted according to actual needs.

[0190] In step S24, the positioning device 4 can include a camera and a display screen, and the camera and the display screen can be located above the carrying platform 2, and the conveying device 3 can be located between the carrying platform 2 and the positioning device 4.

[0191] In step S25, the pressing device 5 can be a roller wheel for rolling pressing or a plate structure for pressing, and the pressing device 5 can roll along the length direction of the carrying platform 2 or move up and down along the height direction of the carrying platform 2, so that the first substrate 14 is tightly attached to the first connecting layer 16.

[0192] Referring to Figure 12 In some embodiments, the first top plate is attached to the side of the first connecting layer away from the first substrate (step S26), which includes:

[0193] S27, placing the first top plate 15 on the conveying device 3;

[0194] S28, driving the carrying platform 2 and the conveying device 3 to move relative to each other, so that the carrying platform 2 and the conveying device 3 move close to each other, and the first substrate 14 with the first connecting layer 16 and the first top plate 15 are moved close to each other;

[0195] S29, using the positioning device 4 to assist in positioning the first substrate 14 with the first connecting layer 16 and the first top plate 15;

[0196] S30, controlling the pressing device 5 to attach the first substrate 14 with the first connecting layer 16 to the first top plate 15.

[0197] In this way, by driving the conveying device 3 and the carrying platform 2 to move relative to each other, and using the positioning device 4 to assist in positioning the first substrate 14 with the first connecting layer 16 and the first top plate 15, the attachment precision of the first substrate 14 with the first connecting layer 16 and the first top plate 15 after being pressed by the pressing device 5 is improved, thereby reducing defects of the first substrate 14 with the first connecting layer 16 and the first top plate 15.

[0198] Specifically, in step S27, the conveying device 3 is provided with a mounting position, and the conveying device 3 can form a negative pressure to adsorb the first top plate 15 to the mounting position.

[0199] In step S28, the conveying device 3 can move or rotate to convey the first top plate 15 from a feeding position away from the carrying platform 2 to an attachment position close to the carrying platform 2. The distance between the conveying device 3 and the carrying platform 2 can be adjusted according to actual needs.

[0200] In step S29, the positioning device 4 can include a camera and a display screen, and the camera and the display screen can be located above the carrying platform 2, and the conveying device 3 can be located between the carrying platform 2 and the positioning device 4.

[0201] In step S30, the pressing device 5 can be a roller for rolling pressing or a plate structure for pressing, and the pressing device 5 can roll along the length direction of the bearing platform 2 or move up and down along the height direction of the bearing platform 2, so that the first substrate 14 with the first connecting layer 16 is tightly adhered to the first top plate 15.

[0202] Referring to Figure 13 In some embodiments, after the pressing device 5 adheres the first substrate 14 with the first connecting layer 16 to the first top plate 15, the method further comprises:

[0203] S31, using a pressure maintaining device to maintain the pressure of the first half 10 after the first substrate 14 and the first top plate 15 are adhered;

[0204] S32, using a bubble removing device to remove bubbles from the first half 10 after the pressure is maintained.

[0205] In this way, by maintaining the pressure of the first half 10 after the first substrate 14 and the first top plate 15 are adhered and removing bubbles, the adhesion between the first substrate 14 and the first top plate 15 can be increased, and the structural stability of the first half 10 can be improved.

[0206] Specifically, in step S31, the pressure and time of the pressure maintaining device can be preset, and then the first half 10 is placed in the pressure maintaining position of the pressure maintaining device, and the start button is pressed to maintain the pressure of the first half 10. In one embodiment, the pressure maintaining device is provided with a pressure maintaining mechanism, which can first maintain the pressure of the first substrate 14 and then maintain the pressure of the first top plate 15, or first maintain the pressure of the first top plate 15 and then maintain the pressure of the first substrate 14. In another embodiment, the pressure maintaining device is provided with an upper and lower pressure maintaining mechanism, which can simultaneously maintain the pressure of the first substrate 14 and the first top plate 15.

[0207] In step S32, during the adhering process, bubbles are generated between the first substrate 14, the first top plate 15 and the first connecting layer 16. The bubble removing device uses an air compressor to inject high pressure gas into the cabin, so that a working environment with high pressure is formed in the cabin. The first half 10 with bubbles is placed in the cabin, and the high pressure environment in the cabin and the air in the first half 10 form a pressure difference, so that the bubbles in the first half 10 are squeezed out, achieving the effect of removing bubbles.

[0208] Referring to Figure 14 In some embodiments, the first substrate 14 is realized by the following steps:

[0209] S1, forming a plurality of through holes 13 on a wafer;

[0210] S2, cutting the wafer along a predetermined path to obtain a plurality of first substrates 14.

[0211] Thus, by forming the through holes 13 on the wafer first, and then cutting the wafer along the predetermined path to obtain the first substrate 14, it can be determined whether the cutting path is the predetermined path according to the position of the through holes 13 on the first substrate 14, which facilitates the adjustment of the cutting path in advance, improves the production yield of the first substrate 14, and thus reduces the production cost of the first substrate 14.

[0212] Specifically, the predetermined path refers to the cutting path for cutting the first substrate 14 from the wafer, and the predetermined path also constitutes the contour shape of the edges of all the first substrates 14 cut from the wafer. That is, by cutting along the predetermined path, the first substrate 14 can be separated from the wafer.

[0213] The embodiment can use existing drawing or modeling software to design the cutting track on the wafer, and the drawing or modeling software used to design the predetermined path is not specifically limited in the embodiment. It can be understood that the step of designing the predetermined path can be performed when the current first substrate 14 is prepared, that is, the predetermined path of the current first substrate 14 is designed before the cutting operation; or the corresponding execution method can be saved when the cutting of the first substrate 14 of the same specification is performed for the first time, and the previously saved execution method can be called in the step of cutting the first substrate 14 of the same specification on the wafer of the same specification, and the existing predetermined path design scheme is used.

[0214] In step S2, the predetermined path can be set on the wafer based on the area of the required first substrate 14 and the area of the wafer, and one or more first substrates 14 can be cut along the predetermined path. It should be understood that the predetermined path can include one or more cutting track units, and one first substrate 14 can be obtained by cutting along each cutting track unit. The number of cutting track units on the wafer is determined based on the area of the required first substrate 14 and the area of the wafer, and in an effective embodiment, the number of cutting track units is the maximum number of first substrates 14 that can be obtained in the effective area of the wafer. In a possible embodiment, one cutting track unit corresponding to the edge shape of the first substrate 14 is set on the wafer, and regardless of the way the cutting track unit is set, the other areas outside the cutting track unit are not sufficient to form a second completely consistent cutting track unit. In another possible embodiment, two cutting track units corresponding to the edge shape of the first substrate 14 are set on the wafer, and regardless of the way the cutting track unit is set, the other areas outside the two cutting track units are not sufficient to form a third completely consistent cutting track unit. In another possible embodiment, n cutting track units corresponding to the edge shape of the first substrate 14 are set on the wafer, and regardless of the way the cutting track unit is set, the other areas outside the n cutting track units are not sufficient to form an (n+1)th completely consistent cutting track unit.

[0215] Referring to Figure 15 In some embodiments, the manufacturing method further comprises:

[0216] S300, providing the seal 200;

[0217] S400, laminating the third connecting layer 300 with the seal 200;

[0218] S500, laminating the seal 200 with the third connecting layer 300 with the first half 10 and the second half 20, and making the connecting hole 210 of part of the seal 200 communicate with the through hole 13.

[0219] In this way, the connecting hole 210 can communicate the through hole 13 with the external component, and the seal 200 can seal the connection between the first substrate 14 and the external component, reducing the probability of leakage of the reagent solution.

[0220] Specifically, in step S300, the number of seals 200 can be four, and the four seals 200 are laminated with the two ends of the first half 10 and the second half 20 respectively.

[0221] In step S400, the number of third connecting layers 300 can be four, and the four third connecting layers 300 can be laminated with the four seals 200 in sequence, for example, two of the third connecting layers 300 are laminated with two of the seals 300 first, and then the other two third connecting layers 300 are laminated with the other two seals 300; or the four third connecting layers 300 can be laminated with the four seals 200 at the same time.

[0222] In step S500, two of the seals 200 with the third connecting layer 300 can be laminated with the two ends of the bottom surface of the first half 10 first, and then the other two seals 200 with the third connecting layer 300 can be laminated with the two ends of the bottom surface of the second half 20; or two of the seals 200 with the third connecting layer 300 can be laminated with one end of the bottom surface of the first half 10 and the second half 20 first, and then the other two seals 200 with the third connecting layer 300 can be laminated with the other end of the bottom surface of the first half 10 and the second half 20; or the four seals 200 with the third connecting layer 300 can be laminated with the two ends of the bottom surface of the first half 10 and the second half 20 at the same time.

[0223] Referring to Figure 16 In some embodiments, the first half 10 and the second half 20 of the chip assembly 100 are arranged side by side along the width direction of the chip 1 on the frame 400 (step S200), which comprises:

[0224] S210, laminating the fourth connecting layer 500 with the two ends of the first half 10 and the second half 20;

[0225] S220, the first half 10 and the second half 20 with the fourth connecting layer 500 are attached to the frame 400.

[0226] In this way, the first half 10 and the second half 20 can be arranged side by side on the frame 400 along the width direction of the chip 1 to form the chip 1.

[0227] Specifically, in step S210, the number of the fourth connecting layer 500 can be four, two of which can be attached to the top surface of the first half 10 at both ends, and the other two of which can be attached to the top surface of the second half 20 at both ends; or the four fourth connecting layers 500 can be simultaneously attached to the top surface of the first half 10 and the second half 20 at both ends.

[0228] In step S220, the first half 10 with the fourth connecting layer 500 can be attached to the bottom surface of the frame 400 first, and then the second half 20 with the fourth connecting layer 500 is attached to the bottom surface of the frame 400; or the first half 10 and the second half 20 with the fourth connecting layer 500 can be simultaneously attached to the bottom surface of the frame 400.

[0229] In the description of the present specification, the description referring to the terms "one embodiment", "certain embodiments", "exemplary embodiment", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the exemplary description of the above terms does not necessarily mean the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0230] Although the embodiments of the present application have been shown and described, those skilled in the art can understand that various changes, modifications, replacements and variations can be made to these embodiments without departing from the principles and purposes of the present application, and the scope of the present application is defined by the claims and their equivalents.

Claims

1. A chip, characterized in that, The chip assembly includes a first half and a second half arranged side-by-side with the first half along the width direction of the chip, wherein the first half is provided with a first channel. The first half has a first bottom surface, and the first half has a through hole that penetrates the first bottom surface and communicates with the first channel; the second half has a second bottom surface that is flush with the first bottom surface, and the second bottom surface is a continuous and complete plane.

2. The chip according to claim 1, characterized in that, The first half and the second half are separate structures.

3. The chip according to claim 1, characterized in that, The first half includes a first substrate and a first top plate disposed opposite to the first substrate, the first channel being formed between the first substrate and the first top plate, the first substrate having the first bottom surface and having the through hole formed thereon.

4. The chip according to claim 3, characterized in that, The first half further includes a first connecting layer disposed between the first substrate and the first top plate, the first connecting layer having the first channel, the first channel penetrating the first connecting layer along the thickness direction of the first connecting layer.

5. The chip according to claim 3, characterized in that, The second half includes a second substrate and a second top plate disposed opposite to the second substrate. The second substrate has a second bottom surface, and a second channel is formed between the second substrate and the second top plate.

6. The chip according to claim 5, characterized in that, The second half further includes a second connecting layer disposed between the second substrate and the second top plate, the second connecting layer having the second channel extending through the second connecting layer along its thickness direction.

7. The chip according to claim 4, characterized in that, The second half includes a second substrate, a second top plate, and a second connecting layer disposed between the second substrate and the second top plate. The second substrate has a second bottom surface, and the second connecting layer is a solid sheet with a continuous structure.

8. The chip according to claim 7, characterized in that, The first connection layer and the second connection layer are an integral structure.

9. The chip according to any one of claims 5-8, characterized in that, The first top plate and the second top plate are separate structures.

10. The chip according to any one of claims 5-8, characterized in that, The first substrate and the second substrate are separate structures.

11. The chip according to any one of claims 1-8, characterized in that, The chip includes a sealing element disposed on the first bottom surface, and the sealing element has a connection hole communicating with the through hole.

12. The chip according to any one of claims 1-4, characterized in that, The second half is a single-piece plate.

13. The chip according to any one of claims 1-8, characterized in that, The chip includes a frame with a window, and the first half and the second half are both fixed to the frame and exposed at least partially through the window.

14. The chip according to any one of claims 1-8, characterized in that, The ends of the first channel along its length are converging, and the through hole is connected to the ends of the first channel along its length. When the chip is provided with a second channel, the ends of the second channel along its length are clustered together, and the through hole is connected to the ends of the second channel along its length.

15. The chip according to claim 14, characterized in that, The number of the first channels is multiple, and in the two outermost first channels, the ends of the first channels in the longitudinal direction converge towards each other; and / or, There are multiple second channels, and in the two outer second channels, the ends of the second channels in the length direction converge toward each other.

16. The chip according to claim 15, characterized in that, The number of the first channels is multiple and they are arranged in pairs. In a pair of first channels, the ends of the two first channels in the length direction converge towards each other. And / or, The number of the second channels is multiple and they are arranged in pairs. In a pair of second channels, the ends of the two second channels in the length direction converge toward each other.

17. The chip according to claim 15, characterized in that, In a pair of first channels, the two first channels are symmetrically arranged along their length; and / or, In a pair of second channels, the two second channels are arranged symmetrically along their length.

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