CN110129893A - A kind of preparation method and applications of chip - Google Patents

A kind of preparation method and applications of chip Download PDF

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Publication number
CN110129893A
CN110129893A CN201910228224.0A CN201910228224A CN110129893A CN 110129893 A CN110129893 A CN 110129893A CN 201910228224 A CN201910228224 A CN 201910228224A CN 110129893 A CN110129893 A CN 110129893A
Authority
CN
China
Prior art keywords
chip
layer
preparation
nucleic acid
silicon dioxide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201910228224.0A
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Chinese (zh)
Inventor
胡军
王文忠
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Weikang (suzhou) Gene Technology Co Ltd
Original Assignee
Weikang (suzhou) Gene Technology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Weikang (suzhou) Gene Technology Co Ltd filed Critical Weikang (suzhou) Gene Technology Co Ltd
Priority to CN201910228224.0A priority Critical patent/CN110129893A/en
Publication of CN110129893A publication Critical patent/CN110129893A/en
Pending legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6834Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00Libraries per se, e.g. arrays, mixtures
    • C40B40/04Libraries containing only organic compounds
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00Libraries per se, e.g. arrays, mixtures
    • C40B40/04Libraries containing only organic compounds
    • C40B40/06Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis

Abstract

The present invention provides a kind of preparation method and applications of chip, the chip includes hypothallus, silicon wafer layer and silicon dioxide layer, containing different nucleic acid fragment point samples on chip, passes through mass spectral analysis precise measurement target dna sequence.The chip can measure nucleic acid molecules (A, T, C, G), nucleic acid small fragment;Other small molecules, such as amino acid, urea small molecule compound can also be measured simultaneously.Detection for nucleic acid fragment and other small molecules is provided convenience.Chip detection simply, conveniently, can be realized high-throughput detection, be with a wide range of applications.

Description

A kind of preparation method and applications of chip
Technical field
The present invention relates to biochip field, in particular to a kind of nucleic acid mass spectrum chip and preparation method thereof and application.
Background technique
The present invention relates to biochip field, in particular to a kind of nucleic acid mass spectrum chip and preparation method thereof and application, institute Stating nucleic acid mass spectrum chip includes hypothallus, silicon wafer layer and silicon dioxide layer;The material requested for preparing of the nucleic acid mass spectrum chip is The silicon wafer and hydroxy-picolinic acid of high-purity, by the preparation of wafer, wafer photolithography development, etching form silicon dioxide layer, hydroxyl Yl pyridines formic acid is prepared made from three steps of coating;Nucleic acid mass spectrum chip manufacturing of the invention is simple, low manufacture cost.This hair The nucleic acid mass spectrum chip of bright offer may be implemented on nucleic acid mass spectrograph, and after point sample, by laser, nucleic acid fragment in the electric field, leads to The difference of charge-mass ratio is crossed, the nucleic acid fragment of different molecular weight size is separated.
The separation that the present invention is intended to be used in nucleic acid molecules on nucleic acid mass spectrum, lays a good foundation thus for Genotyping.
Summary of the invention
It is an object of the invention to develop a kind of nucleic acid mass spectrum chip, it is mainly used for nucleic acid molecules or other small molecules It detects and separates.
To achieve the goals above, the present invention the following technical schemes are provided:
A kind of chip, the chip includes hypothallus, silicon wafer layer and silicon dioxide layer, containing different nucleic acid fragment point samples in core On piece passes through mass spectral analysis precise measurement target dna sequence.
The preparation method of chip of the present invention, comprising the following steps:
(1) basal layer of the preparation for chip preparation, is silicon wafer layer, and the purity of silicon is 99.999%;
It (2) is silicon dioxide layer in preparing middle layer on basal layer, silicon dioxide layer is developed by wafer photolithography, etches shape At silicon dioxide layer;
It (3) is hypothallus in preparing superficial layer in middle layer, matrix layer formula is hydroxy-picolinic acid.
Chip of the invention includes hypothallus, silicon wafer layer and silicon dioxide layer.The purity of silicon dioxide layer, silicon is 99.999%.It is silicon dioxide layer for being good for layer in chip preparation, silicon dioxide layer is developed by wafer photolithography, etching is formed Silicon dioxide layer;Superficial layer for chip preparation is hypothallus, and matrix layer formula is hydroxy-picolinic acid.
Preferably, there is everybody 200 μm of hypothallus of 96 length and width on the silicon wafer layer.
Preferably, there is each 40 μm of a length and width of small frame block among two neighboring hypothallus, be used for laser alignment.
Application of the above-described chip in nucleic acid molecules or amino acid, the detection of urea small molecule.
The beneficial effects of the present invention are: the present invention provides a kind of preparation method and applications of chip, which can be with It measures nucleic acid molecules (A, T, C, G), nucleic acid small fragment;Other small molecules, such as small point of amino acid, urea can also be measured simultaneously Sub- compound.Detection for nucleic acid fragment and other small molecules is provided convenience.Chip detection simply, conveniently, can be realized High throughput detection, is with a wide range of applications.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of chip of the invention.
Fig. 2 is the constituent analysis figure of chip hydroxy-picolinic acid of the present invention.
Fig. 3 is the constituent analysis figure of chip silica of the present invention.
Fig. 4 is the constituent analysis figure of chip high purity silicon of the present invention.
Fig. 5 is the result analysis chart for detecting HPV.
Specific embodiment
The present invention will be further described in detail below with reference to the embodiments, to enable those skilled in the art referring to specification Text can be implemented accordingly.
A kind of chip, the chip include hypothallus, silicon wafer layer and silicon dioxide layer, contain different nucleic acid fragment point samples On chip, pass through mass spectral analysis precise measurement target dna sequence.
The preparation method of chip of the present invention, comprising the following steps:
(1) basal layer of the preparation for chip preparation, is silicon wafer layer, and the purity of silicon is 99.999%;
It (2) is silicon dioxide layer in preparing middle layer on basal layer, silicon dioxide layer is developed by wafer photolithography, etches shape At silicon dioxide layer;
It (3) is hypothallus in preparing superficial layer in middle layer, matrix layer formula is hydroxy-picolinic acid.
Fig. 1 is the structural schematic diagram of chip of the invention, and 200 μm of black of circle is hypothallus in figure, 40 μm of silver color Circle is used for laser alignment, and bottom is silicon wafer.
Table 1 is the constituent analysis table of chip of the present invention, and #1 is hydroxy-picolinic acid in table 1, and #2 is silica, and #3 is height Purity silicon, corresponding component content difference are as shown in Figure 2,3, 4.
Table 1
Chip of the invention includes hypothallus, silicon wafer layer and silicon dioxide layer.Silicon dioxide layer, the purity of silicon are 99.999%. It is silicon dioxide layer for being good for layer in chip preparation, silicon dioxide layer is developed by wafer photolithography, etching forms silica Layer;Superficial layer for chip preparation is hypothallus, and matrix layer formula is hydroxy-picolinic acid.
There is everybody 200 μm of hypothallus of 96 length and width on the silicon wafer layer.
There is each 40 μm of a length and width of small frame block among two neighboring hypothallus, is used for laser alignment.
The chip prepared with this method, detects HPV, and result is as shown in Figure 5.

Claims (5)

1. a kind of chip, which is characterized in that the chip includes hypothallus, silicon wafer layer and silicon dioxide layer, contains different core Acid fragment point sample passes through mass spectral analysis precise measurement target dna sequence on chip.
2. the preparation method of chip described in claim 1, which comprises the following steps:
(1) basal layer of the preparation for chip preparation, is silicon wafer layer, and the purity of silicon is 99.999%;
It (2) is silicon dioxide layer in preparing middle layer on basal layer, silicon dioxide layer is developed by wafer photolithography, etches shape At silicon dioxide layer;
It (3) is hypothallus in preparing superficial layer in middle layer, matrix layer formula is hydroxy-picolinic acid.
3. preparation method according to claim 2, which is characterized in that have on the silicon wafer layer 96 length and width everybody 200 μm Hypothallus.
4. preparation method according to claim 3, which is characterized in that there is length and width each 40 among two neighboring hypothallus μm small frame block, be used for laser alignment.
5. application of the chip described in claim 1 in nucleic acid molecules or amino acid, the detection of urea small molecule.
CN201910228224.0A 2019-03-25 2019-03-25 A kind of preparation method and applications of chip Pending CN110129893A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910228224.0A CN110129893A (en) 2019-03-25 2019-03-25 A kind of preparation method and applications of chip

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910228224.0A CN110129893A (en) 2019-03-25 2019-03-25 A kind of preparation method and applications of chip

Publications (1)

Publication Number Publication Date
CN110129893A true CN110129893A (en) 2019-08-16

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910228224.0A Pending CN110129893A (en) 2019-03-25 2019-03-25 A kind of preparation method and applications of chip

Country Status (1)

Country Link
CN (1) CN110129893A (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6300076B1 (en) * 1995-03-17 2001-10-09 Sequenom, Inc. DNA diagnostics based on mass spectrometry
CN101965221A (en) * 2008-01-15 2011-02-02 塞昆纳姆股份有限公司 Compositions and processes for improved mass spectrometry analysis
CN107192757A (en) * 2017-07-05 2017-09-22 北京毅新博创生物科技有限公司 A kind of dual-purpose detection kit of mass spectrum
CN108008002A (en) * 2017-10-31 2018-05-08 北京毅新博创生物科技有限公司 Correct the method and product of the accuracy rate of Mass Spectrometer Method nucleic acid samples

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6300076B1 (en) * 1995-03-17 2001-10-09 Sequenom, Inc. DNA diagnostics based on mass spectrometry
CN101965221A (en) * 2008-01-15 2011-02-02 塞昆纳姆股份有限公司 Compositions and processes for improved mass spectrometry analysis
CN107192757A (en) * 2017-07-05 2017-09-22 北京毅新博创生物科技有限公司 A kind of dual-purpose detection kit of mass spectrum
CN108008002A (en) * 2017-10-31 2018-05-08 北京毅新博创生物科技有限公司 Correct the method and product of the accuracy rate of Mass Spectrometer Method nucleic acid samples

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
有机质谱专业委员会: "《现代有机质谱技术及应用》", 31 August 1999, 中国人民公安大学出版社 *

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