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WO2025102290A1 - Puce pour séquençage et procédé de fabrication associé - Google Patents

Puce pour séquençage et procédé de fabrication associé Download PDF

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Publication number
WO2025102290A1
WO2025102290A1 PCT/CN2023/131964 CN2023131964W WO2025102290A1 WO 2025102290 A1 WO2025102290 A1 WO 2025102290A1 CN 2023131964 W CN2023131964 W CN 2023131964W WO 2025102290 A1 WO2025102290 A1 WO 2025102290A1
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WO
WIPO (PCT)
Prior art keywords
layer
adsorption
sequencing chip
forming
isolation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2023/131964
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English (en)
Chinese (zh)
Inventor
刘定文
田畅
黄恒
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MGI Tech Co Ltd
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MGI Tech Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by MGI Tech Co Ltd filed Critical MGI Tech Co Ltd
Priority to PCT/CN2023/131964 priority Critical patent/WO2025102290A1/fr
Publication of WO2025102290A1 publication Critical patent/WO2025102290A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869—Methods for sequencing

Definitions

  • the present application relates to the field of gene sequencing technology, and in particular to a sequencing chip and a method for preparing the same.
  • sequencing chips generally use chemically modified surfaces (such as surfaces modified by APTMS (3-aminopropyl-trimethoxysilane)) to adsorb biological samples (for example, DNA (deoxyribonucleic acid) molecular nanospheres (DNBs), etc.), and chemically modified pattern arrays are made on the surface of a silicon substrate by photolithography and chemical vapor deposition (CVD), and then the surface chemical modification (such as APTMS) is used to adsorb biological samples.
  • Sequencing chips using the above structure need to go through chemical vapor deposition, spin gel, degumming and other processes before sequencing.
  • the sequencing chip using the above structure generally has the following defects:
  • the sequencing chip needs to be chemically treated on the surface and needs to be protected by spin gel before cutting. After cutting, wet gel stripping is required. There is a risk of residual gel after gel stripping, which in turn affects the preparation yield of the sequencing chip and causes unstable sequencing quality of the sequencing chip.
  • sequencing chips The procurement cost of sequencing chips is high, and the preparation process is relatively complicated. After the sequencing chips are obtained from suppliers, they need to undergo CVD, gel coating and other treatments, which further increases the cost of the sequencing chips.
  • the present application also provides a sequencing chip prepared by the aforementioned preparation method.
  • the present application provides a method for preparing a sequencing chip, comprising:
  • a plurality of hole structures are formed in the isolation layer so that the adsorption layer is exposed through the hole structures.
  • the step of forming an adsorption layer for adsorbing biological samples on the surface of the substrate includes:
  • An adsorption material for adsorbing biological samples is deposited on the surface of the substrate to form the adsorption layer.
  • the adsorption material includes at least one of titanium nitride, titanium oxide, silver, zirconium oxide, and zinc oxide.
  • the adsorption layer has a thickness of 20 nm to 500 nm.
  • the isolation layer is formed by depositing an isolation material on the surface of the adsorption layer, and the isolation material includes silicon oxide or silicon nitride.
  • the step of forming the hole structure in the isolation layer includes:
  • the remaining photoresist layer and the anti-reflective layer are removed.
  • the step of forming a photoresist layer on the surface of the anti-reflective layer includes:
  • the photoresist layer is formed on the surface of the adhesion promoting coating layer.
  • the anti-reflection layer is formed by depositing an anti-reflection material on the surface of the isolation layer, and the anti-reflection material includes silicon oxynitride or a bottom anti-reflection coating.
  • the step of forming the hole structure in the isolation layer includes:
  • the embossing layer is removed.
  • the step of forming an adsorption layer for adsorbing biological samples on the surface of the substrate includes:
  • the adsorption layer for adsorbing biological samples is formed on the surface of the buffer layer.
  • the buffer layer is formed by depositing a buffer material on the surface of the substrate, and the buffer material includes silicon oxide or silicon nitride.
  • the pore structure has a pore diameter of 100 nm to 300 nm; and/or,
  • the depth of the pore structure is 20 nm to 150 nm; and/or,
  • the distance between the centers of two adjacent pore structures is 200nm-1000nm.
  • the present application also provides a sequencing chip, comprising: a substrate, an adsorption layer and an isolation layer, wherein the adsorption layer The attachment layer is located on the surface of the substrate, and the adsorption layer is used to adsorb biological samples; the isolation layer is located on the surface of the adsorption layer, and the isolation layer has a plurality of pore structures, and the adsorption layer is exposed from the pore structures.
  • the adsorption layer includes an adsorption material for adsorbing biological samples, and the adsorption material includes at least one of titanium nitride, titanium oxide, silver, zirconium oxide, and zinc oxide.
  • the adsorption layer has a thickness of 20 nm to 500 nm.
  • the material of the isolation layer includes silicon oxide or silicon nitride.
  • a buffer layer is further provided between the substrate and the adsorption layer, and a material of the buffer layer includes silicon oxide or silicon nitride.
  • the pore structure has a pore diameter of 100 nm to 300 nm; and/or,
  • the depth of the pore structure is 20 nm to 150 nm; and/or,
  • the distance between the centers of two adjacent pore structures is 200nm-1000nm.
  • the sequencing chip and preparation method thereof provided in the embodiments of the present application have been comprehensively optimized in terms of the structure and preparation process of the sequencing chip.
  • An adsorption layer such as titanium nitride and an isolation layer such as silicon oxide are deposited on a substrate, and then a nanometer-sized pore structure array is formed on the isolation layer.
  • the adsorption layer exposed by the pore structure is used to adsorb biological samples.
  • the process is simple and the pore structure has high dimensional accuracy, thereby improving the sequencing stability and quality of the sequencing chip.
  • the pore structure on the isolation layer can achieve isolation between adjacent pore structures, thereby achieving physical isolation between samples (such as DNA molecule nanospheres), solving the problem of signal interference between samples in high-density sequencing chips, and is beneficial to improving the sequencing quality of high-density sequencing chips.
  • the sequencing chip can be reused, thereby saving costs.
  • FIG1 is a schematic diagram of the structure of a sequencing chip according to an embodiment of the present application.
  • FIG. 2 is a schematic diagram of the process of preparing the sequencing chip of the present application.
  • FIG3 is a schematic diagram of a process for preparing a sequencing chip using an etching method according to an embodiment of the present application.
  • FIG. 4 a is a cross-sectional schematic diagram of the chip structure during the execution of step 101 and step 102 in FIG. 3 .
  • FIG. 4 b is a schematic cross-sectional view of the chip structure in the stage of executing step 103 in FIG. 3 .
  • FIG. 4 c is a schematic cross-sectional view of the chip structure in the stage of executing step 104 in FIG. 3 .
  • FIG. 4 d is a schematic cross-sectional view of the chip structure in the stage of executing step 105 in FIG. 3 .
  • FIG. 4 e is a schematic cross-sectional view of the chip structure at the stage of executing step 106 in FIG. 3 .
  • FIG. 4 f is a schematic cross-sectional view of the chip structure at the stage of executing step 107 in FIG. 3 .
  • FIG. 4g is a cross-sectional schematic diagram of the chip structure at the stage of executing step 108 in FIG. 3 .
  • FIG5 is a schematic diagram of a process for preparing a sequencing chip using an imprinting method according to an embodiment of the present application.
  • FIG. 6 a is a cross-sectional schematic diagram of the chip structure in the stage of executing step 201 in FIG. 5 .
  • FIG. 6 b is a cross-sectional schematic diagram of the chip structure in the stage of executing step 202 in FIG. 5 .
  • FIG. 6 c is a schematic cross-sectional view of the chip structure in the stage of executing step 203 in FIG. 5 .
  • FIG. 6 d is a cross-sectional schematic diagram of the chip structure in the stage of executing step 204 in FIG. 5 .
  • FIG. 6 e is a schematic cross-sectional view of the chip structure in the stage of executing step 205 in FIG. 5 .
  • FIG. 6 f is a schematic cross-sectional view of the chip structure in the stage of executing step 206 in FIG. 5 .
  • FIG. 6g is a cross-sectional schematic diagram of the chip structure at the stage of executing step 207 in FIG. 5 .
  • an embodiment of the present application provides a sequencing chip 100, wherein the sequencing chip 100 includes a substrate 1, an adsorption layer 2 located on the surface of the substrate 1, and an isolation layer 3 located on the surface of the adsorption layer 2.
  • the substrate 1 may be, for example, a silicon substrate (silicon material plate).
  • the adsorption layer 2 is used to adsorb biological samples.
  • the adsorption layer 2 may be formed by an adsorption material that can adsorb biological samples.
  • the isolation layer 3 has a plurality of pore structures 4, and the adsorption layer 2 can be exposed by the pore structures 4, that is, the adsorption layer 2 at the bottom of the pore structures 4 is exposed, so that the biological sample can be adsorbed and fixed in the pore structures 4, and each pore structure 4 can serve as a reaction area of the sequencing chip 100.
  • the adsorption material may include at least one of titanium nitride, titanium oxide, silver, zirconium oxide, zinc oxide, etc.
  • the adsorption material may be titanium nitride or titanium oxide.
  • the thickness of the adsorption layer 2 may be 20 nm to 500 nm, further 30 nm to 300 nm, further 50 nm to 100 nm.
  • the thickness of the adsorption layer 2 may be 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 120 nm, 150 nm, 180 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm or 500 nm, etc.
  • the isolation layer 3 is made of silicon oxide, silicon nitride, or other oxides or other nitrides.
  • the thickness of the isolation layer 3 may be 20 nm to 150 nm, and the thickness of the isolation layer 3 may be designed according to the actual depth of the pore structure 4 .
  • the size of the pore structure 4, including the pore depth, pore diameter, and pore shape, can be designed according to the capacity required for each reaction area in the sequencing chip 100. Specifically, a plurality of pore structures 4 can be arranged in an array. In some embodiments, the depth of the pore structure 4 can be 20nm to 150nm, further 30nm to 100nm. Exemplarily, the depth of the pore structure 4 can be 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm, 110nm, 120nm, 130nm, 140nm or 150nm, etc.
  • the pore diameter of the pore structure 4 can be 100nm to 300nm, further 120nm to 250nm, and further 150nm to 200nm.
  • the pore size of the pore structure 4 can be 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm or 300 nm, etc.
  • the distance between the centers of two adjacent pore structures 4 may be 200 nm to 1000 nm. Further, 250nm to 800, and further 300nm to 600. Exemplarily, the distance between the centers of the holes of two adjacent pore structures 4 can be 200nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 550nm, 600nm, 650nm, 700nm, 750nm, 800nm, 850nm, 900nm, 950nm or 1000nm, etc. High-density sequencing can be achieved and sequencing efficiency can be improved by adjusting the pore spacing. In addition, the samples (such as nanospheres) between adjacent pore structures 4 can be made not to interfere with each other by adjusting the pore spacing, thereby improving sequencing quality.
  • a buffer layer 5 is further provided between the substrate 1 and the adsorption layer 2, and the material of the buffer layer 5 includes silicon oxide, silicon nitride, or other oxides or other nitrides.
  • a 20nm to 1000nm buffer layer 5, such as a SiO2 layer can be first deposited on the surface of the substrate 1.
  • the sequencing chip 100 provided in the embodiment of the present application has been comprehensively optimized in structure.
  • an adsorption layer 2 such as titanium nitride and an isolation layer 3 such as silicon oxide
  • the isolation layer 3 has a large number of nanoscale pore structures 4 arranged in an array
  • the adsorption layer 2 can be exposed to adsorb the biological sample within the reaction area defined by the pore structure 4, thereby improving the sequencing stability and quality of the sequencing chip 100; moreover, the pore structure 4 on the isolation layer 3 can achieve isolation between adjacent pore structures 4, thereby achieving physical isolation between samples (such as DNA nanoballs), solving the problem of signal interference between samples in high-density sequencing chips, and facilitating improving the sequencing quality of high-density sequencing chips; in addition, the sequencing chip 100 can be reused, thereby saving costs.
  • the present application also provides a method for preparing the aforementioned sequencing chip, which specifically includes the following steps:
  • Step S1 forming an adsorption layer for adsorbing biological samples on the surface of a substrate.
  • Step S2 forming an isolation layer on the surface of the adsorption layer.
  • Step S3 forming a plurality of hole structures in the isolation layer so that the adsorption layer is exposed from the hole structures to obtain the sequencing chip.
  • step S1 before forming the adsorption layer, the preparation method further includes:
  • a buffer layer is formed on the surface of the substrate, wherein the adsorption layer is located on the surface of the buffer layer.
  • the buffer layer is formed by depositing a buffer material on the surface of the substrate, and the buffer material includes silicon oxide, silicon nitride, or other oxides or other nitrides.
  • step S1 the method for forming the adsorption layer includes:
  • adsorption material for adsorbing biological samples on the surface of the substrate to form the adsorption layer, wherein the adsorption material includes at least one of titanium nitride, titanium oxide, silver, zirconium oxide, zinc oxide, etc., for example, titanium nitride or titanium oxide.
  • the isolation layer is formed by depositing an isolation material on the surface of the adsorption layer, and the isolation material includes silicon oxide, silicon nitride, or other oxides or other nitrides.
  • a method for patterning the isolation layer is an etching method: in step S3, forming the hole structure in the isolation layer specifically includes the following steps:
  • Step S31 forming an anti-reflection layer on the surface of the isolation layer.
  • the anti-reflection layer is formed by depositing an anti-reflection material on the surface of the isolation layer, and the anti-reflection material includes silicon oxynitride or a bottom anti-reflection coating (Bottom Anti-Reflection Coating, BARC).
  • Step S32 forming a photoresist layer on the surface of the anti-reflection layer.
  • an adhesion-promoting coating layer needs to be formed on the surface of the anti-reflective layer.
  • the photoresist layer is located on a surface of the adhesion promoting coating layer.
  • Step S33 forming an etching hole in the photoresist layer.
  • Step S34 removing the adhesion-promoting coating, the anti-reflection layer and the isolation layer corresponding to the etching hole to expose the adsorption layer.
  • Step S35 removing the remaining photoresist layer, the adhesion-promoting coating layer and the anti-reflection layer.
  • step S3 forming the hole structure in the isolation layer specifically includes the following steps:
  • Step S31' forming an embossed adhesive layer on the surface of the isolation layer.
  • Step S32' forming an imprint layer having etching holes corresponding to the hole structure on the imprint glue layer.
  • Step S33' removing the isolation layer corresponding to the etching hole to expose the adsorption layer.
  • Step S34' removing the embossing layer.
  • the preparation method of the sequencing chip provided in the embodiment of the present application has been comprehensively optimized in the preparation process.
  • an adsorption layer such as titanium nitride and an isolation layer such as silicon oxide
  • the isolation layer such as silicon oxide
  • the adsorption layer exposed by the pore structure is used to adsorb biological samples.
  • the process is simple and the pore structure has high dimensional accuracy, thereby improving the sequencing stability and quality of the sequencing chip. It effectively reduces the steps of sequencing chip preparation, avoids the risk of residual glue during photoresist removal, effectively reduces the processes of glue coating, APTMS CVD, and glue removal, improves the yield of sequencing chips, and reduces labor costs.
  • Step 101 As shown in FIG. 4a, a substrate 1 is provided.
  • an 8-inch or 12-inch silicon substrate 1 is provided, for example, a silicon substrate with a thickness of about 725 ⁇ m.
  • this embodiment does not specifically limit the type and size of the substrate, and the corresponding selection and Adjustment.
  • Step 102 depositing silicon oxide material on the surface of the substrate 1 to form a buffer layer 5 .
  • silicon oxide is deposited on the surface of the silicon substrate 1 by chemical vapor deposition to form a buffer layer 5 with a thickness ranging from 20nm to 1000nm, for example, silicon dioxide with a thickness of about 35nm is deposited as the buffer layer 5, which can be selected and adjusted accordingly according to actual needs. It is understandable that the buffer layer 5 may not be formed on the substrate 1.
  • Step 103 as shown in FIG. 4 b , an adsorption material for adsorbing biological samples is deposited on the surface of the buffer layer 5 to form an adsorption layer 2 .
  • an adsorption material for adsorbing biological samples is deposited on the surface of the buffer layer 5 to form an adsorption layer 2 for adsorbing biological samples with a thickness ranging from 20nm to 500nm.
  • a layer of titanium nitride adsorption material with a thickness of about 60nm is deposited on the buffer layer 5 by physical vapor deposition.
  • the adsorption layer can be embodied in the form of an adsorption film. If the thickness of the adsorption film is too thin, it will be difficult to implement its deposition process and there will be uniformity problems. If the thickness is too thick, it will affect the sequencing quality. Therefore, the thickness of the adsorption layer 2 can be controlled within the above-mentioned optional thickness range, thereby ensuring process stability while ensuring sequencing quality.
  • the adsorption material may be TiN, and the adsorption layer is a TiN layer, but it is not limited thereto, and the adsorption material may also be at least one of TiO 2 , Ag, ZrO 2 , ZnO, etc., and may be adjusted and selected accordingly according to actual needs or possible needs.
  • the biological sample may be, for example, a DNA nanosphere, but is not limited thereto, and may be selected and adjusted accordingly according to actual needs.
  • Step 104 deposit silicon oxide material on the adsorption layer 2 to form an isolation layer 3 .
  • silicon oxide material is deposited on the adsorption layer 2 for adsorbing biological samples to form an isolation layer 3 with a thickness ranging from 20nm to 150nm.
  • silicon dioxide with a thickness of about 45nm is deposited as the isolation layer 3 by chemical vapor deposition.
  • the thickness of the isolation layer 3 can be controlled within the above-mentioned optional thickness range, thereby ensuring process stability while ensuring sequencing quality.
  • Step 105 referring to FIG. 4 d , an anti-reflection material is deposited on the isolation layer 3 to form an anti-reflection layer 10 .
  • an anti-reflection material is deposited on the isolation layer 3 to form an anti-reflection material layer 10 with a thickness ranging from 50 nm to 70 nm.
  • the anti-reflection material may be a SiON material, and the anti-reflection layer 10 may be a SiON layer.
  • this embodiment does not have The type and thickness of the anti-reflection material layer can be selected and adjusted accordingly according to actual needs.
  • Step 106 as shown in FIG. 4 e , a photoresist layer 20 is formed on the surface of the anti-reflection layer 10 , and exposure and development are performed to form etching holes 21 on the photoresist layer 20 .
  • a layer of HMDS is first spin-coated on the surface of the anti-reflective layer 10 as an adhesion-enhancing coating (not shown), and then photoresist is spin-coated on the surface of the adhesion-enhancing coating to form a photoresist layer 20. Then, a DUV photolithography machine is used to perform exposure and development operations to form a regularly arranged circular hole array pattern (i.e., etching holes 21) on the photoresist layer 20.
  • a DUV photolithography machine is used to perform exposure and development operations to form a regularly arranged circular hole array pattern (i.e., etching holes 21) on the photoresist layer 20.
  • the thickness of the photoresist layer 20 may range from 250 nm to 350 nm.
  • Step 107 referring to FIG. 4 f , dry etching is used to etch through the anti-reflection layer 10 and the isolation layer 3 in the etching hole 21 to form a plurality of hole structures 4 , so that a portion of the surface of the adsorption layer 2 is exposed through the hole structures 4 .
  • the adhesion promoting coating within the hole is also removed simultaneously.
  • the anti-reflection layer 10 and the isolation layer 3 are dry etched to form a plurality of hole structures 4 with a preset aperture d on the anti-reflection layer 10 and the isolation layer 3.
  • the preset aperture d may range from 100 nm to 300 nm, and may be adjusted and set accordingly according to actual needs.
  • the thickness h (ie, the hole depth) of the hole wall of each hole structure 4 may range from 20 nm to 150 nm, and may be selected and adjusted accordingly according to actual needs.
  • the depth of the hole structure 4 can be controlled within the above-mentioned optional thickness range, thereby ensuring process stability while ensuring sequencing quality.
  • a pitch that is, the distance s between the centers of each two adjacent holes, ranges from 200 nm to 1000 nm, and can be adjusted and set accordingly according to actual needs.
  • Step 108 as shown in Figure 4g, combined with reference to Figure 1, the remaining photoresist layer 20 is removed by dry etching and wet etching, and then the anti-reflective layer 10 is etched away by dry etching to form a hole structure 4 on the surface of the substrate 1, thereby obtaining a sequencing chip 100.
  • the pore structure 4 is arranged in a regular array, the bottom pore size of the pore structure 4 can be about 200nm, the pore spacing between adjacent pore structures 4 can be about 715nm, the depth of the pore structure 4 can be about 45nm, and the bottom surface of the pore structure 4 is an adsorption layer 2 that can adsorb nanospheres.
  • the method for preparing a sequencing chip using the imprinting method is described in detail below, and specifically comprises the following steps:
  • Step 201 provides a substrate 1. This step is substantially the same as the aforementioned step 101.
  • This step is substantially the same as the aforementioned step 101.
  • Step 202 as shown in FIG. 6 b , an adsorption material for adsorbing biological samples is deposited on the surface of the substrate 1 to form an adsorption layer 2 .
  • step 203 as shown in FIG. 6 c , a silicon oxide material is deposited on the surface of the adsorption layer 2 to form an isolation layer 3 .
  • This step is substantially the same as the aforementioned step 104. Please refer to the aforementioned step 104 for details, and no further elaboration is given here.
  • Step 204 as shown in FIG. 6 d, a layer of adhesion promoter is spin-coated on the surface of the isolation layer 3, and then a layer of embossing adhesive layer 40 is spin-coated thereon.
  • step 205 as shown in FIG. 6 e , a pre-prepared working mold is used to emboss the embossed adhesive layer 40 , and after curing and demolding processes, the pattern of the working mold is transferred to the embossed adhesive layer 40 , thereby forming an embossed layer 50 with etching holes 51 .
  • step 206 as shown in FIG. 6 f , the residual glue and the isolation layer 3 in the etching hole 51 are etched away by dry etching to form a hole structure 4 , and the adsorption layer 2 at the bottom of the hole structure 4 is exposed.
  • Step 207 as shown in FIG6g, the imprinting layer 50 is completely removed by dry etching and wet etching to obtain a sequencing chip, wherein the sequencing chip is a sequencing chip without a buffer layer.
  • the bottom pore size of the sequencing chip pore structure 4 can be about 200nm, the distance between adjacent pore structures can be about 715nm, the depth of the pore structure 4 can be about 45nm, and the bottom surface of the pore structure 4 is a titanium nitride adsorption layer that can adsorb nanospheres.
  • the structure and size of the sequencing chip can refer to the structure and size involved in the preparation method of the sequencing chip in the previous embodiment, so they are not described in detail.

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Abstract

Puce pour séquençage et procédé de préparation associé, le procédé de préparation comportant : la formation sur la surface d'un substrat (1) d'une couche d'adsorption (2) pour adsorber des échantillons biologiques ; la formation d'une couche d'isolation (3) sur la surface de la couche d'adsorption (2) ; et la formation d'une pluralité de structures de pores (4) dans la couche d'isolation (3), de sorte que la couche d'adsorption (2) est exposée à partir des structures de pores (4), ce qui permet d'obtenir une puce pour séquençage. En déposant une couche d'adsorption et une couche d'isolation sur un substrat, en constituant un réseau de pores dans la couche d'isolation, puis en utilisant la couche d'adsorption pour adsorber des échantillons biologiques, la puce de séquençage fait intervenir un processus simple et présente des structures de pores d'une grande précision dimensionnelle, ce qui améliore la stabilité et la qualité du séquençage des puces de séquençage ; une isolation physique entre les échantillons peut être réalisée, ce qui résout le problème de l'interférence des signaux entre les échantillons dans une puce de séquençage à haute densité ; en outre, la puce de séquençage peut être utilisée de manière répétée, ce qui permet de réaliser des économies de coûts.
PCT/CN2023/131964 2023-11-16 2023-11-16 Puce pour séquençage et procédé de fabrication associé Pending WO2025102290A1 (fr)

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CN110964793A (zh) * 2018-09-30 2020-04-07 深圳华大智造极创科技有限公司 测序芯片的制备方法及测序芯片、测序仪
WO2020154831A1 (fr) * 2019-01-28 2020-08-06 深圳华大生命科学研究院 Puce pour séquençage et procédé de fabrication correspondant
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WO2023049192A1 (fr) * 2021-09-22 2023-03-30 Ultima Genomics, Inc. Procédés et systèmes de fonctionnalisation de substrat
CN116103134A (zh) * 2021-11-10 2023-05-12 深圳华大生命科学研究院 测序芯片及其制备方法

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