CN102649931A - Preparation method for microarray biochip - Google Patents
Preparation method for microarray biochip Download PDFInfo
- Publication number
- CN102649931A CN102649931A CN2012101673476A CN201210167347A CN102649931A CN 102649931 A CN102649931 A CN 102649931A CN 2012101673476 A CN2012101673476 A CN 2012101673476A CN 201210167347 A CN201210167347 A CN 201210167347A CN 102649931 A CN102649931 A CN 102649931A
- Authority
- CN
- China
- Prior art keywords
- array
- biochip
- micro
- preparation
- sample
- 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
Landscapes
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention relates to a preparation method for a microarray biochip. M print spray heads are used to constitute a spray head group, the spray heads are installed in the direction parallel to the X direction, and are arranged along the Y direction; a biochip substrate and the spray head group move step by step relatively along the Y direction, the action of a corresponding nozzle on the spray head corresponding to each step position is controlled by a driving signal, and a biomolecule solution of one index is sprayed onto the preset position of one or a plurality of microarray biochip substrates arranged along the X direction; and through the sequential action of the M spray heads, the biomolecule solutions of M indexes are sequentially sprayed onto the preset position of the biochip substrate to form a sample application array. The preparation for the microarray biochip used for multi-index and multi-user parallel detection can be realized. Compared with the existing product, the biochip prepared in the method disclosed by the invention has the characteristics of high speed, high precision, wide applicability, high efficiency, small cross contamination, easiness in maintenance and use, low manufacturing cost and the like, and the method is very suitable for the large-scale production of microarray biochips and is also suitable for scientific research and application.
Description
Technical field
The present invention relates to a kind of biochip technology of preparing, particularly a kind of microarray parallel detection is with the preparation method of micro-array biochip.
Background technology
The preparation method of existing biochip can be divided into two types basically: one type is original position synthetic (promptly at support surface direct in-situ synthetic oligonucleotide probe); One type is directly point sample of synthetic in advance back, and minim DNA solution is directly put and is solidificated on the biochip matrix with the form point of microarray.Because in-situ synthetic method is very complicated, so most dna microarray chip all is to adopt synthetic point sample method.And the preparation of protein chip, because the restriction of method all is the method preparation of adopting synthetic earlier back point sample.Synthetic point sample method is with after, the quantitative analysis purified through the synthetic good probe of liquid phase chemical in advance; Through the microarray sample application platform; Accurately and rapidly with the quantitative point sample of different probe sample on corresponding positions such as positively charged nylon membrane or silicon chip, promptly obtain dna microarray or protein chip after the curing.
The mode of tradition point sample is divided two kinds, and one of which is the contact point sample, and promptly point needle directly contacts with the biochip stromal surface, and sample is stayed on the matrix; It two is contactless point sample, uses special-purpose little specking appearance shower nozzle of piezoelectric principle or micro-SV break-make principles, through kapillary sample is sprayed onto the biochip stromal surface.
In the contact point sample, point needle needs to immerse in the source plate earlier to dip in sample thief, mentions the back forms certain volume on the top of pin drop; Move on the corresponding slide position, the contact substrate forms sampling point to sample transfer; Constantly repeat this process, accomplish until the chip preparation.Contact point sample shortcoming is obvious: it is very little that solid point needle carries sample size, each sampling can only point sample once, production process is very slow; Every chip differs from the distance of source plate, and point needle takes time to chip from microwell plate transfer sample and do not wait, and evaporation alters a great deal to the influence degree of drop, makes that sampling point diameter homogeneity is relatively poor: the sampling point diameter near from source plate is bigger, and diameter far away is then less.
In the contactless point sample, hollow point needle immerses earlier draws a spot of sample in the source plate, and the point needle nozzle is ejected into the sample pointwise on the chip surface then.Than the contact point sample, contactless point needle can once be inhaled repeatedly point sample of appearance, can improve point sample efficient relatively, but still needs pointwise spray appearance, can't carry out many person-portions, many indexs point sample simultaneously.
Show that through investigation and experiment industrial ink gun physical accuracy can reach 185dpi-360dpi, the I of drop volume reaches 14pL-80pL and does not wait, and can be used in the spray of biochip fully.
Summary of the invention
The present invention be directed to present biological preparation efficiency low, can't many parts the problem of point samples simultaneously; A kind of micro-array biochip preparation method has been proposed; Use " spray printing formula " micro-array biochip preparation method of industrial inkjet printing head, can realize that many indexs, many person-portions detect the quick production with micro-array biochip.
Technical scheme of the present invention is: a kind of micro-array biochip preparation method specifically comprises the steps:
1) use M printing head to form jet head sets, shower nozzle is parallel to directions X to be installed, and arranges along the Y direction;
2) biochip matrix is along the relative step motion with jet head sets of Y direction; Through the action of respective nozzle on the corresponding shower nozzle of each stepping position of actuate signal control institute, the biomolecule solution of an index is ejected into along on the predetermined position of one or more micro-array biochip matrix of directions X arrangement;
3), the biomolecule solution of M index is ejected on the predetermined position of biochip matrix the formation sample application array successively line by line through the sequentially-operating through M shower nozzle.
The spacing of said point sample density and sample application array realizes through the gating that actuate signal is controlled a determining deviation upper spray nozzle; If the spacing of adjacent nozzle is e, then the sampling point spacing is ne in the sample application array, and promptly two main jet spacings are ne; N is two nozzles between main jet numbers at interval; The interval controlling method of sample application array is similar, remembers that adjacent two sample application array spacings are me, m the injector spacing of promptly being separated by.
The size of said point sample is by the amplitude size and the frequency control of actuate signal.
Said each shower nozzle only sprays a kind of biomolecule solution of index.
Sampling point spacing on directions X and Y direction is identical in the said sample application array, is the integral multiple of injector spacing.
The pairing nozzle of the sample spot of the same index of arranging on the said directions X is by same drive.
Said chip matrix can be that jet head sets is moved along Y direction and jet head sets relative movement, and chip matrix is fixed; Also can be that jet head sets is fixed, the chip matrix motion.
Said employed shower nozzle mode of operation can be piezoelectric type or heating power formula.
Said biomolecule solution can be nucleic acid or protein, and nucleic acid comprises dna probe.
Said biochip matrix can be one or more membrane matrix, also can be one or more slides, can also be one or more porous plate.
Beneficial effect of the present invention is: micro-array biochip preparation method of the present invention, can realize the preparation of many indexs, the parallel detection of many person-portions with micro-array biochip; Compare with present existing products, characteristics such as speed is fast, precision is high, suitability is wide, efficient is high, crossed contamination is few, maintenance is easy to use, low cost of manufacture are highly suitable for the large-scale production of biochip, also are suitable for scientific research and application.
Description of drawings
Fig. 1 is used to prepare the point sample instrument jet head sets synoptic diagram of biochip for the present invention;
Fig. 2 is a micro-array biochip preparation method example schematic of the present invention;
Fig. 3 is the prepared biochip micro array structure figure of micro-array biochip preparation method of the present invention.
Embodiment
Like Fig. 1 or shown in Figure 2,1-8 is the jet head sets that shower nozzle is formed, and 9 is biological chip matrix, and 10-17 is the illustrated position of main jet, and a, b are the different index sampling points of two kinds in the exemplary array structure.Biochip matrix 9 moves along the Y direction, when the predetermined position of chip matrix 9 moves to the position of first shower nozzle 1, and the nozzle action that 10,11 and 12,13 places of actuate signal control shower nozzle 1 are corresponding, a is ejected on the matrix with the biomolecule solution sample.
When the chip predetermined position moves to second shower nozzle 2 position, the nozzle action that 14,15 and 16,17 places of actuate signal control shower nozzle are corresponding, b is ejected on the matrix with the biological solution sample.First row point sample row so just on directions X, have been accomplished.The preparation method of other point sample row is identical, accomplishes net result biochip micro array structure as shown in Figure 3 figure by 3 to No. 8 shower nozzles respectively.
The spacing of point sample density and sample application array realizes through the gating that actuate signal is controlled a determining deviation upper spray nozzle.If the spacing of adjacent nozzle 10,11 is e, then the sampling point spacing is ne in the sample application array, and promptly two main jet spacings are ne, and n is two nozzles between main jet numbers at interval.Number is more little at interval for nozzle between the main jet of gating, and the sampling point spacing is more little, and point sample density is high more.The interval controlling method of sample application array is similar, remembers that adjacent two sample application array spacings are me, m the injector spacing of promptly being separated by.
The size of sampling point is by the amplitude size and the frequency control of actuate signal; The less actuate signal of amplitude produces small droplets; The signal that amplitude is bigger can produce medium-sized drop; And two pulses closely can spray small droplets and medium-sized drop continuously, and they accomplish merging process aloft, drop on the bigger sampling point of formation on the matrix.
The inventive method can realize the preparation with micro-array biochip of many indexs, the parallel detection of many person-portions.Compare with present existing products, speed is fast, and is faster than contact mechanical deposition method and the noncontact specking appearance pin type point sample speed that declines, especially scale operation; Precision is high, and ink jet type point sample drop is little, and density is high, and precision is good, quantitatively accurate, sampling point homogeneous, favorable reproducibility; Suitability is wide, can carry out point sample to the sheet base of multiple material, can be membrane matrixs such as one or more nylon membrane or nitrocellulose membrane, also can be rigid matrixs such as one or more slides, can also be one or more porous plate; Efficient is high, and this sample application platform laterally can be to a plurality of person-portions while point samples in the ink-jet scope, the operations simultaneously of also a plurality of jet head sets; Vertically can be to many person-portions streamline operration, and can carry out the point sample of many indexs sample, improved point sample efficient greatly; Crossed contamination is few, and an ejection head unit only is responsible for the sample of one of them index of point, and scavenging period when having saved the replacing sample has also effectively reduced the crossed contamination of different sample rooms.
Claims (10)
1. a micro-array biochip preparation method is characterized in that, specifically comprises the steps:
1) use M printing head to form jet head sets, shower nozzle is parallel to directions X to be installed, and arranges along the Y direction;
2) biochip matrix is along the relative step motion with jet head sets of Y direction; Through the action of respective nozzle on the corresponding shower nozzle of each stepping position of actuate signal control institute, the biomolecule solution of an index is ejected into along on the predetermined position of one or more micro-array biochip matrix of directions X arrangement;
3), the biomolecule solution of M index is ejected on the predetermined position of biochip matrix the formation sample application array successively line by line through the sequentially-operating through M shower nozzle.
2. according to the said micro-array biochip preparation method of claim 1, it is characterized in that the spacing of said point sample density and sample application array realizes through the gating that actuate signal is controlled a determining deviation upper spray nozzle; If the spacing of adjacent nozzle is e, then the sampling point spacing is ne in the sample application array, and promptly two main jet spacings are ne; N is two nozzles between main jet numbers at interval; The interval controlling method of sample application array is similar, remembers that adjacent two sample application array spacings are me, m the injector spacing of promptly being separated by.
3. according to the said micro-array biochip preparation method of claim 1, it is characterized in that the size of said point sample is by the amplitude size and the frequency control of actuate signal.
4. micro-array biochip preparation method according to claim 1 is characterized in that said each shower nozzle only sprays a kind of biomolecule solution of index.
5. micro-array biochip preparation method according to claim 1 is characterized in that, sampling point spacing on directions X and Y direction is identical in the said sample application array, is the integral multiple of injector spacing.
6. micro-array biochip preparation method according to claim 1 is characterized in that, the pairing nozzle of the sample spot of the same index of arranging on the said directions X is by same drive.
7. micro-array biochip preparation method according to claim 1 is characterized in that, said chip matrix can be that jet head sets is moved along Y direction and jet head sets relative movement, and chip matrix is fixed; Also can be that jet head sets is fixed, the chip matrix motion.
8. micro-array biochip preparation method according to claim 1 is characterized in that, said employed shower nozzle mode of operation can be piezoelectric type or heating power formula.
9. micro-array biochip preparation method according to claim 1 is characterized in that said biomolecule solution can be nucleic acid or protein, and nucleic acid comprises dna probe.
10. micro-array biochip preparation method according to claim 1 is characterized in that, said biochip matrix can be one or more membrane matrix, also can be one or more slides, can also be one or more porous plate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101673476A CN102649931A (en) | 2012-05-28 | 2012-05-28 | Preparation method for microarray biochip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101673476A CN102649931A (en) | 2012-05-28 | 2012-05-28 | Preparation method for microarray biochip |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102649931A true CN102649931A (en) | 2012-08-29 |
Family
ID=46692058
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101673476A Pending CN102649931A (en) | 2012-05-28 | 2012-05-28 | Preparation method for microarray biochip |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102649931A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103869075A (en) * | 2012-12-14 | 2014-06-18 | 仓怀兴 | Preparation device of protein chip by real-time quantitative detection and capillary electrophoresis |
| CN104593870A (en) * | 2015-02-02 | 2015-05-06 | 上海理工大学 | Linear-array-sprayer multi-sampling-point method for dynamically preparing biochips |
| CN105842171A (en) * | 2015-01-15 | 2016-08-10 | 中国科学院苏州纳米技术与纳米仿生研究所 | Biochemical detection system |
| TWI641833B (en) * | 2018-02-07 | 2018-11-21 | 國立臺灣師範大學 | Marking equipment for making biochips |
| CN112218708A (en) * | 2018-05-15 | 2021-01-12 | 生物复制有限公司 | Microarray transducer |
| CN112881494A (en) * | 2020-11-09 | 2021-06-01 | 北京大学 | Field effect transistor type biosensing device for multi-index detection |
| CN112973592A (en) * | 2019-12-16 | 2021-06-18 | 天津大学 | High-throughput DNA synthesis device and method based on array type ink-jet printing |
| CN113324813A (en) * | 2021-05-27 | 2021-08-31 | 江西烈冰生物科技有限公司 | Biological probe sample application method and process based on high-density dot matrix |
| CN115452507A (en) * | 2022-09-01 | 2022-12-09 | 广西大学 | Array type biochip sample application device |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1186888A1 (en) * | 2000-04-03 | 2002-03-13 | Riken | Microarray fabricating device |
| CN101334405A (en) * | 2007-06-26 | 2008-12-31 | 上海裕隆生物科技有限公司 | Biological chips sample application platform |
| CN101334403A (en) * | 2007-06-26 | 2008-12-31 | 上海裕隆生物科技有限公司 | Assembly line biological chips sample application platform |
| CN102080072A (en) * | 2010-11-29 | 2011-06-01 | 中国科学院化学研究所 | Biochip and preparation method thereof |
| WO2011156836A1 (en) * | 2010-06-17 | 2011-12-22 | Geneasys Pty Ltd | Apparatus for loading oligonucleotide spotting devices and spotting oligonucleotide probes |
-
2012
- 2012-05-28 CN CN2012101673476A patent/CN102649931A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1186888A1 (en) * | 2000-04-03 | 2002-03-13 | Riken | Microarray fabricating device |
| CN101334405A (en) * | 2007-06-26 | 2008-12-31 | 上海裕隆生物科技有限公司 | Biological chips sample application platform |
| CN101334403A (en) * | 2007-06-26 | 2008-12-31 | 上海裕隆生物科技有限公司 | Assembly line biological chips sample application platform |
| WO2011156836A1 (en) * | 2010-06-17 | 2011-12-22 | Geneasys Pty Ltd | Apparatus for loading oligonucleotide spotting devices and spotting oligonucleotide probes |
| CN102080072A (en) * | 2010-11-29 | 2011-06-01 | 中国科学院化学研究所 | Biochip and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 焦炳华 等: "《现代生物工程》", 31 March 2007 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103869075A (en) * | 2012-12-14 | 2014-06-18 | 仓怀兴 | Preparation device of protein chip by real-time quantitative detection and capillary electrophoresis |
| CN105842171A (en) * | 2015-01-15 | 2016-08-10 | 中国科学院苏州纳米技术与纳米仿生研究所 | Biochemical detection system |
| CN105842171B (en) * | 2015-01-15 | 2019-05-17 | 中国科学院苏州纳米技术与纳米仿生研究所 | A kind of biochemistry detection system |
| CN104593870A (en) * | 2015-02-02 | 2015-05-06 | 上海理工大学 | Linear-array-sprayer multi-sampling-point method for dynamically preparing biochips |
| TWI641833B (en) * | 2018-02-07 | 2018-11-21 | 國立臺灣師範大學 | Marking equipment for making biochips |
| CN112218708A (en) * | 2018-05-15 | 2021-01-12 | 生物复制有限公司 | Microarray transducer |
| CN112973592A (en) * | 2019-12-16 | 2021-06-18 | 天津大学 | High-throughput DNA synthesis device and method based on array type ink-jet printing |
| CN112881494A (en) * | 2020-11-09 | 2021-06-01 | 北京大学 | Field effect transistor type biosensing device for multi-index detection |
| CN113324813A (en) * | 2021-05-27 | 2021-08-31 | 江西烈冰生物科技有限公司 | Biological probe sample application method and process based on high-density dot matrix |
| CN115452507A (en) * | 2022-09-01 | 2022-12-09 | 广西大学 | Array type biochip sample application device |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102649931A (en) | Preparation method for microarray biochip | |
| US7005293B2 (en) | Multiple axis printhead adjuster for non-contact fluid deposition devices | |
| CN202705345U (en) | Microarray biochip preparation device | |
| US5658802A (en) | Method and apparatus for making miniaturized diagnostic arrays | |
| US20090033690A1 (en) | Ink jet device and method for releasing a plurality of substances onto a substrate | |
| US20080303870A1 (en) | Ink Jet Device for the Positioning of a Substance Onto a Substrate, Method for the Positioning of a Substance Onto a Substrate and Use of an Ink Jet Device | |
| US20080309701A1 (en) | Ink Jet Device for Releasing Controllably a Plurality of Substances Onto a Substrate, Method of Discrimination Between a Plurality of Substances and Use of an Ink Jet Device | |
| Zaugg et al. | Drop-on-demand printing of protein biochip arrays | |
| Rose | Microfluidic technologies and instrumentation for printing DNA microarrays | |
| US20090170729A1 (en) | Method and a machine for ex situ fabrication of low and medium integration biochip arrays | |
| US20150018247A1 (en) | Method of manufacturing biomedical molecular detection platform and the detection platform manufactured therefrom | |
| EP1281441A2 (en) | Liquid ejection device and sample carrier preparation apparatus | |
| US10761104B2 (en) | Systems and methods for transferring liquids | |
| Hsieh et al. | Ultra-high-throughput microarray generation and liquid dispensing using multiple disposable piezoelectric ejectors | |
| CN112574851B (en) | Single cell screener, screening assembly, screening method and application | |
| IL152050A (en) | Method and device for producing biopolymer arrays | |
| CN110835599A (en) | Biological detection device and method based on microfluidic impact printing | |
| JP3691486B2 (en) | Method for forming detection point in detection chip for analyte | |
| US20040120859A1 (en) | Biomolecular micro-deposition system | |
| CN103028354A (en) | Preparation method for droplet-in-oil array structure | |
| JP2004077393A (en) | Gel plate for electrophoresis, and its preparing method | |
| CN1195984C (en) | Surface tension driving liquid flow chiplized high-density micro-array liquid transferring equipment | |
| CN104630902B (en) | The method and apparatus that microarray formula prepares biochip | |
| CN113324813A (en) | Biological probe sample application method and process based on high-density dot matrix | |
| CN104562216A (en) | Method and apparatus for continuous preparation of biochips |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120829 |