CN106220700A - A kind of high flux DNA synthesizer - Google Patents

A kind of high flux DNA synthesizer Download PDF

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Publication number
CN106220700A
CN106220700A CN201610735467.XA CN201610735467A CN106220700A CN 106220700 A CN106220700 A CN 106220700A CN 201610735467 A CN201610735467 A CN 201610735467A CN 106220700 A CN106220700 A CN 106220700A
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China
Prior art keywords
valve
plate
container
air inlet
reagent
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Granted
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CN201610735467.XA
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CN106220700B (en
Inventor
朱中亚
王迎枫
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JIANGSU LINGKUN BIOTECHNOLOGY CO.,LTD.
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Jiangsu Lead Biotechnology Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives

Abstract

The invention discloses a kind of high flux DNA synthesizer, including frame, container rack, the first cylinder, the second cylinder, hard board load bearing unit, dispensing unit, dispensing unit installing plate, gas-liquid road unit and controller;Described container rack is fixed in described frame, and described container rack is placed with soda liquor container and multiple reagent container;Described hard board load bearing unit carries hard board, and described hard board has multiple synthesis post;Described dispensing unit is arranged on described dispensing unit installing plate, and described dispensing unit includes multiple dispensing nozzle;Described gas-liquid road unit includes source of the gas, described soda liquor container and the plurality of reagent container;Described first cylinder is used for driving described hard board load bearing unit to move horizontally, and described second cylinder is used for driving described dispensing unit installing plate vertically to move.The synthesizer of the present invention is capable of being automatically synthesized of DNA.

Description

A kind of high flux DNA synthesizer
Technical field
The present invention relates to biological technical field, be specifically related to a kind of high flux DNA synthesizer.
Background technology
Artificial-synthetic DNA is the unique channel of the directional transformation gene order being currently known, and is widely used in protein and changes Make and multiple fields such as life sciences, such as nucleic acid drug, enzyme engineering, gene therapy etc..DNA synthesizer needs de-in building-up process The different steps such as protection, activation link, block, oxidation, building-up process needs under inert gas environment is protected to synthesis post The different reagent of interior injection, question response will synthesize reagent emptying in post after completing.The waste liquid discharged is transported to waste liquid tank by pipeline, from And reduce waste liquid residual in a device to greatest extent, both can ensure that again synthesis matter with the health of Protection personnel Amount;Industrial synthesizer, refers mainly to synthesize flux big, and single-column synthetic product is the DNA synthesizer of 10-1000nmol.Industry The common synthesis post number of type synthesizer is 96 posts, 192 posts, and the synthesizer of 384 posts or more synthesis post number is the most rarely seen.Main suitable For large-scale experiment room, public experiment porch and be commercially synthesized mechanism.Work, north are given birth in the domestic main mechanism such as Shanghai that is commercially synthesized Capital SBS Genetech, Shanghai JaRa, Hua Da gene, Jin Site, Jin Weisi etc..The type DNA synthesizer is relative compared with Laboratary type brand Less, common brand has U.S. biolytic, Denmark oligomaker, U.S. mermade, U.S. polyplex etc..In Europe Continent, polygen 96 post synthetic work station and 384 post synthetic towers are also one of industrial synthesizers more typically.Due to people institute The base pair of the longer nucleic acid chain that the base pair quantity of the most of nucleic acid needed can synthesize considerably beyond current DNA synthesizer Quantity, therefore also needs to constantly improve synthesis technique and just can obtain longer nucleic acid molecules.The main production of current dna synthesizer Manufacturer be devoted to machine performance improve and the developing of application and high efficiency, high yield instrument exploitation with grind Study carefully.The most domestic also do not have a high flux, high efficiency, the DNA synthesizer of low cost.
Summary of the invention
Goal of the invention: it is contemplated that overcome the defect of prior art to provide a kind of high flux DNA synthesizer.
Technical scheme: a kind of DNA synthesizer, holds including frame, container rack, the first cylinder, the second cylinder, hard board Carrier unit, dispensing unit, dispensing unit installing plate, gas-liquid road unit and controller;Described container rack is fixed on described machine On frame, described container rack is placed with soda liquor container and multiple reagent container;Described hard board load bearing unit carries conjunction Become plate, described hard board has multiple synthesis post;Described dispensing unit is arranged on described dispensing unit installing plate, described point Note unit includes multiple dispensing nozzle;Described gas-liquid road unit includes that source of the gas, described soda liquor container and the plurality of reagent hold Device;Described first cylinder is used for driving described hard board load bearing unit to move horizontally, and described second cylinder is used for driving described point Note unit installing plate vertically moves.
Further, described hard board load bearing unit includes loading plate, rectangle frame and waste liquid storehouse;Described loading plate includes using In the rectangular opening of the described hard board of receiving, the lower section of described rectangular opening, institute are fixed and be positioned to described waste liquid storehouse and described loading plate State rectangle frame between described waste liquid storehouse and described hard board for carrying described hard board;The side in described waste liquid storehouse has Waste liquid storehouse lateral opening, has the waste liquid Cang Gai closing described lateral opening, described lateral opening and institute at described lateral opening State and there is between the lid of waste liquid storehouse sealing gasket, bottom described waste liquid storehouse, there is waste discharge fluid apertures.
Further, described waste liquid storehouse covers has observation window, and described waste liquid storehouse is towards the open top of described rectangle frame Place has stage portion, and described rectangle frame is placed in described stage portion, and described waste liquid storehouse is held described in fixing being bolted to Below support plate.
Further, described dispensing unit includes valve plate installing plate, multiple valve plate, multiple valve and multiple dispensing nozzle; Described valve plate installing plate is fixed on described dispensing unit installing plate, and described valve plate includes bar shaped plate body, described bar shaped plate body bag Include two feed liquor portions at two ends and putting in an arrangement between said two feed liquor portion multiple go out liquid portion, described plate Internal have run through two feed liquor portions and all of go out liquid portion elongate holes, each go out liquid portion include one with described strip The inlet opening of hole connection and a liquid outlet running through described plate body upper and lower surface, described in go out liquid portion there is groove, described feed liquor The aperture in hole and one of them aperture of described liquid outlet are respectively positioned in described groove, and each described feed liquor portion has and described length First inlet of bar hole connection;The plurality of valve plate is fixed on described valve plate installing plate, right on described valve plate installing plate Should have a through hole running through valve plate installing plate upper and lower surface by each liquid outlet, each through hole is also connected with a dispensing spray Mouth;Being fixed with a described valve in each described groove, the liquid feeding end of described valve connects described inlet opening, described valve Liquid outlet connects described liquid outlet.
Further, each described feed liquor portion also has second inlet connected with described elongate holes, described Second inlet is cylindrical inlet, the axis of described second inlet and the axis co-axial of described elongate holes;Each valve It is provided with at plug, and one of them inlet of two the first inlets at two the second inlets of plate and is provided with plug;Institute Stating valve is two three-way electromagnetic valves;Described dispensing nozzle and described through hole are threadably secured connection, and described dispensing nozzle is positioned at Below described valve plate installing plate.
Further, described dispensing unit installing plate lower surface is provided with air bag, and described air bag has air inlet, intake valve Door, gas outlet and valve of giving vent to anger;Described source of the gas is for supplying described air bag, and described synthesizer also includes for by described dispensing The 3rd cylinder that unit installing plate and described loading plate seal.
Further, described gas-liquid road unit includes source of the gas, soda liquor container, multiple reagent container, multiple valve plate and many Individual first three-way valve;Described source of the gas connects one end of main pipe rail, and the other end of described main pipe rail connects the first pipeline and the second pipe Road;Air inlet pipe and drain pipe all it is inserted with on the lid of described soda liquor container and all reagent containers;All of air inlet pipe all connects Connecing described first pipeline, the drain pipe of soda liquor container connects the first inlet of a valve plate, each reagent container go out liquid Pipe connects the first port of at least one the first three-way valve, and described second pipeline connects the second port of all first three-way valve, 3rd port of each first three-way valve connects the first inlet of at least one valve plate.
Further, described gas-liquid road unit also includes air valve, cleanout fluid valve and the second three-way valve, on described second pipeline Being provided with air valve, the second pipeline between described air valve and described main pipe rail connects the first port of the second three-way valve by pipeline, The drain pipe road of described soda liquor container is connected with the second port of described second three-way valve, the 3rd end of described second three-way valve Mouth connects the first inlet of a valve plate, and the 3rd port of described second three-way valve is also connected with the first end of described cleanout fluid valve Mouthful, the second port of described cleanout fluid valve connects the second pipeline, the second port of described cleanout fluid valve and described second pipeline Junction point is between described air valve and the plurality of first three-way valve.
Further, described unit includes a soda liquor container, contains acetonitrile;Described reagent container has 9, contains respectively Dress couplant, the first block reagent, the second block reagent, thymus pyrimidine, adenine, cytosine, guanine, deprotecting regent, Oxidant;Described first block reagent and the second block reagent are different reagent.The air inlet pipe of described soda liquor container and coupling The air inlet pipe of mixture reagent container is all connected with the first main line;The air inlet pipe of described first block reagent and the second block reagent Air inlet pipe is all connected with the second main line;The air inlet pipe of described thymus pyrimidine reagent container, the air inlet pipe of adenine reagent container, born of the same parents The air inlet pipe of pyrimidine reagent container and the air inlet pipe of guanine reagent container are all connected with the 3rd main line;Described first main line, The air inlet pipe of the second main line, the 3rd main line, the air inlet pipe of deprotecting regent reagent container and oxidant reagent container all connects Connect described first pipeline.
Further, described first main line, the second main line, the 3rd main line, the entering of deprotecting regent reagent container It is equipped with pressure regulator valve and Pressure gauge on trachea, the air inlet pipe of oxidant reagent container, the second pipeline and main pipe rail;Described cleanout fluid The air inlet pipe of container, the air inlet pipe of couplant reagent container, the second main line, the 3rd main line, deprotecting regent reagent container Air inlet pipe and the air inlet pipe of oxidant reagent container be equipped with check valve.
Further, described source of the gas is argon gas bomb.
Further, described frame is hinged with inverted L shape briquetting, described dispensing unit installing plate is fixed with the 3rd gas Cylinder, the free end of described 3rd cylinder can abut described L-type briquetting horizontal side thus by described dispensing unit installing plate and Described loading plate seals.
Further, described inverted L shape briquetting divides both sides to arrange, every side has 7;3rd cylinder divides both sides to arrange, every side There are 7;7 of every side are connected to L-type briquetting by connecting rod.
Further, described loading plate is rectangular slab, and described loading plate passes described frame, by described first air cylinder driven Described frame moves horizontally.
Further, described synthesizer also includes upright guide rail, dispensing unit installing plate described in described second air cylinder driven Move up and down along described upright guide rail.
Further, described source of the gas is connected with described air intake valve;Described first, second and third cylinder is connected with described source of the gas.
Further, described rectangular opening, rectangle frame and waste liquid storehouse have two.
Further, dispensing unit installing plate is provided with two dispensing unit, equipped with 10 valves on each valve plate installing plate Plate;Described bar shaped plate body includes that 8 go out liquid portion;Described dispensing unit includes 80 dispensing nozzles.
Further, described hard board is provided with multiple row synthesis post and places position, often shows 16 synthesis posts and places position, each Synthesis post is placed position and is placed with a synthesis post.
Further, 10 valve plates on valve plate installing plate be divided into proper alignment first five and proper alignment rear five Individual, first five valve plate described and described rear five valve plates are staggeredly arranged, and the distance staggered is equal to adjacent liquid outlet on a valve plate Between distance.Thus 16 synthesis posts of string, the nozzle alignment first row 1,3,5,7 of first valve plate ... .., No. 15 synthesis During post, 2,4, the 6 of another row of the nozzle alignment of the 6th valve plate ... ..16 synthesis post.
Further, the drain pipe of each reagent container is for the inlet feed flow to 2 valve plates.
Beneficial effect: the DNA synthesizer synthesis cycle of the present invention is short, speed is fast, and synthetic agent consumption is minimum, and synthesis can The highest by property, stability is best.Powerful control software is that instrument failure rate is extremely low, stablizes.The design of gas circuit makes entirety Equipment flexible and convenient operation, hardware expanding is strong, and upgrading is convenient;Once it is capable of the synthesis to multiple synthesis posts, and synthesis Operation achieves automatization.
Accompanying drawing explanation
Fig. 1 is synthesizer general illustration;
Fig. 2 is that two dispensing unit are arranged on synthesis unit installing plate schematic diagram;
Fig. 3 is, by the 3rd cylinder, dispensing unit installing plate and loading plate are sealed schematic diagram;
Fig. 4 is dispensing unit installing plate lower surface air bag schematic diagram;
Fig. 5 is hard board bogey schematic diagram of the present invention;
Fig. 6 is hard board bogey decomposing schematic representation of the present invention;
Fig. 7 is dispenser schematic diagram;
Fig. 8 is valve plate the first schematic diagram;
Fig. 9 is valve plate the second schematic diagram;
Figure 10 is valve plate the 3rd schematic diagram;
Figure 11 is valve plate the 4th schematic diagram;
Figure 12 is gas-liquid road cell schematics.
Detailed description of the invention
Reference: 1.1 frames;1.2 container racks;1.3 hard board load bearing units;1.4 dispensing unit;1.5 dispensing Unit installing plate;1.6 first cylinders;1.7 second cylinders;1.8 the 3rd cylinders;1.9 inverted L shape briquettings;1.10 connecting rod;1.11 gas Capsule;2 valve plate installing plates;3 electromagnetic valves;4 dispensing nozzles;5 plate bodys;5.1 feed liquor portions;5.1.1 the first inlet;5.1.2 second enters Liquid mouth;5.2 go out liquid portion;5.2.1 inlet opening;5.2.2 liquid outlet;5.3 elongate holes;6 loading plates;6.1 rectangular opening;7 rectangle frames; 8 hard boards;9 waste liquid storehouses;9.1 waste discharge fluid apertures;9.2 sealing gasket;9.3 waste liquid Cang Gai;9.4 observation window;9.5 stage portion.20.1 couplings Mixture container;20.2 first block reagent containers;20.3 second block reagent containers;20.4 thymus pyrimidine container;20.5 gland is fast Purine container;20.6 cytosine container;20.7 guanine container;20.8 deprotecting regent reagent container;20.9 oxidant vessel; 20.10 soda liquor containers;30 sources of the gas;31 Pressure gauges;32 pressure regulator valves;33 check valves;34 cleanout fluid valves;35 air valves;36.1 first Three-way valve;36.2 the second three-way valve;40 main pipe rails;41 first pipelines;42 second pipelines;43.1 the first main line;43.2 second Main line;43.3 the 3rd main lines.
A kind of DNA synthesizer, including frame 1.1, container rack the 1.2, first cylinder the 1.6, second cylinder 1.7, synthesis Plate load bearing unit 1.3, dispensing unit 1.4, dispensing unit installing plate 1.5, gas-liquid road unit and controller;Described container rack 1.2 are fixed in described frame 1.1, and described container rack 1.2 is placed with soda liquor container 20.10 and multiple reagent container 20.1-20.9;Described dispensing unit 1.4 is arranged on described dispensing unit installing plate 1.5;Described first cylinder 1.6 is used for driving Dynamic described hard board load bearing unit 1.3 moves horizontally, and described second cylinder 1.7 is used for driving described dispensing unit installing plate 1.5 The most mobile.
Described hard board load bearing unit 1.3 includes loading plate 6, rectangle frame 7 and waste liquid storehouse 9;Described loading plate 6 include for Accommodating the rectangular opening 6.1 of described hard board 8, described waste liquid storehouse 9 is fixing with described loading plate 6 and is positioned at described rectangular opening 6.1 Lower section, described rectangle frame 7 is used for carrying described hard board 8 between described waste liquid storehouse 9 and described hard board 8;Described waste liquid The side in storehouse 9 has waste liquid storehouse lateral opening, has the waste liquid storehouse lid 9.3 closing described lateral opening at described lateral opening, There is between described lateral opening and described waste liquid storehouse lid 9.3 sealing gasket 9.2, bottom described waste liquid storehouse 9, there is waste discharge fluid apertures 9.1.Having observation window 9.4 on described waste liquid storehouse lid 9.3, described waste liquid storehouse 9 has towards the top open part of described rectangle frame Stage portion 9.5, described rectangle frame 7 is placed in described stage portion 9.5, and described waste liquid storehouse 9 is by described in fixing being bolted to Below loading plate 6.
Described dispensing unit 1.4 includes valve plate installing plate 2, multiple valve plate 5, multiple valve 3 and multiple dispensing nozzle 4;Institute Stating valve plate installing plate 2 to be fixed on described dispensing unit installing plate 1.5, described valve plate 5 includes bar shaped plate body, described bar shaped plate body Including two feed liquor portions 5.1 at two ends and putting in an arrangement between said two feed liquor portion 5.1 multiple go out liquid Portion 5.2, have in described plate body run through two feed liquor portions 5.1 and all of go out liquid portion 5.2 elongate holes 5.3, each go out liquid Portion 5.2 include an inlet opening 5.2.1 connected with described elongate holes 5.3 and one run through going out of described plate body upper and lower surface Fluid apertures 5.2.2, described in go out liquid portion 5.2 there is groove, the aperture of described inlet opening 5.2.1 and described liquid outlet 5.2.2 are wherein One aperture is respectively positioned in described groove, and each described feed liquor portion 5.1 has the first feed liquor connected with described elongate holes 5.3 Mouth 5.1.1;The plurality of valve plate 5 is fixed on described valve plate installing plate 2, corresponding each liquid outlet on described valve plate installing plate 2 5.2.2 having a through hole running through valve plate installing plate 2 upper and lower surface, each through hole is also connected with a dispensing nozzle 4;Often Being fixed with a described valve 3 in individual described groove, the liquid feeding end of described valve 3 connects described inlet opening 5.2.1, described valve Liquid outlet connect described liquid outlet 5.2.2.Each described feed liquor portion 5.1 also has one and connects with described elongate holes 5.3 The second inlet 5.1.2, described second inlet 5.1.2 be cylindrical inlet, the axis of described second inlet 5.1.2 Axis co-axial with described elongate holes 5.3;It is provided with plug, and two at two the second inlet 5.1.2 of each valve plate 5 It is provided with plug at one of them inlet 5.1.1 of the first inlet 5.1.1;Described valve 3 is two three-way electromagnetic valves;Described dispensing Nozzle and described through hole are threadably secured connection, and described dispensing nozzle 4 is positioned at below described valve plate installing plate 2.
Described dispensing unit installing plate 1.5 lower surface is provided with air bag 1.11, and described air bag 1.11 has air inlet, intake valve Door, gas outlet and valve of giving vent to anger;Described source of the gas is for supplying described air bag, and described synthesizer also includes for by described dispensing The 3rd cylinder 1.8 that unit installing plate and described loading plate seal.Inverted L shape briquetting 1.9 it is hinged with in described frame 1.1, described Being fixed with the 3rd cylinder 1.8 on dispensing unit installing plate 1.5, the free end of described 3rd cylinder 1.8 can abut described L-type pressure The horizontal side of block 1.9 thus described dispensing unit installing plate 1.5 and described loading plate 6 are sealed.When dispensing unit is pacified by needs When dress plate 1.5 lifts, inverted L shape briquetting 1.9 can be rotated outside frame, otherwise briquetting 1.9 inwardly be rotated in inverted L shape, profit Abut briquetting with the 3rd cylinder 1.8, thus loading plate 6 and synthesis unit installing plate 1.5 are sealed.As it is shown on figure 3, described inverted L Type briquetting divides both sides to arrange, every side has 7;3rd cylinder divides both sides to arrange, every side has 7;7 of every side to L-type pressure Block is connected by connecting rod.
Described gas-liquid road unit includes source of the gas 30, soda liquor container 20.10, multiple reagent container 20.1-20.9, Duo Gefa Plate 5 and multiple first three-way valve 36.1;Described source of the gas 30 connects one end of main pipe rail 40, and the other end of described main pipe rail 40 connects First pipeline 41 and the second pipeline 42;On the lid of described soda liquor container 20.10 and all reagent container 20.1-20.9 the most slotting There are air inlet pipe and drain pipe;All of air inlet pipe is all connected with described first pipeline 41, and the drain pipe of soda liquor container 20.10 connects First inlet of one valve plate 5, the drain pipe of each reagent container connects the first end of at least one the first three-way valve 36.1 Mouthful, described second pipeline 42 connects the second port of all first three-way valve 36.1, the 3rd end of each first three-way valve 36.1 Mouth connects the first inlet of at least one valve plate 5.Described gas-liquid road unit also includes air valve 35, cleanout fluid valve 34 and the 2nd 3 Logical valve 36.2, described second pipeline 42 is provided with air valve 35, and the second pipeline between described air valve 35 and described main pipe rail 40 leads to Cross pipeline and connect the first port of the second three-way valve 36.2, the drain pipe road of described soda liquor container 20.10 and the described 2nd 3 Second port of logical valve 36.2 connects, and the 3rd port of described second three-way valve 36.2 connects the first inlet of a valve plate 5, 3rd port of described second three-way valve 36.2 is also connected with the first port of described cleanout fluid valve, the second end of described cleanout fluid valve Mouthful connecting the second pipeline, the second port of described cleanout fluid valve and the junction point of described second pipeline are positioned at described air valve and described Between multiple first three-way valve.Described unit includes a soda liquor container 20.10, contains acetonitrile;Described reagent container has 9 Individual, contain couplant, the first block reagent, the second block reagent, thymus pyrimidine, adenine, cytosine, guanine respectively, take off Protection reagent, oxidant;Described first block reagent and the second block reagent are different reagent.Entering of described soda liquor container The air inlet pipe of trachea and couplant reagent container is all connected with the first main line 43.1;The air inlet pipe of described first block reagent and The air inlet pipe of two block reagent is all connected with the second main line 43.2;The air inlet pipe of described thymus pyrimidine reagent container, adenine try The air inlet pipe of the air inlet pipe of agent container, the air inlet pipe of cytosine reagent container and guanine reagent container is all connected with the 3rd main line 43.3;Described first main line the 43.1, second main line the 43.2, the 3rd main line 43.3, the entering of deprotecting regent reagent container The air inlet pipe of trachea and oxidant reagent container is all connected with described first pipeline 41.Described first main line 43.1, second is responsible for Road the 43.2, the 3rd main line 43.3, the air inlet pipe of deprotecting regent reagent container, the air inlet pipe of oxidant reagent container, second Pressure regulator valve 32 and Pressure gauge 31 it is equipped with on pipeline 42 and main pipe rail 40;The air inlet pipe of described soda liquor container, couplant reagent The air inlet pipe of container, the second main line, the 3rd main line, the air inlet pipe of deprotecting regent reagent container and oxidant reagent container Air inlet pipe be equipped with check valve 33.
Described source of the gas is argon gas bomb.
Described loading plate 6 is rectangular slab, and described loading plate 6, through described frame 1.1, is driven by described first cylinder 1.6 Described frame 1.1 moves horizontally.Described synthesizer also includes that upright guide rail, described second cylinder 1.7 drive described dispensing Unit installing plate moves up and down along described upright guide rail.Described source of the gas is connected with described air intake valve;Described first, second and third Cylinder is connected with described source of the gas.A source of the gas is utilized can gas-liquid road unit, air bag, first, second and third cylinder to be supplied.
Described rectangular opening, rectangle frame 7 and waste liquid storehouse 9 have two.Dispensing unit installing plate is provided with two dispensing unit, Equipped with 10 valve plates on described valve plate installing plate;Described bar shaped plate body includes that 8 go out liquid portion;Described dispensing unit includes 80 points Note nozzle.Described hard board 8 is provided with multiple row synthesis post and places position, often shows 16 synthesis posts and places position, and each synthesis post is put Set is placed with a synthesis post.10 valve plates on valve plate installing plate be divided into proper alignment first five and proper alignment after Five, first five valve plate described and described rear five valve plates are staggeredly arranged, the distance staggered equal on a valve plate adjacent go out liquid Distance between hole.Thus 16 synthesis posts of string, the nozzle alignment first row 1,3,5,7 of first valve plate ... .., No. 15 conjunctions When becoming post, 2,4, the 6 of another row of the nozzle alignment of the 5th valve plate ... ..16 nozzle.
As shown in figure 12, the drain pipe of each reagent container is for the inlet feed flow to 2 valve plates.
When the synthesizer of the present invention works, inverted L shape briquetting is arranged to as it is shown on figure 3, air bag is filled a certain amount of argon by source of the gas Gas, loading plate and dispensing unit installing plate are sealed by the 3rd cylinder, utilize nozzle synthesis post is carried out operation or divides afterwards The operation of note reagent;During discharge opeing, realize discharge opeing by dispensing nozzle to synthesis post spray argon;After discharge opeing completes, the 3rd cylinder pine Opening, air bag deflation, the first air cylinder driven loading plate moves a segment distance and makes to synthesize accordingly the nozzle in post alignment downstream, gas afterwards Capsule is inflated, the 3rd cylinder-pressing, carries out the dispensing operation of next reagent, then carries out discharge opeing operation, after discharge opeing completes, unclamps the Three cylinders, air bags, the first air cylinder driven loading plate moves a segment distance, so circulates, until the equal dispensing of all of reagent React complete, complete the synthesis of DNA.
For a dispensing nozzle and a synthesis post, during fluid injection, liquid comes from pipeline, enters strip from inlet Enter behind hole each go out liquid portion inlet opening, from inlet opening flow into electromagnetic valve, out enter liquid outlet from electromagnetic valve, eventually pass Dispensing nozzle enters in synthesis post, it is achieved cleanout fluid cleans and reagent dispensing operates.Similarly, it is also possible to by argon stream from pipe Pass by, enter from inlet enter after elongate holes each go out liquid portion inlet opening, flow into electromagnetic valve from inlet opening, from electromagnetism Valve out enters liquid outlet, eventually pass dispensing nozzle enter synthesis post in, it is achieved argon purge and by residual agent discharge Come.
The synthesizer of the present invention once can carry two hard boards, it is adaptable to high-throughout DNA synthesizes, and injection needle When carrying out the synthesis fluid injection of post and discharge opeing operation, the waste liquid of generation is directly entered waste liquid storehouse, will not pollute laboratory or Person's instrument itself, will not be to synthetically produced harmful effect;And observation window can observe the situation in waste liquid storehouse at any time, prevents Waste liquid in waste liquid storehouse is too much.The waste liquid storehouse of the present invention can connect waste discharge fluid apertures by pipeline and be drained by waste liquid at any time, it is possible to To arrange the stopper closing described waste discharge fluid apertures, after having saved bit by bit a certain amount of waste liquid, open stopper and discharge waste liquid.
When the gas liquid-way system of the present invention works, making second and third port of all of first three-way valve connect, air valve is beaten Opening, cleanout fluid valve cuts out, and first and third port of the second three-way valve is connected such that it is able to utilize multiple valve plate to be exhausted operation, Argon purge can be realized, it is also possible to realize argon and discharge the operation of residual agent in synthesis post.Make all of first three-way valve Second and third port connect, air valve is closed, and cleanout fluid valve opens, and second and third port of the second three-way valve is connected, such that it is able to Go out cleanout fluid from multiple valve plates and be carried out operation.First and third port making all of first three-way valve is connected, air valve closedown, Cleanout fluid valve cuts out, second and third port of the second three-way valve is connected, and can pass through the reagent that valve plate dispensing is different, such that it is able to Carry out injecting the operation of reagent in synthesis post, have two valve plates can be with dispensing cleanout fluid simultaneously.
Although the present invention is illustrated with regard to preferred implementation and has been described, it is understood by those skilled in the art that Without departing from scope defined by the claims of the present invention, the present invention can be carried out variations and modifications.

Claims (10)

1. a high flux DNA synthesizer, it is characterised in that include frame, container rack, the first cylinder, the second cylinder, conjunction Become plate load bearing unit, dispensing unit, dispensing unit installing plate, gas-liquid road unit and controller;Described container rack is fixed on In described frame, described container rack is placed with soda liquor container and multiple reagent container;Described hard board load bearing unit holds It is loaded with hard board, described hard board has multiple synthesis post;Described dispensing unit is arranged on described dispensing unit installing plate, Described dispensing unit includes multiple dispensing nozzle;Described gas-liquid road unit includes source of the gas, described soda liquor container and the plurality of Reagent container;Described first cylinder is used for driving described hard board load bearing unit to move horizontally, and described second cylinder is used for driving Described dispensing unit installing plate vertically moves.
High flux DNA synthesizer the most according to claim 1, it is characterised in that described hard board load bearing unit includes holding Support plate, rectangle frame and waste liquid storehouse;Described loading plate includes the rectangular opening for accommodating described hard board, and described waste liquid storehouse is with described The lower section of described rectangular opening is fixed and be positioned to loading plate, and described rectangle frame is used between described waste liquid storehouse and described hard board Carry described hard board;The side in described waste liquid storehouse has waste liquid storehouse lateral opening, has closing described at described lateral opening The waste liquid Cang Gai of lateral opening, has sealing gasket between described lateral opening and described waste liquid storehouse lid, have bottom described waste liquid storehouse There is waste discharge fluid apertures.
High flux DNA synthesizer the most according to claim 2, it is characterised in that described waste liquid storehouse covers has observation window, Described waste liquid storehouse has stage portion towards the top open part of described rectangle frame, and described rectangle frame is placed in described stage portion, Described waste liquid storehouse is bolted to below described loading plate by fixing.
4. according to the high flux DNA synthesizer described in Claims 2 or 3, it is characterised in that described dispensing unit includes that valve plate is pacified Dress plate, multiple valve plate, multiple valve and multiple dispensing nozzle;Described valve plate installing plate is fixed on described dispensing unit installing plate On, described valve plate includes that bar shaped plate body, described bar shaped plate body include being positioned at two feed liquor portions at two ends and be positioned at said two and enter Between liquid portion put in an arrangement multiple go out liquid portion, have in described plate body run through two feed liquor portions and all of go out liquid portion Elongate holes, each go out liquid portion include an inlet opening connected with described elongate holes and one run through following table on described plate body The liquid outlet in face, described in go out liquid portion there is groove, the aperture of described inlet opening and the equal position, one of them aperture of described liquid outlet In described groove, each described feed liquor portion has the first inlet connected with described elongate holes;The plurality of valve plate is solid Being scheduled on described valve plate installing plate, on described valve plate installing plate, corresponding each liquid outlet has one to run through valve plate installing plate upper and lower The through hole on surface, each through hole is also connected with a dispensing nozzle;A described valve, institute it is fixed with in each described groove The liquid feeding end stating valve connects described inlet opening, and the liquid outlet of described valve connects described liquid outlet.
High flux DNA synthesizer the most according to claim 4, it is characterised in that each described feed liquor portion also has one The second inlet connected with described elongate holes, described second inlet is cylindrical inlet, described second inlet Axis and the axis co-axial of described elongate holes;It is provided with plug, and two first at two the second inlets of each valve plate It is provided with plug at one of them inlet of inlet;Described valve is two three-way electromagnetic valves;Described dispensing nozzle and described through Hole is threadably secured connection, and described dispensing nozzle is positioned at below described valve plate installing plate.
High flux DNA synthesizer the most according to claim 5, it is characterised in that described dispensing unit installing plate lower surface Being provided with air bag, described air bag has air inlet, air intake valve, gas outlet and valve of giving vent to anger;Described source of the gas is for described air bag Supply, described synthesizer also includes the 3rd cylinder for described dispensing unit installing plate and described loading plate being sealed.
High flux DNA synthesizer the most according to claim 5, it is characterised in that described gas-liquid road unit includes source of the gas, clear Wash liquor vessel, multiple reagent container, multiple valve plate and multiple first three-way valve;Described source of the gas connects one end of main pipe rail, described The other end of main pipe rail connects the first pipeline and the second pipeline;On the lid of described soda liquor container and all reagent containers the most slotting There are air inlet pipe and drain pipe;All of air inlet pipe is all connected with described first pipeline, and the drain pipe of soda liquor container connects a valve First inlet of plate, the drain pipe of each reagent container connects the first port of at least one the first three-way valve, and described second Pipeline connects the second port of all first three-way valve, and the 3rd port of each first three-way valve connects the of at least one valve plate One inlet.
High flux DNA synthesizer the most according to claim 7, it is characterised in that described gas-liquid road unit also include air valve, Cleanout fluid valve and the second three-way valve, described second pipeline is provided with air valve, the second pipe between described air valve and described main pipe rail Road connects the first port of the second three-way valve by pipeline, the drain pipe road of described soda liquor container and described second three-way valve Second port connects, and the 3rd port of described second three-way valve connects the first inlet of a valve plate, described second three-way valve The 3rd port be also connected with the first port of described cleanout fluid valve, the second port of described cleanout fluid valve connects the second pipeline, institute The junction point of the second port and described second pipeline of stating cleanout fluid valve be positioned at described air valve and the plurality of first three-way valve it Between.
High flux DNA synthesizer the most according to claim 8, it is characterised in that described unit includes that a cleanout fluid holds Device, contains acetonitrile;Described reagent container has 9, contains couplant, the first block reagent, the second block reagent, thymus respectively phonetic Pyridine, adenine, cytosine, guanine, deprotecting regent, oxidant;Described first block reagent and the second block reagent are not Same reagent.The air inlet pipe of described soda liquor container and the air inlet pipe of couplant reagent container are all connected with the first main line;Described The air inlet pipe of the first block reagent and the air inlet pipe of the second block reagent are all connected with the second main line;Described thymus pyrimidine reagent holds Entering of the air inlet pipe of device, the air inlet pipe of adenine reagent container, the air inlet pipe of cytosine reagent container and guanine reagent container Trachea is all connected with the 3rd main line;Described first main line, the second main line, the 3rd main line, deprotecting regent reagent container Air inlet pipe and the air inlet pipe of oxidant reagent container be all connected with described first pipeline.
High flux DNA synthesizer the most according to claim 9, it is characterised in that described first main line, the second supervisor Road, the 3rd main line, the air inlet pipe of deprotecting regent reagent container, the air inlet pipe of oxidant reagent container, the second pipeline and total Pressure regulator valve and Pressure gauge it is equipped with on pipeline;The air inlet pipe of described soda liquor container, the air inlet pipe of couplant reagent container, second The air inlet pipe of main line, the 3rd main line, the air inlet pipe of deprotecting regent reagent container and oxidant reagent container is equipped with list To valve.
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CN107880088A (en) * 2017-11-23 2018-04-06 希施生物科技(上海)有限公司 One kind is used for nucleic acid DNA/RNA pilot scale type automatic synthesizers
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CN114573653A (en) * 2022-01-26 2022-06-03 北京擎科生物科技有限公司 Gas-liquid path system for automatic synthesis of nucleic acid and synthesis system
CN115253953A (en) * 2022-09-29 2022-11-01 江苏汉邦科技股份有限公司 Nucleic acid synthesis system

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