WO2018126696A1 - 基因测序芯片、基因测序设备及基因测序方法 - Google Patents
基因测序芯片、基因测序设备及基因测序方法 Download PDFInfo
- Publication number
- WO2018126696A1 WO2018126696A1 PCT/CN2017/098024 CN2017098024W WO2018126696A1 WO 2018126696 A1 WO2018126696 A1 WO 2018126696A1 CN 2017098024 W CN2017098024 W CN 2017098024W WO 2018126696 A1 WO2018126696 A1 WO 2018126696A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- substrate
- electrode
- gene sequencing
- insulating layer
- signal
- Prior art date
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/333—Ion-selective electrodes or membranes
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
- G01N33/48721—Investigating individual macromolecules, e.g. by translocation through nanopores
-
- 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
- C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3275—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
- G01N27/3276—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction being a hybridisation with immobilised receptors
Definitions
- the present disclosure relates to the field of gene sequencing, and in particular to a gene sequencing chip, a gene sequencing device, and a gene sequencing method.
- Gene sequencing technology is the most commonly used technology in modern molecular biology research. Since the development of the first generation of gene sequencing in 1977, gene sequencing technology has made considerable progress, including the first generation of sanger sequencing technology, the second generation of Qualcomm Sequencing technology, third-generation single-molecule sequencing technology and fourth-generation nanopore sequencing technology. The current mainstream sequencing technology is still based on the second generation of high-throughput sequencing.
- the second generation of high-throughput sequencing technologies include Illumina's edge synthesis sequencing technology, Thermo Fisher's ion semiconductor sequencing technology, ligation sequencing technology and Roche's pyrosequencing technology.
- the ion semiconductor gene sequencing method comprises the following steps: first, preparing the library, breaking the DNA to be detected into a small chain by a spray method, and adding a different linker at both ends of the small chain to construct a single-stranded DNA library; Emulsion amplification, these single-stranded DNA were bound to water-oil coated magnetic beads of about 20 um in diameter, and incubated and annealed thereon. After amplification, each small chain will be amplified approximately 1 million times to achieve the amount of DNA required for subsequent sequencing. Finally, sequencing is performed, and the magnetic beads are placed in the micropores. When sequencing, one nucleotide molecule continuously flows through the micropores of the chip.
- the deoxynucleotide is complementary to the DNA molecule in the specific micropore, the deoxynucleotide is It is synthesized into a DNA molecule and releases hydrogen ions, and the pH of the solution of the well changes. When the ion sensor detects a change in pH, it instantly changes from chemical information to digital electronic information.
- the above detection method requires an ion sensor to be fabricated under the micropores.
- the ion sensor adopts a CMOS process, including two Metal-Oxide-Semiconductor Field-Effect Transistors (MOSFETs) and one ion-sensitive field. Ion-Sensitive Field-Effect Transistor (ISFET).
- MOSFETs Metal-Oxide-Semiconductor Field-Effect Transistors
- ISFET Ion-Sensitive Field-Effect Transistor
- the present disclosure provides a gene sequencing chip that does not require any FET, has a simple manufacturing process, and can greatly reduce manufacturing difficulty and cost.
- the present disclosure also relates to a gene sequencing device including the gene sequencing chip.
- the present disclosure also provides a gene sequencing method which can directly and conveniently perform gene sequencing using the gene sequencing chip of the present disclosure.
- the present disclosure provides a gene sequencing chip comprising: a substrate; an electrode on the substrate; a signal lead, the signal lead being connected to the electrode, configured to input a signal to the electrode and a signal output of the electrode sensing; a first insulating layer, the first insulating layer is located on a side of the electrode away from the substrate; and a retaining wall, a side of the retaining wall away from the substrate and the substrate.
- the vertical distance is greater than a vertical distance between the side of the first insulating layer away from the substrate and the substrate, and the retaining wall and the first insulating layer enclose micropores; wherein the micro holes are on the substrate
- the orthographic projection at least partially overlaps the orthographic projection of the electrode on the substrate.
- the gene sequencing chip further includes an ion-sensitive film that is in contact with the first insulating layer and located on a side of the first insulating layer away from the substrate, the ion-sensitive film may be The signal changes sensed by the electrodes are more pronounced.
- the material of the ion-sensitive film is silicon nitride, and the ion-sensitive film made of silicon nitride is more sensitive to hydrogen ions.
- the first insulating layer covers the entire substrate, and the retaining wall is located on a side of the first insulating layer away from the substrate.
- the orthographic projection of the first insulating layer on the substrate completely coincides with the orthographic projection of the microwells on the substrate.
- the first insulating layer and the retaining wall are a unitary structure of the same material.
- the orthographic projection of the microwell on the substrate completely coincides with the orthographic projection of the electrode on the substrate.
- the signal lead is disposed in the same layer as the electrode.
- a second insulating layer is disposed between the signal lead and the electrode, and the signal lead is connected to the electrode through a via hole in the second insulating layer.
- the electrode and the signal lead are made of a metal such as molybdenum, aluminum, copper, or the like, and the retaining wall, the first insulating layer, and the second insulating layer are silicon nitride or oxidized. Made of silicon.
- the signal leads may be arranged on one or both sides of the substrate.
- the present disclosure also provides a gene sequencing device comprising a gene sequencing chip according to the present disclosure.
- the gene sequencing device further includes a detection chip for transmitting a signal to the electrode through a signal lead and receiving the signal sensed by the electrode.
- the present disclosure also provides a gene sequencing method using the gene sequencing device according to the present disclosure, comprising the steps of: adding DNA beads containing DNA strands to microwells of a gene sequencing chip for PCR amplification; sequentially adding four to the microwells a deoxyribonucleoside triphosphate; the detection chip applies a signal to the electrode of the gene sequencing chip through a signal lead of the gene sequencing chip, and detects whether the signal value sensed by the electrode changes; and adds when the signal value changes according to the signal value
- the type of deoxyribonucleoside triphosphate determines the type of base on the DNA strand.
- the deoxyribonucleoside triphosphate is a reversible termination of deoxyribonucleoside triphosphate
- the gene sequencing method further comprises: washing the reversible stop deoxyribonucleoside triphosphate added to the micropore, And add a base reagent.
- FIG. 1 shows a top view of a gene sequencing chip in accordance with an embodiment of the present disclosure
- FIG. 2 to 4 are cross-sectional views of the gene sequencing chip taken along line AA' of FIG. 1 according to an embodiment of the present disclosure
- FIG. 5 illustrates a top view of a gene sequencing chip in accordance with another embodiment of the present disclosure
- 6 to 8 are cross-sectional views of the gene sequencing chip taken along line AA' of FIG. 5, according to another embodiment of the present disclosure
- FIG. 9 is a flow chart showing a gene sequencing method in accordance with an embodiment of the present disclosure.
- FIG. 1 shows a top view of a gene sequencing chip in accordance with an embodiment of the present disclosure.
- 2 is a cross-sectional view of the gene sequencing chip taken along line AA' of FIG. 1 in accordance with an embodiment of the present disclosure.
- a gene sequencing chip includes a substrate 1, and an electrode 7 and a signal lead 8 are disposed on the substrate 1.
- the signal lead 8 is connected to the electrode 7, which is configured to input a signal to the electrode 7 and output a signal sensed by the electrode 7 to the signal transmission end.
- the gene sequencing chip further includes a first insulating layer 3 and a retaining wall 2, the first insulating layer 3 is located on a side of the electrode 7 away from the substrate 1, and the vertical distance D between the side of the retaining wall 2 away from the substrate 1 and the substrate 1 The vertical distance d between the side of the first insulating layer 3 remote from the substrate 1 and the substrate 1 is different, and the retaining wall 2 and the first insulating layer 3 enclose the micro holes 5.
- the orthographic projection of the microholes 5 on the substrate 1 at least partially overlaps with the orthographic projection of the electrodes 7 on the substrate 1.
- the gene sequencing chip of the present disclosure does not need to form a field effect tube, and the manufacturing process is simple, which reduces manufacturing difficulty and cost. And according to the gene sequencing method of the present disclosure, gene sequencing can be performed simply and conveniently.
- the surfaces of the first insulating layer 3 and the retaining wall 2 may also be uneven, for example, the lowest point of the plane of the retaining wall 2 away from the side of the substrate 1 and the highest point of the plane of the first insulating layer 3 away from the side of the substrate 1. There is a difference in distance between them, and micropores can also be formed.
- the retaining wall 2 may be made of an insulating material, and the material for forming the retaining wall 2 may include, but is not limited to, silicon oxide, silicon nitride, silicon oxynitride or an insulating resin material.
- the electrode 7 and the signal lead 8 may be made of a metal such as molybdenum, aluminum, or copper.
- the orthographic projection of the microholes 5 on the substrate 1 completely coincides with the orthographic projection of the electrodes 7 on the substrate 1.
- the electrode 7 can sense a signal change caused by the reaction in the entire micropore 5, further improving the detection sensitivity.
- the gene sequencing chip may further include a detecting chip 10, one end of the signal lead 8 is connected to the electrode 7, and the other end is connected to the detecting chip 10 as a signal transmitting end.
- the signal lead 8 is used to input a signal from the detecting chip 10 to the electrode 7, and output the signal sensed by the electrode 7 to the detecting chip 10.
- the detecting chip 10 is illustrated on the substrate 1 in FIG. 1, the solution of the present disclosure is not limited thereto.
- the detection chip 10 can be formed as an element separate from the gene sequencing chip of the present disclosure.
- the detecting chip 10 in the present disclosure transmits a voltage pulse signal to the electrode 7 through the signal lead 8, and detects whether the signal value sensed by the electrode 7 changes.
- the electrode 7 and the signal lead 8 are disposed in different layers, and the electrode 7 is connected to the signal lead 8 through the via 9 in the second insulating layer 4.
- the first insulating layer 3 is an entire layer, that is, completely covers the surface of the substrate 1 on which the electrodes 7 and the leads 8 are formed.
- the retaining wall 2 is disposed on the first insulating layer 3, and the vertical distance between the side of the retaining wall 2 away from the substrate 1 and the substrate 1 D is larger than the vertical distance d between the side of the first insulating layer 3 away from the substrate 1 and the substrate 1, so as to surround the micropores 5 through the retaining wall 2 and the first insulating layer 3.
- the orthographic projection of the microholes 5 on the substrate 1 may at least partially overlap with the orthographic projection of the electrodes 7 on the substrate 1.
- the material of the second insulating layer 4 may be silicon nitride or silicon oxide or the like. Since the electrode 7 and the signal lead 8 are disposed in different layers, it is not necessary to reserve the wiring space of the signal lead 8 between the adjacent electrodes 7, and the electrode 7 on the substrate 1 can be disposed more densely, thereby increasing the substrate 1 The number of electrodes 7.
- the micro-hole 5 is provided with an ion-sensitive film 6 that is in contact with the first insulating layer 3 and located on a side of the first insulating layer 3 away from the substrate 1.
- the material of the ion-sensitive film 6 is silicon nitride, and the ion-sensitive film made of silicon nitride is more sensitive to hydrogen ions.
- FIG. 3 and 4 illustrate a modified example in accordance with an embodiment of the present disclosure.
- the retaining wall 2 and the first insulating layer 3 are arranged differently than in the embodiment shown in FIG.
- the orthographic projection of the first insulating layer 3 on the substrate 1 and the orthographic projection of the micro holes 5 on the substrate 1 are shown. Completely coincident.
- the retaining wall 2 and the first insulating layer 3 may be integrally formed of the same material, thereby contributing to further reduction in manufacturing difficulty and cost.
- FIG. 5 shows a top view of a gene sequencing chip in accordance with another embodiment of the present disclosure.
- 6 is a cross-sectional view of the gene sequencing chip taken along line AA' of FIG. 5, in accordance with another embodiment of the present disclosure.
- the differences between the gene sequencing chip of the present embodiment and the gene sequencing chip of each of the foregoing embodiments will be mainly described below. Descriptions of the same points will be omitted for the sake of brevity, in which the same reference numerals denote the same parts.
- the signal lead 8 and the electrode 7 can be disposed in the same layer.
- the electrode 7 and the signal lead 8 can be fabricated simultaneously, further reducing manufacturing difficulty and cost.
- FIG. 7 and 8 illustrate a modified example in accordance with an embodiment of the present disclosure.
- the retaining wall 2 and the first insulating layer 3 are arranged differently in comparison to the illustrated embodiment.
- the orthographic projection of the first insulating layer 3 on the substrate 1 completely coincides with the orthographic projection of the microholes 5 on the substrate 1.
- the retaining wall 2 and the first insulating layer 3 may be integrally formed of the same material, thereby contributing to further reduction in manufacturing difficulty and cost.
- the ion sensitive membrane 6 shown in Figures 2 to 4 and Figures 6 to 8 is not required.
- hydrogen radicals are released when base-complementary pairing occurs in the micropores 5.
- the released hydrogen ions can affect the voltage pulse signal on the electrode 7, so that the base type on the DNA strand can be determined based on the deoxyribonucleoside triphosphate added when the signal value changes.
- the gene sequencing chip according to the embodiment of the present disclosure does not need to form a field effect transistor, and can also perform gene sequencing according to the change of the voltage pulse signal on the electrode 7, and also reduces the manufacturing difficulty and cost.
- At least one embodiment of the present disclosure provides a gene sequencing device comprising the above-described gene sequencing chip.
- At least one embodiment of the present disclosure provides a gene sequencing apparatus comprising the above-described gene sequencing chip and detection chip 10 for transmitting a signal to the electrode 7 through the signal lead 8 and receiving the electrode 7 sensed signal.
- Figure 9 shows a flow chart of a gene sequencing method in accordance with an embodiment of the present disclosure.
- a gene sequencing device may include a gene sequencing chip and a detection chip according to the present disclosure. As shown in FIG. 9, the gene sequencing method using the gene sequencing device according to the present disclosure includes the steps of:
- S101 adding DNA beads containing DNA strands to microwells 5 of a gene sequencing chip for PCR amplification;
- S104 determining a base type on the DNA strand according to the deoxyribonucleoside triphosphate added when the signal value changes.
- the deoxyribonucleoside triphosphate applied in step S102 is a reversible termination of deoxyribonucleoside triphosphate, and may include, for example, reversible termination of adenine triphosphate deoxyribonucleotide, reversible termination of triphosphate Thymine deoxyribonucleotides, reversible termination of cytosine deoxyribonucleotides and reversible termination of guanine deoxyribonucleotide triphosphate.
- the voltage pulse signal can be transmitted to the electrode 7 and the sensed signal can be received from the electrode 7 by the detecting chip 10, that is, the voltage pulse signal is first input to the electrode 7 through the signal lead 8. Then, the signal sensed by the electrode 7 is also received through the signal lead 8.
- the deoxyribonucleoside triphosphate in the microwell 5 is synthesized into a DNA molecule, hydrogen ions are released. Hydrogen ions have an effect on the voltage pulse signal on the electrode 7.
- hydrogen ions if the ion sensitive membrane 6 is disposed in the micropore 5, hydrogen ions induce a Nernst potential on the surface of the ion sensitive membrane 6, which also produces a voltage pulse signal on the electrode 7. influences.
- the type of base on the DNA strand can be determined based on the deoxyribonucleoside triphosphate added when the signal value changes.
- the DNA strand to be tested is The base is thymine; if the deoxyribonucleoside triphosphate added to the micropore 5 is thymidine triphosphate deoxyribonucleotide, then the base on the DNA strand to be tested is adenine; if it is microporous
- the deoxyribonucleoside triphosphate added in 5 is a cytosine deoxyribonucleotide triphosphate, and the base on the DNA strand to be tested is guanine; if the deoxyribonucleoside triphosphate is added to the micropore 5 For guanine deoxyribonucleotide triphosphate, the base on the DNA strand to be tested is cytosine.
- the reversible termination of the deoxyribonucleoside triphosphate added to the micropore 5 is washed, and the sulfhydryl reagent is added.
- the common reversible termination of deoxyribonucleoside triphosphates at the 3' end of an azide group does not form a phosphodiester bond during DNA synthesis, thus disrupting DNA synthesis. If a sulfhydryl reagent is added, the azide group will be broken and a hydroxyl group will be formed at the original position. After adding the sulfhydryl reagent, the base class in the subsequent position can be continued. Type detection.
Abstract
Description
Claims (13)
- 一种基因测序芯片,包括:基板(1);电极(7),所述电极(7)位于所述基板(1)上;信号引线(8),所述信号引线(8)与所述电极(7)连接,其被配置为向所述电极(7)输入信号并将所述电极(7)感测的信号输出;第一绝缘层(3),所述第一绝缘层(3)位于所述电极(7)远离所述基板(1)的一侧;以及挡墙(2),所述挡墙(2)远离所述基板(1)的一侧与所述基板(1)之间的垂直距离大于所述第一绝缘层(3)远离所述基板(1)的一侧与所述基板(1)之间的垂直距离,所述挡墙(2)和所述第一绝缘层(3)围成微孔(5);其中,所述微孔(5)在基板(1)上的正投影与所述电极(7)在所述基板(1)上的正投影至少部分重叠。
- 根据权利要求1所述的基因测序芯片,其中,还包括离子敏感膜(6),其与所述第一绝缘层(3)接触且位于所述第一绝缘层(3)远离所述基板(1)的一侧。
- 根据权利要求2所述的基因测序芯片,其中,所述离子敏感膜(6)的材料是四氮化三硅。
- 根据权利要求1所述的基因测序芯片,其中,所述第一绝缘层(3)覆盖整个基板(1),所述挡墙(2)位于所述第一绝缘层(3)远离所述基板(1)的一侧。
- 根据权利要求1所述的基因测序芯片,其中,所述第一绝缘层(3)在所述基板(1)上的正投影与所述微孔(5)在所述基板(1) 上的正投影完全重合。
- 根据权利要求4或5所述的基因测序芯片,其中,所述第一绝缘层(3)和挡墙(2)是相同材料的一体结构。
- 根据权利要求1所述的基因测序芯片,其中,所述微孔(5)在所述基板(1)上的正投影与所述电极(7)在所述基板(1)上的正投影完全重合。
- 根据权利要求1所述的基因测序芯片,其中,所述信号引线(8)与所述电极(7)同层设置。
- 根据权利要求1所述的基因测序芯片,其中,所述信号引线(8)与所述电极(7)之间设置有第二绝缘层(4),并且所述信号引线(8)与所述电极(7)通过所述第二绝缘层(4)中的过孔(9)连接。
- 一种基因测序设备,包括权利要求1-9中任一项所述的基因测序芯片。
- 根据权利要求10所述的基因测序设备,还包括侦测芯片(10),所述侦测芯片(10)用于通过所述信号引线(8)向所述电极(7)发送信号并接收所述电极(7)感测的信号。
- 一种使用权利要求1的基因测序芯片的基因测序方法,包括以下步骤:将包含DNA链的DNA微珠加入基因测序芯片的微孔(5)中进行PCR扩增;依次向微孔(5)中加入四种脱氧核糖核苷三磷酸;通过基因测序芯片的信号引线(8)向电极(7)施加信号,并 检测电极(7)感测的信号值是否发生变化;以及根据所述信号值发生变化时加入的脱氧核糖核苷三磷酸的类型确定DNA链上的碱基类型。
- 根据权利要求12所述的基因测序方法,其中,所述脱氧核糖核苷三磷酸为可逆终止脱氧核糖核苷三磷酸,并且所述基因测序方法还包括:清洗加入至微孔(5)中的可逆终止脱氧核糖核苷三磷酸,并加入疏基试剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/752,603 US20190025242A1 (en) | 2017-01-03 | 2017-08-18 | Gene sequencing chip, gene sequencing apparatus, and gene sequencing method |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710003178.5A CN106497774A (zh) | 2017-01-03 | 2017-01-03 | 基因测序芯片、基因测序设备及基因测序方法 |
CN201710003178.5 | 2017-01-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2018126696A1 true WO2018126696A1 (zh) | 2018-07-12 |
Family
ID=58344978
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2017/098024 WO2018126696A1 (zh) | 2017-01-03 | 2017-08-18 | 基因测序芯片、基因测序设备及基因测序方法 |
Country Status (3)
Country | Link |
---|---|
US (1) | US20190025242A1 (zh) |
CN (1) | CN106497774A (zh) |
WO (1) | WO2018126696A1 (zh) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106497774A (zh) * | 2017-01-03 | 2017-03-15 | 京东方科技集团股份有限公司 | 基因测序芯片、基因测序设备及基因测序方法 |
CN107090404B (zh) * | 2017-04-21 | 2019-08-13 | 京东方科技集团股份有限公司 | 一种基因测序芯片及基因测序方法、基因测序装置 |
CN107118954B (zh) * | 2017-04-28 | 2019-07-23 | 京东方科技集团股份有限公司 | 基因测序芯片、装置以及方法 |
CN107164466B (zh) | 2017-05-11 | 2019-03-26 | 京东方科技集团股份有限公司 | 芯片基板及其制作工艺、基因测序芯片及基因测序方法 |
CN107118960B (zh) * | 2017-05-15 | 2019-10-01 | 京东方科技集团股份有限公司 | 一种基因测序芯片、基因测序系统及其测序方法 |
CN109266727B (zh) | 2017-07-17 | 2021-01-29 | 京东方科技集团股份有限公司 | 基因测序结构、芯片、系统和基因测序方法 |
CN107402199B (zh) * | 2017-07-31 | 2019-09-10 | 京东方科技集团股份有限公司 | 基因测序芯片及其测序方法以及基因测序装置 |
CN108220412B (zh) | 2018-01-03 | 2021-10-01 | 京东方科技集团股份有限公司 | 一种基因测序基板及其制备方法、基因测序装置 |
CN112175815B (zh) * | 2019-07-05 | 2023-04-11 | 京东方科技集团股份有限公司 | Pcr基板、芯片、系统及液滴拉出方法 |
WO2021092798A1 (zh) * | 2019-11-13 | 2021-05-20 | 京东方科技集团股份有限公司 | 检测芯片及其制备方法和使用方法、反应系统 |
CN114045211A (zh) * | 2021-11-18 | 2022-02-15 | 上海天马微电子有限公司 | 基因测序结构、基因测序装置及基因测序方法 |
CN114262660A (zh) * | 2021-12-21 | 2022-04-01 | 上海天马微电子有限公司 | 一种基因测序面板及其制作方法 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5187096A (en) * | 1991-08-08 | 1993-02-16 | Rensselaer Polytechnic Institute | Cell substrate electrical impedance sensor with multiple electrode array |
CN1273364A (zh) * | 1999-05-06 | 2000-11-15 | 杨梦甦 | 病原菌和疾病相关基因突变诊断专用dna芯片的检测方法 |
CN1876834A (zh) * | 2004-06-07 | 2006-12-13 | 索尼株式会社 | 包括具有凹陷部分电极的杂交检测装置和包括该检测装置的dna芯片 |
CN104487592A (zh) * | 2012-04-19 | 2015-04-01 | 生命技术公司 | 进行数字pcr的方法 |
CN104614404A (zh) * | 2015-02-06 | 2015-05-13 | 中国科学院微电子研究所 | 离子敏感场效应管传感器及其读出电路 |
CN104698708A (zh) * | 2015-04-01 | 2015-06-10 | 上海天马微电子有限公司 | 阵列基板及其制作方法、显示装置 |
CN106497774A (zh) * | 2017-01-03 | 2017-03-15 | 京东方科技集团股份有限公司 | 基因测序芯片、基因测序设备及基因测序方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050009004A1 (en) * | 2002-05-04 | 2005-01-13 | Jia Xu | Apparatus including ion transport detecting structures and methods of use |
DE10259820B4 (de) * | 2002-12-19 | 2006-05-24 | Siemens Ag | DNA-Chip |
WO2013119719A1 (en) * | 2012-02-06 | 2013-08-15 | Ludwig, Lester, F. | Microprocessor-controlled microfluidic platform for pathogen, toxin, biomarker, and chemical detection with removable updatable sensor array for food and water safety, medical, and laboratory apllications |
-
2017
- 2017-01-03 CN CN201710003178.5A patent/CN106497774A/zh active Pending
- 2017-08-18 US US15/752,603 patent/US20190025242A1/en not_active Abandoned
- 2017-08-18 WO PCT/CN2017/098024 patent/WO2018126696A1/zh active Application Filing
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5187096A (en) * | 1991-08-08 | 1993-02-16 | Rensselaer Polytechnic Institute | Cell substrate electrical impedance sensor with multiple electrode array |
CN1273364A (zh) * | 1999-05-06 | 2000-11-15 | 杨梦甦 | 病原菌和疾病相关基因突变诊断专用dna芯片的检测方法 |
CN1876834A (zh) * | 2004-06-07 | 2006-12-13 | 索尼株式会社 | 包括具有凹陷部分电极的杂交检测装置和包括该检测装置的dna芯片 |
CN104487592A (zh) * | 2012-04-19 | 2015-04-01 | 生命技术公司 | 进行数字pcr的方法 |
CN104614404A (zh) * | 2015-02-06 | 2015-05-13 | 中国科学院微电子研究所 | 离子敏感场效应管传感器及其读出电路 |
CN104698708A (zh) * | 2015-04-01 | 2015-06-10 | 上海天马微电子有限公司 | 阵列基板及其制作方法、显示装置 |
CN106497774A (zh) * | 2017-01-03 | 2017-03-15 | 京东方科技集团股份有限公司 | 基因测序芯片、基因测序设备及基因测序方法 |
Also Published As
Publication number | Publication date |
---|---|
US20190025242A1 (en) | 2019-01-24 |
CN106497774A (zh) | 2017-03-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2018126696A1 (zh) | 基因测序芯片、基因测序设备及基因测序方法 | |
CN1294260C (zh) | 电位滴定dna微阵列、其制造方法及核酸解析方法 | |
TWI422818B (zh) | 氫離子感測場效電晶體及其製造方法 | |
ES2928247T3 (es) | Aparato para medir analitos con un área superficial de puerta flotante extendida | |
US8962366B2 (en) | Self-aligned well structures for low-noise chemical sensors | |
US8841217B1 (en) | Chemical sensor with protruded sensor surface | |
JP6671274B2 (ja) | 薄伝導性素子を有する化学装置 | |
EP3315461B1 (en) | Micro-porous electrode and method for analysis of chemical substances | |
EP2653861A2 (en) | Methods and apparatus for measuring analytes using large scale FET arrays | |
JP2005518541A5 (zh) | ||
WO2019024524A1 (zh) | 基因测序芯片及其测序方法以及基因测序装置 | |
WO2013096897A1 (en) | Method and apparatus for calibration of a sensor array | |
GB0105831D0 (en) | Method for dna sequencing utilising enzyme linked field effect transistors | |
WO2013096906A1 (en) | Data compression of waveforms associated with a chemical event occuring on a sensor array | |
EP2307577A2 (en) | Methods and apparatus for measuring analytes using large scale fet arrays | |
WO2018196307A1 (zh) | 基因测序芯片、装置以及方法 | |
US20140191293A1 (en) | Methods for manufacturing well structures for low-noise chemical sensors | |
US20170108464A1 (en) | System and method for forming microwells | |
US9080968B2 (en) | Methods and systems for point of use removal of sacrificial material | |
US20180187248A1 (en) | Gene sequencing chip, gene sequencing apparatus and gene sequencing method | |
JP6797931B2 (ja) | 遺伝子配列決定構造、チップ、システムおよび遺伝子配列決定方法 | |
WO2019010955A1 (zh) | 用于医学检测的基板及其基因测序方法以及基因测序芯片 | |
TWI647842B (zh) | 具薄導電元件之化學裝置 | |
US20230151408A1 (en) | Gene sequencing structure, gene sequencing device and gene sequencing method | |
JPH04142454A (ja) | 半導体化学センサ |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17889572 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 17889572 Country of ref document: EP Kind code of ref document: A1 |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 18/12/2019) |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 17889572 Country of ref document: EP Kind code of ref document: A1 |