CN110229747A - Gene sequencing chip, equipment and preparation method - Google Patents
Gene sequencing chip, equipment and preparation method Download PDFInfo
- Publication number
- CN110229747A CN110229747A CN201910526700.7A CN201910526700A CN110229747A CN 110229747 A CN110229747 A CN 110229747A CN 201910526700 A CN201910526700 A CN 201910526700A CN 110229747 A CN110229747 A CN 110229747A
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- Prior art keywords
- main body
- base main
- gene sequencing
- slot
- sequencing
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- 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 invention discloses gene sequencing chip, equipment and preparation methods, the gene detecting chip includes: base main body, first side of the base main body is provided at least one sequencing slot, first side of the base main body and be provided in the region of the sequencing slot and take photo structure, it is described take photo structure for will be located in the base main body and be taken described in directive the light of photo structure from the first of the base main body it is side-draw go out.The gene sequencing chip further improves the accuracy of genetic test.
Description
Technical field
The present invention relates to gene sequencing field, in particular to a kind of gene sequencing chip, a kind of gene sequencing equipment, one kind
The preparation method of gene sequencing chip.
Background technique
In existing gene sequencing chip, setting sequencing slot (or claiming sequencing hole) usually in base main body.It is glimmering
The a certain base analog (one of adenine, thymus gland purine, cytimidine, guanine) of light group label is in the illumination of specific wavelength
In the case where be excited and issue the light of particular color.The light issued and being stimulated to fluorophor detects, in turn
It is inferred to the sequence of base in gene.The light part that fluorophor in sequencing slot is issued directly is penetrated from sequencing notch outward
Out, in the medium other than part directive sequencing groove sidewall, and reflection or total reflection finally occurs in the top surface of the medium.Directive is surveyed
The light of medium other than sequence groove sidewall can be only detected on a small quantity, be unfavorable for further mentioning for the accuracy of gene sequencing
It rises.
Summary of the invention
The present invention is directed at least solve one of the technical problems existing in the prior art, a kind of gene sequencing core is proposed
Piece, a kind of gene sequencing equipment, a kind of preparation method of gene sequencing chip.
To achieve the above object, a kind of gene sequencing chip is provided, comprising: base main body, the first of the base main body
Side is provided at least one sequencing slot, the first side of the base main body and is provided in the region of the sequencing slot and takes light
Structure, it is described to take photo structure for that be located in the base main body and take the light of photo structure from the substrate master described in directive
The first of body is side-draw out.
Optionally, the first side of the base main body and except be provided with it is described sequencing slot in addition to other regions be respectively provided with
Photo structure is taken described in having.
It is optionally, described that take photo structure include: to be set to the first side of the base main body and more in periodic arrangement
A micro-groove.
Optionally, the cross sectional shape on the surface of the first side for being parallel to the base main body of the micro-groove is circle.
Optionally, the diameter d1 of the circular cross-section of the micro-groove meets: 20nm≤d1≤250nm.
Optionally, the groove depth h1 of the micro-groove meets: 20nm≤h1≤300nm.
Optionally, it is taken in photo structure described, the distance between central point of two micro-grooves of arbitrary neighborhood p1 is full
Foot: 40nm≤p1≤500nm.
Optionally, the cross sectional shape on the surface of the first side for being parallel to the base main body of the sequencing slot is circle.
Optionally, the diameter d2 of the circular cross-section of the sequencing slot meets: 100nm≤d2≤2um.
Optionally, the groove depth h2 of the sequencing slot meets: 100nm≤h2≤2um.
Optionally, it is described sequencing slot quantity be it is multiple, arbitrary neighborhood two it is described sequencing slot central points between away from
Meet from p2: 200nm≤p2≤5um.
To achieve the above object, a kind of gene sequencing equipment is provided, comprising: such as above-mentioned gene sequencing chip.
To achieve the above object, a kind of preparation method of gene sequencing chip is provided, the gene sequencing chip is above-mentioned
Gene sequencing chip, the preparation method includes:
The base main body is provided；
The sequencing slot, and the shape on the first side of the base main body are formed on the first side of the base main body
Photo structure is taken at described.
Optionally, the step of offer base main body specifically includes:
Coining glue is formed on underlay substrate；
It is described that the sequencing slot is formed on the first side of the base main body, and in the first side of the base main body
The step of taking photo structure described in upper formation specifically includes:
Coining processing is carried out to the coining glue using scheduled nano-imprint stamp, to form the sequencing slot and described
Micro-groove.
Detailed description of the invention
Fig. 1 is the sectional view of the gene sequencing chip of the embodiment of the present invention；
Fig. 2 is the top view of the gene sequencing chip of the embodiment of the present invention；
Fig. 3 is the index path of the gene sequencing chip of the embodiment of the present invention；
Fig. 4 is the flow chart of the preparation method of the gene sequencing chip of the embodiment of the present invention；
Wherein, appended drawing reference are as follows: 1, base main body；2, slot is sequenced；3, photo structure is taken；31, micro-groove；4, testing gene；
5, fluorophor.
Specific embodiment
To make those skilled in the art more fully understand technical solution of the present invention, the present invention is mentioned with reference to the accompanying drawing
Gene sequencing chip, equipment and the preparation method of confession are described in detail.
Embodiment 1:
Referring to Fig.1-3, the present embodiment provides a kind of gene sequencing chips, comprising: base main body 1, the first of base main body 1
Side is provided at least one sequencing slot 2, the first side of base main body 1 and is provided in the region of sequencing slot 2 and takes photo structure
3, take photo structure 3 for will be located in base main body 1 and directive take the light of photo structure 3 from the first of base main body 1 it is side-draw go out.
Base main body 1 can be homogenous material formation, is also possible to multilayer material lamination or is mixed to form.
When carrying out gene sequencing, testing gene 4 is located in sequencing slot 2, and specific fluorescent group 5 marks in testing gene 4.
With Fig. 3 current visual angle, the wide part that fluorophor 5 is stimulated and issues is projected (with Fig. 3 upwards by the notch of sequencing slot 2
In thicker arrow indicate).
In the prior art, fluorophor 5 can be in Jie being sequenced other than 2 side wall of slot to the light that the side wall of sequencing slot 2 projects
Sounding reflection or total reflection on the surface of matter, the final only a small part meeting directive of this part light are opposite with gene sequencing chip
Optical detection device (not shown).This is unfavorable for the accuracy for improving gene sequencing.And the scheme of the present embodiment is used, this part
Light can be taken photo structure 3 to take out (indicating this part light with arrow thin in Fig. 3).In this way, being examined with the light of gene sequencing chip cooperation
It surveys device and is able to detect that the light of greater strength, to be conducive to improve the accuracy of gene sequencing.
Certainly it takes photo structure 3 that can surround sequencing slot 2 completely, is also possible to part and surrounds sequencing slot 2.No matter which kind of side
Formula can improve the utilization rate that directive takes the lateral light out of 3 corresponding position of photo structure.
Optionally, in the first side of base main body 1 and other regions in addition to being provided with sequencing slot 2 are provided with and take light
Structure 3.I.e. as shown in Fig. 2, taking light binding structure is the region being covered between adjacent sequencing slot 2, and completely by each sequencing slot 2
It surrounds.In this way, the rate that above-mentioned lateral light out on the one hand can be improved to a greater degree is used to, manufacture work on the other hand can simplify
Skill.Certainly, by taking Fig. 3 as an example, Fig. 3 center position takes photo structure 3 that can remove, and is still able to achieve each sequencing slot 2
Photo structure 3 is all taken to surround completely.
In the present invention, taking photo structure 3 can be the absolute construction for being placed in the first side of base main body 1, be also possible to
The integrally formed structure of base main body 1, two kinds of situations all belong to the scope of protection of the present invention.Exception, in practical applications, also
It can according to need and photo structure 3 is being taken also to should belong to backwards to the side of base main body 1 setting other structures (for example, cover board)
Protection scope of the present invention.
Optionally, as depicted in figs. 1 and 2, taking photo structure 3 includes: to be set to the first side of base main body 1 and in periodically
Multiple micro-grooves 31 of arrangement.The structure that multiple micro-grooves 31 of periodic arrangement are constituted, which is equivalent to, to be periodically alternately distributed
Two media (one of which be air, a kind of material for 1 corresponding position of base main body).It is micro- in example shown in Fig. 2
Type groove 31 is periodically arranged in both directions, is equivalent to and is constituted 2 D photon crystal.Experiment discovery, this structure have very
Good takes light characteristic, and the especially total reflection light by script where it on interface becomes part reflected light.Certain micro-groove 31
Shape is not limited to circle, and the both direction of periodic arrangement is not limited to vertical both direction.
Optionally, the cross sectional shape on the surface of the first side for being parallel to base main body 1 of micro-groove 31 is circle.
Optionally, the diameter d1 of the circular cross-section of micro-groove 31 meets: 20nm≤d1≤250nm.
Optionally, the groove depth h1 of micro-groove 31 meets: 20nm≤h1≤300nm.
Optionally, in taking photo structure 3, the distance between central point of two micro-grooves 31 of arbitrary neighborhood p1 meets:
40nm≤p1≤500nm。
The groove depth of micro-groove 31, the size of shape and correspondingly-shaped, center away from etc. parameters the light of light can be taken to it
Wave-length coverage impact.Above-mentioned value range is particularly corresponding to the wave-length coverage of visible light.
Optionally, the cross sectional shape that the surface of the first side for being parallel to base main body 1 of slot 2 is sequenced is circle.
Optionally, the diameter d2 that the circular cross-section of slot 2 is sequenced meets: 100nm≤d2≤2um.
Optionally, the groove depth h2 that slot 2 is sequenced meets: 100nm≤h2≤2um.
Optionally, the quantity of sequencing slot 2 is multiple, and the distance between central point of arbitrary neighborhood two sequencing slots 2 p2 is full
Foot: 200nm≤p2≤5um.
The dimensional parameters of the above sequencing slot 2 may make the fluorophor 5 in sequencing slot 2 to issue the big portion in whole light
Dividing can final directive optical detection device.
Embodiment 2:
The present embodiment provides a kind of gene sequencing equipment, comprising: gene sequencing chip, the gene sequencing chip is using implementation
The gene sequencing chip that example 1 provides.
The detection that the gene sequencing equipment goes out light to gene sequencing chip side in it is more accurate, so that gene sequencing
Result it is more accurate.
Embodiment 3:
Referring to Fig. 4 and Fig. 1-3 is combined, the present embodiment provides a kind of preparation method of gene sequencing chip, gene sequencing cores
Piece is the gene sequencing chip of embodiment 1, and preparation method includes:
Step S1, base main body is provided.
Step S2, sequencing slot is formed on the first side of base main body, and is formed and taken on the first side of base main body
Photo structure.
It, can be to glimmering on the testing gene 4 of placement subsequent in it according to gene sequencing chip made from the manufacturing method
The light that light group 5 issues greatly is utilized, to improve the accuracy of gene sequencing.
Sequencing slot 2 is formed by for step S2 and takes the specific descriptions of photo structure 3, reference can be made to corresponding in previous embodiment
Content, details are not described herein again.
Optionally, in a specific example, detailed preparation method includes the following steps.
The first step forms coining glue on underlay substrate.In this embodiment, base main body 1 includes one layer of substrate base
Plate and a lamination print glue.
Second step carries out coining processing to coining glue using scheduled nano-imprint stamp, to form sequencing slot 2 and miniature
Slot 31.I.e. by the technique of coining, sequencing slot 2 and micro-groove 31 are formed simultaneously in coining glue.Certainly, periodic arrangement is micro-
Type groove 31, which constitutes, takes photo structure 3.
Certainly, sequencing slot 2 for example can be by being initially formed to the technique that underlay substrate performs etching, then again to survey
Sequence slot 2 performs etching to obtain micro-groove 31 with the top layer of the underlay substrate material of exterior domain.31 structure of micro-groove of periodic arrangement
At taking photo structure 3.Those skilled in the art can design a variety of different detailed step of preparation process.The present embodiment is to this
It is not specially limited.
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 (14)
1. a kind of gene sequencing chip characterized by comprising base main body, the first side of the base main body be provided with to
A few sequencing slot, the first side of the base main body and is provided in the region that slot is sequenced and takes photo structure, described
Take photo structure for that will be located in the base main body and take the light of photo structure from the first of the base main body described in directive
It is side-draw go out.
2. gene sequencing chip according to claim 1, which is characterized in that
The base main body the first side and other regions in addition to being provided with the sequencing slot be provided with and described take light
Structure.
3. gene sequencing chip according to claim 1 or 2, which is characterized in that described to take photo structure include: to be set to institute
It states the first side of base main body and is in multiple micro-grooves of periodic arrangement.
4. gene sequencing chip according to claim 3, which is characterized in that the micro-groove is parallel to the substrate master
The cross sectional shape on the surface of the first side of body is circle.
5. gene sequencing chip according to claim 4, which is characterized in that the diameter d1 of the circular cross-section of the micro-groove
Meet: 20nm≤d1≤250nm.
6. gene sequencing chip according to claim 3, which is characterized in that the groove depth h1 of the micro-groove meets: 20nm
≤h1≤300nm。
7. gene sequencing chip according to claim 3, which is characterized in that taken in photo structure described, arbitrary neighborhood two
The distance between the central point of a micro-groove p1 meets: 40nm≤p1≤500nm.
8. gene sequencing chip according to claim 1, which is characterized in that the sequencing slot is parallel to the substrate master
The cross sectional shape on the surface of the first side of body is circle.
9. gene sequencing chip according to claim 8, which is characterized in that the diameter d2 of the circular cross-section of the sequencing slot
Meet: 100nm≤d2≤2um.
10. gene sequencing chip according to claim 8, which is characterized in that the groove depth h2 of the sequencing slot meets:
100nm≤h2≤2um。
11. gene sequencing chip according to claim 8, which is characterized in that it is described sequencing slot quantity be it is multiple, arbitrarily
The distance between the central point of two neighboring sequencing slot p2 meets: 200nm≤p2≤5um.
12. a kind of gene sequencing equipment characterized by comprising the gene sequencing as described in the claims 1-11 is any
Chip.
13. a kind of preparation method of gene sequencing chip, which is characterized in that the gene sequencing chip is the claims 1-
Any gene sequencing chip, the preparation method include: in 11
The base main body is provided；
The sequencing slot is formed on the first side of the base main body, and forms institute on the first side of the base main body
It states and takes photo structure.
14. preparation method according to claim 13, which is characterized in that when the gene sequencing chip is wanted for aforesaid right
When seeking gene sequencing chip described in 3；
The step of offer base main body, specifically includes:
Coining glue is formed on underlay substrate；
It is described that the sequencing slot, and the shape on the first side of the base main body are formed on the first side of the base main body
It is specifically included at described the step of taking photo structure:
Coining processing is carried out to the coining glue using scheduled nano-imprint stamp, to form the sequencing slot and the micro-groove.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201910526700.7A CN110229747A (en) | 2019-06-18 | 2019-06-18 | Gene sequencing chip, equipment and preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910526700.7A CN110229747A (en) | 2019-06-18 | 2019-06-18 | Gene sequencing chip, equipment and preparation method |
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| CN110229747A true CN110229747A (en) | 2019-09-13 |
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| CN201910526700.7A Pending CN110229747A (en) | 2019-06-18 | 2019-06-18 | Gene sequencing chip, equipment and preparation method |
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Cited By (1)
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| CN110591903A (en) * | 2019-09-19 | 2019-12-20 | 京东方科技集团股份有限公司 | Gene sequencing substrate, manufacturing method thereof and gene sequencing chip |
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