CN106226540B - Full-automatic protein chip analyzer - Google Patents

Full-automatic protein chip analyzer Download PDF

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Publication number
CN106226540B
CN106226540B CN201610789335.5A CN201610789335A CN106226540B CN 106226540 B CN106226540 B CN 106226540B CN 201610789335 A CN201610789335 A CN 201610789335A CN 106226540 B CN106226540 B CN 106226540B
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reaction
reactor
rack
sample
chip
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CN106226540A (en
Inventor
韩克兵
王磊
周庭波
张思宇
郑世阳
任占涛
刘炜进
曾世洪
陈汉柒
綦小三
刘念
王雪静
张亚
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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
    • G01N35/00029Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21Polarisation-affecting properties
    • G01N21/211Ellipsometry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • 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
    • G01N35/00584Control arrangements for automatic analysers
    • 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
    • G01N35/0099Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • 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
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/025Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
    • 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
    • G01N35/00029Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099Characterised by type of test elements
    • G01N2035/00158Elements containing microarrays, i.e. "biochip"
    • 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
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0401Sample carriers, cuvettes or reaction vessels
    • G01N2035/0437Cleaning cuvettes or reaction vessels

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  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plasma & Fusion (AREA)
  • Robotics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The invention provides a full-automatic protein chip analyzer, which belongs to the field of research equipment and comprises a rack, a sample container, an observation system, a reaction system, an electric control system and a motion system, wherein the observation system, the reaction system, the motion system and the electric control system are all connected with the rack, the sample container is used for containing a sample, the sample is used for contacting with a reactor and reacting, the rack comprises a workbench, the reaction system comprises a reaction table, the reaction table is connected with the workbench, the motion system and the reaction system are all electrically connected with the electric control system, the reaction system comprises the reactor, the observation system is used for observing the reaction condition of the reactor, the motion system comprises a mechanical arm used for carrying out experimental operation, the mechanical arm is used for transferring the reactor to the reaction table, and the mechanical arm is also used for grabbing a disposable suction head and adding the sample into the reactor. The device changes the steps of protein analysis into automation, reduces the probability of cross infection in the test, and improves the efficiency and accuracy of the test.

Description

Full-automatic ProteinChip Analysis instrument
Technical field
The present invention relates to research clothing arts, in particular to full-automatic ProteinChip Analysis instrument.
Background technology
Currently, the detection technique in medical institutions is mainly immunized using enzyme-linked immunization, Full-automatic chemiluminescence and is divided The traditional immunization determination techniques of analysis method carry out single index detection.Enzyme linked immunological law technology mainly educates device, enzyme mark by sample-adding plate, ovum Instrument, board-washing machine, data processing module composition.The basic principle of the technology is:1. antigen or antibody is made to be attached to certain solid phase load Body surface face, and keep its immunocompetence.2. antigen or antibody is made to connect into enzyme-labelled antigen or antibody with certain enzyme, this enzyme mark is anti- Former or antibody had not only retained its immunocompetence, but also retained the activity of enzyme.Measure when, by examine sample (measure antibody therein or Antigen) and enzyme-labelled antigen or antibody react by the antigen or antibody of different step and surface of solid phase carriers.With the side of washing Method makes the antigen antibody complex formed on solid phase carrier be separated with other substances, finally combine enzyme amount on solid phase carrier with The amount of tested substance is at certain ratio in sample.After the substrate of enzyme reaction is added, substrate becomes color products by enzymatic, production The amount of object is directly related with the amount of tested substance in sample, therefore can qualitatively or quantitatively be divided according to the depth of color reaction Analysis.Chemiluminescent basic principle is molecule (reactant, product, intermediate or the fluorescence of certain substance in reaction system Matter) energy for reacting discharged is absorbed by ground state transition to excitation state, ground state then is returned to from excitation state again, while will Amount is released in the form of light radiation, generates chemiluminescence, is generally examined by sample disk, reagent disc, incubation reaction disk, electrochemistry Examining system, computer control system composition.
Inventor has found that existing technology is complicated due to marking the requirement to reagent, complex for operation step, fixed under study for action Amount is difficult, and label be easy to cause cross contamination, and multinomial marker detection then needs prolonged cumbersome labour and higher expense With, therefore be difficult to promote.
Invention content
The present invention provides a kind of full-automatic ProteinChip Analysis instrument, and one of its goals is to reduce protein analysis The manual operation of experiment;Its second purpose is, avoids the cross contamination generated in experimentation;Its third purpose is, contracts The time of short protein analysis experiment, improve the efficiency of experiment.
The invention is realized in this way:
A kind of full-automatic ProteinChip Analysis instrument, including rack, sample container, observing system, reaction system, automatically controlled system System and kinematic system, the observing system, reaction system, kinematic system and electric-control system are connect with the rack, the sample Product container is for accommodating sample, and for the sample for contacting and reacting with the reactor, the rack includes workbench, The reaction system includes reaction bench, and the reaction bench is connect with the workbench, the kinematic system and the reaction system It is electrically connected with the electric-control system, the reaction system includes reactor, and the observing system is for observing the reactor Response situation, the kinematic system includes the mechanical arm for carrying out experimental implementation, and the mechanical arm is used for the reaction Device is transferred to the reaction bench, and the rack further includes suction nozzle box, and the suction nozzle box are for placing disposable tip, the machinery Arm is additionally operable to capture the disposable tip and adds the sample into the reactor.
In a preferred embodiment of the invention, the rack includes guide rail, and the mechanical arm is slidably connected with the guide rail, The electric-control system is slided for controlling the mechanical arm along the guide rail.
In a preferred embodiment of the invention, the mechanical arm include first and second, described first with it is described Guide rail is slidably connected, and described first includes X direction guiding rails, and the X direction guiding rails are arranged along the short transverse of the rack, and described the Two are slidably connected with the X direction guiding rails, and the electric-control system is additionally operable to drive described second to slide along the X direction guiding rails.
In a preferred embodiment of the invention, the analyzer further includes rotating disk and suction nozzle box, the suction nozzle box and institute Workbench or rack connection are stated, the suction nozzle box storage has multiple disposable tips, the rotating disk and the workbench It is rotatablely connected, at least one sample container and at least one reactor is placed at the top of the rotating disk, it is described automatically controlled System is additionally operable to that the rotating disk is driven to rotate, and the mechanical arm is additionally operable to capture the disposable tip to extract the sample Product, and the sample is transferred to the reactor, the height of the rotary centerline direction and the rack of the rotating disk It is parallel to spend direction.
In a preferred embodiment of the invention, the workbench is additionally provided with for concentrating losing for the disposable tip used up Mouth is abandoned, the rack further includes discarded collecting box, and the discarded collecting box is located at the bottom of the workbench, the disposable suction Head can fall into the discarded collecting box from the discarding mouth.
In a preferred embodiment of the invention, the rack further includes benchmark table top and matter storage lattice, the matter storage lattice setting In the bottom of the benchmark table top, the workbench is arranged at the top of the benchmark table top.
In a preferred embodiment of the invention, the reactor includes the chip and reactor body being detachably connected, institute The surface for stating chip is provided with active organism probe, and the active organism probe is set as multiple arrays, each bioactivity Probe corresponds to a protein array micro unit, and the active organism probe is for combining target molecule and generates biomolecule Compound, the observing system are used to observe the change procedure of active organism probe.
In a preferred embodiment of the invention, the analyzer further includes the turnover device for overturning the chip, institute It states turnover device to connect with the reaction bench, the turnover device includes rotatable movable part, in the rotation of the movable part Heart line is horizontal, and the chip can rotate 180 ° by the turnover device.
In a preferred embodiment of the invention, the observing system includes observation platform, oval thickness component and CCD camera shootings Machine, the observation platform are connect with the rack, and the observation platform is used for the reactor after placing response, the oval thickness component For extending polarized lightwave and irradiating the reactor, the CCD camera is believed due to the sample being loaded in detection reflecting light It ceases and is stored in the form of generating digital picture.
In a preferred embodiment of the invention, the analyzer further includes the clear of the surface residue for purge reactor Clean system, the cleaning systems are electrically connected with the electric-control system, and the cleaning systems include rinsing table, nitrogen machine, conduit, note Pump and soda liquor container are penetrated, one end of the conduit is connected to the soda liquor container, described in the other end direction of the conduit Rinsing table, the cleaning solution in the soda liquor container for being moved along conduit and being rinsed the rinsing table, institute by the syringe pump It states rinsing table to connect with the workbench, the nitrogen machine is used to dry up the reactor on the observation platform, the machinery The roof that arm is additionally operable to the reactor after reaction being moved to the rinsing table is rinsed, and the reactor after flushing is placed in The observation platform.
The beneficial effects of the invention are as follows:Experimental implementation is carried out using electric-control system drive motion system 200, in kinematic system Mechanical arm replace manually being tested, and reactor is studied by observing system, alleviates artificial labour.Number The control of controlization can effectively reduce the mistake that manual operation error may be brought, and improve the accuracy of experimental result, accelerate real The efficiency tested.
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 a kind of overall schematic for full-automatic ProteinChip Analysis instrument that the embodiment of the present invention 1 provides;
Fig. 2 is the front view of Fig. 1;
Fig. 3 is the rearview of Fig. 1;
Fig. 4 is the vertical view of Fig. 1;
Fig. 5 is the front view for the reactor that the embodiment of the present invention 2 provides;
Fig. 6 is the upward view of Fig. 5;
Fig. 7 is the sectional view of Fig. 5;
Fig. 8 is the partial schematic diagram of Fig. 7;
Fig. 9 is the structural schematic diagram for the reactor that the embodiment of the present invention 3 provides;
Figure 10 is the left view of Fig. 9;
Figure 11 is the structural schematic diagram for the reactor that the embodiment of the present invention 4 provides;
Figure 12 is the structural schematic diagram for the reactor that the embodiment of the present invention 5 provides.
Reference numeral summarizes:
Reactor 100;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 is anti- Answer channel 113;Reaction bench 114;Peristaltic pump 115;Sample container 200;Sample 210;Observing system 300;Observation platform 310;It is ellipse inclined Optical module 320;CCD camera 330;Rack 400;Guide rail 410;Benchmark table top 420;Matter storage lattice 430;Workbench 440;It abandons Mouth 441;Discarded collecting box 450;Electric-control system 500;Kinematic system 600;Mechanical arm 610;First 611;X direction guiding rails 612;The Two 613;Rotating disk 700;Suction nozzle box 800;Disposable tip 810;Turnover device 900;Movable part 901;Cleaning systems 1000; Clean hatch 1010.
Specific implementation mode
Existing technology is complicated due to marking the requirement to reagent, and complex for operation step, difficult quantitation, label is easy to make At cross contamination, multinomial marker detection then needs prolonged cumbersome labour and higher expense, therefore is difficult to promote.
In consideration of it, the present invention provides a kind of full-automatic ProteinChip Analysis instrument, pass through each system of Automatic Control System, eliminates manual operation, improves the efficiency of experiment.
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 "center", " longitudinal direction ", " transverse direction ", " length ", " width ", " thickness ", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom" "inner", "outside", " up time The orientation or positional relationship of the instructions such as needle ", " counterclockwise " is to be based on the orientation or positional relationship shown in the drawings or the invention Product using when the orientation or positional relationship usually put or the orientation that usually understands of those skilled in the art or position close System is merely for convenience of the description present invention, do not indicate or imply the indicated equipment or element must have a particular orientation, With specific azimuth configuration and operation, therefore it is 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 1
- Fig. 4 is please referred to Fig.1, the embodiment of the present invention 1 provides a kind of 102 analyzer of full-automatic protein-chip, including machine Frame 400, sample container 200, rotating disk 700, turnover device 900, cleaning systems 1000, observing system 300, reaction system, electricity Control system 500 and kinematic system 600.
Observing system 300, cleaning systems 1000, rotating disk 700, turnover device 900, reaction system, 600 and of kinematic system Electric-control system 500 is connect with rack 400.
Rack 400 includes workbench 440, and reaction system includes reaction bench 114, and reaction bench 114 is connect with workbench 440, Kinematic system 600 and reaction system are electrically connected with electric-control system 500, and reaction system includes reactor 100, observing system 300 For the response situation of observing response device 100, kinematic system 600 includes the mechanical arm 610 for carrying out experimental implementation, mechanical arm 610 by reactor 100 for being transferred to reaction bench 114, and rack 400 further includes suction nozzle box 800, and suction nozzle box 800 are for placing one Secondary property suction nozzle 810, sample container 200 are used to contact and react with reactor 100 for accommodating sample 210, sample 210, Mechanical arm 610 is additionally operable to crawl disposable tip 810 and adds sample 210 into reactor 100.
Rack 400 includes guide rail 410, and mechanical arm 610 is slidably connected with guide rail 410, and electric-control system 500 is used for control machinery Arm 610 is slided along guide rail 410.
In order to realize the movement of mechanical arm 610 in the vertical direction, the mechanical arm 610 in the present embodiment includes first 611 and second 613, first 611 is slidably connected with guide rail 410, and first 611 includes X direction guiding rails 612, X direction guiding rails 612 Short transverse along rack 400 is arranged, and second 613 is slidably connected with X direction guiding rails 612, and electric-control system 500 is additionally operable to driving the It is slided along X direction guiding rails 612 for two 613.
Suction nozzle box 800 are connect with workbench 440 or rack 400, and the storage of suction nozzle box 800 has multiple disposable tips 810, revolves Turntable 700 and workbench 440 are rotatablely connected, and the top of rotating disk 700 is placed at least one sample container 200 and at least one Reactor 100, electric-control system 500 are additionally operable to driving rotating disk 700 and rotate, and mechanical arm 610 is additionally operable to crawl disposable tip 810 To extract sample 210, and sample 210 is transferred to reactor 100, the rotary centerline direction and rack of rotating disk 700 400 short transverse is parallel.
Using the rotational motion of rotating disk 700, the position of the sample container 200 in rotating disk 700 can be adjusted.It is logical The method is crossed, can multiple sample containers 200 be set in the top of rotating disk 700.Since mechanical arm 610 is slided along guide rail 410, Therefore, the mobile route of mechanical arm 610 is fixed.It, can be by automatically controlled when more bottles of sample containers 200 are arranged in rotating disk 700 System 500 drives rotating disk 700 to rotate so that sample container 200 is moved to the lower section of mechanical arm 610, so that mechanical arm 610 carries Take sample 210.
Workbench 440 is additionally provided with the discarding mouth 441 for concentrating the disposable tip 810 used up, and rack 400 further includes Discarded collecting box 450, discarded collecting box 450 are located at the bottom of workbench 440, and disposable tip 810 can be fallen from mouth 441 is abandoned Enter discarded collecting box 450.
Rack 400 further includes benchmark table top 420 and matter storage lattice 430, and matter storage lattice 430 is arranged in the bottom of benchmark table top 420, Workbench 440 is arranged at the top of benchmark table top 420.Matter storage lattice 430 can be used not only for storage and test relevant article, also profit With the space of rack 400, the height of benchmark table top 420 and workbench 440 is improved, also provides space to recovery system.
Reactor 100 includes that the chip 102 being detachably connected and reactor body 104, the surface of chip 102 are provided with life Object active probe, active organism probe are set as multiple arrays, each active organism probe corresponds to a protein array Micro unit, active organism probe is for combining target molecule and generates bimolecular complexes, and observing system 300 is for observing life The change procedure of object active probe.Mechanical arm 610 can detach chip 102 with reactor body 104.
When sensitive surface and the solution containing target molecule contact, if matching on target molecule and probe in solution Base molecule is specifically bound, and will generate bimolecular complexes, and surface of solids biomolecule surface density changes, this Variation can be observed by oval thickness imaging system high-resolution.
Turnover device 900 is used for turning-over of chip 102, and turnover device 900 is connect with reaction bench 114, and turnover device 900 includes The rotary centerline of rotatable movable part 901, movable part 901 is horizontal, and chip 102 can be rotated by turnover device 900 180°。
900 turning-over of chip 102 of turnover device so that the top and bottom of the multielement protein chip 102 of plate exchange.Overturning Meaning be, reason of the chip 102 from the virtual condition and chip 102 when being separated in reactor 100 on observation platform 310 State difference is thought, if the information that observing system 300 obtains can not caused inaccurate by overturning.Inventor is not direct Change the layout of the reaction environment and observing system 300 of reactor 100, but is converted by the turnover device of addition 900 more The angle of first protein chip 102, in order to observing response result.
In a preferred embodiment of the invention, observing system 300 includes observation platform 310, oval thickness component 320 and CCD Video camera 330, observation platform 310 are connect with rack 400, and observation platform 310 is used for the reactor 100 after placing response, oval thickness Component 320 is for extending polarized lightwave and irradiating reactor 100, and CCD camera 330 is due to detecting the sample being loaded in reflecting light 210 information of product is simultaneously stored in the form of generating digital picture.
CCD camera 330 refers to the video camera with CCD chip 102.CCD refers to charge coupling device.It is ellipse by being imaged The inclined technology of circle, researcher can realize the ellipsometry analysis under extra small piece of film analysis, ellipsometry in situ, various liquid environments And it may be implemented to be combined with multiple technologies.When being utilized to the combination of research albumen, experimenter is not necessarily to as fluorescent immune method, enzyme Linked immunosorbent assay and radioimmunology like that use the biomolecule detected the secondary antibody reagent of label, to biology point to be measured Sub- activity undisturbed and damage.In addition, the high sensitivity of detection, can identify the biological membranous layer variation of 0.1nm.
In the present embodiment, cleaning systems 1000 are electrically connected with electric-control system 500, cleaning systems 1000 include rinsing table, One end of nitrogen machine, conduit, syringe pump and soda liquor container, conduit is connected to soda liquor container, and the other end of conduit is directed toward clearly Platform is washed, syringe pump is used to that rinsing table, rinsing table and workbench 440 to be moved and rinsed along conduit by the cleaning solution in soda liquor container Connection, nitrogen machine are used to dry up the reactor 100 on observation platform 310, and mechanical arm 610 is additionally operable to the reactor after reacting 100 roofs for being moved to rinsing table are rinsed, and the reactor 100 after flushing is placed in observation platform 310.
In addition, it is further, in order to avoid the cross-infection in experimentation, sample container 200, disposable tip 810 It is disposable product with reactor 100.
The present apparatus at work, first drives whether all parts unit meets testing conditions by electric-control system 500, then electric 500 drive motion system 600 of control system works, and reactor 100 is transferred to reaction bench 114 by mechanical arm 610.Then mechanical arm 610 capture disposable tip 810 and draw quantitative sample 210 again, and sample 210 is assigned in enzyme-linked box, then will disposably be inhaled First 810 lose into discarding mouth 441.PBST and deionized water are separately added into reactor 100 again.Reaction system includes peristaltic pump 115,500 drive response system of electric-control system work, peristaltic pump 115 send sample 210 to the core of reactor 100 as power source On piece 102.After the reaction of chip 102, the first driving machine tool arm 610 of electric-control system 500 is independent from reactor 100 by chip 102 Rinsing table is removed and be transferred to, then cleaning systems 1000 is driven to work, rinses out the residue on 102 surface of chip, and by chip 102 dryings.Electric-control system 500 drives mechanical arm 610 to operate, and chip 102 is transferred to turnover device 900.Electric-control system 500 drives Dynamic 180 ° of the movement of turnover device 900 overturning so that the top and bottom of chip 102 exchange.After the completion of exchange, mechanical arm 610 is again Chip 102 is moved to observation platform 310, analysis and data processing are carried out to chip 102 by observing system 300.Finally, mechanical arm 610 abandon the reactor body 104 of chip 102 and reactor 100 to mouth 441 is abandoned, and complete experiment or continue to start next Secondary experiment.
As shown in figure 4, in whole experiment process, the transfer of chip 102, turnover device are completed for the ease of mechanical arm 610 900, rotating disk 700, discarding mouth 441, reaction bench 114, observation platform 310, suction nozzle box 800 and clean hatch 1010 are all located at mechanical arm 610 along guide rail 410 motion path vertically below.
Embodiment 2
Fig. 5-Fig. 8 is please referred to, the embodiment of the present invention 2 provides a kind of reactor, including chip carrier 101, the first reaction film 103, 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 3
Fig. 9 and Figure 10 are please referred to, the embodiment of the present invention 3 provides a kind of reactor, including chip carrier 101, first reacts Film 103, reactor body 104, crawl hole 107, peristaltic pump 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.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.
Embodiment 4
The one-time reaction liquid suction in reactor, with embodiment 2 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 2, 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 figure 11, in the present embodiment, the second feeding-passage 113 is four channels being mutually parallel, the arrow in Figure 11 Head represents the flow direction of reaction solution.Reaction solution is added from the first feeding-passage 112 first, is being set to tapping channel thereafter Under the power of 111 ends drives, the reaction solution in the first feeding-passage 112 enters in the second feeding-passage 113, and instead with first It answers film 103 to react, is extracted thereafter by tapping channel 111.In the present embodiment, tapping channel 111 is similarly 4, and every goes out Expect that channel 111 is corresponding with second feeding-passage 113.
Embodiment 5
The one-time reaction liquid suction in reactor, with embodiment 2 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 2 , details are not described herein.
Specifically, in the present embodiment, as shown in figure 12, arrow direction represents the flow direction of reaction solution in the reactor in figure, Wherein, 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, Feeding-passage 110 and tapping channel 111 are arranged in reciprocal back and forth in reactor body 104, and the fluid channel being back and forth arranged Upper and lower ends are contacted with the first reaction film 103 and the second reaction film 106 respectively, and such reaction solution is at by tapping channel 111 It flowing reciprocal back and forth in fluid channel between feeding-passage 110 and tapping channel 111 and is reacted with first under power drives 106 haptoreaction of film 103 and the second reaction film can greatly improve reaction solution and the first reaction film 103 and the second reaction film 106 Between contact area and the reaction time, improve reaction effect.
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.
The technique effect and preceding method embodiment phase of the device that the embodiment of the present invention is provided, realization principle and generation Together, to briefly describe, device embodiment part does not refer to place, can refer to corresponding contents in preceding method embodiment.
In all examples being illustrated and described herein, any occurrence should be construed as merely illustrative, without It is as limitation, therefore, other examples of exemplary embodiment can have different values.
It should be noted that:Similar label and letter indicate similar terms in following attached drawing, therefore, once a certain Xiang Yi It is defined, then it further need not be defined and explained in subsequent attached drawing in a attached drawing.
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 (9)

1. a kind of full-automatic ProteinChip Analysis instrument, which is characterized in that including rack, sample container, observing system, reaction system System, electric-control system and kinematic system, the observing system, reaction system, kinematic system and electric-control system connect with the rack It connects, the reaction system includes reactor, and the sample container is for accommodating sample, and the sample with the reactor for connecing It touches and reacts, the rack includes workbench, and the reaction system includes reaction bench, the reaction bench and the workbench Connection, the kinematic system and the reaction system are electrically connected with the electric-control system, and the observing system is for observing institute The response situation of reactor is stated, the kinematic system includes the mechanical arm for carrying out experimental implementation, and the mechanical arm is used for will The reactor is transferred to the reaction bench, and the rack further includes suction nozzle box, and the suction nozzle box are used to place disposable tip, The mechanical arm is additionally operable to capture the disposable tip and adds the sample into the reactor;The reactor includes Chip carrier, the first reaction film, reactor body and the chip for detecting reaction process, the chip are connected to the chip carrier Bottom, the roof of first reaction film contacts with the bottom wall of the chip, the roof of the reactor body and described the The bottom wall of one reaction film contacts, and the reactor body is provided with feed pathway and liquid outlet channel, the feed pathway and described Liquid outlet channel extends vertically through the reactor body, and the bottom of the feed pathway with reaction solution for contacting, and described the One reaction film is provided with drainage lumens, and the feed pathway and the liquid outlet channel are connected to the drainage lumens,
The reactor includes the chip and reactor body being detachably connected, and the analyzer further includes for overturning the core The turnover device of piece, the turnover device are connect with the reaction bench, and the turnover device includes rotatable movable part, described The rotary centerline of movable part is horizontal, and the chip can rotate 180 ° by the turnover device.
2. analyzer according to claim 1, which is characterized in that the rack includes guide rail, the mechanical arm with it is described Guide rail is slidably connected, and the electric-control system is slided for controlling the mechanical arm along the guide rail.
3. analyzer according to claim 2, which is characterized in that the mechanical arm includes first and second, described First is slidably connected with the guide rail, and described first includes X direction guiding rails, and the X direction guiding rails are along the height side of the rack To setting, described second is slidably connected with the X direction guiding rails, the electric-control system be additionally operable to drive described second along described X direction guiding rails slide.
4. analyzer according to claim 1, which is characterized in that the analyzer further includes rotating disk and suction nozzle box, institute It states suction nozzle box to connect with the workbench or the rack, the suction nozzle box storage has multiple disposable tips, the rotating disk It is rotatablely connected with the workbench, at least one sample container and at least one reaction is placed at the top of the rotating disk Device, the electric-control system are additionally operable to drive the rotating disk to rotate, the mechanical arm be additionally operable to capture the disposable tip with The sample is extracted, and the sample is transferred to the reactor, the rotary centerline direction of the rotating disk and institute The short transverse for stating rack is parallel.
5. analyzer according to claim 4, which is characterized in that the workbench is additionally provided with for concentrating use up one The discarding mouth of secondary property suction nozzle, the rack further include discarded collecting box, and the discarded collecting box is located at the bottom of the workbench, The disposable tip can fall into the discarded collecting box from the discarding mouth.
6. analyzer according to claim 1, which is characterized in that the rack further includes benchmark table top and matter storage lattice, institute It states matter storage lattice to be arranged in the bottom of the benchmark table top, the workbench is arranged at the top of the benchmark table top.
7. analyzer according to claim 1, which is characterized in that the surface of the chip is provided with active organism probe, The active organism probe is set as multiple arrays, each active organism probe corresponds to a protein array micro unit, The active organism probe is for combining target molecule and generates bimolecular complexes, and the observing system is for observing biology The change procedure of active probe.
8. analyzer according to claim 1, which is characterized in that the observing system includes observation platform, oval thickness group Part and CCD camera, the observation platform are connect with the rack, and the observation platform is used for the reactor after placing response, described Oval thickness component is for extending polarized lightwave and irradiating the reactor, and the CCD camera is due in detection reflecting light The sample message that is loaded with simultaneously is stored in the form of generating digital picture.
9. analyzer according to claim 8, which is characterized in that the analyzer further includes the table for purge reactor The cleaning systems of face residue, the cleaning systems are electrically connected with the electric-control system, and the cleaning systems include rinsing table, nitrogen Mechanism of qi, conduit, syringe pump and soda liquor container, one end of the conduit are connected to the soda liquor container, the conduit it is another The rinsing table is directed toward in one end, and the syringe pump by the cleaning solution in the soda liquor container along conduit for moving and rinsing institute Rinsing table is stated, the rinsing table is connect with the workbench, and the nitrogen machine is used to dry up the reaction on the observation platform Device, the roof that the mechanical arm is additionally operable to the reactor after reaction being moved to the rinsing table are rinsed, and will be after flushing Reactor be placed in the observation platform.
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