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EP-4060014-B1 - TEST CHIP, PREPARATION METHOD THEREFOR AND METHOD OF USE THEREOF, AND REACTION SYSTEM

EP4060014B1EP 4060014 B1EP4060014 B1EP 4060014B1EP-4060014-B1

Inventors

  • ZHAO, ZIJIAN
  • LAU, Shinying
  • DENG, Ruijun

Dates

Publication Date
20260506
Application Date
20191113

Claims (15)

  1. A detection chip (100), comprising: a first substrate (10); a micro-cavity definition layer (11) on the first substrate (10) and defining a plurality of micro-reaction chambers (110); and a heating electrode (12) on the first substrate (10) and closer to the first substrate (10) than the micro-cavity definition layer (11), configured to release heat after being energized, wherein the heating electrode (12) comprises a first electrode portion (121) and at least one second electrode portion (122) electrically connected to the first electrode portion (121), orthographic projections of the plurality of micro-reaction chambers (110) on the first substrate (10) are within an orthographic projection of the first electrode portion (121) on the first substrate (10), the orthographic projections of the plurality of micro-reaction chambers (110) on the first substrate (10) do not overlap with an orthographic projection of the second electrode portion (122) on the first substrate (10), and a resistance value of the first electrode portion (121) is greater than a resistance value of the second electrode portion (122), characterized by that the heating electrode (12) is located between the first substrate (10) and the micro-cavity definition layer (11), and the heating electrode (12) is a planar electrode made of a transparent conductive material.
  2. The detection chip (100) according to claim 1, wherein a thickness of the first electrode portion (121) in a direction perpendicular to the first substrate (10) is smaller than a thickness of the second electrode portion (122) in the direction perpendicular to the first substrate (10).
  3. The detection chip (100) according to claim 1 or 2, wherein a material of the first electrode portion (121) and a material of the second electrode portion (122) are a transparent conductive material.
  4. The detection chip (100) according to any one of claims 1-3, further comprising a hydrophilic layer (13), wherein the hydrophilic layer (13) covers a sidewall (111) and a bottom (112) of each of the plurality of micro-reaction chambers (110); for example, a material of the hydrophilic layer (13) is silicon oxide that is subjected to a surface alkali treatment or silicon oxynitride that is subjected to a surface alkali treatment.
  5. The detection chip (100) according to any one of claims 1-4, further comprising a hydrophobic layer (14), wherein the hydrophobic layer (14) covers a spacing region between the plurality of micro-reaction chambers (110) in the micro-cavity definition layer (11); for example, a material of the hydrophobic layer (14) is silicon nitride that is subjected to a plasma modification treatment.
  6. The detection chip (100) according to any one of claims 1-5, further comprising a control circuit layer (15) and a first insulating layer (16) which are sequentially stacked, wherein the control circuit layer (15) comprises a control circuit (151), the first insulating layer (16) comprises a via hole (161), the control circuit (151) is electrically connected to the heating electrode (12) through the via hole (161), and the control circuit (151) is configured to apply an electrical signal to the heating electrode (12) to energize the heating electrode (12).
  7. The detection chip (100) according to claim 6, wherein the control circuit layer (15) further comprises a connection electrode (152), and the connection electrode (152) is not covered by the first insulating layer (16) and is exposed to atmosphere.
  8. The detection chip (100) according to claim 7, wherein the detection chip (100) comprises a reaction region (21), a peripheral region (22), and a cooling region (23), the plurality of micro-reaction chambers (110) are in the reaction region (21), the connection electrode (152) is in the peripheral area (22), the first electrode portion (121) is in the reaction region (21), and the second electrode portion (122) is in the cooling region (23).
  9. The detection chip (100) according to any one of claims 1-8, further comprising a second insulating layer (17), wherein the second insulating layer (17) is between the heating electrode (12) and the micro-cavity definition layer (11).
  10. The detection chip (100) according to any one of claims 1-9, further comprising a second substrate (18), wherein the second substrate (18) is opposite to the first substrate (10), and a gap is between the second substrate (18) and the first substrate (10) so as to form a space for containing liquid; for example, the first substrate (10) and the second substrate (18) comprise glass substrates, and a material of the micro-cavity definition layer (11) is photoresist.
  11. A reaction system (200), comprising a control device (210) and the detection chip (100, 200) according to any one of claims 1-10, wherein the control device (210) is electrically connected to the detection chip (100, 200), and is configured to apply an electrical signal to the detection chip (100, 200).
  12. A method for manufacturing the detection chip (100) according to any one of claims 1-3, comprising: forming the heating electrode (12) on the first substrate (10); and forming the micro-cavity definition layer (11) on the heating electrode (12).
  13. The method according to claim 12, wherein, in a case where the detection chip (100) further comprises a hydrophilic layer (13), the method further comprises: forming a silicon oxide layer or a silicon oxynitride layer on the micro-cavity definition layer (11); and immersing a portion, covering a sidewall (111) and a bottom (112) of each of the plurality of micro-reaction chambers (110), of the silicon oxide layer or the silicon oxynitride layer with an alkaline solution to perform surface modification, so as to form the hydrophilic layer (13).
  14. The method according to claim 13, wherein the alkaline solution is a potassium hydroxide solution; for example, a mass fraction of the potassium hydroxide solution is 0.4%.
  15. A method for operating the detection chip (100) according to any one of claims 1-10, comprising: allowing a reaction system solution to enter the plurality of micro-reaction chambers (110); and energizing the heating electrode (12) to allow the heating electrode (12) to release heat.

Description

TECHNICAL FIELD Embodiments of the present disclosure relate to a detection chip, a method for manufacturing a detection chip, a method for operating a detection chip, and a reaction system. BACKGROUND The polymerase chain reaction (PCR) is a molecular biology technology used for amplifying specific DNA fragments, and the PCR can copy a large amount of deoxyribonucleic acid (DNA) and greatly increase the amount of DNA. Different from traditional PCR technology, digital polymerase chain reaction (dPCR) chip technology can implement the absolute quantitative detection of single molecule DNA by sufficiently diluting the nucleic acid sample to allow the amount of target molecules (i.e., DNA templates) in each reaction unit to be less than or equal to one, performing PCR amplification on the target molecule in each reaction unit, respectively, and then statistically analyzing the fluorescent signal of each reaction unit after the amplification. Because the dPCR has advantages of high sensitivity, strong specificity, high detection throughput, accurate quantification, etc., the dPCR is widely used in the fields of clinical diagnosis, gene instability analysis, single-cell gene expression, environmental microorganism detection, prenatal diagnosis, etc. EP2332654A1 discloses a system for cycling liquid samples, e.g. in PCR, through a series of temperature excursions, comprising: a plurality of open-top reaction vessels for containing said samples, said reaction vessels being enclosed by one or more covers; a temperature-controlled block for generating or adsorbing heat thermally coupled to said reaction vessels; a detection arrangement for detecting radiation disposed in an emission beam path to detect emission beams emitted from said samples received through said one or more covers; a heating arrangement for generating heat including a heating element disposed between said reaction vessels and said detection arrangement and being thermally coupled to said one or more covers, said heating element including an optically transparent substrate provided with one or more heating lines, said heating lines being disposed in said emission beam path in a manner to obtain a predetermined minimum optical transmission of said heating element; a controller, set up to control cycling of the samples. It further relates to a method for cycling liquid samples using said system. EP 3 912 720 A1 describes another PCR system of the prior art. SUMMARY At least one embodiment of the present disclosure provides a detection chip, a reaction system, a method for manufacturing the detection chip and a method for operating the detection chip, which can solve one or more problems in the art. The object is achieved by the features of the respective independent claims. Further embodiments are defined in the respective dependent claims. BRIEF DESCRIPTION OF THE DRAWINGS In order to clearly illustrate the technical solution of the embodiments of the present disclosure, the drawings of the embodiments will be briefly described in the following. It is obvious that the described drawings in the following are only related to some embodiments of the present disclosure and thus are not limitative of the present disclosure. FIG. 1 is a schematic block diagram of a detection chip provided by some embodiments of the present disclosure;FIG. 2 is a schematic planar diagram of a detection chip provided by some embodiments of the present disclosure;FIG. 3A is a schematic cross-sectional diagram of the detection chip illustrated in FIG. 2 along A-A';FIG. 3B is a schematic cross-sectional diagram of the detection chip illustrated in FIG. 2 along B-B';FIG. 4 is a schematic cross-sectional diagram of another detection chip provided by some embodiments of the present disclosure;FIG. 5A is a schematic diagram of a surface hydrophilicity and hydrophobicity test performed on a micro-reaction chamber before surface modification;FIG. 5B is a schematic diagram of a surface hydrophilicity and hydrophobicity test performed on a micro-reaction chamber after surface modification;FIG. 6 is a schematic block diagram of a reaction system provided by some embodiments of the present disclosure;FIG. 7 is a schematic flowchart of a method for manufacturing a detection chip provided by some embodiments of the present disclosure;FIG. 8 is a schematic flowchart of another method for manufacturing a detection chip provided by some embodiments of the present disclosure;FIG. 9A is a schematic scanning electron microscope diagram of a micro-cavity definition layer of a detection chip provided by some embodiments of the present disclosure;FIG. 9B is a schematic scanning electron microscope diagram of a micro-reaction chamber of a detection chip provided by some embodiments of the present disclosure; andFIG. 10 is a schematic flowchart of a method for operating a detection chip provided by some embodiments of the present disclosure. DETAILED DESCRIPTION In order to make objects, technical