WO2019023948A1 - 基因测序反应设备、基因测序系统和基因测序反应方法 - Google Patents

基因测序反应设备、基因测序系统和基因测序反应方法 Download PDF

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Publication number
WO2019023948A1
WO2019023948A1 PCT/CN2017/095512 CN2017095512W WO2019023948A1 WO 2019023948 A1 WO2019023948 A1 WO 2019023948A1 CN 2017095512 W CN2017095512 W CN 2017095512W WO 2019023948 A1 WO2019023948 A1 WO 2019023948A1
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WIPO (PCT)
Prior art keywords
chip
gene sequencing
sequencing reaction
soaking
sequencing
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PCT/CN2017/095512
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English (en)
French (fr)
Inventor
马炜
徐讯
伍家波
倪鸣
魏栋
唐建生
Original Assignee
深圳华大智造科技有限公司
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Application filed by 深圳华大智造科技有限公司 filed Critical 深圳华大智造科技有限公司
Priority to CN201780093149.0A priority Critical patent/CN110892057A/zh
Priority to US16/635,347 priority patent/US11241692B2/en
Priority to EP17920580.2A priority patent/EP3663389A4/en
Priority to PCT/CN2017/095512 priority patent/WO2019023948A1/zh
Publication of WO2019023948A1 publication Critical patent/WO2019023948A1/zh
Priority to US17/569,903 priority patent/US11857973B2/en
Priority to US18/516,598 priority patent/US20240082846A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/02—Water baths; Sand baths; Air baths
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869—Methods for sequencing
    • C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/185—Means for temperature control using fluid heat transfer medium using a liquid as fluid
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides

Definitions

  • the invention relates to the field of gene sequencing technology, in particular to a gene sequencing reaction device, a gene sequencing system and a gene sequencing reaction method.
  • DNA sequencing molecules (sequencing reaction templates) need to be loaded onto the sequencing chip before gene sequencing (also referred to as DNA sequencing), and then the gene sequencing reaction is further completed to add nucleotides to the sequencing reaction template, and the detection is performed. By adding the type of nucleotide, the sequence of the gene can be detected.
  • the Chinese utility model patent CN205133580U provides a currently widely used sequencing chip.
  • the chip is provided with an internal flow channel. Different chemical reagents are injected into the flow channel from the inlet, and flow through the flow channel and then discharged from the outlet, whether it is loading or sequencing of the DNA sample. Both need to implement the above process.
  • a sequencing reagent is injected to cause a sequencing chemical reaction of the DNA sample, which has the following disadvantages:
  • the silicon surface of the chip can be used only in the area of the flow channel, and other parts cannot be effectively utilized, so that the silicon wafer cannot be utilized to the utmost extent.
  • the object of the present invention is to provide a gene sequencing reaction device, a gene sequencing system and a gene sequencing reaction method for realizing a gene sequencing reaction by using a immersion method.
  • the first aspect of the present invention provides a gene sequencing reaction device, comprising: a support platform; a soaking container, disposed on the support platform, the soaking container has a soaking reaction zone, and the soaking reaction zone is used for holding a genetic test
  • the sequencing reaction uses a chemical reagent and is used for immersing a sequencing chip having a DNA sample loading structure on the surface and having a DNA sample loaded in the chemical reagent for gene sequencing reaction; a temperature control device for controlling the chemical reagent of the immersion reaction zone a temperature; a transfer device for inserting or extracting the sequencing chip into the immersion reaction zone.
  • the genetic sequencing reaction device includes a plurality of the soaking containers; and/or the soaking container includes a plurality of the soaking reaction zones isolated from each other.
  • the infusion container includes an overflow port.
  • the temperature control device includes a temperature control portion for holding a liquid capable of transferring heat, a water bath, the soaking container is disposed in the water bath, and the temperature control portion controls the The temperature of the liquid in the water bath controls the temperature of the chemical in the soaking reaction zone.
  • the gene sequencing reaction device further includes: an upper material storage device for placing the sequencing chip to be subjected to a gene sequencing reaction; and/or a lower material storage device for placing the completed gene sequencing reaction The sequencing chip.
  • the upper material storage device and/or the lower material storage device comprise: a storage box, the top of the storage box is open and has a slot and a drain hole, the slot is used for Positioning the sequencing chip, the liquid discharging hole is disposed on a bottom wall of the storage box for discharging liquid in the storage box; and a liquid storage box is disposed in the liquid discharging hole Below, it is used to receive the liquid discharged from the drain hole.
  • the gene sequencing reaction device further includes a container lid that is openably and closably covered on the soaking container to prevent evaporation of the chemical agent.
  • the container cover comprises a plurality of covers, each of the cover bodies being arranged to correspond to one or more of the immersion reaction zones to prevent evaporation of chemical reagents in the corresponding immersion reaction zone, and at least one The cover can be opened and closed independently of the other covers.
  • the gene sequencing reaction device further includes a flip mechanism that is drivingly coupled to the container cover to drive the container lid to open and close.
  • the transfer device includes a connection portion for connection with the sequencing chip and a motion mechanism that is drivingly coupled to the connection portion to change a working position of the connection portion.
  • the plurality of immersion reaction zones are arranged in a row or rows in a lateral direction;
  • the movement mechanism comprises a lateral movement mechanism, a longitudinal movement mechanism and a vertical movement mechanism, and the longitudinal movement mechanism is disposed on the support platform,
  • the lateral movement mechanism is disposed on the longitudinal movement mechanism, and the vertical movement mechanism is disposed on the lateral movement machine Constructing,
  • the connecting portion is disposed on the vertical moving mechanism,
  • the longitudinal moving mechanism drives the longitudinal movement of the lateral movement mechanism, and the lateral movement mechanism drives the vertical movement mechanism to laterally move, the vertical direction
  • the moving mechanism drives the connecting portion to move vertically.
  • the gene sequencing reaction device further includes a chip holding device, the chip holding device includes one or more chip mounting positions, and the sequencing chip is mounted on the chip mounting position to move by moving the chip holding device Said sequencing chip.
  • the two sides of the sequencing chip have the DNA sample loading structure;
  • the chip mounting position includes a chip mounting port, the sequencing chip is installed in the chip mounting opening, and the chip mounting opening is open on both sides. The mouth.
  • the chip holding device includes a chip frame on which the chip mounting position is disposed, a surface of the chip frame is a hydrophobic surface, and/or a lower end of the chip frame is gradually tapered from top to bottom. .
  • the chip holding device includes a chip frame on which one or more chip mounting positions are disposed, and an upper end of the chip frame is provided with a bayonet;
  • the transfer device includes a jaw connected to the chip frame and a movement mechanism drivingly coupled to the jaw to change a working position of the jaw, the jaw comprising a positioning bracket and a clamp, the positioning bracket being coupled to the movement mechanism
  • the clamping block is movably disposed on the positioning frame, and the positioning frame is provided with a positioning hole for inserting the upper end of the chip frame, and the clamping jaw and the bayonet of the chip frame inserted into the positioning hole The card is snapped to clamp the chip frame.
  • the gene sequencing reaction apparatus further includes a control device, wherein the control device is coupled to the temperature control device to control a temperature of the chemical reagent; and/or the control device is coupled to the transfer device To control the soaking time and/or soaking sequence of the sequencing chip in the soaking reaction zone.
  • the gene sequencing reaction device includes the sequencing chip, and the surface of the sequencing chip has a DNA sample loading structure.
  • the gene sequencing reaction device includes a protective cover, and the soaking container is disposed in the protective cover.
  • the gene sequencing reaction device includes an insufflation device for blowing off a chemical agent on a surface of the sequencing chip and/or a surface of a chip holding device on which the sequencing chip is mounted.
  • a second aspect of the present invention provides a gene sequencing system comprising a DNA sample loading device and a gene sequencing reaction device, the gene sequencing reaction device being the gene sequencing reaction device according to any one of the first aspects of the present invention.
  • a third aspect of the present invention provides a gene sequencing reaction method, comprising: adding a chemical reagent for gene sequencing reaction in a soaking reaction zone of a soaking vessel; and controlling a temperature of the chemical reagent in the infusion reaction zone; A sequencing chip having a DNA sample loading structure on its surface and loaded with a DNA sample is immersed in the chemical reagent for a predetermined time and taken out.
  • the gene sequencing reaction method comprises: adding different genetic sequencing reaction chemical reagents in a plurality of immersion reaction zones, and sequentially squeezing the sequencing chips in the plurality of immersion reaction zones in a predetermined order. time.
  • the soaking vessel has a soaking reaction zone, and the soaking reaction zone is used for holding a chemical reagent for gene sequencing reaction and is used for soaking a sequencing chip having a DNA sample loading structure and having a DNA sample loaded thereon.
  • the gene sequencing reaction is carried out in a chemical reagent; the temperature control device is used to control the temperature of the immersion reaction zone; and the transfer device is used for inserting the sequencing chip into the immersion reaction zone or withdrawing from the immersion reaction zone.
  • the gene sequencing reaction device can be used to achieve gene sequencing reaction by soaking.
  • the sequencing chip is immersed in the chemical reagents in different immersion reaction zones to complete the various steps required for the sequencing reaction.
  • the chemical reagents in the immersion reaction zone can be reused, thereby reducing the cost of consumables.
  • the sequencing chip receives a uniform pressure in the soaking cylinder and is evenly heated, so that deformation does not occur.
  • the gene sequencing reaction device is automatically controlled by the control device to achieve automated operation.
  • the gene sequencing system and the gene sequencing reaction method of the present invention have similar technical effects as the gene sequencing reaction device of the present invention.
  • FIG. 1 is a schematic perspective view showing the structure of a gene sequencing reaction device in an embodiment of the present invention
  • FIG. 2 is a schematic perspective view showing the structure of the gene sequencing reaction device of FIG. 1 after removing the container cover;
  • FIG. 3 is a schematic perspective view showing another perspective of the gene sequencing reaction device shown in FIG. 1;
  • FIG. 4 is a schematic perspective view showing the jaws, the sequencing chip, and the chip holding device of the transfer device of the gene sequencing reaction device shown in FIG. 1.
  • Fig. 5 is a perspective view showing another perspective of the jaw, the sequencing chip and the chip holding device of the transfer device shown in Fig. 4.
  • Fig. 6 is an exploded perspective view showing the jaws, the sequencing chip, and the chip holding device of the transfer device shown in Fig. 4.
  • Fig. 7 is an exploded perspective view showing the jaw of the transfer device shown in Fig. 4, the sequencing chip, and the chip holding device at another angle.
  • Figure 8 is a perspective view showing the structure of the upper material storage device (lower material storage device) of the gene sequencing reaction device shown in Figure 1;
  • Figure 9 is a schematic exploded view of the upper material storage device (lower material storage device) shown in Figure 8;
  • Figure 10 is a perspective view showing the structure of the soaking tank of the gene sequencing reaction apparatus shown in Figure 1;
  • Fig. 11 is a schematic enlarged view showing a portion I of the gene sequencing reaction apparatus shown in Fig. 1.
  • orientations such as “front, back, up, down, left, right", “horizontal, vertical, vertical, horizontal” and “top, bottom” and the like are indicated. Or the positional relationship is generally based on the orientation or positional relationship shown in the drawings, and is merely for the convenience of the description of the invention and the simplification of the description, which are not intended to indicate or imply the indicated device or component. It must be constructed and operated in a specific orientation or in a specific orientation, and thus is not to be construed as limiting the scope of the invention; the orientations “inside and outside” refer to the inside and outside of the contour of the components themselves.
  • lateral direction used in the following description refers to the left-right direction of the gene sequencing reaction device 1 shown in FIGS. 1 to 3
  • longitudinal direction refers to the front-rear direction of the gene sequencing reaction device 1 shown in FIGS. 1 to 3
  • vertical direction refers to the up and down direction of the gene sequencing reaction device 1 shown in FIGS. 1 to 3.
  • FIG. 1 to 11 show the structure of a gene sequencing reaction device 1 of an embodiment of the present invention.
  • an embodiment of the present invention discloses a gene sequencing reaction device 1.
  • the gene sequencing reaction device 1 includes a support platform 8, a soaking container, a temperature control device 5, and a transfer device 6.
  • the infusion container is disposed on the support platform 8.
  • the soaking vessel has a soaking reaction zone for holding a chemical reagent for gene sequencing reaction and is used for immersing a sequencing chip 2 having a DNA sample loading structure on the surface and having a DNA sample loaded in a chemical reagent for gene sequencing reaction.
  • the temperature control device 5 is used to control the temperature of the chemical reagent in the immersion reaction zone.
  • the transfer device 6 is used to insert or remove the sequencing chip 2 from the soak reaction zone.
  • the DNA sample in this embodiment is a sequencing reaction template, and the labeled nucleotide can be added to the sequencing reaction mode. In the board.
  • the gene sequencing reaction device 1 can realize the gene sequencing reaction by using the immersion method.
  • the sequencing chip 2 is immersed in the chemical reagents of different immersion reaction zones, and can complete various steps required for the sequencing reaction.
  • the chemical reagents in the immersion reaction zone can be reused, thereby reducing the cost of consumables.
  • the sequencing chip 2 receives a uniform pressure in the immersion reaction zone and is evenly heated, so that deformation does not occur. No complicated fluid system, few parts, easy assembly and low manufacturing cost. Multiple sequencing chips 2 can be immersed at the same time, which has the advantage of high throughput.
  • the gene sequencing reaction device 1 is automatically controlled by the control device 23, and an automated operation can be realized.
  • the gene sequencing reaction device 1 of the embodiment of the invention includes a sequencing chip 2, a soaking container, a temperature control device 5, a transfer device 6, a chip holding device, an upper material storage device 14, and a lower storage device.
  • the material device 15, the container cover 4, the flip mechanism 22, the air blowing device 25, the control device 23, and the support platform 8.
  • the surface of the sequencing chip 2 has a DNA sample loading structure, and the DNA sample loading structure of the sequencing chip 2 has been loaded with the DNA sample before the gene sequencing reaction.
  • the sequencing chip 2 is a silicon wafer, and a joint capable of capturing DNA molecules is preset on both sides of the silicon wafer. After a series of chemical reactions, DNA molecules can be captured by these joints and eventually adhere to the surface of the silicon wafer.
  • the linker can be formed, for example, by modifying the surface of the silicon wafer with an amino group. During the gene sequencing reaction, the DNA sample is always attached to the sequencing chip 2.
  • the DNA sample referred to in this embodiment may be a nanosphere molecule as disclosed in U.S. Patent No. 8,445,197 B2, which may also be referred to as DNB.
  • the genomic DNA is first fragmented, coupled with a linker sequence, and cyclized to form a single-stranded circular DNA, and then the single-stranded circular DNA is amplified by a rolling circle amplification technique by 2 to 3 orders of magnitude to become DNB.
  • the soaking vessel has a soaking reaction zone for holding a chemical reagent for gene sequencing reaction and is used for immersing a sequencing chip 2 having a DNA sample loading structure on the surface and having a DNA sample loaded in a chemical reagent for gene sequencing reaction.
  • the sequencing chip 2 is immersed in the chemical reaction reagent for gene sequencing reaction in the immersion reaction zone to complete the step of the gene sequencing reaction.
  • the temperature control device 5 is capable of controlling the temperature of the chemical reagent in the immersion reaction zone to provide suitable temperature conditions for the gene sequencing reaction.
  • the gene sequencing reaction device 1 includes a plurality of soaking containers. As shown in FIGS. 1 to 3, the infusion container is specifically an soaking tank 3. Each soaking tank 3 has a soaking reaction zone. Multiple soaking tanks 3 arranged On the temperature control device 5. The temperature control device 5 is disposed on the support platform 8. The transfer device 6 can insert and withdraw the sequencing chip 2 from the soaking tank 3. In this embodiment, each of the soaking tanks 3 is filled with a chemical reagent, and the chemical reagents required for each gene sequencing step are loaded into different soaking tanks.
  • the transfer device 6 After the transfer device 6 holds the sequencing chip 2 for immersion in each of the immersion tanks 3 for a predetermined time, it is possible to add nucleotides to the DNA sample (sequencing reaction template) of the sequencing chip 2. Thereafter, by placing the sequencing chip 2 on an external optical imaging device for imaging, it is possible to detect the type of nucleotide added. By continuously cycling through the above steps, the sequence of the gene can be read.
  • the soaking tanks 3 can also be grouped, with each set of soaking tanks being filled with a chemical reagent.
  • the gene sequencing reaction apparatus 1 includes two rows of immersion cylinders 3 arranged laterally, and the number of immersion cylinders 3 per row is 17.
  • the infusion vessel may also include a plurality of soaking reaction zones isolated from one another, each or each set of soaking reaction zones containing a chemical reagent.
  • the dip tank 3 includes an overflow port 29.
  • the liquid in the immersion tank 3 exceeds a certain water level, it overflows from the overflow port 29, so that the liquid level in the immersion tank 3 can be prevented from being excessively high.
  • the temperature control device 5 is used to control the temperature of the chemical reagent in the immersion reaction zone.
  • the temperature control device 5 is disposed on the support platform 8, and the infusion container is disposed on the support platform 8 through the temperature control device 5.
  • the temperature control device 5 includes a temperature control portion and a water bath.
  • the water bath is used to hold a liquid that can transfer heat.
  • the soaking container is placed in a water bath.
  • the temperature control unit controls the temperature of the liquid in the water bath to control the temperature of the chemical in the infusion vessel.
  • the temperature control unit is a heat exchange tube disposed in the wall of the water bath, and the heat exchange tube can input heat to the liquid in the water bath or absorb heat from the liquid in the water bath, so that the water bath The heat transfer liquid can be heated or cooled down.
  • the heat transfer liquid in the water bath can be heated or lowered, and the soaking tank 3 is immersed in the heat transfer liquid, thereby being able to control the chemical reagent in the soaking tank 3. temperature.
  • the use of a liquid as a heat transfer medium can more uniformly control the temperature of the chemical agent in each of the soaking tanks 3. Moreover, the temperature of the chemical reagent is more stable and is not easily changed rapidly.
  • a direct temperature control method for directly heating or cooling the soaking tank 3 or the liquid therein may also be adopted by a thermostat (for example, a Peltier temperature controller), but the direct temperature control method is The indirect temperature control method using the water bath is more prone to uneven heating and cooling.
  • the upper stock storage device 14 is used to place the sequencing chip 2 to be subjected to a gene sequencing reaction.
  • the lower stock storage device 15 is used to place the sequencing chip 2 on which the gene sequencing reaction has been performed.
  • the upper stocker 14 and the lower stocker 15 each include a magazine and a reservoir 18.
  • the top of the magazine is open and has a slot 16 and a drain hole 17.
  • the slot 16 is disposed on the inner surface of the side wall of the storage box for positioning the sequencing chip 2.
  • a drain hole 17 is provided in the bottom wall of the magazine for discharging the liquid in the magazine.
  • the liquid discharge hole 17 can drain the chemical reagent flowing down the surface of the chip frame 9 and the sequencing chip 2.
  • the sequencing chip 2 is mounted on the chip frame 9, and the sequencing chip 2 is moved by moving the chip frame 9.
  • the slot 16 is used to position the chip frame 9 to position and place the sequencing chip 2 through the chip frame 9.
  • the chip frame 9 is inserted into the slot 16 to position and place the sequencing chip 2 thereon in the magazine.
  • the number of the slots 16 of the upper stocker 14 and the lower stocker 15 preferably corresponds to the number of positioning holes 13 on the jaws 7 which will be described later, to ensure that the jaws 7 accurately hold and place the chips Frame 9.
  • the number of the positioning holes 13 of the jaws 7 is three; as shown in FIGS. 8 and 9 , the upper material storage device 14 and the lower material storage device 15
  • the number of slots 16 is also three.
  • the liquid storage tank 18 is disposed below the liquid discharge hole 17 for receiving the liquid discharged from the liquid discharge hole 17.
  • the liquid storage case 18 in this embodiment is formed into a drawer type case, and can be taken out when the liquid storage case 18 is filled with liquid or the gene sequencing reaction device 1 is stopped.
  • the upper material storage device 14 and the lower material storage device 15 of the gene sequencing reaction device 1 in the present embodiment each include a storage box and a liquid storage case 18, in other embodiments not shown.
  • the specific structure of the upper material storage device 14 and the lower material storage device 15 can also be set in other manners.
  • the structures of the upper stocker 14 and the lower stocker 15 may be the same or different.
  • neither the upper stocker 14 nor the lower stocker 15 are necessary.
  • the sequencing chip 2 after the sequencing chip 2 is mounted on the chip holding device, it can be directly placed in the corresponding immersion reaction zone of the first reaction step of the gene sequencing reaction without setting the upper material storage device 14.
  • the sequencing chip 2 after the sequencing chip 2 completes the sequencing reaction, it can be directly sent to an external optical imaging device for imaging without setting the lower material storage device 15.
  • the container lid 4 is openably and closably covered on the soaking container to prevent evaporation of chemical agents.
  • the container lid 4 comprises a plurality of lids, each lid being adapted to correspond to one or more soaking reaction zones to prevent chemistry in the corresponding soaking reaction zone.
  • the reagent was evaporated.
  • the covers can be opened and closed independently of the other covers.
  • the container cover 4 includes two rows of covers, and the number of each cover is six. Each cover is covered on a plurality of soaking cylinders 3.
  • the clamshell mechanism 22 is drivingly coupled to the container lid 4 to drive the container lid 4 to open and close.
  • the flip mechanism 22 is provided on the support platform 8.
  • the flip mechanism 22 includes a push-pull rod 26 corresponding to the cover body.
  • the push-pull rod 26 is connected to the cover body of the container cover 4 .
  • the cover body is opened, and when the push-pull rod 26 pushes the cover body, The cover is closed.
  • the transfer device 6 is used to insert or remove the sequencing chip 2 from the soak reaction zone.
  • the transfer device 6 is used to move the sequencing chip 2 to insert the sequencing chip 2 into each immersion reaction zone or to withdraw from each immersion reaction zone.
  • the transfer device 6 of the present embodiment can move the sequencing chip 2 in any one of the soaking tanks 3 into another soaking tank 3.
  • the sequencing chip 2 to be subjected to the gene sequencing reaction may be placed in the slot 16 of the upper material storage device 14 by another external transfer device, or the sequencing chip 2 may be manually placed in the upper material storage device 14. In slot 16. Similarly, the sequencing chip 2 that has undergone the gene sequencing reaction can be taken away by another external transfer device, or the sequencing chip 2 can be manually removed.
  • the setting of the transfer device 6 can improve the automation degree of the gene sequencing reaction device 1, reduce the error rate caused by the manual operation, and can accurately control the soaking sequence and the soaking time by cooperation with the control device 23, thereby facilitating the high-quality completion of the gene sequencing. reaction.
  • the transfer device 6 is used to move the sequencing chip 2, including a connection portion for connection with the sequencing chip 2 and a motion mechanism for drivingly connecting with the connection portion to change the working position of the connection portion.
  • the transfer device 6 is mounted on a support platform 8. In other embodiments not shown, the transfer device 6 can also be mounted on other supports as long as the function of connecting and moving the sequencing chip 2 can be achieved.
  • the moving mechanism includes a lateral moving mechanism 19, a longitudinal moving mechanism 20, and a vertical moving mechanism 21.
  • the longitudinal moving mechanism 20 is disposed on the support platform 8.
  • the lateral movement mechanism 19 is provided on the longitudinal movement mechanism 20.
  • the vertical movement mechanism 21 is provided on the lateral movement mechanism 19.
  • the connecting portion is provided on the vertical moving mechanism 21.
  • the longitudinal moving mechanism 20 drives the lateral movement mechanism 19 to move longitudinally.
  • the lateral movement mechanism 19 drives the vertical movement mechanism 21 to move laterally.
  • the vertical moving mechanism 21 drives the vertical movement of the connecting portion.
  • the connecting portion in this embodiment includes a jaw 7 for holding the sequencing chip 2.
  • the plurality of dip tanks 3 are arranged in two rows in the lateral direction.
  • the longitudinal movement machine The combination of the structure 20 and the vertical movement mechanism 21 ensures that the jaws 7 can insert and withdraw the sequencing chip 2 from any one of the soaking cylinders 3.
  • each of the immersion cylinders 3 may also be arranged in a ring shape.
  • the movement mechanism may include a slewing mechanism.
  • the connection portion may also be in other forms, for example, a vacuum chuck, an electromagnetic chuck, or the like that cooperates with a chip holding device for supporting the sequencing chip 2.
  • the moving soaking container can also be relied upon solely. Or moving the soaking container and the sequencing chip 2 at the same time to achieve a desired change in the positional relationship between the sequencing chip 2 and the infusion container.
  • the chip holding device is used to fix the sequencing chip 2, so that the sequencing chip 2 moves along with the chip holding device.
  • the chip holding device includes one or more chip mounting locations 24 that are mounted to the chip mounting location 24 to move the sequencing chip 2 by the mobile chip holding device.
  • the chip holding device can reduce the pollution caused by directly operating the sequencing chip 2 on the one hand, and can simultaneously move the plurality of sequencing chips 2 and keep the plurality of sequencing chips 2 at a predetermined interval through the chip holding device as needed, thereby improving the sequencing chip. 2 flux.
  • the bilateral surface of the sequencing chip 2 has a DNA sample loading structure.
  • the chip mounting position 24 includes a chip mounting port, the sequencing chip 2 is mounted in the chip mounting port, and the chip mounting port is a double-opened port. This arrangement enables soaking of both sides of the sequencing chip 2, which can increase the number of DNA sample molecules loaded by the single-chip sequencing chip 2.
  • the chip frame 9 is transferred between different soaking cylinders 3. In order to minimize the cross-contamination between different chemical reagents, it is generally required that the liquid remaining on the surface of the chip frame 9 is drained and then transferred to the next soaking tank 3. . In order to speed up the liquid dripping speed on the surface of the chip frame 9, as shown in FIGS. 4 to 7, in the present embodiment, the lower end of the chip frame 9 is gradually tapered from top to bottom. In an alternative embodiment, the surface of the chip frame 9 can be provided as a hydrophobic surface. It is of course also possible to make the surface of the chip frame 9 a hydrophobic surface while the chip frame 9 has a lower end which tapers from top to bottom, thereby achieving faster dripping of the chemical agent.
  • the upper end of the chip frame 9 is provided with a bayonet 10; the moving mechanism of the transfer device 6 is drivingly coupled to the jaws 7 to change the working position of the jaws 7, and the jaws 7 are used for the chip frame 9 connection.
  • the clamping jaw 7 includes a positioning frame 11 and a clamping block 12.
  • the positioning frame 11 is connected to the moving mechanism, and the clamping block 12 is movably disposed on the positioning frame 11.
  • the positioning frame 11 is provided with an upper end for inserting the chip frame 9. Positioning The hole 13 and the jaw 7 are engaged with the bayonet 10 of the chip frame 9 inserted into the positioning hole 13 to sandwich the chip frame 9.
  • each chip frame 9 is provided with two bayonet ports 10 oppositely.
  • the jaws 7 are also correspondingly provided with two opposing jaws 12.
  • Two clamp blocks 12 are located at the upper end of the positioning hole 13. After the chip frame 9 passes upward through the positioning hole 13, the two clamping blocks 12 move relative to each other and are respectively inserted into the two mounting openings 10 of the chip frame 9, and the chip frame 9 is fixed in the positioning hole 13.
  • the positioning frame 11 of the present embodiment is designed with three positioning holes 13 which are arranged equidistantly. In other embodiments not shown, the number of positioning holes 13 may be set to be more or less, for example, may be set to 1, 2, 4, 5, etc., to simultaneously operate a corresponding number of sequencing chips. 2.
  • the number and position of the immersion reaction zones and the number and position of the slots 16 vary depending on the number of locating holes 13.
  • the jaws 7 of the transfer device 6 indirectly sandwich the sequencing chip 2 by the chip holding device to realize the connection between the transfer device 6 and the sequencing chip 2. Indirect clamping of the sequencing chip 2 prevents cross-contamination of the jaws 7 after clamping the different sequencing chips 2.
  • the clamping jaws 7 indirectly clamp the sequencing chip 2 by clamping the chip frame 9, and only need to process the clamping structure on the chip frame 9, without processing the clamping structure on the sequencing chip 2, thereby reducing the processing of the sequencing chip 2. The cost also maximizes the surface area of the sequencing chip 2.
  • the transfer device 6 and the sequencing chip 2 may be connected by directly clamping the sequencing chip 2 with the jaws 7.
  • the gene sequencing reaction device 1 comprises a protective cover, and the soaking container is disposed in the protective cover.
  • the sequencing reaction process can be completely open if environmental conditions permit, such as when operating in a sterile environment. However, in many cases, in order to avoid external interference, the sequencing reaction process needs to be carried out in a closed environment.
  • the soaking container is placed inside the protective cover to provide a closed reaction environment to ensure the quality of the gene sequencing reaction.
  • the transfer device 6 can also be selected or not disposed in the protective cover as needed.
  • the blowing device 25 is for blowing off the surface of the sequencing chip 2 and/or the chemical agent on the surface of the chip holding device on which the sequencing chip is mounted.
  • the air blowing device 25 is used to blow off residual chemical reagents on the surface of the sequencing chip 2 and the chip frame 9.
  • the air blowing device 25 includes a nozzle.
  • the nozzle is used to eject the gas, and the ejected gas blows off the residual chemical reagents on the surface of the sequencing chip 2 and the chip frame 9.
  • the control device 23 is used to control and monitor the operation of the gene sequencing reaction device 1.
  • the control device 23 is coupled to the temperature control device 5 to control the temperature of the chemical reagent, and is also coupled to the transfer device 6 to control the sequencing core.
  • control device 23 is a built-in control device and is disposed on the support platform 8.
  • an external control device can also be coupled to the gene sequencing reaction device 1 to control and monitor the operation of the gene sequencing reaction device 1.
  • the control device 23 By controlling the temperature control device 5 and the transfer device 6 by the control device 23, the automated operation of the gene sequencing reaction device 1 can be realized, and the quality and efficiency of gene sequencing can be improved.
  • the support platform 8 in this embodiment is a cabinet.
  • the aforementioned soaking container, the temperature control device 5, the transfer device 6, the upper material storage device 14, the lower material storage device 15, the container cover 4, the flip mechanism 22, the air blowing device 25, and the control device 23 are all disposed on the top of the cabinet.
  • the reagents and tools required for the gene sequencing reaction can be stored and stored in the cabinet.
  • casters 27 are mounted under the cabinet.
  • the support platform 8 can also be a support plate.
  • a signal lamp 28 can be added to the gene sequencing reaction device 1 for alarming when an abnormality occurs in the gene sequencing reaction device 1.
  • a chemical reagent for gene sequencing reaction is loaded in each of the immersion reaction zones, and the transfer device 6 holds a set of sequencing chips 2 and soaks in a set of immersion reaction zones for a period of time, and then the set of sequencing chips 2 Transfer to the next set of soaking reaction zones for a period of time, and cycle accordingly.
  • the sequencing chips 2 of the sequencing chip 2 of the group can be subjected to a sequencing reaction process after being immersed in a plurality of immersion reaction zones.
  • the sequencing chip is clamped in groups of three, and can be numbered from right to left as No. 1 chip, No. 2 chip, No. 3 chip, and soaking tank 3 from The rear row starts from right to left and is numbered to the last one, and then continues from the front row from left to right to the last one, which is the No. 1 soaking tank (the far right side of the rear row), the No. 2 soaking tank, and the No. 3 soaking tank. , ..., No. 17 soaking tank (the left side of the rear row), No. 18 soaking tank (the left side of the front row), No. 19 soaking tank, ..., No. 34 soaking tank (the far right side of the front row).
  • the No. 3 chip When starting the gene sequencing reaction, the No. 3 chip is immersed in the No. 1 soaking tank; after soaking for a predetermined time, the No. 3 chip is transferred to the No. 2 soaking tank to continue to soak, and at the same time, the No. 2 chip is immersed in the No. 1 soaking tank to start soaking and soaking. After the scheduled time, transfer the No. 3 chip to the No. 3 soaking tank and continue to soak. At the same time, the No. 2 chip is immersed in the No. 2 soaking tank to continue to soak, and the No. 1 chip is immersed in the No. 1 soaking tank to start soaking.
  • the sequencing chips 2 are sequentially transferred to the soaking cylinders larger than the number of the respective soaking cylinders to continue to soak until all the sequencing chips 2 are in the respective soaking cylinders.
  • the corresponding soaking process is completed.
  • the soaking process in the soaking tanks of No.16 ⁇ 17, the soaking tanks of No.18 ⁇ 19 and the soaking tanks of No.33 ⁇ 34 is similar to the process of soaking in the soaking tank of No.1 ⁇ 2, which can make the part
  • the sequencing chip 2 is soaked and part of the sequencing chip 2 does not participate in the soaking.
  • one of the soaking cylinders or the plurality of soaking cylinders of the head and/or the tail of the at least one row of the soaking cylinders (the specific number can be set according to the number of sequencing chips per clamping) as an empty container. Or place the same chemical reagents as the adjacent soaking tanks or place reagents that have no effect on the gene sequencing reaction so that the sequencing chip 2 that does not participate in the soaking is also in the soaking tank.
  • the soaking tanks (or soaking reaction zones) can also be grouped, for example, the soaking tanks (or soaking reaction zones) can be grouped by the number of sequencing chips held each time, and each set of soaking tanks (or The soaking reaction zone holds the same chemical reagent, and each time it is immersed, a set of sequencing chips are immersed in a set of soaking cylinders containing the same chemical reagent.
  • This setup can increase the efficiency of the gene sequencing reaction, but requires more soaking tanks (or soaking reaction zones).
  • the gene sequencing system of the present embodiment includes a DNA sample loading device and a gene sequencing reaction device 1, and the gene sequencing reaction device 1 is the aforementioned gene sequencing reaction device 1.
  • the gene sequencing reaction method of the embodiment comprises: adding a chemical reagent for gene sequencing reaction in the immersion reaction zone of the immersion container; controlling the temperature of the chemical reagent in the immersion reaction zone; and having the DNA sample loading structure on the surface and loading the DNA sample
  • the sequencing chip 2 is immersed in the chemical reagent for a predetermined time and taken out.
  • different genetic sequencing reaction chemicals are added to the plurality of immersion reaction zones, and the sequencing chips 2 are sequentially immersed in the plurality of immersion reaction zones in a predetermined order for a predetermined time.
  • the chemical reagent for gene sequencing reaction is carried in the soaking tank 3, the heat conductive liquid in the water bath is adjusted to a suitable temperature, and the sequencing chip 2 to be subjected to the gene sequencing reaction is mounted on the chip frame 9, all the chips The frame 9 is placed into the upper stocker 14.
  • the jaws 7 of the transfer device 6 hold the chip frame 9 and cause the chip frames 9 to be immersed in the soaking cylinders 3 for a period of time; when the chip frames 9 are completely soaked in a row of the soaking tanks 3, the longitudinal movement is performed.
  • the mechanism 20 drives the lateral movement mechanism 19 to move longitudinally so that each chip frame 9 can be immersed one by one in the other row of soaking cylinders 3 until all the soaking tanks 3 are soaked.
  • the transfer device 6 places the chip frame 9 into the lower material storage device 15, and the DNA sample on the sequencing chip 2 completes the sequencing reaction process and waits for removal.
  • the DNA sample on the sequencing chip 2 completes the sequencing reaction process, it is transferred to an optical imaging device for imaging.
  • the gene sequencing system and the gene sequencing reaction method of the present invention have similar technical effects as the gene sequencing reaction device 1 of the present invention.
  • the gene sequencing reaction device 1 can be used to achieve a gene sequencing reaction by soaking.
  • the chemical reagents in the immersion reaction zone can be reused, thereby reducing the cost of consumables.
  • the method of immersion does not have the problem of uneven liquid flow rate, and the surface of the sequencing chip 2 is less likely to generate bubbles, which can ensure a more uniform and sufficient chemical reaction.
  • the liquid pressure received by the sequencing chip 2 in the immersion tank 3 is uniform and uniform in heat, so that deformation does not occur.
  • Multiple sequencing chips 2 can be immersed at the same time, which has the advantage of high throughput.
  • the gene sequencing reaction device 1 is automatically controlled by the control device 23 to realize an automated operation.

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Abstract

一种基因测序反应设备、基因测序系统和基因测序反应方法。基因测序反应设备包括支撑平台(8)；浸泡容器，设置于所述支撑平台(8)上，所述浸泡容器具有浸泡反应区，所述浸泡反应区用于盛放基因测序反应用化学试剂并用于将表面具有DNA样品加载结构且已加载有DNA样品的测序芯片(2)浸泡于所述化学试剂中进行基因测序反应；温控装置，用于控制所述浸泡反应区的化学试剂的温度；转移装置，用于将所述测序芯片(2)插入所述浸泡反应区或从所述浸泡反应区中抽离。该基因测序反应设备可以通过将测序芯片浸泡于化学试剂的方式实现基因测序反应过程。

Description

基因测序反应设备、基因测序系统和基因测序反应方法 技术领域
本发明涉及基因测序技术领域，特别涉及一种基因测序反应设备、基因测序系统和基因测序反应方法。
背景技术
按照目前的技术水平，基因测序(也可以称为DNA测序)前需要将DNA样品分子(测序反应模板)加载到测序芯片上，然后进一步完成基因测序反应向测序反应模板加入核苷酸，通过检测加入核苷酸的类型，就能够检测出基因的序列。
中国实用新型专利CN205133580U提供了一种目前普遍使用的测序芯片，芯片设有内部流道，不同的化学试剂从入口注入流道，流经流道后由出口排出，无论是DNA样品的加载还是测序，都需要实施上述过程。这种传统的测序芯片，DNA样品加载至其流道表面之后，就要注入测序试剂，使DNA样品发生测序化学反应，它具有以下不足：
(1)化学试剂只能使用一次，导致测序成本高昂；
(2)化学试剂在流道内的流速不均匀，也容易存在化学试剂无法流到的角落，这将导致化学反应不均匀、不充分，从而容易发生基因测序错误的问题；而且流动的化学试剂容易将已加载至芯片表面的DNA分子冲落；
(3)化学试剂在流道内产生的压强容易导致芯片表面出现压塌的现象，芯片表面变形将增加DNA测序的错误率；
(4)芯片的硅表面可利用面积只有流道内的部分，其它部分无法有效利用，导致硅片不能最大程度被利用。
发明内容
本发明的目的在于提供一种利用浸泡方式实现基因测序反应的基因测序反应设备、基因测序系统和基因测序反应方法。
本发明第一方面提供一种基因测序反应设备，包括：支撑平台；浸泡容器，设置于所述支撑平台上，所述浸泡容器具有浸泡反应区，所述浸泡反应区用于盛放基因测 序反应用化学试剂并用于将表面具有DNA样品加载结构且已加载有DNA样品的测序芯片浸泡于所述化学试剂中进行基因测序反应；温控装置，用于控制所述浸泡反应区的化学试剂的温度；转移装置，用于将所述测序芯片插入所述浸泡反应区或从所述浸泡反应区中抽离。
进一步地，所述基因测序反应设备包括多个所述浸泡容器；和/或，所述浸泡容器包括彼此隔离的多个所述浸泡反应区。
进一步地，所述浸泡容器包括溢流口。
进一步地，所述温控装置包括温度控制部和水浴锅，所述水浴锅用于盛放能够传递热量的液体，所述浸泡容器设置于所述水浴锅中，所述温度控制部控制所述水浴锅内的液体的温度以控制所述浸泡反应区内的化学试剂的温度。
进一步地，所述基因测序反应设备还包括：上件储料装置，用于放置待进行基因测序反应的所述测序芯片；和/或，下件储料装置，用于放置已完成基因测序反应的所述测序芯片。
进一步地，所述上件储料装置和/或所述下件储料装置包括：储料盒，所述储料盒的顶部敞口并具有插槽和排液孔，所述插槽用于定位放置所述测序芯片，所述排液孔设于所述储料盒的底壁上，用于排出所述储料盒内的液体；和，储液盒，设置于所述排液孔的下方，用于承接所述排液孔排出的液体。
进一步地，所述基因测序反应设备还包括容器盖，所述容器盖可开闭地盖设于所述浸泡容器上以防止所述化学试剂蒸发。
进一步地，所述容器盖包括多个盖体，每个所述盖体用于与一个或多个所述浸泡反应区对应设置以防止对应的浸泡反应区内的化学试剂蒸发，且至少一个所述盖体相对于其它盖体可独立地开闭。
进一步地，所述基因测序反应设备还包括翻盖机构，所述翻盖机构与所述容器盖驱动连接以驱动所述容器盖开闭。
进一步地，所述转移装置包括用于与所述测序芯片连接的连接部和与所述连接部驱动连接以改变所述连接部的工作位置的运动机构。
进一步地，所述多个浸泡反应区沿横向排列成一排或多排；所述运动机构包括横向移动机构、纵向移动机构和竖向移动机构，所述纵向移动机构设于所述支撑平台上，所述横向移动机构设于所述纵向移动机构上，所述竖向移动机构设于所述横向移动机 构上，所述连接部设于所述竖向移动机构上，所述纵向移动机构驱动所述横向移动机构纵向运动，所述横向移动机构驱动所述竖向移动机构横向运动，所述竖向移动机构驱动所述连接部竖向运动。
进一步地，所述基因测序反应设备还包括芯片固持装置，所述芯片固持装置包括一个或多个芯片安装位，所述测序芯片安装于所述芯片安装位以通过移动所述芯片固持装置移动所述测序芯片。
进一步地，所述测序芯片的双侧表面具有所述DNA样品加载结构；所述芯片安装位包括芯片安装口，所述测序芯片安装于所述芯片安装口内，所述芯片安装口为双侧敞开的通口。
进一步地，所述芯片固持装置包括芯片框架，所述芯片框架上设置有所述芯片安装位，所述芯片框架的表面为疏水表面和/或所述芯片框架的下端从上至下逐渐变尖。
进一步地，所述芯片固持装置包括芯片框架，所述芯片框架上设置有一个或多个所述芯片安装位，所述芯片框架的上端设置有卡口；所述转移装置包括用于与所述芯片框架连接的夹爪和与所述夹爪驱动连接以改变所述夹爪的工作位置的运动机构，所述夹爪包括定位架和夹块，所述定位架与所述运动机构连接，所述夹块可移动地设置于所述定位架上，所述定位架上设有供所述芯片框架上端插入的定位孔，所述夹爪与插入所述定位孔的所述芯片框架的卡口卡接以夹持所述芯片框架。
进一步地，所述基因测序反应设备还包括控制装置，其中，所述控制装置与所述温控装置耦合以控制所述化学试剂的温度；和/或，所述控制装置与所述转移装置耦合以控制所述测序芯片在所述浸泡反应区内的浸泡时间和/或浸泡次序。
进一步地，所述基因测序反应设备包括所述测序芯片，所述测序芯片的表面具有DNA样品加载结构。
进一步地，所述基因测序反应设备包括保护罩，所述浸泡容器罩设于所述保护罩内。
进一步地，所述基因测序反应设备包括用于吹除所述测序芯片表面和/或安装所述测序芯片的芯片固持装置表面的化学试剂的吹气装置。
本发明第二方面提供一种基因测序系统，包括DNA样品加载设备和基因测序反应设备，所述基因测序反应设备为根据本发明第一方面中任一项所述的基因测序反应设备。
本发明第三方面提供一种基因测序反应方法，所述基因测序反应方法包括：在浸泡容器的浸泡反应区内加入基因测序反应用化学试剂；控制浸泡反应区内的所述化学试剂的温度；将表面具有DNA样品加载结构并加载有DNA样品的测序芯片浸泡于所述化学试剂预定时间后取出。
进一步地，所述基因测序反应方法包括：在多个浸泡反应区内加注不同的基因测序反应用化学试剂，按预定顺序将所述测序芯片顺次在所述多个浸泡反应区内浸泡预定时间。
基于本发明提供的基因测序反应设备，其浸泡容器具有浸泡反应区，浸泡反应区用于盛放基因测序反应用化学试剂并用于将表面具有DNA样品加载结构且已加载有DNA样品的测序芯片浸泡于化学试剂中进行基因测序反应；其温控装置用于控制浸泡反应区的温度；其转移装置，用于将测序芯片插入浸泡反应区或从浸泡反应区中抽离。使用该基因测序反应设备能采用浸泡方式实现基因测序反应。
测序芯片在不同浸泡反应区的化学试剂中浸泡，能够完成测序反应所需的各个步骤。
浸泡反应区中的化学试剂可以重复利用，从而可以降低耗材成本。
浸泡方式不存在液体流速不均匀的问题，测序芯片表面不易产生气泡，可以保证化学反应更均匀、更充分。
测序芯片在浸泡缸内所受的液体压强均匀、受热均匀，因此不会发生变形的现象。
没有复杂的流体系统，零部件少，装配容易，制造成本低。可以同时浸泡多张测序芯片，具有通量高的优势。
基因测序反应设备由控制装置自动控制，可实现自动化作业。
本发明的基因测序系统和基因测序反应方法具有与本发明的基因测序反应设备类似的技术效果。
通过以下参照附图对本发明的示例性实施例的详细描述，本发明的其它特征及其优点将会变得清楚。
附图说明
此处所说明的附图用来提供对本发明的进一步理解，构成本申请的一部分，本发明的示意性实施例及其说明用于解释本发明，并不构成对本发明的不当限定。在附图 中：
图1是本发明实施例中基因测序反应设备的立体结构示意图；
图2是图1中的基因测序反应设备移除容器盖后的立体结构示意图；
图3是图1所示的基因测序反应设备的另一角度的立体结构示意图；
图4是图1所示的基因测序反应设备的转移装置的夹爪、测序芯片和芯片固持装置的立体结构示意图。
图5是图4所示的转移装置的夹爪、测序芯片和芯片固持装置的另一角度的立体结构示意图。
图6是图4所示的转移装置的夹爪、测序芯片和芯片固持装置的分解结构示意图。
图7是图4所示的转移装置的夹爪、测序芯片和芯片固持装置的另一角度的分解结构示意图。
图8是图1所示的基因测序反应设备的上件储料装置(下件储料装置)的立体结构示意图；
图9是图8所示的上件储料装置(下件储料装置)的分解结构示意图；
图10是图1所示的基因测序反应设备的浸泡缸的立体结构示意图；
图11是图1所示的基因测序反应设备的I部放大结构示意图。
图1至图11中，各附图标记分别代表：
1、基因测序反应设备；2、测序芯片；3、浸泡缸；4、容器盖；5、温控装置；6、转移装置；7、夹爪；8、支撑平台；9、芯片框架；10、卡口；11、定位架；12、夹块；13、定位孔；14、上件储料装置；15、下件储料装置；16、插槽；17、排液孔；18、储液盒；19、横向移动机构；20、纵向移动机构；21、竖向移动机构；22、翻盖机构；23、控制装置；24、芯片安装位；25、吹气装置；26、推拉杆；27、脚轮；28、信号灯；29、溢流口。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。以下对至少一个示例性实施例的描述实际上仅仅是说明性的，决不作为对本发明及其应用或使用的任何限制。基于本发明中的实施例，本领域普通技术人员在没有作出创 造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
除非另外具体说明，否则在这些实施例中阐述的部件和步骤的相对布置、数字表达式和数值不限制本发明的范围。同时，应当明白，为了便于描述，附图中所示出的各个部分的尺寸并不是按照实际的比例关系绘制的。对于相关领域普通技术人员已知的技术、方法和设备可能不作详细讨论，但在适当情况下，所述技术、方法和设备应当被视为授权说明书的一部分。在这里示出和讨论的所有示例中，任何具体值应被解释为仅仅是示例性的，而不是作为限制。因此，示例性实施例的其它示例可以具有不同的值。应注意到：相似的标号和字母在下面的附图中表示类似项，因此，一旦某一项在一个附图中被定义，则在随后的附图中不需要对其进行进一步讨论。
在本发明的描述中，需要理解的是，使用“第一”、“第二”等词语来限定零部件，仅仅是为了便于对相应零部件进行区别，如没有另行声明，上述词语并没有特殊含义，因此不能理解为对本发明保护范围的限制。
在本发明的描述中，需要理解的是，方位词如“前、后、上、下、左、右”、“横向、竖向、垂直、水平”和“顶、底”等所指示的方位或位置关系通常是基于附图所示的方位或位置关系，仅是为了便于描述本发明和简化描述，在未作相反说明的情况下，这些方位词并不指示和暗示所指的装置或元件必须具有特定的方位或者以特定的方位构造和操作，因此不能理解为对本发明保护范围的限制；方位词“内、外”是指相对于各部件本身的轮廓的内外。
以下描述中使用的“横向”指图1至图3所示的基因测序反应设备1的左右方向、“纵向”指图1至图3所示的基因测序反应设备1的前后方向、“竖向”指图1至图3所示的基因测序反应设备1的上下方向。
图1至图11示出了本发明实施例的基因测序反应设备1的结构。如图1至图11所示，本发明实施例公开了一种基因测序反应设备1。该基因测序反应设备1包括支撑平台8、浸泡容器、温控装置5和转移装置6。浸泡容器设置于支撑平台8上。浸泡容器具有浸泡反应区，浸泡反应区用于盛放基因测序反应用化学试剂并用于将表面具有DNA样品加载结构且已加载有DNA样品的测序芯片2浸泡于化学试剂中进行基因测序反应。温控装置5用于控制浸泡反应区的化学试剂的温度。转移装置6用于将测序芯片2插入浸泡反应区或从浸泡反应区中抽离。
本实施例中的DNA样品是一种测序反应模板，标记的核苷酸可加入到测序反应模 板中。
基于本发明提供的基因测序反应设备1能采用浸泡方式实现基因测序反应。测序芯片2在不同浸泡反应区的化学试剂中浸泡，能够完成测序反应所需的各个步骤。浸泡反应区中的化学试剂可以重复利用，从而可以降低耗材成本。浸泡方式不存在液体流速不均匀的问题，测序芯片2表面不易产生气泡，可以保证化学反应更均匀、更充分。测序芯片2在浸泡反应区内所受的液体压强均匀、受热均匀，因此不会发生变形的现象。没有复杂的流体系统，零部件少，装配容易，制造成本低。可以同时浸泡多张测序芯片2，具有通量高的优势。基因测序反应设备1由控制装置23自动控制，可实现自动化作业。
以下结合图1至图11详细说明本发明实施例。
如图1至图11所示，本发明实施例的基因测序反应设备1包括测序芯片2、浸泡容器、温控装置5、转移装置6、芯片固持装置、上件储料装置14、下件储料装置15、容器盖4、翻盖机构22、吹气装置25、控制装置23和支撑平台8。
测序芯片2表面具有DNA样品加载结构，在进行基因测序反应前，测序芯片2的DNA样品加载结构上已加载有DNA样品。本实施例中，测序芯片2是一块硅片，在硅片的双侧表面上均预设了可以捕获DNA分子的接头。DNA分子通过一系列化学反应后就能够被这些接头捕获，最终粘附在硅片表面。接头例如可以通过氨基对硅片表面修饰形成。基因测序反应期间，DNA样品始终粘附于测序芯片2上。
本实施例所称的DNA样品可以是美国专利US8445197B2所公开的一种纳米球分子，亦可称为DNB。其中，基因组DNA首先经过片段化处理，再加上接头序列，并环化形成单链环状DNA，随后使用滚环扩增技术将单链环状DNA扩增2至3个数量级，成为DNB。
浸泡容器具有浸泡反应区，浸泡反应区用于盛放基因测序反应用化学试剂并用于将表面具有DNA样品加载结构且已加载有DNA样品的测序芯片2浸泡于化学试剂中进行基因测序反应。测序芯片2在浸泡反应区中浸泡于基因测序反应用化学试剂中以完成基因测序反应的步骤。温控装置5能够控制浸泡反应区的化学试剂温度，从而为基因测序反应提供合适的温度条件。
本实施例中，基因测序反应设备1包括多个浸泡容器。如图1至图3所示，浸泡容器具体地为浸泡缸3。每个浸泡缸3具有一个浸泡反应区。多个浸泡缸3排列设置 于温控装置5上。温控装置5设于支撑平台8上。转移装置6可将测序芯片2插入和从浸泡缸3中抽离。本实施例中，每个浸泡缸3装入一种化学试剂，不同的浸泡缸中装入每个基因测序环节所需的化学试剂。转移装置6夹持测序芯片2在各个浸泡缸3中浸泡预定时间后，就能够将核苷酸加入到测序芯片2的DNA样品(测序反应模板)上。之后，将测序芯片2放置到外部的光学成像装置上成像，就能够检测出加入的核苷酸类型。不断循环上述步骤，就能够读取出基因的序列。
在其它未示出的实施例中，也可以将浸泡缸3分组，每组浸泡缸装入一种化学试剂。
参考图1至图3。本实施例中，基因测序反应设备1包括横向布置的两排浸泡缸3，每排浸泡缸3的数量为17个。
在其它未图示的实施例中，浸泡容器也可以包括彼此隔离的多个浸泡反应区，每个或每组浸泡反应区装入一种化学试剂。
如图10所示，本实施例中，浸泡缸3包括溢流口29。当浸泡缸3内的液体超过一定水位时从溢流口29溢出，从而可以防止浸泡缸3内的液位超高。
温控装置5用于控制浸泡反应区的化学试剂的温度。温控装置5设置于支撑平台8上，浸泡容器通过温控装置5设置于支撑平台8上。
本实施例中，如图1至图3所示，温控装置5包括温度控制部和水浴锅。水浴锅用于盛放能够传递热量的液体。浸泡容器设置于水浴锅中。温度控制部控制水浴锅内的液体的温度以控制浸泡容器内的化学试剂的温度。
本实施例中，温度控制部为设置于水浴锅的锅壁内的换热管，换热管可以向水浴锅内的液体输入热量或从水浴锅内的液体吸走热量，从而水浴锅中的导热液体可以随之升温或降温。
通过对水浴锅的锅壁或对水浴锅内的液体输入或输出热量，水浴锅中的导热液体可以随之升温或降温，浸泡缸3浸泡在导热液体中，从而能够控制浸泡缸3内化学试剂的温度。采用液体作为导热介质，可以更均匀地控制各浸泡缸3内的化学试剂的温度。而且，化学试剂温度更加稳定，不易快速变化。
在其它未示出的实施例中，也可以采用温控器(例如珀耳贴温控器)对浸泡缸3或其内液体进行直接加热或冷却的直接温控方式，但直接温控方式与利用水浴锅间接温控的方式相比易发生冷热不均的现象。
上件储料装置14用于放置待进行基因测序反应的测序芯片2。下件储料装置15用于放置已进行基因测序反应的测序芯片2。
如图8和图9所示，本实施例中，上件储料装置14和下件储料装置15均包括储料盒和储液盒18。储料盒的顶部敞口并具有插槽16和排液孔17。插槽16设置于所述储料盒的侧壁内表面，用于定位放置测序芯片2。排液孔17设于储料盒的底壁，用于排出储料盒内的液体。本实施例中，排液孔17可以排走芯片框架9和测序芯片2表面流下的化学试剂。
本实施例中，在基因测序反应过程中，测序芯片2安装于芯片框架9上，通过移动芯片框架9移动测序芯片2。其中，插槽16用于定位放置芯片框架9以通过芯片框架9定位和放置测序芯片2。芯片框架9插装于插槽16中即可将其上的测序芯片2定位和放置于储料盒内。
上件储料装置14和下件储料装置15的插槽16的数量优选地与后面将描述的夹爪7上的定位孔13的数量对应，以保证夹爪7准确地夹持和放置芯片框架9。如图4至图7所示，本实施例中，夹爪7的定位孔13的数量为三个；如图8和图9所示，上件储料装置14和下件储料装置15的插槽16数量也各为三个。
储液盒18设置于排液孔17的下方，用于承接排液孔17排出的液体。本实施例中的储液盒18制成抽屉式盒体，当储液盒18装满液体后或基因测序反应设备1停止使用时可以将其取出倒掉。
需要说明的是，虽然本实施例中基因测序反应设备1的上件储料装置14和下件储料装置15均包括储料盒和储液盒18，但在其它未图示的实施例中，上件储料装置14和下件储料装置15的具体结构也可以设置为其它方式。上件储料装置14和下件储料装置15的结构可以相同也可以不同。
另外，上件储料装置14和下件储料装置15均不是必须的。例如，在测序芯片2安装于芯片固持装置上后，可直接置于基因测序反应第一个反应环节对应的浸泡反应区内，而无需设置上件储料装置14。再例如，在测序芯片2完成测序反应后，可以直接送至外部的光学成像装置上成像，而无需设置下件储料装置15。
容器盖4可开闭地盖设于浸泡容器上以防止化学试剂蒸发。
如图1、图2和图11所示，优选地，容器盖4包括多个盖体，每个盖体用于与一个或多个浸泡反应区对应设置以防止对应的浸泡反应区内的化学试剂蒸发。至少一 个盖体相对于其它盖体可独立地开闭。本实施例中，对应于两排浸泡缸3，容器盖4包括两排盖体，每排盖体的数量为六个。每个盖体盖在若干个浸泡缸3上。
翻盖机构22与容器盖4驱动连接以驱动容器盖4开闭。如图1至图3所示，该翻盖机构22设于支撑平台8上。另外参见图11，翻盖机构22包括与盖体对应设置的推拉杆26，推拉杆26与容器盖4的盖体连接，推拉杆26拉动盖体时盖体开启，推拉杆26推动盖体时，盖体关闭。
转移装置6用于将测序芯片2插入浸泡反应区或从浸泡反应区中抽离。本实施例中，转移装置6用于移动测序芯片2以将测序芯片2插入各浸泡反应区或从各浸泡反应区中抽离。
本实施例的转移装置6可以将任一个浸泡缸3中的测序芯片2移动到另一个浸泡缸3内。
本实施例中，待进行基因测序反应的测序芯片2可由外部另一个转移装置放入上件储料装置14的插槽16中，也可以人工将测序芯片2放入上件储料装置14的插槽16中。同样地，已进行基因测序反应的测序芯片2可由外部另一个转移装置将它们取走，也可以人工将测序芯片2取走。
转移装置6的设置可以提高基因测序反应设备1的自动化程度，减少人工操作引起的失误率，还可以通过与控制装置23的配合精确控制浸泡顺序和浸泡时间，从而有利于高质量地完成基因测序反应。
本实施例中，转移装置6用于移动测序芯片2，包括用于与测序芯片2连接的连接部和与连接部驱动连接以改变连接部的工作位置的运动机构。
转移装置6安装在支撑平台8上。在其它未图示的实施例中，转移装置6也可以安装在其他支撑物上，只要能够实现连接和移动测序芯片2的功能即可。
本实施例中，如图1至图3所示，运动机构包括横向移动机构19、纵向移动机构20和竖向移动机构21。纵向移动机构20设于支撑平台8上。横向移动机构19设于纵向移动机构20上。竖向移动机构21设于横向移动机构19上。连接部设于竖向移动机构21上。纵向移动机构20驱动横向移动机构19纵向运动。横向移动机构19驱动竖向移动机构21横向运动。竖向移动机构21驱动连接部竖向运动。本实施例中连接部包括用于夹持测序芯片2的夹爪7。
如前所述，多个浸泡缸3沿横向排列两排。通过横向移动机构19、纵向移动机 构20和竖向移动机构21三者的结合使用，可以保证夹爪7能够将测序芯片2插入和抽离任何一个浸泡缸3。
另外，各浸泡缸3也可以按环形排列，此时，运动机构就可以包括回转机构。连接部也可以是其它形式，例如还可以是与用于支持测序芯片2的芯片固持装置配合的真空吸盘、电磁吸盘等。
另外，虽然本实施例中通过运动机构和连接部移动测序芯片2实现测序芯片2在不同的浸泡缸3之间的移动，但在其它未示出的实施例中，也可以单纯依靠移动浸泡容器或同时移动浸泡容器和测序芯片2实现所需的测序芯片2与浸泡容器之间的位置关系变化。
芯片固持装置用于固定测序芯片2，使测序芯片2随同芯片固持装置运动。芯片固持装置包括一个或多个芯片安装位24，测序芯片2安装于芯片安装位24以通过移动芯片固持装置移动测序芯片2。
设置芯片固持装置一方面可以减少直接操作测序芯片2引起的污染，另一方面可以根据需要通过芯片固持装置同时移动多个测序芯片2并使多个测序芯片2保持预定的间隔，从而提高测序芯片2的通量。
本实施例中，测序芯片2的双侧表面具有DNA样品加载结构。如图4至图7所示，芯片安装位24包括芯片安装口，测序芯片2安装于芯片安装口内，芯片安装口为双侧敞开的通口。该设置使测序芯片2双面都能够得到浸泡，可以提高单片测序芯片2加载的DNA样品分子的数量。
另外，芯片框架9在不同的浸泡缸3之间转移，为了尽可能减少不同化学试剂之间的交叉污染，一般需要待芯片框架9表面残余的液体滴尽后再转移至下一个浸泡缸3中。为了加快芯片框架9表面的液体滴尽速度，如图4至图7所示，本实施例中，芯片框架9的下端从上至下逐渐变尖。在一个替代的实施方式中，芯片框架9的表面可以设置为疏水表面。当然也可以在芯片框架9具有从上至下逐渐变尖的下端的同时将芯片框架9的表面为疏水表面，从而实现化学试剂的更快速的滴落。
如图5至图7所示，芯片框架9的上端设置有卡口10；转移装置6的运动机构与夹爪7驱动连接以改变夹爪7的工作位置，夹爪7用于与芯片框架9连接。
本实施例中，夹爪7包括定位架11和夹块12，定位架11与运动机构连接，夹块12可移动地设置于定位架11上，定位架11上设有供芯片框架9上端插入的定位 孔13，夹爪7与插入定位孔13的芯片框架9的卡口10卡接以夹持芯片框架9。
如图4至图7所示，每片芯片框架9相对设有两个卡口10。夹爪7也对应设置有相对的两个夹块12。两个夹块12位于定位孔13的上端。当芯片框架9向上穿过定位孔13后，两个夹块12相对运动，分别卡入芯片框架9的两个卡口10中，将芯片框架9固定在定位孔13中。本实施例的定位架11设计了三个定位孔13，三个定位孔13等距排列。在其它未图示的实施例中，定位孔13的数量可以设置得更多或更少，例如可以设置为1个、2个、4个、5个等等，以同时操作相应数量的测序芯片2。浸泡反应区的数量和位置以及插槽16的数量和位置相应于定位孔13的数量变化而变化。
本实施例中，转移装置6的夹爪7通过芯片固持装置间接地夹持测序芯片2以实现转移装置6与测序芯片2之间的连接。间接夹持测序芯片2可以防止夹爪7夹持不同的测序芯片2后发生交叉污染。另外，夹爪7通过夹持芯片框架9间接地夹持测序芯片2，只需要在芯片框架9上加工夹持结构，而无需在测序芯片2上加工夹持结构，降低了测序芯片2的加工成本，也最大化利用了测序芯片2的表面积。
当然，在其它未图示的实施例中，也可以采用夹爪7直接夹持测序芯片2的方式连接转移装置6与测序芯片2。
优选地，基因测序反应设备1包括保护罩，浸泡容器罩设于保护罩内。如果环境条件允许，例如在无菌环境下操作时，测序反应过程是可以完全敞开的。但是在许多情况下，为了避免外界干扰，测序反应过程需要在封闭环境下进行，将浸泡容器位于保护罩内，能够提供一个封闭的反应环境，确保基因测序反应的质量。转移装置6也可以根据需要选择设置于或不设置于保护罩内。
吹气装置25用于吹除测序芯片2表面和/或安装所述测序芯片的芯片固持装置表面的化学试剂。本实施例中，吹气装置25用于吹除测序芯片2和芯片框架9表面残余的化学试剂。吹除测序芯片2和芯片框架9表面残余的化学试剂，可以尽量避免测序芯片2浸泡到下一个浸泡反应区时发生交叉污染。
参见图11，本实施例中，吹气装置25包括喷嘴。喷嘴用于喷射气体，喷射出的气体吹除测序芯片2和芯片框架9表面残余的化学试剂。
控制装置23用于控制和监控基因测序反应设备1的工作。本实施例中，控制装置23与温控装置5耦合以控制化学试剂的温度，还与转移装置6耦合以控制测序芯 片2在浸泡反应区内的浸泡时间和/或浸泡次序。
本实施例中，控制装置23为内置的控制装置，设置在支撑平台8上。在其它未图示的实施例中，也可以采用外置的控制装置与基因测序反应设备1耦合来控制和监控基因测序反应设备1工作。
通过控制装置23对温控装置5和转移装置6进行控制，可以实现基因测序反应设备1的自动化作业，提高基因测序质量和效率。
如图1至图3所示，本实施例中支撑平台8是一个箱柜。前述浸泡容器、温控装置5、转移装置6、上件储料装置14、下件储料装置15、容器盖4、翻盖机构22、吹气装置25和控制装置23等均设置于箱柜顶面上。箱柜内可以储存、收纳基因测序反应所需的试剂、工具等。为了方便基因测序反应设备1移动，箱柜下安装有脚轮27。
在其它未图示的实施例中，支撑平台8也可以为支撑板。
如图1至图3所示，本实施例中，基因测序反应设备1上可以加设信号灯28，用于基因测序反应设备1发生异常时报警。
本实施例中，每个浸泡反应区内装入一种基因测序反应用化学试剂，转移装置6夹持一组测序芯片2在一组浸泡反应区中浸泡一段时间后，再将该组测序芯片2转移至下一组浸泡反应区中浸泡一段时间，依此循环。该组测序芯片2的各测序芯片2在多个浸泡反应区中浸泡后就能够完成一次测序反应过程。
例如，在如图1至3所示的实施例中，测序芯片按3个为一组被夹持，可从右到左编号为1号芯片、2号芯片、3号芯片，浸泡缸3从后排开始从右到左依次编号至最后一个，再从前排从左到右继续依次编号至最后一个，分别为1号浸泡缸(后排最右侧)、2号浸泡缸、3号浸泡缸、……、17号浸泡缸(后排最左侧)、18号浸泡缸(前排最左侧)、19号浸泡缸、……、34号浸泡缸(前排最右侧)。开始基因测序反应时，使3号芯片浸入1号浸泡缸内；浸泡至预定时间后，将3号芯片转移至2号浸泡缸内继续浸泡，同时，2号芯片浸入1号浸泡缸开始浸泡浸泡至预定时间后，将3号芯片转移至3号浸泡缸内继续浸泡，同时，2号芯片浸入2号浸泡缸内继续浸泡，1号芯片浸入1号浸泡缸内开始浸泡。依此类推，一组芯片在一组浸泡缸浸泡完成后，使各测序芯片2依次转移到比各自浸泡缸的编号大1的浸泡缸内继续浸泡，直到全部的测序芯片2在各浸泡缸内均完成相应的浸泡过程。在16～17号浸泡缸、18～19号浸泡缸和33～34号浸泡缸中的浸泡过程类似在1～2号浸泡缸中浸泡的过程，可使部 分测序芯片2浸泡而部分测序芯片2不参与浸泡。
在一些实施例中，还可以使至少一排浸泡缸的头部和/或尾部的1个浸泡缸或多个浸泡缸(具体数量可以根据每次夹持的测序芯片的数量设置)为空容器或放置与相邻的浸泡缸相同的化学试剂或放置对基因测序反应没有影响的试剂，以使不参与浸泡的测序芯片2也处于浸泡缸内。
在一些实施例中，还可以对浸泡缸(或浸泡反应区)分组，例如可以按每次夹持的测序芯片的数量对浸泡缸(或浸泡反应区)分组，并使每组浸泡缸(或浸泡反应区)盛放同样的化学试剂，每次浸泡时，使一组测序芯片在一组盛放同样化学试剂的浸泡缸内浸泡。这样设置可以提高基因测序反应的效率，但需要更多的浸泡缸(或浸泡反应区)。
本实施例的基因测序系统包括DNA样品加载设备和基因测序反应设备1，基因测序反应设备1为前述的基因测序反应设备1。
本实施例的基因测序反应方法包括：在浸泡容器的浸泡反应区内加入基因测序反应用化学试剂；控制浸泡反应区内的化学试剂的温度；将表面具有DNA样品加载结构并加载有DNA样品的测序芯片2浸泡于化学试剂预定时间后取出。
优选地，在多个浸泡反应区内加注不同的基因测序反应用化学试剂，按预定顺序将测序芯片2顺次在多个浸泡反应区内浸泡预定时间。
以下结合图1～图3，简要描述应用以上实施例的基因测序反应设备1和基因测序反应方法进行基因测序反应的工作过程。
1、初始状态，在浸泡缸3中盛入基因测序反应用化学试剂，调整水浴锅内的导热液体至合适的温度，将待进行基因测序反应的测序芯片2安装至芯片框架9上，所有芯片框架9放置到上件储料装置14中。
2、转移装置6的夹爪7夹持芯片框架9，并使得各芯片框架9在逐个浸泡缸3中浸泡一段时间；当各芯片框架9在一排浸泡缸3中全部浸泡完毕时，纵向移动机构20驱动横向移动机构19纵向移动，使得各芯片框架9能够在另一排浸泡缸3中逐个浸泡，直至全部浸泡缸3浸泡完毕为止。
3、各芯片框架9在全部浸泡缸3浸泡完毕后，转移装置6将芯片框架9放置到下件储料装置15中，测序芯片2上的DNA样品完成测序反应过程，等待取走。
测序芯片2上的DNA样品完成测序反应过程后，转移至光学成像装置上成像。
应当理解，上述步骤仅为基因测序反应设备1可以实施的其中一种工作过程，并不代表它只能实施这些步骤，也不用于限制本发明的保护范围。另外，由于本发明涉及的化学反应不属于本发明要求保护的内容，而且不公开该内容也不影响本领域技术人员理解本发明，因此，本文不公开上述化学反应。
本发明的基因测序系统和基因测序反应方法具有与本发明的基因测序反应设备1类似的技术效果。
根据以上描述可知，本发明以上实施例能实现以下技术效果至少之一：
使用该基因测序反应设备1能采用浸泡方式实现基因测序反应。
由于测序芯片2在不同浸泡反应区的化学试剂中浸泡，能够完成测序反应所需的各个步骤。
浸泡反应区中的化学试剂可以重复利用，从而可以降低耗材成本。
浸泡的方式不存在液体流速不均匀的问题，测序芯片2表面不易产生气泡，可以保证化学反应更均匀、更充分。
测序芯片2在浸泡缸3内所受的液体压强均匀、受热均匀，因此不会发生变形的现象。
可以同时浸泡多张测序芯片2，具有通量高的优势。
没有复杂的流体系统，零部件少，具有装配容易，制造成本低的优点。
基因测序反应设备1由控制装置23自动控制，实现自动化作业。
最后应当说明的是：以上实施例仅用以说明本发明的技术方案而非对其限制；尽管参照较佳实施例对本发明进行了详细的说明，所属领域的普通技术人员应当理解：依然可以对本发明的具体实施方式进行修改或者对部分技术特征进行等同替换；而不脱离本发明技术方案的精神，其均应涵盖在本发明请求保护的技术方案范围当中。

Claims (22)

  1. 一种基因测序反应设备(1)，其特征在于，包括：
    支撑平台(8)；
    浸泡容器，设置于所述支撑平台(8)上，所述浸泡容器具有浸泡反应区，所述浸泡反应区用于盛放基因测序反应用化学试剂并用于将表面具有DNA样品加载结构且已加载有DNA样品的测序芯片(2)浸泡于所述化学试剂中进行基因测序反应；
    温控装置，用于控制所述浸泡反应区的化学试剂的温度；
    转移装置，用于将所述测序芯片(2)插入所述浸泡反应区或从所述浸泡反应区中抽离。
  2. 根据权利要求1所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)包括多个所述浸泡容器；和/或，所述浸泡容器包括彼此隔离的多个所述浸泡反应区。
  3. 根据权利要求1所述的基因测序反应设备(1)，其特征在于，所述浸泡容器包括溢流口(29)。
  4. 根据权利要求1所述的基因测序反应设备(1)，其特征在于，所述温控装置包括温度控制部和水浴锅，所述水浴锅用于盛放能够传递热量的液体，所述浸泡容器设置于所述水浴锅中，所述温度控制部控制所述水浴锅内的液体的温度以控制所述浸泡反应区内的化学试剂的温度。
  5. 根据权利要求1所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)还包括：
    上件储料装置(14)，用于放置待进行基因测序反应的所述测序芯片(2)；和/或，
    下件储料装置(15)，用于放置已完成基因测序反应的所述测序芯片(2)。
  6. 根据权利要求5所述的基因测序反应设备(1)，其特征在于，所述上件储料装置(14)和/或所述下件储料装置(15)包括：
    储料盒，所述储料盒的顶部敞口并具有插槽(16)和排液孔(17)，所述插槽(16)用于定位放置所述测序芯片(2)，所述排液孔(17)设于所述储料盒的底壁上，用于排出所述储料盒内的液体；和，
    储液盒(18)，设置于所述排液孔(17)的下方，用于承接所述排液孔(17)排出的液体。
  7. 根据权利要求1所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)还包括容器盖(4)，所述容器盖(4)可开闭地盖设于所述浸泡容器上以防止所述化学试剂蒸发。
  8. 根据权利要求7所述的基因测序反应设备(1)，其特征在于，所述容器盖(4)包括多个盖体，每个所述盖体用于与一个或多个所述浸泡反应区对应设置以防止对应的浸泡反应区内的化学试剂蒸发，且至少一个所述盖体相对于其它盖体可独立地开闭。
  9. 根据权利要求7所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)还包括翻盖机构(22)，所述翻盖机构(22)与所述容器盖(4)驱动连接以驱动所述容器盖(4)开闭。
  10. 根据权利要求1所述的基因测序反应设备(1)，其特征在于，所述转移装置(6)包括用于与所述测序芯片(2)连接的连接部和与所述连接部驱动连接以改变所述连接部的工作位置的运动机构。
  11. 根据权利要求10所述的基因测序反应设备(1)，其特征在于，所述多个浸泡反应区沿横向排列成一排或多排；所述运动机构包括横向移动机构(19)、纵向移动机构(20)和竖向移动机构(21)，所述纵向移动机构(20)设于所述支撑平台(8)上，所述横向移动机构(19)设于所述纵向移动机构(20)上，所述竖向移动机构(21)设于所述横向移动机构(19)上，所述连接部设于所述竖向移动机构(21)上，所述纵向移动机构(20)驱动所述横向移动机构(19)纵向运动，所述横向移动机构(19)驱动所述竖向移动机构(21)横向运动，所述竖向移动机构(21)驱动所述连接部竖向运动。
  12. 根据权利要求1至11中任一项所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)还包括芯片固持装置，所述芯片固持装置包括一个或多个芯片安装位(24)，所述测序芯片(2)安装于所述芯片安装位(24)以通过移动所述芯片固持装置移动所述测序芯片(2)。
  13. 根据权利要求12所述的基因测序反应设备(1)，其特征在于，所述测序芯片(2)的双侧表面具有所述DNA样品加载结构；所述芯片安装位(24)包括芯片安 装口，所述测序芯片(2)安装于所述芯片安装口内，所述芯片安装口为双侧敞开的通口。
  14. 根据权利要求12所述的基因测序反应设备(1)，其特征在于，所述芯片固持装置包括芯片框架(9)，所述芯片框架(9)上设置有所述芯片安装位(24)，所述芯片框架(9)的表面为疏水表面和/或所述芯片框架(9)的下端从上至下逐渐变尖。
  15. 根据权利要求12所述的基因测序反应设备(1)，其特征在于，所述芯片固持装置包括芯片框架(9)，所述芯片框架(9)上设置有一个或多个所述芯片安装位(24)，所述芯片框架(9)的上端设置有卡口(10)；所述转移装置(6)包括用于与所述芯片框架(9)连接的夹爪(7)和与所述夹爪(7)驱动连接以改变所述夹爪(7)的工作位置的运动机构，所述夹爪(7)包括定位架(11)和夹块(12)，所述定位架(11)与所述运动机构连接，所述夹块(12)可移动地设置于所述定位架(11)上，所述定位架(11)上设有供所述芯片框架(9)上端插入的定位孔(13)，所述夹爪(7)与插入所述定位孔(13)的所述芯片框架(9)的卡口(10)卡接以夹持所述芯片框架(9)。
  16. 根据权利要求1至11中任一项所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)还包括控制装置(23)，其中，
    所述控制装置(23)与所述温控装置耦合以控制所述化学试剂的温度；和/或，
    所述控制装置(23)与所述转移装置(6)耦合以控制所述测序芯片(2)在所述浸泡反应区内的浸泡时间和/或浸泡次序。
  17. 根据权利要求1至11中任一项所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)包括所述测序芯片(2)，所述测序芯片(2)的表面具有DNA样品加载结构。
  18. 根据权利要求1至11中任一项所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)包括保护罩，所述浸泡容器罩设于所述保护罩内。
  19. 根据权利要求1至11中任一项所述的基因测序反应设备(1)，其特征在于，所述基因测序反应设备(1)包括用于吹除所述测序芯片(2)表面和/或安装所述测序芯片的芯片固持装置表面的化学试剂的吹气装置(25)。
  20. 一种基因测序系统，包括DNA样品加载设备和基因测序反应设备(1)，其 特征在于，所述基因测序反应设备(1)为根据权利要求1至19中任一项所述的基因测序反应设备(1)。
  21. 一种基因测序反应方法，其特征在于，所述基因测序反应方法包括：
    在浸泡容器的浸泡反应区内加入基因测序反应用化学试剂；
    控制浸泡反应区内的所述化学试剂的温度；
    将表面具有DNA样品加载结构并加载有DNA样品的测序芯片(2)浸泡于所述化学试剂预定时间后取出。
  22. 根据权利要求21所述的基因测序反应方法，其特征在于，所述基因测序反应方法包括：在多个浸泡反应区内加注不同的基因测序反应用化学试剂，按预定顺序将所述测序芯片(2)顺次在所述多个浸泡反应区内浸泡预定时间。
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