WO2021056445A1 - 流动池及应用所述流动池的生化物质反应装置 - Google Patents

流动池及应用所述流动池的生化物质反应装置 Download PDF

Info

Publication number
WO2021056445A1
WO2021056445A1 PCT/CN2019/108642 CN2019108642W WO2021056445A1 WO 2021056445 A1 WO2021056445 A1 WO 2021056445A1 CN 2019108642 W CN2019108642 W CN 2019108642W WO 2021056445 A1 WO2021056445 A1 WO 2021056445A1
Authority
WO
WIPO (PCT)
Prior art keywords
flow cell
hole
flow
outlet
inlet
Prior art date
Application number
PCT/CN2019/108642
Other languages
English (en)
French (fr)
Inventor
徐洪
梅平
甘勇
梁埈模
比彻乔迪
吴特雷莎
Original Assignee
深圳华大智造科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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/CN2019/108642 priority Critical patent/WO2021056445A1/zh
Priority to CN201980100244.8A priority patent/CN114391037B/zh
Priority to JP2022504730A priority patent/JP7330358B2/ja
Priority to EP19947064.2A priority patent/EP4036204A4/en
Priority to US17/763,270 priority patent/US20220339632A1/en
Publication of WO2021056445A1 publication Critical patent/WO2021056445A1/zh
Priority to JP2023129349A priority patent/JP2023153989A/ja

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/56—Labware specially adapted for transferring fluids
    • B01L3/565—Seals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869—Methods for sequencing
    • C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0605—Valves, specific forms thereof check valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip

Definitions

  • the invention relates to a flow cell carrying a sample for reaction in the field of biochemical reaction and a biochemical substance reaction device using the flow cell.
  • a flow cell In the biochemical reaction field, a flow cell is generally configured to carry samples.
  • the flow cell is a sample carrier for loading samples of biochemical substances and performing detection and analysis reactions. It usually contains a cavity for containing samples and fluids.
  • the flow cell In the case of sequencing, the flow cell is a sequencing chip, and in other cases, the flow cell may be other sample carriers. The following uses a sequencing chip as an example to illustrate the current status of the flow cell.
  • the sequencing chip In the field of gene sequencing, the sequencing chip is usually used as a consumable for the instrument for single use. In the sequencing process, the loading of the sample and the biochemical reaction of fluorescent labeling are all completed in the gene sequencing chip.
  • the current second-generation sequencing technologies mainly include fluorescent labeling methods based on optical detection, and chemical sequencing methods that identify bases through changes in hydrogen ion concentration. Among them, the chemical sequencing method based on the change of hydrogen ion concentration to identify bases has advantages in the size and speed of the detection instrument, but there are problems of homopolymer errors and low throughput.
  • the second-generation sequencing technology based on optical detection and recognition has the highest base recognition accuracy and the largest current throughput.
  • flow cells are generally called flow cells, reaction cells, chips, sequencing chips, gene sequencing chips, or cartridges, etc. Common English names are FlowCell, Flowcell, Chip, ChipKit, Cartridge, etc.
  • the gene sequencing flow cell uses silicon wafers, glass or polymer as the substrate, and cooperates with micro-electromechanical automation or other precision processing technologies to produce high-tech components that enable researchers Can quickly screen a large number of biological analytes for various purposes, from disease diagnosis to bioterrorism detection.
  • the traditional sequencing loading flow cell is a narrow fluid channel. Due to the limitation of the optical diffraction limit, it is impossible to achieve ultra-high-throughput sample detection in a single flow cell.
  • traditional chips use negative pressure pumping for reagent spreading and replacement, which has the problem of large reagent replacement ratio and slow reagent replacement speed, which is not conducive to the establishment of an ultra-high-throughput sequencing system.
  • an optical-mechanical system can match up to 2 sequencing loading flow cell fluid platforms to work at the same time, which is not conducive to the simultaneous operation of multiple flow cells of ultra-high-throughput sequencing systems. Sequencing, and due to the thermal effect of the flow cell carrying platform, the complete decoupling of the working states of multiple flow cells cannot be achieved, that is, it is impossible to achieve sequential or combined operation of multiple flow cells;
  • the RFID module is separated from the optical identification tag (two-dimensional code), high cost and risk of mismatch;
  • the inlet and outlet reagents of the sequencing loading flow cell are matched and sealed between the loading platform and the inlet and outlet holes of the flow cell through a sealing ring fixed on the loading platform. Since the sealing ring needs to be connected to the flow cell multiple times, the sealing effect will decrease as the number of uses increases. In some systems, the optical and fluid platforms of the flow cell are separated, and the flow cell needs to be transferred multiple times. The sealing effect of the sealing ring Face a greater test in the process of use. At the same time, reagent overflow at the inlet and outlet is also a potential risk point of the system.
  • the seal ring is easy to be mismatched at the end of the liquid inlet module, which affects the liquid inlet and causes the risk of liquid leakage; the aging of the seal ring needs to be replaced regularly, which increases the workload of the operator and requires higher operations; the clearance fit of the seal ring is shifting During the process, it is unavoidable that liquid leakage at the gap leads to the crystallization of the reagent at the interface and affects the sealing effect.
  • a flow cell in a first aspect, includes a flow cell body, the flow cell body includes a frame and a flow chamber provided in the frame, and the flow chamber includes a reaction area that allows fluid to pass through, the frame A liquid inlet hole, a liquid outlet hole, and an exhaust hole are opened to communicate with the flow chamber.
  • the fluid input from the liquid inlet hole flows through the reaction area of the flow chamber and then is output from the liquid outlet hole.
  • the holes are used to discharge trapped air in the flow chamber when the fluid flows through the reaction zone.
  • a flow cell in a second aspect, includes a plurality of sealing rings, and one or more of the plurality of sealing rings are provided corresponding to the through holes that the flow cell communicates with the outside.
  • a biochemical substance reaction device which is used to load the above-mentioned flow cell and input reactant substances to the flow cell to cause the sample in the flow cell to react; or, the biological substance
  • the substance reaction device is further used to detect the reacted sample to obtain a signal reflecting the biological characteristics of the sample.
  • the flow cell and the biochemical substance reaction device provided in the embodiment of the present invention can reduce the ratio of length to width of the flow cell by providing vent holes on the flow cell, make full use of round wafers, and realize rapid and effective fluid spreading.
  • the integrated arrangement of the sealing ring and the flow cell can effectively prevent the fluid from infiltrating the substrate and affecting the vacuum adsorption of the flow cell on different platforms; at the same time, it can also avoid the deterioration of the sealing performance caused by the long-term use and aging of the sealing ring.
  • Fig. 1 is a three-dimensional schematic diagram of a flow cell in an embodiment of the present invention.
  • Fig. 2 is a perspective schematic view of the flow cell shown in Fig. 1 from another angle.
  • Fig. 3 is an exploded view of the flow cell shown in Fig. 1.
  • Fig. 4 is a cross-sectional view taken along the line IV-IV shown in Fig. 1.
  • Fig. 5 is an enlarged view of the V area shown in Fig. 4.
  • Fig. 6 is an enlarged view of the VI area shown in Fig. 4.
  • Fig. 7 is a partial cross-sectional view taken along the line VII-VII shown in Fig. 1.
  • Fig. 8 is a schematic diagram of a flow cell installed on a carrying platform in another embodiment of the present invention.
  • Fig. 9 is a schematic diagram of the separation of the flow cell and the carrying platform shown in Fig. 8.
  • Fig. 10 is a partial cross-sectional view taken along line X-X shown in Fig. 8.
  • Fig. 11 is a partial cutaway schematic view of a sealing ring provided on the outlet of the flow cell shown in Fig. 8.
  • Fig. 12 is a partial cut-away schematic view of a sealing ring provided on the inlet of the flow cell in another embodiment.
  • Fig. 13 is a schematic diagram of a biochemical substance reaction device provided by an embodiment of the present invention.
  • FIGS. 1 to 3 are two-angle three-dimensional schematic diagrams and exploded views of the flow cell in an embodiment of the present invention.
  • the flow cell 1 includes a flow cell body 2 and an outer frame 3 arranged on the outside of the flow cell.
  • the flow cell 1 includes a front side 11 and a back side 13 opposite to the front side 11.
  • a plurality of sealing rings 4 are provided on the back side 13 of the flow cell 1, and the sealing rings 4 are used to realize the cooperation and sealing with different bearing platforms.
  • the coordination includes the coordination of the inlet and outlet of the flow cell 1.
  • the flow cell body 2 includes a frame 20 and a flow chamber 25 formed in the frame 20.
  • the frame 20 includes a base 21 and a cover sheet 23 in turn from the back side 13 to the front side 11.
  • the cover sheet 23 allows light to pass through so that the fluid movement in the flow chamber 25 can be observed on the front side 11 of the flow cell 1.
  • the cover sheet 23 is optical glass
  • the substrate 21 is a rectangular cut silicon wafer.
  • the substrate 21 is a rectangular cut silicon wafer of high-density nano-lattice based on genetic patterned array technology.
  • the surrounding area of the cover sheet 23 is connected to the surrounding area of the base 21 through the glue 26.
  • the flow chamber 25 is arranged corresponding to the central area of the cover sheet 23 and the base 21.
  • the glue 26 is cured glue, such as ultraviolet curing glue.
  • the gel 26 is continuously distributed around the cover sheet 23 and the surrounding area of the substrate 21 to form a sealed enclosure.
  • the gel 26 is mixed with microspheres of a specific size or other shapes that can separate the cover sheet 23 from the substrate 21.
  • the particles are separated by a predetermined distance so as to form the flow chamber 25 corresponding to the central area of the cover sheet 23 and the base 21.
  • the surrounding of the flow chamber 25 is sealed by the colloid 26, so that the flow chamber 25 becomes a closed reaction chamber that allows the fluid to react with the sample.
  • the flow cell 1 is rectangular or square
  • the flow cell body 2 is rectangular or square
  • the frame 20 is rectangular or square
  • the flow chamber 25 is also rectangular or square.
  • the flow cell 1, the flow cell body 2, the frame 20 and/or the flow chamber 25 can also be other polygons.
  • a supporting point is provided in the flow chamber 25.
  • the supporting point is a colloidal supporting point 251.
  • the colloidal support points 251 connect and support the cover sheet 23 and the base 21 at both ends, thereby strengthening the internal structural strength of the flow cell body 2.
  • the colloidal support points 251 also use ultraviolet curing glue, and the colloidal support points 251 are also mixed with microspheres of a specific size or particles of other shapes that can separate the cover sheet 23 and the substrate 21 by a predetermined distance.
  • the material of the substrate 21 may be optical glass, fused silica, monocrystalline silicon wafer, polycrystalline silicon wafer or other ceramic materials.
  • the diameter of the microspheres is any value in the range of 30 to 80 microns.
  • the back side 13 of the flow cell 1 is provided with the liquid inlet 252, the liquid outlet 253, and the exhaust holes 254a and 254b of the flow chamber 25 on the base 21.
  • the liquid inlet hole 252 and the liquid outlet hole 253 are arranged at a pair of diagonal positions of the flow chamber 25, and an exhaust hole 254a (hereinafter referred to as the "inlet side exhaust hole 254a") and the liquid inlet hole 252 are arranged
  • a diversion groove 255a (hereinafter referred to as "inlet diversion groove 255a”) is connected between the liquid inlet hole 252 and the inlet side exhaust hole 254a.
  • the other exhaust hole 254b (hereinafter referred to as “outlet side exhaust hole 254b") is provided on the same side as the outlet hole 253, and the diversion groove 255b (hereinafter referred to as “outlet hole 254b") is connected between the outlet hole 253 and the outlet side exhaust hole 254b.
  • Outlet diversion slot 255b" In this embodiment, the inlet diversion groove 255a and the outlet diversion groove 255b are respectively arranged on opposite sides of the flow chamber 25, and the inlet diversion groove 255a and the outlet diversion groove 255b are substantially parallel. In this embodiment, the inlet-side exhaust hole 254a and the outlet-side exhaust hole 254b are respectively provided at another pair of diagonal positions of the flow chamber 25.
  • the inlet diversion groove 255a includes a bottom surface 2551a, side walls 2552a and side walls 2553a, and an opening 2554a.
  • the opening 2554a is opposite to the bottom surface 2551a, and the opening 2554a communicates with the inlet diversion groove 255a and the flow chamber 25.
  • the side wall 2552a and the side wall 2553a are connected between the opening 2554a and the bottom surface 2551a, and the side wall 2553a is closer to the middle area of the flow chamber 25 than the side wall 2552a.
  • the side wall 2552a is substantially perpendicular to the bottom surface 2551a and the opening 2554a
  • the side wall 2553a is an inclined wall that is inclined to the bottom surface 2551a and the opening 2554a.
  • the side wall 2553a starts from the bottom of the connecting bottom surface 2551a and extends upwards toward the middle area of the flow chamber 25, making the top of the side wall 2553a closer to the opening 2554a closer to the middle area of the flow chamber 25 than the bottom.
  • the part where the top of the side wall 2553a is connected to the surface of the base 21 is set to have rounded corners, so that a smooth and smooth transition is formed between the side wall 2553a and the base 21.
  • the opening 2554a of the inlet diversion groove 255a is enlarged, and at the same time, by providing a smooth transition between one of the side walls and the surface of the base 21, the liquid inlet hole 252 is avoided.
  • the nearby fluid disturbance weakens the vortex state under high-speed flow and improves the uniformity of the biochemical reaction near the liquid inlet 252.
  • the fluid After the fluid enters the flow chamber 25 from the inlet hole 252, it first flows along the inlet guide groove 255a toward the inlet side exhaust hole 254a. As the incoming fluid increases, the fluid flows from the inlet hole 252 and the inlet guide groove 255a as a whole. The inlet end 25a flows toward the outlet end 25b where the outlet hole 253 and the outlet diversion groove 255b are located, and finally merges into the outlet diversion groove 255b, from the outlet diversion groove 255b to the liquid hole 253, and passes through the liquid hole 253. Flow out of the flow chamber 25.
  • the fluid can be uniformly spread over all the flow areas (reaction areas) that the flow chamber 25 allows the fluid to pass through, so as to ensure uniform biochemical reactions everywhere in the flow chamber 25 Sex.
  • the side wall 2552a may also be an inclined surface.
  • the side wall 2552a is inclined such that the top of the side wall 2552a near the opening 2554a is closer to the edge area of the flow chamber 25 than the bottom connected to the bottom surface 2551a.
  • the outlet diversion groove 255b is connected between the liquid outlet hole 253 and the outlet side exhaust hole 254b.
  • the outlet diversion groove 255b includes a bottom surface 2551b, side walls 2552b and side walls 2553b, and an opening 2554b. Wherein, the opening 2554b is opposite to the bottom surface 2551b, and the opening 2554b communicates with the outlet diversion groove 255b and the flow chamber 25.
  • the side wall 2552b and the side wall 2553b are connected between the opening 2554b and the bottom surface 2551b.
  • the side walls 2552b and 2553b are both substantially perpendicular to the bottom surface 2551b and the opening 2554b. In other embodiments, any or all of the side walls 2552b and 2553b may be inclined surfaces.
  • the outlet diversion groove 255b may be symmetrically arranged with the inlet diversion groove 255a.
  • the outer frame 3 is arranged around the circumference of the flow cell body 2 in a semi-enclosing manner as a whole.
  • the outer frame 3 includes a fixing portion 31 and a positioning portion 32.
  • the fixing portion 31 is arranged inside the positioning portion 32, and the fixing portion 31 fixes the outer frame 3 to the cover sheet 23.
  • the fixing portion 31 is glued to the surrounding area of the cover sheet 23 by glue.
  • the positioning portion 32 is disposed outside the fixing portion 31. Compared with the positioning portion 32, the fixing portion 31 has a thinner thickness.
  • the ultra-thin fixing portion 31 avoids the interference problem of the optical scanning system. Compared with the fixed portion 31, the positioning portion 32 protrudes toward the back side 13 of the flow cell 1.
  • a plurality of grabbing structures 321 are provided on the positioning portion 32, and the grabbing structures 321 are grabbed by a mobile device (not shown) to move the flow cell 1 in different positions.
  • the mobile device can grasp the flow cell through the grasping structure 321 on the positioning part 32 1.
  • the flow cell 1 can be moved repeatedly between the fluid reaction zone and the optical photographing zone.
  • the grasping structure 321 is a hole portion opened on the positioning portion 32.
  • the grasping structure 321 is a rectangular hole opened on the four corner regions 322 of the positioning portion 32.
  • the grasping structure 321 may be a hole with other shapes, for example, a circular hole.
  • the grabbing structure 321 can be provided in other positions of the positioning portion 32.
  • the positioning part 32 is also provided with a positioning structure 323, which provides positioning when the mobile device moves and places the flow cell 1 on the carrier platform, so that the flow cell can be accurately located on the carrier platform at different positions.
  • the positioning structure 323 is a V-shaped oblique slot hole.
  • each V-shaped oblique slot hole is provided on one side of a hole portion of the grasping structure 321 and communicates with the hole portion.
  • the positioning structure 323 can be integrated with the grabbing structure 321, that is, the same structure can be used for the mobile device to grab the flow cell 1, and it can also be used for the mobile device to move and place the flow cell. 1 Provide positioning when on the carrying platform. For example, some holes with azimuth characteristics, such as triangles, can be used as positioning structure 323 and grasping structure 321 at the same time.
  • the positioning portion 32 surrounds the cover sheet 23 and the base 21 of the flow cell 1 as a whole, thereby also protecting the flow cell 1.
  • the outer frame 3 is made by injection molding, and the material of the outer frame may be glass fiber, carbon fiber reinforced polymer plastic or other common plastic types.
  • the side of the outer frame 3 facing the front side 11 of the flow cell 1 is also provided with an electronic label 33.
  • the electronic label 33 is affixed to the outer frame 3.
  • the machine non-contact identifier 331 of further includes a machine inductive identification element 332 provided inside the electronic tag 33.
  • the electronic tag 33 also includes a text identification symbol 333.
  • the machine non-contact identification symbol 331 may be an optically identifiable symbol such as a one-dimensional code or a two-dimensional code
  • the machine inductive identification element 332 may be an RFID (Radio Frequency Identification) module.
  • the outer frame 3 is provided with an electronic tag 33 that is recessed downward to form a groove 34.
  • the electronic tag 33 is accommodated in the groove 34, so as to prevent the electronic tag 33 from protruding from the surface of the outer frame 3. Part interference.
  • a plurality of sealing rings 4 are provided on the back side 13 of the flow cell 1, and the sealing rings 4 correspond to the liquid inlet 252, the liquid outlet 253, and the exhaust hole 254a, respectively. , 254b settings.
  • the flow cell 1 is matched and sealed with different load-bearing platforms through the sealing ring 4.
  • the sealing ring 4 is fixed to the back side 13 of the flow cell 1 by a sealing ring fixing device 5.
  • the sealing ring fixing device 5 is a rectangular frame, and fixing structures 51 are provided on the rectangular frame at four positions corresponding to the liquid inlet 252, the liquid outlet 253, and the exhaust holes 254a and 254b.
  • the fixing structure 51 fixes the sealing ring 4.
  • the fixing structure 51 is a fixing hole 512, and the sealing ring 4 is installed in the fixing hole 512.
  • Each sealing ring 4 includes a ring body 41 and a through hole 42 enclosed by the ring body 41.
  • the through hole 42 may be straight cylindrical or conical.
  • the ring body 41 is provided with at least one engaging structure 411 that matches the inner structure of the fixing hole 512.
  • the engaging structure 411 is embedded in the fixing hole 512.
  • the engagement structure 411 of each sealing ring 4 is a protrusion 411a provided on the outer side of the ring body 41, and a matching structure 513 is also provided in the fixing hole 512 corresponding to each sealing ring 4. 513 cooperates with the engaging structure 411 of the sealing ring 4 to fix the sealing ring 4 in the fixing hole 512.
  • the mating structure 513 of each fixing hole 512 is a concave portion 513 a provided in the fixing hole 512, and the concave portion 513 a fixes the sealing ring 4 in the fixing hole 512 by accommodating the protrusion 411 a on the sealing ring 4.
  • the engaging structure 411 of the sealing ring 4 may be a recess provided on the ring body 41, and the mating structure in the fixing hole 512 may be a protrusion provided in the fixing hole 512. It can be understood that, in other embodiments, the engaging structure 411 of the sealing ring 4 may be the outer surface of the ring body 41, and the mating structure in the fixing hole 512 may be the inner surface of the fixing hole 512, and the outer surface of the sealing ring 4 and The interference fit of the inner surface of the fixing hole 512 fixes the sealing ring 4 in the fixing hole 512. It can be understood that in other embodiments, the sealing ring 4 may also be fixed in the fixing hole 512 by means of gluing or the like.
  • each fixing hole 512 is further provided with a positioning boss 514. After being fixed in the fixing hole 512, one end of the sealing ring 4 protrudes from the positioning boss 514 so that the positioning boss 514 is sleeved on The outer side of the sealing ring 4.
  • the positioning boss 514 is used to cooperate with corresponding parts on the carrying platform (for example, with the liquid inlet and outlet holes on the fluid platform) to assist in positioning and prevent the sealing ring 4 from being deformed by force and affecting the fluid flow.
  • the seal ring fixing device 5 is fixed to the back side 13 of the flow cell 1. Specifically, the sealing ring fixing device 5 is pasted on the back side 13 of the flow cell 1 by a glue such as double-sided tape. In this embodiment, one sealing ring fixing device 5 is used to simultaneously fix a plurality of sealing rings 4 to the back side 13 of the flow cell 1. In other embodiments, the sealing ring fixing device 5 can be divided into a plurality of independent sub-units. Fixing device, each sub-fixing device fixes a sealing ring 4.
  • FIG. 8 are schematic diagrams of the cooperation between the flow cell and the carrying platform in another embodiment of the present invention.
  • the structure of the flow cell 6 is substantially the same as that of the flow cell 1 in the previous embodiment.
  • the main difference lies in: a one-way sealing device is further provided in the through hole 42 of the sealing ring 4 used in the flow cell 6.
  • the one-way sealing device is a valve device, wherein the through hole 42 of the sealing ring 4 corresponding to the liquid inlet hole 252 is provided with a liquid inlet valve device corresponding to the through hole of the liquid outlet hole 253 and the exhaust holes 254a and 254b
  • a liquid outlet valve device 421 is provided in 42.
  • FIG. 10 shows one of the outlet valve devices 421.
  • the outlet valve device 421 includes a plurality of valves 422.
  • Each valve 422 includes a root portion 422a connected to the wall of the through hole 42 and a root portion 422a.
  • the top portion 422b extending to the center and outside of the through hole 42 makes the outlet valve device 421 a tapered or nearly tapered shape with a top end toward the outside of the through hole 42 as a whole.
  • the roots 422a of all the valves 422 can be connected in sequence, or the roots 422a of all the valves 422 can be separated from each other, and the separated roots 422a are close to and enclosed together.
  • the tops 422b of all valves 422 are separated from each other, and the separated tops 422b are enclosed together to form a sealing device that only allows the liquid in the flow cell 6 to flow in one direction.
  • the inlet valve device is not shown in Fig. 10.
  • the inlet valve device has the same principle as the outlet valve device 421, and is used to allow only one-way flow of liquid in the flow cell 6 from the inlet hole 252 to the outlet hole 253.
  • the valve device is similar in structure to the outlet valve device 421. The only difference is that the top of the inlet valve of the inlet valve device extends from the root to the center and the inside of the through hole 42 so that the entire top of the inlet valve device faces the inside of the through hole 42 The cone-shaped or approximately cone-shaped.
  • the carrying platform is a fluid platform 7, and the fluid platform 7 corresponds to the liquid inlet 252, the liquid outlet 253, and the exhaust holes 254a and 254b of the flow cell 6. ⁇ 71 ⁇ The flow path 71.
  • the fluid platform 7 defines a receiving groove 72 corresponding to the fluid channel 71 where the fluid inlet 252, the fluid outlet 253 or the exhaust holes 254a, 254b are connected.
  • the boss 514 is positioned and sealed
  • the ring 4 extends into the receiving groove 72, the end of the sealing ring 4 abuts against the bottom of the receiving groove 72, the through hole 42 in the sealing ring 4 is butted with the flow channel 71, so that a fluid channel is formed between the flow cell 6 and the fluid platform 7 .
  • the sealing ring 4 includes a ring body 41, a through hole 42 enclosed by the ring body 41, and a sealing device arranged in the through hole 42.
  • the sealing device is a normally closed membrane 423.
  • the root of the normally closed membrane 423 is connected to the wall of the through hole 42 to close the through hole 42 so as to realize the flow cell using the sealing ring 4 in It is completely closed when it is not assembled to the fluid platform, effectively avoiding fluid overflow after the flow cell is separated from the fluid platform.
  • the normally closed membrane 423 is punctured by the liquid inlet/outlet needle to realize the communication between the flow cell and the flow channel of the fluid platform.
  • FIG. 13 is a biochemical substance reaction device 8 using the flow cell 1 (6).
  • the biochemical substance reaction device is used to load the flow cell and input reactant materials to the flow cell to cause the sample in the flow cell to react; or, the biochemical substance reaction device is further used to detect the occurrence The reacted sample obtains a signal reflecting the biological characteristics of the sample.
  • the biochemical substance reaction device 8 can be a gene sequencer, a liquid chromatograph, a biochemical analyzer, medical equipment, and the like.
  • the flow cell includes a flow cell body, the flow cell body includes a frame and a flow chamber defined by the frame, and the flow chamber as a whole constitutes a flow channel and includes The reaction area through which the fluid passes, the frame is provided with a liquid inlet hole and a liquid outlet hole to communicate with the flow chamber, and the fluid input from the liquid inlet hole flows through the reaction area of the flow chamber and then is output from the liquid outlet hole .
  • the frame is provided with a liquid inlet hole, a liquid outlet hole, and an exhaust hole to communicate with the flow chamber, and the fluid input from the liquid inlet hole flows through the flow chamber.
  • the reaction area of the chamber is then output from the liquid outlet hole, and the exhaust hole is used to discharge trapped air when the fluid flows through the reaction area.
  • the exhaust hole includes an inlet-side exhaust hole, and an inlet diversion groove is connected between the inlet-side exhaust hole and the liquid inlet hole.
  • the exhaust hole includes an outlet-side exhaust hole, and an outlet diversion groove is connected between the outlet-side exhaust hole and the liquid outlet hole. Both the inlet diversion groove and the outlet diversion groove have openings to communicate with the flow chamber.
  • the inlet diversion groove and the outlet diversion groove are both opened on the frame, the inlet diversion groove is connected to the two side walls of the liquid inlet hole and the inlet side exhaust hole, and the side wall close to the middle area of the flow chamber faces the middle area It is inclined, and the inclined side wall is arranged with rounded corners at the opening of the inlet diversion groove.
  • supporting points are arranged in the flow chamber.
  • the supporting points may be multiple, and the multiple supporting points are arranged at intervals, thereby enhancing the structural strength of the flow cell.
  • the supporting point may be a colloidal supporting point, and particles or microspheres of a specific size are mixed in the colloid to support the flow chamber.
  • the frame of the flow cell includes a base, a cover sheet, and a sealing fence connecting and sealing the base and the cover sheet, and the flow chamber is formed between the base, the cover sheet and the sealing fence.
  • the sealing fence adopts a colloid, and particles or microspheres of a specific size are mixed in the colloid to separate the substrate and the cover sheet by a predetermined distance to form the flow cell.
  • the flow cell body is arranged in a rectangular or square shape, the liquid inlet and the liquid outlet are arranged at the diagonal position of the flow cell body, and the two exhaust holes are arranged in the other of the flow cell. Diagonal position. Cutting the main body of the flow cell into a rectangle or even a square can maximize the use of the wafer area with nano-patterns; by adding two vent holes, positive pressure can be used to pump in reagents, and the reagents can spread evenly on the surface of the substrate for biochemical reactions at the same time Compared with negative pressure pumping, it has faster reagent flow speed and shorter reagent replacement time, as well as less reagent replacement ratio.
  • the flow cell provided by the embodiment of the present invention further includes an outer frame fixed on the outside of the flow cell body, and the outer frame is used for moving the flow cell by a mobile device.
  • the outer frame includes a grasping structure, and The grabbing structure is a hole opened on the outer frame.
  • the outer frame is also used to provide positioning for the mobile device to move the flow cell and place the flow cell on a carrying platform.
  • the outer frame includes a positioning structure that is opened on The outer frame has a hole portion with azimuth pointing characteristics.
  • the grasping structure and the positioning structure are the same structure.
  • the outer frame includes a fixing portion and a positioning portion provided on the outside of the fixing portion. The fixing portion is glued to the cover sheet.
  • the thickness of the fixing portion is thinner, and the ultra-thin fixing portion avoids
  • the positioning part protrudes toward the back side of the flow cell, which facilitates the movement and positioning of the flow cell, and also protects the flow cell.
  • the outer frame is formed by high-precision injection molding, which effectively fixes and protects the flow cell body while maintaining a low cost, and provides a grasping site for the mobile device to move the flow cell.
  • the ultra-thin fixed part avoids the need for the optical scanning system. Interference.
  • the flow cell provided by the embodiment of the present invention further includes an electronic label arranged on the outer frame.
  • the electronic tag not only provides human-readable specification information of the flow cell, but also electronically readable information of the flow cell, which reduces manual operations and avoids human input errors.
  • the flow cell provided by the embodiment of the present invention further includes a sealing ring provided on the back side of the flow cell to realize the coordination and sealing between the flow cell and one or more bearing platforms.
  • the integrated arrangement of the sealing ring and the flow cell can effectively prevent the fluid from infiltrating the substrate and affecting the vacuum adsorption of the flow cell on different platforms; at the same time, it can also avoid the deterioration of the sealing performance caused by the long-term use of the sealing ring.
  • There are a plurality of the sealing rings which are respectively arranged corresponding to the liquid inlet hole and the liquid outlet hole.
  • the sealing ring is also provided corresponding to the vent hole. Further, the sealing ring is fixed on the back side of the flow cell by a sealing ring fixing device.
  • the sealing ring fixing device is pasted on the back side of the flow cell, and pasted by glue such as double-sided tape, the sealing ring and the liquid inlet and outlet holes can be reliably and effectively sealed within the accuracy range.
  • the sealing ring fixing device includes a fixing structure, and the sealing ring is fixed by the fixing structure.
  • the fixing structure is a fixing hole, and the sealing ring is installed in the fixing hole.
  • each of the sealing rings includes a ring body and a through hole surrounded by the ring body, the through hole is arranged corresponding to the liquid inlet, the liquid outlet, or the exhaust hole, and a card is provided on the ring body.
  • the fixing structure is provided with a matching structure on the fixing hole, and the sealing ring is fixed in the fixing hole through the cooperation of the clamping structure and the matching structure.
  • the engaging structure is a protrusion provided on the outer side of the ring body
  • the matching structure is a recess provided in the fixing hole
  • the engaging structure is provided on the outer side of the ring body
  • the mating structure is a protrusion set in the fixing hole; or, the engaging structure is the outer surface of the ring body, and the mating structure is the inner surface of the fixing hole.
  • the sealing ring fixing device further includes a positioning boss, the positioning boss is arranged on the fixing structure and sleeved on the outside of the sealing ring, and the positioning boss is positioned on the auxiliary flow cell and the carrying platform assembling and positioning At the same time, it plays a role of fixing and strengthening the sealing ring to prevent the sealing ring from being deformed by force and affecting fluid flow.
  • a one-way sealing device, a normally closed membrane and/or a valve device are arranged in the through hole of the sealing ring, which can effectively avoid reagent overflow and evaporation and crystallization in the flow cell during the transfer process.
  • the flow cell provided by the embodiment of the present invention achieves the following effects: (1) Fully utilize round wafers to achieve rapid and effective spreading of reagents when the length and width dimensions are similar; (2) Provide The transfer structure between platforms ensures high-precision and repeated automatic positioning of different platforms, decouples the optomechanical platform and the biochemical reaction platform, and realizes the sequential or combined operation of multiple sequencing flow cells; (3) Flow cell RFID module and optical identification tag Uniformity; (4) The sealing ring and the flow cell are integrated assembling without matching clearance.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Dispersion Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

一种流动池，包括流动池本体，所述流动池本体包括框架及设于框架内的流动室，所述流动室内包括允许流体经过的反应区域，所述框架上开设进液孔、出液孔及排气孔连通所述流动室，从所述进液孔输入的流体流经所述流动室的反应区域后从所述出液孔输出，所述排气孔用于在流体流经所述反应区域的过程中排出所述流动室中的困气。还提供一种密封圈一体设置的流动池及应用所述流动池的生化物质反应装置。

Description

流动池及应用所述流动池的生化物质反应装置 技术领域
本发明涉及生化反应领域搭载样品进行反应的流动池及应用所述流动池的生化物质反应装置。
背景技术
生化反应领域一般配置流动池搭载样品，所述流动池是一种样品载体，用于加载生化物质的样品并发生检测分析反应，其通常含有容纳样品和流体的腔体。在测序情况下，所述流动池是测序芯片，在其它情况下，所述流动池可为其它样品载体。以下以测序芯片为例说明流动池现况。
在基因测序领域，测序芯片通常作为仪器配套耗材单次使用。在测序过程中，样品的承载和荧光标记的生化反应都是在基因测序芯片内完成。目前的二代测序技术主要有基于光学检测的荧光标记法，以及通过氢离子浓度变化识别碱基的化学测序方法。其中基于氢离子浓度变化识别碱基的化学测序法具有检测仪器体积和速度上的优势，但是存在同聚物错误(homopolymer errors)和通量不高问题。基于光学检测识别的二代测序技术则有着最高的碱基识别准确度和当前最大的通量。在测序领域，流动池一般也会被称为流动槽、反应池、芯片、测序芯片、基因测序芯片或者卡盒等，常见的英文名称有Flow Cell、Flowcell、Chip、Chip Kit和Cartridge等。
二代测序技术中都是首先经过一系列的反应，再通过对荧光信号或者电信号的分析识别间接得到DNA的序列。凭借二代测序的高通量优势，基因测序载样流动池以硅晶圆、玻璃或高分子为基材，配合微机电自动化、或其他精密加工技术，所制作的高科技元件，使研究人员能够 快速筛选大量的生物分析物用于各种目的，从疾病的诊断到生物恐怖主义的检测。传统的测序载样流动池为细窄的流体通道，由于光学衍射极限限制，无法在单张流动池内实现超高通量的样本检测。且由于设计原因，传统芯片使用负压抽液的方式进行试剂铺展及替代，存在试剂替代比列大，试剂替代速度慢的问题，不利于超高通量测序系统的搭建。
除了上述问题，现有技术中还存在如下问题：
(1)单流向设计芯片无法充分利用圆形晶圆；芯片长宽比例过大，对高精密成像扫描平台尺寸要求高；负压抽液速度慢；
(2)传统测序仪器由于光机系统滑动平台尺寸及重量承载限制，一套光机系统最多匹配2张测序载样流动池流体平台同时工作，不利于超高通量测序系统的多流动池同时测序，而且由于流动池承载平台的热效应，无法实现多流动池工作状态的完全解耦，即无法实现多流动池的顺序上机或者组合上机；
(3)RFID模块与光学识别标签(二维码)分离，高成本同时有错配风险；
(4)当前测序载样流动池的进、出试剂是通过承载平台上固定的密封圈实现承载平台和流动池进、出液孔的配合与密封。由于密封圈需要多次对接流动池，密封效果会随着使用次数增加而可靠性降低，在有些系统中流动池的光学和流体平台分开，需要对流动池进行多次转移，密封圈的密闭效果在使用过程中面临较大考验。同时，进、出液口的试剂溢出也是系统的潜在风险点。密封圈在进液模块端容易位置错配而影响进液，导致漏液风险；密封圈的老化需要定期进行更换，增加操作人员工作量的同时也对操作要求较高；密封圈间隙配合在转移过程中无法避免间隙处漏液导致接口部位试剂结晶而影响密封效果。
发明内容
为了解决现有技术的上述部分或全部问题以及其他潜在问题，有必 要提出一种流动池及应用所述流动池的生化物质反应装置。
第一方面，提供一种流动池，所述流动池包括流动池本体，所述流动池本体包括框架及设于框架内的流动室，所述流动室内包括允许流体经过的反应区域，所述框架上开设进液孔、出液孔及排气孔连通所述流动室，从所述进液孔输入的流体流经所述流动室的反应区域后从所述出液孔输出，所述排气孔用于在流体流经所述反应区域的过程中排出所述流动室中的困气。
第二方面，提供一种流动池，所述流动池包括多个密封圈，所述多个密封圈中的一或多个对应所述流动池与外界连通的通孔设置。
第三方面，提供一种生化物质反应装置，所述生化物质反应装置用于加载上述的流动池及输入反应物质至所述流动池以使所述流动池内的样品发生反应；或者，所述生物物质反应装置还进一步用于检测所述发生反应后的样品以获得反应所述样品生物特征的信号。
本发明实施方式中提供的流动池及生化物质反应装置，通过在流动池上设置排气孔，可将流动池长宽比例变小，充分利用圆形晶圆，实现流体的快速、有效铺展，而通过密封圈与流动池一体化设置，可以有效避免流体浸润基底而影响流动池在不同平台的真空吸附；同时还可以避免由于密封圈长期使用老化导致的密封性降低。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对本发明实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是本发明一实施方式中的流动池的立体示意图。
图2是图1所示流动池另一角度的立体示意图。
图3是图1所示流动池的分解视图。
图4是沿图1所示IV-IV线的剖视图。
图5是图4所示V区域放大图。
图6是图4所示VI区域放大图。
图7是沿图1所示VII-VII线的局部剖视图。
图8是本发明另一实施方式中一流动池被安装至一承载平台上的示意图。
图9是图8所示流动池与承载平台的分离的示意图。
图10是沿图8所示X-X线的局部剖视图。
图11是图8所示流动池出口上设置的密封圈的局部剖切示意图。
图12是另一实施方式中的设置于流动池入口上的密封圈的局部剖切示意图。
图13是本发明一实施方式提供的生化物质反应装置的示意图。
如下具体实施方式将结合上述附图进一步说明本发明。
主要元件符号说明
Figure PCTCN2019108642-appb-000001
Figure PCTCN2019108642-appb-000002
具体实施方式
以下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。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。
需要说明的是，当组件被称为“固定于”、“安装于”另一个组件，它可以直接在另一个组件上或者也可以存在居中的组件。当一个组件被认为是“设置于”另一个组件，它可以是直接设置在另一个组件上或者可能同时存在居中组件。本文所使用的术语“及/或”包括一个或多个相关的所列项目的所有的和任意的组合。
请参阅图1至图3所示，为本发明一实施方式中的流动池两个角度的立体示意图及分解视图。所述流动池1包括流动池本体2及设置于流动池外侧的外框架3。所述流动池1包括正面侧11及与正面侧11相背的背面侧13。所述流动池1的背面侧13上设置了多个密封圈4，通过所述密封圈4实现与不同承载平台的配合与密封。其中，所述配合包括所述流动池1的进出液配合。
请同时参阅图4与图5所示，所述流动池本体2包括框架20及形成于框架20内的流动室25。所述框架20从背面侧13至正面侧11依次包括基底21与盖片23，盖片23允许光线通过以使流动室25内流体运动情况在流动池1的正面侧11可被观察。在本实施例中，所述盖片23为光学玻璃，所述基底21为矩形切割硅片，进一步地，所述基底21为基因patterned array技术的高密度纳米点阵的矩形切割硅片。所述盖片23周围区域通过胶体26与基底21的周围区域连接。所述流动室25对应盖片23与基底21的中心区域设置。在本实施方式中，所述胶体26为固化胶水，如紫外固化胶水。所述胶体26环绕盖片23与基底21周围区域连续分布形成一个密封围栏，所述胶体26内混合有特定尺寸微球或其他形状的可将所述微球将盖片23与基底21之间隔开预设距离的微粒，从而对应盖片23与基底21的中心区域形成所述流动室25。所述流动室25周围由所述胶体26密封，使所述流动室25成为允许流体与样品进行反应的密闭反应腔室。
在本实施方式中，所述流动池1为矩形或方形，所述流动池本体2为矩形或方形，所述框架20为矩形或方形，所述流动室25亦为矩形或 方形。在其他实施方式中，所述流动池1、流动池本体2、框架20及/或流动室25亦可为其他多边形。
请参阅图1与图3所示，所述流动室25内设置支撑点，在本实施方式中，所述支撑点为胶体支撑点251。所述胶体支撑点251两端连接和支撑盖片23与基底21，从而加强流动池本体2的片内结构强度。在本实施方式中，所述胶体支撑点251同样采用紫外固化胶水，胶体支撑点251内同样混合有特定尺寸微球或其他形状的可将盖片23与基底21之间隔开预设距离的微粒。在本实施方式中，所述胶体支撑点251为多个，所述多个胶体支撑点251间隔排列。
在本实施方式中，基底21的材料可为光学玻璃、熔融石英、单晶硅片、多晶硅片或其他陶瓷材料。所述微球直径为30～80微米中的任一数值。
所述流动池1的背面侧13，在所述基底21上设置了流动室25的进液孔252、出液孔253、及排气孔254a与254b。在本实施方式中，进液孔252与出液孔253设置在流动室25的一对对角位置，一个排气孔254a(下称“入口侧排气孔254a”)与进液孔252设置在同侧，进液孔252与入口侧排气孔254a之间连接导流槽255a(下称“入口导流槽255a”)。另一个排气孔254b(下称“出口侧排气孔254b”)与出液孔253设置在同侧，出液孔253与出口侧排气孔254b之间连接导流槽255b(下称“出口导流槽255b”)。在本实施方式中，入口导流槽255a与出口导流槽255b分别设置在流动室25相对的两侧边部，入口导流槽255a与出口导流槽255b二者大致平行。在本实施方式中，入口侧排气孔254a与出口侧排气孔254b还分别设置于流动室25的另一对对角位置。
请参阅图4至图6所示，所述入口导流槽255a包括底面2551a、侧壁2552a与侧壁2553a、及开口2554a。其中，开口2554a与底面2551a相对，开口2554a连通入口导流槽255a与流动室25。侧壁2552a与侧壁2553a连接于开口2554a与底面2551a之间，相比侧壁2552a，侧壁 2553a更靠近流动室25的中间区域。在本实施方式中，侧壁2552a大致垂直底面2551a与开口2554a，侧壁2553a为一斜壁，与底面2551a、开口2554a呈倾斜状态。侧壁2553a由连接底面2551a的底部开始，向上的同时朝向流动室25中间区域延伸，使侧壁2553a靠近开口2554a的顶部相比底部更靠近流动室25的中间区域。进一步地，在本实施方式中，侧壁2553a顶部与基底21表面相连的部位被设置呈圆角，从而使侧壁2553a与基底21之间呈平缓且圆滑的过渡。通过将入口导流槽255a的其中一侧壁倾斜设置、扩大了入口导流槽255a的开口2554a，同时，通过在其中一侧壁与基底21表面之间设置平滑的过渡，避免进液孔252附近的流体扰动，减弱了高速流动下的涡流状态，提高了进液孔252附近的生化反应均匀性。
流体从进液孔252进入流动室25后，首先顺着入口导流槽255a朝向入口侧排气孔254a流动，随着进入的流体增加，流体整体从进液孔252与入口导流槽255a所在的入口端25a朝向出液孔253与出口导流槽255b所在的出口端25b流动，最终汇入出口导流槽255b，由出口导流槽255b导流至出液孔253、通过出液孔253流出流动室25。通过排气孔254a、254b与导流槽255a、255b的设置，可使流体均匀铺满流动室25允许流体经过的所有流动区域(反应区域)，从而保证流动室25内各处生化反应的均匀性。
在其他实施方式中，侧壁2552a亦可为斜面，例如，侧壁2552a被倾斜成：侧壁2552a靠近开口2554a处的顶部相比与底面2551a相连的底部更靠近流动室25的边缘区域。
所述出口导流槽255b连接于出液孔253与出口侧排气孔254b之间，出口导流槽255b包括底面2551b、侧壁2552b与侧壁2553b、及开口2554b。其中，开口2554b与底面2551b相对，开口2554b连通出口导流槽255b与流动室25。侧壁2552b与侧壁2553b连接于开口2554b与底面2551b之间。在本实施方式中，侧壁2552b、2553b均大致垂直 于底面2551b与开口2554b。在其他实施方式中，侧壁2552b、2553b中任一或全部均可为斜面。例如，出口导流槽255b可与入口导流槽255a对称设置。
请参阅图3与图5、图6，所述外框架3整体呈半包围方式环绕流动池本体2周侧设置。所述外框架3包括固定部31与定位部32。其中，固定部31设置于定位部32的内侧，固定部31将外框架3固定至盖片23上，在本实施方式中，固定部31通过胶体粘合至盖片23的周围区域。定位部32设置于固定部31的外侧，相比定位部32，固定部31的厚度较薄，超薄的固定部31避免了光学扫描系统的干涉问题。相比固定部31，定位部32朝向流动池1的背面侧13突出。固定部31朝向流动池1的背面侧13的一面被粘合至盖片23的周围区域上。从而将外框架3固定至盖片23上。定位部32上设置多个抓取结构321，所述抓取结构321供移动装置(图未示)抓取以将流动池1在不同位置移动。例如，在流动池1用于基因测序时，流动池1需在流体反应区与光学拍照区之间反复移动，此时，移动装置通过定位部32上的抓取结构321便可抓取流动池1并可在流体反应区与光学拍照区之间反复移动流动池1。在本实施方式中，所述抓取结构321为开设于定位部32上的孔部。进一步地，在本实施方式中，抓取结构321为开设于定位部32的四个角部区域322上的矩形孔。在其他实施方式中，所述抓取结构321可为其他形状的孔部，如，为圆形的孔部。所述抓取结构321可设于定位部32的其他位置。定位部32上还设有定位结构323，所述定位结构323为移动装置移动及放置流动池1于承载平台上时提供定位，以便流动池可被精确定位于不同位置的承载平台上。在本实施方式中，所述定位结构323为V形斜槽孔，进一步地，在本实施方式中，所述定位结构323为两个，每个定位结构323为V形斜槽孔。更进一步地，在本实施方式中，每个V形斜槽孔设置于一作为抓取结构321的孔部的一侧，且与该孔部相连通。在其他实施方式中，定位结构323可与抓取结构321 一体设置，也就是说，同一结构即可被用于移动装置抓取流动池1，也可被用于移动装置在移动及放置流动池1于承载平台上时提供定位，例如，一些具有方位指向特征的孔部，如三角形，就可被用于同时做为定位结构323与抓取结构321。在本实施方式中，所述定位部32整体环绕在流动池1的盖片23与基底21外侧，从而亦对流动池1起保护作用。在本实施方式中，外框架3采用注塑成型制成，所述外框架的材料可为玻璃纤维、碳纤维增强聚合物塑料或者其他常见塑料类型。
所述外框架3朝向流动池1的正面侧11的一侧还设有电子标签33，在本实施方式中，电子标签33被粘贴于外框架3上，电子标签33不仅包括设于电子标签外面的机器非接触识别符331，还包括设于电子标签33内部的机器感应识别元件332，进一步地，在本实施方式中，电子标签33还包括文字识别符号333。其中，在本实施方式中，机器非接触识别符号331可为一维码、二维码等光学可识别符号，机器感应识别元件332可为RFID(射频识别)模块。
所述外框架3上设置电子标签33处朝向下凹陷形成一凹槽34，所述电子标签33被容置于所述凹槽34内，从而避免电子标签33突出于外框架3表面而与其他部件干涉。
请参阅图2、图3与图7所示，所述流动池1的背面侧13上设置了多个密封圈4，密封圈4分别对应进液孔252、出液孔253及排气孔254a、254b设置。流动池1通过密封圈4实现与不同承载平台的配合及密封。
密封圈4通过密封圈固定装置5固定于流动池1的背面侧13。在本实施方式中，所述密封圈固定装置5为一矩形框架，在矩形框架上对应进液孔252、出液孔253、排气孔254a与254b的四个位置设置了固定结构51，通过所述固定结构51把密封圈4固定。进一步地，在本实施方式中，所述固定结构51为固定孔512，所述密封圈4被安装于固定孔512中。每一密封圈4包括圈体41及被圈体41围合形成的通孔 42。通孔42可为直筒状或圆锥状。圈体41上设置了与所述固定孔512内结构相配合的至少一个卡合结构411。通过所述卡合结构411嵌入所述固定孔512中。在本实施方式中，每一密封圈4的卡合结构411为设置于圈体41外侧的凸块411a，对应每一密封圈4的固定孔512中亦设置了配合结构513，所述配合结构513与密封圈4的卡合结构411相配合，将密封圈4固定于固定孔512中。在本实施方式中，每一固定孔512的配合结构513为设置于固定孔512中的凹部513a，凹部513a通过收容密封圈4上的凸块411a而将密封圈4固定于固定孔512中。
可以理解，在其他实施方式中，密封圈4的卡合结构411可以是设置于圈体41上的凹部，固定孔512中的配合结构可以是设置于固定孔512中的凸块。可以理解，在其他实施方式中，密封圈4的卡合结构411可以是圈体41的外侧表面，固定孔512中的配合结构可以是固定孔512的内表面，通过密封圈4的外侧表面与固定孔512的内表面的过盈配合，将密封圈4固定于固定孔512中。可以理解，在其他实施方式中，密封圈4还可通过胶粘等方式固定于固定孔512中。
在本实施方式中，每一固定孔512上进一步设置了定位凸台514，在固定至固定孔512中后，密封圈4一端从定位凸台514上伸出，使定位凸台514套设于所述密封圈4外侧。定位凸台514用于与承载平台上的对应部位配合(如与流体平台上的进、出液孔配合)，辅助定位的同时，避免密封圈4受力形变而影响流体流动。
在本实施方式中，密封圈固定装置5被固定于流动池1的背面侧13。具体地，密封圈固定装置5被胶体如双面胶粘贴于流动池1的背面侧13。在本实施方式中，利用一个密封圈固定装置5同时将多个密封圈4固定至流动池1的背面侧13，在其他实施方式中，密封圈固定装置5可以被分割为多个独立的子固定装置，每个子固定装置固定一个密封圈4。
请参阅图8至图11所示，为本发明另一实施方式中的流动池与承 载平台的配合示意图。所述流动池6结构大体与前一实施方式中的流动池1相同，不同主要在于：流动池6中采用的密封圈4的通孔42内进一步设置了单向密封装置，在本实施方式中，所述单向密封装置为瓣膜装置，其中，对应进液孔252的密封圈4的通孔42内设置了进液瓣膜装置，对应出液孔253、及排气孔254a与254b的通孔42内设置了出液瓣膜装置421。图10示出了其中一个出液瓣膜装置421，在本实施方式中，所述出液瓣膜装置421包括多个瓣膜422，每个瓣膜422包括连接通孔42孔壁的根部422a及由根部422a向通孔42中心及外侧延伸形成的顶部422b，从而使出液瓣膜装置421整体呈顶端朝向通孔42外侧的锥状或近似锥状。其中，所有瓣膜422的根部422a可以依次连接为一体，或者，所有瓣膜422的根部422a也可以彼此分开，彼此分开的根部422a紧靠并围合在一起。所有瓣膜422的顶部422b彼此分开，彼此分开的顶部422b围合在一起，形成仅允许流动池6内液体单向流动的密封装置。图10中未示出进液瓣膜装置，进液瓣膜装置与出液瓣膜装置421原理相同，用于仅允许流动池6内液体从进液孔252至出液孔253的单向流动，进液瓣膜装置与出液瓣膜装置421结构相似，不同仅在于进液瓣膜装置的进液瓣膜的顶部由根部向通孔42中心及内侧延伸形成，从而使进液瓣膜装置整体呈顶端朝向通孔42内侧的锥状或近似锥状。
请参阅图10所示，在本实施方式中，承载平台为一流体平台7，所述流体平台7上对应流动池6的进液孔252、出液孔253及排气孔254a与254b分别开设了流道71。流体平台7对应流道71对接进液孔252、出液孔253或排气孔254a、254b的部位开设一收容槽72，在流动池6安装至流体平台7上后，定位凸台514及密封圈4伸入收容槽72中，密封圈4端部抵持收容槽72底部，密封圈4中的通孔42与流道71对接，从而使流动池6与流体平台7之间构成一流体通道。
请参阅图12所示，为另一实施方式中的密封圈4的局部剖切示意 图。所述密封圈4包括圈体41、被圈体41围合形成的通孔42及设置于通孔42内的密封装置。在本实施方式中，所述密封装置为常闭膜423，所述常闭膜423根部连接至通孔42的壁上，将通孔42封闭，从而实现应用所述密封圈4的流动池在没有装配至流体平台时的完全封闭，有效避免了流动池脱离流体平台后流体的溢出。而装配至流体平台后，通过进/出液针穿刺常闭膜423，即可实现流动池与流体平台流道的连通。
请参阅图13所示，为应用所述流动池1(6)的生化物质反应装置8。所述生化物质反应装置用于加载所述的流动池及输入反应物质至所述流动池以使所述流动池内的样品发生反应；或者，所述生化物质反应装置还进一步用于检测所述发生反应后的样品以获得反应所述样品生物特征的信号。所述生化物质反应装置8可以为基因测序仪、液相色谱仪、生化分析仪和医疗器械等。
综上所述，本发明实施方式提供的流动池，所述流动池包括流动池本体，所述流动池本体包括框架及由框架界定的流动室，所述流动室整体构成一个流道并包括允许流体经过的反应区域，所述框架上开设进液孔与出液孔连通所述流动室，从所述进液孔输入的流体流经所述流动室的反应区域后从所述出液孔输出。
综上所述，本发明实施方式提供的流动池，所述框架上开设进液孔、出液孔及排气孔连通所述流动室，从所述进液孔输入的流体流经所述流动室的反应区域后从所述出液孔输出，所述排气孔用于在流体流经所述反应区域的过程中排出困气。
综上所述，本发明实施方式提供的流动池，所述排气孔包括入口侧排气孔，所述入口侧排气孔与进液孔之间连接入口导流槽。所述排气孔包括出口侧排气孔，所述出口侧排气孔与出液孔之间连接出口导流槽。所述入口导流槽与出口导流槽均具有开口连通流动室。通过排气孔与导流槽的设置，可使流体均匀铺满流动室、允许流体经过所有流动区域(反应区域)，从而保证流动室内各处生化反应的均匀性。
进一步地，入口导流槽与出口导流槽均开设于框架上，入口导流槽连接进液孔与入口侧排气孔的两个侧壁中，靠近流动室中间区域的侧壁朝向中间区域倾斜，且所述倾斜的侧壁在所述入口导流槽的开口处呈圆角设置。通过倾斜侧壁及/或侧壁在开口处的圆角设置，避免进液孔附近的流体扰动，减弱了高速流动下的涡流状态，提高了进液孔附近的生化反应均匀性。
本发明实施方式提供的流动池，流动室内设置支撑点，进一步地，所述支撑点可以为多个，多个支撑点间隔排列，从而加强了流动池的片内结构强度。进一步地，所述支撑点可以为胶体支撑点，胶体内混合有特定尺寸微粒或微球以支撑所述流动室。
本发明实施方式提供的流动池，流动池的框架包括基底、盖片及将基底与盖片连接及密封的密封围栏，所述流动室形成于所述基底、盖片及密封围栏之间。所述密封围栏采用胶体，所述胶体内混合有特定尺寸微粒或微球以将所述基底与盖片隔开预设距离以形成所述流动池。通过采用混合有特定直径微粒或微球支撑的胶水形成支撑点与密封围栏，可通过点胶机和工装化后完成高精度的流动池结构封装，通过微粒高度或微球直径实现流动池微米级高度控制。
本发明实施方式提供的流动池，将流动池本体设置成矩形或方形，将进液孔与出液孔设置于流动池本体的一对角线位置，将两个排气孔设置于流动池另一对角线位置。将流动池主体切割为矩形甚至方形，可最大程度的利用带有纳米图形的晶圆面积；通过增加两个排气孔，可利用正压力泵入试剂，均匀试剂铺展基底表面进行生化反应的同时，相比负压抽液具有更快的试剂流动速度和更短的试剂替换时间，以及更少的试剂替代比。
本发明实施方式提供的流动池，还包括固定于流动池本体外侧的外框架，所述外框架用于供移动装置移动所述流动池，进一步地，所述外框架包括抓取结构，所述抓取结构为开设于所述外框架上的孔部。所述 外框架还用于为所述移动装置移动所述流动池及放置所述流动池于一承载平台上时提供定位，进一步地，所述外框架包括定位结构，所述定位结构为开设于所述外框架上具有方位指向特征的孔部，进一步地，所述抓取结构与所述定位结构为同一结构。进一步地，所述外框架包括固定部与设于固定部外侧的定位部，所述固定部被粘贴至所述盖片上，相比定位部，固定部的厚度较薄，超薄的固定部避免了光学扫描系统的干涉问题，相比固定部，定位部朝向流动池的背面侧突出，在便于移动、定位流动池的同时，亦对流动池起保护作用。外框架采用高精度注塑形成，在维持较低成本的同时，有效固定和保护了流动池本体，为移动装置移动流动池提供了抓取位点，超薄的固定部又避免了对光学扫描系统的干涉。
本发明实施方式提供的流动池，还包括设于所述外框架上的电子标签。电子标签既提供肉眼可读的流动池规格信息的同时，提供了流动池电子可读信息，减少了人工操作的同时避免了人为的输入错误。
本发明实施方式提供的流动池，还包括设置于流动池背面侧的密封圈，用于实现所述流动池与一或多个承载平台之间的配合及密封。密封圈与流动池一体化设置，可以有效避免流体浸润基底而影响流动池在不同平台的真空吸附；同时还可以避免由于密封圈长期使用老化导致的密封性降低。所述密封圈为多个，分别对应所述进液孔与出液孔设置。所述密封圈还对应所述排气孔设置。进一步地，所述密封圈被密封圈固定装置固定于所述流动池背面侧。进一步地，所述密封圈固定装置被粘贴于所述流动池背面侧，通过胶体如双面胶粘贴，可以在精度范围要求内可靠、有效的实现密封圈与进、出液孔的密封。进一步地，所述密封圈固定装置包括固定结构，通过所述固定结构固定所述密封圈。进一步地，所述固定结构为固定孔，所述密封圈被安装于所述固定孔中。进一步地，每一所述密封圈包括圈体及被所述圈体围合形成的通孔，所述通孔对应进液孔、出液孔或排气孔设置，所述圈体上设置卡合结构，所述固定孔 上设置配合结构，通过所述卡合结构与配合结构的配合将密封圈固定于所述固定孔中。进一步地，所述卡合结构为设置于所述圈体外侧的凸块，所述配合结构为设置于所述固定孔中的凹部，或者，所述卡合结构为设置于所述圈体外侧的凹部，所述配合结构为设置于所述固定孔中的凸块；或者，所述卡合结构为所述圈体的外侧表面，所述配合结构为所述固定孔的内表面。进一步地，所述密封圈固定装置还包括定位凸台，所述定位凸台设置于所述固定结构上，套设于所述密封圈外侧，定位凸台在辅助流动池与承载平台装配定位的同时，对密封圈起到固定加固作用，避免密封圈受力变形而影响流体流动。进一步地，所述密封圈的通孔内设置了单向密封装置、常闭膜及/或瓣膜装置，可以有效避免流动池在转移过程中的试剂外溢及蒸发结晶。
综上所述，本发明实施例提供的流动池，实现了下述效果：(1)充分利用圆形晶圆，在长宽尺寸相近的情况下实现试剂的快速、有效铺展；(2)提供平台间转移结构，保证不同平台的高精度重复自动定位，解耦光机平台和生化反应平台，实现多测序流动池的顺序上机或者组合上机；(3)流动池RFID模块与光学识别标签统一；(4)密封圈与流动池无配合间隙一体化装配。
最后应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或等同替换，而不脱离本发明技术方案的精神和范围。

Claims (33)

  1. 一种流动池，包括流动池本体，其特征在于，所述流动池本体包括框架及设于框架内的流动室，所述流动室内包括允许流体经过的反应区域，所述框架上开设进液孔、出液孔及排气孔连通所述流动室，从所述进液孔输入的流体流经所述流动室的反应区域后从所述出液孔输出，所述排气孔用于在流体流经所述反应区域的过程中排出所述流动室中的困气。
  2. 如权利要求1所述的流动池，其特征在于，所述流动池本体包括入口端及出口端，所述排气孔包括入口侧排气孔与出口侧排气孔，所述进液孔与所述入口侧排气孔隔开一定距离设置于所述入口端，所述出液孔与所述出口侧排气孔隔开一定距离设置于所述出口端。
  3. 如权利要求2所述的流动池，其特征在于，所述入口侧排气孔与所述出口侧排气孔分置于所述进液孔与所述出液孔所在连线的两侧。
  4. 如权利要求2所述的流动池，其特征在于，所述流动室呈矩形或方形，所述进液孔与所述出液孔对应于所述流动室一对角线所在位置设置，所述入口侧排气孔与所述出口侧排气孔分置于所述对角线的两侧，或者所述入口侧排气孔与所述出口侧排气孔对应于所述流动室另一对角线所在位置设置。
  5. 如权利要求2所述的流动池，其特征在于，所述框架上还开设入口导流槽，所述入口导流槽连接所述进液孔与所述入口侧排气孔，所述入口导流槽具有底面及与所述底面相对的开口，所述入口导流槽的所述开口连通所述入口导流槽与所述流动室。
  6. 如权利要求5所述的流动池，其特征在于，所述框架上还开设出口导流槽，所述出口导流槽连接所述出液孔与所述出口侧排气孔，所述出口导流槽具有底面及与所述底面相对的开口，所述出口导流槽的所述开口连通所述出口导流槽与所述流动室。
  7. 如权利要求5所述的流动池，其特征在于，所述入口导流槽还包括 连接所述底面与所述开口的两个侧壁，其中，所述两个侧壁包括一靠近所述流动池中间区域的第一侧壁及一远离所述流动池中心区域的第二侧壁，所述第一侧壁为斜面，或者，所述第一侧壁为朝向中间区域倾斜的斜面。
  8. 如权利要求5或7所述的流动池，其特征在于，所述第一侧壁在所述入口导流槽的开口处呈圆角设置。
  9. 如权利要求1所述的流动池，其特征在于，所述流动池内设置支撑点，所述支撑点支撑所述流动室以加强所述流动池强度。
  10. 如权利要求9所述的流动池，其特征在于，所述支撑点为多个，多个所述支撑点间隔排列。
  11. 如权利要求9或10所述的流动池，其特征在于，所述支撑点为胶体支撑点，所述胶体支撑点内混合有特定尺寸微粒或微球以支撑所述流动池。
  12. 如权利要求1至11任一项所述的流动池，其特征在于，所述框架包括基底、盖片及将所述基底与盖片连接及密封的密封围栏，所述流动室形成于所述基底、盖片及密封围栏之间。
  13. 如权利要求12所述的流动池，其特征在于，所述密封围栏采用胶体，所述胶体内混合有特定尺寸微粒或微球以将所述基底与盖片隔开预设距离以形成所述流动池。
  14. 如权利要求1至13任一项所述的流动池，其特征在于，所述流动池还包括外框架，所述外框架置于所述流动池本体外侧，用于供移动装置移动所述流动池。
  15. 如权利要求14所述的流动池，其特征在于，所述外框架上设有抓取结构，所述抓取结构用于供所述移动装置抓取并移动所述流动池；及/或，所述抓取结构为开设于所述外框架上的孔部；及/或，所述外框架上设有定位结构，所述定位结构用于为所述移动装置移动所述流动池及放置所述流动池于一承载平台上时提供定位；及/或，所 述定位结构为开设于所述外框架上的孔部。
  16. 如权利要求14所述的流动池，其特征在于，所述外框架包括固定于所述流动池本体上的固定部及设于所述固定部外侧的定位部，所述定位部用于供所述移动装置移动所述流动池；及/或，所述定位部用于供所述移动装置在移动所述流动池时定位所述流动池；及/或，所述定位部用于供所述移动装置放置所述流动池于一承载平台上时提供定位；及/或，所述定位部套设于所述流动池本体外侧以保护所述流动池本体。
  17. 如权利要求14所述的流动池，其特征在于，所述流动池包括正面侧及与所述正面侧相背的背面侧，所述进液孔、出液孔及排气孔设置于所述背面侧，所述外框架包括固定部及设于所述固定部外侧的定位部，所述固定部固定于所述正面侧上或者所述固定部被粘贴于所述正面侧的周边区域。
  18. 如权利要求17所述的流动池，其特征在于，所述固定部沿所述正面侧至背面侧的厚度小于所述定位部沿所述正面侧至背面侧的厚度。
  19. 如权利要求14所述的流动池，其特征在于，所述外框架上设有电子标签，或者，所述外框架上设有凹槽，所述凹槽收容一电子标签。
  20. 如权利要求1至19任一项所述的流动池，其特征在于，所述流动池包括多个密封圈，所述密封圈分别对应所述进液孔、出液孔及排气孔设置。
  21. 如权利要求20所述的流动池，其特征在于，每一所述密封圈被一固定结构固定于所述流动池上，或者，每一所述密封圈被一固定孔固定于所述流动池上。
  22. 如权利要求21所述的流动池，其特征在于，所述流动池包括正面侧及与所述正面侧相背的背面侧，所述进液孔、出液孔及排气孔设置于所述背面侧，所述固定结构或所述固定孔设置于一密封圈固定装置上，所述密封圈固定装置被固定或粘贴至所述背面侧。
  23. 如权利要求22所述的流动池，其特征在于，还包括多个定位凸台，每一所述定位凸台套设于一对应的所述密封圈外侧并固定连接至一对应的所述固定结构或固定孔上。
  24. 如权利要求20所述的流动池，其特征在于，每一所述密封圈内设置单向密封装置、常闭膜或者瓣膜装置。
  25. 一种流动池，其特征在于，所述流动池包括多个密封圈，所述多个密封圈中的一或多个对应所述流动池与外界连通的通孔设置。
  26. 如权利要求25所述的流动池，其特征在于，所述多个密封圈中的一或多个对应所述流动池的进液孔、出液孔设置。
  27. 如权利要求25所述的流动池，其特征在于，所述多个密封圈中的一或多个对应所述流动池的排气孔设置。
  28. 如权利要求25所述的流动池，其特征在于，每一所述密封圈被一固定结构固定于所述流动池上，或者，每一所述密封圈被一固定孔固定于所述流动池上。
  29. 如权利要求28所述的流动池，其特征在于，所述固定结构或所述固定孔设置于一密封圈固定装置上，所述密封圈固定装置被固定或粘贴至所述背面侧。
  30. 如权利要求28或29所述的流动池，其特征在于，每一所述密封圈外侧设置定位凸台，每一所述定位凸台连接至对应的所述固定结构或固定孔上。
  31. 如权利要求30所述的流动池，其特征在于，每一所述密封圈内设置单向密封装置、常闭膜或者瓣膜装置，每一所述单向密封装置、常闭膜或者瓣膜装置封闭所述流动池与外界连通的所述通孔。
  32. 一种生化物质反应装置，其特征在于，所述生化物质反应装置用于加载如权利要求1至31任一项所述的流动池及输入反应物质至所述流动池以使所述流动池内的样品发生反应；或者，所述生物物质反应装置还进一步用于检测所述发生反应后的样品以获得反映所述样 品生物特征的信号。
  33. 如权利要求22所述的生化物质反应装置，其特征在于，所述生化物质反应装置为基因测序仪、液相色谱仪、生化分析仪或医疗器械。
PCT/CN2019/108642 2019-09-27 2019-09-27 流动池及应用所述流动池的生化物质反应装置 WO2021056445A1 (zh)

Priority Applications (6)

Application Number Priority Date Filing Date Title
PCT/CN2019/108642 WO2021056445A1 (zh) 2019-09-27 2019-09-27 流动池及应用所述流动池的生化物质反应装置
CN201980100244.8A CN114391037B (zh) 2019-09-27 2019-09-27 流动池及应用所述流动池的生化物质反应装置
JP2022504730A JP7330358B2 (ja) 2019-09-27 2019-09-27 フローセル及びそれを適用する生化学物質反応装置
EP19947064.2A EP4036204A4 (en) 2019-09-27 2019-09-27 FLOW CELL AND REACTION DEVICE FOR BIOCHEMICAL SUBSTANCE USING THE FLOW CELL
US17/763,270 US20220339632A1 (en) 2019-09-27 2019-09-27 Flow cell and biochemical substance reaction device using the flow cell
JP2023129349A JP2023153989A (ja) 2019-09-27 2023-08-08 フローセル及びそれを適用する生化学物質反応装置

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/108642 WO2021056445A1 (zh) 2019-09-27 2019-09-27 流动池及应用所述流动池的生化物质反应装置

Publications (1)

Publication Number Publication Date
WO2021056445A1 true WO2021056445A1 (zh) 2021-04-01

Family

ID=75166299

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/108642 WO2021056445A1 (zh) 2019-09-27 2019-09-27 流动池及应用所述流动池的生化物质反应装置

Country Status (5)

Country Link
US (1) US20220339632A1 (zh)
EP (1) EP4036204A4 (zh)
JP (2) JP7330358B2 (zh)
CN (1) CN114391037B (zh)
WO (1) WO2021056445A1 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021159285A1 (zh) * 2020-02-12 2021-08-19 深圳华大智造科技股份有限公司 光学成像系统及应用所述光学成像系统的生化物质检测系统
WO2024098385A1 (zh) * 2022-11-11 2024-05-16 深圳华大智造科技股份有限公司 流体运输系统、基因测序仪及流体运输方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004099757A1 (en) * 2003-04-07 2004-11-18 Systec, Inc. Flow cells utilizing photometric techniques
US20110072914A1 (en) * 2008-02-14 2011-03-31 Illumina, Inc. Flow Cells And Manifolds Having An Electroosmotic Pump
CN104394990A (zh) * 2012-03-29 2015-03-04 考利达基因组股份有限公司 用于高密度阵列芯片的流动池
CN109351368A (zh) * 2018-10-23 2019-02-19 深圳市博瑞生物科技有限公司 微流控芯片
CN208591844U (zh) * 2018-08-09 2019-03-12 清华大学 微流控芯片、微流控芯片封装用封装配件
CN208776710U (zh) * 2018-08-16 2019-04-23 深圳华大智造科技有限公司 加载装置及基因测序系统
CN110142066A (zh) * 2019-04-25 2019-08-20 深圳市刚竹医疗科技有限公司 微流控芯片及分析系统
CN305312364S (zh) * 2018-10-24 2019-08-20

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4732479A (en) * 1985-10-18 1988-03-22 Canon Kabushiki Kaisha Particle analyzing apparatus
WO2007019479A2 (en) 2005-08-04 2007-02-15 Helicos Biosciences Corporation Multi-channel flow cells
US9080941B2 (en) * 2012-04-27 2015-07-14 General Electric Company Microfluidic flow cell assemblies for imaging and method of use
EP3143380B1 (en) 2014-05-15 2020-04-15 General Electric Company Microfluidic flow cell assemblies and method of use
CN118348265A (zh) * 2019-09-24 2024-07-16 深圳华大智造科技股份有限公司 生化物质分析系统、方法及装置
WO2021212276A1 (zh) * 2020-04-20 2021-10-28 深圳华大智造科技股份有限公司 铺液装置、铺液方法、铺液系统及组合装置与过液装置

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004099757A1 (en) * 2003-04-07 2004-11-18 Systec, Inc. Flow cells utilizing photometric techniques
US20110072914A1 (en) * 2008-02-14 2011-03-31 Illumina, Inc. Flow Cells And Manifolds Having An Electroosmotic Pump
CN104394990A (zh) * 2012-03-29 2015-03-04 考利达基因组股份有限公司 用于高密度阵列芯片的流动池
CN208591844U (zh) * 2018-08-09 2019-03-12 清华大学 微流控芯片、微流控芯片封装用封装配件
CN208776710U (zh) * 2018-08-16 2019-04-23 深圳华大智造科技有限公司 加载装置及基因测序系统
CN109351368A (zh) * 2018-10-23 2019-02-19 深圳市博瑞生物科技有限公司 微流控芯片
CN305312364S (zh) * 2018-10-24 2019-08-20
CN110142066A (zh) * 2019-04-25 2019-08-20 深圳市刚竹医疗科技有限公司 微流控芯片及分析系统

Also Published As

Publication number Publication date
CN114391037A (zh) 2022-04-22
JP2023153989A (ja) 2023-10-18
CN114391037B (zh) 2024-07-02
EP4036204A4 (en) 2023-01-25
JP7330358B2 (ja) 2023-08-21
EP4036204A1 (en) 2022-08-03
US20220339632A1 (en) 2022-10-27
JP2022542135A (ja) 2022-09-29

Similar Documents

Publication Publication Date Title
US10775369B2 (en) Fluidic systems for analyses
CN103191791B (zh) 生物微粒高通量分选和计数检测的集成芯片系统及应用
JP2023153989A (ja) フローセル及びそれを適用する生化学物質反応装置
US20100167318A1 (en) Fluidic Structures Including Meandering and Wide Channels
US20090111675A1 (en) Microchip and Method of Using the Same
US20170157606A1 (en) Microfluidic chip, manufacturing method therefor and analysis device using same
TW201928331A (zh) 與矽基感測器集成之射出成型微流體/流體卡匣
KR101491823B1 (ko) 미세 유체 유동 블럭과 미세 유체 유동 블럭 연결 방법.
CN110387321B (zh) 基因测序芯片及基因测序装置
CN211826084U (zh) 光栅波导微流体检测系统
JP5017723B2 (ja) 光学測定用キュベットを有するマイクロチップおよびその使用方法
CN113115587B (zh) 检测芯片
CN211603214U (zh) 光栅波导微流体检测系统
TW202206814A (zh) 生物晶片結構及其製備方法
US20190283022A1 (en) Highly parallel microfluidic blood separation device
US20230137571A1 (en) Microfluidic chip
EP3984639A1 (en) Detection chip and preparation method therefor
EP4171813A1 (en) Microfluidic chip and pumping device
JP2002014093A (ja) ウェルプレート

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19947064

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2022504730

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2019947064

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2019947064

Country of ref document: EP

Effective date: 20220428