WO2019023947A1 - Dna样品加载设备、基因测序系统和dna样品加载方法 - Google Patents

Dna样品加载设备、基因测序系统和dna样品加载方法 Download PDF

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Publication number
WO2019023947A1
WO2019023947A1 PCT/CN2017/095505 CN2017095505W WO2019023947A1 WO 2019023947 A1 WO2019023947 A1 WO 2019023947A1 CN 2017095505 W CN2017095505 W CN 2017095505W WO 2019023947 A1 WO2019023947 A1 WO 2019023947A1
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WIPO (PCT)
Prior art keywords
dna sample
loading
biochip
sample loading
loading device
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PCT/CN2017/095505
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English (en)
French (fr)
Inventor
倪鸣
徐讯
魏栋
伍家波
马炜
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 CN201780093168.3A priority Critical patent/CN110914403B/zh
Priority to PCT/CN2017/095505 priority patent/WO2019023947A1/zh
Publication of WO2019023947A1 publication Critical patent/WO2019023947A1/zh

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    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

Definitions

  • the invention relates to the field of gene sequencing technology, in particular to a DNA sample loading device, a gene sequencing system and a DNA sample loading method.
  • DNA samples need to be loaded onto a biochip (sequencing chip) before the gene sequencing reaction.
  • the DNA sample loading process is actually the process by which DNA molecules adhere to the surface of the biochip.
  • 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.
  • the DNA sample is loaded (adhered) on the inner wall of the flow channel.
  • Chemical reagents can only be used once, resulting in high operating costs.
  • the flow rate of the chemical reagent in the flow channel is not uniform, and there is a tendency that the chemical reagent cannot flow to the corner, which causes the chemical reaction to be uneven and insufficient, and thus the DNA sample is unevenly loaded and unstable.
  • flowing chemical reagents tend to wash off DNA molecules that have been loaded onto the surface of the chip.
  • the pressure generated by the chemical reagent in the flow channel easily causes the surface of the chip to collapse, and the deformation of the chip surface will increase the error rate of DNA sequencing.
  • the available area of the chip is only the part inside the flow channel, and other parts cannot be effectively utilized, so that the chip cannot be utilized to the utmost extent.
  • a first aspect of the invention provides a DNA sample loading device comprising: a loading device comprising a soaking module, the soaking module comprising a soaking container for holding a chemical reagent for loading a DNA sample and for using the surface to have DNA a biochip of the sample loading structure is immersed in the chemical reagent; a temperature control device for controlling a temperature of the chemical reagent in the infusion container; and a moving device for inserting the biochip into the Immerse the container or withdraw from the soaking container.
  • the infusion module includes a plurality of the infusion containers; and/or the infusion container includes a plurality of infusion spaces that are isolated from each other.
  • the DNA sample loading device further includes a support platform, the temperature control device is disposed on the support platform, and the loading device is disposed on the support platform by the temperature control device.
  • the temperature control device comprises a loading temperature control module
  • the loading temperature control module comprises a loading temperature control portion and a loading water bath
  • the loading water bath is for holding a liquid capable of transferring heat
  • the soaking container setting In the loading water bath, the loading temperature control unit controls the temperature of the liquid in the loading water bath to control the temperature of the chemical in the soaking container.
  • the loading device further includes: a loading module, the biochip for placing a DNA sample to be loaded; and/or a blanking module, wherein the blanking module is used to place the loaded DNA sample Biochip.
  • the loading module includes an loading container for placing a biochip to be loaded with a DNA sample; and/or the blanking module includes a blanking container for placing a biochip loaded with a DNA sample.
  • the infusion container includes an overflow port; and/or the loading container includes an overflow port; and/or the blanking container includes an overflow port.
  • the mobile device is further configured to: insert or remove the biochip into the loading container; insert the biochip into the blanking container or from the blanking Pull away from the container.
  • the temperature control device is further configured to control a temperature of the loading module; and/or the temperature control device is further configured to control a temperature of the blanking module.
  • the loading module includes a loading container for placing a biochip to be loaded with a DNA sample
  • the temperature control device further includes a loading temperature control module
  • the loading temperature control module includes a loading temperature control unit.
  • a feed water bath for holding a liquid capable of transferring heat
  • the loading container being disposed in the feed water bath
  • the loading temperature control portion for controlling the upper a temperature of the liquid in the water bath
  • the blanking module includes a blanking container for placing a biochip loaded with the DNA sample
  • the temperature control device further comprising a blanking temperature control module, the lower
  • the material temperature control module includes a blanking temperature control portion and a blanking water bath, the discharging water bath is for holding a liquid capable of transferring heat, and the blanking container is disposed in the blanking water bath, the lower
  • the material temperature control unit is for controlling the temperature of the liquid in the water bath.
  • the mobile device is configured to move the biochip, including a connection portion for connecting with the biochip and a motion mechanism drivingly connected with the connection portion to change a working position of the connection portion.
  • a plurality of the infusion containers are arranged in a lateral direction;
  • the movement mechanism includes a lateral movement axis and a vertical movement axis, the lateral movement axis is disposed on the support platform, and the vertical movement axis is disposed on the On the lateral movement axis, the connecting portion is disposed on the vertical moving shaft, the lateral moving shaft drives the vertical moving shaft to move laterally, and the vertical moving shaft drives the connecting portion to move vertically.
  • the DNA sample loading device further includes a chip holding device including one or more chip mounting positions, the biochip being mounted on the chip mounting position to move by moving the chip holding device Said biochip.
  • the double-sided surface of the biochip has the DNA sample loading structure;
  • the chip mounting position includes a chip mounting port, the biochip is mounted 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 frame clamp and one or more chip frames connected to the frame clamp, and the chip frame is provided with one or more of the chip mounting positions, the mobile device and the The frame fixture is connected.
  • the frame clamp comprises a fixing plate, a clamping block and a positioning pin, one or more of the clamping blocks are disposed on the fixing plate, the clamping block is provided with at least one slot, and the chip frame is inserted at one end In the slot, the clamping block is provided with a pin slot at two ends of the slot, and the chip frame is provided with an opening corresponding to the pin slot, and the positioning pin is inserted into the pin slot And the chip frame is fixedly mounted on the clip in the opening, and the moving device is connected to the fixing plate.
  • the positioning pin is provided with a plug shaft
  • the chip frame is provided with a jack in the opening, and the plug shaft is inserted into the jack.
  • the frame fixture further includes a bolt
  • the clamping block is provided with screw holes penetrating the clamping block on both sides of the pin slot, the bolt is matched with the screw hole, and the positioning pin is arranged There is a through hole corresponding to the screw hole, and the bolt is locked in the screw hole through the fixing plate, and the bolt also passes through the through hole of the positioning pin.
  • the DNA sample loading device 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 mobile device To control the soaking time and/or soaking sequence of the biochip within the soaking container.
  • the DNA sample loading device includes the biochip, the surface of the biochip having a loading structure for loading a DNA sample.
  • the DNA sample loading device further includes a cover plate disposed above the loading device and having an aperture corresponding to the container opening of the infusion container.
  • the DNA sample loading device includes a protective cover, and the loading device is disposed in the protective cover.
  • a second aspect of the present invention provides a gene sequencing system comprising a DNA sample loading device and a gene sequencing reaction device, which is the DNA sample loading device according to any one of the first aspects of the invention.
  • a third aspect of the present invention provides a DNA sample loading method, comprising: adding a chemical reagent for loading a DNA sample into a soaking container; controlling a temperature of the chemical reagent in the infusion container; and having a DNA sample on the surface
  • the biochip loaded with the structure is immersed in the chemical reagent for a while and then taken out.
  • the DNA sample loading method comprises: adding a plurality of chemical reagents for loading DNA samples in a plurality of infusion containers or a plurality of infusion spaces, sequentially ordering the biochips in the plurality of infusion containers in a predetermined order Or soaking for a predetermined time in the plurality of soaking spaces.
  • the loading device comprises a soaking module, the soaking module comprises a soaking container, the soaking container is used for holding a chemical reagent for loading the DNA sample and is used for immersing the biochip having the DNA sample loading structure on the surface in the chemical In the reagent; the temperature control device is for controlling the temperature of the chemical reagent in the infusion container; and the moving device is for inserting the biochip into or from the infusion container.
  • the DNA sample loading device can load a DNA sample onto a biochip by immersing the biochip in a chemical reagent.
  • the DNA sample loading device of the present invention can achieve at least one of the following technical effects: by loading different chemical reagents in different soaking spaces of different infusion containers or infusion containers, and placing the biochip in different soaking containers or Soaking in the soaking space can complete all aspects of DNA sample loading.
  • Chemical reagents can be reused, saving reagent costs.
  • DNA molecules that have adhered to the biochip during the chemical reaction are not washed away by chemical reagents.
  • the liquid pressure of the biochip in the infusion container is uniform and uniform in heat, and therefore, the phenomenon of surface collapse deformation does not occur.
  • the surface utilization of the biochip is maximized, which increases the flux of DNA sample loading.
  • the gene sequencing system and DNA sample loading method of the present invention have similar technical effects as the DNA sample loading device of the present invention.
  • FIG. 1 is a schematic perspective view showing the structure of a DNA sample loading device according to an embodiment of the present invention
  • Figure 2 is a perspective view showing the structure of the DNA sample loading device of Figure 1 after removing the cover;
  • Figure 3 is a perspective view showing another perspective of the DNA sample loading device shown in Figure 1;
  • FIG. 4 is a schematic view showing the structure of a chip holding device of the DNA sample loading device shown in FIG. 1.
  • Figure 5 is a schematic exploded view of Figure 4.
  • Figure 6 is a schematic exploded view showing the frame clamp of the DNA sample loading device shown in Figure 1;
  • Figure 7 is an exploded perspective view showing another angle of the frame clamp of the DNA sample loading device shown in Figure 1;
  • Figure 8 is a perspective view showing the structure of the chip of the DNA sample loading device shown in Figure 1;
  • FIG. 9 is a schematic structural view of a chip frame and a biochip in which the biochip is not mounted in the DNA sample loading device shown in FIG. 1;
  • Fig. 10 is a perspective view showing the structure of a soaking container of the DNA sample loading device 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.
  • the embodiment of the invention discloses a DNA sample loading device 1.
  • the DNA sample loading device 1 mainly includes a loading device 3, a temperature control device 4, and a moving device 5.
  • the loading device 3 includes a soaking module 24, and the soaking module 24 includes a soaking container 301 for holding a chemical reagent for loading a DNA sample and for immersing the biochip 2 having a DNA loading structure on the surface in a chemical reagent; 4 for controlling the temperature of the chemical agent in the infusion container 301; the moving device 5 is for inserting or withdrawing the biochip 2 from the infusion container 301.
  • the DNA sample loading device 1 can load a DNA sample onto the biochip 2 by immersing the biochip 2 in a chemical reagent.
  • the DNA sample loading device 1 can also achieve at least one of the following technical effects:
  • the various steps of DNA sample loading can be performed by loading different chemical reagents in different soaking containers 301 or different soaking spaces of the infusion container, and soaking the biochip 2 in different soaking containers 301 or soaking spaces.
  • Chemical reagents can be reused, saving reagent costs. Does not exist in the process of chemical reaction In the problem of uneven liquid flow rate, the surface of the biochip 2 is less likely to generate bubbles, which ensures that the chemical reaction is more uniform and sufficient, so that the DNA sample can be more uniformly and stably loaded onto the biochip 2.
  • the DNA molecules that have adhered to the biochip 2 during the chemical reaction are not washed away by the chemical reagent.
  • the liquid pressure of the biochip 2 in the soaking container 301 is uniform and uniform in heat, and therefore, the phenomenon of surface collapse deformation does not occur.
  • the surface utilization of the biochip 2 is maximized, which can increase the flux of DNA sample loading.
  • the DNA sample loading device 1 of the present embodiment includes a biochip 2, a loading device 3, a temperature control device 4, a moving device 5, a chip holding device, a support platform 7, and a control device 26.
  • the biochip 2 is used for loading DNA samples and gene sequencing.
  • the surface of the biochip 2 has a DNA sample loading structure.
  • the biochip 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.
  • the DNA sample referred to in this embodiment may be a nanoball 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 2-3 orders of magnitude using a rolling circle amplification technique to become DNB.
  • the loading device 3 in this embodiment includes a soaking module 24, a loading module 23 and a blanking module 25.
  • the soak module 24 is used to load a DNA sample on the biochip 2.
  • the loading module 23 is used to place the biochip 2 to which the DNA sample is to be loaded.
  • the blanking module 25 is used to place the biochip 2 to which the DNA sample has been loaded.
  • the soaking module 24 includes a plurality of infusion containers 301.
  • the soaking container 301 is used for holding the chemical reagent for loading the DNA sample and for immersing the biochip 2 in the chemical reagent, and the corresponding step of loading the DNA sample can be realized by the immersion method.
  • the soaking module 24 includes a plurality of infusion containers 301.
  • a plurality of infusion containers 301 are used to hold different chemical reagents for loading DNA samples, and a plurality of infusion containers 301 are arranged on the support platform 7.
  • the loading module 23 includes one or more loading containers 302 for placing the biochip 2 to be loaded with a DNA sample.
  • the loading container 302 houses a chemical reagent for holding the biochemical substance activity of the biochip 2.
  • the setting of the loading container 302 can be used to temporarily place a biochip to be loaded with a DNA sample.
  • the blanking module 25 includes one or more blanking containers 303 for placing the biochip 2 loaded with the DNA sample.
  • the blanking container 303 contains a chemical reagent for maintaining the biochemical activity of the biochip.
  • the setting of the blanking container 303 can be used to temporarily place a biochip loaded with a DNA sample.
  • the soaking container 301, the loading container 302, and the dropping container 303 are all soaking cylinders having the same structure.
  • the loading module 23 includes 10 soaking cylinders, and the 10 soaking cylinders are divided into 5 groups according to two groups, and the 5 groups of soaking cylinders are arranged in the horizontal direction in the left portion of the loading device 3.
  • the immersion module 24 includes 16 immersion cylinders, and the 16 immersion cylinders are divided into 8 groups according to two groups.
  • the 8 groups of immersion cylinders are arranged laterally on the right side of the loading module 23 and are located in the middle section of the loading device 3.
  • the blanking module 25 includes 10 soaking cylinders, and the 10 soaking cylinders are divided into 5 groups according to two groups of each group, and the 5 groups of soaking cylinders are arranged in the lateral direction of the right portion of the loading device 3.
  • each set of the soaking container 301 respectively contains various reagents required for loading various steps of the DNA sample, so as to complete the different loading links of the DNA loading by soaking the biochip 2 in each group of soaking cylinders. .
  • the infusion container may also include a plurality of infusion spaces, and the plurality of infusion spaces may place different chemical reagents in groups.
  • the soaking module 24 may also include a plurality of infusion containers, each of which includes a plurality of infusion spaces. The chemical reagents in the plurality of immersion spaces may be set to be the same (as a group) or different as needed.
  • the temperature control device 4 is disposed on the support platform 7, and the loading device 3 is disposed on the support platform 7 through the temperature control device 4.
  • the temperature control device 4 includes a loading temperature control module 401, a loading temperature control module 402, and a blanking temperature control module 403.
  • the loading temperature control module 401 is used to control the temperature of the chemical reagent in the infusion vessel 301.
  • the loading temperature control module 402 is used to control the temperature of the chemical reagent in the loading container 302 of the loading module 23.
  • the blanking temperature control module 403 is used to control the temperature of the chemical reagent in the blanking module 25.
  • the loading temperature control module 401 includes a loading temperature control unit and a loading water bath, the loading water bath is for holding a liquid capable of transferring heat, and the soaking container 301 is disposed in the loading water bath, and the loading temperature is controlled.
  • the portion controls the temperature of the liquid in the water bath to control the temperature of the chemical in the soaking vessel 301.
  • the feeding temperature control module 402 comprises a feeding temperature control unit and a feeding water bath, the feeding water bath is for holding the liquid capable of transferring heat, and the loading container 302 is disposed in the feeding water bath, and the feeding temperature control unit controls The temperature of the liquid in the water bath is fed to control the temperature of the chemical in the loading vessel 302.
  • the blanking temperature control module 403 includes a blanking temperature control unit and a blanking water bath, the discharging water bath is for holding the liquid capable of transferring heat, and the blanking container 303 is disposed in the discharging water bath, and the feeding temperature control unit controls The temperature of the liquid in the water bath is drained, thereby controlling the temperature of the chemical in the blanking vessel 303.
  • the water bath is used to indirectly control the temperature of the soaking tank and the chemical reagent therein, and the water bath The liquid capable of transferring heat is placed in the corresponding water bath.
  • the heat transfer liquid in the water bath can be heated or cooled, and the soaking tank is immersed in the heat transfer liquid, thereby being able to control the temperature of the chemical reagent in the bath.
  • the use of a liquid as a heat transfer medium allows a more uniform control of the temperature of the chemical reagents in each soaking cylinder.
  • a direct temperature control method in which the temperature controller is used to directly heat or cool the soaking cylinder or the liquid therein may be used, but the direct temperature control method is compared with the indirect temperature control method using the water bath. It is prone to uneven heat and cold.
  • each temperature control module includes a respective temperature control portion and a water bath, so The loading module 23, the soaking module 24, and the blanking module 25 perform temperature control, respectively.
  • the temperature control device 4 can uniformly control the temperature of the loading device 3, for example, each of the three modules is placed in the same water bath.
  • different temperature control can be performed on the soaking cylinders for different loading stages.
  • the loading temperature control module 401 may include more than two loading temperature control portions and corresponding two or more loading water baths, and set the soaking containers 301 having different temperature requirements in different water baths.
  • At least one of the infusion container 301, the loading container 302, and the blanking container 303 may include an overflow port.
  • the soaking tank as the infusion container 301 includes an overflow port 304.
  • the liquid in the immersion tank exceeds a certain water level, it overflows from the overflow port 304, thereby preventing the liquid level in the immersion tank from being extremely high.
  • the loading module 23 includes the loading container 302 and the blanking module 25 includes the blanking container 302.
  • the specific method of 25 can also be different. Even the loading module 23 and the blanking module 25 are not required.
  • the biochip 2 after the biochip 2 is mounted on the chip holding device, it can be directly placed in the soaking container 301 corresponding to the first step of loading the DNA without passing through the loading module 23.
  • the biochip is loaded with the DNA sample, it can be directly sent to the gene sequencing device for gene sequencing reaction without going through the blanking module 25.
  • the mobile device 5 is used to move the biochip 2 to insert or withdraw the biochip 2 from the infusion container 301; the mobile device 5 can also be used to move the biochip 2 to insert the biochip 2
  • the material container 302 is either withdrawn from the loading container 302; the mobile device 5 can also be used to move the biochip 2 to insert or withdraw the biochip 2 into the blanking container 303. Therefore, the mobile device 5 of the embodiment may be one of any one of the loading module 23, the immersion module 24, and the blanking module 25 of the loading device 3.
  • the biochip 2 in one soaking tank moves into another soaking tank of the same module or different modules.
  • the biochip 2 to be loaded with the DNA sample may be placed in the loading container 302 of the loading module 23 by another external moving device, or the biochip 2 may be manually placed in the loading container 302.
  • the biochip 2 to which the DNA sample has been loaded may be taken away by another external mobile device, or the biochip 2 may be manually removed.
  • the setting of the mobile device 5 can improve the automation degree of the DNA loading device 1 on the one hand, reduce the error rate caused by the manual operation, and can precisely control the soaking sequence and the soaking time by cooperation with the control device 26, thereby facilitating the high quality of DNA. Sample loading work.
  • the mobile device 5 includes a connection portion for connection with the biochip 2 and a motion mechanism that is drivingly coupled to the connection portion to change the working position of the connection portion.
  • the mobile device 5 can be mounted on the support platform 7, or can be mounted on other supports as long as the function of connecting and moving the biochip 2 can be realized.
  • the connecting portion in this embodiment includes a jaw 6 for holding the biochip 2.
  • a plurality of loading containers 302, a plurality of infusion containers 301, and a plurality of blanking containers 303 are arranged in the lateral direction.
  • the moving mechanism of the moving device 5 includes a lateral moving shaft 21 and a vertical moving shaft 22, the lateral moving shaft 21 is disposed on the supporting platform 7, the vertical moving shaft 22 is disposed on the lateral moving shaft 21, and the connecting portion is disposed on the vertical moving shaft 22 on.
  • the lateral movement axis 21 drives the vertical movement axis 22 to move laterally, and the vertical movement shaft 22 drives the joint portion to move vertically.
  • the jaws 6 are suspended above the immersion cylinders, and the biochip 2 can be placed in any one of the immersion cylinders, or any one of the immersion cylinders The biochip 2 is extracted.
  • the motion mechanism can be in other forms, for example, the motion mechanism can also cause the joint to perform a three-dimensional motion.
  • each of the soaking cylinders may also be arranged in a ring shape, and at this time, the moving mechanism may include a turning function.
  • the connecting 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 biochip 2.
  • the movement of the biochip 2 between different soaking cylinders is realized by moving the biochip 2 through the moving mechanism and the connecting portion in this embodiment, in other embodiments not shown, it is also possible to rely solely on the mobile loading device or At the same time, the mobile loading device and the biochip realize a change in the positional relationship between the required biochip and the loading device.
  • the chip holding device is used to fix the biochip 2 so that the biochip 2 moves along with the chip holding device.
  • the chip holding device includes one or more chip mounting positions for mounting the biochip 2, and the mobile device 5 passes the control core The position of the sheet holding device is moved to the biochip 2 mounted at the chip mounting position.
  • the chip holding device can reduce the pollution caused by directly operating the biochip on the one hand, and can simultaneously move the plurality of bio chips 2 through the chip holding device and keep the plurality of biochips 2 at a predetermined interval as needed, thereby improving the biochip 2 Flux.
  • the jaws 6 of the mobile device 5 indirectly sandwich the biochip 2 by the chip holding device to realize the connection between the mobile device and the biochip 2. Indirect clamping of the biochip 2 prevents cross-contamination of the jaws 6 after clamping the different biochips 2.
  • the mobile device and the biochip can also be connected by directly clamping the biochip with the jaws.
  • the chip holding device includes a frame jig 9 and four chip frames 8 connected to the frame jig 9.
  • a chip mounting position is provided on each chip frame 8.
  • the frame clamp 9 is used to connect with the mobile device 5 to move the biochip 2.
  • more or fewer chip frames 8 may be connected to each frame jig 9, and two or more may be disposed on each chip frame 8. Chip mounting bit.
  • the bilateral surface of the biochip 2 has a DNA sample loading structure.
  • the chip mounting position includes a chip mounting opening 33, the biochip 2 is mounted in the chip mounting opening 33, and the chip mounting opening 33 is a double-opened opening. This setting can increase the number of DNA sample molecules loaded by the single piece of biochip 2.
  • the frame jig 9 includes a fixing plate 11, a clamp block 10, and a positioning pin 12.
  • the two clamp blocks 10 are arranged side by side on the fixed plate 11.
  • the clamping block 10 is provided with two slots 13 .
  • One end of the chip frame 8 is inserted into a slot 13 .
  • the clamping block 10 defines a pin slot 14 at two ends of the slot 13 , and the chip frame 8 is provided with a corresponding pin slot 14 .
  • the opening 15, the positioning pin 12 is inserted into the pin groove 14 and the opening 15, and the chip frame 8 is fixedly mounted on the clamping block 10.
  • the moving device 5 is used for connecting with the fixing plate 11 to move the biochip 2.
  • the positioning pin 12 When the positioning pin 12 is inserted into the pin groove 14, since the opening 15 of the chip frame 8 is aligned with the pin groove 14, the positioning pin 12 is also caught in the opening 15, and the chip frame 8 is fixedly mounted on the holder 10.
  • a notch 27 may be formed at one end of the pin groove 14 to facilitate the folding of the positioning pin 12.
  • a pin slot 14 and a corresponding positioning pin 12 are disposed on each side of each clamping block 10 .
  • the pin groove 14 may be provided only on one side of the clamping block 10
  • the slot 13 may be provided with a structure that can be snapped into the other side opening 15 of the chip frame 8, so that the positioning is only inserted on one side.
  • Pin 12 The chip frame 8 can be fixed. This structure is very convenient for loading and unloading the chip frame 8.
  • the positioning pin 12 is provided with a insertion shaft 16, which is provided with a chip frame 8.
  • An insertion hole 17 is provided in the opening 15, and the insertion shaft 16 is inserted into the insertion hole 17.
  • the frame clamp 9 further includes a bolt 18. Screw holes 19 penetrating the clamp block 10 are provided on both sides of the pin groove 14 of the clamp block 10, and the bolts 18 are fitted with the screw holes 19.
  • the positioning pin 12 is provided with a through hole 20 corresponding to the screw hole 19. The bolt 18 is locked in the screw hole 19 through the fixing plate 11. The bolt 18 also passes through the through hole 20 of the positioning pin 12. Therefore, the positioning pin 12 is fixed in the pin groove 14 by the bolt 18, and does not fall off due to vibration.
  • the fixing plate 11 can also have a recess 28 for the jaws 6 to be caught to more firmly hold the fixing plate 11.
  • the chip frame 8 is transferred between different immersion cylinders. In order to minimize cross-contamination between different chemical reagents, it is generally required that the liquid remaining on the surface of the chip frame 8 is drained and then transferred to the next immersion tank. In order to speed up the liquid dropping speed on the surface of the chip frame 8, as shown in Figs. 8 and 9, in the present embodiment, the lower end of the chip frame 8 is gradually tapered from top to bottom.
  • the surface of the chip frame 8 can be provided as a hydrophobic surface. It is of course also possible to make the surface of the chip frame 8 a hydrophobic surface while the chip frame 8 has a lower end which tapers from top to bottom, thereby achieving faster dripping of the chemical agent.
  • the frame clamp 9 in this embodiment includes two clamp blocks 10, each of which is provided with two slots 13, each of which can be inserted into a chip frame 8, so that a frame clamp 9 can be mounted.
  • Chip frame 8 the mobile device 5 is connected to one frame jig 9 to be able to simultaneously move the four biochips 2 by moving the frame jig 9.
  • more or fewer clips 10 can be disposed on the frame fixture 9 according to actual needs, and more or fewer slots 13 are opened on each of the clips 10. The more the clips 10 and the slots 13 are More, the more biochips 2 that can be clamped and transferred at the same time.
  • control device 26 is provided on the support platform 7 for controlling and monitoring the operation of the DNA sample loading device 1.
  • control device 26 is coupled to temperature control device 4 to control the temperature of each module of loading device 3, such as the temperature of the chemical reagent within soaking vessel 301.
  • the control device 26 is also coupled to the mobile device 5 to control the soaking sequence and/or soaking time of the biochip 2 within the infusion container 301.
  • the process of loading a DNA sample can be completely open if environmental conditions permit, such as when operating in a sterile environment.
  • the DNA sample loading device 1 preferably includes a protective cover in which the loading device 3 is located. This provides a closed environment for the DNA sample loading process.
  • the mobile device 5 can also be as needed To choose to set or not in the protective cover.
  • the support platform 7 can be a support plate or a bin. As shown in FIG. 1 to FIG. 3, the support platform 7 in this embodiment is a cabinet. The reagents and tools required for gene sequencing can be stored and stored in the cabinet. In order to facilitate the movement of the DNA sample loading device 1, casters 29 are mounted under the cabinet.
  • a signal lamp 31 can be added to the DNA sample loading device 1 for alarming when an abnormality occurs in the DNA sample loading device 1.
  • the loading device 3 is also provided with a cover 30.
  • the cover plate 30 is provided with an opening corresponding to the container opening of each of the soaking container 301, the loading container 302, and the discharging container 303.
  • each set of the soaking container 301 is loaded with a chemical reagent for loading a DNA sample, and the mobile device 5 holds the biochip 2 in a soaking container 301 for a period of time, and then transfers the biochip 2 to the next.
  • the group soaking container 301 is immersed for a period of time and circulated accordingly.
  • the biochip 2 can be loaded onto the biochip 2 after being immersed in a plurality of immersion containers 301.
  • the process of immersing the biochip 2 in a chemical reagent is actually a process in which a chemical reaction takes place.
  • the temperature control device 4 is capable of producing a suitable temperature for the chemical reaction.
  • the present embodiment also provides a gene sequencing system comprising a DNA sample loading device and a gene sequencing reaction device, and the DNA sample loading device is the aforementioned DNA sample loading device 1.
  • the embodiment further provides a DNA sample loading method, comprising: adding a chemical reagent for loading a DNA sample into the immersion container 301; controlling the temperature of the chemical reagent in the immersion container 301; and having a DNA sample loading structure on the surface
  • the biochip 2 is immersed in the chemical reagent for a while and then taken out.
  • the biochip 2 is sequentially immersed in the plurality of immersion containers 301 in a predetermined order for a predetermined time.
  • each of the soaking cylinders of each module of the loading device 3 is filled with the required chemical reagent, and each water bath of the temperature control device 4 is adjusted to a suitable temperature, and the biochip 2 to be loaded with the DNA sample is all installed.
  • the chip frame 8 all the chip frames 8 are mounted on the frame jig 9; the frame jigs 9 on which the chip frames 8 are mounted are placed on the cover 30 above the loading module 23, and the chip frames 8 are all passed through the holes in the cover plate.
  • the ports are inserted into the respective loading containers 302 of the loading module 23.
  • the jaws 6 hold the frame clamp 9 closest to the soaking module 24, that is, the last frame clamp 9 in the loading module 23, transferring and inserting the chip frame 8 into the nearest soaking container 301, that is, soaking In the first soaking container 301 in the module 24, the biochip 2 is allowed to soak for a certain time in the corresponding soaking container 301.
  • the jaw 6 transfers the penultimate frame clamp 9 in the loading module 23, so that the chip frame 8 is inserted into the last loading container 302 of the loading module 23, and the frame clamps of the loading module 23 are arranged in this manner. 9 Transfer one position to the right in turn.
  • the frame jig 9 is moved to the second soaking container 301 of the soaking module 24, and the front frame jig 9 is transferred to the right side in this manner. .

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Abstract

一种DNA样品加载设备、基因测序系统和DNA样品加载方法。DNA样品加载设备包括：加载装置，包括浸泡模块，浸泡模块包括浸泡容器，浸泡容器用于盛放加载DNA样品的化学试剂并用于将表面具有DNA样品加载结构的生物芯片浸泡于化学试剂中；温控装置用于控制浸泡容器内的化学试剂的温度；移动装置用于将生物芯片插入浸泡容器或从浸泡容器中抽离。该DNA样品加载设备可以通过将生物芯片浸泡于化学试剂的方式将DNA样品加载至生物芯片上。

Description

DNA样品加载设备、基因测序系统和DNA样品加载方法 技术领域
本发明涉及基因测序技术领域，特别涉及一种DNA样品加载设备、基因测序系统和DNA样品加载方法。
背景技术
现有技术中，基因测序反应前需要将DNA样品加载到生物芯片(测序芯片)上。DNA样品加载过程实际上是DNA分子粘附到生物芯片表面的过程。
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。DNA样品加载(粘附)在流道的内壁。
在实现本发明的过程中，发明人发现现有技术的测序芯片及DNA样品加载技术具有以下不足之处：
化学试剂只能使用一次，导致操作成本高昂。
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，从而会出现DNA样品加载不均匀、不牢固的现象。
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。
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。
芯片的可利用面积只有流道内的部分，其它部分无法有效利用，导致芯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DNA样品加载的DNA样品加载设备、基因测序系统和DNA样品加载方法。
本发明第一方面提供一种DNA样品加载设备，包括：加载装置，包括浸泡模块，所述浸泡模块包括浸泡容器，所述浸泡容器用于盛放加载DNA样品的化学试剂并用于将表面具有DNA样品加载结构的生物芯片浸泡于所述化学试剂中；温控装置，用于控制所述浸泡容器内的所述化学试剂的温度；移动装置，用于将所述生物芯片插入所述 浸泡容器或从所述浸泡容器中抽离。
进一步地，所述浸泡模块包括多个所述浸泡容器；和/或，所述浸泡容器包括多个彼此隔离的浸泡空间。
进一步地，所述DNA样品加载设备还包括支撑平台，所述温控装置设置于所述支撑平台上，所述加载装置通过所述温控装置设置于所述支撑平台上。
进一步地，所述温控装置包括加载温控模块，所述加载温控模块包括加载温度控制部和加载水浴锅，所述加载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加载水浴锅中，所述加载温度控制部控制所述加载水浴锅内的液体的温度以控制所述浸泡容器内的化学试剂的温度。
进一步地，所述加载装置还包括：上料模块，所述上料模块用于放置待加载DNA样品的生物芯片；和/或，下料模块，所述下料模块用于放置已加载DNA样品的生物芯片。
进一步地，所述上料模块包括用于放置待加载DNA样品的生物芯片的上料容器；和/或，所述下料模块包括用于放置已加载DNA样品的生物芯片的下料容器。
进一步地，所述浸泡容器包括溢流口；和/或，所述上料容器包括溢流口；和/或，所述下料容器包括溢流口。
进一步地，所述移动装置还用于：将所述生物芯片插入所述上料容器或从所述上料容器中抽离；将所述生物芯片插入所述下料容器或从所述下料容器中抽离。
进一步地，所述温控装置还用于控制所述上料模块的温度；和/或，所述温控装置还用于控制所述下料模块的温度。
进一步地，所述上料模块包括用于放置待加载DNA样品的生物芯片的上料容器，所述温控装置还包括上料温控模块，所述上料温控模块包括上料温度控制部和上料水浴锅，所述上料水浴锅用于盛放能够传递热量的液体，所述上料容器设置于所述上料水浴锅中，所述上料温度控制部用于控制所述上料水浴锅内的液体的温度；和/或，所述下料模块包括用于放置已加载DNA样品的生物芯片的下料容器，所述温控装置还包括下料温控模块，所述下料温控模块包括下料温度控制部和下料水浴锅，所述下料水浴锅用于盛放能够传递热量的液体，所述下料容器设置于所述下料水浴锅中，所述下料温度控制部用于控制所述下料水浴锅内的液体的温度。
进一步地，所述移动装置用于移动所述生物芯片，包括用于与所述生物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，多个所述浸泡容器沿横向排列；所述运动机构包括横向移动轴和竖向移动轴，所述横向移动轴设于所述支撑平台上，所述竖向移动轴设于所述横向移动轴上，所述连接部设于所述竖向移动轴上，所述横向移动轴驱动所述竖向移动轴横向运动，所述竖向移动轴驱动所述连接部竖向运动。
进一步地，所述DNA样品加载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，所述生物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生物芯片。
进一步地，所述生物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，所述生物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框架夹具和连接于所述框架夹具上的一个或多个芯片框架，所述芯片框架上设置有一个或多个所述芯片安装位，所述移动装置与所述框架夹具连接。
进一步地，所述框架夹具包括固定板、夹块和定位销，一个或多个所述夹块设置于所述固定板上，所述夹块设有至少一个插槽，所述芯片框架一端插于所述插槽中，所述夹块在所述插槽的两端开设有销槽，所述芯片框架设有与所述销槽对应的开口，所述定位销插设于所述销槽和所述开口中将所述芯片框架固定安装于所述夹块上，所述移动装置与所述固定板连接。
进一步地，所述定位销设有插轴，所述芯片框架在所述开口内设有插孔，所述插轴插于所述插孔中。
进一步地，所述框架夹具还包括螺栓，所述夹块在所述销槽的两侧设有贯穿所述夹块的螺孔，所述螺栓与所述螺孔适配，所述定位销设有与所述螺孔对应的通孔，所述螺栓穿过所述固定板锁紧于所述螺孔内，所述螺栓还穿过所述定位销的通孔。
进一步地，所述DNA样品加载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移动装置耦合以控制所述生物芯片在所述浸泡容器内的浸泡时间和/或浸泡次序。
进一步地，所述DNA样品加载设备包括所述生物芯片，所述生物芯片的表面具有用于加载DNA样品的加载结构。
进一步地，所述DNA样品加载设备还包括盖板，所述盖板设置于所述加载装置的上方，并具有与所述浸泡容器的容器口对应的孔口。
进一步地，所述DNA样品加载设备包括保护罩，所述加载装置罩设于所述保护罩内。
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DNA样品加载设备为本发明第一方面中任一项所述的DNA样品加载设备。
本发明第三方面提供一种DNA样品加载方法，所述DNA样品加载方法包括：在浸泡容器内加入加载DNA样品的化学试剂；控制浸泡容器内的所述化学试剂的温度；将表面具有DNA样品加载结构的生物芯片浸泡于所述化学试剂一段时间后取出。
进一步地，所述DNA样品加载方法包括：在多个浸泡容器或多个浸泡空间内加注不同的加载DNA样品的化学试剂，按预定顺序将所述生物芯片顺次在所述多个浸泡容器或所述多个浸泡空间内浸泡预定时间。
基于本发明提供的DNA样品加载设备，其加载装置包括浸泡模块，浸泡模块包括浸泡容器，浸泡容器用于盛放加载DNA样品的化学试剂并用于将表面具有DNA样品加载结构的生物芯片浸泡于化学试剂中；其温控装置用于控制浸泡容器内的化学试剂的温度；其移动装置用于将生物芯片插入浸泡容器或从浸泡容器中抽离。该DNA样品加载设备可以通过将生物芯片浸泡于化学试剂的方式将DNA样品加载至生物芯片上。
进一步地，本发明的DNA样品加载设备还能实现以下技术效果至少之一：通过在不同的浸泡容器或浸泡容器的不同浸泡空间装入不同的化学试剂，并将生物芯片在不同的浸泡容器或浸泡空间内进行浸泡，可以完成DNA样品加载的各个环节。化学试剂能够重复利用，节约试剂成本。发生化学反应的过程中不存在液体流速不均匀的问题，生物芯片表面不易产生气泡，可以保证化学反应更均匀、更充分，从而，DNA样品能够更均匀、更稳固地加载至生物芯片上。发生化学反应的过程中已粘附至生物芯片上的DNA分子不会被化学试剂冲落。生物芯片在浸泡容器内所受的液体压强均匀、受热均匀，因此，不会发生表面压塌变形的现象。生物芯片的表面利用率最大化，能够提高DNA样品加载的通量。
本发明的基因测序系统和DNA样品加载方法具有与本发明的DNA样品加载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DNA样品加载设备的立体结构示意图；
图2是图1中的DNA样品加载设备移除盖板后的立体结构示意图；
图3是图1所示的DNA样品加载设备的另一角度的立体结构示意图；
图4是图1所示的DNA样品加载设备的芯片固持装置的结构示意图。
图5是图4的分解结构示意图；
图6是图1所示的DNA样品加载设备的框架夹具的分解结构示意图；
图7是图1所示的DNA样品加载设备的框架夹具的另一角度的分解结构示意图；
图8是图1所示的DNA样品加载设备的芯片框架的立体结构示意图；
图9是图1所示的DNA样品加载设备的未安装有生物芯片的芯片框架和生物芯片的结构示意图；
图10是图1所示的DNA样品加载设备的浸泡容器的立体结构示意图。
图1至图10中，各附图标记分别代表：
1、DNA样品加载设备，2、生物芯片，3、加载装置，4、温控装置，5、移动装置，6、夹爪，7、支撑平台，8、芯片框架，9、框架夹具，10、夹块，11、固定板，12、定位销，13、插槽，14、销槽，15、开口，16、插轴，17、插孔，18、螺栓，19、螺孔，20、通孔，21、横向移动轴，22、竖向移动轴，23、上料模块，24、浸泡模块，25、下料模块，26、控制装置，27、缺口，28、凹槽，29、脚轮，30、盖板，31、信号灯，32、圆孔，33、芯片安装口，301、浸泡容器，302、上料容器，303、下料容器，304、溢流口，401、加载温控模块，402、上料温控模块，403、下料温控模块。
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。
本发明实施例公开了一种DNA样品加载设备1。
如图1至图10所示，该DNA样品加载设备1主要包括加载装置3、温控装置4和移动装置5。加载装置3包括浸泡模块24，浸泡模块24包括浸泡容器301，浸泡容器301用于盛放加载DNA样品的化学试剂并用于将表面具有DNA加载结构的生物芯片2浸泡于化学试剂中；温控装置4用于控制浸泡容器301内的化学试剂的温度；移动装置5用于将生物芯片2插入浸泡容器301或从浸泡容器301中抽离。
该DNA样品加载设备1可以通过将生物芯片2浸泡于化学试剂的方式将DNA样品加载至生物芯片2上。
该DNA样品加载设备1还能实现以下技术效果至少之一：
通过在不同的浸泡容器301内或浸泡容器的不同浸泡空间装入不同的化学试剂，并将生物芯片2在不同的浸泡容器301或浸泡空间内进行浸泡，可以执行DNA样品加载的各个环节。化学试剂能够重复利用，节约试剂成本。发生化学反应的过程中不存 在液体流速不均匀的问题，生物芯片2表面不易产生气泡，可以保证化学反应更均匀、更充分，从而，DNA样品能够更均匀、更稳固地加载至生物芯片2上。发生化学反应的过程中已粘附至生物芯片2上的DNA分子不会被化学试剂冲落。生物芯片2在浸泡容器301内所受的液体压强均匀、受热均匀，因此，不会发生表面压塌变形的现象。生物芯片2的表面利用率最大化，能够提高DNA样品加载的通量。
以下结合图1至图10对本发明实施例进行详细说明。
如图1至图3所示，本实施例的DNA样品加载设备1包括生物芯片2、加载装置3、温控装置4、移动装置5、芯片固持装置、支承平台7和控制装置26。
其中，生物芯片2用于加载DNA样品及基因测序。生物芯片2表面具有DNA样品加载结构。本实施例中，生物芯片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。
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(nanoball)，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2-3个数量级，成为DNB。
如图1至图3所示，本实施例中加载装置3包括浸泡模块24、上料模块23和下料模块25。浸泡模块24用于在生物芯片2上加载DNA样品。上料模块23用于放置待加载DNA样品的生物芯片2。下料模块25用于放置已加载DNA样品的生物芯片2。
如图1至图3所示，浸泡模块24包括多个浸泡容器301。浸泡容器301用于盛放加载DNA样品的化学试剂并用于将生物芯片2浸泡于化学试剂中，通过浸泡方式可实现DNA样品加载的相应环节。本实施例中，浸泡模块24包括多个浸泡容器301。多个浸泡容器301用于盛放不同的加载DNA样品的化学试剂，多个浸泡容器301排列设置于支撑平台7上。
上料模块23包括用于放置待加载DNA样品的生物芯片2的一个或多个上料容器302。上料容器302容纳用于保持生物芯片2的生化物质活性的化学试剂。上料容器302的设置可以用于暂时放置待进行DNA样品加载的生物芯片。
下料模块25包括用于放置已加载DNA样品的生物芯片2的一个或多个下料容器303。下料容器303容纳用于保持生物芯片的生化物质活性的化学试剂。下料容器303的设置可以用于暂时放置已加载DNA样品的生物芯片。
本实施例中，浸泡容器301、上料容器302和下料容器303均为结构相同的浸泡缸。
参考如图1至图3。上料模块23包括10个浸泡缸，10个浸泡缸按每组两个分为5组，5组浸泡缸沿横向排列于加载装置3的左段。浸泡模块24包括16个浸泡缸，16个浸泡缸按每组两个分为8组，8组浸泡缸沿横向排列于上料模块23的右侧，并位于加载装置3的中段。下料模块25包括10个浸泡缸，10个浸泡缸按每组两个分为5组，5组浸泡缸沿横向排列于加载装置3的右段。
本实施例中，浸泡模块24中，每组浸泡容器301内分别盛装加载DNA样品各环节所需的各种试剂，以通过在各组浸泡缸内浸泡生物芯片2而完成DNA加载的不同加载环节。
在其它未图示的实施例中，浸泡容器也可以包括多个浸泡空间，多个浸泡空间可以按组放置不同的化学试剂。当然，浸泡模块24还可以是包括多个浸泡容器，而每个浸泡容器包括多个浸泡空间。多个浸泡空间内的化学试剂可以根据需要设置为相同(作为一组)也可以不同。
温控装置4设置于支撑平台7上，加载装置3通过温控装置4设置于支撑平台7上。
本实施例中，温控装置4包括加载温控模块401、上料温控模块402和下料温控模块403。加载温控模块401用于控制浸泡容器301内的化学试剂的温度。上料温控模块402用于控制上料模块23的上料容器302内的化学试剂的温度。下料温控模块403用于控制下料模块25内的化学试剂的温度。
如图1至图3所示，加载温控模块401包括加载温度控制部和加载水浴锅，加载水浴锅用于盛放能够传递热量的液体，浸泡容器301设置于加载水浴锅中，加载温度控制部控制加载水浴锅内的液体的温度，从而控制浸泡容器301内的化学试剂的温度。
上料温控模块402包括上料温度控制部和上料水浴锅，上料水浴锅用于盛放能够传递热量的液体，上料容器302设置于上料水浴锅中，上料温度控制部控制上料水浴锅内的液体的温度，从而控制上料容器302内的化学试剂的温度。
下料温控模块403包括下料温度控制部和下料水浴锅，下料水浴锅用于盛放能够传递热量的液体，下料容器303设置于下料水浴锅中，下料温度控制部控制下料水浴锅内的液体的温度，从而控制下料容器303内的化学试剂的温度。
本发明实施例中选用水浴锅对浸泡缸及其内化学试剂进行间接温度控制，水浴锅 盛放能够传递热量的液体，浸泡缸设置于对应的水浴锅中。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，浸泡缸浸泡在导热液体中，从而能够控制浸泡缸内化学试剂的温度。采用液体作为导热介质，可以更均匀地控制各浸泡缸内的化学试剂的温度。
在其它未示出的实施例中，也可以采用温控器对浸泡缸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。
本实施例中，由于温控装置4包括加载温控模块401、上料温控模块402和下料温控模块403，各温控模块均包括各自的温度控制部和水浴锅，因此，可以对上料模块23、浸泡模块24和下料模块25分别进行温度控制。当然，如果不需要三个模块控制在不同的温度，温控装置4可以对加载装置3的温度进行统一控制，例如，将三个模块中的各浸泡缸设置于同一个水浴锅内。或者，即使在同一模块内部，也可以对不同的加载环节针对的浸泡缸进行不同的温度控制。例如，加载温控模块401可以包括两个以上加载温度控制部和对应的两个以上加载水浴缸，并将有不同温度要求的浸泡容器301设置于不同的水浴锅内。
优选地，浸泡容器301、上料容器302和下料容器303中至少一种可以包括溢流口。以浸泡容器301为例，如图10所示，作为浸泡容器301的浸泡缸包括溢流口304。当浸泡缸内的液体超过一定水位时从溢流口304溢出，从而可以防止浸泡缸内的液位超高。
需要说明的是，虽然本实施例中，上料模块23包括上料容器302、下料模块25包括下料容器302，但在其它未图示的实施例中，上料模块23和下料模块25的具体方式也可以不同。甚至上料模块23和下料模块25均不是必须的。例如，在生物芯片2安装于芯片固持装置上后，可直接置于加载DNA的第一个环节对应的浸泡容器301内，而无需经过上料模块23。再例如，在生物芯片加载好DNA样品后，可以直接送入基因测序设备进行基因测序反应，而无需经过下料模块25。
本实施例中，移动装置5用于移动生物芯片2以将生物芯片2插入浸泡容器301或从浸泡容器301中抽离；移动装置5还可以用于移动生物芯片2以将生物芯片2插入上料容器302或从上料容器302中抽离；移动装置5还可以用于移动生物芯片2以将生物芯片2插入下料容器303或从下料容器303中抽离。因此，本实施例的移动装置5可以将加载装置3的上料模块23、浸泡模块24和下料模块25中任一模块中的一 个浸泡缸内的生物芯片2移动到同一模块或不同模块的另一个浸泡缸内。
本实施例中，待加载DNA样品的生物芯片2可由外部另一个移动装置放入上料模块23的上料容器302中，也可以人工将生物芯片2放入上料容器302。同样地，已加载DNA样品的生物芯片2可由外部另一个移动装置将它们取走，也可以人工将生物芯片2取走。
移动装置5的设置一方面可以提高DNA加载设备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26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实现DNA样品加载工作。
本实施例中，移动装置5包括用于与生物芯片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。移动装置5可以安装在支撑平台7上，也可以安装在其他支撑物上，只要能够实现连接和移动生物芯片2的功能即可。
本实施例中连接部包括用于夹持生物芯片2的夹爪6。
如图1至图3所示，本实施例中，多个上料容器302、多个浸泡容器301和多个下料容器303沿横向排列。移动装置5的运动机构包括横向移动轴21和竖向移动轴22，横向移动轴21设于支撑平台7上，竖向移动轴22设于横向移动轴21上，连接部设于竖向移动轴22上。横向移动轴21驱动竖向移动轴22横向运动，竖向移动轴22驱动连接部竖向运动。
由于加载装置3各模块的多个浸泡缸沿着横向移动轴21排列，夹爪6悬在这些浸泡缸之上，能够将生物芯片2放入任何一个浸泡缸中，或者将任何一个浸泡缸中的生物芯片2抽出。
在其它示出的实施例中，运动机构可以为其它形式，例如，运动机构也可以使连接部执行三维运动。另外，各浸泡缸也可以按环形排列，此时，运动机构就可以包括回转功能。连接部也可以是其它形式，例如还可以是与用于支持生物芯片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生物芯片2实现生物芯片2在不同的浸泡缸之间的移动，但在其它未示出的实施例中，也可以单纯依靠移动加载装置或同时移动加载装置和生物芯片实现所需的生物芯片与加载装置之间的位置关系变化。
芯片固持装置用于固定生物芯片2，使生物芯片2随同芯片固持装置运动。芯片固持装置包括一个或多个用于安装生物芯片2的芯片安装位，移动装置5通过控制芯 片固持装置的位置移动安装于芯片安装位的生物芯片2。
设置芯片固持装置一方面可以减少直接操作生物芯片引起的污染，另一方面可以根据需要通过芯片固持装置同时移动多个生物芯片2并使多个生物芯片2保持预定的间隔，从而提高生物芯片2的通量。
本实施例中，移动装置5的夹爪6通过芯片固持装置间接地夹持生物芯片2以实现移动装置与生物芯片2之间的连接。间接夹持生物芯片2可以防止夹爪6夹持不同的生物芯片2后发生交叉污染。
当然，在其它未示出的实施例中，也可以采用夹爪直接夹持生物芯片的方式连接移动装置与生物芯片。
如图4和图5所示，芯片固持装置包括框架夹具9和连接于框架夹具9上的四个芯片框架8。每个芯片框架8上设置有一个芯片安装位。框架夹具9用于与移动装置5连接以移动生物芯片2。本实施例中具体地，在其它未图示的实施例中，每个框架夹具9上可以连接更多的或更少的芯片框架8，每个芯片框架8上可以设置两个或两个以上的芯片安装位。
本实施例中，生物芯片2的双侧表面具有DNA样品加载结构。如图4、图5和图8所示，芯片安装位包括芯片安装口33，生物芯片2安装于芯片安装口33内，芯片安装口33为双侧敞开的通口。该设置可以提高单片生物芯片2加载的DNA样品分子的数量。
如图4至图7所示，框架夹具9包括固定板11、夹块10和定位销12。两个夹块10并排设于固定板11上。夹块10设有两个插槽13，芯片框架8一端插于一个插槽13中，夹块10在插槽13的两端开设有销槽14，芯片框架8设有与销槽14对应的开口15，定位销12插设于销槽14和开口15中将芯片框架8固定安装于夹块10上，移动装置5用于与固定板11连接以移动生物芯片2。
当定位销12插入销槽14时，由于芯片框架8的开口15与销槽14对齐，定位销12也会卡入开口15中，于是芯片框架8就被固定安装在夹块10上。
为了便于卸下定位销12，可以在销槽14一端开设一个缺口27，便于撬下定位销12。
如图4至图7所示，本实施例中每个夹块10的两侧各设置了一条销槽14及对应的定位销12。在其它未图示的实施例中，可以只在夹块10的一侧设置销槽14，插槽13内设置可以卡入芯片框架8另一侧开口15的结构，这样只在一侧插入定位销12就 能够固定芯片框架8。该结构十分方便芯片框架8的装卸。
另外，为了便于确定定位销12相对于夹块10的位置及更牢固地连接芯片框架8与夹块10，如图6和图7所示，定位销12上设有插轴16，芯片框架8在开口15内设有插孔17，插轴16插于插孔17中。
为了牢固地连接芯片框架8与夹块10、定位销12和固定板11，框架夹具9还包括螺栓18。在夹块10上销槽14的两侧设有贯穿夹块10的螺孔19，螺栓18与螺孔19适配。定位销12设有与螺孔19对应的通孔20。螺栓18穿过固定板11锁紧于螺孔19内。螺栓18还穿过定位销12的通孔20。因此，定位销12被螺栓18固定在销槽14内，不会因振动而脱落。
另外，固定板11还可以开设凹槽28，供夹爪6卡入，以更稳固地夹持固定板11。
另外，芯片框架8在不同的浸泡缸之间转移，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8表面残余的液体滴尽后再转移至下一个浸泡缸中。为了加快芯片框架8表面的液体滴尽速度，如图8和图9所示，本实施例中，芯片框架8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8的表面可以设置为疏水表面。当然也可以在芯片框架8具有从上至下逐渐变尖的下端的同时将芯片框架8的表面为疏水表面，从而实现化学试剂的更快速的滴落。
本实施例中的框架夹具9包括两个夹块10，每个夹块10设有两个插槽13，每个插槽13可插入一个芯片框架8，于是一个框架夹具9上就能够安装4个芯片框架8。换言之，移动装置5与一个框架夹具9连接就能够通过移动框架夹具9同时移动四块生物芯片2。当然，还可以根据实际需要在框架夹具9上设置更多的或更少的夹块10，每个夹块10上开设更多个或更少个插槽13，夹块10和插槽13越多，一次能够同时夹持、转移的生物芯片2就越多。
控制装置26设置在支撑平台7上，用于控制和监控DNA样品加载设备1的工作。本实施例中，控制装置26与温控装置4耦合以控制加载装置3的各模块的温度，例如浸泡容器301内的化学试剂的温度。控制装置26还与移动装置5耦合以控制生物芯片2在浸泡容器301内的浸泡次序和/或浸泡时间。
如果环境条件允许，例如在无菌环境下操作时，加载DNA样品的过程是可以完全敞开。但是在许多情况下，为了避免外界的干扰，加载DNA样品的过程需要在封闭环境下进行的，因此，DNA样品加载设备1优选地包括保护罩，加载装置3位于保护罩内。这样就能够为DNA样品加载过程提供一个封闭的环境。移动装置5也可以根据需 要选择设置于或不设置于保护罩内。
支撑平台7可以是支撑板，也可以是箱柜。如图1至图3所示，本实施例中支撑平台7是一个箱柜。箱柜内可以储存、收纳基因测序所需的试剂、工具等。为了方便DNA样品加载设备1移动，箱柜下安装有脚轮29。
如图1至图3所示，本实施例中，DNA样品加载设备1上可以加设信号灯31，用于DNA样品加载设备1发生异常时报警。
为了加固安装浸泡缸、便于芯片固持装置放置，以及防止异物跌落入水浴锅，加载装置3上还设置了盖板30。盖板30上设置与各浸泡容器301、上料容器302和下料容器303的容器口对应的孔口。
本实施例中，每组浸泡容器301内装入一种加载DNA样品的化学试剂，移动装置5夹持生物芯片2在一个浸泡容器301中浸泡一段时间后，再将该生物芯片2转移至下一组浸泡容器301中浸泡一段时间，依此循环。生物芯片2在多个浸泡容器301中浸泡后就能够将DNA样品分子加载至该生物芯片2上。生物芯片2在化学试剂中浸泡的过程实际上是发生化学反应的过程。温控装置4能够为化学反应制造合适的温度。
本实施例还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，DNA样品加载设备为前述的DNA样品加载设备1。
本实施例还提供一种DNA样品加载方法，DNA样品加载方法包括：在浸泡容器301内加入加载DNA样品的化学试剂；控制浸泡容器301内的化学试剂的温度；将表面具有DNA样品加载结构的生物芯片2浸泡于化学试剂一段时间后取出。
其中，在多个浸泡容器301内加注不同的加载DNA样品的化学试剂，按预定顺序将生物芯片2顺次在多个浸泡容器301内浸泡预定时间。
以下结合图1至图3，简要描述本实施例的DNA样品加载设备1的工作过程：
1、在初始状态，加载装置3的各模块的各浸泡缸中盛入所需的化学试剂，温控装置4的各水浴锅调整至合适的温度，将待加载DNA样品的生物芯片2全部安装至芯片框架8上，所有芯片框架8安装至框架夹具9上；将安装了芯片框架8的框架夹具9放置于上料模块23上方的盖板30上，芯片框架8均通过盖板上的孔口插入上料模块23的各上料容器302中。
2、夹爪6夹持最靠近浸泡模块24的框架夹具9，也就是上料模块23中的最后一个框架夹具9，将其芯片框架8转移并插入至最接近的浸泡容器301，也就是浸泡模块24中的第一个浸泡容器301中，令生物芯片2在对应的浸泡容器301中浸泡若干时间。
3、夹爪6转移上料模块23中的倒数第二个框架夹具9，使其芯片框架8插入上料模块23的最后一个上料容器302中，按照该方式将上料模块23各框架夹具9依次往右侧转移一个位置。
4、浸泡模块24中的第一组生物芯片2浸泡完毕后，将其框架夹具9移至浸泡模块24的第二个浸泡容器301，按照该方式将前一个框架夹具9往右侧转移一个位置。
5、不断循环步骤2～4，当安装在同一芯片固持装置上的一组生物芯片2在浸泡模块24的全部浸泡容器301中分别浸泡完毕后，就将该芯片固持装置及其上该组生物芯片2转移至下料模块25的下料容器303中。
6、不断循环步骤2～5。
从而，通过将生物芯片2从左至右逐个位置转移，使其在每一个浸泡容器301中都能够得到浸泡。
应当理解，上述步骤仅为DNA样品加载设备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。
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 (26)

  1. 一种DNA样品加载设备(1)，其特征在于，包括：
    加载装置(3)，包括浸泡模块(24)，所述浸泡模块(24)包括浸泡容器(301)，所述浸泡容器(301)用于盛放加载DNA样品的化学试剂并用于将表面具有DNA样品加载结构的生物芯片(2)浸泡于所述化学试剂中；
    温控装置(4)，用于控制所述浸泡容器(301)内的所述化学试剂的温度；
    移动装置，用于将所述生物芯片(2)插入所述浸泡容器(301)或从所述浸泡容器(301)中抽离。
  2. 根据权利要求1所述的DNA样品加载设备(1)，其特征在于，所述浸泡模块(24)包括多个所述浸泡容器(301)；和/或，所述浸泡容器包括多个彼此隔离的浸泡空间。
  3. 根据权利要求2所述的DNA样品加载设备(1)，其特征在于，所述DNA样品加载设备(1)还包括支撑平台(7)，所述温控装置(4)设置于所述支撑平台(7)上，所述加载装置(3)通过所述温控装置(4)设置于所述支撑平台(7)上。
  4. 根据权利要求1所述的DNA样品加载设备(1)，其特征在于，所述温控装置(4)包括加载温控模块(401)，所述加载温控模块(401)包括加载温度控制部和加载水浴锅，所述加载水浴锅用于盛放能够传递热量的液体，所述浸泡容器(301)设置于所述加载水浴锅中，所述加载温度控制部控制所述加载水浴锅内的液体的温度以控制所述浸泡容器(301)内的化学试剂的温度。
  5. 根据权利要求1所述的DNA样品加载设备(1)，其特征在于，所述加载装置(3)还包括：
    上料模块(23)，所述上料模块(23)用于放置待加载DNA样品的生物芯片(2)；和/或，
    下料模块(25)，所述下料模块(25)用于放置已加载DNA样品的生物芯片(2)。
  6. 根据权利要求5所述的DNA样品加载设备(1)，其特征在于，
    所述上料模块(23)包括用于放置待加载DNA样品的生物芯片(2)的上料容器(302)；和/或，
    所述下料模块(25)包括用于放置已加载DNA样品的生物芯片(2)的下料容器(303)。
  7. 根据权利要求6所述的DNA样品加载设备(1)，其特征在于，所述浸泡容器(301)包括溢流口(304)；和/或，所述上料容器(302)包括溢流口；和/或，所述下料容器(303)包括溢流口。
  8. 根据权利要求6所述的DNA样品加载设备(1)，其特征在于，所述移动装置还用于：
    将所述生物芯片(2)插入所述上料容器(302)或从所述上料容器(302)中抽离；
    将所述生物芯片(2)插入所述下料容器(303)或从所述下料容器(303)中抽离。
  9. 根据权利要求5所述的DNA样品加载设备(1)，其特征在于，所述温控装置(4)还用于控制所述上料模块(23)的温度；和/或，所述温控装置(4)还用于控制所述下料模块(25)的温度。
  10. 根据权利要求9所述的DNA样品加载设备(1)，其特征在于，
    所述上料模块(23)包括用于放置待加载DNA样品的生物芯片(2)的上料容器(302)，所述温控装置(4)还包括上料温控模块(402)，所述上料温控模块(402)包括上料温度控制部和上料水浴锅，所述上料水浴锅用于盛放能够传递热量的液体，所述上料容器(302)设置于所述上料水浴锅中，所述上料温度控制部用于控制所述上料水浴锅内的液体的温度；和/或，
    所述下料模块(25)包括用于放置已加载DNA样品的生物芯片(2)的下料容器(303)，所述温控装置(4)还包括下料温控模块(403)，所述下料温控模块(403)包括下料温度控制部和下料水浴锅，所述下料水浴锅用于盛放能够传递热量的液体，所述下料容器(303)设置于所述下料水浴锅中，所述下料温度控制部用于控制所述下料水浴锅内的液体的温度。
  11. 根据权利要求1至10中任一项所述的DNA样品加载设备(1)，其特征在于，所述移动装置(5)用于移动所述生物芯片(2)，包括用于与所述生物芯片(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。
  12. 根据权利要求11所述的DNA样品加载设备(1)，其特征在于，多个所述浸泡容器(301)沿横向排列；所述运动机构包括横向移动轴(21)和竖向移动轴(22)，所述横向移动轴(21)设于支撑平台(7)上，所述竖向移动轴(22)设于所述横向移动轴(21)上，所述连接部设于所述竖向移动轴(22)上，所述横向移动轴(21)驱动所述竖向移动轴(22)横向运动，所述竖向移动轴(22)驱动所述连接部竖向运动。
  13. 根据权利要求1至10中任一项所述的DNA样品加载设备(1)，其特征在于，所述DNA样品加载设备(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，所述生物芯片(2)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生物芯片(2)。
  14. 根据权利要求13所述的DNA样品加载设备(1)，其特征在于，所述生物芯片(2)的双侧表面具有所述DNA样品加载结构；所述芯片安装位包括芯片安装口(33)，所述生物芯片(2)安装于所述芯片安装口(33)内，所述芯片安装口(33)为双侧敞开的通口。
  15. 根据权利要求13所述的DNA样品加载设备(1)，其特征在于，所述芯片固持装置包括芯片框架(8)，所述芯片框架(8)上设置有所述芯片安装位，所述芯片框架(8)的表面为疏水表面和/或所述芯片框架(8)的下端从上至下逐渐变尖。
  16. 根据权利要求13所述的DNA样品加载设备(1)，其特征在于，所述芯片固持装置包括框架夹具(9)和连接于所述框架夹具(9)上的一个或多个芯片框架(8)，所述芯片框架(8)上设置有一个或多个所述芯片安装位，所述移动装置(5)与所述框架夹具(9)连接。
  17. 根据权利要求16所述的DNA样品加载设备(1)，其特征在于，所述框架夹具(9)包括固定板(11)、夹块(10)和定位销(12)，一个或多个所述夹块(10)设置于所述固定板(11)上，所述夹块(10)设有至少一个插槽(13)，所述芯片框架(8)一端插于所述插槽(13)中，所述夹块(10)在所述插槽(13)的两端开设有销槽(14)，所述芯片框架(8)设有与所述销槽(14)对应的开口(15)，所述定位销(12)插设于所述销槽(14)和所述开口(15)中将所述芯片框架(8)固定安装于所述夹块(10)上，所述移动装置(5)与所述固定板(11)连接。
  18. 根据权利要求17所述的DNA样品加载设备(1)，其特征在于，所述定位销(12)设有插轴(16)，所述芯片框架(8)在所述开口(15)内设有插孔(17)，所述插轴(16)插于所述插孔(17)中。
  19. 根据权利要求17所述的DNA样品加载设备(1)，其特征在于，所述框架夹具(9)还包括螺栓(18)，所述夹块(10)在所述销槽(14)的两侧设有贯穿所述夹块(10)的螺孔(19)，所述螺栓(18)与所述螺孔(19)适配，所述定位销(12)设有与所述螺孔(19)对应的通孔(20)，所述螺栓(18)穿过所述固定板(11)锁 紧于所述螺孔(19)内，所述螺栓(18)还穿过所述定位销(12)的通孔(20)。
  20. 根据权利要求1至10中任一项所述的DNA样品加载设备(1)，其特征在于，所述DNA样品加载设备(1)还包括控制装置(26)，其中，
    所述控制装置(26)与所述温控装置(4)耦合以控制所述化学试剂的温度；和/或，
    所述控制装置(26)与所述移动装置(5)耦合以控制所述生物芯片(2)在所述浸泡容器(301)内的浸泡时间和/或浸泡次序。
  21. 根据权利要求1至10中任一项所述的DNA样品加载设备(1)，其特征在于，所述DNA样品加载设备(1)包括所述生物芯片(2)，所述生物芯片(2)的表面具有用于加载DNA样品的加载结构。
  22. 根据权利要求1至10中任一项所述的DNA样品加载设备(1)，其特征在于，所述DNA样品加载设备(1)还包括盖板(30)，所述盖板(30)设置于所述加载装置(3)的上方，并具有与所述浸泡容器(301)的容器口对应的孔口。
  23. 根据权利要求1至10中任一项所述的DNA样品加载设备(1)，其特征在于，所述DNA样品加载设备(1)包括保护罩，所述加载装置(3)罩设于所述保护罩内。
  24. 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，其特征在于，所述DNA样品加载设备为根据权利要求1至23中任一项所述的DNA样品加载设备(1)。
  25. 一种DNA样品加载方法，其特征在于，所述DNA样品加载方法包括：
    在浸泡容器(301)内加入加载DNA样品的化学试剂；
    控制浸泡容器(301)内的所述化学试剂的温度；
    将表面具有DNA样品加载结构的生物芯片(2)浸泡于所述化学试剂一段时间后取出。
  26. 根据权利要求25所述的DNA样品加载方法，其特征在于，所述DNA样品加载方法包括：在多个浸泡容器(301)或多个浸泡空间内加注不同的加载DNA样品的化学试剂，按预定顺序将所述生物芯片(2)顺次在所述多个浸泡容器(301)或所述多个浸泡空间内浸泡预定时间。
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