CN1322147C - Automatic reaction instrument for biological chip - Google Patents
Automatic reaction instrument for biological chip Download PDFInfo
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- CN1322147C CN1322147C CNB2005100242590A CN200510024259A CN1322147C CN 1322147 C CN1322147 C CN 1322147C CN B2005100242590 A CNB2005100242590 A CN B2005100242590A CN 200510024259 A CN200510024259 A CN 200510024259A CN 1322147 C CN1322147 C CN 1322147C
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Abstract
The present invention discloses an automatic reaction instrument for a biological chip, which comprises a platform, a biological chip microfluid reaction apparatus, an automatic sample feeding system, a power supply circuit and a control system, wherein the biological chip microfluid reaction apparatus comprises a temperature control platform, a biological chip bearing stage, a biological chip on which a micro reaction cabin is stuck, and a lifting structure connected with a liquid feeding capillary pipe and a liquid discharging capillary pipe, wherein the liquid feeding capillary pipe is connected with a reagent pipe, and the liquid discharging capillary pipe is connected with a peristaltic pump capable of rotating to dual directions, and the lifting structure and the two capillary pipes are connected into a sealed structure; the biological chip microfluid reaction apparatus is placed on the platform; the automatic sample feeding system comprises a lifting arm which is driven by a first motor and is connected with the liquid feeding capillary pipe, and a horizontal moving table driven by a second motor, wherein the reagent pipe is placed on the horizontal moving table. With the adoption of the technical scheme, the sample feeding and the reaction of a biological chip can be operated in a fully automatic mode. Thus, the instrument of the present invention meets the requirements in the field.
Description
Technical field
The present invention relates generally to the biochip field, in particular, relate to a kind of biochip reaction equipment of automatization.
Background technology
Biochip is one of great science and technology progress of the tool characteristics of the times that occurred in high-tech area in recent years.It is with the gene probe (oligonucleotide probe, cDNA clone, PCR product etc.) of large number of biological information in the energy reflected sample, antigen-antibody etc., being fixed on solid support (as the slide glass of aldehyde radical, amino, sulfydryl, carboxyl isoreactivity base group modification or silicon chip, nylon membrane, nitrocellulose filter) in order goes up and forms array, by carrying out hybridization with actual sample (or amplified production), only need once experiment, but obtain the information of aspects such as all genes to be checked, albumen with regard to high-throughput.The characteristics of this parallel detection, high information flux make its application at aspects such as gene test, drug testing, clinical chemistries be subjected to paying attention to widely.Related data about Application of Biochips and development can be with reference to the upright people of horse, Jiang Zhonghua chief editor's " biochip ", and the 1-130 page or leaf was published by Chemical Industry Press in 2000.
The outstanding feature of biochip is exactly high information quantity and automatization.U.S. Patent number 5231029 discloses a kind of full automatic equipment that can carry out hybridization to biochip, adopts conventional fluid control technology, and not only reagent dosage is big, and full-automatic in order to realize, the structure of equipment and complexity thereof.Took the lead in having released a kind of hybridization instrument of new generation that once can carry out 4 biochip hybridization reactions in 2002 abroad, the product of PE company: Hybarray
TM12, but because equipment adopts conventional fluid control technology, and reagent dosage is big, crucial hybridization solution also needs operator to add by hand in order to reduce consumption.Because required sample and reagent are all very precious in biochip reaction, for reducing the consumption of sample and reagent, be convenient to simultaneously operation again, many chip manufacturers begin to paste a reaction cabin on chip, because the volume of reaction cabin is changeable, paste, remove conveniently, use the extensive welcome [ABgene company product, the production code member: AB-0576 that are subjected to the market user flexibly, AB-0577, AB-0630].But the biochip that posts reaction cabin in use, needs manual manipulation micropipet repeated multiple times ground to add or the sucking-off all ingredients, operates very loaded down with trivial details.Intensive automatization demand is arranged in the practice.
Summary of the invention
Purpose of the present invention just provides a kind of biochip reaction equipment of automatization, satisfies the automatization demand.
According to the present invention, a kind of automatic reaction instrument for biological chip is provided, comprising:
One platform;
One biochip fluid reaction device is positioned on the described platform, and this biochip fluid reaction device comprises:
One temperature control platform;
One biochip bearing platform is positioned on the described temperature control platform, and biochip bearing platform tilts;
One biological chip places on the described biochip bearing platform; On this biochip micro reaction cabin is arranged, stick on the biochip, the top of micro reaction cabin has two apertures;
One liftable structure is connected in described biochip bearing platform; This liftable structure is connected with feed liquor kapillary and fluid kapillary, and other structures that is tightly connected are fixed or adopted to the liftable structure with two modes that can stick with glue that are connected capillaceous; Wherein the feed liquor kapillary is connected to the reagent pipe, and the fluid kapillary is connected to peristaltic pump;
Described peristaltic pump can two-wayly rotate, and at first forward rotation makes the reagent in the described reagent pipe fill with described micro reaction cabin, carries out forward, reverse alternate rotation repeatedly with predetermined space afterwards; One automatic sample handling system is placed on the described platform of what, comprising:
One lifting arm, by first electric motor driving, described feed liquor kapillary is fixed on the described lifting arm;
One moves horizontally platform, and by second electric motor driving, described reagent pipe is placed on described moving horizontally on the platform;
Power source circuit links to each other with automatic sample handling system with described biochip fluid reaction device, and electric power is provided;
Controlling System links to each other with automatic sample handling system with described biochip fluid reaction device, controls its sampling and reaction automatically automatically.
According to one embodiment of the invention, the pitch angle of described temperature control platform is 5-60 °.Described predetermined space is 1-10 second.
In the above-mentioned automatic reaction instrument for biological chip, described liftable structure comprises:
One shell;
One cap ned;
One interface board, interface board links to each other with cap ned;
One lifting screw, link to each other with cap ned by a connection bearing, have one on the lifting screw in conjunction with nut, the outside screw of lifting screw and internal thread interlock mutually in conjunction with nut, be fixed on the shell in conjunction with nut, the shell both sides are fixed with two solid bearings, link to each other with biochip bearing platform both sides slide shaft respectively, and the liftable structure can be slided along slide shaft; There is a lifting button on the top of lifting screw, and the lifting button can drive the lifting screw rotation, by regulate the height of cap ned with respect to shell in conjunction with nut.
In the above-mentioned automatic reaction instrument for biological chip, described interface board comprises:
The interface sheet frame has one or more interface slide bars on the interface sheet frame;
The interface draw runner is connected on the interface slide bar slidably;
Have a pair of or several on interface sheet frame and the interface draw runner to aperture, each comprises a fluid hole and an inlet opening to aperture, the higher hole of level attitude was fluid hole when the equipment of being always chosen in used, and fluid hole is the fixing feed liquor kapillary of fluid kapillary and inlet opening fixedly.
The quantity of the biochip that can place on the right quantity of described interface sheet frame and the aperture on the interface draw runner and the plummer is corresponding; If be placed with the multi-disc biochip, aperture between spacing equal the spacing of reaction cabin import and export on the biochip.
Have on interface sheet frame and the interface draw runner a pair of or several to aperture by O RunddichtringO sealing fluid kapillary and feed liquor kapillary and reaction cabin goes out, the combining site of fluid inlet.
According to embodiments of the invention, material capillaceous is silicon rubber or tetrafluoroethylene.Described biochip is to constitute by the array way fixing biological molecules with the standard slide glass.Biochip bearing platform is that metal or other materials with preferable thermal conductivity are made.
Adopt technical scheme of the present invention, can realize the full-automatic operation of biochip sample introduction, reaction, satisfy in this area demand this.
Description of drawings
Above-mentioned and other feature, character and advantage of the present invention will become more obvious to the description of embodiment in conjunction with the accompanying drawings by following, and identical Reference numeral is represented identical feature in the accompanying drawing, wherein:
Fig. 1 is the structure iron according to automatic reaction instrument for biological chip of the present invention;
Fig. 2 is the structure iron according to the liftable structure in the automatic reaction instrument for biological chip of the present invention;
Fig. 3 is the decomposition chart according to liftable structure in the automatic reaction instrument for biological chip of the present invention.
Embodiment
Further specify technical scheme of the present invention below in conjunction with drawings and Examples.
Fig. 1 shows the structure iron of automatic reaction instrument for biological chip 100 of the present invention, and it comprises:
One platform 102;
One biochip fluid reaction device is positioned on the platform 102, and this biochip fluid reaction device comprises:
One temperature control platform 104, temperature control platform 104 link to each other with the temperature control circuit of being made up of semi-conductor heat block and linear temperature sensor and interlock circuit 105 in this embodiment.
One biochip bearing platform 106 is positioned on the temperature control platform, and this biochip bearing platform 106 tilts; In this embodiment, the pitch angle is 5-60 °, it is because the width of micro reaction cabin is far longer than diameter capillaceous that temperature control platform 104 needs a pitch angle, to from stream, discharge or be pressed into air by the peristaltic pump rotating and make liquid to-and-fro movement in the reaction cabin, then the inlet of reaction cabin must have certain angle with the outlet line, otherwise air can not promote liquid to be moved, and only can produce a large amount of bubbles in reaction cabin, thereby the influence reaction is carried out.This biochip bearing platform is that metal or other materials with preferable thermal conductivity are made.The temperature of biochip bearing platform 106 is controlled by thermal conduction by temperature control platform 104.
One biological chip 108 places on the biochip bearing platform 106; On this biochip 108 micro reaction cabin 110 is arranged, stick on the biochip 108, the top of micro reaction cabin 110 has two apertures; Biochip 108 is with standard slide glass (2.5cm * 7.5cm) constitute by the array way fixing biological molecules.The both sides of plummer 106 respectively have a slide shaft 160,162 (with reference to figure 2).
One liftable structure 112, the concrete structure figure of liftable structure 112 can be with reference to figure 2, and it links to each other with slide shaft 160,162 respectively by two solid bearings 164,166, and liftable structure 112 can be slided along slide shaft.Liftable structure 112 comprises a shell 122, is fixed with on the shell in conjunction with nut 132, and in conjunction with a nut 132 and lifting screw 128 interlock mutually, the top of lifting screw 128 has a lifting button 134.Groove 168 is carved with in the position of placing biochip 108 on the biochip bearing platform 106, and biochip 108 each positions of placing are all fixed.This liftable structure 112 is connected with feed liquor kapillary 114 and fluid kapillary 116, and liftable structure 112 is fixed or adopted other structure places that are tightly connected that sealed structure is arranged with two modes that can stick with glue that are connected capillaceous; Wherein feed liquor kapillary 114 is connected to reagent pipe 118, and fluid kapillary 116 is connected to peristaltic pump 120, and material capillaceous is silicon rubber or tetrafluoroethylene.The decomposition chart of liftable structure 112 can be with reference to figure 3, and as shown in Figure 3, it comprises:
Shell 122 (not shown among Fig. 3, as can to show shell 122) with reference to figure 2;
Cap ned 124;
Interface board 126, interface board 126 links to each other with cap ned 124;
Above-mentioned interface board 126 has following structure:
Interface sheet frame 136 has one or more interface slide bars 138 on the interface sheet frame 136, show two slide bar 138a and 138b in this embodiment;
Interface draw runner 140 is connected on the interface slide bar 138 slidably;
Have a pair of or several on interface sheet frame 136 and the interface draw runner 140 to aperture 142,144, each comprises a fluid hole 142 and an inlet opening 144 to aperture 142,144, fluid hole 142 is the fixing feed liquor kapillary 114 of fluid kapillary 116 and inlet opening 144 fixedly, shows 3 pairs of apertures and 3 pairs of kapillaries in this embodiment altogether.In other application, the aperture on interface sheet frame 136 and the interface draw runner 140 is corresponding to the quantity of the biochip that can place on 142,144 quantity and the plummer 106; If be placed with the multi-disc biochip, aperture equals the spacing of reaction cabin import and export on the biochip to the spacing between 142,144.For the pitch-row difference that the reaction cabin on the different biochips may exist, can use the slip of interface draw runner 140 on interface slide bar 138 to regulate.
A pair of or several combining sites that aperture 142,144 sealed fluid kapillaries 116 and feed liquor kapillary 114 and reaction cabin by O RunddichtringO 146 on interface sheet frame 136 and interface draw runner 140.
Get back to Fig. 1, continue to discuss the structure of automatic reaction instrument for biological chip 100:
Above-mentioned peristaltic pump 120 can two-wayly rotate, and at first forward rotation makes the reagent in the reagent pipe 118 fill with micro reaction cabin 110, carries out forward, reverse alternate rotation repeatedly with predetermined space afterwards; In this embodiment, be generally the numerical value of 1-10 in second pitch time, rotation duration depends on the capacity of micro reaction cabin 106, and rotation duration should be wanted the liquid volume of 5%-10% in the mobile response cabin each time.Peristaltic pump 120 is finished until hybridization so repeatedly.
Except biochip fluid reaction device, this automatic reaction instrument for biological chip 100 also comprises:
One automatic sample handling system on placement and the platform 102, comprising:
One lifting arm 150 is driven by first motor 152, and feed liquor kapillary 114 is fixed on the lifting arm 150;
One moves horizontally platform 154, is driven by second motor 156, and reagent pipe 118 is placed on and moves horizontally on the platform 154;
Under the driving of first and second motors 152,156, feed liquor kapillary 114 can at first be promoted to the position that is higher than reagent pipe 118 mouth of pipe height by lifting arm 150, reagent pipe 118 moves horizontally under the driving that moves horizontally platform 154 afterwards, move to the position of needed reagent, lifting arm 150 puts down feed liquor kapillary 114 carry out sample introduction to needed reagent pipe 118 afterwards.
Automatic reaction instrument for biological chip 100 of the present invention also comprises following parts:
Power source circuit 156 links to each other with automatic sample handling system with biochip fluid reaction device, and electric power is provided;
Controlling System 158 links to each other with automatic sample handling system with biochip fluid reaction device, controls its sampling and reaction automatically automatically, and Controlling System 158 is a computer in this embodiment.
In this embodiment, the output flow of the peristaltic pump of selecting for use preferably is 10~200ul/min, and that the output torque of first motor and second motor is preferable is 0.3N/m.
The workflow of automatic reaction instrument for biological chip 100 of the present invention is as follows:
At first open host power supply, start earlier the control software on the computer, import the flow process and the parameter of biochip reaction then as requested: the pipe of temperature, time and the agents useful for same of steps such as prehybridization, hybridization, washing, colour developing number;
The reagent pipe that fills corresponding reagent is put into specified location on the equipment sample plate;
The rotation and lifting knob rises interface, and lifting structure slided backward, expose biochip bearing platform, the biochip (once being no more than 5) that is stained with reaction cabin is placed on the plummer, again with lifting structure to front slide, cover biochip bearing platform, dock with reaction cabin realization sealing after reverse rotation lifting knob descends interface;
Control software then brings into operation, equipment will move according to software program automatically: lifting arm was moved horizontally to the top of reagent pipe before this, lifting arm descends, kapillary inserts in the reagent pipe, the peristaltic pump forward rotation sucks the reagent of setting volume, mentions lifting arm, peristaltic pump continues forward rotation, reagent is drawn in the reaction cabin fully, and temperature controller begins to heat, and reaches temperature afterreaction certain hour, lifting arm descends, insert in the reagent pipe (or sewer pipe), peristaltic pump is oppositely wriggled again, sends reagent back to reagent pipe (also can directly send into sewer pipe) again, then lifting arm move to next reagent pipe again the top according to program run, up to EP (end of program).
Adopt technical scheme of the present invention, can realize the full-automatic operation of biochip sample introduction, reaction, satisfy in this area demand this.
The foregoing description provides to being familiar with the person in the art and realizes or use of the present invention; those skilled in the art can be under the situation that does not break away from invention thought of the present invention; the foregoing description is made various modifications or variation; thereby protection scope of the present invention do not limit by the foregoing description, and should be the maximum range that meets the inventive features that claims mention.
Claims (10)
1. an automatic reaction instrument for biological chip is characterized in that, comprising:
One platform;
One biochip fluid reaction device is positioned on the described platform, and this biochip fluid reaction device comprises:
One temperature control platform;
One biochip bearing platform is positioned on the described temperature control platform, and biochip bearing platform tilts;
One biological chip places on the described biochip bearing platform; On this biochip micro reaction cabin is arranged, stick on the biochip, the top of micro reaction cabin has two apertures;
One liftable structure is connected in described biochip bearing platform; This liftable structure is connected with feed liquor kapillary and fluid kapillary, liftable structure and two sealed structures that are connected to capillaceous; Wherein the feed liquor kapillary is connected to the reagent pipe, and the fluid kapillary is connected to peristaltic pump;
Described peristaltic pump can two-wayly rotate, and at first forward rotation makes the reagent in the described reagent pipe fill with described micro reaction cabin, carries out forward, reverse alternate rotation repeatedly with predetermined space afterwards;
One automatic sample handling system is placed on the described platform of what, comprising:
One lifting arm, by first electric motor driving, described feed liquor kapillary is fixed on the described lifting arm;
One moves horizontally platform, and by second electric motor driving, described reagent pipe is placed on described moving horizontally on the platform;
Power source circuit links to each other with automatic sample handling system with described biochip fluid reaction device, and electric power is provided;
Controlling System links to each other with automatic sample handling system with described biochip fluid reaction device, controls its sampling and reaction automatically automatically.
2. automatic reaction instrument for biological chip as claimed in claim 1 is characterized in that, the pitch angle of described temperature control platform is 5-60 °.
3. automatic reaction instrument for biological chip as claimed in claim 1 is characterized in that, described predetermined space is 1-10 second.
4. automatic reaction instrument for biological chip as claimed in claim 1 is characterized in that, described liftable structure comprises:
One shell;
One cap ned;
One interface board, interface board links to each other with cap ned;
One lifting screw, link to each other with cap ned by a connection bearing, have one on the lifting screw in conjunction with nut, the outside screw of lifting screw and internal thread interlock mutually in conjunction with nut, be fixed on the shell in conjunction with nut, there is a lifting button on the top of lifting screw, and the lifting button can drive the lifting screw rotation, by regulate the height of cap ned with respect to shell in conjunction with nut.
5. automatic reaction instrument for biological chip as claimed in claim 4 is characterized in that, described interface board comprises:
The interface sheet frame has one or more interface slide bars on the interface sheet frame;
The interface draw runner is connected on the interface slide bar slidably;
Have a pair of or several on interface sheet frame and the interface draw runner to aperture, each comprises a fluid hole and an inlet opening to aperture, the higher hole of level attitude was fluid hole when the equipment of being always chosen in used, and fluid hole is the fixing feed liquor kapillary of fluid kapillary and inlet opening fixedly.
6. automatic reaction instrument for biological chip as claimed in claim 5 is characterized in that, the quantity of the biochip of placing on the right quantity of described interface sheet frame and the aperture on the interface draw runner and the plummer is corresponding; If be placed with the multi-disc biochip, aperture between spacing equal the spacing in reaction cabin liquid inlet and outlet hole on the biochip.
7. automatic reaction instrument for biological chip as claimed in claim 5, it is characterized in that, have on interface sheet frame and the interface draw runner a pair of or several to aperture by O RunddichtringO sealing fluid kapillary and feed liquor kapillary and biological chip reaction cabin goes out, the combining site of import.
8. automatic reaction instrument for biological chip as claimed in claim 1 is characterized in that, material capillaceous is silicon rubber or tetrafluoroethylene.
9. automatic reaction instrument for biological chip as claimed in claim 1 is characterized in that, described biochip is to constitute by the array way fixing biological molecules with the standard slide glass.
10. automatic reaction instrument for biological chip as claimed in claim 1 is characterized in that, described biochip bearing platform is that metal or other materials with preferable thermal conductivity are made.
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CNB2005100242590A CN1322147C (en) | 2005-03-09 | 2005-03-09 | Automatic reaction instrument for biological chip |
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CNB2005100242590A CN1322147C (en) | 2005-03-09 | 2005-03-09 | Automatic reaction instrument for biological chip |
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CN1322147C true CN1322147C (en) | 2007-06-20 |
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Families Citing this family (5)
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CN102507965B (en) * | 2011-10-31 | 2013-08-14 | 南京裕隆生物医学发展有限公司 | Holding platform of full-automatic reactor |
CN102681454B (en) * | 2012-05-23 | 2015-09-02 | 盛司潼 | A kind of biochemical reaction workstation |
CN106199027B (en) * | 2016-08-31 | 2018-06-29 | 贵州金玖生物技术有限公司 | Micro-channel replacement reaction sealing base |
CN109517731A (en) * | 2017-09-19 | 2019-03-26 | 德诺杰亿(北京)生物科技有限公司 | Microfluidic control system |
CN109055203A (en) * | 2018-09-21 | 2018-12-21 | 中国人民解放军军事科学院军事医学研究院 | A kind of full-automatic biological chips work station and its detection method |
Citations (1)
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CN1412320A (en) * | 2001-10-11 | 2003-04-23 | 宋克 | Joint treatment system of gene chip and its related technique |
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CN1412320A (en) * | 2001-10-11 | 2003-04-23 | 宋克 | Joint treatment system of gene chip and its related technique |
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