CN101334403A - Assembly line biological chips sample application platform - Google Patents
Assembly line biological chips sample application platform Download PDFInfo
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- CN101334403A CN101334403A CNA2007100426606A CN200710042660A CN101334403A CN 101334403 A CN101334403 A CN 101334403A CN A2007100426606 A CNA2007100426606 A CN A2007100426606A CN 200710042660 A CN200710042660 A CN 200710042660A CN 101334403 A CN101334403 A CN 101334403A
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Abstract
The invention discloses a stream-lined biochip spotting platform which relates to the preparation of a microarray biochip. The stream-lined biochip spotting platform essentially consists of a fixed platform of a mechanical hand, a precise motion platform, 2 to 20 spotting units, an electric control box and a computer. Each spotting unit consists of an XYZ three-dimensional mechanical hand, a spotting head, a sample slot, a cleaning trough and a chip fixture, wherein, each XYZ three-dimensional mechanical hand utilizes three electric translation stages for constitution. The spotting units are equidistantly arranged along the motion direction of the motion platform according to a certain distance or angle. Biochip matrices are arranged and clamped in the chip fixture and also equidistantly arranged on the motion platform along the motion direction of the motion platform according to the distance or the angle of the spotting units. The electric control box, the precision motion platform and all the spotting units are operated under the control of software of the computer, thereby realizing the simultaneous stream-lined spotting of a plurality of spotting units and finally forming the complete chip. The spotting platform is characterized by broad applicability, high efficiency, good uniformity, less cross-infection, and simple and convenient maintenance and use, etc., thereby being very applicable to the scale production of the biochips and also being applicable to scientific research and applications.
Description
Technical field
The present invention relates to the preparation of micro-array biochip, more precisely, relate to the pipelining sample application platform of a kind of many indexs, many person-portions parallel detection usefulness micro-array biochip.
Background technology
Biochip (biochip) is meant methods such as adopting the synthetic or micro-sampling of photoconduction original position, with big molecular proportion of large number of biological such as nucleic acid fragment, peptide molecule even histotomy, biological samples such as cell solidify in holder in an orderly manner (as slide, silicon chip, polyacrylamide gel, carriers such as nylon membrane) surface, form intensive two-dimentional molecules align, then with the molecular hyridization that hits of the biological sample to be measured of mark, intensity of hybridization signal is carried out fast such as laser confocal scanning or electric charge coupling photography camera (CCD) by specific instrument, parallel, check and analysis efficiently, thereby the quantity of target molecule in the judgement sample.Because slide/silicon chip commonly used is as solid support, and in the technology of preparing of preparation process analog computation machine chip, so be referred to as biochip technology.According to the fixing probe difference on the chip, biochip comprises genetic chip, protein-chip, cell chip, organization chip.Owing to can be fixed in extremely a large amount of probes on the holder simultaneously with this technology, so once can carry out check and analysis, thereby solve traditional nucleic acid blot hybridization (Southern Blotting and NorthernBlotting etc.) technical sophistication, automaticity is low, the testing goal molecular amounts is few, small throughput (low through-put) etc. not enough to a large amount of biomolecule.And, by designing different probe arrays, use specific analytical approach can make this technology have multiple different using value, measure as gene expression profile, sudden change detects, polymorphism analysis, genomic library mapping and sequencing by hybridization (Sequencing by hybridization, SBH) etc., for the research of " post genome project " gene function in period and the development of modern medicine science and medical diagnosis provide strong tool, will make the discovery of new gene, gene diagnosis, drug screening, aspects such as administration personalization obtain important breakthrough, change for whole human society brings deeply widely.This technology is cited as one of the 1998 annual worlds, ten big science and technology progress.
The research purpose difference, the chip type difference that expectation is made, the preparation chip method also is not quite similar, and is example with the DNA chip, can be divided into two big classes basically: a class is that original position is synthetic, promptly at support surface direct in-situ synthetic oligonucleotide probe; One class is a directly point sample of pre-synthetic back, and minim DNA solution is directly put and is solidificated on the chip carrier 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 back point sample.
Synthetic point sample method is with after, the quantitative test purified by the synthetic good probe of liquid phase chemical in advance, by the microarray sample application platform, accurately and rapidly with the quantitative point sample of different probe sample on relevant positions such as positively charged nylon membrane or silicon chip, promptly obtain dna microarray or protein chip after the curing.The mode of point sample is divided two kinds, and one is the contact point sample, and promptly spotting needle directly contacts with the solid support surface, and sample is stayed on the solid support; It two is contactless point sample, i.e. specking, and it is with piezoelectric principle or micro-solenoid valve break-make principle sample directly to be sprayed onto the solid support surface by kapillary.The microarray sample application platform of having developed in the market generally all is made up of the three-dimensional mobile device of a cover computer control one cover, a plurality of printing/spray printing pin, a damping base, contain porous plate and a plurality of chip of probe in can putting above the base, a plurality of printings/spray printing pin is connected on the three-dimensional mobile device above base and moves, and probe is taken out directly printing or spray printing on chip from porous plate.This kind equipment has many deficiencies: be limited to the three-dimensional mobile device of a cover, not only point sample speed is slow, and cleaning printing/spray printing pin has taken the plenty of time, inefficiency; Because the plant bottom case size is limited, one time point sample can only prepare the number of chips that can put at most, so a point sample capacity is restricted; With a plurality of printings/same sample of spray printing pin mark, because the individual difference of a plurality of printings/spray printing pin certainly will be brought bigger point sample difference; And same set of printing/spray printing pin gives me a little different samples, and cross-contamination issue is inevitable.Also exist just because of these problems, the preparation equipment of biochip only has the scientific research type at present, does not have quick plant-size equipment.
And the said equipment mostly is import equipment, costs an arm and a leg, and the consumables cost height is not suitable for promoting at home.This kind equipment all is to be designed to probe points on rigid carriers such as slide at present, seldom a bit on flexible carriers such as film.
Summary of the invention
The purpose of this invention is to provide a kind of micro-array biochip streamline and prepare platform, can overcome the deficiency of above-mentioned technology, can be applied to the quick production preparation of many indexs, many person-portions detection usefulness micro-array biochip.The present invention has that cost is low, applicability is wide, efficient is high, good, the no cross pollution of homogeneity, safeguard and use characteristics such as easy and simple to handle, and the biochip technology industry can extensively be promoted and fast-developing at home.
The invention provides a kind of assembly line biological chips sample application platform, it is characterized in that, it mainly is made up of a mechanical arm stationary platform (1), precision movement platform (2), 2～20 point sample unit, electric cabinet and computing machines.
Each point sample unit is made up of XYZ three-dimensional mechanical hand, sampling head (7), sample cell (8), rinse bath (9), chip fixture (3), and wherein each XYZ three-dimensional mechanical hand is made up of X-axis electronic control translation stage (6), Y-axis electronic control translation stage (5), Z axle electronic control translation stage (4).X-axis electronic control translation stage (6) is fixed on the mechanical arm stationary platform (1), and Y-axis electronic control translation stage (5) connects X-axis electronic control translation stage (6), and sampling head (7) is connected on the Z axle electronic control translation stage (4) by the sampling head link.The point sample unit is equidistantly arranged according to certain angle or distance along the direction of motion of motion platform (2).Sample cell of each point sample unit (8) and rinse bath (9) are fixed on the mechanical arm stationary platform (1), are positioned within this point sample unit X-axis (6), Y-axis (5), Z axle (4) the motion effective travel scope.Have 1 spotting needle on the sampling head of each point sample unit (7), be responsible for the point sample of one of them sample in the chip preparation process.
It has a plurality of chip fixtures (3), by draw-in groove or screw can mode for convenience detach being fixed on the precision movement platform (2).Biochip matrix is installed in the chip fixture (3), and dependence precision movement platform (2) moves and locatees, and also equidistantly arranges according to the distance or the angle of point sample unit in its direction of motion of motion platform (2) upper edge.Biochip matrix can be one or more nylon membrane or nitrocellulose membrane, also can be one or more slides, can also be one or more porous plate.
With data line the X-axis (6) of precision movement platform (2) and each point sample unit, Y-axis (5), Z axle (4) electronic control translation stage are connected to electric cabinet, electric cabinet connects computing machine.Under control of computer software, operate electric cabinet, precision movement platform (2) and each point sample unit, realize a plurality of point samples unit streamline point sample simultaneously, form complete biochip at last.
Among the present invention computer-controlled program design a model be each point sample unit of control the XYZ three-dimensional mechanical hand of enabling, control each point sample unit, control precision movement platform (2) motion and accurately location, control point sample pipe system the point sample action, control the number of point sample and can on identical point, repeat.
Said precision movement platform (2) among the present invention refers to the accurate rotation platform of broad sense, that is to say that having comprised when its diameter is infinitely great is the situation of Precision Linear Moving platform (10).
Compare with present existing products, major advantage of the present invention is:
1) applicability is wide.The applicable multiple point sample matrix of chip fixture in this sample application platform 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.
2) efficient height.Adopt a plurality of point samples unit simultaneously a plurality of chips to be carried out point sample in this sample application platform, the use of a plurality of point sample mechanical arms has improved point sample speed greatly.Simultaneously only be responsible for a sample of point or a few sample during the each point sample of every spotting needle, effectively reduced the time that is used to clean spotting needle when putting different sample, improved point sample efficient greatly.
3) homogeneity is good.All finish with the same a kind of sample on chip piece and all chips, effectively avoided the individual difference between the spotting needle, improved the homogeneity of point sample by a spotting needle on the point sample module.
4) cross pollution is few.A point sample unit is responsible for some one of them samples specially, has not only reduced the scavenging period when putting different sample, has also effectively reduced the cross pollution of different sample rooms.Even can be responsible for the cross pollution that a kind of sample of point be avoided sample room by special of a point sample unit.
5) safeguard that use is easy and simple to handle.This equipment adopts modular point sample unit form; and the parts of each point sample unit can be general; so the operation of working service is all very easy; in case find a point sample unit trip problem; can in time substitute its work with other point sample unit; perhaps replace this point sample unit, the time waste that whole equipment all must shutdown maintenance when effectively having avoided parts trip fault with unnecessary point sample whole unit.
6) cost of instrument itself is low.This equipment adopts the point sample module of the miniaturization of standard, and not only price Ben Shen is lower, can also further bring down prices by the advantage of quantity.An external cover instrument price is generally the hundreds of thousands dollar, and the cost of this equipment hundreds of thousands yuan only, but its point sample efficient is to be equivalent to many cover overseas equipments.
In a word, this sample application platform has characteristics such as applicability is wide, efficient is high, homogeneity is good, cross pollution is few, maintenance is easy to use, low cost of manufacture, is highly suitable for the large-scale production of biochip, also is suitable for scientific research and application.
Description of drawings
Figure .1 is the synoptic diagram of one embodiment of the present of invention (motion platform is accurate rotation platform form), the present invention includes but is not limited only to the quantity and the arrangement mode of unit of point sample shown in the figure and chip fixture (3);
Figure .2 is the synoptic diagram of one embodiment of the present of invention (motion platform is a Precision Linear Moving platform form), the present invention includes but is not limited only to the quantity and the arrangement mode of unit of point sample shown in the figure and chip fixture (3).
Embodiment
The present invention is further described below in conjunction with drawings and Examples:
As shown in the figure, micro-array biochip streamline of the present invention prepares platform, comprise following assembly: (1) is XYZ mechanical arm stationary platform, (2) be accurate rotation platform, (3) be chip fixture, (4) be a Z axle electronic control translation stage in the point sample unit, (5) be a Y-axis electronic control translation stage in the point sample unit, (6) be an X-axis electronic control translation stage in the point sample unit, (7) are sampling head, are used for installing spotting needle, (8) be sample cell, (9) be rinse bath, linear motion platform when (10) are infinitely great for the diameter when accurate rotation platform also has electric cabinet and computing machine in addition.
Each point sample unit is made up of XYZ three-dimensional mechanical hand, sampling head (7), sample cell (8), rinse bath (9).Wherein each XYZ three-dimensional mechanical hand is divided into X-axis (6), Y-axis (5), (4) three axles of Z axle, and each is made up of an accurate motorized precision translation stage.X-axis electronic control translation stage (6) is fixed on the mechanical arm stationary platform (1), and Y-axis electronic control translation stage (5) connects X-axis electronic control translation stage (6), and sampling head (7) is connected on the Z axle electronic control translation stage (4) by the sampling head link.The point sample unit is equidistantly arranged according to certain angle or distance along the direction of motion of motion platform (2).Sample cell of each point sample unit (8) and rinse bath (9) are fixed on the mechanical arm stationary platform (1), are positioned within this point sample unit X-axis (6), Y-axis (5), Z axle (4) the electronic control translation stage motion effective travel scope.Have 1 spotting needle on the sampling head of each point sample unit (7), be responsible for the point sample of one of them sample in the chip preparation process.
Biochip matrix is installed in the chip fixture (3), and dependence precision movement platform (2) moves and locatees, and also equidistantly arranges according to the distance or the angle of point sample unit in its direction of motion of motion platform (2) upper edge.Biochip matrix can be one or more nylon membrane or nitrocellulose membrane, also can be one or more slides, can also be one or more porous plate.
With data line the electronic control translation stage X-axis (6) of each point sample unit, Y-axis (5), Z axle (4) are connected to electric cabinet, electric cabinet connects computing machine.Under control of computer software, operate electric cabinet, control the motion and the location of accurate rotation platform (2) or precision level motion platform (10), coordinate each point sample unit of control simultaneously, transmission chip matrix by accurate rotation platform (2) or precision level motion platform (10), a plurality of point samples unit carries out point sample according to setting program simultaneously, realize many indexs, the preparation of many person-portions micro-array biochip streamline, form complete biochip at last.
Among the present invention computer-controlled program design a model be each point sample unit of control the XYZ three-dimensional mechanical hand of enabling, control each point sample unit, control precision movement platform (2) motion and accurately location, control point sample pipe system the point sample action, control the number of point sample and can on identical point, repeat.
Below in conjunction with a kind of point sample matrix wherein---the point sample on the nylon membrane is further introduced using method of the present invention:
At first nylon membrane is fixed on glass plate or other rigid support things, again this rigid support thing is installed in the chip fixture (3), open the electric cabinet power supply, start computing machine and open the electric cabinet Control Software, the accurate electronic control translation stage (4) (5) of the XYZ of each point sample unit (6) made zero reset, precision movement platform (2) also moves to assigned address, and the sample that will need point sample adds in the sample cell (8) in the different point sample unit successively, after choosing the point sample unit that needs, the design spotting template is also carried out the point sample program, when first sample is finished all these sample point samples in first chip, precision movement platform (2) motion is automatically delivered to second point sample unit with this chip, by second point sample unit it is carried out the point sample of second sample, and second chip block enters the point sample that first point sample unit carries out first sample simultaneously, and the like, whenever a point sample unit after finishing the point sample of this sample on the chip, enter next point sample unit, if during the chip vacancy in the previous chip fixture of first point sample unit, the new chip of can packing into enters the point sample streamline, up to the point sample of finishing all chips.
Should be understood that those skilled in the art can do various increases and decreases or modification to the present invention after reading foregoing of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (7)
1. assembly line biological chips sample application platform, it is characterized in that, it mainly is made up of a precision movement platform (2), 2～20 point sample unit, a mechanical arm stationary platform (1), electric cabinet and computing machines, wherein each point sample unit is made up of XYZ three-dimensional mechanical hand, sampling head (7), sample cell (8), rinse bath (9), chip fixture (3), and wherein each XYZ three-dimensional mechanical hand is made up of X-axis electronic control translation stage (6), Y-axis electronic control translation stage (5), Z axle electronic control translation stage (4);
X-axis electronic control translation stage (6) is fixed on the mechanical arm stationary platform (1), and Y-axis electronic control translation stage (5) connects X-axis electronic control translation stage (6), and sampling head (7) is connected on the Z axle electronic control translation stage (4) by link; Sample cell (8) and rinse bath (9) all are fixed on the mechanical arm stationary platform (1); Chip fixture (3) is fixed on the precision movement platform (2);
XYZ three-dimensional mechanical hand and precision movement platform (2) are connected to electric cabinet by data line, and electric cabinet connects computing machine by data line again, by the running of computer-controlled program control electric cabinet, motion platform (2) and each point sample unit.
2. according to a kind of assembly line biological chips sample application platform of claim 1, it is characterized in that described point sample unit is equidistantly arranged according to certain angle or distance along the direction of motion of precision movement platform (2).
3. according to the point sample unit in a kind of assembly line biological chips sample application platform of claim 1, it is characterized in that sample cell of described each point sample unit (8) and rinse bath (9) are positioned within this point sample unit XYZ three-dimensional machinery hands movement effective travel scope.
4. according to the point sample unit in a kind of assembly line biological chips sample application platform of claim 1, it is characterized in that having 1 spotting needle on the sampling head of described each point sample unit (7), be responsible for the point sample of one of them sample in the chip preparation process.
5. according to a kind of assembly line biological chips sample application platform of claim 1, it is characterized in that, described chip fixture (3) by draw-in groove or screw can mode for convenience detach being fixed on the precision movement platform (2).
6. according to a kind of assembly line biological chips sample application platform of claim 1, it is characterized in that, described precision movement platform (2) refers to the accurate rotation platform of broad sense, that is to say that having comprised when its diameter is infinitely great is the situation of Precision Linear Moving platform (10).
7. according to a kind of assembly line biological chips sample application platform of claim 1, it is characterized in that, described computer-controlled program design a model be each point sample unit of control the XYZ three-dimensional mechanical hand of enabling, control each point sample unit, control precision movement platform (2) motion and accurately location, control point sample pipe system the point sample action, control the number of point sample and can on identical point, repeat.
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| CNA2007100426606A CN101334403A (en) | 2007-06-26 | 2007-06-26 | Assembly line biological chips sample application platform |
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| CNA2007100426606A CN101334403A (en) | 2007-06-26 | 2007-06-26 | Assembly line biological chips sample application platform |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102649931A (en) * | 2012-05-28 | 2012-08-29 | 上海理工大学 | Preparation method for microarray biochip |
| CN101696971B (en) * | 2009-10-19 | 2012-12-19 | 深港产学研基地 | Biochip analyzer and control system thereof |
| CN103115808A (en) * | 2012-07-17 | 2013-05-22 | 上海聚阵生物科技有限公司 | Biological chip sample application device and usage thereof |
| CN103149376A (en) * | 2013-03-26 | 2013-06-12 | 山东博科生物产业有限公司 | Automatic sampling mechanism |
| CN103278365A (en) * | 2013-06-08 | 2013-09-04 | 上海理工大学 | Drum type biochip spotting device and method thereof |
| CN103869075A (en) * | 2012-12-14 | 2014-06-18 | 仓怀兴 | Preparation device of protein chip by real-time quantitative detection and capillary electrophoresis |
| WO2014161432A1 (en) * | 2013-04-03 | 2014-10-09 | Abon Biohparm (Hangzhou) Co., Ltd | An apparatus and methods for identifying the front and the rear of a test board |
| CN104630901A (en) * | 2015-02-02 | 2015-05-20 | 上海理工大学 | Method and system for dynamically preparing biochip by using linear-array sprayers |
| CN104965097A (en) * | 2015-05-22 | 2015-10-07 | 天津智通机器人有限公司 | Automatic sample applicator |
| CN107111123A (en) * | 2014-10-27 | 2017-08-29 | 阿科尼生物系统公司 | Turn round sample positioning apparatus |
| CN107137094A (en) * | 2017-05-06 | 2017-09-08 | 党冬梅 | A kind of paediatrics blood drawing care device |
| CN107966522A (en) * | 2016-10-20 | 2018-04-27 | 京元电子股份有限公司 | The titration module and its titration test equipment of biochip |
| CN109596528A (en) * | 2018-12-11 | 2019-04-09 | 迪瑞医疗科技股份有限公司 | A kind of automatic coagulation analyzer and its analysis method |
| CN113189357A (en) * | 2021-05-06 | 2021-07-30 | 中国科学院上海微系统与信息技术研究所 | Preparation method of dipping type sample applicator and micro-cantilever sensor chip |
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2007
- 2007-06-26 CN CNA2007100426606A patent/CN101334403A/en active Pending
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101696971B (en) * | 2009-10-19 | 2012-12-19 | 深港产学研基地 | Biochip analyzer and control system thereof |
| CN102649931A (en) * | 2012-05-28 | 2012-08-29 | 上海理工大学 | Preparation method for microarray biochip |
| CN103115808A (en) * | 2012-07-17 | 2013-05-22 | 上海聚阵生物科技有限公司 | Biological chip sample application device and usage thereof |
| CN103115808B (en) * | 2012-07-17 | 2015-05-20 | 上海聚阵生物科技有限公司 | Biological chip sample application device and usage thereof |
| CN103869075A (en) * | 2012-12-14 | 2014-06-18 | 仓怀兴 | Preparation device of protein chip by real-time quantitative detection and capillary electrophoresis |
| CN103149376A (en) * | 2013-03-26 | 2013-06-12 | 山东博科生物产业有限公司 | Automatic sampling mechanism |
| CN104330550B (en) * | 2013-04-03 | 2017-05-10 | 艾博生物医药(杭州)有限公司 | Apparatus and method for identifying front and back directions of detection board |
| WO2014161432A1 (en) * | 2013-04-03 | 2014-10-09 | Abon Biohparm (Hangzhou) Co., Ltd | An apparatus and methods for identifying the front and the rear of a test board |
| CN104330550A (en) * | 2013-04-03 | 2015-02-04 | 艾博生物医药(杭州)有限公司 | Apparatus and method for identifying front and back directions of detection board |
| CN105122061A (en) * | 2013-04-03 | 2015-12-02 | 艾博生物医药(杭州)有限公司 | An apparatus and methods for identifying the front and the rear of a test board |
| CN103278365B (en) * | 2013-06-08 | 2015-06-24 | 上海理工大学 | Drum type biochip spotting device and method thereof |
| CN103278365A (en) * | 2013-06-08 | 2013-09-04 | 上海理工大学 | Drum type biochip spotting device and method thereof |
| CN107111123A (en) * | 2014-10-27 | 2017-08-29 | 阿科尼生物系统公司 | Turn round sample positioning apparatus |
| CN104630901A (en) * | 2015-02-02 | 2015-05-20 | 上海理工大学 | Method and system for dynamically preparing biochip by using linear-array sprayers |
| CN104630901B (en) * | 2015-02-02 | 2017-01-11 | 上海理工大学 | Method and system for dynamically preparing biochip by using linear-array sprayers |
| CN104965097A (en) * | 2015-05-22 | 2015-10-07 | 天津智通机器人有限公司 | Automatic sample applicator |
| CN107966522A (en) * | 2016-10-20 | 2018-04-27 | 京元电子股份有限公司 | The titration module and its titration test equipment of biochip |
| CN107966522B (en) * | 2016-10-20 | 2020-09-08 | 京元电子股份有限公司 | Titration module of biochip and titration test equipment thereof |
| CN107137094A (en) * | 2017-05-06 | 2017-09-08 | 党冬梅 | A kind of paediatrics blood drawing care device |
| CN109596528A (en) * | 2018-12-11 | 2019-04-09 | 迪瑞医疗科技股份有限公司 | A kind of automatic coagulation analyzer and its analysis method |
| CN109596528B (en) * | 2018-12-11 | 2021-12-31 | 迪瑞医疗科技股份有限公司 | Full-automatic coagulation analyzer and analysis method thereof |
| CN113189357A (en) * | 2021-05-06 | 2021-07-30 | 中国科学院上海微系统与信息技术研究所 | Preparation method of dipping type sample applicator and micro-cantilever sensor chip |
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Application publication date: 20081231 |