CN106248979B - Disposable reaction liquid suction reactor - Google Patents

Disposable reaction liquid suction reactor Download PDF

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Publication number
CN106248979B
CN106248979B CN201610789358.6A CN201610789358A CN106248979B CN 106248979 B CN106248979 B CN 106248979B CN 201610789358 A CN201610789358 A CN 201610789358A CN 106248979 B CN106248979 B CN 106248979B
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reaction
chip
reactor
reaction film
channel
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CN106248979A (en
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王磊
韩克兵
周庭波
郑世阳
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Guizhou Jin Jiu Biotech Co ltd
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Guizhou Jin Jiu Biotech Co ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention provides a disposable reaction liquid suction reactor, which belongs to the field of research equipment and comprises a chip holder, a first reaction film, a reactor main body and a chip for detecting a reaction process, wherein the chip is connected to the bottom of the chip holder, the top wall of the first reaction film is contacted with the bottom wall of the chip, the top wall of the reactor main body is contacted with the bottom wall of the first reaction film, the reactor main body is provided with a liquid inlet channel and a liquid outlet channel, the liquid inlet channel and the liquid outlet channel vertically penetrate through the reactor main body, the bottom of the liquid inlet channel is used for being contacted with reaction liquid, the first reaction film is provided with a drainage cavity, and the liquid inlet channel and the liquid outlet channel are communicated with the drainage cavity. The device has stable reaction and is convenient for chip detection.

Description

One-time reaction liquid draws reactor
Technical field
The present invention relates to research clothing arts, and reactor is drawn in particular to one-time reaction liquid.
Background technology
The research of protein group is one of basic task of genome times afterwards comprehensively.The development of proteomics research is more The development of dependency analysis means, currently used for protein analysis major technique be two-dimensional gel electrophoresis, computer image analysis, Protein identification techniques, high performance liquid chromatography, Capillary Electrophoresis etc..It is biologically most widely used be two-dimensional gel electrophoresis, Although this method comparative maturity, that cannot carry out automation mechanized operation and cannot be carried out due to technology itself Analysis under high electric field, entire analytic process is loaded down with trivial details and time-consuming, and party's standard measure is inaccurate.
The identification technology of protein mainly has amino acid sequence analysis, composition analysis, peptide mapping fingerprinting, these requirements egg White matter sample is simple sample, and purity requirement is very high, and itself is a extremely complex processes for protein purification.
Although high performance liquid chromatography can carry out analysis faster, which is to be based on protein in stationary phase Reservation different analyzed, it means that the analysis between protein is that the hydrophobic difference based on protein is detached , and it cannot be carried out at the same time Multi-example separation, this is inadequate for the analysis of a large amount of protein samples.
In the various clastotypes of Capillary Electrophoresis, be suitble to protein analysis pattern be mainly isoelectric focusing electrophoresis and There are glue or Non-gel Sieving Electrophoresis, discretely principle is that the isoelectric point based on protein is carried out with molecular size difference respectively for they Analysis, being can not possibly molecular dimension having the same based on the protein with identical isoelectric point.By the two link up into The two-dimensional capillary electrophoresis of row protein is best analysis method, but is to need professional in the connection of two capillary columns Operation, does not have generality, and the research for protein group is very unfavorable.
Inventor has found that the analysis means of protein used at present mainly carry out protein example under study for action Separation analysis, obtains the one-dimension information of sample, to obtain more information and a variety of analysis means is needed to be used in combination, such as by egg After white matter separation, the collection of protein is carried out, the enzyme hydrolysis of obtained protein progress protease will be collected, it is main using special Property protease, obtained hydrolysate (mainly peptide fragment) carries out separation analysis, mainly uses high performance liquid chromatography/matter Spectrum, Capillary Electrophoresis/mass spectrum, mass spectrum are analyzed, and such process is more loaded down with trivial details, and has many processes to can not achieve automatically Change, and to expend long time.
Invention content
The purpose of the present invention is to provide a kind of one-time reaction liquid to draw reactor, to shorten the time of analytic process, Improve analysis efficiency.
The invention is realized in this way:
A kind of one-time reaction liquid draws reactor, including chip carrier, the first reaction film, reactor body and for detecting The chip of reaction process, the chip are connected to the bottom of the chip carrier, roof and the chip of first reaction film Bottom wall contact, the roof of the reactor body contacts with the bottom wall of first reaction film, and the main body of the reactor is set It is equipped with feed pathway and liquid outlet channel, the feed pathway and the liquid outlet channel extend vertically through the reactor body, For being contacted with reaction solution, first reaction film is provided with drainage lumens for the bottom of the feed pathway, the feed pathway and The liquid outlet channel is connected to the drainage lumens.
The beneficial effects of the invention are as follows:It is followed by the feed pathway and liquid outlet channel of setting to carry out the liquid of reaction solution The power of ring, imbibition can be solved by external peristaltic pump.The drainage lumens conduct formed between reaction film and reactor body It is connected to the exclusive path of feed pathway and liquid outlet channel so that flowing through the reaction solution of drainage lumens can connect with the first reaction film It touches so that generate and react between the first reaction film and reaction solution, convenient for observation, in addition, stablizing the reaction solution introduced can make Reaction in drainage lumens persistently occurs, convenient for analysis.
Description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment attached Figure is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not construed as pair The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this A little attached drawings obtain other relevant attached drawings.
Fig. 1 is the front view that a kind of one-time reaction liquid that the embodiment of the present invention one provides draws reactor;
Fig. 2 is the upward view of Fig. 1;
Fig. 3 is the sectional view of Fig. 1;
Fig. 4 is the partial schematic diagram of Fig. 3;
Fig. 5 is the structural schematic diagram that a kind of one-time reaction liquid provided by Embodiment 2 of the present invention draws reactor;
Fig. 6 is the left view of Fig. 5;
Fig. 7 is the structural schematic diagram that the one-time reaction liquid that the embodiment of the present invention 3 provides draws reactor;
Fig. 8 is the structural schematic diagram that the one-time reaction liquid that the embodiment of the present invention 4 provides draws reactor.
Reference numeral summarizes:
Chip carrier 101;Chip 102;First reaction film 103;Reactor body 104;Convex block 105;Second reaction film 106; Capture hole 107;Drainage lumens 109;Feed pathway 110;Liquid outlet channel 111, the first feeding-passage 112;Second reaction channel 113.
Specific implementation mode
The analysis means of protein used at present mainly carry out separation analysis to protein example, obtain sample One-dimension information will obtain more information and a variety of analysis means is needed to be used in combination, for example by after Separation of Proteins, carry out albumen The collection of matter will collect the enzyme hydrolysis of obtained protein progress protease, the main protease using specificity, obtained water Solution product (mainly peptide fragment) carries out separation analysis, mainly uses high performance liquid chromatography/mass spectrum, Capillary Electrophoresis/mass spectrum, matter Spectrum is analyzed, and such process is more loaded down with trivial details, and has many processes to can not achieve automation, and to expend long time.
In consideration of it, the present invention provides a kind of one-time reaction liquid to draw reactor, pass through endlessly abstraction reaction Liquid, and the first reaction film and the second reaction film are successively set on the path of reaction solution, promote present apparatus analysis protein Efficiency.
It should be noted that in the absence of conflict, the feature in embodiment and embodiment in the present invention can phase Mutually combine.
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with the embodiment of the present invention In attached drawing, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described embodiment is A part of the embodiment of the present invention, instead of all the embodiments.The present invention being usually described and illustrated herein in the accompanying drawings is implemented The component of example can be arranged and be designed with a variety of different configurations.Therefore, below to the reality of the present invention provided in the accompanying drawings The detailed description for applying example is not intended to limit the range of claimed invention, but is merely representative of the selected implementation of the present invention Example.Based on the embodiments of the present invention, those of ordinary skill in the art are obtained without creative efforts Every other embodiment, shall fall within the protection scope of the present invention.
In the description of the present invention, it is to be understood that, term "upper", "lower", "front", "rear", "left", "right", " perpendicular To ", "horizontal", "top", "bottom" "inner", the instructions such as "outside" orientation or positional relationship be orientation based on ... shown in the drawings or position The relationship invention product using when the orientation or positional relationship usually put or those skilled in the art it is usual The orientation or positional relationship of understanding is merely for convenience of the description present invention, does not indicate or imply the indicated equipment or element It must have a particular orientation, with specific azimuth configuration and operation, therefore be not considered as limiting the invention.
In addition, term " first ", " second " are used for description purposes only, it is not understood to indicate or imply relative importance Or implicitly indicate the quantity of indicated technical characteristic.Define " first " as a result, the feature of " second " can be expressed or Implicitly include one or more this feature.In the description of the present invention, the meaning of " plurality " is two or more, Unless otherwise specifically defined.
In the present invention unless specifically defined or limited otherwise, term " installation ", " connected ", " connection ", " fixation " etc. Term shall be understood in a broad sense, for example, it may be being fixedly connected, may be a detachable connection, or integral;Can be that machinery connects It connects, can also be electrical connection;It can be directly connected, can also can be indirectly connected through an intermediary in two elements The interaction relationship of the connection in portion or two elements.It for the ordinary skill in the art, can be according to specific feelings Condition understands the concrete meaning of above-mentioned term in the present invention.
In the present invention unless specifically defined or limited otherwise, fisrt feature the "upper" of second feature or "lower" It may include that the first and second features are in direct contact, can also not be to be in direct contact but pass through it including the first and second features Between other characterisation contact.Moreover, fisrt feature second feature " on ", " top " and " above " include first special Sign is right over second feature and oblique upper, or is merely representative of fisrt feature level height and is higher than second feature.Fisrt feature exists Second feature " under ", " lower section " and " following " include fisrt feature immediately below second feature and obliquely downward, or be merely representative of Fisrt feature level height is less than second feature.
Embodiment one
- Fig. 4 is please referred to Fig.1, the embodiment of the present invention one provides a kind of one-time reaction liquid absorption reactor, including chip The 101, first reaction film 103 of seat, reactor body 104 and the chip 102 for detecting reaction process.
Chip 102 is fixed on the bottom of chip carrier 101, and the roof of the first reaction film 103 is contacted with the bottom wall of chip 102, The roof of reactor body 104 is contacted with the bottom wall of the first reaction film 103, and the main body of reactor is provided with 110 He of feed pathway Liquid outlet channel 111, feed pathway 110 and liquid outlet channel 111 extend vertically through reactor body 104, the bottom of feed pathway 110 For being contacted with reaction solution, the first reaction film 103 is provided with drainage lumens 109 in portion, feed pathway 110 and liquid outlet channel 111 with Drainage lumens 109 are connected to.
The liquid circulation of reaction solution is carried out by the feed pathway 110 and liquid outlet channel 111 of setting, the power of imbibition can To be solved by external peristaltic pump.The drainage lumens 109 formed between reaction film and reactor body 104 are logical as feed liquor is connected to The exclusive path in road 110 and liquid outlet channel 111 so that flowing through the reaction solution of drainage lumens 109 can connect with the first reaction film 103 It touches so that generate and react between the first reaction film 103 and reaction solution, convenient for observation, in addition, stablizing the reaction solution introduced can make The reaction obtained in drainage lumens 109 persistently occurs, convenient for analysis.
In the preferred embodiment of the present invention, reactor further includes the second reaction film 106, the second reaction film 106 with react The bottom wall of device main body 104 is bonded, and liquid outlet channel 111 connects with the second reaction film 106.
Second reaction film 106 is for carrying out another single step reaction so that and the present apparatus can carry out many experiments, and second step Reaction solution is the liquid after the reaction of the first step.The mode of multistep reaction makes the more efficient of the present apparatus.
The first reaction film 103 and the second reaction film 106 in the present embodiment all can be PDMS films.PDMS material cost It is low, using simple, with having good adhesiveness between silicon chip, and there is good chemical inertness.
Reactor body 104 further includes convex block 105, and convex block 105 is arranged in the bottom of reactor body 104, feed pathway 110 run through convex block 105.
The setting of convex block 105 with the bottom port of liquid outlet channel 111 so that there is height in the bottom port of feed pathway 110 Difference on direction, so that when drawing reaction solution, reaction solution will not be contacted directly with the second reaction film 106, convenient for rule The path of model reaction solution.In addition, the convex block 105 of protrusion also allows for feed pathway 110 connecting with the container where reaction solution.
Further, feed pathway 110 be 24, liquid outlet channel 111, drainage lumens 109 and 110 three of feed pathway number Amount is consistent, and each drainage lumens 109 are connected to a liquid outlet channel 111 and a feed pathway 110 simultaneously.The quantity of convex block 105 is 4 A and 2 group of bumps of composition, each group of bumps include two convex blocks 105, between two convex blocks 105 in same group of bumps There are one the second reaction films 106 for setting.
It is improved by structure, improves the line density of reaction solution, and making will not phase between different reaction solution paths Mutually interference, avoids cross contamination.In this case, the reaction efficiency of the reaction solution under the control of the present apparatus greatly improves.
The quantity of convex block 105 increases, and the quantity of feed pathway 110 can also further increase.Controlling the second reaction film Higher utilization rate can also be possessed under 106 quantity.
In addition, the quantity of group of bumps and the total quantity of feed pathway 110 can also be changed, carried out according to actual conditions Change.Only there are one convex block 105 or only, there are one the case where feed pathway 110 can also achieve the object of the present invention.
In the present embodiment, chip 102 is micro-fluidic chip.Further, chip 102 is quartz or glass-chip, is drawn Stream chamber table wall be provided be bonded by coupling agent by organic polymer or protein made of decorative layer.
Micro-fluidic chip has liquid flowing controllable, consumption sample and reagent is few, analyze speed tenfold hundreds of times The features such as raising, it is analyzed while can carrying out a sample up to a hundred within a few minutes even shorter time, and can be Line realizes pretreatment and the analysis overall process of sample.Its target is the function entire laboratory, including sampling, dilution plus Reagent, reaction, separation, detection etc. are integrated on microchip, and can be used for multiple times.
Organic polymer mainly has polyvinyl alcohol, polyvinylacetate, hydroxyalkyl vinyl cellulose, polyethylene glycol, polyacrylamide Amine, glycan etc.;Protein such as bovine serum albumin(BSA).Decorative layer can promote the accuracy of chip detection reaction.
In addition, chip 102 or plastic chip.In order to preferably cater to the demand of the present apparatus, chip can carry out Corona treatment, photo-irradiation treatment, hydrophily processing or hydrophobicity processing.
By the present apparatus, the association reaction of the assembly and specific one's share of expenses for a joint undertaking of aglucon can be carried out, sample transport, surface are implemented The a series of experiments steps such as formatting, aglucon assembling, surface clean, surface-closed and albumen qualitative response.
Reactor in the present embodiment is disposable, is independent functional unit, can according to particular detection sample into Row targeted design detects while realizing nine indexs of blood examination and tumor-marker, has reference cell and recessive control unit Deng high-throughput reaction member.
Embodiment two
Fig. 5 and Fig. 6 are please referred to, second embodiment of the present invention provides a kind of one-time reaction liquid to draw reactor, including core Tablet seat 101, the first reaction film 103, reactor body 104, crawl hole 107, peristaltic pump and the chip for detecting reaction process 102。
Chip 102 is fixed on the bottom of chip carrier 101, and the roof of the first reaction film 103 is contacted with the bottom wall of chip 102, The roof of reactor body 104 is contacted with the bottom wall of the first reaction film 103.The main body of reactor is provided with 110 He of feed pathway Liquid outlet channel 111, feed pathway 110 and liquid outlet channel 111 extend vertically through reactor body 104, the bottom of feed pathway 110 For being contacted with reaction solution, the first reaction film 103 is provided with drainage lumens 109 in portion, feed pathway 110 and liquid outlet channel 111 with Drainage lumens 109 are connected to.The side wall of chip carrier 101 and the side wall of reactor body 104 are both provided with crawl hole 107, chip carrier 101 Crawl hole 107 with support member for being connected.In the preferred embodiment of the present invention, reactor further includes second anti- Film 106, the second reaction film 106 is answered to be bonded with the bottom wall of reactor body 104, liquid outlet channel 111 and 106 phase of the second reaction film It connects.
Peristaltic pump is connect with liquid outlet channel 111.Peristaltic pump provides the power of reaction solution flowing, ensures reaction solution according to rule The path flowing drawn.
Crawl hole 107 is used to fix the position of the present apparatus, and chip carrier 101 and reactor body 104 are both provided with crawl hole 107 so that can provide active force to keep the relative position between chip carrier 101 and reactor body 104 when fixed, keep away Exempt to loosen between chip carrier 101 and reactor body 104, and then enables the path of reaction solution generate and obscure.
The connection of peristaltic pump belongs to common knowledge, and details are not described herein.And unmentioned part and implementation in the present embodiment Example one is identical, those skilled in the art's reference implementation example one.
Unless specifically stated otherwise, component, step, numerical expression and the numerical value otherwise illustrated in these embodiments is simultaneously It does not limit the scope of the invention.
Embodiment three
The one-time reaction liquid suction in reactor, with embodiment 1 is drawn the present embodiment provides a kind of one-time reaction liquid Take reactor difference lies in the set-up modes of feeding-passage and tapping channel it is different, remaining content refering to embodiment 1, This is repeated no more.
Specifically, in the present embodiment, feeding-passage includes 113 two parts of the first feeding-passage 112 and the second feeding-passage, Wherein, the first feeding-passage 112 is for operating personnel's sample introduction, and the second feeding-passage 113 it is vertically arranged and with tapping channel 111 simultaneously Row's setting, as shown in fig. 7, in the present embodiment, the second feeding-passage 113 is four channels being mutually parallel, the arrow generation in Fig. 7 The flow direction of table reaction solution.Reaction solution is added from the first feeding-passage 112 first, is being set to 111 end of tapping channel thereafter Under the power at end drives, the reaction solution in the first feeding-passage 112 enters in the second feeding-passage 113, and with the first reaction film 103 reactions, are extracted thereafter by tapping channel 111.In the present embodiment, tapping channel 111 is similarly 4, and every discharging is logical Road 111 is corresponding with second feeding-passage 113.
Example IV
The one-time reaction liquid suction in reactor, with embodiment 1 is drawn the present embodiment provides a kind of one-time reaction liquid Take reactor difference lies in the set-up mode difference of feeding-passage 110 and tapping channel 111, remaining content is refering to embodiment 1 , details are not described herein.
Specifically, in the present embodiment, as shown in figure 8, arrow direction represents the flow direction of reaction solution in the reactor in figure, In, the first reaction film 103 is set to 104 upper end of reactor body, and the second reaction film is set to 104 lower end of reactor body, into Channel 110 and tapping channel 111 are expected in reciprocal setting back and forth in reactor body 104, and the fluid channel being back and forth arranged is upper Lower both ends are contacted with the first reaction film 103 and the second reaction film 106 respectively, and such reaction solution is by dynamic at tapping channel 111 Under power drives flowing reciprocal back and forth in fluid channel between feeding-passage 110 and tapping channel 111 and with the first reaction film 103 and 106 haptoreaction of the second reaction film, it can greatly improve between reaction solution and the first reaction film 103 and the second reaction film 106 Contact area and the reaction time, improve reaction effect.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, any made by repair Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.

Claims (8)

1. a kind of one-time reaction liquid draws reactor, which is characterized in that including chip carrier, the first reaction film, reactor body With the chip for detecting reaction process, the chip is connected to the bottom of the chip carrier, the roof of first reaction film It is contacted with the bottom wall of the chip, the roof of the reactor body is contacted with the bottom wall of first reaction film, the reaction Device main body is provided with feed pathway and liquid outlet channel, and the feed pathway and the liquid outlet channel extend vertically through the reaction Device main body, for being contacted with reaction solution, first reaction film is provided with drainage lumens, the feed liquor for the bottom of the feed pathway Channel and the liquid outlet channel are connected to the drainage lumens, and the reactor further includes the second reaction film, second reaction Film is bonded with the bottom wall of the reactor body, and the liquid outlet channel connects with second reaction film, feeding-passage and discharging Reciprocal setting back and forth in channel and reactor body, and the upper and lower ends for the fluid channel being back and forth arranged respectively with the first reaction film With the second reaction film contact so that reaction solution by tapping channel power drive under between feeding-passage and tapping channel In fluid channel flowing reciprocal back and forth and with the first reaction film and the second reaction film haptoreaction, the reactor body also wraps Convex block is included, the convex block is arranged in the bottom of the reactor body, and the feed pathway runs through the convex block.
2. reactor according to claim 1, which is characterized in that be respectively provided with that there are one described the between two convex blocks Two reaction films.
3. reactor according to claim 1, which is characterized in that the feed pathway is at least two, it is described go out liquid it is logical Road, the drainage lumens are consistent with the quantity of feed pathway three, go out liquid described in the connection one simultaneously of each drainage lumens Channel and a feed pathway.
4. according to the reactor described in claim 1-3 any one, which is characterized in that the side wall of the chip carrier and described anti- The side wall of device main body is answered to be both provided with crawl hole, crawl hole with support member for being connected described in the chip carrier.
5. according to the reactor described in claim 1-3 any one, which is characterized in that the chip is micro-fluidic chip.
6. reactor according to claim 5, which is characterized in that the chip is quartz or glass-chip, the drainage The table wall of chamber is provided be bonded by coupling agent by organic polymer or protein made of decorative layer.
7. reactor according to claim 5, which is characterized in that the chip is plastic chip, and the chip carries out Corona treatment, photo-irradiation treatment, hydrophily processing or hydrophobicity processing.
8. according to the reactor described in claim 1-3 any one, which is characterized in that the reactor further includes peristaltic pump, The peristaltic pump is connect with the liquid outlet channel.
CN201610789358.6A 2016-08-31 2016-08-31 Disposable reaction liquid suction reactor Active CN106248979B (en)

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Citations (1)

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CN2702313Y (en) * 2004-06-11 2005-05-25 中国科学院力学研究所 Biological chip production and chip-on biomolecule fixing and detection integrated system
EP1773498B1 (en) * 2004-07-06 2012-06-13 The University of Utah Research Foundation Spotting device and method for high concentration spot deposition on microarrays and other microscale devices
CN101896275A (en) * 2007-12-17 2010-11-24 龚海庆 Microfluidic device
JP5692164B2 (en) * 2012-05-22 2015-04-01 ウシオ電機株式会社 Reagent supply method to microchip and reagent supply apparatus to microchip
CN104792767B (en) * 2015-05-08 2017-11-17 厦门大学 A kind of micro-fluidic chip and its application method for sol method SERS detections
CN206038701U (en) * 2016-08-31 2017-03-22 贵州金玖生物技术有限公司 Once only react liquid and absorb reactor

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CN1523354A (en) * 2003-02-17 2004-08-25 中国科学院力学研究所 Method and apparatus for bio-molecular chip minute quantity sample application and reaction

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