CN105273979A - DNA (deoxyribonucleic acid) sequencer reaction recording subsystem - Google Patents

DNA (deoxyribonucleic acid) sequencer reaction recording subsystem Download PDF

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Publication number
CN105273979A
CN105273979A CN201510716526.4A CN201510716526A CN105273979A CN 105273979 A CN105273979 A CN 105273979A CN 201510716526 A CN201510716526 A CN 201510716526A CN 105273979 A CN105273979 A CN 105273979A
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reaction
assembly
warehouse
turning
chip
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CN105273979B (en
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张睿
冯玉臣
范东雨
王者馥
王绪敏
殷金龙
任鲁风
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Beijing Zhongkezixin Technology Co Ltd
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Beijing Zhongkezixin Technology Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869Methods for sequencing

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  • Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Engineering & Computer Science (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention relates to a DNA (deoxyribonucleic acid) sequencer reaction recording subsystem. The DNA sequencer reaction recording subsystem comprises a reaction assembly, a movement platform assembly, a movement control unit, a CCD (charge coupled device) camera and a platform supporting assembly, wherein a reaction chip assembly is arranged in the reaction bin assembly; under effects of a control system, reaction liquid enters a reaction chip and reacts chemically so as to generate visible light; the movement platform assembly feeds the CCD camera to an appropriate photographing position so that the CCD camera can photograph and acquire visible light information generated in the reaction chip; the platform supporting assembly supports the reaction bin assembly and the movable platform assembly; and the movement control unit controls running of the CCD camera and running of the reaction chip in real time, drives the movement platform assembly to move to a photographing position of the CCD camera and detects and controls the temperature of a reaction bin. The DNA sequencer reaction recording subsystem has a multi-adjustment stable structure, various structures are convenient to mount and compact, and stability is high.

Description

A kind of DNA sequencer reacting record sub-system
Technical field
The present invention relates to DNA sequencing field, particularly relate to a kind of DNA sequencer reacting record sub-system.
Background technology
In DNA sequencing technical field, pyrosequencing techniques (pyrosequencing), it is a kind of novel enzyme cascade sequencing technologies grown up in 1987 by people such as Nyren, its repeatable and accurate performance and Sanger method DNA sequencing technology compare favourably, and speed improves greatly.Pyrosequencing techniques is by the enzyme cascade chemiluminescence reaction in 4 kinds of enzymatic same reaction systems.
The principle of pyrosequencing techniques is: after primer and template DNA are annealed, under the synergy of archaeal dna polymerase (DNApolymerase), ATP sulfurylase (ATPsulfurylase), luciferase (luciferase) and apyrase (Apyrase) four kinds of enzymes, the release coupling of the polymerization of each dNTP on primer and an optical signal is got up, by detecting release and the intensity of light, reach the object of the real time measure DNA sequence dna.The reaction system of pyrosequencing techniques is made up of reaction substrate, strand to be measured, sequencing primer and four kinds of enzymes.Reaction substrate is 5 '-phosphosulfate (adenosine-5 '-phosphosulfate, APS) and fluorescein (luciferin).Take turns in sequencing reaction at each, a kind of deoxynucleotide triphosphoric acid (dNTP) is only added in reaction system, if it can just with the next base pairing of DNA profiling, then can under the effect of archaeal dna polymerase, add 3 ' end of sequencing primer to, discharge the tetra-sodium (PPi) of a molecule simultaneously.Under the effect of ATP sulfurylase, the PPi of generation can combine with APS and form ATP, and under the catalysis of luciferase, the ATP of generation can combine with fluorescein again and form oxyluciferin, produces visible ray simultaneously.A special detected peaks can be obtained by Weak light detection device and process software, the height of peak value then and the base number matched be directly proportional.After last round of reaction completes, add another kind of dNTP, above-mentioned reaction is repeated, namely the peak value figure according to obtaining can read DNA sequence dna information accurately.
Integrated operation flow process is described below: DNA sample is by after fragmentation, application is built storehouse reagent and is carried out adding joint, strand is caught, be bonded to microballoon, microemulsion pcr amplification, breakdown of emulsion liquid, obtain the DNA library be based upon on microballoon, application adds model by laies such as the enzymes of library and sequencing reaction needs to the sequence testing chip with micro reaction pool, sequence testing chip and sequencing reagent are mounted on main frame, order-checking program is started according to module number and position by computer for controlling, sequencing reaction is carried out in automatization, the data transmission produced is to Data Analysis Computer, after completing order-checking, computation analysis software carries out image procossing, sequence reads, mass analysis, the work such as sequence assembly, finally obtain the sequence information of DNA sample.。Micro reaction pool sequence testing chip is the carrier of sequencing reaction, and the DNABeads and the various sequencing reaction enzyme that are loaded with sequencing template are all arranged in the sequence testing chip being carved with micro reaction pool.
In sequencing procedure, chemical reaction occurs sequence testing chip, produce visible ray, the optical signal produced by CCD (ChargeCoupleDevice) cameras capture sequencing reaction, can obtain required order-checking information.In sequenator, reacting record sub-system is to the information of sequencing reaction, and require that reaction warehouse has enough precision and the adjustable of installation, reaction warehouse, as the main carriers of test reaction, also should have enough stability.
In view of above-mentioned defect, creator of the present invention obtains this creation finally through long research and practice.
Summary of the invention
The object of the present invention is to provide a kind of DNA sequencer reacting record sub-system, in order to overcome above-mentioned technological deficiency.
For achieving the above object, the invention provides a kind of DNA sequencer reacting record sub-system, it comprises reaction warehouse assembly, motion platform assembly, motion control unit, CCD camera and platform supporting component, wherein,
Described reaction warehouse assembly, arranges reaction chip assembly in it, under the effect of Controlling System, reaction solution enters in reaction chip and carries out chemical reaction, produces visible ray;
Described motion platform assembly, CCD camera is fed into suitable picture-taking position by it, to take pictures collection to the visible ray information produced in reaction chip to make CCD camera;
Described platform assembly, its support described in reaction warehouse assembly, motion platform assembly;
Described motion control unit, it controls in real time to the operation of CCD camera and reaction chip, and actuation movement platform assembly moves to the picture-taking position of CCD camera, detects and controls the temperature of reaction warehouse;
Described reaction warehouse assembly comprises the vertical door frame be arranged on described platform assembly, the top in the outside of door frame is provided with turning reaction warehouse assembly, turnable basement is connected with in the lower end of turning reaction warehouse assembly, turnable basement is fixed on the middle part of door frame, turning reaction warehouse assembly can rotate around described turnable basement, in order to take out or to put into reaction chip;
Described turning reaction warehouse assembly comprises turning warehouse, the inner side of turning warehouse is provided with reaction chip assembly, in reaction chip assembly, is provided with reaction chip, and reagent solution is by reaction chip generation chemical reaction.
Further, described platform assembly comprises vibration damper plate and is arranged on the first damping wing plate and the second damping wing plate of vibration damper plate both sides, is respectively arranged with dampening assembly in the lower end of two damping wing plates;
Platform assembly is indentations, and reaction warehouse assembly is arranged on vibration damper plate, and two ends contact with two vibration damper plates respectively.
Further, described damping wing plate comprises back up pad, and it has certain height, the reaction warehouse assembly described in support;
The centre of the integrated upper head plate of back up pad is provided with the mounting groove of motion control unit, is provided with the circuit card of motion control unit and various circuit in it;
Be stiffening plate in the lower end of mounting groove, in order to offer mounting groove.
Further, described motion platform assembly comprises motor, the lead screw guide rails assembly be connected with motor output shaft, the supporting seat supporting lead screw assembly and detection components, camera support assembly;
The output shaft of motor is connected by shaft coupling with leading screw, and motor and leading screw junction are provided with supporting seat, and the end of leading screw is provided with bearing and axial positioning sleeve;
Leading screw is connected with nut, and nut is arranged on nut mount pad; The upper end of nut mount pad is connected with web plate, and the upper end of web plate is connected with camera mount pad; At bearing end, bearing friction top is set;
Described nut mount pad is arranged on the slide block with guide rail contact, and on slide block, drive CCD camera to move.
Further, described detection components comprises check-out console permanent seat, and it is arranged on the sidepiece of web plate, and the end of check-out console permanent seat is connected with position detection plate; Be provided with position transducer mount pad at the sidepiece of base, arrange contiguous block in the upper end of position sensor installation seat, contiguous block upper end is fixed with position transducer;
Described sensor installation seat comprises the threaded hole being arranged on side, is mounting groove, in order to installation site sensor in the centre of mount pad; Slide recess is provided with between sidepiece baffle plate and bottom surface.
Further, the bottom of described turning warehouse is provided with the first rotating part, it comprises the first container cavity, and in order to hold turnable basement, the first container cavity is arranged on the mid-way of bottom;
Be symmetrically arranged first lug in the first container cavity both sides, the centre of the first lug is provided with through hole; In order to be connected with described turnable basement.
Further, reaction chip assembly comprises reaction chip mount pad, reaction warehouse base assembly and by reaction warehouse base assembly and the locking of reaction chip mount pad, the shading positioning component opened;
At the middle portion of reaction chip mount pad, reaction chip is installed, a side portion of reaction chip mount pad is provided with mount pad supporting component, its in order to take out or chip placement time, the reaction chip mount pad described in support.
Further, be also provided with electronic lock assembly in the left side of the upper end of described door frame, electronic lock assembly comprises electronics lock and inductive switch, and described inductive switch is arranged on electronics lock, and electronics lock is arranged on the sidepiece of turning warehouse;
The sidepiece of described turning warehouse is provided with dead bolt open holes; Enter after dead bolt stretches out be arranged on turning warehouse sidepiece dead bolt hole in.
Further, the middle part of reaction warehouse base is provided with electrical heating wire, it is arranged in the nichrome wire mounting groove of base; In the temperature sensor mounting groove on electrical heating wire top, be provided with temperature sensor and control unit, in order to detection reaction pond temperature and according to setting threshold value regulate; Also watered sealing member at temperature sensor and control unit, it is encapsulating resin.
Further, between turning reaction warehouse and reaction warehouse base, be provided with self-adaptative adjustment part, the end spring of self-adaptative adjustment part and the end contact of reaction warehouse base; Self-adaptative adjustment part can change the position of reaction chip assembly according to the change in location of camera;
Turning reaction warehouse assembly and the coaxially movement of reaction chip assembly, be also provided with tail rod between the two.
Compared with prior art beneficial effect of the present invention is: DNA sequencing reaction record sub-system of the present invention has the robust structure of multiple adjustment, easy for installation between each structure, and compact construction, stability is high.Reaction warehouse assembly can be installed, fix and reaction chip described in adjusting, ensure that reaction chip reacts in stable environment, and reaction chip can conveniently take out and lock.
Accompanying drawing explanation
Fig. 1 is the one-piece construction schematic diagram of DNA sequencer reacting record sub-system of the present invention;
Fig. 2 is the first perspective view of reaction warehouse assembly of the present invention;
Fig. 3 is the second perspective view of reaction warehouse assembly of the present invention;
Fig. 4 be reaction warehouse assembly of the present invention face structural representation;
Fig. 5 a is the perspective view of turning reaction warehouse assembly of the present invention;
Fig. 5 b is the first perspective view of turning warehouse of the present invention;
Fig. 5 c is the second perspective view of turning warehouse of the present invention;
Fig. 5 d is the first perspective view of preset pieces of the present invention;
Fig. 5 e is the second perspective view of preset pieces of the present invention;
Fig. 6 a is the structural representation of electronic lock of the present invention;
Fig. 6 b is the structural representation of electronics lock of the present invention;
Fig. 6 c is the sectional structure schematic diagram of electronic lock of the present invention;
Fig. 7 is the sectional structure schematic diagram of turning reaction warehouse assembly of the present invention along the first lug;
Fig. 8 is the 3rd perspective view of turning warehouse of the present invention;
Fig. 9 a is the structural representation of reaction chip assembly of the present invention;
Fig. 9 b is the structural representation of reaction chip mount pad of the present invention;
Fig. 9 c is the structural representation of the medial surface of reaction warehouse base of the present invention;
Fig. 9 d is the structural representation of the outer side of reaction warehouse base of the present invention;
Fig. 9 e is the structural representation of temperature control assembly cover plate of the present invention;
Figure 10 a is the structural representation of shading positioning component of the present invention;
Figure 10 b is the first structural representation of slidably positioning and locking block of the present invention;
Figure 10 c is the second structural representation of slidably positioning and locking block of the present invention;
Figure 10 d is the structural representation of turnable basement assembly of the present invention;
Figure 10 e is the structural representation of spring assembly of the present invention;
Figure 11 a is the sectional structure schematic diagram along liquid inlet and outlet of reaction chip assembly of the present invention;
Figure 11 b is the sectional structure schematic diagram of turning reaction warehouse assembly of the present invention along self-adaptative adjustment part;
Figure 11 c is the sectional structure schematic diagram of turning reaction warehouse assembly of the present invention along tail rod;
Figure 12 is that turning reaction warehouse assembly of the present invention is along the A-A in Fig. 4 to sectional structure schematic diagram;
Figure 13 a is the sectional structure schematic diagram of back shroud of the present invention;
Figure 13 b is the perspective view of back shroud assembly of the present invention;
Figure 13 c is the perspective view of back shroud of the present invention;
Figure 14 a is the structural representation of sealing-ring of the present invention;
Figure 14 b is sealing-ring sectional structure schematic diagram of the present invention;
Figure 14 c is the using state schematic diagram that the present invention observes the sealing-ring of right side reaction chip;
Figure 15 a is the structural representation of platform assembly of the present invention;
Figure 15 b is the structural representation of vibration damper plate of the present invention;
Figure 16 is the structural representation of motion platform assembly of the present invention;
Figure 17 is the sectional structure schematic diagram of motion platform assembly of the present invention;
Figure 18 a is the structural representation of nut mount pad of the present invention;
Figure 18 b is the structural representation of the supporting seat of motor of the present invention and leading screw junction;
Figure 18 c is the structural representation of the detection components in the embodiment of the present invention;
Figure 18 d is the structural representation of position transducer mount pad of the present invention.
Embodiment
Below in conjunction with accompanying drawing, to above-mentioned being described in more detail with other technical characteristic and advantage of the present invention.
Refer to shown in Fig. 1, it is the one-piece construction schematic diagram of DNA sequencer reacting record sub-system of the present invention, reacting record sub-system in the embodiment of the present invention comprises reaction warehouse assembly 12, motion platform assembly 14, motion control unit 15, CCD camera 101 and platform supporting component 13, wherein
Described reaction warehouse assembly 12, arranges reaction chip assembly in it, under the effect of Controlling System, reaction solution enters in reaction chip and carries out chemical reaction, produces visible ray; Described motion platform assembly 14, CCD camera is fed into suitable picture-taking position by it, to take pictures collection to the visible ray information produced in reaction chip; Described platform assembly 13, its support described in reaction warehouse assembly 12, motion platform assembly 14; Described motion control unit, it controls in real time to the operation of CCD camera and reaction chip.
In embodiments of the present invention, described reaction warehouse assembly 12 can be installed, fix and reaction chip described in adjusting, ensure that reaction chip reacts in stable environment, and reaction chip can conveniently take out and lock.
Refer to shown in Fig. 2-4, described reaction warehouse assembly 12 comprises the door frame 121 of the vertical setting be arranged on described platform assembly 13, the top in the outside of door frame 121 is provided with turning reaction warehouse assembly 124, turnable basement 122 is connected with in the lower end of turning reaction warehouse assembly 124, turnable basement 122 is fixed on the middle part of door frame 121, turning reaction warehouse assembly 124 can rotate around described turnable basement 122, in order to take out or to put into reaction chip.
Also be provided with electronic lock assembly 125 in the left side of the upper end of described door frame 121, only when electronic lock assembly 125 is opened, turning reaction warehouse assembly 124 can be rotated, reaction chip is operated.In embodiments of the present invention, be provided with door frame 121, support reaction chip and dependency structure, substantially increase the stability of system.
Turning reaction warehouse assembly 124 comprises turning warehouse, is provided with back shroud 1242, in order to encapsulate Reagent Tube at the middle portion of described turning warehouse; Be provided with the first rotating part in bottom, it comprises the first container cavity 1243, and in order to hold turnable basement 122, the first container cavity 1243 is arranged on the mid-way of bottom; Be symmetrically arranged first lug 1244 in the first container cavity both sides, the centre of the first lug 1244 is provided with through hole 1246; In order to be connected with described turnable basement 122.Turnable basement rotates in the first container cavity 1243 relative to turning warehouse, has higher stability, and the transmission of guaranteed reagent,G.R. and data is unimpeded simultaneously.
Refer to shown in Fig. 5 a-5c, in the inner side of the centre of described turning warehouse, reaction chip assembly is installed, accordingly, the first cavity 1785 holding reagent pipeline is provided with in the centre of turning warehouse, the bottom of the first cavity 1785 is provided with the first boss 1784, first boss 1784 is in order to carry the strut member of described reaction chip assembly, first boss 1784 is provided with four tail rod open holess 1786, tail rod open holes 1786 is through the two ends of turning warehouse, reaction chip assembly and strut member, reaction chip assembly is connected with turning warehouse, the second boss 1783, second boss 1784 is provided with in order to locate described strut member in the upper end of the first described boss 1784, the second described boss 1784 upper end is provided with locating surface 1782, locating surface 1782 is provided with locking screw nail 1787.Reaction chip assembly described in above-mentioned first cavity configuration location, and reaction chip assembly, when normally working, can not rotate, and is merely able to move along tail rod.
The upper surface of the first container cavity 1243 of described turning warehouse is provided with Reagent Tube open holes 1788 and electric wire open holes, pipe clamp 03 is installed in Reagent Tube open holes 1788, through having Reagent Tube 02 and electric wire 01 in pipe clamp 03.
The dead bolt open holes of the dead bolt 1252 in electronic lock assembly 125 is also provided with at the sidepiece of described turning warehouse; Under the effect of locking piece, turning warehouse and door frame 121 are fixed together.
Shown in Fig. 6 a and 6b, electronic lock assembly 125 of the present invention comprises electronics lock and inductive switch 1251, described inductive switch is arranged on electronics lock, electronics lock is arranged on the sidepiece of turning warehouse, in embodiments of the present invention, electronics lock comprises sidepiece mounting plate 1843, and sidepiece mounting plate 1483 offers open holes 1844; Electronic lock is done to be fixed on turning warehouse by open holes 1844 and mounting screw.Be provided with the first symmetrical framework 1841 and the second framework 1842 in described sidepiece mounting plate 1483 side, leave the space of installing inductive switch 1251 in the centre of the first framework and the second framework.
In embodiments of the present invention, described inductive switch 1251 comprises the framework 1255 being arranged on outside, and a side of framework 1255 is provided with connecting thread hole 1256, and itself and described electronics lock are fixed by coupling screw 1254; Described coupling screw 1254 by the lug 1258 on side and the first framework 1841, second framework 1842, in order to increase the strength of joint of electronics lock.Described inductive switch 1251 is also connected with control circuit 1252, in order to control inductive switch 1251.
Refer to shown in Fig. 6 c, described electronic lock assembly 125 is arranged on the sidepiece of turning warehouse and door frame 121, enter after dead bolt 1253 stretches out be arranged on turning warehouse sidepiece dead bolt hole 1247 in, realize locking; When under the effect of dead bolt 1253 in electricity irritation, when retracting in dead bolt hole 1247, described turning warehouse can be rotated.
The upper end in the outside of described turning warehouse is provided with pressing piece 1241, only described turning warehouse can be made to rotate by pressing piece 1241 pressing setting.Refer to shown in Figure 12, in embodiments of the present invention, the structure that described pressing piece 1241 one end are provided with opening 1730, one end is provided with hook, described hook is connected with the upper end-stopping plate of door frame, when pressing piece 1241 is subject to downward reactive force, hook and door frame baffle plate depart from, and turning reaction warehouse body can rotate relative to door frame.
In embodiments of the present invention, described pressing piece 1241 is arranged in a positioning block 1762, the lower end of preset pieces 1762 is provided with spring 1761, spring is arranged in spring support 1763, and spring support 1763 screw thread is arranged in the spring base hole 1781 of intermediate throughholes 1785 upper surface of turning reaction warehouse.
Shown in Fig. 5 b-5d, preset pieces 1762 is arranged in the preset pieces installation cavity 1791 of turning reaction warehouse upper end, is provided with positioning step 1790 in cavity.Preset pieces 1762 in the embodiment of the present invention comprises through hole 1794 and lower through-hole 1797, both one of by described pressing piece 1241; Locating and machining hole 1796 and open holes 1795 are set in the side of preset pieces.The lower end of the through hole installing pressing piece 1241 is provided with spring eye, and spring is contacted with the bottom of pressing piece 1241 by this hole.
The embodiment of the present invention arranges electronic lock assembly and pressing piece, carries out twice locking to turning reaction warehouse assembly and door frame, adopts mode that is automatically controlled and physical construction respectively, ensures that reaction chip runs in security context, avoids mishandle.
Refer to shown in Fig. 2 and 7, turnable basement in the embodiment of the present invention 122 has the connection base of two the second lugs 1221, second lug 1221 is symmetricly set on a side 1223 of base, communicating pores 1224 is provided with in the middle of it, coaxially install with the through hole 1246 arranged in the middle of the first lug 1244 on described turning warehouse, further, the second lug 1221 is arranged on the inner side of the first lug 1244.
Shown in Fig. 2, in embodiments of the present invention, door frame 121 has the structure of sidepiece baffle plate 1211 for side mask, and it is one-body molded, and the both sides of described turnable basement 122 to be arranged in sidepiece baffle plate 1211 and to contact with sidepiece baffle plate 1211 and locate; The first described lug 1224 is after installing with the second lug 1221 is coaxial, the upper-end contact of end and turnable basement 122, and, the sidepiece of turning warehouse contacts with sidepiece baffle plate 1211 medial surface of door frame 121, ensures that turning warehouse and turnable basement 122 are just positioned at sidepiece baffle plate 1211.
Door frame 121 is also provided with the accommodation hole passed through for reaction chip assembly.The use of door frame, not only can make the Stability Analysis of Structures of reaction chip assembly, and, also make turning warehouse and turnable basement compact construction, convenient operation; The location of CCD camera and reaction chip is more accurate.
The first open holes 1210 is provided with, in order to be connected and fixed with motion platform assembly 14 in the bottom of door frame 121; The second open holes be connected with turnable basement sidepiece is also provided with in the middle part of door frame.
Shown in Fig. 7, in embodiments of the present invention, in order to save the stable of structure space and guaranteed reagent,G.R. transmission, Reagent Tube first fixation kit is provided with in the through hole 1246 arranged in the middle of the first described lug 1244 and the communicating pores of the second lug 1221, it comprises the pipe joint 1265 be arranged in the lug of left side, first packing ring 1264, first turning axle 1261, and the Reagent Tube joint 1266 be arranged in the lug of right side, second packing ring 1267, second turning axle 1269, wherein, the first described packing ring 1264 and the second packing ring 1267 are arranged between turning warehouse and turnable basement, in the present embodiment, the diameter of the through hole 1246 arranged in the middle of the first described lug 1244 is less than the diameter of the communicating pores of the second lug 1221, the location rib to packing ring location is formed at both medial ends, after installing two packing rings, inside diameter of gasket is just identical with the diameter of the communicating pores of the second lug 1221.Location rib and packing ring are set in embodiments of the present invention, ensure gapless between turning warehouse and turnable basement, both good stabilities after combining, can not rock because there is gap, and, packing ring adds both contact area, and stress is between the two reduced, extension device work-ing life.
The structure that the inner side of through hole 1246 arranged in the middle of the first lug 1244 and the inner side of packing ring are provided with the first turning axle 1261 and the second turning axle 1269, two turning axles is identical, is the quill shaft with positioning convex ring; In one end of turning axle, positioning convex ring is set, be provided with connecting thread hole, in order to be connected and fixed with the lug connection portion 1263 of described turning warehouse, accordingly, be provided with the positioning recess of locating described positioning convex ring in the end of described through hole 1246.Be recess in the centre at the both ends of turning axle 1269, inner side recess is in order to install locate with described pipe joint 1265, Reagent Tube joint 1266.In pipe joint 1265, Reagent Tube joint 1266, be separately installed with electric wire and Reagent Tube 02, it leads in reaction chip assembly respectively.Owing to arranging the assembly that can mutually overturn in the embodiment of the present invention, when overturning, for avoiding impacting pipe fitting, in through-holes Reagent Tube being installed, substantially increasing the safety performance of Reagent Tube.
Refer to shown in Fig. 8, in embodiments of the present invention, described reaction chip assembly is arranged on the inner side of described turning warehouse.Be provided with the observation section 1724 contacted with CCD camera in the inner side of reaction chip assembly, be provided with transparent baffle plate, to take pictures to reaction process.
Refer to shown in Fig. 9 a, the shading positioning component 128 that reaction chip assembly of the present invention comprises reaction chip mount pad 127, reaction warehouse base assembly 126 and reaction warehouse base assembly 126 and reaction chip mount pad 127 locked, opens; In order to take out reaction chip easily and close, reaction chip mount pad 127 can rotate relatively with reaction warehouse base assembly 126.
Refer to shown in Fig. 9 b, it is the structural representation of reaction chip mount pad of the present invention, is provided with reaction chip at the middle portion of reaction chip mount pad 127, and reaction chip is provided with cover plate 1277; In the both sides of reaction chip, chute pressing plate 1279 is installed, in order to be fixed reaction chip.A side portion of reaction chip mount pad 127 is provided with mount pad supporting component, its in order to take out or chip placement time, the reaction chip mount pad described in support; It comprises torsional-spring supported portion 1273, be arranged on mount pad, in order to support described torsion spring, described torsional-spring supported portion 1273 is one with the recess of protruding end 1274, when the reaction chip mount pad 127 described in rotating, protruding end 1274 contacts with 1261 at first, and in the present embodiment, described protruding end 1274 is arranged on the middle part at the edge of recess and chip installation position; Adopt the structure of mount pad itself to support reaction chip mount pad, better reliability, ensure that chip can take out safely and place.
Described mount pad supporting component also comprises torsion spring 1272, be connected with torsion spring 1272 and be arranged on the tension axle 1271 at torsion spring two ends, described tension axle 1271 is arranged on lug boss 1275, when starting reaction chip mount pad, described torsion spring 1272 supports mount pad, and the final location relying on protruding end 1274, realize supporting.
The first rotary shaft hole 1276 is also provided with, in order to be connected with reaction warehouse base 1261 in the end of described lug boss 1275.Locating slot 1278 is also provided with at the sidepiece of reaction chip mount pad.
Refer to shown in Fig. 9 c, it is the structural representation of the medial surface of reaction warehouse base of the present invention, reaction tank body 1266 is provided with in the medial surface of reaction warehouse, at reaction tank body 1266 middle portion, reaction tank 1267 is set, the surrounding 1706 of reaction tank 1267 is provided with sealing-ring, prevents reaction reagent from leaking.One end of reaction warehouse base 1261 is provided with raised line 1705, in order to install after cover plate locate.The other end is provided with the torsional-spring supported structure corresponding with reaction chip mount pad, and it comprises symmetrically arranged two protruding ends 1268, is provided with the second rotary shaft hole 1269 thereon, and it is coaxial with the first rotary shaft hole 1276, and turning axle is successively through holes; Also being provided with the region 1260 for torsion spring activity and locating area 1707 in this end, being provided with in this region in order to the threaded hole 1712 by installing reaction warehouse cover plate.
Refer to shown in Fig. 9 d, it is the structural representation of the outer side of reaction warehouse base of the present invention, the middle portion of the outer side of reaction warehouse base is provided with temperature control assembly, the middle portion of reaction warehouse base is provided with temperature sensor mounting groove 1262, the bottom of mounting groove 1262 is provided with nichrome wire mounting groove 1704, places nichrome wire and temperature sensor respectively.In mounting groove, be also provided with a positioning boss 1703, locate when it is in order to install with temperature control assembly cover plate 1263.As shown in figure 9e, temperature control assembly cover plate 1263 is provided with the positioning recess 1702 corresponding with positioning boss 1703.
The surrounding of temperature sensor mounting groove 1262 is provided with four tail rod open holess 1742, upper and lower sides is provided with self-adaptation spring mounting hole 1741; Cover plate 1263 is also provided with guiding rod aperture 1701.
Reaction warehouse base is also provided with shading positioning component mounting groove 1265, in order to install described shading positioning component 128, is provided with installation base 1744 within it.
Refer to shown in Figure 10 a, it is the structural representation of shading positioning component of the present invention, it comprises slidably positioning and locking block 1281 and turnable basement assembly 1283, wherein, described slidably positioning and locking block 1281 is provided with locking jaw 1282, after installation is complete, the upper surface of described slidably positioning and locking block 1281 contacts with the medial surface of reaction chip mount pad 127, and locking jaw 1282 is hooked on the outboard end of reaction chip mount pad 127; Described turnable basement assembly 1283 is arranged on the medial end of reaction warehouse base, is provided with threaded hole 1830.After installation is complete, described shading positioning component 128 is fixed together with reaction warehouse base, when opening reaction chip mount pad, outside pressing is positioning and locking block 1281 slidably, and under the action of the spring, slidably positioning and locking block 1281 is outward-dipping, locking jaw more than 1282 reaction warehouse mount pad departs from, under the effect of the torsion spring of reaction warehouse mount pad end, reaction warehouse mount pad overturns, and can change reaction chip.
Shown in Figure 10 b, described slidably positioning and locking block 1281 comprises and is arranged on the pressing plate 1823 on top and the elastic locking assembly of bottom homonymy, be lower convex joint face 1821 at the middle portion of pressing plate 1823, it coordinates with described turnable basement assembly 1283.Shown in Figure 10 c, described elastic locking assembly comprises symmetrically arranged first spring support 1822, second spring support 1828, be arranged on the first recess 1827 between two spring supports; In two spring supports, be respectively arranged with spring assembly, spring assembly comprises the upper spring card slot 1281 shown in Figure 10 e, lower spring draw-in groove 1283, and upper and lower two spring card slots surround spring eye 1771, and spring eye is shoulder hole, is provided with spring 1820 in it; Wherein, upper spring card slot 1281 is provided with external part, it is arranged hook claw, in order to be connected with the end of described pressing plate 1823.
In embodiments of the present invention, spring support and the first recess are formed by continuous print vertical baffle 1826 isolation, and both sides arrange vertical rib 1829; Elastic locking assembly is arranged on pressing plate on integrated first flat board 1825, and it is vertical with pressing plate 1823 is arranged.
Refer to shown in Figure 10 d, the slidably positioning and locking block 1281 in the embodiment of the present invention can symmetrical coordinate with turnable basement assembly 1283, and be provided with the first projection 1832 in the centre of turnable basement, itself and the first recess 1827 snap together; First projection 1832 both sides are provided with the space that can hold vertical baffle 1826; Accordingly, the second recess 1833, second recess of the spring support be provided with described in accommodation in the first projection 1832 zygomorphy is surrounded by continuous print vertical edge 1834; Said structure is arranged on integrated second flat board 1831; In use, by spring assembly by being pressed in spring support, slip positioning and locking block 1281 and turnable basement assembly 1283 are snapped together.The embodiment of the present invention, arranges shading positioning component, locking reaction chip that not only can be stable, and when changing reaction chip, simple to operate, only need press slip positioning and locking block 1281 and open, and without the need to dismantling reaction chip mount pad, save time.
Refer to shown in Figure 11 a and 11b, the middle part of reaction warehouse base is provided with electrical heating wire 1754, it is arranged in the nichrome wire mounting groove 1704 of base; In the temperature sensor mounting groove 1262 on electrical heating wire top, be provided with temperature sensor 1720 and control unit, in order to detection reaction pond temperature and according to setting threshold value regulate; Also water at temperature sensor 1720 and control unit 1753 and have sealing member 1263, it is encapsulating resin.
Be respectively arranged with Reagent Tube at the two ends of reaction tank and threaded hole 1721 be installed, in order to be connected with Reagent Tube; The end installing threaded hole 1721 at Reagent Tube is provided with fluid inlet 1723 and liquid outlet 1713, and liquid inlet and outlet communicates with the two ends of reaction tank, in order to cycle detection reagent.
The avris of the interior grooves of reaction tank is provided with sealing-ring 1713.Be provided with reaction chip 04 in the centre of reaction chip mount pad, reagent flows through reaction chip and reacts.
In embodiments of the present invention, Reagent Tube 02 is by the Reagent Tube open holes 1788 of turning warehouse, and the centre being arranged on turning warehouse is provided with the first cavity 1785 holding reagent pipeline, final ligation pond body, reagent cartridge is through the sealing of various cavity, and stability is high, not fragile.
Back shroud 1242 is fixed with at the rear side of reaction warehouse, the centre of back shroud 1242 is provided with self-adaptative adjustment part 1751, refer to shown in Figure 13 a-13c, in the middle of the inner side of back shroud 1242, be provided with two rows raised line 1809 is installed, the centre of installing raised line 1809 is provided with the first installation base 1812 and the second installation base 1811, installation base offers threaded hole 1802, and self-adaptative adjustment part 1751 is arranged in this threaded hole 1802.
In embodiments of the present invention, described self-adaptative adjustment part 1751 is thread end with the coupling end of back shroud, is the polished rod 1805 being provided with spring 1806, is provided with nut 1804 between the ends and positions with the coupling end of reaction warehouse assembly, after installation is complete, nut 1804 is close to installation base.
Be passage 1803 between described two raised lines 1809, Reagent Tube can be made to pass through; Back shroud is also provided with the reinforcement gusset 1812 vertical with raised line 1809; At upper surface 1810 bit plane of raised line 1809 with boss; Below, the centre of the peripheral framework 1807 of plate and corner are provided with fastening screw nail 1801, in order to be connected and fixed with described turning reaction warehouse.
Above-mentioned back shroud assembly, not only can carry out face seal to reaction warehouse assembly, and can also install fixing self-adaptative adjustment part, structure is simple.
In embodiments of the present invention, be provided with self-adaptative adjustment part 1751 between turning reaction warehouse and reaction warehouse base 126, refer to shown in Figure 12, the end spring of self-adaptative adjustment part 1751 and the end contact of reaction warehouse base; When using CCD camera feeding, when camera and reaction chip component touch, when adjusting camera position, movable mode can be adopted to adjust, now, self-adaptative adjustment part can change the position of reaction chip assembly according to the change in location of camera, ensure to have higher accuracy of detection, meanwhile, avoid causing damage to system.
In embodiments of the present invention, in order to ensure that turning reaction warehouse assembly and reaction chip assembly can coaxially movements, convenient adjustment, also be provided with tail rod 1758 between the two, refer to shown in Figure 11 c, reaction warehouse base arranges guiding rod aperture 1742, turning warehouse arranges tail rod open holes 1786, tail rod 1742 is successively through holes.Described tail rod 1758 comprises reaction warehouse locating flange 1757, in order to locate with guiding rod aperture 1742; Located by nut 1755 end face with tail rod open holes 1786 at the other end, between be also provided with pad 1756.
In embodiments of the present invention, in order to test the different positions of reaction chip, adopt the sealing-ring 1713 that can change test area; Refer to shown in Figure 14 a-14c, described sealing-ring 1713 is hexagon, and it comprises outer rim 1716 and be arranged on the first blend stop 1714 of opposite side and the second blend stop 1715, first blend stop 1714 and the second blend stop 1715 and reagent is divided into three parts.In an embodiment, sidepiece rib and blend stop upper end be respectively first protruding 1718 and the second projection 1719, two projections ranged flow that reagent is being limited, reagent liquid inlet and outlet is arranged in the chamfering between two blend stops.When not using blend stop, it is inner that reagent flows into whole sealing-ring by the chamfering between two blend stops, now, can observe the reaction of whole reaction chip; When state as shown in figures 14a, the region of the reaction chip between two blend stops can only be observed; When state as shown in figure 14 c, can only region on the right side of observing response chip.
In embodiments of the present invention, when described reaction warehouse assembly 12 works, above-mentioned reaction chip assembly is arranged in turning reaction warehouse, installs tail rod 1758 and self-adaptative adjustment part 1751, and packaged back shroud; After turnable basement assembly 122 installation, lock turning reaction warehouse and door frame by electronic lock assembly and pressing piece, and the reaction warehouse assembly 12 of installation is arranged on platform assembly 13.
Refer to shown in Figure 15 a-15b, the platform assembly of the embodiment of the present invention comprises vibration damper plate 1497 and is arranged on the first damping wing plate 1492 and the second damping wing plate 1491 of vibration damper plate 1497 both sides, is respectively arranged with dampening assembly 1493 in the lower end of two damping wing plates.After installation is complete, platform assembly is indentations, and reaction warehouse assembly 12 is arranged on vibration damper plate 1497, and two ends contact with two vibration damper plates respectively.
Damping wing plate comprises back up pad 1497, and it has certain height, the reaction warehouse assembly described in support; The centre of the integrated upper head plate 1495 of back up pad 1497 is provided with the mounting groove 1492 of motion control unit 15, is provided with the circuit card of motion control unit 15 and various circuit in it; Be stiffening plate 1496 in the lower end of mounting groove 1492, in order to offer mounting groove 1492.The platform assembly of the embodiment of the present invention can either be symmetrical arranged the stability of guarantee system, can arrange control unit again, saves space, compact construction.
Platform assembly 13 is also provided with motion platform assembly 14 and CCD camera 101, refer to shown in Figure 16, described motion platform assembly 14 comprises motor 136, the lead screw guide rails assembly be connected with motor output shaft, the supporting seat supporting lead screw assembly and detection components, camera support assembly.
Refer to shown in Figure 17, the output shaft of motor 136 is connected by shaft coupling 1377 with leading screw 137, and motor and leading screw junction are provided with supporting seat 1361, is provided with bearing 1371 and axial positioning sleeve 1376 in the end of leading screw.Leading screw is connected with nut 1374, and nut is arranged on nut mount pad 1375; The upper end of nut mount pad 1375 is connected with web plate 1012, and the upper end of web plate 1012 is connected with camera mount pad 1011; At bearing end, bearing friction top 1372 is set.
Described nut mount pad 1375 is arranged on the slide block 1012 that contacts with guide rail 132, and on slide block, drive camera to move.
Refer to Figure 18 a, it is the structural representation of nut mount pad, and its upper end is provided with web plate open holes 1401, and middle portion is provided with through hole 1402, in order to pass leading screw; The surrounding of through hole 1402 is fastening screw pit 1403, in order to install with nut.
Refer to shown in Figure 18 b, it is the structural representation of the supporting seat of motor and leading screw junction, and it comprises leading screw installing sleeve 1363, arranges positioning step 1364 in it; The end of installing sleeve is connected with mounting plate 1362, in order to be connected with motor end face.
Refer to shown in Figure 18 c, the detection components in the embodiment of the present invention comprises check-out console permanent seat 1353, and it is arranged on the sidepiece of web plate 1012, and the end of check-out console permanent seat 1353 is connected with position detection plate 1352; Be provided with position transducer mount pad 1351 at the sidepiece of base, arrange contiguous block 1356 in the upper end of position sensor installation seat 1351, contiguous block upper end is fixed with position transducer 135.
Refer to shown in Figure 18 d, it is the structural representation of position transducer mount pad of the present invention, and it comprises the threaded hole 1415 being arranged on side 1411, is mounting groove 1412, in order to installation site sensor in the centre of mount pad; Slide recess 1413 is provided with between sidepiece baffle plate and bottom surface.
Above-mentioned detailed description is illustrating for one of them possible embodiments of the present invention, and this embodiment is also not used to limit the scope of the claims of the present invention, and the equivalence that all the present invention of disengaging do is implemented or changed, and all should be contained in the scope of technical solution of the present invention.

Claims (10)

1. a DNA sequencer reacting record sub-system, is characterized in that, it comprises reaction warehouse assembly, motion platform assembly, motion control unit, CCD camera and platform supporting component, wherein,
Described reaction warehouse assembly, arranges reaction chip assembly in it, under the effect of Controlling System, reaction solution enters in reaction chip and carries out chemical reaction, produces visible ray;
Described motion platform assembly, CCD camera is fed into suitable picture-taking position by it, to take pictures collection to the visible ray information produced in reaction chip to make CCD camera;
Described platform assembly, its support described in reaction warehouse assembly, motion platform assembly;
Described motion control unit, it controls in real time to the operation of CCD camera and reaction chip, and actuation movement platform assembly moves to the picture-taking position of CCD camera, detects and controls the temperature of reaction warehouse;
Described reaction warehouse assembly comprises the vertical door frame be arranged on described platform assembly, the top in the outside of door frame is provided with turning reaction warehouse assembly, turnable basement is connected with in the lower end of turning reaction warehouse assembly, turnable basement is fixed on the middle part of door frame, turning reaction warehouse assembly can rotate around described turnable basement, in order to take out or to put into reaction chip;
Described turning reaction warehouse assembly comprises turning warehouse, the inner side of turning warehouse is provided with reaction chip assembly, in reaction chip assembly, is provided with reaction chip, and reagent solution is by reaction chip generation chemical reaction.
2. DNA sequencer reacting record sub-system according to claim 1, it is characterized in that, described platform assembly comprises vibration damper plate and is arranged on the first damping wing plate and the second damping wing plate of vibration damper plate both sides, is respectively arranged with dampening assembly in the lower end of two damping wing plates;
Platform assembly is indentations, and reaction warehouse assembly is arranged on vibration damper plate, and two ends contact with two vibration damper plates respectively.
3. DNA sequencer reacting record sub-system according to claim 2, is characterized in that, described damping wing plate comprises back up pad, and it has certain height, the reaction warehouse assembly described in support;
The centre of the integrated upper head plate of back up pad is provided with the mounting groove of motion control unit, is provided with the circuit card of motion control unit and various circuit in it;
Be stiffening plate in the lower end of mounting groove, in order to offer mounting groove.
4. DNA sequencer reacting record sub-system according to claim 2, it is characterized in that, described motion platform assembly comprises motor, the lead screw guide rails assembly be connected with motor output shaft, the supporting seat supporting lead screw assembly and detection components, camera support assembly;
The output shaft of motor is connected by shaft coupling with leading screw, and motor and leading screw junction are provided with supporting seat, and the end of leading screw is provided with bearing and axial positioning sleeve;
Leading screw is connected with nut, and nut is arranged on nut mount pad; The upper end of nut mount pad is connected with web plate, and the upper end of web plate is connected with camera mount pad; At bearing end, bearing friction top is set;
Described nut mount pad is arranged on the slide block with guide rail contact, and on slide block, drive CCD camera to move.
5. DNA sequencer reacting record sub-system according to claim 4, it is characterized in that, described detection components comprises check-out console permanent seat, and it is arranged on the sidepiece of web plate, and the end of check-out console permanent seat is connected with position detection plate; Be provided with position transducer mount pad at the sidepiece of base, arrange contiguous block in the upper end of position sensor installation seat, contiguous block upper end is fixed with position transducer;
Described sensor installation seat comprises the threaded hole being arranged on side, is mounting groove, in order to installation site sensor in the centre of mount pad; Slide recess is provided with between sidepiece baffle plate and bottom surface.
6. the DNA sequencer reacting record sub-system according to claim 2 or 4, it is characterized in that, the bottom of described turning warehouse is provided with the first rotating part, and it comprises the first container cavity, in order to hold turnable basement, the first container cavity is arranged on the mid-way of bottom;
Be symmetrically arranged first lug in the first container cavity both sides, the centre of the first lug is provided with through hole; In order to be connected with described turnable basement.
7. the DNA sequencer reacting record sub-system according to claim 2 or 4, it is characterized in that, the shading positioning component that reaction chip assembly comprises reaction chip mount pad, reaction warehouse base assembly and reaction warehouse base assembly and reaction chip mount pad are locked, opened;
At the middle portion of reaction chip mount pad, reaction chip is installed, a side portion of reaction chip mount pad is provided with mount pad supporting component, its in order to take out or chip placement time, the reaction chip mount pad described in support.
8. the DNA sequencer reacting record sub-system according to claim 2 or 4, it is characterized in that, electronic lock assembly is also provided with in the left side of the upper end of described door frame, electronic lock assembly comprises electronics lock and inductive switch, described inductive switch is arranged on electronics lock, and electronics lock is arranged on the sidepiece of turning warehouse;
The sidepiece of described turning warehouse is provided with dead bolt open holes; Enter after dead bolt stretches out be arranged on turning warehouse sidepiece dead bolt hole in.
9. DNA sequencer reacting record sub-system according to claim 7, is characterized in that, the middle part of reaction warehouse base is provided with electrical heating wire, and it is arranged in the nichrome wire mounting groove of base; In the temperature sensor mounting groove on electrical heating wire top, be provided with temperature sensor and control unit, in order to detection reaction pond temperature and according to setting threshold value regulate; Also watered sealing member at temperature sensor and control unit, it is encapsulating resin.
10. DNA sequencer reacting record sub-system according to claim 7, is characterized in that, between turning reaction warehouse and reaction warehouse base, be provided with self-adaptative adjustment part, the end spring of self-adaptative adjustment part and the end contact of reaction warehouse base; Self-adaptative adjustment part can change the position of reaction chip assembly according to the change in location of camera;
Turning reaction warehouse assembly and the coaxially movement of reaction chip assembly, be also provided with tail rod between the two.
CN201510716526.4A 2015-10-29 2015-10-29 A kind of DNA sequencer reacting record subsystem Expired - Fee Related CN105273979B (en)

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CN102703311A (en) * 2012-05-24 2012-10-03 中国科学院北京基因组研究所 Reaction bin for adaptive regulation of DNA (Deoxyribose Nucleic Acid) sequencer
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