WO2019061353A1 - 基因测序反应设备和基因测序系统 - Google Patents

基因测序反应设备和基因测序系统 Download PDF

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Publication number
WO2019061353A1
WO2019061353A1 PCT/CN2017/104587 CN2017104587W WO2019061353A1 WO 2019061353 A1 WO2019061353 A1 WO 2019061353A1 CN 2017104587 W CN2017104587 W CN 2017104587W WO 2019061353 A1 WO2019061353 A1 WO 2019061353A1
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WIPO (PCT)
Prior art keywords
gene sequencing
loading
chip
blanking
sequencing
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PCT/CN2017/104587
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English (en)
French (fr)
Inventor
马炜
徐讯
伍家波
倪鸣
魏栋
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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 PCT/CN2017/104587 priority Critical patent/WO2019061353A1/zh
Priority to CN202410338420.4A priority patent/CN118006457A/zh
Priority to CN201780093178.7A priority patent/CN110892058B/zh
Publication of WO2019061353A1 publication Critical patent/WO2019061353A1/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
    • 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

Definitions

  • the invention relates to the field of gene sequencing technology, in particular to a gene sequencing reaction device and a gene sequencing system.
  • the second generation of gene sequencing technology is based on the development of the first generation of Sanger sequencing technology, with low cost, high throughput, automation and other characteristics, greatly promoting the development of the gene sequencing industry.
  • the second generation of gene sequencing technology has been widely used in whole genome sequencing, transcriptome sequencing, and metagenomic sequencing. It is a powerful tool for analyzing the evolution and classification of organisms, studying diseases related genes such as cancer and autism, and conducting in vitro diagnostics. Tools have promoted people's understanding of life sciences and promoted the development of health industry.
  • the sequence of DNA is determined by capturing the newly synthesized end-label, which mainly includes: 1) sequencing library preparation, randomly breaking DNA into small fragments; PCR amplification, generating thousands of repeats; 3) adding different fluorescent labels to different bases for fluorescence imaging sequencing.
  • the second generation gene sequencing technology mainly includes Illumina's SBS sequencing technology, and BGI's CPAS sequencing technology. Both sequencing technologies are based on the reversible end-circulation of DNA synthesis, ie the blocking and regeneration of 3'-OH reversibility.
  • the basic principles are: 1) loading the sample to be tested onto the chip; 2) at dNTP (dATP) , dCTP, dGTP, dTTP) 3'-OH plus one block, add a detection group to the base; 3) each reaction, only one complementary dNTP is added because of the block; 4 After detecting the group carried by the dNTP by technical means, the blocking group is excised with a reagent, and the next reaction is carried out (P085, genomics, 2016 first edition, Yang Huanming).
  • Sequencing chip preparation The genomic DNA is first fragmented, coupled with a linker sequence, and cyclized to form a single-stranded circular DNA, which is then used to amplify single-stranded circular DNA using Rolling circle amplification (RCA). Three orders of magnitude, the resulting amplification product is called DNA nanosphere (DNB), and the DNA nanospheres are plated onto the amino surface-modified silicon wafer, each amino repair The decoration site only fixes one nanosphere, forms a regular array of DNA nanospheres on the surface of the silicon wafer, and then encapsulates it to form a sequencing chip.
  • RCA Rolling circle amplification
  • the liquid system controls DNA synthesis. Sequencing primers and fluorescently labeled probes with different luminescent wavelengths enter the sequencing chip through the liquid path system, and the primers and probes complete DNA synthesis under the action of DNA ligase, and complete the corresponding elution and excision regeneration process.
  • Imaging detection The laser is used to excite the fluorescent probe to emit light, and different emission wavelengths represent different bases.
  • the emitted fluorescence is recorded by CCD/CMOS via a microscopic imaging system.
  • System control software automates the sequencing process.
  • the entire sequencing process includes infusion, optical focusing and photographing, image acquisition and storage, platform movement and scanning, all automatically controlled by software.
  • the object of the present invention is to provide a gene sequencing reaction device and a gene sequencing system capable of realizing a gene sequencing reaction by using a immersion method.
  • a first aspect of the present invention provides a gene sequencing reaction apparatus comprising: a immersion reaction device comprising a plurality of immersion reaction zones for containing a chemical reagent for gene sequencing reaction to have a DNA sample loading structure on a surface thereof And the sequencing chip loaded with the DNA sample is immersed in the chemical reagent to realize the gene sequencing reaction;
  • the internal transfer device includes an internal material moving unit that moves cyclically along the closed trajectory, and the plurality of immersion reaction zones are sequentially arranged along the closed trajectory.
  • the internal transfer unit is configured to acquire, carry and release the sequencing chip to insert the sampling chip into or out of the immersion reaction zone.
  • the internal transfer device further includes a closed rail structure, the internal transfer unit is mounted on the closed rail structure, and the closed rail structure includes a movement that drives the internal moving unit to move along the closed trajectory Material unit drive unit.
  • the closed rail structure further includes a closed trajectory forming portion and an edge for forming the closed trajectory
  • the moving mounting portion of the closed trajectory moving, the moving unit driving portion is drivingly connected to the moving mounting portion, and the internal moving unit is mounted on the moving mounting portion.
  • the closed track forming portion includes a closed track
  • the moving mounting portion includes a slider slidably disposed on the closed track
  • the moving mounting portion includes a trolley that is rolled on the closed track
  • the shifting unit drive portion includes a power source that drives the closed transport structure to move along the closed trajectory and a closed transport structure that is fixed to the closed transport structure.
  • the internal transfer device includes a plurality of the internal material moving units sequentially disposed along the closed track.
  • the closed trajectory is a planar trajectory.
  • plane track is horizontally set.
  • the internal transfer device further includes a positioning mechanism for accurately positioning the position of the internal material moving unit when the internal material moving unit moves to a position corresponding to the immersion reaction zone.
  • the positioning mechanism includes a positioning driving mechanism, a first positioning structure and a second positioning structure, the first positioning structure is drivingly connected with the positioning driving mechanism, and the second positioning structure is moved relative to the internal positioning
  • the unit is fixedly disposed, and the positioning mechanism drives the first positioning structure to move to the second positioning structure to form a shape with the second positioning structure to achieve precise positioning of the internal material moving unit.
  • one of the first positioning structure and the second positioning structure includes a convex portion, and the other includes a concave portion in which the convex portion is form-fitted.
  • the internal material moving unit includes a material moving drive mechanism and an internal material picking portion that is drivingly coupled to the material moving drive mechanism.
  • the gene sequencing reaction device includes a moving unit driving unit that drives the internal moving unit to move along the closed trajectory
  • the internal transfer device includes a plurality of internal moving units sequentially disposed along the closed trajectory
  • the internal material moving unit includes a power source, and each of the internal material moving units is drivingly connected to the power source and synchronously moved by the power source; or the internal material moving unit includes A plurality of power sources, each of which drives the internal material moving unit in groups, and the internal material moving units of a group of internal material moving units driven by the same power source move synchronously.
  • the gene sequencing reaction apparatus further includes a loading device, the loading device including an loading storage position for placing the sequencing chip, the loading device being located near the closed track to make the interior
  • the seeding unit is capable of obtaining the sequencing chip from the loading storage location; and/or the genetic sequencing reaction device further includes a blanking device, the blanking device comprising a blanking storage location for placing the sequencing chip, the blanking device being located adjacent the closed track to enable the internal transfer unit to release the sequencing chip to The blanking storage bit.
  • the loading device includes a plurality of the loading locations; and/or the blanking device includes a plurality of the blanking storage locations.
  • the loading device further includes a feeding rotating portion, the plurality of loading storage positions are disposed on the feeding rotating portion and can follow the feeding rotating portion to rotate; and/or, the lower portion
  • the material device further includes a blanking rotating portion, wherein the plurality of blanking storage positions are disposed on the cutting rotating portion and can follow the rotating portion of the blanking.
  • the loading device further includes a feeding rotation driving mechanism, the feeding rotation driving mechanism is drivingly connected with the feeding rotating portion to drive the feeding rotating portion to rotate; and/or the cutting
  • the apparatus further includes a blanking drive mechanism, and the blanking feed drive mechanism is drivingly coupled to the blanking rotating portion to drive the lowering rotating portion to rotate.
  • the loading device further includes a loading chip sensing device, wherein the loading chip sensing device is configured to detect whether the loading storage location stores the sequencing chip according to the loading chip sensing device The detection result determines whether the sequencing chip is released at the loading location and/or whether the sequencing chip is removed from the loading location; and/or the blanking device further includes a blanking chip sensing device, The blanking chip sensing device is configured to detect whether the blanking storage bit stores the sequencing chip to determine whether to release the sequencing chip and/or in the blanking storage position according to the detection result of the blanking chip sensing device. Whether the sequencing chip is taken out from the blanking storage location.
  • the loading chip sensing device includes a first loading sensing unit, and the first loading sensing unit is configured to detect whether the loading location stores the sequencing chip to be according to the first The detection result of the loading sensing unit determines whether the sequencing chip is released at the loading location; and/or the loading chip sensing device includes a second loading sensing unit, the second loading sensing The unit is configured to detect whether the loading storage location stores the sequencing chip to determine whether to acquire a sequencing chip from the loading storage location according to the detection result of the second loading sensing unit; and/or, the lower
  • the chip sensing device includes a first blanking sensing unit, and the first blanking sensing unit is configured to detect whether the blanking storage bit stores a sequencing chip according to the detection result of the first blanking sensing unit Determining whether to release the sequencing chip at the blanking storage location; and/or, the blanking chip sensing device includes a second blanking sensing unit, and the second blanking sensing unit is configured to detect the blanking Whether the storage bit stores the sequencing chip According to the detection result of the
  • the internal material moving unit further includes a loading sensing device, the loading device further includes a loading sensing device, and the loading sensing device is configured to be coupled to the internal material moving unit loading sensing device. Determining whether the internal material transfer unit reaches the loading device; and/or, the internal material moving unit further includes a blanking sensing device, the cutting device further comprising a blanking sensing device, the blanking An inductive device is coupled to the internal transfer unit blank sensing device to determine if the internal transfer unit reaches the blanking device.
  • the gene sequencing reaction device further includes a counting device for recording the number of reactions of the sequencing chip.
  • the counting device includes a loading counter for recording the number of times the sequencing chip is loaded; and/or the counting device includes a blanking counter for recording the number of times the sequencing chip is to be unloaded.
  • the immersion reaction device further includes a temperature control device for controlling the temperature of the chemical reagent in the immersion reaction zone.
  • the soaking reaction device comprises one or more infusion vessels, the infusion vessel comprising one or more of the soaking reaction zones.
  • 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 immersion reaction device further includes a bracket and a clamp, and the immersion container is disposed on the bracket through the clamp.
  • the position of the clamp and/or the bracket is adjustably disposed.
  • the gene sequencing reaction device includes a stent position adjusting device for adjusting the position of the stent.
  • the gene sequencing reaction device further includes an electrical slip ring, and at least one electrical device of the gene sequencing reaction device is electrically connected to the power source through the electrical slip ring.
  • the gene sequencing reaction device further includes a control device for controlling the operation of the gene sequencing reaction device.
  • a second aspect of the present invention provides a gene sequencing system comprising a gene sequencing reaction device, characterized in that the gene sequencing reaction device is the gene sequencing reaction device according to any one of the first aspects of the present invention.
  • the gene sequencing system further includes an optical detecting device and an external transfer device, the external shifting The sending device takes out the sequencing chip to be optically detected from the gene sequencing reaction device, sends it to the detection position of the optical detecting device, and takes out the detected sequencing chip from the optical detecting position and sends it to the gene sequencing system.
  • optical detecting device and the genetic sequencing reaction device are arranged around the external transfer device.
  • the optical detecting device includes a plurality of optical platforms, each of the optical platforms including at least one detecting position, the plurality of optical platforms being sequentially disposed and arranged in an arc shape around the external transfer device, A gene sequencing reaction device is located at an arcuate opening formed by the plurality of optical platforms.
  • the external transfer device includes a robot and an external material moving unit connected to the robot, the robot controls a position of the external material moving unit, and the external material moving unit is used to acquire, carry, and release the Sequencing chip.
  • the gene sequencing system includes a master control device that controls the operation of the gene sequencing system.
  • the gene sequencing reaction device provided by the invention can realize the gene sequencing reaction by using the immersion method.
  • 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 internal transfer unit of the internal transfer device circulates along the closed trajectory, and the plurality of immersion reaction zones are arranged along the closed trajectory, so that the genetic sequencing reaction can be performed in an orderly manner in each immersion reaction zone arranged in a closed trajectory, which facilitates the orderly control of the gene sequencing reaction. , reduce operational errors or control errors.
  • the chemical reagents in the immersion reaction zone can be reused, thereby reducing the cost of consumables.
  • the liquid in the immersion reaction zone of the sequencing chip is uniform in pressure and uniform in heat, so that deformation does not occur.
  • the gene sequencing reaction device has no complicated fluid system, few components, easy assembly, and low manufacturing cost. It is also possible to soak multiple sequencing chips at the same time, which has the advantage of high throughput.
  • the gene sequencing reaction device includes a control device for controlling the gene sequencing reaction device, and the entire gene sequencing reaction device is automatically controlled by the control device to realize an automated operation.
  • the gene sequencing system provided based on the present invention includes the aforementioned gene sequencing reaction device, and thus has all the technical effects possessed by the gene sequencing reaction device.
  • FIG. 1 is a schematic perspective view showing the structure of a gene sequencing system according to an embodiment of the present invention
  • FIG. 2 is a schematic perspective view showing the external structure of the external transfer device of the gene sequencing system shown in FIG. 1;
  • FIG. 3 is a schematic perspective view showing an optical structure of an optical detecting apparatus of the gene sequencing system shown in FIG. 1;
  • FIG. 4 is a schematic perspective view showing a perspective of a gene sequencing reaction device of the gene sequencing system shown in FIG. 1;
  • FIG. 5 is a schematic perspective view showing another perspective of a gene sequencing reaction device of the gene sequencing system shown in FIG. 1;
  • Figure 6 is a perspective view showing the internal structure of the internal transfer device of the gene sequencing reaction device shown in Figures 4 and 5;
  • Figure 7 is a perspective view showing the angle of the closed rail structure of the internal transfer device shown in Figure 6;
  • Figure 8 is a perspective view showing another perspective of the closed rail structure of the internal transfer device shown in Figure 6;
  • Figure 9 is a perspective view showing the internal structure of the internal transfer unit of the internal transfer device shown in Figure 6;
  • Figure 10 is a schematic enlarged view showing a portion I of the gene sequencing reaction device shown in Figure 5;
  • Figure 11 is a schematic enlarged plan view showing the loading device of the gene sequencing reaction device shown in Figure 5;
  • Figure 12 is a schematic enlarged plan view showing the unloading device of the gene sequencing reaction device shown in Figure 5;
  • Figure 13 is a schematic view showing the structure of the soaking reaction apparatus of the gene sequencing reaction apparatus shown in Figures 4 and 5;
  • Fig. 14 is a view showing the combined structure of a reagent tank, a jig and a holder of the immersion reaction apparatus shown in Fig. 13.
  • each reference numeral represents: 100, external transfer device; 110, six-axis robot; 120, external material transfer unit; 121, cylinder; 122, jaw; 200, optical detection device; Optical platform; 211, optical detection unit; 300, gene sequencing reaction equipment; 310, soaking reaction device; 311, water bath; 312, reagent tank; 313, fixture; 314, bracket; 315, bracket position adjustment device; 320, internal Transfer device; 321, closed rail structure; 3211, power source; 3212, closed conveyor; 3213, closed track; 3214, slider; 322, internal material transfer unit; 3221, electric cylinder; 3222, jaw; 3223, loading Sensing device; 3224, blank sensing device; 323, positioning mechanism; 3231, positioning cylinder; 3232, positioning wheel; 3233, positioning block; 3234, connecting rod; 3235, rotating shaft; 3236, rotating block; 330, loading Device; 331, loading positioning slot; 332, Feeding turntable; 333, feeding rotation driving mechanism; 3341, first loading sensing unit; 3342
  • the embodiment provides a gene sequencing reaction device and a gene sequencing system.
  • the gene sequencing reaction device 300 of the present embodiment mainly includes an immersion reaction device 310 and an internal transfer device 320 .
  • the soaking reaction device 310 includes a plurality of soaking reaction zones.
  • the immersion reaction zone is used to hold a gene sequencing reaction chemical reagent to achieve a gene sequencing reaction by immersing a sequencing chip 400 having a DNA sample loading structure on the surface and loaded with a DNA sample in a chemical reagent.
  • the internal transfer device 320 includes an internal transfer unit 322 that moves cyclically along a closed trajectory.
  • the plurality of immersion reaction zones are sequentially disposed along a closed trajectory, and the internal transfer unit 322 is configured to acquire, carry, and release the sequencing chip 400 to insert the sequencing chip 400. Immerse the reaction zone or withdraw from the immersion reaction zone.
  • the gene sequencing reaction device 300 provided based on the present invention can realize a gene sequencing reaction by using a soaking method.
  • the internal transfer unit 322 of the internal transfer device 320 cyclically moves along a closed trajectory, and a plurality of immersion reaction zones are along the closed track.
  • the arrangement of the traces enables the sequence sequencing reaction of the soaking reaction zones arranged in a closed trajectory, which facilitates the orderly control of the gene sequencing reaction and reduces operational errors or control errors.
  • the sequencing chip 400 is immersed in the chemical reagents of different immersion reaction zones, and can complete various steps required for the gene sequencing reaction.
  • the chemical reagents in the immersion reaction zone can be reused, thereby reducing the cost of consumables.
  • the sequencing chip 400 receives uniform pressure and uniform heat in the immersion reaction zone, so that deformation does not occur. No complicated fluid system, few parts, easy assembly and low manufacturing cost. Multiple sequencing chips 400 can be immersed at the same time, which has the advantage of high throughput.
  • the gene sequencing reaction device 300 of the present embodiment will be described in detail below with reference to Figs. 1 and 4 to 14.
  • the gene sequencing reaction device 300 of the present embodiment mainly includes an immersion reaction device 310 , an internal transfer device 320 , a loading device 330 , a blanking device 340 , a control device (not shown ) and a support. Platform 350.
  • the immersion reaction device 310, the internal transfer device 320, the loading device 330, and the unloading device 340 are all disposed on the support platform 350.
  • the soaking reaction device 310 includes a plurality of soaking reaction zones.
  • the immersion reaction zone is used to hold a gene sequencing reaction chemical reagent to achieve a gene sequencing reaction by immersing a sequencing chip 400 having a DNA sample loading structure on the surface and loaded with a DNA sample in a chemical reagent.
  • the surface of the sequencing chip 400 has a DNA sample loading structure, and the DNA sample loading structure of the sequencing chip 400 has been loaded with a DNA sample before the gene sequencing reaction.
  • the sequencing chip 400 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 400.
  • a DNA sample is a sequencing reaction template.
  • 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 immersion reaction device 310 may include one or more immersion containers, and the immersion container may include one or more immersion reaction zones.
  • the infusion container is specifically a reagent tank 312. Each reagent tank 312 has a soak reaction zone.
  • the immersion reaction device 310 further comprises a temperature control device for controlling the immersion reaction zone.
  • the temperature control device can control the temperature of the chemical reagent in the immersion reaction zone to provide suitable temperature conditions for the gene sequencing reaction.
  • the temperature control device includes a temperature control portion and a water bath 311.
  • the water bath 311 is for holding a liquid capable of transferring heat.
  • the soaking container is disposed in the water bath 311.
  • the temperature control unit controls the temperature of the liquid in the water bath 311 to control the temperature of the chemical agent in the immersion reaction zone. Wherein the soaking container can transfer heat between the outside of the infusion container and the soaking reaction zone in the wall of the infusion container through the wall of the container.
  • the temperature control device may include a plurality of water baths 311.
  • the temperature control device includes seven water baths 311.
  • the temperature of the liquid in each water bath 311 may be the same or different depending on the temperature requirements of the chemical reagents required for each soaking step of the gene sequencing reaction. As shown in FIG. 1, each water bath 311 is disposed on the support platform 350.
  • the temperature control unit is a heat exchange tube disposed in the wall of the water bath 311, and the heat exchange tube can input heat to the liquid in the water bath 311 or absorb heat from the liquid in the water bath 311, thereby allowing the water bath.
  • the heat transfer liquid in the pot 311 can be heated or lowered in temperature.
  • the heat transfer liquid in the water bath 311 can be heated or lowered, and the soaking container is immersed in the heat conductive liquid, thereby being able to control the soaking of the soaking container.
  • the temperature of the chemical reagent in the reaction zone is beneficial to ensure that the biochemical reaction proceeds smoothly.
  • the use of a liquid as a heat transfer medium allows a more uniform control of the temperature of the chemical reagents in each of the infusion containers. Moreover, the temperature of the chemical reagent is more stable and is not easily changed rapidly.
  • the liquid in the water bath 311 can be, for example, water or oil.
  • a temperature controller such as a Peltier temperature controller may be used to directly heat or cool the infusion container or the chemical reagent therein, but the direct temperature control method and the water bath are used.
  • the method of indirect temperature control of the pot 311 is more prone to uneven heating and cooling.
  • the immersion reaction device 310 further includes a bracket 314 and a clamp 313 , and the immersion container is disposed on the bracket 314 by the clamp 313 .
  • the position of the clamp 313 and/or the bracket 314 is adjustably disposed.
  • the gene sequencing reaction apparatus 300 includes a rack position adjusting device 315 for adjusting the position of the bracket 314.
  • the bracket position adjusting device 315 is disposed on the support platform 350, and the bracket 314 is disposed on the bracket position adjusting device 315.
  • the bracket position adjusting device 315 can simultaneously adjust the height and the rotation angle of the bracket 314 to adjust the position of the reagent tank 312.
  • the internal transfer device 320 includes an internal transfer unit 322 that moves cyclically along a closed trajectory.
  • the plurality of immersion reaction zones are sequentially disposed along a closed trajectory, and the internal transfer unit 322 is configured to acquire, carry, and release the sequencing chip 400 to insert the sequencing chip 400. Immerse the reaction zone or withdraw from the immersion reaction zone.
  • the internal transfer device 320 includes a plurality of internal transfer units 322 that are sequentially disposed along a closed track.
  • a plurality of internal material moving units 322 are disposed, which can be operated simultaneously for different immersion reaction zones, and, due to the setting of the closed trajectory, the internal movement unit 322 can be mutually interfered with each other, thereby improving the gene sequencing reaction device.
  • the closed trajectory is a planar trajectory, that is, the closed trajectories are all located in the same plane as a whole. More preferably, the planar trajectory is horizontally set. Specifically, in this embodiment, the closed trajectory is an oblong planar trajectory disposed along a horizontal plane.
  • the planar trajectory and horizontal arrangement facilitate processing and placement of the internal transfer device and its components, and have better operability with respect to stereoscopic trajectories or non-horizontal arranged planar trajectories.
  • the stereo trajectory and the non-horizontal arrangement of the planar trajectory are not excluded, and both have better arrangement flexibility with respect to the horizontally arranged planar trajectory.
  • the closed trajectory may also be other forms of planar trajectories or stereo trajectories, such as a circular circle, an ellipse, a polygonal trajectory with rounded transitions, or the like, or a partial concave curve.
  • the closed trajectory of the present invention may also be a planar trajectory at an angle to the horizontal.
  • the internal transfer device 320 further includes a closed rail structure 321 , the internal transfer unit 322 is mounted on the closed rail structure 321 , and the closed rail structure 321 includes the internal transfer material.
  • the unit 322 moves the unit moving unit along the closed trajectory.
  • the closed rail structure 321 further includes a closed track forming portion for forming a closed track and a moving mounting portion moving along the closed track.
  • the transfer unit drive unit is drivingly coupled to the mobile mounting unit.
  • the internal transfer unit 322 is mounted on the mobile mounting portion.
  • the closed track forming portion includes an oblong closed track 3213
  • the moving mounting portion includes a slider 3214 that is slidably disposed on the closed track 3213.
  • the mobile mounting portion may also include a trolley that is rolled over the closed track 3213.
  • the internal material moving unit 322 is fixed to the outside of the outer side surface of the slider 3214. Among them, the inside and outside are relative to the closed trajectory. As shown in FIG. 6, the internal material moving unit 322 is entirely below the slider 3214.
  • the shifting unit driving portion includes a power source 3211 and a closed transmission structure.
  • Power source 3211 drives the closed transmission structure to move along the closed trajectory.
  • the mobile mounting portion is secured to the closed transport structure.
  • the power source 3211 is a rotating electrical machine.
  • the closed transmission structure is an endless conveyor belt 3212.
  • the rotary motor drives the endless belt 3212 to move by the pulley.
  • the slider 3214 is fixedly coupled to the endless belt 3212 such that the endless belt 3212 moves the slider 3214 and the internal transfer unit 322 on the slider 3214 to move along a closed trajectory defined by the closed track 3213.
  • the power source 3211 can also be in other forms, such as a hydraulic motor.
  • the closed transport structure can also be in other forms, such as a conveyor chain, a toothed belt, and the like.
  • a plurality of power sources may be provided according to the requirements of gene sequencing, each of the power sources driving the internal material moving unit in groups, and the internal materials of a group of internal material moving units driven by the same power source.
  • the unit moves synchronously.
  • each group of internal material moving units may include one or more internal material moving units.
  • each power source drives an internal material moving unit one by one.
  • Each power source drives the internal material moving unit in groups to control the reaction time of the sequencing chip or the sequencing step, thereby improving control flexibility.
  • the closed rail structure 321 includes 24 sliders 3214, and thus, 24 internal shifting units 322 can be assembled.
  • the number of internal transfer units 322 can be set according to the requirements of the gene sequencing reaction device 300, and does not necessarily coincide with the number of sliders 3214.
  • the genetic sequencing reaction device 300 may include two or more internal transfer devices 320 and a soak reaction zone disposed in cooperation with the internal transfer device 320.
  • the chemical reagents in the immersion reaction zone corresponding to the two or more internal transfer devices 320 may be the same to increase the throughput of the sequencing chip 400, or may be different to complete different gene sequencing reaction steps.
  • the internal material moving unit 322 includes a material moving drive mechanism and an internal material take-up portion that is drivingly coupled to the material moving drive mechanism.
  • the transfer drive mechanism includes an electric cylinder 3221, and the internal reclaiming portion includes a driving connection with the electric cylinder 3221. Claw 3222.
  • the electric cylinder 3221 is a modular product designed by integrating a servo motor and a lead screw, and converts the rotary motion of the servo motor into a linear motion, thereby realizing high-precision linear motion.
  • the electric cylinder 3221 is advantageous for improving the accuracy of movement of the inner take-up portion.
  • the electric cylinder 3221 can also be replaced with other drive mechanisms, such as hydraulic cylinders and the like.
  • the internal reclaiming portion may also be in other forms, such as a vacuum chuck, an electromagnetic chuck, or the like that cooperates with the chip holding device 500 for supporting the sequencing chip 400.
  • the chip holding device 500 is used to fix the sequencing chip 400, so that the sequencing chip 400 moves along with the chip holding device 500.
  • the chip holding device 500 can include one or more chip mounting locations, including a chip mounting location in this embodiment.
  • the sequencing chip 400 is mounted to a chip mounting location to move the sequencing chip 400 by the mobile chip holding device 500.
  • the chip holding device 500 can reduce the pollution caused by directly operating the sequencing chip 400 on the one hand, and can simultaneously move the plurality of sequencing chips 400 through the chip holding device 500 and maintain the plurality of sequencing chips 400 at a predetermined interval as needed, thereby improving The throughput of the sequencing chip 400.
  • the bilateral surface of the sequencing chip 400 has a DNA sample loading structure.
  • the chip mounting position includes a chip mounting port, the sequencing chip 400 is installed 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 400, which can increase the number of DNA sample molecules loaded by the single-chip sequencing chip 400.
  • the jaws 3222 of the internal material moving unit 322 indirectly sandwich the sequencing chip 400 through the chip holding device 500 to realize the connection between the internal material moving unit 322 and the sequencing chip 400. Indirect clamping of the sequencing chip 400 can prevent cross-contamination after the jaws 3222 are clamped to different sequencing chips 400.
  • the clamping jaws 3222 indirectly clamp the sequencing chip 400 by clamping the chip holding device 500, and only need to process the clamping structure on the chip holding device 500 without processing the clamping structure on the sequencing chip 400, thereby reducing the sequencing chip 400. The processing cost also maximizes the surface area of the sequencing chip 400.
  • the internal transfer unit 322 and the sequencing chip 400 may be connected by directly clamping the sequencing chip 400 with the clamping jaws 3222.
  • the internal material moving unit 322 further includes a loading sensing device 3223 and a blanking sensing device 3224 for determining whether the internal material moving unit 322 reaches the loading device of the loading device 330. position.
  • the blank sensing device 3224 is used to determine whether the internal material moving unit 322 reaches the blanking position of the blanking device 340.
  • the internal transfer device 320 In order to accurately position the relative position of the internal transfer device and the immersion reaction zone, the internal transfer device 320 also includes a positioning mechanism 323.
  • the positioning mechanism 323 is for accurately positioning the position of the internal material moving unit 322 when the internal material moving unit 322 is moved to a position corresponding to the immersion reaction zone.
  • the positioning mechanism 323 includes a positioning driving mechanism, a first positioning structure, and a second positioning structure.
  • the first positioning structure is drivingly coupled with the positioning driving mechanism, and the second positioning structure is fixedly disposed with respect to the internal moving unit 322.
  • the precise positioning of the internal material moving unit 322 is achieved by the positioning drive mechanism driving the first positioning structure to move to the second positioning structure to form a shape with the second positioning structure.
  • one of the first positioning structure and the second positioning structure includes a raised portion and the other includes a concave shaped portion of the raised portion.
  • a plurality of positioning mechanisms 323 are provided along the closed trajectory.
  • the positioning driving mechanism of each positioning mechanism 323 is a positioning cylinder 3231;
  • the first positioning structure includes a positioning wheel 3232 that is drivingly coupled to the positioning cylinder 3231, and the convex surface of the positioning wheel 3232 forms a convex portion;
  • the second positioning structure includes a fixed positioning portion A positioning block 3233 outside the slider 3214, and a central portion of the positioning block 3233 is provided with a concave portion that is shaped to fit the positioning wheel 3232.
  • one positioning cylinder 3231 can simultaneously drive a plurality of positioning wheels 3232 to operate.
  • the piston rod end of the positioning cylinder 3231 is hinged with the first end of the connecting rod 3234, the second end of the connecting rod 3234 is fixedly connected with the rotating shaft 3235, and the rotating shaft 3235 is simultaneously distributed with a plurality of rotating blocks 3236 in the axial direction.
  • Each of the rotating blocks 3236 is relatively fixedly disposed with the rotating shaft 3235, and a positioning wheel 3232 is disposed at the bottom of each rotating block 3236.
  • the piston rod of the positioning cylinder 3231 protrudes, and the rotating shaft 3235 is rotated by the connecting rod 3234, and the rotating shaft 3235 drives the positioning wheel 3232 to move closer to the positioning block 3233 by the rotating block 3236.
  • the positioning wheel 3232 is form-fitted with the recess of the corresponding positioning block 3233 to more precisely define the position of the internal material moving unit 322 relative to the closed track.
  • the piston rod of the positioning cylinder 3231 is retracted, and the positioning wheel 3232 moves in a direction away from the positioning block 3233 to release the engagement with the concave portion.
  • the arrangement of the positioning mechanism 323 can reduce or eliminate the transmission error from the power source 3211 to the slider 3214, and therefore, even if the transmission of the endless belt 3212 or the like closed transmission structure or the like is not accurate enough, it can be compensated by the positioning mechanism 323, thereby reducing the interior. The probability of the movement of the moving unit 322 is wrong.
  • the specific implementation of the positioning mechanism 323 may be different, for example, positioning.
  • the cylinder 3231 can be replaced by an electric cylinder, a cylinder, a linear motor or the like.
  • the structure of the first positioning structure itself and the connection mode with the positioning drive mechanism can be changed, and the structure and installation position of the second positioning structure itself can also be changed.
  • the loading device 330 includes a loading location for placing the sequencing chip 400, and the loading device 330 is located adjacent the closed track to enable the internal transfer unit 322 to take the sequencing chip 400 from the loading location.
  • the loading device 330 includes a plurality of loading locations. As shown in FIGS. 5 and 11, each of the loading locations is formed by a loading positioning slot 331.
  • the loading device 330 further includes a feeding rotating portion, and the plurality of loading storage positions are disposed on the feeding rotating portion and can rotate according to the feeding rotating portion.
  • the feeding rotating portion specifically includes a feeding turntable 332, and 12 loading positioning slots 331 are evenly placed around the rotating center on the loading turntable 332, and one loading slot 331 can be loaded in each loading positioning slot 331 Sequencing chip 400.
  • the loading device 330 further includes a feeding rotation driving mechanism 333, and the feeding rotation driving mechanism 333 is drivingly coupled with the feeding rotating portion to drive the feeding rotating portion to rotate.
  • the feeding rotation driving portion is a feeding servo motor.
  • the loading device 330 further includes a loading chip sensing device, and the loading chip sensing device is configured to detect whether the loading storage location stores the sequencing chip 400 to determine whether to release the loading location according to the detection result of the loading chip sensing device.
  • the loading chip sensing device includes a first loading sensing unit 3341, and the first loading sensing unit 3341 is configured to detect whether the loading storage location stores the sequencing chip 400 according to the first loading sensing unit.
  • the detection result of 3341 determines whether the sequencing chip 400 is released in the loading location;
  • the loading chip sensing device further includes a second loading sensing unit 3342, and the second loading sensing unit 3342 is configured to detect whether the loading location is stored.
  • the sequencing chip 400 determines whether the sequencing chip 400 is taken out from the loading location according to the detection result of the second loading sensing unit 3342.
  • the first loading sensing unit 3341 and the second loading sensing unit 3342 are both photoelectric sensors.
  • the photosensor as the first loading sensing unit 3341 detects whether the sequencing chip 400 is present in the loading positioning slot 331 on the feeding rotating portion. If the sequencing chip 400 is not detected, the external transfer device 100 will take the slave optical platform 210. The detected sequencing chip 400 taken out at the detection position is inserted into the loading positioning slot 331.
  • the photosensor as the second loading sensing unit 3342 detects whether the sequencing chip 400 is present in the loading positioning slot 331 when the loading position is in the loading position.
  • the loading rotating portion moves one position until When the sequencing chip 400 is detected in the loading positioning slot 331 in the loading position, the jaws 3222 of the internal material moving unit 322 take the sequencing chip 400 out from the corresponding loading positioning slot 331 of the loading rotating portion. Then move to the phase The soaking reaction zone should be.
  • the loading device 330 further includes a loading sensing device 335 for coupling with the loading sensing device 3223 of the internal material moving unit 322 to determine whether the internal material moving unit 322 has arrived. The loading position of the loading device 330.
  • the blanking device 340 includes a blanking storage location for placing the sequencing chip 400, and the blanking device 340 is located adjacent the closed track to enable the internal transfer unit 322 to release the sequencing chip 400 to the blanking storage location.
  • the blanking device 340 includes a plurality of blanking storage locations. As shown in FIGS. 5 and 12, each of the blanking storage locations is formed by a blanking positioning slot 341.
  • the unloading device 340 further includes a blanking rotating portion, and a plurality of blanking storage positions are disposed on the cutting rotating portion and can follow the turning rotating portion.
  • the unloading rotating portion specifically includes a blanking turntable 342.
  • the blanking turntable 342 uniformly places 12 blank positioning slots 341 around the rotating center, and each of the blanking positioning slots 341 can be loaded with one. Sequencing chip 400.
  • the unloading device 340 further includes a blanking drive mechanism 343, and the unloading rotary drive mechanism is drivingly coupled to the blanking rotating portion to drive the lowering rotating portion to rotate.
  • the blanking drive unit is a blanking servo motor.
  • the unloading device 340 further includes a blanking chip sensing device, and the blanking chip sensing device is configured to detect whether the blanking storage location stores the sequencing chip 400 to determine whether to release the sequencing in the blanking storage position according to the detection result of the blanking chip sensing device. The chip 400 and/or whether the sequencing chip 400 is removed from the blanking storage location.
  • the blanking chip sensing device includes a first blanking sensing unit 3441, and the first blanking sensing unit 3441 is configured to detect whether the blanking storage location stores the sequencing chip 400 according to the first blanking sensing unit.
  • the detection result of 3441 determines whether the sequencing chip 400 is released at the blanking storage location.
  • the blanking chip sensing device further includes a second blanking sensing unit 3442, and the second blanking sensing unit 3442 is configured to detect whether the blanking storage location stores the sequencing chip 400 according to the detection result of the second blanking sensing unit 3442. It is determined whether the sequencing chip 400 is taken out from the blanking storage bit.
  • the first blanking sensing unit 3441 and the second blanking sensing unit 3442 are both photoelectric sensors.
  • the photoelectric sensor of the first blanking sensing unit 3441 detects whether the sequencing chip 400 exists in the blank positioning slot 341 when the blanking position is in the blanking position, if the sequencing chip 400 is not detected, the internal moving unit The jaws 3222 of 322 insert the sequencing chip 400 that completed the last gene sequencing reaction into the blank positioning slot 341.
  • the photosensor as the second blanking sensing unit 3442 detects whether the sequencing chip 400 is present in the blank positioning slot 341. If the sequencing chip 400 is not detected, the blanking portion moves to a position until the positioning of the blanking is sensed.
  • the external transfer device 100 positions the blanking slot.
  • the sequencing chip 400 in 341 is transferred to the detection position of an optical table 210 for optical detection.
  • the blanking device 340 further includes a blanking sensing device 345 for coupling with the blanking sensing device 3224 of the internal material moving unit 322 to determine whether the internal material moving unit 322 has arrived.
  • the blanking position of the unloading device 340 is not limited to the blanking sensing device 345.
  • the loading sensing device 335 includes a loading sensing piece
  • the blanking sensing device 345 includes a blanking sensing piece.
  • the blanking sensing device 3224 of the internal material moving unit 322 senses the blanking sensing piece and feeds back to the control device, and the control device sends the internal loading unit 322
  • the sequencing chip 400 is inserted into the instruction blank positioning slot 341.
  • the sequencing chip 400 is mounted on the chip holding device 500 during the loading storage position, the immersion reaction zone, the blanking storage location, the detection location, and the transfer by the internal transfer device 320 and the external transfer device 100.
  • the gene sequencing reaction device 300 further includes counting means for recording the number of reactions of the sequencing chip 400.
  • the counting device may include a loading counter for recording the number of times the sequencing chip 400 is loaded; for example, the counting device may include a blanking counter for recording the number of times the sequencing chip 400 is to be unloaded.
  • the counting device is a scanner 360 disposed at the unloading device 340.
  • the gene sequencing reaction device 300 further includes an electrical slip ring, and at least one electrical device of the genetic sequencing reaction device 300 is electrically connected to the power source through an electrical slip ring. Electrically connecting the electrical device of the gene sequencing reaction to the power source through the electrical slip ring can prevent problems such as air tube and/or wire entanglement.
  • the control device is used to control the operation of the gene sequencing reaction device 300. Automated operations for gene sequencing reactions can be controlled by control devices.
  • control device is coupled with the power source 3211 of the mobile unit driving unit and the material moving drive mechanism and the related detecting device to control the action of the internal material moving unit 322, thereby automatically controlling the internal material moving unit 322 to the sequencing chip 400.
  • the various operations can improve the automation degree of the gene sequencing reaction device 300, reduce the error rate caused by the manual operation, and accurately control the soaking sequence and the soaking time by cooperation with the control device, thereby facilitating the high-quality completion of the gene sequencing. reaction.
  • control device can also be coupled to the temperature control device to control the temperature of the chemical reagent.
  • the control device can be a built-in control device disposed on the support platform 350.
  • An external control device can also be coupled to the gene sequencing reaction device 300 to control and monitor the operation of the gene sequencing reaction device 300.
  • the control device By controlling the temperature control device and the internal material moving unit 322 by the control device, the automated operation of the gene sequencing reaction device 300 can be realized, and the quality and efficiency of gene sequencing can be improved.
  • the support platform 350 is a cabinet.
  • the reagents and tools required for the gene sequencing reaction can be stored and stored in the cabinet.
  • casters are installed under the cabinet.
  • support of portions of the gene sequencing reaction device 300 can also be achieved by a support frame.
  • this embodiment also provides a gene sequencing system, including the aforementioned gene sequencing reaction device 300.
  • the gene sequencing system further includes an optical detecting device 200 and an external transfer device 100.
  • the external transfer device 100 takes out the sequencing chip 400 to be optically detected from the gene sequencing reaction device 300 and sends it to the detecting position of the optical detecting device 200. And the sequencing chip 400 that has taken out the detection from the optical detection position is sent to the gene sequencing reaction device 300.
  • the optical detecting device 200 and the gene sequencing reaction device 300 are arranged around the external transfer device 100.
  • the gene sequencing system includes a set of gene sequencing reaction devices 300. In other embodiments not shown, the gene sequencing system may include two or more sets of gene sequencing reaction devices 300.
  • the optical detecting device 200 includes a plurality of optical platforms 210, each of which includes at least one detecting position.
  • the plurality of optical platforms 210 are sequentially disposed and arranged in an arc around the external transfer device 100, and the genetic sequencing reaction device 300 is located.
  • a plurality of optical platforms 210 are formed at arcuate openings.
  • the optical detecting apparatus 200 of the present embodiment specifically includes ten optical stages 210.
  • the external transfer device 100 includes a robot and an external transfer unit 120 coupled to the robot.
  • the robot controls the position of the external transfer unit 120, and the external transfer unit 120 is used to acquire, carry, and release the sequencing chip 400.
  • the external transfer device 100 includes one robot and a corresponding external material moving unit 120. In other embodiments not shown, the external transfer device 100 can set more robots and corresponding external shifts according to sequencing requirements. Material unit 120.
  • the robot is preferably a six-axis robot 110.
  • the six-axis robot 110 has greater travel and freedom to ensure that the sequencing chip 400 is transferred between the 10 sets of optical platforms 210 and the gene sequencing reaction device 300.
  • the external material moving unit 120 preferably includes a cylinder 121 and a jaw 122 that is drivingly coupled to the cylinder 121.
  • the cylinder 121 can be replaced by other driving mechanisms such as an oil cylinder and an electric cylinder; similarly to the internal material retrieving portion, a structure such as a suction cup can also be used as the external material moving unit.
  • the optical platform 210 is divided into two layers.
  • the lower rack mainly stores the industrial computer and the liquid path system, and the upper layer mainly sets the optical detecting unit 211 and the detecting position.
  • the optical detecting unit 211 is configured to take an image, read image data, and then analyze, process, store, and the like the image data, and finally obtain a gene sequence to realize gene sequencing.
  • the gene sequencing system can include a master control device that controls the operation of the gene sequencing system.
  • the external transfer device 100, the optical detecting device 200, and the gene sequencing reaction device 300 can be collectively controlled by the master control device.
  • the master control device may exchange data with the control device of the gene sequencing reaction device 300; in other embodiments, the master device may completely replace the function of the control device of the gene sequencing reaction device 300.
  • the control device of the gene sequencing reaction device 300 is not essential.
  • the basic operation flow of the gene sequencing reaction device 300 of the present embodiment and the gene sequencing system having the same is as follows:
  • the 12 chips are manually placed in the 12 loading positioning slots 331 on the loading turntable 332, and the loading turntable 332 is rotated by the loading servo motor, and the sequencing chip 400 follows the feeding turntable 332.
  • the internal material moving unit 322 grabs the sequencing chip 400 and moves upward, and takes out the sequencing chip from the corresponding loading positioning slot 331. 400.
  • the movement of the moving material driving mechanism of the closed rail structure 321 moves, and after the internal material moving unit 322 moves to the position above the reagent tank 312 in the water bath 311, the sequencing chip 400 is driven to move downward and inserted into the reagent tank 312 for biochemistry. reaction. Due to the limitation of the biochemical reaction procedure and the experimental procedure, each of the sequencing chips 400 needs to be sequentially sequentially subjected to a biochemical reaction in the desired reagent tank 312 disposed along the closed trajectory. After the first sequencing chip 400 completes the grasping movement action, the loading turntable 332 rotates and moves one station, and the next internal moving unit 322 takes out the second sequencing chip 400 from the next loading positioning slot 331 and sequentially Different soaking reaction zones are transferred to the sequencing chip 400.
  • Each internal material moving unit 322 sequentially completes the reclaiming and sequentially transfers the sequencing chip 400 in different immersion reaction zones to complete the biochemical reaction.
  • the internal transfer unit 322 brings the sequencing chip 400 into the reagent tank 312, it is put into the chemical reagent in the reagent tank 312 for reaction at a set time.
  • the reaction times of all the sequencing chips 400 are uniform.
  • the sequencing chip 400 When a sequencing chip 400 completes the biochemical reaction in the last immersion reaction zone, the sequencing chip 400 is grasped by the internal transfer unit 322 and placed in the blank positioning slot 341. After the first sequencing chip 400 has been stored in the blank positioning slot 341, the blanking tray 342 rotates one station, waits for the second sequencing chip 400 to be unloaded, and so on.
  • the external transfer device 100 grabs the first sequencing chip 400 and places it on the first optical platform 210 for image capturing, image processing, data storage analysis, and the like.
  • the detection work is the first genetic sequencing procedure.
  • the second sequencing chip 400 is taken from the next blank positioning slot 341 and placed on the second optical platform 210 for the same Work, in turn, complete the detection of other sequencing chips 400.
  • the first sequencing chip 400 completes one round of inspection work, it is grasped by the external transfer device 100 and placed in the loading positioning slot 331 of the loading device 330 to start a new round of biochemical reaction and The detection work is repeated for 50-100 times, and the sequencing of a sequencing chip 400 is completed.
  • the above embodiment of the present invention has at least one of the following technical effects:
  • the gene sequencing reaction device 300 can perform a gene sequencing reaction by using a soaking method.
  • the internal transfer unit 322 of the internal transfer device 320 cyclically moves along a closed trajectory, and a plurality of immersion reaction regions are arranged along a closed trajectory, so that the genetic sequencing reaction can be performed in an orderly manner in each immersion reaction zone arranged in a closed trajectory, which facilitates the gene sequencing reaction. Order control to reduce operational errors or control errors.
  • the sequencing chip 400 is immersed in chemical reagents in different immersion reaction zones to complete the various steps required for the sequencing reaction.
  • the sequencing chip 400 receives uniform pressure and uniform heat in the immersion reaction zone, so that deformation does not occur.
  • the full automation of the gene sequencing reaction device 300 and the gene sequencing system can be realized, allowing multiple chips to continuously perform biochemical reactions at the same time, which is suitable for fully automated large-scale gene sequencing work, and significantly improves the efficiency of gene sequencing.
  • the number of sequencing chips 400 used can be determined according to the sequencing requirements, and the scalability is good, the flux is high, and the flexibility is good.

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Abstract

一种基因测序反应设备和基因测序系统。基因测序反应设备包括：浸泡反应装置，包括多个浸泡反应区，浸泡反应区用于盛放基因测序反应用化学试剂以通过将表面具有DNA样品加载结构并加载有DNA样品的测序芯片浸泡于化学试剂内实现基因测序反应；内部转移装置，包括沿闭合轨迹循环移动的内部移料单元，多个浸泡反应区沿闭合轨迹依次设置，内部移料单元用于取得、携带和释放测序芯片，以将测序芯片插入浸泡反应区或从浸泡反应区中抽离。基因测序系统包括前述的基因测序反应设备。所述基因测序反应设备和基因测序系统能采用浸泡方式实现基因测序反应。

Description

基因测序反应设备和基因测序系统 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和基因测序系统。
背景技术
第二代基因测序技术基于第一代Sanger测序技术发展而来，具有低成本，高通量，自动化等特征，极大地推进了基因测序产业的发展。第二代基因测序技术目前已经广泛应用于全基因组测序、转录组测序、宏基因组测序等，是分析生物的进化与分类，研究癌症、自闭症等疾病相关基因，以及进行体外诊断等的有力工具，促进了人们对于生命科学的进一步了解，也推动了健康产业的发展。
经过十年的发展，第二代基因测序技术已相对较为成熟，新的测序平台和产品也代次更迭，朝着低成本和高通量的趋势迅猛发展。以目前最常用的边合成边测序的基因测序方法为例，其通过捕捉新合成的末端的标记来确定DNA的序列，主要包括：1)测序文库制备，将DNA随机打断成小片段；2)PCR扩增，产生成千上万重复片段；3)不同碱基添加不同的荧光标记，进行荧光成像测序。
现有技术中，第二代基因测序技术主要包括Illumina的SBS测序技术，和BGI的CPAS测序技术。这两种测序技术都基于DNA合成的可逆性末端循环，即3’-OH可逆性的阻断和再生，其基本原理是：1)将待测样品装载到芯片上；2)在dNTP(dATP，dCTP，dGTP，dTTP)的3’-OH加一个阻断，在碱基上加一个检测基团；3)每次反应时，因为阻断的存在，只会加上一个互补的dNTP；4)用技术手段检测该dNTP所携带的基团后，用试剂对阻断基团进行切除，进行下一步反应(P085，基因组学，2016年第一版，杨焕明著)。
以BGI的CPAS测序技术为例，其主要包括以下过程：
测序芯片制备。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，随后使用的滚环扩增技术(Rolling circle amplification，RCA)可将单链环状DNA扩增2-3个数量级，所产生的扩增产物称为DNA纳米球(DNA nanoball，DNB)，把DNA纳米球平铺到经过氨基表面修饰的硅片上，每个氨基修 饰位点仅固定一个纳米球，在硅片表面形成DNA纳米球规则阵列，再加以封装，形成测序芯片。
液路系统控制DNA合成。测序引物和不同发光波长的荧光标记探针通过液路系统进入测序芯片，引物和探针在DNA连接酶的作用下完成DNA的合成，并且完成相应的洗脱和切除再生过程。
成像检测。使用激光激发荧光探针发光，不同发光波长代表不同的碱基。发出的荧光经显微成像系统被CCD/CMOS记录。
系统控制软件实现测序过程的自动化。整个测序过程包括进液、光学聚焦和拍照，图像采集和存储、平台移动和扫描等都由软件自动控制完成。
图像处理和分析。由CCD/CMOS记录的荧光信号经过计算机进行图像处理和分析，实现碱基识别。
以上现有技术的第二代测序方法需要精确的温度控制和流体控制，成本较高，且容易出现反应不均匀现象。基因测序反应所用的化学试剂都是一次性使用，利用率较低，进一步提高了测序成本。另外，现有技术的基因测序系统，还普遍存在通量较低的情况。
发明内容
本发明的目的在于提供一种能采用浸泡方式实现基因测序反应的基因测序反应设备和基因测序系统。
本发明第一方面提供一种基因测序反应设备，包括：浸泡反应装置，包括多个浸泡反应区，所述浸泡反应区用于盛放基因测序反应用化学试剂以通过将表面具有DNA样品加载结构并加载有DNA样品的测序芯片浸泡于化学试剂内实现基因测序反应；内部转移装置，包括沿闭合轨迹循环移动的内部移料单元，所述多个浸泡反应区沿所述闭合轨迹依次设置，所述内部移料单元用于取得、携带和释放所述测序芯片，以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，所述内部转移装置还包括闭合轨结构，所述内部移料单元安装于所述闭合轨结构上，所述闭合轨结构包括带动所述内部移料单元沿所述闭合轨迹移动的移料单元驱动部。
进一步地，所述闭合轨结构还包括用于形成所述闭合轨迹的闭合轨迹形成部和沿 所述闭合轨迹移动的移动安装部，所述移料单元驱动部与所述移动安装部驱动连接，所述内部移料单元安装于所述移动安装部上。
进一步地，所述闭合轨迹形成部包括闭合轨道，所述移动安装部包括滑动设置于所述闭合轨道上的滑块和/或所述移动安装部包括滚动设置于所述闭合轨道上的小车。
进一步地，所述移料单元驱动部包括动力源和闭合传输结构，所述动力源驱动所述闭合传输结构沿所述闭合轨迹移动，所述移动安装部固定于所述闭合传输结构上。
进一步地，所述内部转移装置包括沿所述闭合轨迹依次设置的多个所述内部移料单元。
进一步地，所述闭合轨迹为平面轨迹。
进一步地，所述平面轨迹水平设置。
进一步地，所述内部转移装置还包括定位机构，所述定位机构用于在所述内部移料单元移动至与浸泡反应区对应的位置时，精确定位所述内部移料单元的位置。
进一步地，所述定位机构包括定位驱动机构、第一定位结构和第二定位结构，所述第一定位结构与所述定位驱动机构驱动连接，所述第二定位结构相对于所述内部移料单元固定设置，通过所述定位驱动机构驱动所述第一定位结构向所述第二定位结构移动以与所述第二定位结构形状配合实现所述内部移料单元的精确定位。
进一步地，所述第一定位结构和所述第二定位结构中的一个包括凸起部，另一个包括所述凸起部形状配合的凹入部。
进一步地，所述内部移料单元包括移料驱动机构和与所述移料驱动机构驱动连接的内部取料部。
进一步地，所述基因测序反应设备包括带动所述内部移料单元沿所述闭合轨迹移动的移料单元驱动部，所述内部转移装置包括沿所述闭合轨迹依次设置的多个内部移料单元，其中，所述内部移料单元包括一个动力源，各所述内部移料单元均与所述动力源驱动连接并在所述动力源的带动下同步移动；或者，所述内部移料单元包括多个动力源，每个动力源按组驱动内部移料单元，由同一个动力源驱动的一组内部移料单元的各内部移料单元同步移动。
进一步地，所述基因测序反应设备还包括上料装置，所述上料装置包括用于放置所述测序芯片的上料存储位，所述上料装置位于所述闭合轨迹附近以使所述内部移料单元能够从所述上料存储位取得所述测序芯片；和/或，所述基因测序反应设备还包括 下料装置，所述下料装置包括用于放置所述测序芯片的下料存储位，所述下料装置位于所述闭合轨迹附近以使所述内部移料单元能够将所述测序芯片释放至所述下料存储位。
进一步地，所述上料装置包括多个所述上料存储位；和/或，所述下料装置包括多个所述下料存储位。
进一步地，所述上料装置还包括上料转动部，所述多个上料存储位设置于所述上料转动部上并能跟随所述上料转动部转动；和/或，所述下料装置还包括下料转动部，所述多个下料存储位设置于所述下料转动部上并能跟随所述下料转动部转动。
进一步地，所述上料装置还包括上料转动驱动机构，所述上料转动驱动机构与所述上料转动部驱动连接以驱动所述上料转动部转动；和/或，所述下料装置还包括下料转动驱动机构，所述下料转料驱动机构与所述下料转动部驱动连接以驱动所述下料转动部转动。
进一步地，所述上料装置还包括上料芯片传感装置，所述上料芯片传感装置用于检测所述上料存储位是否存放所述测序芯片以根据所述上料芯片传感装置的检测结果确定是否在所述上料存储位释放测序芯片和/或是否从所述上料存储位取出所述测序芯片；和/或，所述下料装置还包括下料芯片传感装置，所述下料芯片传感装置用于检测所述下料存储位是否存放所述测序芯片以根据所述下料芯片传感装置的检测结果确定是否在所述下料存储位释放测序芯片和/或是否从所述下料存储位取出所述测序芯片。
进一步地，所述上料芯片传感装置包括第一上料传感单元，所述第一上料传感单元用于检测所述上料存储位是否存放所述测序芯片以根据所述第一上料传感单元的检测结果确定是否在所述上料存储位释放测序芯片；和/或，所述上料芯片传感装置包括第二上料传感单元，所述第二上料传感单元用于检测所述上料存储位是否存放所述测序芯片以根据所述第二上料传感单元的检测结果确定是否从所述上料存储位取出测序芯片；和/或，所述下料芯片传感装置包括第一下料传感单元，所述第一下料传感单元用于检测所述下料存储位是否存放测序芯片以根据所述第一下料传感单元的检测结果确定是否在所述下料存储位释放测序芯片；和/或，所述下料芯片传感装置包括第二下料传感单元，所述第二下料传感单元用于检测所述下料存储位是否存放所述测序芯片以根据所述第二下料传感单元的检测结果确定是否从所述下料存储位取出所述测序芯 片。
进一步地，所述内部移料单元还包括上料传感装置，所述上料装置还包括上料感应装置，所述上料感应装置用于与所述内部移料单元上料传感装置耦合以确定所述内部移料单元是否到达所述上料装置；和/或，所述内部移料单元还包括下料传感装置，所述下料装置还包括下料感应装置，所述下料感应装置用于与所述内部移料单元下料传感装置耦合以确定所述内部移料单元是否到达所述下料装置。
进一步地，所述基因测序反应设备还包括用于记录所述测序芯片的反应次数的计数装置。
进一步地，所述计数装置包括用于记录所述测序芯片的上料次数的上料计数器；和/或，所述计数装置包括用于记录所述测序芯片的下料次数的下料计数器。
进一步地，所述浸泡反应装置还包括温控装置，所述温控装置用于控制所述浸泡反应区的化学试剂的温度。
进一步地，所述浸泡反应装置包括一个或多个浸泡容器，所述浸泡容器包括一个或多个所述浸泡反应区。
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，所述浸泡反应装置还包括支架和夹具，所述浸泡容器通过所述夹具设置于所述支架上。
进一步地，所述夹具和/或所述支架的位置可调节地设置。
进一步地，所述基因测序反应设备包括用于调节所述支架的位置的支架位置调节装置。
进一步地，所述基因测序反应设备还包括电气滑环，所述基因测序反应设备的至少一个用电装置通过所述电气滑环与电源电连接。
进一步地，所述基因测序反应设备还包括用于控制所述基因测序反应设备运行的控制装置。
本发明第二方面提供一种基因测序系统，包括基因测序反应设备，其特征在于，所述基因测序反应设备为根据本发明第一方面任一项所述的基因测序反应设备。
进一步地，所述基因测序系统还包括光学检测设备和外部移送设备，所述外部移 送设备从所述基因测序反应设备取出待进行光学检测的测序芯片并送至所述光学检测设备的检测位置以及从所述光学检测位置取出检测完毕的测序芯片送至所述基因测序系统。
进一步地，所述光学检测设备与所述基因测序反应设备环绕在所述外部移送设备的周围布置。
进一步地，所述光学检测设备包括多个光学平台，每个所述光学平台包括至少一个检测位置，所述多个光学平台在所述外部移送设备的周围依次设置并布置成弧形，所述基因测序反应设备位于所述多个光学平台形成的弧形的开口处。
进一步地，所述外部移送设备包括机器人和与所述机器人连接的外部移料单元，所述机器人控制所述外部移料单元的位置，所述外部移料单元用于取得、携带以及释放所述测序芯片。
进一步地，所述基因测序系统包括控制所述基因测序系统运行的总控装置。
基于本发明提供的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。内部转移装置的内部移料单元沿闭合轨迹循环移动，多个浸泡反应区沿闭合轨迹布置，使得基因测序反应可以按照闭合轨迹布置的各浸泡反应区有序进行，利于基因测序反应的有序控制，减少操作失误或控制失误。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。该基因测序反应设备没有复杂的流体系统，零部件少、装配容易、制造成本低。还可以同时浸泡多张测序芯片，具有通量高的优势。
另外，基因测序反应设备包括用于控制基因测序反应设备的控制装置，整个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。
基于本发明提供的基因测序系统包括前述的基因测序反应设备，因此具有基因测序反应设备具有的全部技术效果。
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是本发明实施例的基因测序系统的立体结构示意图；
图2是图1所示的基因测序系统的外部移送设备的立体结构示意图；
图3是图1所示的基因测序系统的光学检测设备的一个光学平台的立体结构示意图；
图4是图1所示的基因测序系统的基因测序反应设备的一个角度的立体结构示意图；
图5是图1所示的基因测序系统的基因测序反应设备的另一个角度的立体结构示意图；
图6是图4和图5所示的基因测序反应设备的内部转移装置的立体结构示意图；
图7是图6所示的内部转移装置的闭合轨结构的一个角度的立体结构示意图；
图8是图6所示的内部转移装置的闭合轨结构的另一个角度的立体结构示意图；
图9是图6所示的内部转移装置的内部移料单元的立体结构示意图；
图10是图5所示的基因测序反应设备的I部放大结构示意图；
图11是图5所示的基因测序反应设备的上料装置处的放大结构示意图；
图12是图5所示的基因测序反应设备的下料装置处的放大结构示意图；
图13是图4和图5所示的基因测序反应设备的浸泡反应装置的结构示意图；
图14是图13所示的浸泡反应装置的试剂槽、夹具和支架的组合结构示意图。
图1至图14中，各附图标记分别代表：100、外部移送设备；110、六轴机器人；120、外部移料单元；121、气缸；122、夹爪；200、光学检测设备；210、光学平台；211、光学检测单元；300、基因测序反应设备；310、浸泡反应装置；311、水浴锅；312、试剂槽；313、夹具；314、支架；315、支架位置调节装置；320、内部转移装置；321、闭合轨结构；3211、动力源；3212、闭合传送带；3213、闭合轨道；3214、滑块；322、内部移料单元；3221、电缸；3222、夹爪；3223、上料传感装置；3224、下料传感装置；323、定位机构；3231、定位气缸；3232、定位轮；3233、定位块；3234、连杆；3235、转轴；3236、转动块；330、上料装置；331、上料定位插槽；332、 上料转盘；333、上料转动驱动机构；3341、第一上料传感单元；3342、第二上料传感单元；335、上料感应装置；340、下料装置；341、下料定位插槽；342、下料转盘；343、下料转动驱动机构；3441、第一下料传感单元；3442、第二下料传感单元；345、下料感应装置；350、支撑平台；360、扫码器；400、测序芯片；500、芯片固持装置。
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。
如图1至图14所示，本实施例提供了一种基因测序反应设备和基因测序系统。
如图1、图4至图14所示，本实施例的基因测序反应设备300主要包括浸泡反应装置310和内部转移装置320。浸泡反应装置310包括多个浸泡反应区。浸泡反应区用于盛放基因测序反应用化学试剂以通过将表面具有DNA样品加载结构并加载有DNA样品的测序芯片400浸泡于化学试剂内实现基因测序反应。内部转移装置320包括沿闭合轨迹循环移动的内部移料单元322，多个浸泡反应区沿闭合轨迹依次设置，内部移料单元322用于取得、携带和释放测序芯片400，以将测序芯片400插入浸泡反应区或从浸泡反应区中抽离。
基于本发明提供的基因测序反应设备300能采用浸泡方式实现基因测序反应。内部转移装置320的内部移料单元322沿闭合轨迹循环移动，多个浸泡反应区沿闭合轨 迹布置，使得基因测序反应可以按照闭合轨迹布置的各浸泡反应区有序进行，利于基因测序反应的有序控制，减少操作失误或控制失误。测序芯片400在不同浸泡反应区的化学试剂中浸泡，能够完成基因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400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400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400，具有通量高的优势。
以下结合图1、图4至图14对本实施例的基因测序反应设备300进行详细说明。
参见图1、图4至图14，本实施例的基因测序反应设备300主要包括浸泡反应装置310、内部转移装置320、上料装置330、下料装置340、控制装置(未图示)和支撑平台350。浸泡反应装置310、内部转移装置320、上料装置330和下料装置340均设置于支撑平台350上。
浸泡反应装置310包括多个浸泡反应区。浸泡反应区用于盛放基因测序反应用化学试剂以通过将表面具有DNA样品加载结构并加载有DNA样品的测序芯片400浸泡于化学试剂内实现基因测序反应。
测序芯片400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400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400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400上。
DNA样品是一种测序反应模板。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。
其中，浸泡反应装置310可以包括一个或多个浸泡容器，浸泡容器可以包括一个或多个浸泡反应区。本实施例中，浸泡容器具体地为试剂槽312。每个试剂槽312具有一个浸泡反应区。
优选地，浸泡反应装置310还包括温控装置，温控装置用于控制浸泡反应区的化 学试剂的温度。温控装置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。
如图1、图4、图5和图13所示，本实施例优选地，温控装置包括温度控制部和水浴锅311。水浴锅311用于盛放能够传递热量的液体。浸泡容器设置于水浴锅311中。温度控制部控制水浴锅311内的液体的温度以控制浸泡反应区内的化学试剂的温度。其中，浸泡容器可以通过其容器壁在浸泡容器外部与浸泡容器壁内的浸泡反应区之间传递热量。
温控装置可以包括多个水浴锅311。本实施例中，温控装置包括7个水浴锅311。根据基因测序反应的各浸泡步骤所需的化学试剂的温度要求，各水浴锅311内液体的温度可以相同，也可以不同。如图1所示，各水浴锅311均设置于支撑平台350上。
本实施例中，温度控制部为设置于水浴锅311的锅壁内的换热管，换热管可以向水浴锅311内的液体输入热量或从水浴锅311内的液体吸走热量，从而水浴锅311中的导热液体可以随之升温或降温。
通过对水浴锅311的锅壁或对水浴锅311内的液体输入或输出热量，水浴锅311中的导热液体可以随之升温或降温，浸泡容器浸泡在导热液体中，从而能够控制浸泡容器的浸泡反应区内的化学试剂的温度，利于保证生化反应顺利进行。采用液体作为导热介质，可以更均匀地控制各浸泡容器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。水浴锅311内的液体例如可以为水或油。
在其它未图示的实施例中，也可以采用温控器例如珀耳贴温控器对浸泡容器或其内化学试剂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311间接温控的方式相比易发生冷热不均的现象。
本实施例中，如图13和图14所示，浸泡反应装置310还包括支架314和夹具313，浸泡容器通过夹具313设置于支架314上。
为了调节浸泡容器的位置，以使内部移料单元322与闭合轨迹之间的相对位置更加准确，优选地，夹具313和/或支架314的位置可调节地设置。
本实施例中，如图13所示，基因测序反应设备300包括用于调节支架314的位置的支架位置调节装置315。支架位置调节装置315设置于支撑平台350上，支架314设置于支架位置调节装置315上。本实施例中，支架位置调节装置315可以同时调节支架314的高度和旋转角度，从而调节试剂槽312的位置。
内部转移装置320包括沿闭合轨迹循环移动的内部移料单元322，多个浸泡反应区沿闭合轨迹依次设置，内部移料单元322用于取得、携带和释放测序芯片400，以将测序芯片400插入浸泡反应区或从浸泡反应区中抽离。
本实施例中，如图4至图6所示，内部转移装置320包括沿闭合轨迹依次设置的多个内部移料单元322。设置多个内部移料单元322，可以针对不同的浸泡反应区同时进行操作，并且，由于闭合轨迹的设置，可以作到各内部移料单元322彼此的动作互不干涉，从而提高基因测序反应设备300的工作效率以及具有该基因测序反应设备300的基因测序系统的工作效率。
优选地，闭合轨迹为平面轨迹，即闭合轨迹整体均位于同一个平面内。更优选地，平面轨迹水平设置。本实施例中具体地，闭合轨迹为长圆形的沿水平面设置的平面轨迹。平面轨迹及水平设置利于内部移送装置及其组成部分的加工和布置，并且相对于立体轨迹或非水平布置的平面轨迹而言具有更好的可操作性。当然，在需要的情况下，不排除立体轨迹及非水平布置的平面轨迹，相对于水平布置的平面轨迹而言二者有更好的布置灵活性。
在其它未图示的实施例中，闭合轨迹也可以为其它形式的平面轨迹或立体轨迹，例如可以正圆形、椭圆形、采用圆角过渡的多边形轨迹等，也可以是局部包括内凹曲线的闭合轨迹、立体的闭合曲线轨迹等。另外，如前所述，本发明的闭合轨迹也可以为与水平面成一定夹角的平面轨迹。
如图1、图4至图8所示，本实施例中，内部转移装置320还包括闭合轨结构321，内部移料单元322安装于闭合轨结构321上，闭合轨结构321包括带动内部移料单元322沿闭合轨迹移动的移料单元驱动部。
其中，闭合轨结构321还包括用于形成闭合轨迹的闭合轨迹形成部和沿闭合轨迹移动的移动安装部。移料单元驱动部与移动安装部驱动连接。内部移料单元322安装于移动安装部上。通过移动安装部安装内部移料单元322，可以使内部移料单元322的安装位置具有更多的选择，便于基因测序反应设备300的各组成部分的布置。同时，可以通过控制移动安装部的位置控制内部移料单元322的位置。
如图6至图8所示，本实施例中，闭合轨迹形成部包括长圆形的闭合轨道3213，移动安装部包括滑动设置于闭合轨道3213上的滑块3214。在其它未图示的实施例中，移动安装部也可以包括滚动设置于闭合轨道3213上的小车。
本实施例中，内部移料单元322固定于滑块3214的外侧面外侧。其中，内和外是相对于闭合轨迹而言的。如图6所示，内部移料单元322整体上位于滑块3214的下方。
本实施例中，移料单元驱动部包括动力源3211和闭合传输结构。动力源3211驱动闭合传输结构沿闭合轨迹移动。移动安装部固定于闭合传输结构上。
本实施例中，动力源3211为旋转电机。闭合传输结构为环形传送带3212。旋转电机通过带轮带动环形传送带3212运动。滑块3214与环形传送带3212固定连接，从而环形传送带3212运动带动滑块3214及滑块3214上的内部移料单元322沿由闭合轨道3213限定的闭合轨迹移动。
在其它未图示的实施例中，动力源3211也可以为其它形式，例如液压马达。闭合传输结构也可以为其它形式，例如传送链、齿形带等。
由于以上基因测序反应设备300是以一个动力源3211带动所有的内部移料单元322，所以各测序芯片400在各反应环节的反应时间都是一致的。
在未图示的实施例中，可以根据基因测序需求设置多个动力源，每个动力源按组驱动内部移料单元，由同一个动力源驱动的一组内部移料单元的各内部移料单元同步移动。其中，每组内部移料单元可以包括一个或多个内部移料单元，当每组内部移料单元均只有一个内部移料单元时，各动力源一一对应地驱动一个内部移料单元。每个动力源按组驱动内部移料单元可以达到对测序芯片或测序环节按组控制反应时间，从而提高控制灵活性。
本实施例中，闭合轨结构321包括24个滑块3214，因此，可以装配24个内部移料单元322。当然，内部移料单元322的数量可以根据基因测序反应设备300的需求设置，而不一定与滑块3214的数量一致。
本实施例中，仅包括一个内部转移装置320，在其它未图示的实施例中，基因测序反应设备300可以包括两个以上内部转移装置320及与内部转移装置320配合设置的浸泡反应区，两个以上内部转移装置320对应的浸泡反应区内的化学试剂可以是对应相同的，以提高测序芯片400的通量，也可以是不同的，以完成不同的基因测序反应步骤。
如图9所示，本实施例中，内部移料单元322包括移料驱动机构和与移料驱动机构驱动连接的内部取料部。
具体地，移料驱动机构包括电缸3221，内部取料部包括与电缸3221驱动连接的 夹爪3222。电缸3221是将伺服电机与丝杠一体化设计的模块化产品，将伺服电机的旋转运动转换成直线运动，可以实现高精度直线运动。通过内部移料单元322整体沿闭合轨迹的移动及电缸3221的驱动端沿上下方向的运动，可以保证夹爪3222能够夹持或释放支持测序芯片400的芯片固持装置500，从而将测序芯片400插入和抽离对应的浸泡反应区。
电缸3221对于提高内部取料部的运动精度而言是有利的。但是，电缸3221也可以用其它驱动机构代替，例如液压缸等。内部取料部也可以是其它形式，例如还可以是与用于支持测序芯片400的芯片固持装置500配合的真空吸盘、电磁吸盘等。
芯片固持装置500用于固定测序芯片400，使测序芯片400随同芯片固持装置500运动。芯片固持装置500可以包括一个或多个芯片安装位，本实施例中包括一个芯片安装位。测序芯片400安装于芯片安装位以通过移动芯片固持装置500移动测序芯片400。设置芯片固持装置500一方面可以减少直接操作测序芯片400引起的污染，另一方面可以根据需要通过芯片固持装置500同时移动多个测序芯片400并使多个测序芯片400保持预定的间隔，从而提高测序芯片400的通量。
本实施例中，测序芯片400的双侧表面具有DNA样品加载结构。芯片安装位包括芯片安装口，测序芯片400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400双面都能够得到浸泡，可以提高单片测序芯片400加载的DNA样品分子的数量。
本实施例中，内部移料单元322的夹爪3222通过芯片固持装置500间接地夹持测序芯片400以实现内部移料单元322与测序芯片400之间的连接。间接夹持测序芯片400可以防止夹爪3222夹持不同的测序芯片400后发生交叉污染。另外，夹爪3222通过夹持芯片固持装置500间接地夹持测序芯片400，只需要在芯片固持装置500上加工夹持结构，而无需在测序芯片400上加工夹持结构，降低了测序芯片400的加工成本，也最大化利用了测序芯片400的表面积。
当然，在其它未图示的实施例中，也可以采用夹爪3222直接夹持测序芯片400的方式连接内部移料单元322与测序芯片400。
如图9所示，内部移料单元322还包括上料传感装置3223和下料传感装置3224，上料传感装置3223用于确定内部移料单元322是否到达上料装置330的上料位置。下料传感装置3224用于确定内部移料单元322是否到达下料装置340的下料位置。
为了精确定位内部移料装置与浸泡反应区的相对位置，内部转移装置320还包括定位机构323。定位机构323用于在内部移料单元322移动至与浸泡反应区对应的位置时，精确定位内部移料单元322的位置。
在一些优选的实施例中，定位机构323包括定位驱动机构、第一定位结构和第二定位结构，第一定位结构与定位驱动机构驱动连接，第二定位结构相对于内部移料单元322固定设置，通过定位驱动机构驱动第一定位结构向第二定位结构移动以与第二定位结构形状配合实现内部移料单元322的精确定位。
在一些优选地实施例中，第一定位结构和第二定位结构中的一个包括凸起部，另一个包括凸起部形状配合的凹入部。
如图5和图10所示，本实施例中，沿闭合轨迹设置了多个定位机构323。每个定位机构323的定位驱动机构为定位气缸3231；第一定位结构包括与定位气缸3231驱动连接的定位轮3232，定位轮3232的外凸表面形成凸起部；第二定位结构包括固定设置于滑块3214外侧的定位块3233，定位块3233的中部设有与定位轮3232形状配合的凹入部。
如图10所示，本实施例中，一个定位气缸3231可以同时驱动多个定位轮3232动作。如图10所示，定位气缸3231的活塞杆端与连杆3234的第一端铰接，连杆3234的第二端与转轴3235固定连接，转轴3235上同时沿轴向分布多个转动块3236，每个转动块3236与转轴3235相对固定设置，且每个转动块3236的底部设置一个定位轮3232。
当内部移料单元322移动至试剂槽312上方时，定位气缸3231的活塞杆伸出，通过连杆3234带动转轴3235转动，转轴3235通过转动块3236带动定位轮3232向靠近定位块3233的方向移动，并最终定位轮3232与相应定位块3233的凹入部形状配合，从而更精确地限定内部移料单元322相对于闭合轨迹的位置。当内部移料单元322需要离开时，定位气缸3231的活塞杆缩回，定位轮3232向离开定位块3233的方向运动从而解除与凹入部的配合。
定位机构323的设置可以减少或消除从动力源3211至滑块3214的传送误差，因此，即使环形传送带3212或类似的闭合传输结构等的传送不够精确，也可以通过定位机构323弥补，从而降低内部移料单元322动作失误的几率。
在其它未图示的实施例中，定位机构323的具体实现形式可以不同，例如，定位 气缸3231可以用电缸、油缸、直线电机等代替，第一定位结构本身的结构以及与定位驱动机构的连接方式可以作出变化，第二定位结构本身的结构以及安装位置也可以发生变化等等。
上料装置330包括用于放置测序芯片400的上料存储位，上料装置330位于闭合轨迹附近以使内部移料单元322能够从上料存储位取得测序芯片400。
本实施例中优选地，上料装置330包括多个上料存储位。如图5和图11所示，每个上料存储位由一个上料定位插槽331形成。
上料装置330还包括上料转动部，多个上料存储位设置于上料转动部上并能跟随上料转动部转动。本实施例中，上料转动部具体地包括上料转盘332，上料转盘332上围绕转动中心均匀放置12个上料定位插槽331，每个上料定位插槽331中可以装入一张测序芯片400。
上料装置330还包括上料转动驱动机构333，上料转动驱动机构333与上料转动部驱动连接以驱动上料转动部转动。本实施例中，上料转动驱动部为上料伺服电机。
上料装置330还包括上料芯片传感装置，上料芯片传感装置用于检测上料存储位是否存放测序芯片400以根据上料芯片传感装置的检测结果确定是否在上料存储位释放测序芯片400和/或是否从上料存储位取出测序芯片400。本实施例中，上料芯片传感装置包括第一上料传感单元3341，第一上料传感单元3341用于检测上料存储位是否存放测序芯片400以根据第一上料传感单元3341的检测结果确定是否在上料存储位释放测序芯片400；上料芯片传感装置还包括第二上料传感单元3342，第二上料传感单元3342用于检测上料存储位是否存放测序芯片400以根据第二上料传感单元3342的检测结果确定是否从上料存储位取出测序芯片400。
本实施例中，第一上料传感单元3341和第二上料传感单元3342均为光电传感器。作为第一上料传感单元3341的光电传感器检测上料转动部上的上料定位插槽331中是否存在测序芯片400，如果未检测到测序芯片400，外部移送设备100将把从光学平台210的检测位置拿出的检测后的测序芯片400插入到此上料定位插槽331中。作为第二上料传感单元3342的光电传感器检测到处于上料位置时的上料定位插槽331中是否存在测序芯片400，如果未检测到测序芯片400，上料转动部移动一个位置，直到感应到处于上料位置的上料定位插槽331内有测序芯片400时，内部移料单元322的夹爪3222将该测序芯片400从上料转动部的相应上料定位插槽331中取出，然后移动到相 应的浸泡反应区。
另外，如图13所示，上料装置330还包括上料感应装置335，上料感应装置335用于与内部移料单元322的上料传感装置3223耦合以确定内部移料单元322是否到达上料装置330的上料位置。
下料装置340包括用于放置测序芯片400的下料存储位，下料装置340位于闭合轨迹附近以使内部移料单元322能够将测序芯片400释放至下料存储位。
下料装置340包括多个下料存储位。如图5和图12所示，每个下料存储位由一个下料定位插槽341形成。
下料装置340还包括下料转动部，多个下料存储位设置于下料转动部上并能跟随下料转动部转动。本实施例中，下料转动部具体地包括下料转盘342，下料转盘342上围绕转动中心均匀放置12个下料定位插槽341，每个下料定位插槽341中可以装入一张测序芯片400。
下料装置340还包括下料转动驱动机构343，下料转料驱动机构与下料转动部驱动连接以驱动下料转动部转动。本实施例中，下料转动驱动部为下料伺服电机。
下料装置340还包括下料芯片传感装置，下料芯片传感装置用于检测下料存储位是否存放测序芯片400以根据下料芯片传感装置的检测结果确定是否在下料存储位释放测序芯片400和/或是否从下料存储位取出测序芯片400。
本实施例中，下料芯片传感装置包括第一下料传感单元3441，第一下料传感单元3441用于检测下料存储位是否存放测序芯片400以根据第一下料传感单元3441的检测结果确定是否在下料存储位释放测序芯片400。下料芯片传感装置还包括第二下料传感单元3442，第二下料传感单元3442用于检测下料存储位是否存放测序芯片400以根据第二下料传感单元3442的检测结果确定是否从下料存储位取出测序芯片400。
本实施例中，第一下料传感单元3441和第二下料传感单元3442均为光电传感器。作为第一下料传感单元3441的光电传感器检测下料转动部上的处于下料位置时的下料定位插槽341中是否存在测序芯片400，如果未检测到测序芯片400，内部移料单元322的夹爪3222将完成了最后一个基因测序反应环节的测序芯片400插入到此下料定位插槽341中。作为第二下料传感单元3442的光电传感器检测到下料定位插槽341中是否存在测序芯片400，如果未检测到测序芯片400，下料转动部移动一个位置，直到感应到下料定位插槽341内有测序芯片400时，外部移送设备100将该下料定位插槽 341内的测序芯片400移送至一个光学平台210的检测位置以进行光学检测。
另外，如图13所示，下料装置340还包括下料感应装置345，下料感应装置345用于与内部移料单元322的下料传感装置3224耦合以确定内部移料单元322是否到达下料装置340的下料位置。
本实施例中，上料感应装置335包括上料感应片，下料感应装置345包括下料感应片，当内部移料单元322移动到上料感应片所在位置时，内部移料单元322的上料传感装置3223感应到上料感应片，反馈给控制装置，由控制装置给内部移料单元322发指令将上料定位插槽331内的测序芯片400取走。当内部移料单元322移动到下料感应片所在位置时，内部移料单元322的下料传感装置3224感应到下料感应片，反馈给控制装置，由控制装置给内部移料单元322发指令向下料定位插槽341内插入测序芯片400。
本实施例中，测序芯片400在上料存储位置、浸泡反应区内、下料存储位置、检测位置以及通过内部转移装置320和外部移送设备100转移的过程中均安装于芯片固持装置500上。
本实施例中，基因测序反应设备300还包括用于记录测序芯片400的反应次数的计数装置。例如，计数装置可以包括用于记录测序芯片400的上料次数的上料计数器；再例如，计数装置可以包括用于记录测序芯片400的下料次数的下料计数器。如图12所示，本实施例中具体地，计数装置为设置于下料装置340处的扫码器360。
另外，基因测序反应设备300还包括电气滑环，基因测序反应设备300的至少一个用电装置通过电气滑环与电源电连接。通过电气滑环使基因测序反应的用电装置与电源电连接可以防止气管和/或电线缠绕等问题。
控制装置用于控制基因测序反应设备300的运行。通过控制装置控制可实现基因测序反应的自动化作业。
本实施例中，控制装置与移料单元驱动部的动力源3211和移料驱动机构以及相关检测装置均耦合以控制内部移料单元322的动作，从而自动控制内部移料单元322对测序芯片400的各种操作，因此可以提高基因测序反应设备300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。另外，控制装置还可以与温控装置耦合以控制化学试剂的温度。
控制装置可以为内置的控制装置，设置在支撑平台350上。也可以采用外置的控制装置与基因测序反应设备300耦合来控制和监控基因测序反应设备300工作。
通过控制装置对温控装置和内部移料单元322进行控制，可以实现基因测序反应设备300的自动化作业，提高基因测序质量和效率。
本实施例中支撑平台350是一个箱柜。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300移动，箱柜下安装有脚轮。在其它未图示的实施例中，还可以通过支撑架实现基因测序反应设备300的各部分的支撑。
如图1所示，本实施例还提供一种基因测序系统，包括前述的基因测序反应设备300。
如图1所示，基因测序系统还包括光学检测设备200和外部移送设备100，外部移送设备100从基因测序反应设备300取出待进行光学检测的测序芯片400并送至光学检测设备200的检测位置以及从光学检测位置取出检测完毕的测序芯片400送至基因测序反应设备300。
本实施例中，光学检测设备200与基因测序反应设备300环绕在外部移送设备100的周围布置。
本实施例中，基因测序系统包括一套基因测序反应设备300，在其它未图示的实施例中，基因测序系统可以包括两套以上基因测序反应设备300。
其中，光学检测设备200包括多个光学平台210，每个光学平台210包括至少一个检测位置，多个光学平台210在外部移送设备100的周围依次设置并布置成弧形，基因测序反应设备300位于多个光学平台210形成的弧形的开口处。如图1所示，本实施例的光学检测设备200具体地包括10个光学平台210。
如图2所示，外部移送设备100包括机器人和与机器人连接的外部移料单元120，机器人控制外部移料单元120的位置，外部移料单元120用于取得、携带以及释放测序芯片400。本实施例中，外部移送设备100包括1台机器人及相应的外部移料单元120，在其它未图示的实施例中，外部移送设备100可以根据测序需求设置更多的机器人及相应的外部移料单元120。
机器人优选地为六轴机器人110。六轴机器人110具有更大的行程和自由度，能够保证在10套光学平台210与基因测序反应设备300之间移送测序芯片400。
其中，外部移料单元120优选地包括气缸121和与气缸121驱动连接的夹爪122。 其中气缸121可以用油缸、电缸等其它驱动机构替代；与内部取料部类似地，也可以采用吸盘等结构作为外部移料单元。
如图3所示，光学平台210分为两层，下层机架主要存放工控机和液路系统，上层主要设置光学检测单元211和检测位置。光学检测单元211用来进行拍摄图像，读取图像数据，然后对图像数据进行分析、处理、存放等，最后得到基因序列实现基因测序。
另外，基因测序系统可以包括控制基因测序系统运行的总控装置。通过总控装置可以对外部移送设备100、光学检测设备200和基因测序反应设备300进行统一控制。在一些实施例上，总控装置可以与基因测序反应设备300的控制装置进行数据交换；在另一些实施例中，总控装置可以全部替代基因测序反应设备300的控制装置的功能，此时，基因测序反应设备300的控制装置不是必须的。
本实施例的基因测序反应设备300及具有其的基因测序系统的基本操作流程如下：
1.人工将12张芯片放置于上料转盘332上的12个上料定位插槽331中，通过上料伺服电机控制上料转盘332旋转，测序芯片400跟随上料转盘332转动。
2.当上料转盘332旋转至上料定位插槽331位于内部移料单元322下方时，内部移料单元322抓取测序芯片400并向上移动，从相应的上料定位插槽331中取出测序芯片400。
3.闭合轨结构321的移料驱动机构运动，内部移料单元322移动至水浴锅311中的试剂槽312上方位置后，带动测序芯片400向下运动，并将其插入试剂槽312中进行生化反应。因生化反应程序和实验步骤的限制，需要抓取每张测序芯片400依次在沿闭合轨迹设置的所需试剂槽312中依次进行生化反应。第一张测序芯片400完成抓取移动动作之后，上料转盘332旋转运动一个工位，下一个内部移料单元322从下一个上料定位插槽331中取出第二张测序芯片400并依次在不同的浸泡反应区移送测序芯片400。每个内部移料单元322依次完成取料并依次在不同的浸泡反应区移送测序芯片400，完成生化反应。其中，内部移料单元322将测序芯片400带入到试剂槽312中时，按照程序设定的时间将其放入该试剂槽312内的化学试剂中反应。本实施例中，由于全部内部移料单元322由同一个旋转电机及同一个环形传送带3212带动，所以所有测序芯片400的反应时间都是一致的。
4.当一个测序芯片400完成在最后一个浸泡反应区的生化反应后，由内部移料单元322抓取该测序芯片400并放置于下料定位插槽341中。当第一张测序芯片400已存放在下料定位插槽341中之后，下料转盘342旋转一个工位，等待第二张测序芯片400下料，依此类推。
5.当检测到下料定位插槽341中具有测序芯片400之后，外部移送设备100抓取第一张测序芯片400放置于第一台光学平台210上进行图像拍摄、图像处理和数据存储分析等检测工作，即进行第一次基因测序程序。从下料定位插槽341中取完第一张测序芯片400之后再从下一个下料定位插槽341中取第二张测序芯片400并将其放到第二台光学平台210上进行同样的工作，依次完成其他测序芯片400的检测工作。
6.当第一张测序芯片400完成一轮检测工作后，由外部移送设备100将其抓取并放到上料装置330的上料定位插槽331中，开始新的一轮的生化反应和检测工作，一共循环50-100次，一个测序芯片400的基因测序工作完成。
7.重复上述过程，直至完成所有测序芯片400的整个基因测序程序。
应当理解，上述步骤仅为基因测序反应设备300及基因测序系统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，本文未涉及上述化学反应。
根据以上描述可知，本发明以上实施例至少具有如下技术效果之一：
基因测序反应设备300能采用浸泡方式实现基因测序反应。
内部转移装置320的内部移料单元322沿闭合轨迹循环移动，多个浸泡反应区沿闭合轨迹布置，使得基因测序反应可以按照闭合轨迹布置的各浸泡反应区有序进行，利于基因测序反应的有序控制，减少操作失误或控制失误。
测序芯片400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。
浸泡方式不存在液体流速不均匀的问题，测序芯片400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400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。
不需要复杂的温度和流体控制系统，反应较均匀，从而显著降低基因测序成本， 满足科研和临床需求。
可以实现基因测序反应设备300和基因测序系统的全自动化，允许多张芯片同时连续不断的进行生化反应，适用于全自动化大规模基因测序工作，显著地提高了基因测序的效率。
配合优化过的生化反应方案，重复利用生化试剂，降低第二代测序技术的硬件和生化成本，解决现有测序平台的反应不均匀问题，提高数据产出量，对现有第二代基因测序技术形成有益改进，利于实现基因测序的“绿色”化。
可以根据测序要求决定所用的测序芯片400数目，扩展性好，通量高，灵活性较好。
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 (36)

  1. 一种基因测序反应设备(300)，其特征在于，包括：
    浸泡反应装置(310)，包括多个浸泡反应区，所述浸泡反应区用于盛放基因测序反应用化学试剂以通过将表面具有DNA样品加载结构并加载有DNA样品的测序芯片(400)浸泡于化学试剂内实现基因测序反应；
    内部转移装置(320)，包括沿闭合轨迹循环移动的内部移料单元(322)，所述多个浸泡反应区沿所述闭合轨迹依次设置，所述内部移料单元(322)用于取得、携带和释放所述测序芯片(400)，以将所述测序芯片(400)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(300)，其特征在于，所述内部转移装置(320)还包括闭合轨结构(321)，所述内部移料单元(322)安装于所述闭合轨结构(321)上，所述闭合轨结构(321)包括带动所述内部移料单元(322)沿所述闭合轨迹移动的移料单元驱动部。
  3. 根据权利要求2所述的基因测序反应设备(300)，其特征在于，所述闭合轨结构(321)还包括用于形成所述闭合轨迹的闭合轨迹形成部和沿所述闭合轨迹移动的移动安装部，所述移料单元驱动部与所述移动安装部驱动连接，所述内部移料单元(322)安装于所述移动安装部上。
  4. 根据权利要求3所述的基因测序反应设备(300)，其特征在于，所述闭合轨迹形成部包括闭合轨道(3213)，所述移动安装部包括滑动设置于所述闭合轨道(3213)上的滑块(3214)和/或所述移动安装部包括滚动设置于所述闭合轨道(3213)上的小车。
  5. 根据权利要求4所述的基因测序反应设备(300)，其特征在于，所述移料单元驱动部包括动力源(3211)和闭合传输结构，所述动力源(3211)驱动所述闭合传输结构沿所述闭合轨迹移动，所述移动安装部固定于所述闭合传输结构上。
  6. 根据权利要求1所述的基因测序反应设备(300)，其特征在于，所述内部转移装置(320)包括沿所述闭合轨迹依次设置的多个所述内部移料单元(322)。
  7. 根据权利要求1所述的基因测序反应设备(300)，其特征在于，所述闭合轨迹为平面轨迹。
  8. 根据权利要求7所述的基因测序反应设备(300)，其特征在于，所述平面轨迹水平设置。
  9. 根据权利要求1所述的基因测序反应设备(300)，其特征在于，所述内部转移装置(320)还包括定位机构(323)，所述定位机构(323)用于在所述内部移料单元(322)移动至与浸泡反应区对应的位置时，精确定位所述内部移料单元(322)的位置。
  10. 根据权利要求9所述的基因测序反应设备(300)，其特征在于，所述定位机构(323)包括定位驱动机构、第一定位结构和第二定位结构，所述第一定位结构与所述定位驱动机构驱动连接，所述第二定位结构相对于所述内部移料单元(322)固定设置，通过所述定位驱动机构驱动所述第一定位结构向所述第二定位结构移动以与所述第二定位结构形状配合实现所述内部移料单元(322)的精确定位。
  11. 根据权利要求10所述的基因测序反应设备(300)，其特征在于，所述第一定位结构和所述第二定位结构中的一个包括凸起部，另一个包括所述凸起部形状配合的凹入部。
  12. 根据权利要求1所述的基因测序反应设备(300)，其特征在于，所述内部移料单元(322)包括移料驱动机构和与所述移料驱动机构驱动连接的内部取料部。
  13. 根据权利要求1所述的基因测序反应设备(300)，其特征在于，所述基因测序反应设备(300)包括带动所述内部移料单元(322)沿所述闭合轨迹移动的移料单元驱动部，所述内部转移装置(320)包括沿所述闭合轨迹依次设置的多个内部移料单元(322)，其中，
    所述内部移料单元(322)包括一个动力源(3211)，各所述内部移料单元(322)均与所述动力源(3211)驱动连接并在所述动力源(3211)的带动下同步移动；或者，
    所述内部移料单元(322)包括多个动力源(3211)，每个动力源(3211)按组驱动内部移料单元(322)，由同一个动力源(3211)驱动的一组内部移料单元(322)的各内部移料单元(322)同步移动。
  14. 根据权利要求1至13中任一项所述的基因测序反应设备(300)，其特征在于，
    所述基因测序反应设备(300)还包括上料装置(330)，所述上料装置(330)包括用于放置所述测序芯片(400)的上料存储位，所述上料装置(330)位于所述闭合 轨迹附近以使所述内部移料单元(322)能够从所述上料存储位取得所述测序芯片(400)；和/或，
    所述基因测序反应设备(300)还包括下料装置(340)，所述下料装置(340)包括用于放置所述测序芯片(400)的下料存储位，所述下料装置(340)位于所述闭合轨迹附近以使所述内部移料单元(322)能够将所述测序芯片(400)释放至所述下料存储位。
  15. 根据权利要求14所述的基因测序反应设备(300)，其特征在于，
    所述上料装置(330)包括多个所述上料存储位；和/或，
    所述下料装置(340)包括多个所述下料存储位。
  16. 根据权利要求15所述的基因测序反应设备(300)，其特征在于，
    所述上料装置(330)还包括上料转动部，所述多个上料存储位设置于所述上料转动部上并能跟随所述上料转动部转动；和/或，
    所述下料装置(340)还包括下料转动部，所述多个下料存储位设置于所述下料转动部上并能跟随所述下料转动部转动。
  17. 根据权利要求16所述的基因测序反应设备(300)，其特征在于，
    所述上料装置(330)还包括上料转动驱动机构(333)，所述上料转动驱动机构(333)与所述上料转动部驱动连接以驱动所述上料转动部转动；和/或，
    所述下料装置(340)还包括下料转动驱动机构(343)，所述下料转料驱动机构与所述下料转动部驱动连接以驱动所述下料转动部转动。
  18. 根据权利要求14所述的基因测序反应设备(300)，其特征在于，
    所述上料装置(330)还包括上料芯片传感装置，所述上料芯片传感装置用于检测所述上料存储位是否存放所述测序芯片(400)以根据所述上料芯片传感装置的检测结果确定是否在所述上料存储位释放测序芯片(400)和/或是否从所述上料存储位取出所述测序芯片(400)；和/或，
    所述下料装置(340)还包括下料芯片传感装置，所述下料芯片传感装置用于检测所述下料存储位是否存放所述测序芯片(400)以根据所述下料芯片传感装置的检测结果确定是否在所述下料存储位释放测序芯片(400)和/或是否从所述下料存储位取出所述测序芯片(400)。
  19. 根据权利要求18所述的基因测序反应设备(300)，其特征在于，
    所述上料芯片传感装置包括第一上料传感单元(3341)，所述第一上料传感单元(3341)用于检测所述上料存储位是否存放所述测序芯片(400)以根据所述第一上料传感单元(3341)的检测结果确定是否在所述上料存储位释放测序芯片(400)；和/或，所述上料芯片传感装置包括第二上料传感单元(3342)，所述第二上料传感单元(3342)用于检测所述上料存储位是否存放所述测序芯片(400)以根据所述第二上料传感单元(3342)的检测结果确定是否从所述上料存储位取出测序芯片(400)；和/或，
    所述下料芯片传感装置包括第一下料传感单元(3441)，所述第一下料传感单元(3441)用于检测所述下料存储位是否存放测序芯片(400)以根据所述第一下料传感单元(3441)的检测结果确定是否在所述下料存储位释放测序芯片(400)；和/或，所述下料芯片传感装置包括第二下料传感单元(3442)，所述第二下料传感单元(3442)用于检测所述下料存储位是否存放所述测序芯片(400)以根据所述第二下料传感单元(3442)的检测结果确定是否从所述下料存储位取出所述测序芯片(400)。
  20. 根据权利要求14所述的基因测序反应设备(300)，其特征在于，
    所述内部移料单元(322)还包括上料传感装置(3223)，所述上料装置(330)还包括上料感应装置(335)，所述上料感应装置(335)用于与所述内部移料单元(322)上料传感装置(3223)耦合以确定所述内部移料单元(322)是否到达所述上料装置(330)；和/或，
    所述内部移料单元(322)还包括下料传感装置(3224)，所述下料装置(340)还包括下料感应装置(345)，所述下料感应装置(345)用于与所述内部移料单元(322)下料传感装置(3224)耦合以确定所述内部移料单元(322)是否到达所述下料装置(340)。
  21. 根据权利要求1至13中任一项所述的基因测序反应设备(300)，其特征在于，所述基因测序反应设备(300)还包括用于记录所述测序芯片(400)的反应次数的计数装置。
  22. 根据权利要求21所述的基因测序反应设备(300)，其特征在于，
    所述计数装置包括用于记录所述测序芯片(400)的上料次数的上料计数器；和/或，
    所述计数装置包括用于记录所述测序芯片(400)的下料次数的下料计数器。
  23. 根据权利要求1至13中任一项所述的基因测序反应设备(300)，其特征在于，所述浸泡反应装置(310)还包括温控装置，所述温控装置用于控制所述浸泡反应区的化学试剂的温度。
  24. 根据权利要求23所述的基因测序反应设备(300)，其特征在于，所述浸泡反应装置(310)包括一个或多个浸泡容器，所述浸泡容器包括一个或多个所述浸泡反应区。
  25. 根据权利要求24所述的基因测序反应设备(300)，其特征在于，所述温控装置包括温度控制部和水浴锅(311)，所述水浴锅(311)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(311)中，所述温度控制部控制所述水浴锅(311)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。
  26. 根据权利要求24所述的基因测序反应设备(300)，其特征在于，所述浸泡反应装置(310)还包括支架(314)和夹具(313)，所述浸泡容器通过所述夹具(313)设置于所述支架(314)上。
  27. 根据权利要求26所述的基因测序反应设备(300)，其特征在于，所述夹具(313)和/或所述支架(314)的位置可调节地设置。
  28. 根据权利要求27所述的基因测序反应设备(300)，其特征在于，所述基因测序反应设备(300)包括用于调节所述支架(314)的位置的支架位置调节装置(315)。
  29. 根据权利要求1至13中任一项所述的基因测序反应设备(300)，其特征在于，所述基因测序反应设备(300)还包括电气滑环，所述基因测序反应设备(300)的至少一个用电装置通过所述电气滑环与电源电连接。
  30. 根据权利要求1至13中任一项所述的基因测序反应设备(300)，其特征在于，所述基因测序反应设备(300)还包括用于控制所述基因测序反应设备(300)运行的控制装置。
  31. 一种基因测序系统，包括基因测序反应设备(300)，其特征在于，所述基因测序反应设备(300)为根据权利要求1至30中任一项所述的基因测序反应设备(300)。
  32. 根据权利要求31所述的基因测序系统，其特征在于，所述基因测序系统还包括光学检测设备(200)和外部移送设备(100)，所述外部移送设备(100)从所述基因测序反应设备(300)取出待进行光学检测的测序芯片(400)并送至所述光学检测设备(200)的检测位置以及从所述光学检测位置取出检测完毕的测序芯片(400)送 至所述基因测序反应设备(300)。
  33. 根据权利要求31所述的基因测序系统，其特征在于，所述光学检测设备(200)与所述基因测序反应设备(300)环绕在所述外部移送设备(100)的周围布置。
  34. 根据权利要求32所述的基因测序系统，其特征在于，所述光学检测设备(200)包括多个光学平台(210)，每个所述光学平台(210)包括至少一个检测位置，所述多个光学平台(210)在所述外部移送设备(100)的周围依次设置并布置成弧形，所述基因测序反应设备(300)位于所述多个光学平台(210)形成的弧形的开口处。
  35. 根据权利要求31至34中任一项所述的基因测序系统，其特征在于，所述外部移送设备(100)包括机器人和与所述机器人连接的外部移料单元(120)，所述机器人控制所述外部移料单元(120)的位置，所述外部移料单元(120)用于取得、携带以及释放所述测序芯片(400)。
  36. 根据权利要求31至34中任一项所述的基因测序系统，其特征在于，所述基因测序系统包括控制所述基因测序系统运行的总控装置。
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