CN110066723A - Gene sequencing chip, equipment, manufacturing method - Google Patents
Gene sequencing chip, equipment, manufacturing method Download PDFInfo
- Publication number
- CN110066723A CN110066723A CN201910367836.8A CN201910367836A CN110066723A CN 110066723 A CN110066723 A CN 110066723A CN 201910367836 A CN201910367836 A CN 201910367836A CN 110066723 A CN110066723 A CN 110066723A
- Authority
- CN
- China
- Prior art keywords
- gene sequencing
- structures
- microcellular structure
- substrate
- blockage
- 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
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 68
- 238000012163 sequencing technique Methods 0.000 title claims abstract description 67
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 14
- 239000000758 substrate Substances 0.000 claims abstract description 38
- 238000001514 detection method Methods 0.000 claims abstract description 19
- 238000012986 modification Methods 0.000 claims description 8
- 230000004048 modification Effects 0.000 claims description 8
- 230000008033 biological extinction Effects 0.000 claims description 4
- 238000005516 engineering process Methods 0.000 abstract description 6
- 239000000463 material Substances 0.000 description 27
- 229920002120 photoresistant polymer Polymers 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- 238000000059 patterning Methods 0.000 description 6
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 229910052710 silicon Inorganic materials 0.000 description 5
- 239000010703 silicon Substances 0.000 description 5
- 238000001259 photo etching Methods 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 239000002250 absorbent Substances 0.000 description 3
- 230000002745 absorbent Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000005530 etching Methods 0.000 description 3
- 230000003760 hair shine Effects 0.000 description 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- HUTDUHSNJYTCAR-UHFFFAOYSA-N ancymidol Chemical compound C1=CC(OC)=CC=C1C(O)(C=1C=NC=NC=1)C1CC1 HUTDUHSNJYTCAR-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000001312 dry etching Methods 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 150000004767 nitrides Chemical class 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000007641 inkjet printing Methods 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000001039 wet etching Methods 0.000 description 1
Classifications
-
- 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
Abstract
The present invention provides a kind of gene sequencing chip, equipment, manufacturing method, belongs to gene sequencing technology field, and can at least partly solving the problems, such as existing gene sequencing chip, there are crosstalks in application.Gene sequencing chip of the invention, including substrate and the multiple microcellular structures being arranged in substrate, blockage structures are provided between adjacent microcellular structure, blockage structures are used to stop the light emission of the bottom hole from microcellular structure to detection unit corresponding to the blockage structures closed on.
Description
Technical field
The invention belongs to gene sequencing technology fields, and in particular to a kind of gene sequencing chip, a kind of gene sequencing equipment,
A kind of manufacturing method of gene sequencing chip.
Background technique
Gene sequencing, which refers to, analyzes specific gene (DNA molecular with certain length) by physics, chemistry, biological means
In base put in order.Only include four kinds of bases in DNA molecular, is adenine (A), thymidine (T), cytimidine respectively
(C)
With guanine (G).Since being sequenced first generation Sanger method in 1977, gene sequencing technology has been developed three
Generation, including the third using Illumina as the second generation high throughput sequencing technologies of representative, based on Pacific Biosciences
For single-molecule sequencing technology.Although the sequencing technologies in different generations have the characteristics that it is respective, it is all for principle is sequenced
Sequencing be all based on chain termination method, that is, by the chemical modification to a certain base analog (one of A, T, C, G),
Terminate the chain synthesis reaction after it.
Since different classes of base has the fluorophor of different colours, shine when using up excitation fluorophor
When, the type of base can be determined by detecting luminescent color, to obtain the sequence of testing gene.
Shown in fig. 1 is the cross-section structure of traditional gene sequencing equipment.Battle array is formed in the substrate 1 of gene sequencing chip
Multiple microcellular structures 2 of column arrangement (arrangement mode is without being limited thereto).The gene sequencing chip is arranged in gene sequencing equipment
It is interior, one detection unit 5 of each 2 face of microcellular structure.DNA molecular 7 to be detected is placed in microcellular structure 2.It is to be detected
DNA molecular 7 and microcellular structure 2 in fluorescent marker fluorophor 6 (specially base group) combination.In illumination item
Under part, fluorophor 6 shines.And it is diverging, the angle of emergence (angle of radiation direction and 1 normal of substrate) that fluorophor 6, which shines,
Lesser light is detected by the detection unit 5 of face, is analyzed for the sequence to DNA molecular 7.Specifically, detection is single
Member 5 needs the strength information and wavelength information of detection light.The biggish light of the angle of emergence can be mapped to the detection unit 6 closed on.Such as
In Fig. 1, the light that the fluorophor 6 that the DNA molecular 7 in the microcellular structure 2 in middle position currently shines is issued has one
Divide detection unit 5 corresponding to the microcellular structure 2 for being mapped to and closing on.Issuing light in different microcellular structures 2 as a result, can mutual crosstalk.
This can reduce the accuracy of gene sequencing result, and increase the subsequent calculation amount for calculating analysis.
Summary of the invention
The present invention at least partly solves the problems, such as that there are crosstalks in existing gene sequencing chip, provide a kind of gene sequencing
Chip, gene sequencing equipment, the manufacturing method of gene sequencing chip.
Solving technical solution used by present invention problem is a kind of gene sequencing chip, including substrate and setting
Multiple microcellular structures in substrate are provided with blockage structures between adjacent microcellular structure, and blockage structures are for stopping
From microcellular structure bottom hole light emission to detection unit corresponding to the blockage structures closed on.
Optionally, blockage structures include extinction structure or reflective structure.
Optionally, orthographic projection of the microcellular structure in substrate is surrounded in orthographic projection of the blockage structures in substrate.
Optionally, the boundary of the close microcellular structure of orthographic projection of the blockage structures in substrate and the microcellular structure are in base
The overlapping margins of orthographic projection on bottom.
Optionally, the boundary of the close microcellular structure of orthographic projection of the blockage structures in substrate and the microcellular structure are in base
The boundary of orthographic projection on bottom is at a distance of set distance.
It optionally, further include the finishing coat for covering blockage structures, finishing coat in gene sequencing for connecing
By surface modification.
Optionally, the boundary of the close microcellular structure of orthographic projection of the finishing coat in substrate and the microcellular structure are in base
The overlapping margins of orthographic projection on bottom.
Solving technical solution used by present invention problem is a kind of gene sequencing equipment, is surveyed including above-mentioned gene
Sequence chip.
Solve the manufacturing method that technical solution used by present invention problem is a kind of gene sequencing chip, comprising:
The step of multiple microcellular structures are formed on the substrate;The step of blockage structures are formed between adjacent microcellular structure, photoresist
Gear structure is used to stop the light emission of the bottom hole from microcellular structure to detection unit corresponding to the blockage structures closed on.
Optionally, further include the steps that forming the finishing coat of covering blockage structures, wherein finishing coat is used for
Receive surface modification in gene sequencing.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of existing gene sequencing chip;
Fig. 2 a is a kind of sectional view of gene sequencing chip of the embodiment of the present invention;
Fig. 2 b is the working principle diagram that gene sequencing chip shown in Fig. 2 a is applied to gene sequencing equipment;
Fig. 3 a is the sectional view of another gene sequencing chip of the embodiment of the present invention;
Fig. 3 b is the working principle diagram that gene sequencing chip shown in Fig. 3 a is applied to gene sequencing equipment;
Fig. 3 c is the birds-eye perspective of the gene sequencing chip of Fig. 3 a;
Fig. 3 d is a kind of deformation of gene sequencing chip shown in Fig. 3 a;
Fig. 4 is sectional view of the gene sequencing chip shown in Fig. 2 a in the intermediate state of manufacture;
Fig. 5 a- Fig. 5 b is sectional view of the gene sequencing chip shown in Fig. 3 a in the different intermediate state of manufacture;
Wherein, appended drawing reference are as follows: 1, substrate;2, microcellular structure;3, blockage structures;3 ', photoresist layer;4, surface
Decorative layer;4 ', face finish material layer;5, detection unit;6, fluorophor;7, DNA molecular;D, diameter;H, height;P, week
Phase;A, first thickness;D, second thickness;B, the first spacing.
Specific embodiment
Technical solution in order to enable those skilled in the art to better understand the present invention, with reference to the accompanying drawing and specific embodiment party
Present invention is further described in detail for formula.
In the present invention, " patterning processes " refer to the step of forming the structure with specific figure, can be photoetching work
Skill, photoetching process include forming material layer, coating photoresist,
Exposure, development, etching, photoresist lift off and etc. in one or more steps;Certainly, " patterning processes " can also be pressure
Other techniques such as print technique, InkJet printing processes.
Embodiment 1:
A and Fig. 3 a referring to fig. 2, the present embodiment provides a kind of gene sequencing chips, including substrate 1 and setting are in substrate 1
On multiple microcellular structures 2, blockage structures 3 are provided between adjacent microcellular structure 2, blockage structures 3 are for stopping hair
From the light emission of the bottom hole of microcellular structure 2 to detection unit 5 corresponding to the blockage structures 3 closed on.
The material of substrate 1 is, for example, glass, silicon, organic resin class material.1 material of substrate of organic resin class is, for example, poly-
Methyl methacrylate (PMMA).
As shown in Figure 2 a, the boundary of microcellular structure 2 can be formed in substrate 1 and the light blocking knot in substrate 1
On structure 3, finishing coat 4.In another example the boundary of microcellular structure 2 is formed in substrate 1 and finishing coat 4 shown in Fig. 3 a.When
The bottom hole of right microcellular structure 2 is also possible to be formed by the other structures between substrate 1 and blockage structures 3, i.e., in substrate 1 and light
There is also other layer structures between barrier structure 3.Such as it is formed with multi-layered electrode layer, multilayer dielectric layer, micropore on the base 1
The bottom hole of structure 2 is formed on the insulating layer of top layer.How the present invention forms without limitation microcellular structure 2.Certainly, surface
Decorative layer 4 is also optional layer structure.
Blockage structures 3 are set between adjacent microcellular structure 2, it is big its object is to be issued to fluorophor 6
The light of the angle of emergence is stopped, and prevents this part light emission to detection unit 5 corresponding to the microcellular structure 2 closed on.So inhibit
Or to avoid crosstalk bad.
Optionally, blockage structures 3 include extinction structure or reflective structure.I.e. blockage structures 3 can be by fluorophor 6
The light absorption of the larger angle of emergence issued may be selected light absorbent and form blockage structures 3.Optionally light absorbent is, for example,
The organic resin class material of black.The optional material of reflective structure is, for example, the light reflecting metallic materials such as aluminium (Al) or silver-colored (Ag).Only
If specific pattern can be formed by patterning processes and energy extinction or reflective material may be used as the material of blockage structures 3
Material.
B and Fig. 3 b referring to fig. 2, the arrow in figure indicate the light that fluorophor 6 issues.For the light of larger shooting angle,
It is stopped by the blockage structures 3 between adjacent cells structure 2.
Blockage structures 3 also mean that as viewed from the side of gene sequencing chip between adjacent cells structure 2,
Blockage structures 3 are at least partly Chong Die with microcellular structure 2.The case where blockage structures 3 are formed by light absorbent, more
Pay close attention to blockage structures 3 upper surface at a distance from 2 bottom hole of microcellular structure.Blockage structures 3 are formed by reflectorized material
The case where, then be more concerned about the lower surface of blockage structures 3 at a distance from the bottom hole of microcellular structure 2.Specific blockage structures 3
How size and location are arranged, and those skilled in the art can make the adjustment of adaptability, and which is not limited by the present invention.When
So, optionally, according to Fig. 2 a and Fig. 3 a current visual angle, if blockage structures 3 are formed by reflectorized material, its bottom surface is answered
Higher than the bottom surface of microcellular structure 2.
The arrangement mode of microcellular structure 2 on the base 1 can be as shown in Figure 3c as in cross-arranging type distribution (or square
Configuration distribution).The certain arrangement mode of microcellular structure 2 on the base 1 is not limited to this.Those skilled in the art can do this
Flexibly setting out.
Diameter D, height H and the period P of microcellular structure 2 are other in the micron-scale.Representative value is, for example, diameter D and height H is
1um, period P are 3um.
The diameter D of preferred microporous structure 2 is arranged within the scope of 100nm~2um, and the period P setting of microcellular structure 2 exists
In the range of 200nm~5um.The height H of microcellular structure 2 is arranged within the scope of 100nm~2um.The thickness of blockage structures 3 is remembered
For second thickness d, the thickness of finishing coat 4 is denoted as first thickness a, bottom of the bottom surface of blockage structures 3 apart from microcellular structure 2
The distance in face is denoted as the first spacing b, these can be according to actual needs flexible setting.
As long as can inhibit one of them it should be noted that blockage structures 3 are arranged between adjacent cells structure 2
Detection unit 5 corresponding to the fluorescence directive adjacent cells structure 2 issued in microcellular structure 2.Such as it can be only adjacent
Blockage structures 3 are arranged in partial region between microcellular structure 2.If the height H setting of the top surface or bottom surface of blockage structures 3
Properly, the shape design of blockage structures 3 is suitable, even if blockage structures 3 only wrap up the partial region of microcellular structure 2, then
Detection unit 5 corresponding to microcellular structure 2 for the secondary neighbour in addition to 4 microcellular structures 2 of arest neighbors, and not by dry
It disturbs.As shown in Figure 3d, light blocking knot is only arranged in microcellular structure 2 in the partial region opposite with the microcellular structure 2 of arest neighbors
Structure 3 is not provided with blockage structures 3 in the region opposite with the microcellular structure 2 of secondary neighbour.Blockage structures 3 can so be reduced
Material cost.
Optionally, the orthographic projection of microcellular structure 2 on the base 1 is surrounded in the orthographic projection of blockage structures 3 on the base 1.
As shown in Figure 2 a, the boundary of the close microcellular structure 2 of the orthographic projection of blockage structures 3 on the base 1 and the micropore
The overlapping margins of the orthographic projection of structure 2 on the base 1.That is the boundary towards microcellular structure 2 of blockage structures 3 and microcellular structure
What 2 boundary was generally flush with.
Such as shown in Fig. 3 c, the boundary of the close microcellular structure 2 of the orthographic projection of blockage structures 3 on the base 1 is micro- with this
The boundary of the orthographic projection of pore structure 2 on the base 1 is at a distance of set distance.That is the boundary towards microcellular structure 2 of blockage structures 3
The boundary of opposite microcellular structure 2 extends out.In this case, in subsequent applications, blockage structures 3 are not contact with reagent
's.
It illustrates, in Fig. 3 c, since blockage structures 3 are covered by finishing coat 4, therefore only depicts photoresist with dotted line
The boundary of structure 3 is kept off, the shape of photoresist layer 3 understands in combination with Fig. 3 a.
In conjunction with Fig. 3 c, the shape of blockage structures 3 can also for example be changed to intersect anyhow latticed.Certainly, in this way
If the production of mask can be simpler.Those skilled in the art can stop directive adjacent micro- guaranteeing blockage structures 3
Under the premise of detection unit 5 corresponding to pore structure 2, the material cost of blockage structures 3, suitably reduction blockage structures are considered
3 areas occupied on the base 1.Those skilled in the art can make further on the basis of the present embodiment institute offer scheme
Optimization.
It optionally, further include the finishing coat 4 for covering blockage structures 3, finishing coat 4 is used in gene sequencing
Receive surface modification.The chemical compatibility for the reagent being applied in the material and gene sequencing of finishing coat 4 is better than photoresist
Keep off structure 3.The material of finishing coat 4 is, for example, the nitride etc. of the oxide of silicon, silicon, in some embodiments, surface
The material of decorative layer 4 is also possible to organic resin.In most cases, finishing coat 4 is light transmission, therefore when being designed,
It is more concerned about the size i.e. location parameter of blockage structures 3.
Optionally, the boundary of the close microcellular structure 2 of the orthographic projection of finishing coat 4 on the base 1 and the microcellular structure 2
The overlapping margins of orthographic projection on the base 1.I.e. as shown in Figure 2 a, the boundary towards microcellular structure 2 of finishing coat 4 with it is micro-
What pore structure 2 was generally flush with, finishing coat 4, blockage structures 3,1 material of part of substrate together form the side of microcellular structure 2
Face.Certainly, situation as shown in Figure 3a, finishing coat 4 and 1 material of part of substrate together form the side of microcellular structure 2.
Embodiment 2:
The present embodiment provides a kind of gene sequencing equipment, the gene sequencing chip including embodiment 1.
Gene sequencing chip provided by embodiment 1 is applied in gene sequencing equipment.Only show in Fig. 2 b and Fig. 3 b
The detection unit 5 in gene sequencing equipment is gone out.Except the part of gene sequencing chip can be configured according to the prior art, therefore
This will not be repeated here.
It can effectively inhibit or avoid cross-interference issue using the gene sequencing equipment of the gene sequencing chip.
Embodiment 3:
The present embodiment provides a kind of manufacturing methods of gene sequencing chip, comprising: forms multiple microcellular structures on the base 1
2 the step of;The step of blockage structures 3 are formed between adjacent microcellular structure 2, blockage structures 3 are for stopping from micro-
The light emission of the bottom hole of pore structure 2 is to detection unit 5 corresponding to the blockage structures 3 closed on.The gene being so prepared is surveyed
Sequence chip can effectively avoid cross-interference issue.
Optionally, further include the steps that forming the finishing coat 4 of covering blockage structures 3, wherein finishing coat 4
For receiving surface modification in gene sequencing.In this way, the reagent and the surface that carry DNA molecular 7 in subsequent applications can be made
Decorative layer 4 is combined to complete gene sequencing.
The example of two introduced below specific manufacturing processes.Although in the two examples, the bottom hole of microcellular structure 2 is
It is made of substrate 1, but be not limited to this in practical application.
Example 1:
Step S11,3 ' of photoresist layer, 4 ' of face finish material layer are sequentially formed on the base 1.After the completion of the step
Product form referring to fig. 4.
Step S12, using a patterning processes to 3 ' of photoresist layer, 4 ' of face finish material layer, substrate 1 at
Reason obtains microcellular structure 2.Specifically, the pattern of photoresist can be formed using one of mask using photoetching process, certainly
The pattern of etching mask can be formed using the technique of nano impression.Then the region leaked out cruelly to photoresist carries out dry etching or wet
It carves, 1 material of substrate of 4 ' of face finish material layer, 3 ' of photoresist layer and partial depth in the sudden and violent drain region of removal photoresist
Material, obtains microcellular structure 2 shown in such as Fig. 2 a.
Using this manufacture, the quantity of mask plate is few.
Example 2:
Step S21, blockage structures 3 are formed on the base 1 using patterning processes.Specifically it can be first on the base 1
One layer of 3 ' of photoresist layer is formed, then obtains the pattern of photoresist by way of photoetching on 3 ' of the photoresist layer
Or etching mask is formed by way of nano impression.The region leaked cruelly is carved followed by the technique of dry etching or wet etching
Erosion, 3 ' of photoresist layer removed in the sudden and violent drain region of photoresist obtain blockage structures 3.Product form after the completion of the step
Referring to Fig. 5 a.
Step S22, referring to Fig. 5 b, 4 ' of face finish material layer of covering blockage structures 3 is formed.Deposition can specifically be passed through
Technique form the nitride of the oxide of one layer of silicon, silicon.Coating can certainly be used and cured mode forms one layer and has
Machine resin.
Step S23, the base of 4 ' of face finish material layer and partial depth in patterning processes removal partial region are utilized
1 material of bottom, to obtain microcellular structure 2.Blockage structures 3 are located at except the partial region, to obtain knot as shown in Figure 3a
Structure.
It is understood that the principle that embodiment of above is intended to be merely illustrative of the present and the exemplary implementation that uses
Mode, however the present invention is not limited thereto.For those skilled in the art, essence of the invention is not being departed from
In the case where mind and essence, various changes and modifications can be made therein, these variations and modifications are also considered as protection scope of the present invention.
Claims (10)
1. a kind of gene sequencing chip, including substrate and the multiple microcellular structures being arranged in substrate, which is characterized in that adjacent
Microcellular structure between be provided with blockage structures, blockage structures are used to stopping the light emission of the bottom hole from microcellular structure to facing
Detection unit corresponding to close blockage structures.
2. gene sequencing chip according to claim 1, which is characterized in that blockage structures include extinction structure or reflective
Structure.
3. gene sequencing chip according to claim 1, which is characterized in that orthographic projection packet of the blockage structures in substrate
Enclose orthographic projection of the microcellular structure in substrate.
4. gene sequencing chip according to claim 1, which is characterized in that orthographic projection of the blockage structures in substrate
Close to the boundary of microcellular structure and the overlapping margins of orthographic projection of the microcellular structure in substrate.
5. gene sequencing chip according to claim 1, which is characterized in that orthographic projection of the blockage structures in substrate
Close to the boundary of microcellular structure and the boundary of orthographic projection of the microcellular structure in substrate at a distance of set distance.
6. gene sequencing chip according to claim 1, which is characterized in that further include cover blockage structures surface repair
Layer is adornd, finishing coat is for receiving surface modification in gene sequencing.
7. gene sequencing chip according to claim 6, which is characterized in that orthographic projection of the finishing coat in substrate
Close to the boundary of microcellular structure and the overlapping margins of orthographic projection of the microcellular structure in substrate.
8. a kind of gene sequencing equipment, which is characterized in that including gene sequencing described in -7 any one according to claim 1
Chip.
9. a kind of manufacturing method of gene sequencing chip characterized by comprising
The step of multiple microcellular structures are formed on the substrate;
The step of blockage structures are formed between adjacent microcellular structure, blockage structures are for stopping from microcellular structure
The light emission of bottom hole is to detection unit corresponding to the blockage structures closed on.
10. manufacturing method according to claim 9, which is characterized in that further include the surface to form covering blockage structures
The step of decorative layer, wherein finishing coat is for receiving surface modification in gene sequencing.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910367836.8A CN110066723A (en) | 2019-05-05 | 2019-05-05 | Gene sequencing chip, equipment, manufacturing method |
PCT/CN2020/087946 WO2020224511A1 (en) | 2019-05-05 | 2020-04-30 | Gene sequencing chip and method for manufacture thereof, and gene sequencing device |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910367836.8A CN110066723A (en) | 2019-05-05 | 2019-05-05 | Gene sequencing chip, equipment, manufacturing method |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110066723A true CN110066723A (en) | 2019-07-30 |
Family
ID=67369888
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910367836.8A Pending CN110066723A (en) | 2019-05-05 | 2019-05-05 | Gene sequencing chip, equipment, manufacturing method |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN110066723A (en) |
WO (1) | WO2020224511A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020224511A1 (en) * | 2019-05-05 | 2020-11-12 | 京东方科技集团股份有限公司 | Gene sequencing chip and method for manufacture thereof, and gene sequencing device |
CN113115586A (en) * | 2019-11-13 | 2021-07-13 | 京东方科技集团股份有限公司 | Detection chip, preparation method and use method thereof, and reaction system |
CN113308351A (en) * | 2020-02-26 | 2021-08-27 | 京东方科技集团股份有限公司 | Detection chip, preparation method thereof and reaction system |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6297018B1 (en) * | 1998-04-17 | 2001-10-02 | Ljl Biosystems, Inc. | Methods and apparatus for detecting nucleic acid polymorphisms |
US20060228722A1 (en) * | 2005-04-07 | 2006-10-12 | Jong-Bum Kim | Thin film coated microwell arrays and methods of making same |
CN101848757A (en) * | 2007-07-13 | 2010-09-29 | 里兰斯坦福初级大学理事会 | The method and apparatus that is used for the use electric field of improved bioassary method |
CN102124128A (en) * | 2008-06-16 | 2011-07-13 | Plc诊断股份有限公司 | System and method for nucleic acids sequencing by phased synthesis |
CN105008878A (en) * | 2012-12-05 | 2015-10-28 | 吉恩波克公司 | Optical interrogation device |
CN105980580A (en) * | 2013-11-17 | 2016-09-28 | 宽腾矽公司 | Optical system and assay chip for probing, detecting and analyzing molecules |
CN105980832A (en) * | 2013-12-10 | 2016-09-28 | 伊鲁米那股份有限公司 | Biosensors for biological or chemical analysis and methods of manufacturing the same |
CN107003241A (en) * | 2014-08-27 | 2017-08-01 | 加利福尼亚太平洋生物科学股份有限公司 | Integrated analysis device array |
CN108027325A (en) * | 2015-05-20 | 2018-05-11 | 宽腾矽公司 | Shone the method for definite nucleotide sequence using time resolution |
CN108463560A (en) * | 2016-01-15 | 2018-08-28 | 昆塔波尔公司 | Background with reduction is analyzed based on optical nano-pore |
WO2018159055A1 (en) * | 2017-02-28 | 2018-09-07 | 信越ポリマー株式会社 | Fluorescence assay multi-well plate and multi-well plate set, and method for producing fluorescence assay multi-well plate |
US20180326412A1 (en) * | 2017-05-05 | 2018-11-15 | Quantum-Si Incorporated | Substrates having modified surface reactivity and antifouling properties in biological reactions |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE548643T1 (en) * | 2007-03-30 | 2012-03-15 | Pacific Biosciences California | SYSTEM AND METHOD FOR AMPLIFYING FLUORESCENT SIGNALS |
CN102604826B (en) * | 2012-03-16 | 2015-12-16 | 盛司潼 | A kind of gene sequencing equipment |
CN205576142U (en) * | 2016-04-06 | 2016-09-14 | 深圳市瀚海基因生物科技有限公司 | Unimolecule gene sequencer |
CN109706066B (en) * | 2018-12-29 | 2022-08-26 | 赛纳生物科技(北京)有限公司 | Gene sequencing chip micro-pit surface modification method |
CN110066723A (en) * | 2019-05-05 | 2019-07-30 | 京东方科技集团股份有限公司 | Gene sequencing chip, equipment, manufacturing method |
-
2019
- 2019-05-05 CN CN201910367836.8A patent/CN110066723A/en active Pending
-
2020
- 2020-04-30 WO PCT/CN2020/087946 patent/WO2020224511A1/en active Application Filing
Patent Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6297018B1 (en) * | 1998-04-17 | 2001-10-02 | Ljl Biosystems, Inc. | Methods and apparatus for detecting nucleic acid polymorphisms |
US20060228722A1 (en) * | 2005-04-07 | 2006-10-12 | Jong-Bum Kim | Thin film coated microwell arrays and methods of making same |
CN101848757A (en) * | 2007-07-13 | 2010-09-29 | 里兰斯坦福初级大学理事会 | The method and apparatus that is used for the use electric field of improved bioassary method |
CN102124128A (en) * | 2008-06-16 | 2011-07-13 | Plc诊断股份有限公司 | System and method for nucleic acids sequencing by phased synthesis |
CN105008878A (en) * | 2012-12-05 | 2015-10-28 | 吉恩波克公司 | Optical interrogation device |
CN105980580A (en) * | 2013-11-17 | 2016-09-28 | 宽腾矽公司 | Optical system and assay chip for probing, detecting and analyzing molecules |
CN105980832A (en) * | 2013-12-10 | 2016-09-28 | 伊鲁米那股份有限公司 | Biosensors for biological or chemical analysis and methods of manufacturing the same |
CN107003241A (en) * | 2014-08-27 | 2017-08-01 | 加利福尼亚太平洋生物科学股份有限公司 | Integrated analysis device array |
CN108027325A (en) * | 2015-05-20 | 2018-05-11 | 宽腾矽公司 | Shone the method for definite nucleotide sequence using time resolution |
CN108463560A (en) * | 2016-01-15 | 2018-08-28 | 昆塔波尔公司 | Background with reduction is analyzed based on optical nano-pore |
WO2018159055A1 (en) * | 2017-02-28 | 2018-09-07 | 信越ポリマー株式会社 | Fluorescence assay multi-well plate and multi-well plate set, and method for producing fluorescence assay multi-well plate |
US20180326412A1 (en) * | 2017-05-05 | 2018-11-15 | Quantum-Si Incorporated | Substrates having modified surface reactivity and antifouling properties in biological reactions |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020224511A1 (en) * | 2019-05-05 | 2020-11-12 | 京东方科技集团股份有限公司 | Gene sequencing chip and method for manufacture thereof, and gene sequencing device |
CN113115586A (en) * | 2019-11-13 | 2021-07-13 | 京东方科技集团股份有限公司 | Detection chip, preparation method and use method thereof, and reaction system |
CN113115586B (en) * | 2019-11-13 | 2022-12-02 | 京东方科技集团股份有限公司 | Detection chip, preparation method and use method thereof, and reaction system |
CN113308351A (en) * | 2020-02-26 | 2021-08-27 | 京东方科技集团股份有限公司 | Detection chip, preparation method thereof and reaction system |
CN113308351B (en) * | 2020-02-26 | 2022-12-27 | 京东方科技集团股份有限公司 | Detection chip, preparation method thereof and reaction system |
Also Published As
Publication number | Publication date |
---|---|
WO2020224511A1 (en) | 2020-11-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110066723A (en) | Gene sequencing chip, equipment, manufacturing method | |
CN103460797A (en) | Organic light emitting diode, method for manufacturing same, image display device, and illuminating device | |
CN110506336A (en) | Biosensor and its manufacturing method for biological or chemical analysis | |
CN103299396A (en) | Laminate for forming fine pattern, and method for producing laminate for forming fine pattern | |
US8247962B2 (en) | Organic light emitting device and manufacturing method thereof | |
CN110168352A (en) | Biosensor for biological or chemical analysis and method of manufacturing the same | |
EP1291920A3 (en) | Solar cell, method for manufacturing the same, and apparatus for manufacturing the same | |
PT1192448E (en) | Process of using a sensor platform | |
CN109917504A (en) | A kind of the Zero-order diffractive grating and its manufacturing method of light-induced variable polychrome | |
CN107827076A (en) | Nano structural material structures and methods | |
TW591256B (en) | Light coupling-element, method to realize a polarization-independence and method to reduce the drop-size on the light coupling-element with surface-grids | |
US9907168B2 (en) | Ribbed large-format imprinting method | |
CN101908526B (en) | Alignment mark arrangement and alignment mark structure | |
CN106527043B (en) | A kind of method that stamping technique prepares large area photon scintillation crystal | |
CN106415332A (en) | Method for concentrating light and light concentrator | |
CN107850834A (en) | Autoregistration metal pattern based on metal nanoparticle photon sintering | |
CN107195538B (en) | The method for forming pattern | |
Petti et al. | Novel organic LED structures based on a highly conductive polymeric photonic crystal electrode | |
KR20080012752A (en) | Method of manufacturing a patterned color conversion layer, and methods of manufacturing a color conversion filter and an organic el display that use a color conversion layer obtained by the method | |
EP1557717B1 (en) | Method of forming sensors comprising barriers of photoresist material | |
CN105940506A (en) | Light-emitting element and light-emitting device | |
CN110211968A (en) | A kind of display base plate and preparation method thereof, display device | |
WO2013094918A1 (en) | Transparent substrate having nano pattern and method of manufacturing the same | |
CN106252496A (en) | Light-emitting device | |
CN110229747A (en) | Gene sequencing chip, equipment and preparation method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190730 |