WO2019218262A1 - 基因测序仪 - Google Patents

基因测序仪 Download PDF

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Publication number
WO2019218262A1
WO2019218262A1 PCT/CN2018/087046 CN2018087046W WO2019218262A1 WO 2019218262 A1 WO2019218262 A1 WO 2019218262A1 CN 2018087046 W CN2018087046 W CN 2018087046W WO 2019218262 A1 WO2019218262 A1 WO 2019218262A1
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WO
WIPO (PCT)
Prior art keywords
solution
chip
gene
elastic sealing
substrate
Prior art date
Application number
PCT/CN2018/087046
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English (en)
French (fr)
Inventor
隋相坤
孙磊林
龙青山
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.)
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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 CN201880005556.6A priority Critical patent/CN112513242B/zh
Priority to PCT/CN2018/087046 priority patent/WO2019218262A1/zh
Publication of WO2019218262A1 publication Critical patent/WO2019218262A1/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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • C12M1/38—Temperature-responsive control
    • 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

Definitions

  • the invention relates to a genetic sequencer.
  • the gene sequencer is an instrument suitable for sequencing DNA in the biochemical and medical fields, and generally includes a chip platform and a gene sequencing chip placed on the chip platform.
  • the gene sequencing chip is used for loading a solution for DNA samples and reagents for sequencing
  • the chip platform has a chip connection module for introducing a solution into the gene sequencing chip and a solution for completing the sequencing from the gene. Sequencing chip export.
  • how to realize the effective sealing connection between the chip connection module and the gene sequencing chip and avoid the leakage of the solution affect the use of the gene sequencer is a very important issue.
  • the present invention provides a gene sequencer that can effectively seal the connection between the chip connection module and the gene sequencing chip.
  • a gene sequencer comprising a gene sequencing chip, a chip platform, and a sealing and switching module, the chip platform comprising a chip connection module, the chip connection module comprising a substrate, a solution inflow channel disposed on the substrate and The solution exits the channel, the gene sequencing chip includes a solution inlet, a solution outlet, and an internal flow channel between the solution inlet and the solution outlet, the sealing and switching module being located at an outlet of the solution inflow channel Between the solution inlets and between the solution outlet and the inlet of the solution outflow channel, and the sealing and switching module is used to introduce a solution from the solution inflow channel into the gene sequencing chip and to complete sequencing a solution is derived from the gene sequencing chip to the solution outflow channel, the sealing and switching module includes an elastic sealing ring, the elastic sealing ring includes a body and a through hole penetrating the body, the body being clamped to the substrate Between the gene sequencing chip and the gene sequencing chip, the through hole is connected to the solution inlet and the outlet of the solution inflow channel or Connecte
  • the body includes a first end surface corresponding to the gene sequencing chip and a second end surface corresponding to the base of the chip connection module, the through hole penetrating the first end surface and the second end
  • the end surface, the first end surface and/or the second end surface is an arcuate three-dimensional torus having a convex shape in cross section.
  • the body includes a first end surface corresponding to the gene sequencing chip and a second end surface corresponding to the base of the chip connection module, the through hole penetrating the first end surface and the second end
  • the end surface, the first end surface and/or the second end surface is a concave annular surface that is recessed toward the inside.
  • the body includes a first end, a second end, and a connecting portion connected between the first end and the second end, the first end
  • the diameter of the second end portion is larger than the diameter of the connecting portion, the through hole penetrating the first end portion, the connecting portion and the second end portion, and the first end surface is the first end end
  • the portion is adjacent to a surface of the gene sequencing chip, and the second end surface is a surface of the second end portion adjacent to the substrate of the chip connection module.
  • the first end portion further includes a first outer side surface and a first bottom surface, the first outer side surface and the first end surface have a chamfer, and the first bottom surface is connected to the Between the first outer side surface and the outer surface of the connecting portion, the second end portion further includes a second outer side surface and a second bottom surface, and the second outer side surface and the second end surface have a chamfer The second bottom surface is coupled between the second outer side surface and an outer surface of the connecting portion.
  • the sealing and switching module further includes a cover plate sandwiched between the genetic sequencing chip and the chip connection module, the cover plate including a substrate, and the through a first fixing hole of the substrate, the first fixing hole is for receiving and fixing the elastic sealing ring.
  • the cover plate further includes a second fixing hole penetrating the substrate
  • the chip connection module further includes a locking hole corresponding to the second fixing hole disposed on the base body.
  • the sealing and switching module further includes a locking member that is locked to the locking hole through the second fixing hole to fix the sealing and switching module on the chip connection module.
  • the number of the locking members and the locking holes is at least two.
  • the substrate includes a first portion and a second portion connected to the first portion, the first portion having a thickness greater than a thickness of the second portion, the first fixing hole being disposed in the In a first portion, the second fixing hole is disposed at a joint between the second portion and/or the second portion and the first portion.
  • the first portion includes a first upper surface, a connecting surface connecting the second portion, and a first lower surface on a side opposite to the first upper surface, the first lower surface Further including a groove, at least a portion of one end of the elastic sealing ring adjacent to the gene sequencing chip is disposed on the first upper surface, and an end of the elastic sealing ring adjacent to the chip connection module is at least partially received In the groove.
  • the second portion includes a second upper surface connecting the connecting faces and a second lower surface on a side opposite to the second upper surface, the first lower surface and the first lower surface At least a portion of the second lower surface is flush.
  • the substrate includes a sidewall, an upper bottom surface and a lower bottom surface, and the solution inflow channel or the solution outflow channel extends through the upper bottom surface and the lower bottom surface or through the upper bottom surface Side wall.
  • the predetermined area of the upper bottom surface is recessed toward the lower bottom surface to form a recess, and the keyhole and the solution inflow channel or the solution outflow channel are disposed in the recess.
  • the number of the substrates is two, one of the substrates is disposed corresponding to the solution inlet of the gene sequencing chip and has the solution inflow channel, and the other substrate corresponds to the solution outlet of the gene sequencing chip.
  • the number of the elastic sealing rings being two groups, each set of elastic sealing rings having at least one elastic sealing ring, wherein a through hole of a group of elastic sealing rings is connected to the solution inlet and the The solution flows between the outlets of the channels, and a further set of through holes of the elastomeric sealing ring are connected between the solution outlet and the inlet of the solution outflow channel.
  • each set of elastic sealing rings comprises a plurality of elastic sealing rings
  • the genetic sequencing chip comprises a plurality of solution inlets and solution outlets corresponding to the elastic sealing rings, and a through hole connection of each elastic sealing ring Between a corresponding one of the solution inlets and a corresponding one of the solution inflow channels or between the corresponding one of the solution outlets and the corresponding one of the solution outflow channels.
  • the chip platform further includes a stage, the two substrates being respectively located on opposite sides of the stage.
  • the material of the elastomeric seal comprises silicone or rubber.
  • the gene sequencing chip comprises a chip substrate, a top plate disposed on one side of the chip substrate, and the inner flow channel on a side of the top plate adjacent to the chip substrate, the chip substrate having the a solution inlet and the solution outlet, the top plate being disposed on the chip substrate such that the solution inlet communicates with the solution outlet via the internal flow channel.
  • the solution of the chip connection module can be flowed into the channel by an elastic sealing ring having a through hole sandwiched between the chip connection module and the gene sequencing chip.
  • a sealed connection between the chip connection module and the gene sequencing chip is performed on the basis of the solution inlet of the gene sequencing chip or the solution outlet of the gene sequencing chip and the solution outflow channel of the chip connection module. Therefore, it can avoid problems such as solution leakage affecting the work or performance of the gene sequencer.
  • FIG. 1 is a partial structural schematic view of a gene sequencer according to a first embodiment of the present invention.
  • FIG. 2 is a schematic diagram showing the reverse structure of a gene sequencing chip of the gene sequencer shown in FIG. 1.
  • FIG. 3 is a schematic cross-sectional structural view of an elastic sealing ring of the gene sequencer shown in FIG. 1.
  • FIG. 4 is a schematic perspective view showing a partial structure of a genetic sequencer according to a second embodiment of the present invention.
  • Fig. 5 is a perspective exploded view showing a part of the structure of the gene sequencer shown in Fig. 4.
  • Figure 6 is a schematic diagram showing the reverse structure of the gene sequencing chip of the gene sequencer shown in Figure 4.
  • Figure 7 is a perspective exploded view of the sealing and switching module of the genetic sequencer shown in Figure 4.
  • Figure 8 is a schematic view of the reverse side of Figure 7.
  • FIG. 1 is a partial schematic structural diagram of a genetic sequencer 10 according to a first embodiment of the present invention.
  • the gene sequencer 10 includes a gene sequencing chip 11, a chip platform 12, and a sealing and switching module 13.
  • the chip platform 12 includes a loading stage 121 and a chip connection module 122.
  • the chip connection module 122 is disposed on the stage 121.
  • the chip connection module 122 includes a base 123 and a solution flowing in the base 123. Channel 124 and solution flow out of channel 125.
  • FIG. 2 is a schematic diagram showing the reverse structure of the gene sequencing chip 11 shown in FIG.
  • the gene sequencing chip 11 includes a solution inlet 11a, a solution outlet 11b, and an internal flow path 11c between the solution inlet 11a and the solution outlet 11b.
  • the gene sequencing chip 11 includes a chip substrate 111, a top plate 112 disposed on one side of the chip substrate 111, and an inner flow channel 11c on a side of the top plate 112 adjacent to the chip substrate 111.
  • the chip substrate 111 has The solution inlet 11a and the solution outlet 11b cover the top plate 112 on the chip substrate 111 such that the solution inlet 11a communicates with the solution outlet 11b via the internal flow path 11c.
  • the solution inlet 11a and the solution outlet 11b may both be through holes penetrating the chip substrate 111.
  • the sealing and switching module 13 is located between the outlet of the solution inflow passage 124 and the solution inlet 11a and between the solution outlet 11b and the inlet of the solution outflow passage 125, and the sealing and transfer Module 13 is used to introduce a solution from the solution inflow channel 124 into the genetic sequencing chip 11 and to export the solution that has been sequenced from the genetic sequencing chip 11 to the solution outflow channel 125.
  • the solution is loaded in the internal flow channel 11c of the gene sequencing chip 11 for sequencing.
  • the surface of the chip substrate 111 may have a reaction region located in the internal flow channel, and the solution may flow into the solution.
  • the internal flow path flows into the reaction area, and the gene detection result is obtained by irradiating predetermined light to the reaction area and acquiring the emitted light of the reaction area (e.g., by a microscope camera).
  • the top plate may be a light transmissive plate
  • the chip substrate 111 may also have an internal silicon wafer for sequencing and a frame with good compatibility with biological reagents disposed around the internal silicon wafer.
  • the genetic sequencer 10 of the present invention may further include a light source not illustrated in the drawing, Other modules such as microscope cameras and liquid systems.
  • the sealing and switching module 13 includes a plurality of elastic sealing rings 131.
  • FIG. 3 is a schematic cross-sectional structural view of the elastic sealing ring 131.
  • Each elastic sealing ring 131 includes a body 131a and Through the through hole 131b of the body 131a, when the gene sequencer 10 is in operation, the body 131a is sandwiched between the base 123 of the chip connection module 122 and the gene sequencing chip 11, and the through hole 131b is used for An outlet connected to the solution inlet 11a and the solution inflow passage 124 or connected between the solution outlet 11b and the inlet of the solution outflow passage 125 for introducing a solution from the solution inflow passage 124 into the chamber The solution inlet 11a of the gene sequencing chip 11 and the solution to be sequenced are led out from the solution outlet 11b of the gene sequencing chip 11 to the solution outflow channel 125.
  • the body 131a includes a first end surface 132 corresponding to the gene sequencing chip 11 and a second end surface 133 corresponding to the base 123 of the chip connection module 122.
  • the through hole 131b extends through the first end surface 132 and the first end
  • the two end faces 133, the first end face 132 and/or the second end face 133 are curved three-dimensional toroids having a convex shape in cross section.
  • the number of the bases 123 is two, and the two bases 123 may be respectively located on two sides of the stage 121.
  • One of the substrates 123 is disposed corresponding to the solution inlet 11a of the gene sequencing chip 11 and has the solution inflow channel 124, and the other substrate 123 is disposed corresponding to the solution outlet 11b of the gene sequencing chip 11 and has the solution outflow channel 125.
  • each set of elastic sealing rings 131 has at least one elastic sealing ring, wherein a through hole 131b of a group of elastic sealing rings 131 is connected to the solution inlet 11a and the solution inflow channel Between the outlets of 124, a further set of through holes 131b of the elastomeric sealing ring 131 are connected between the solution outlet 11b and the inlet of the solution outflow channel 125.
  • the elastic sealing ring 131 is mainly exemplified by a plurality of elastic sealing rings (such as four), and the genetic sequencing chip 11 includes a plurality of one-to-one correspondence with the elastic sealing ring 131. a plurality of solution inlets 11a and a plurality of solution outlets 11b, and a through hole 131b of each elastic sealing ring 131 is connected between the solution inlet 11a and the outlet of the solution inflow passage 124 or connected to the solution outlet 11b The solution flows out between the inlets of the channels 125.
  • the material of the elastic sealing ring 131 may include silicone rubber or rubber, such as a rubber ring or a silicone ring.
  • the three-dimensional annular surface of the elastic sealing ring 131 can be changed to the base 123 of the chip connecting module 122 and/or the genetic sequencing chip 11 when the pressure is different.
  • the gene sequencer 10 using the elastic sealing ring 131 can not only achieve the gene sequencing chip 11 and the chip connection module 122 well, but also the different sealing effects can be obtained.
  • the seal is connected and the adaptability is strong.
  • the present invention further analyzes the technical solution shown in the first embodiment in order to improve the defects that may exist in the technical solution in the first embodiment, and proposes a second embodiment in which the sealing effect is better.
  • the two end faces 132 and 133 of the elastic sealing ring 131 are three-dimensional torus, and a spring pair is usually used during operation.
  • the chip connection module applies an overall pressure, and the elastic sealing ring 131 is pressed against the solution inlet/outlet of the gene sequencing chip 11, and the whole flow channel is realized by the force deformation of the three-dimensional torus (from the solution into the channel 124)
  • the through hole 131b, the solution inlet 11a, the inner flow channel 11c, the solution outlet 11b, the through hole 131b, and the solution outflow channel 125 are sealed.
  • the sealing scheme described in the first embodiment may have the following problems:
  • the three-dimensional annulus of the elastic sealing ring 131 (i.e., the end faces 132, 133) must be positively pressed to maintain the overall flow path sealed, and the chip connection module 122 is pressed due to mechanical tolerances.
  • the force direction may not always be exactly perpendicular to the surface of the solution inlet 11a or the solution outlet 11b of the genetic sequencing chip 11;
  • each integral flow channel needs an elastic sealing ring 131 to achieve sealing, and the three-dimensional torus of the elastic sealing ring 131 is designed to be integrated or Split type, in the height direction due to the existence of mechanical tolerances, it is impossible to always be consistent. Once there is high or low, it may cause some of the whole flow passages to be compacted, and some of the whole flow passages are difficult to compress;
  • the side of the elastic sealing ring 131 may also press and rub against the inlet of the solution inflow passage 124 or the outlet of the solution outflow passage 125 on the chip connecting module 122, and the friction may cause the elasticity.
  • the pressing force received on the end face 132 of the three-dimensional torus between the sealing ring 131 and the chip connecting module 122 is weakened, thereby causing the elastic sealing ring 131 and the chip connecting module 122 to be incapable of being pressed, but if The frictional force of the side of the elastic sealing ring 131 increases the inlet of the solution inflow passage 124 or the solution outflow passage 125, which may cause the elastic sealing ring 131 to tilt, which also affects the sealing property;
  • a negative pressure module can be added to the stage 121.
  • the negative pressure module is located below the gene sequencing chip 11, and provides a downward adsorption force for the gene sequencing chip 11, so that it can be more stably placed on the stage.
  • a mechanical snap structure may be added to provide a downward pressure on the genetic sequencing chip 11 so that it can be more stably placed on the stage 121.
  • FIG. 4 is a second embodiment of the present invention.
  • FIG. 5 is a perspective exploded view of the gene sequencer 20 shown in FIG.
  • the gene sequencer 20 includes a gene sequencing chip 21, a chip platform 22, and a sealing and switching module 23.
  • the chip platform 22 includes a carrier 221 and a chip connection module 222.
  • the chip connection module 222 is disposed on the carrier 221, and the chip connection module 222 includes a substrate 223 and a solution solution disposed on the substrate 223. Channel 224 and solution flow out of channel 225.
  • FIG. 6 is a schematic diagram showing the reverse structure of the exploded view of the gene sequencing chip 21 shown in FIG.
  • the gene sequencing chip 21 includes a solution inlet 21a, a solution outlet 21b, and an internal flow path 21c between the solution inlet 21a and the solution outlet 21b.
  • the gene sequencing chip 21 includes a chip substrate 211, a top plate 212 disposed on one side of the chip substrate 211, and the inner flow channel 21c on a side of the top plate 212 adjacent to the chip substrate 211, the chip substrate 211 has the solution inlet 21a and the solution outlet 21b, and the top plate 212 is covered on the chip substrate 211 such that the solution inlet 21a communicates with the solution outlet 21b via the internal flow path 21c.
  • the solution inlet 21a and the solution outlet 21b may both be through holes penetrating the chip base 211, and the top plate 212 may be a light transmissive plate.
  • the sealing and switching module 23 is located between the outlet of the solution inflow passage 224 and the solution inlet 21a and between the solution outlet 21b and the inlet of the solution outflow passage 225, and the sealing and transfer Module 23 is used to introduce a solution from the solution inflow channel 224 into the gene sequencing chip 21 and to export the solution that has been sequenced from the gene sequencing chip 21 to the solution outflow channel 225.
  • the solution is loaded in the internal flow channel 21c of the gene sequencing chip 21 for sequencing.
  • the surface of the chip substrate 211 may have a reaction region located in the internal flow channel, and the solution may flow into the solution.
  • the internal flow path flows into the reaction area, and the gene detection result is obtained by irradiating predetermined light to the reaction area and acquiring the emitted light of the reaction area (e.g., by a microscope camera).
  • the top plate may be a light transmissive plate
  • the chip substrate 211 may also have an internal silicon wafer for sequencing and a frame that is well compatible with biological reagents disposed around the internal silicon wafer.
  • the genetic sequencer 20 of the present invention may further include a light source not illustrated in the drawing, Other modules such as microscope cameras and liquid systems are not described here.
  • the sealing and switching module 23 includes a plurality of elastic sealing rings 231. Please refer to FIG. 7 and FIG. 8.
  • FIG. 7 is a perspective exploded view of the sealing and switching module 23, and FIG. The reverse side of the diagram.
  • Each of the elastic sealing rings 231 includes a body 231a and a through hole 231b extending through the body 231a.
  • the body 231a When the gene sequencer 20 is in operation, the body 231a is sandwiched between the base 223 of the chip connection module 222 and the gene sequencing chip 21 And the through hole 231b is for connecting between the solution inlet 21a and the outlet of the solution inflow passage 224 or between the solution outlet 21b and the inlet of the solution outflow passage 225 for The solution into which the solution flows into the channel 224 is introduced into the solution inlet 21a of the gene sequencing chip 21 and the solution from which the sequencing is completed is led from the solution outlet 21b of the gene sequencing chip 21 to the solution outflow channel 225.
  • the number of the bases 223 is two, and the two bases 223 may be respectively located at two sides of the stage 221 .
  • One of the substrates 223 is disposed corresponding to the solution inlet 21a of the gene sequencing chip 21 and has the solution inflow channel 224, and the other substrate 223 is disposed corresponding to the solution outlet 21b of the gene sequencing chip 21 and has the solution outflow channel 225.
  • the number of the elastic sealing rings 231 is two, each set of elastic sealing rings 231 has at least one elastic sealing ring, wherein a through hole 231b of a group of elastic sealing rings 231 is connected to the solution inlet 21a and the solution inflow channel Between the outlets of 224, a further set of through holes 231b of the elastomeric sealing ring 231 are connected between the solution outlet 21b and the inlet of the solution outflow channel 225.
  • the elastic sealing ring 231 is mainly exemplified by a plurality of elastic sealing rings (such as four), and the genetic sequencing chip 21 includes a plurality of one-to-one correspondence with the elastic sealing ring 231. a plurality of solution inlets 21a and a plurality of solution outlets 21b, and a through hole 231b of each elastic sealing ring 231 is connected between the solution inlet 21a and the outlet of the solution inflow passage 224 or is connected to the solution outlet 21b and the chamber The solution flows out between the inlets of the channels 225.
  • the material of the elastic sealing ring 231 may include silicone rubber or rubber, such as a rubber ring or a silicone ring.
  • the body 231a includes a first end surface 232 corresponding to the gene sequencing chip and a second end surface 233 corresponding to the base of the chip connection module.
  • the through hole 231b extends through the first end surface 232 and the second end surface 233.
  • the first end surface 232 and/or the second end surface 233 are concave concave surfaces that are recessed toward the inside.
  • the second end surface is a toroidal surface formed by a concave curved surface.
  • a concave concave surface of another shape may be used.
  • the shape of the first end surface 232 and the second end surface 233 in this embodiment is similar to a funnel shape and a suction cup shape.
  • the body 231a is divided into a first end portion 234, a second end portion 236, and a connecting portion 235 connected between the first end portion 234 and the second end portion 236, the first end
  • the diameter of the second end portion 236 is greater than the diameter of the connecting portion 235, and the through hole 231b extends through the first end portion 234, the connecting portion 235, and the second end portion 236.
  • the first end surface 232 is adjacent to the surface of the genetic sequencing chip 21
  • the second end surface 233 is adjacent to the surface of the base 223 of the chip connection module 222 .
  • the first end 234 further includes a first outer surface 234a and a first bottom surface 234b.
  • the first outer surface 234a and the first end surface 232 have a chamfer 234c.
  • the first bottom surface 234b is connected to the first bottom surface 234b.
  • the second end portion 236 further includes a second outer side 236a and a second bottom surface 236b, the second outer side 236a and the second The end faces 233 have chamfers 236c between them, and the second bottom faces 236b are connected between the second outer side faces 236a and the outer surface of the connecting portion 235.
  • the sealing and switching module 23 further includes a cover plate 237.
  • the cover plate 237 has the same number and one-to-one correspondence with the base body 223.
  • the cover plate 237 is located between the gene sequencing chip 21 and the chip connection module 232.
  • the cover plate 237 includes a substrate 238 and a first fixing hole 239 penetrating the substrate 238.
  • the first fixing hole 239 is used to receive and fix the elastic sealing ring 231. It can be understood that the number of the first fixing holes 239 is the same as that of the elastic sealing ring 231 and corresponds one-to-one.
  • the cover plate 237 further includes a second fixing hole 240 extending through the substrate 238.
  • the chip connection module 222 further includes a locking hole 226 corresponding to the second fixing hole 240 disposed on the base 223.
  • the sealing and switching module further includes a locking member 241 (such as a screw), and the locking member 241 is locked with the locking hole 226 through the second fixing hole 240 to fix the sealing and switching module 23 at The chip is connected to the module 222.
  • the number of the locking member 241 and the locking hole 240 is at least two, and the number of the locking member 241 and the locking hole 240 is mainly exemplified in the drawing.
  • the substrate 238 includes a first portion 238a and a second portion 238b connected to the first portion 238a, the first portion 238a has a maximum thickness greater than a maximum thickness of the second portion 238b, and the first fixing hole 239 is disposed at The first portion 238a, the second fixing hole 240 is disposed at a junction between the second portion 238b and/or the second portion 238b and the first portion 238a.
  • the first portion 238a includes a first upper surface 238c, a connecting surface 238d connecting the second portion 238b, and a first lower surface 238e on a side opposite to the first upper surface 283c, the first lower surface 238e Further including a groove 238f, at least a portion of the elastic sealing ring 231 adjacent to one end of the gene sequencing chip 21 (such as the first end portion 234) is disposed on the first upper surface 238c, the elastic seal One end of the ring 231 adjacent to the chip connection module 222 (such as the second end 236) is at least partially received in the recess 238f. It can be understood that the depth of the groove 238f may be substantially the same as the thickness of the second end portion 236, the former being slightly smaller than the latter.
  • the second portion 238c includes a second upper surface 238g connecting the connecting surface 238d and a second lower surface 238h on a side opposite to the second upper surface 238g, the first lower surface first lower surface 238e At least partially flush with the second lower surface 238h.
  • the base 223 includes a side wall, an upper bottom surface 233a and a lower bottom surface 233b, and the solution inflow passage 224 and the solution outflow passage 225 extend through the upper bottom surface 233a and the lower bottom surface 233b or through the upper bottom surface 233a. Said side wall.
  • a predetermined area (such as an intermediate area) of the upper bottom surface 233a is recessed toward the lower bottom surface to form a recess 233c, and the lock hole 226 and the solution inflow passage 224 and the solution outflow passage 225 are disposed in the recess. unit.
  • the end faces 232, 233 of the concave annular surface of the elastic sealing ring 231 can also be changed with the base 223 and/or the chip connecting module 222 when the pressure is different.
  • the contact area of the gene sequencing chip 21, thereby obtaining different sealing effects, can be required for different solutions. Therefore, the genetic sequencer 20 using the elastic sealing ring 231 can not only realize the gene sequencing chip 11 well.
  • the sealing connection with the chip connection module 222 is strong and adaptable.
  • the end faces 232, 233 of the concave annular surface make the outer edge of the end face more stressed, so that the leakage can be more effectively prevented, and the end faces 232, 233 of the concave annular surface are adaptive.
  • the influence of the height tolerance of the plurality of elastic sealing rings 231 on the sealing effect is negligible, so the design can be applied to a plurality of integral flow paths (from the solution inflow channel 224, the through hole 231b, the solution inlet 21a, The inner flow path 21c, the solution outlet 21b, the through hole 231b, and the solution outflow channel 225 may be formed.
  • the sealing and switching module 23 further includes the cover plate 237, the cover plate 237 is detachable with respect to the chip connection module 222, and the elastic sealing ring 231 is mounted on the cover plate 237. Thereby, the sealing and switching module 23 is conveniently placed and removed.
  • first end portion 234 of the elastic sealing ring 231 and the solution inlet/outlet 21a, 21b of the genetic sequencing chip 21 can be utilized when a negative pressure occurs due to the use of a negative pressure to drive fluid movement within the overall flow path.
  • the pressure difference between the first end portion 234 and the external atmospheric pressure sucks the first end portion 234 at the solution inlet/outlet ports 21a, 21b of the gene sequencing chip 21 to seal the pressure required at the junction of the two. It is greatly reduced that it is even possible to apply a pressure without applying a pressing force to the chip connection module 222.
  • the cover plate 237 presses and seals between the second end portion 236 of the elastic sealing ring 231 and the chip connecting module 222, and is designed to seal the elastic sealing ring 231 and the chip connecting module 222. No longer relying on the pressing force applied to the chip connection module 222; the pressing force required for sealing the two ends of the elastic sealing ring 231 is reduced, so that the pressing force applied to the chip connection module 222 can be designed at the time of design
  • the gene sequencing chip 21 is excessively deformed to a large extent, so as to avoid excessive pressing force.
  • one of the first end surface 232 and the second end surface 233 may also be designed as a concave annular surface, and One end face is designed as a three-dimensional torus in the first embodiment, that is, the elastic seal ring 231 includes a three-dimensional torus and a concave seal of the concave picture; or the plurality of elastic seals 231 may include two The end faces 232 and 233 are both inner ring-shaped sealing rings, the two end faces 232 and 233 are three-dimensional toroidal sealing rings, and any two or three of the three-dimensional toroidal and concave toroidal hybrid sealing rings. Combination of species.
  • the elastic sealing ring 231 not only has a good technical effect in the genetic sequencer 20 of the plurality of integrated flow channels, but also can be applied to a whole sequence flow path genetic sequencer.
  • a negative pressure module can be added to the stage 221, and the negative pressure module is located below the gene sequencing chip 21 to provide a downward adsorption force for the gene sequencing chip 21, so that it can be more stably placed on the stage 221 On the stage 221.
  • a mechanical snap structure may be added to provide a downward pressure on the genetic sequencing chip 21 so that it can be more stably placed on the stage 221.

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Abstract

一种基因测序仪(10)包括基因测序芯片(11)、芯片平台(12)、密封与转接模块(13)，芯片平台(12)包括芯片连接模块(122)，密封与转接模块(13)包括弹性密封圈(131)，弹性密封圈(131)包括本体(131a)及贯穿本体(131a)的通孔(131b)，本体(131a)夹于基体(123)与基因测序芯片(11)之间，通孔(131b)连接于溶液入口(11a)与溶液流入通道(124)的出口或者连接于溶液出口(11b)与溶液流出通道(125)的入口之间。

Description

基因测序仪 技术领域
本发明涉及一种基因测序仪。
背景技术
基因测序仪是一种在生化、医学领域适用的、用于对DNA进行测序的仪器，其通常包括芯片平台及放置于所述芯片平台上的基因测序芯片。其中，所述基因测序芯片内用于加载DNA样本及试剂等溶液以进行测序，所述芯片平台具有芯片连接模块，用于将溶液导入所述基因测序芯片以及将完成测序的溶液从所述基因测序芯片导出。然而，如何实现芯片连接模块与基因测序芯片的有效密封连接、避免溶液漏出影响基因测序仪的使用是一个非常重要的课题。
发明内容
有鉴于此，本发明提出一种可实现芯片连接模块与基因测序芯片有效密封连接的基因测序仪。
一种基因测序仪，其包括基因测序芯片、芯片平台、及密封与转接模块，所述芯片平台包括芯片连接模块，所述芯片连接模块包括基体、设置于所述基体上的溶液流入通道与溶液流出通道，所述基因测序芯片包括溶液入口、溶液出口及位于所述溶液入口与所述溶液出口之间的内部流道，所述密封与转接模块位于所述溶液流入通道的出口与所述溶液入口之间以及所述溶液出口与所述溶液流出通道的入口之间，且所述密封与转接模块用于将来自所述溶液流入通道的溶液导入所述基因测序芯片以及将完成测序的溶液从所述基因测序芯片导出至所述溶液流出通道，所述密封与转接模块包括弹性密封圈，所述弹性密封圈包括本体及贯穿本体的通孔，所述本体夹于所述基体与所述基因测序芯片之间，所述通孔连接于所述溶液入口与所述溶液流入通道的出口或者连接于所述溶液出口与所述溶液流出通道的入口之间。
在一种实施例中，所述本体包括对应所述基因测序芯片的第一端面及对应所述芯片连接模块的基体的第二端面，所述通孔贯穿所述第一端面及所述第二端面，所述第一端面和/或所述第二端面为截面包括 凸起的弧形的三维环面。
在一种实施例中，所述本体包括对应所述基因测序芯片的第一端面及对应所述芯片连接模块的基体的第二端面，所述通孔贯穿所述第一端面及所述第二端面，所述第一端面和/或所述第二端面为朝向内部凹陷的内凹环面。
在一种实施例中，所述本体包括第一端部、第二端部及连接于所述第一端部及所述第二端部之间的连接部，所述第一端部与所述第二端部的直径大于所述连接部的直径，所述通孔贯穿所述第一端部、所述连接部及所述第二端部，所述第一端面为所述第一端部邻近所述基因测序芯片的表面，所述第二端面为所述第二端部邻近所述芯片连接模块的基体的表面。
在一种实施例中，所述第一端部还包括第一外侧面及第一底面，所述第一外侧面与所述第一端面之间具有倒角，所述第一底面连接于所述第一外侧面与所述连接部的外表面之间，所述第二端部还包括第二外侧面及第二底面，所述第二外侧面与所述第二端面之间具有倒角，所述第二底面连接于所述第二外侧面与所述连接部的外表面之间。
在一种实施例中，所述密封与转接模块还包括盖板，所述盖板夹于所述基因测序芯片与所述芯片连接模块之间，所述盖板包括基板、及贯穿所述基板的第一固定孔，所述第一固定孔用于收容并固定所述弹性密封圈。
在一种实施例中，所述盖板还包括贯穿所述基板的第二固定孔，所述芯片连接模块还包括设置于所述基体上的与所述第二固定孔对应的锁孔，所述密封与转接模块还包括锁固件，所述锁固件穿过所述第二固定孔与所述锁孔锁固从而将所述密封与转接模块固定在所述芯片连接模块上。
在一种实施例中，所述锁固件及所述锁孔的数量为至少两个。
在一种实施例中，所述基板包括第一部分及与所述第一部分连接的第二部分，所述第一部分的厚度大于所述第二部分的厚度，所述第一固定孔设置于所述第一部分，所述第二固定孔设置于所述第二部分和/或所述第二部分与所述第一部分之间的连接处。
在一种实施例中，所述第一部分包括第一上表面、连接所述第二部分的连接面及位于所述第一上表面相背一侧的第一下表面，所述第一下表面还包括凹槽，所述弹性密封圈的邻近所述基因测序芯片的一端的至少部分设置于所述第一上表面上，所述弹性密封圈的邻近所述 芯片连接模块的一端至少部分收容于所述凹槽中。
在一种实施例中，所述第二部分包括连接所述连接面的第二上表面及位于所述第二上表面相背一侧的第二下表面，所述第一下表面与所述第二下表面的至少部分平齐。
在一种实施例中，所述基体包括侧壁、上底面与下底面，所述溶液流入通道或所述溶液流出通道贯穿所述上底面及所述下底面或者贯穿所述上底面与所述侧壁。
在一种实施例中，所述上底面的预定区域朝向所述下底面一侧凹陷形成凹陷部，所述锁孔及所述溶液流入通道或所述溶液流出通道设置于所述凹陷部。
在一种实施例中，所述基体的数量为两个，其中一个基体上对应所述基因测序芯片的溶液入口设置且具有所述溶液流入通道，另外一个基体对应所述基因测序芯片的溶液出口设置且具有所述溶液流出通道，所述弹性密封圈的数量为两组，每组弹性密封圈具有至少一个弹性密封圈，其中一组弹性密封圈的通孔连接于所述溶液入口与所述溶液流入通道的出口之间，另外一组弹性密封圈的通孔连接于所述溶液出口与所述溶液流出通道的入口之间。
在一种实施例中，每组弹性密封圈包括多个弹性密封圈，所述基因测序芯片包括多个与弹性密封圈一一对应的溶液入口与溶液出口，每个弹性密封圈的通孔连接于对应的一个溶液入口与对应的一个溶液流入通道的出口之间或者连接于对应的一个溶液出口与对应的一个溶液流出通道的入口之间。
在一种实施例中，所述芯片平台包括还包括载台，所述两个基体分别位于所述载台的两侧。
在一种实施例中，所述弹性密封圈的材料包括硅胶或橡胶。
在一种实施例中，所述基因测序芯片包括芯片基体、设置于芯片基体一侧的顶板、位于所述顶板邻近所述芯片基体一侧的所述内部流道，所述芯片基体具有所述溶液入口与所述溶液出口，所述顶板盖设于所述芯片基体上使得所述溶液入口经由所述内部流道与所述溶液出口连通。
与现有技术相比较，本发明的基因测序仪中，通过夹于所述芯片连接模块与基因测序芯片之间的具有通孔的弹性密封圈，可以在将所述芯片连接模块的溶液流入通道与所述基因测序芯片的溶液入口连接或者将所述基因测序芯片的溶液出口与所述芯片连接模块的溶液流出 通道连接的基础上，实现所述芯片连接模块与基因测序芯片之间的密封连接，从而可以避免溶液泄漏影响基因测序仪工作或性能等问题。
附图说明
图1是本发明第一实施例的基因测序仪的部分结构示意图。
图2是图1所示基因测序仪的基因测序芯片的反面结构示意图。
图3是图1所示基因测序仪的弹性密封圈的剖面结构示意图。
图4是本发明第二实施例的基因测序仪的部分结构立体组装示意图。
图5是图4所示基因测序仪部分结构的立体分解示意图。
图6是图4所示基因测序仪的基因测序芯片的反面结构示意图。
图7是图4所示基因测序仪的密封与转接模块的立体分解示意图。
图8是图7的反面示意图。
主要元件符号说明
基因测序仪         10、20
基因测序芯片       11、21
芯片平台           12、22
密封与转接模块     13、23
顶板               112、212
芯片基体           111、211
载台               121、221
芯片连接模块       122、222
基体               123、223
溶液流入通道       124、224
溶液流出通道       125、225
溶液入口           11a、21a
溶液出口           11b、21b
内部流道           11c、21c
弹性密封圈         131、231
本体               131a、231a
通孔               131b、231b
第一端面           132、232
第二端面           133、233
第一端部            234
第二端部            236
连接部              235
第一外侧面          234a
第一底面            234b
倒角                234c、236c
第二外侧面          236a
第二底面            236b
盖板                237
基板                238
第一固定孔          239
第二固定孔          240
锁孔                226
锁固件              241
第一部分            238a
第二部分            238b
第一上表面          238c
连接面              238d
第一下表面          238e
凹槽                238f
第二上表面          238g
第二下表面          238h
上底面              233a
下底面              233b
凹陷部              233c
如下具体实施方式将结合上述附图进一步说明本发明。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图对本发明的具体实施例做详细的说明。
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似应用，因此本发明不受下面公开的具体实施例的限制。
其次，本发明结合示意图进行详细描述，在详述本发明实施方式时，为便于说明，表示器件结构的剖面图会不依一般比例作局部放大，而且所述示意图只是示例，其在此不应限制本发明保护的范围。此外，在实际制作中应包含长度、宽度及深度的三维空间尺寸。
下面通过实施方式详细描述。
请参阅图1，图1是本发明第一实施例的基因测序仪10的部分结构示意图。所述基因测序仪10包括基因测序芯片11、芯片平台12、及密封与转接模块13。
所述芯片平台12包括载台121及芯片连接模块122，所述芯片连接模块122设置于所述载台121上，所述芯片连接模块122包括基体123、设置于所述基体123上的溶液流入通道124与溶液流出通道125。请参阅图2，图2是图1所示基因测序芯片11处于分解状态的反面结构示意图。所述基因测序芯片11包括溶液入口11a、溶液出口11b及位于所述溶液入口11a与所述溶液出口11b之间的内部流道11c。具体地，所述基因测序芯片11包括芯片基体111、设置于芯片基体111一侧的顶板112、位于所述顶板112邻近所述芯片基体111一侧的内部流道11c，所述芯片基体111具有所述溶液入口11a与所述溶液出口11b，所述顶板112盖设于所述芯片基体111上使得所述溶液入口11a经由所述内部流道11c与所述溶液出口11b连通。本实施例中，所述溶液入口11a与所述溶液出口11b可以均为贯穿所述芯片基体111的通孔。
所述密封与转接模块13位于所述溶液流入通道124的出口与所述溶液入口11a之间以及所述溶液出口11b与所述溶液流出通道125的入口之间，且所述密封与转接模块13用于将来自所述溶液流入通道124的溶液导入所述基因测序芯片11以及将完成测序的溶液从所述基因测序芯片11导出至所述溶液流出通道125。
可以理解，所述基因测序芯片11的内部流道11c内加载所述溶液以进行测序，具体地，所述芯片基体111表面可以具有位于所述内部流道内的反应区域，所述溶液可以流入所述内部流道流入所述反应区域，通过照射预定光至所述反应区域并(如通过显微镜相机)获取所述反应区域的出射光来获取基因检测结果。进一步地，所述顶板可以为透光板，所述芯片基体111也可以具有用于测序的内部硅片及设置在内部硅片周围的对生物试剂兼容性良好的外框。可以理解，除了图1中所示的所述基因测序芯片11、芯片平台12、及密封与转接模块 13外，本发明基因测序仪10还可以包括并未在图示中示意出的光源、显微镜相机、液体系统等其他模块。
本实施例中，所述密封与转接模块13包括多个弹性密封圈131，请参阅图3，图3是所述弹性密封圈131的剖面结构示意图，每个弹性密封圈131包括本体131a及贯穿本体131a的通孔131b，所述基因测序仪10工作时，所述本体131a夹于所述芯片连接模块122的基体123与所述基因测序芯片11之间，且所述通孔131b用于连接于所述溶液入口11a与所述溶液流入通道124的出口或者连接于所述溶液出口11b与所述溶液流出通道125的入口之间，用于将来自所述溶液流入通道124的溶液导入所述基因测序芯片11的溶液入口11a以及将完成测序的溶液从所述基因测序芯片11的溶液出口11b导出至所述溶液流出通道125。
所述本体131a包括对应所述基因测序芯片11的第一端面132及对应所述芯片连接模块122的基体123的第二端面133，所述通孔131b贯穿所述第一端面132及所述第二端面133，所述第一端面132和/或所述第二端面133为截面包括凸起的弧形的三维环面。
进一步地，本实施例中，所述基体123的数量为两个，所述两个基体123可以分别位于所述载台121的两侧。其中一个基体123上对应所述基因测序芯片11的溶液入口11a设置且具有所述溶液流入通道124，另外一个基体123对应所述基因测序芯片11的溶液出口11b设置且具有所述溶液流出通道125，所述弹性密封圈131的数量为两组，每组弹性密封圈131具有至少一个弹性密封圈，其中一组弹性密封圈131的通孔131b连接于所述溶液入口11a与所述溶液流入通道124的出口之间，另外一组弹性密封圈131的通孔131b连接于所述溶液出口11b与所述溶液流出通道125的入口之间。
更进一步地，本实施例中主要以每组弹性密封圈131包括多个弹性密封圈(如4个)进行示例性说明，所述基因测序芯片11包括多个与弹性密封圈131一一对应的多个溶液入口11a与多个溶液出口11b，每个弹性密封圈131的通孔131b连接于所述溶液入口11a与所述溶液流入通道124的出口之间或者连接于所述溶液出口11b与所述溶液流出通道125的入口之间。所述弹性密封圈131的材料可以包括硅胶或橡胶，如为橡胶圈或硅胶圈。
相较于现有技术，本实施例中，所述弹性密封圈131的三维环面可以在受到压力不同时改变与所述芯片连接模块122的基体123和/ 或与所述基因测序芯片11的接触面积，从而获得不同的密封效果，可以应不同溶液的需要，因此，使用所述弹性密封圈131的基因测序仪10不仅可以很好的实现所述基因测序芯片11与所述芯片连接模块122之间的密封连接，而且可适应性较强。
进一步地，本发明还对第一实施例中所示的技术方案进行进一步分析，以期改善第一实施例中的技术方案中可能存在的缺陷，并提出密封效果更佳的第二实施例。具体来说，依据所述基因测序仪10的结构可知，所述第一实施例中，所述弹性密封圈131上下的两个端面132、133均为三维环面，在工作时通常使用弹簧对所述芯片连接模块施加整体的压力，将所述弹性密封圈131压紧在所述基因测序芯片11的溶液入口/出口，依靠三维环面的受力变形实现整体流道(由溶液流入通道124、通孔131b、溶液入口11a、内部流道11c、溶液出口11b、通孔131b、及溶液流出通道125构成)的密封。然而，所述第一实施例中所述的密封方案可能存在以下几个问题：
1)所述弹性密封圈131的三维环面(即所述端面132、133)必须正向压紧才能使整体流道保持密封，而由于机械公差的存在，所述芯片连接模块122的压紧力方向不可能总是十分精确的垂直于所述基因测序芯片11的溶液入口11a或溶液出口11b表面；
2)当所述基因测序芯片11同时有多个整体流道时，每个整体流道都需要一个弹性密封圈131来实现密封，而这些弹性密封圈131三维环面无论是设计成一体式还是分体式，其在高度方向由于机械公差的存在，不可能总是保持一致，一旦出现有高有低，就有可能导致有的整体流道可以压紧，有的整体流道难以压紧；
3)所述弹性密封圈131侧边还可能与所述芯片连接模块122上的溶液流入通道124的入口或所述溶液流出通道125的出口互相挤压和摩擦，该摩擦力会导致所述弹性密封圈131与芯片连接模块122之间的三维环面的端面132上受到的压紧力被削弱，进而导致所述弹性密封圈131与芯片连接模块122之间因为不能压紧，但如果为了削弱所述弹性密封圈131的侧边的摩擦力而将所述溶液流入通道124的入口或所述溶液流出通道125增大，可能会使得所述弹性密封圈131发生倾斜，同样会影响密封性；
4)若想使所述弹性密封圈131与芯片连接模块122之间紧密密封不漏气，通常要对所述芯片连接模块122施加较大的压紧力克服所述弹性密封圈131侧边受到的摩擦力，这样会导致所述基因测序芯片11 在所述溶液入口/出口11a、11b处受到较大的整体外力，使所述基因测序芯片11的形状发生过大的弯曲，对工作原理依赖于光学拍照的基因测序芯片的影响较大。
在本实施例中，可以在载台121上加设负压模块，该负压模块位于基因测序芯片11下方，为基因测序芯片11提供一个向下的吸附力，使其可更稳固地安放于载台121上。或者，也可以增设一个机械卡扣结构，为基因测序芯片11提供一个向下的压力，使其可更稳固地安放于载台121上。
有鉴于此，本发明提出第二实施例的基因测序仪20，用于改善所述第一实施例可能存在的上述问题，具体地，请参阅图4及图5，图4是本发明第二实施例的基因测序仪20的部分结构立体组装示意图，图5是图4所示基因测序仪20的立体分解示意图。所述基因测序仪20包括基因测序芯片21、芯片平台22、及密封与转接模块23。
所述芯片平台22包括载台221及芯片连接模块222，所述芯片连接模块222设置于所述载台221上，所述芯片连接模块222包括基体223、设置于所述基体223上的溶液流入通道224与溶液流出通道225。请参阅图6，图6是图4所示基因测序芯片21分解图的反面结构示意图。所述基因测序芯片21包括溶液入口21a、溶液出口21b及位于所述溶液入口21a与所述溶液出口21b之间的内部流道21c。具体地，所述基因测序芯片21包括芯片基体211、设置于芯片基体211一侧的顶板212、位于所述顶板212邻近所述芯片基体211一侧的所述内部流道21c，所述芯片基体211具有所述溶液入口21a与所述溶液出口21b，所述顶板212盖设于所述芯片基体211上使得所述溶液入口21a经由所述内部流道21c与所述溶液出口21b连通。本实施例中，所述溶液入口21a与所述溶液出口21b可以均为贯穿所述芯片基体211的通孔，所述顶板212可以为透光板。
所述密封与转接模块23位于所述溶液流入通道224的出口与所述溶液入口21a之间以及所述溶液出口21b与所述溶液流出通道225的入口之间，且所述密封与转接模块23用于将来自所述溶液流入通道224的溶液导入所述基因测序芯片21以及将完成测序的溶液从所述基因测序芯片21导出至所述溶液流出通道225。
可以理解，所述基因测序芯片21的内部流道21c内加载所述溶液以进行测序，具体地，所述芯片基体211表面可以具有位于所述内部流道内的反应区域，所述溶液可以流入所述内部流道流入所述反应 区域，通过照射预定光至所述反应区域并(如通过显微镜相机)获取所述反应区域的出射光来获取基因检测结果。进一步地，所述顶板可以为透光板，所述芯片基体211也可以具有用于测序的内部硅片及设置在内部硅片周围的对生物试剂兼容性良好的外框。可以理解，除了图4中所示的所述基因测序芯片21、芯片平台22、及密封与转接模块23外，本发明基因测序仪20还可以包括并未在图示中示意出的光源、显微镜相机、液体系统等其他模块，此处不进行赘述。
本实施例中，所述密封与转接模块23包括多个弹性密封圈231，请参阅图7及图8，图7是所述密封与转接模块23的立体分解示意图，图8是图7的反面示意图。每个弹性密封圈231包括本体231a及贯穿本体231a的通孔231b，所述基因测序仪20工作时，所述本体231a夹于所述芯片连接模块222的基体223与所述基因测序芯片21之间，且所述通孔231b用于连接于所述溶液入口21a与所述溶液流入通道224的出口或者连接于所述溶液出口21b与所述溶液流出通道225的入口之间，用于将来自所述溶液流入通道224的溶液导入所述基因测序芯片21的溶液入口21a以及将完成测序的溶液从所述基因测序芯片21的溶液出口21b导出至所述溶液流出通道225。
进一步地，本实施例中，所述基体223的数量为两个，所述两个基体223可以分别位于所述载台221的两侧。其中一个基体223上对应所述基因测序芯片21的溶液入口21a设置且具有所述溶液流入通道224，另外一个基体223对应所述基因测序芯片21的溶液出口21b设置且具有所述溶液流出通道225，所述弹性密封圈231的数量为两组，每组弹性密封圈231具有至少一个弹性密封圈，其中一组弹性密封圈231的通孔231b连接于所述溶液入口21a与所述溶液流入通道224的出口之间，另外一组弹性密封圈231的通孔231b连接于所述溶液出口21b与所述溶液流出通道225的入口之间。
更进一步地，本实施例中主要以每组弹性密封圈231包括多个弹性密封圈(如4个)进行示例性说明，所述基因测序芯片21包括多个与弹性密封圈231一一对应的多个溶液入口21a与多个溶液出口21b，每个弹性密封圈231的通孔231b连接于所述溶液入口21a与所述溶液流入通道224的出口之间或者连接于所述溶液出口21b与所述溶液流出通道225的入口之间。所述弹性密封圈231的材料可以包括硅胶或橡胶，如为橡胶圈或硅胶圈。
所述本体231a包括对应所述基因测序芯片的第一端面232及对 应所述芯片连接模块的基体的第二端面233，所述通孔231b贯穿所述第一端面232及所述第二端面233，所述第一端面232和/或所述第二端面233为朝向内部凹陷的内凹环面。本实施方式中，所述第二端面为内凹弧面构成的环面，但是，可以理解，在变更实施例中，也可以为其他形状的内凹环面。本实施例中的第一端面232和第二端面233的形状就类似漏斗型状、吸盘型状。
具体地，所述本体231a分为第一端部234、第二端部236及连接于所述第一端部234及所述第二端部236之间的连接部235，所述第一端部234与所述第二端部236的直径大于所述连接部235的直径，所述通孔231b贯穿所述第一端部234、所述连接部235及所述第二端部236，所述第一端面232为所述第一端部234邻近所述基因测序芯片21的表面，所述第二端面233为所述第二端部236邻近所述芯片连接模块222的基体223的表面。
所述第一端部234还包括第一外侧面234a及第一底面234b，所述第一外侧面234a与所述第一端面232之间具有倒角234c，所述第一底面234b连接于所述第一外侧面234a与所述连接部235的外表面之间，所述第二端部236还包括第二外侧面236a及第二底面236b，所述第二外侧面236a与所述第二端面233之间具有倒角236c，所述第二底面236b连接于所述第二外侧面236a与所述连接部235的外表面之间。
进一步地，所述密封与转接模块23还包括盖板237，本实施例中，所述盖板237与所述基体223数量相同且一一对应。所述盖板237位于所述基因测序芯片21与所述芯片连接模块232之间，所述盖板237包括基板238、及贯穿所述基板238的第一固定孔239，所述第一固定孔239用于收容并固定所述弹性密封圈231。可以理解，所述第一固定孔239的数量与所述弹性密封圈231数量相同且一一对应。
所述盖板237还包括贯穿所述基板238的第二固定孔240，所述芯片连接模块222还包括设置于所述基体223上的与所述第二固定孔240对应的锁孔226，所述密封与转接模块还包括锁固件241(如螺丝)，所述锁固件241穿过所述第二固定孔240与所述锁孔226锁固从而将所述密封与转接模块23固定在所述芯片连接模块222上。所述锁固件241及所述锁孔240的数量为至少两个，图示中主要以所述锁固件241及所述锁孔240的数量为两个进行示例性说明。
所述基板238包括第一部分238a及与所述第一部分238a连接的 第二部分238b，所述第一部分238a的最大厚度大于所述第二部分238b的最大厚度，所述第一固定孔239设置于所述第一部分238a，所述第二固定孔240设置于所述第二部分238b和/或所述第二部分238b与所述第一部分238a之间的连接处。
所述第一部分238a包括第一上表面238c、连接所述第二部分238b的连接面238d及位于所述第一上表面283c相背一侧的第一下表面238e，所述第一下表面238e还包括凹槽238f，所述弹性密封圈231的邻近所述基因测序芯片21的一端(如所述第一端部234)的至少部分设置于所述第一上表面238c上，所述弹性密封圈231的邻近所述芯片连接模块222的一端(如所述第二端部236)至少部分收容于所述凹槽238f中。可以理解，所述凹槽238f的深度可以与所述第二端部236的厚度大致相同，前者略小于后者。
所述第二部分238c包括连接所述连接面238d的第二上表面238g及位于所述第二上表面238g相背一侧的第二下表面238h，所述第一下表面第一下表面238e与所述第二下表面238h的至少部分平齐。
所述基体223包括侧壁、上底面233a与下底面233b，所述溶液流入通道224与所述溶液流出通道225贯穿所述上底面233a及所述下底面233b或者贯穿所述上底面233a与所述侧壁。所述上底面233a的预定区域(如中间区域)朝向所述下底面一侧凹陷形成凹陷部233c，所述锁孔226及所述溶液流入通道224、所述溶液流出通道225设置于所述凹陷部。
相较于现有技术，本实施例中，所述弹性密封圈231的内凹环面的端面232、233也可以在受到压力不同时改变与所述芯片连接模块222的基体223和/或与所述基因测序芯片21的接触面积，从而获得不同的密封效果，可以应不同溶液的需要，因此，使用所述弹性密封圈231的基因测序仪20不仅可以很好的实现所述基因测序芯片11与所述芯片连接模块222之间的密封连接，而且可适应性较强。进一步地，所述内凹环面的端面232、233使得端面外边缘受到的压力更大，从而也可以更有效的防止泄漏，而且，所述内凹环面的端面232、233具有自适应性，使得所述多个弹性密封圈231的高度公差对密封效果的影响可以忽略不计，因此这种设计可以使得应用于多个整体流道(由溶液流入通道224、通孔231b、溶液入口21a、内部流道21c、溶液出口21b、通孔231b、及溶液流出通道225构成)的情况。
更进一步地，所述密封与转接模块23还包括所述盖板237，所述 盖板237相对于所述芯片连接模块222可拆卸，所述弹性密封圈231安装在所述盖板237上，从而方便所述密封与转接模块23安放与拆卸。
此外，由于整体流道内使用负压驱动流体运动，所述弹性密封圈231的第一端部234与所述基因测序芯片21的溶液入口/出口21a、21b之间可在负压出现时，利用所述第一端部234与外部大气压的压力差，将所述第一端部234吸紧在所述基因测序芯片21的溶液入口/出口21a、21b，使二者连接处密封所需的压力大大降低，甚至有可能不对所述芯片连接模块222施加压紧力也可以实现密封。
所述盖板237将所述弹性密封圈231的第二端部236与芯片连接模块222之间压紧而密封，这样的设计可以使得所述弹性密封圈231与芯片连接模块222之间的密封不再依赖对芯片连接模块222施加的压紧力；所述弹性密封圈231两端对密封所需的压紧力减少，因此可以在设计时将施加给所述芯片连接模块222的压紧力大幅降低，从而避免压紧力过大导致的所述基因测序芯片21整体变形过大。
可以理解，在所述第二实施例的变更实施例中，所述弹性密封圈231中，所述第一端面232与所述第二端面233也可以其中一个端面设计为内凹环面，另外一个端面设计为第一实施例中的三维环面，即所述弹性密封圈231包括三维环面与内凹画面的混合式密封圈；或者所述多个弹性密封圈231中，可以包括两个端面232、233均为内凹环面的密封圈、两个端面232、233均为三维环面的密封圈、及三维环面与内凹环面的混合式密封圈中的任意两种或三种的组合。当然，所述弹性密封圈231不但在多个整体流道的基因测序仪20具有较好的技术效果，而且同样也可以适用于一个整体流道的基因测序仪。
在本实施例中，可以在载台221上加设负压模块，该负压模块位于基因测序芯片21下方，为基因测序芯片21提供一个向下的吸附力，使其可更稳固地安放于载台221上。或者，也可以增设一个机械卡扣结构，为基因测序芯片21提供一个向下的压力，使其可更稳固地安放于载台221上。
以上所述仅为本发明的实施方式，并非因此限制本发明的专利范围，凡是利用本发明说明书及附图内容所作的等效结构或等效流程变换，或直接或间接运用在其他相关的技术领域，均同理包括在本发明的专利保护范围内。

Claims (18)

  1. 一种基因测序仪，其特征在于：所述基因测序仪包括基因测序芯片、芯片平台、及密封与转接模块，
    所述芯片平台包括芯片连接模块，所述芯片连接模块包括基体、设置于所述基体上的溶液流入通道与溶液流出通道，
    所述基因测序芯片包括溶液入口、溶液出口及位于所述溶液入口与所述溶液出口之间的内部流道，
    所述密封与转接模块位于所述溶液流入通道的出口与所述溶液入口之间以及所述溶液出口与所述溶液流出通道的入口之间，且所述密封与转接模块用于将来自所述溶液流入通道的溶液导入所述基因测序芯片以及将完成测序的溶液从所述基因测序芯片导出至所述溶液流出通道，
    所述密封与转接模块包括弹性密封圈，所述弹性密封圈包括本体及贯穿本体的通孔，所述本体夹于所述基体与所述基因测序芯片之间，所述通孔连接于所述溶液入口与所述溶液流入通道的出口或者连接于所述溶液出口与所述溶液流出通道的入口之间。
  2. 如权利要求1所述的基因测序仪，其特征在于：所述本体包括对应所述基因测序芯片的第一端面及对应所述芯片连接模块的基体的第二端面，所述通孔贯穿所述第一端面及所述第二端面，所述第一端面和/或所述第二端面为截面包括凸起的弧形的三维环面。
  3. 如权利要求1所述的基因测序仪，其特征在于：所述本体包括对应所述基因测序芯片的第一端面及对应所述芯片连接模块的基体的第二端面，所述通孔贯穿所述第一端面及所述第二端面，所述第一端面和/或所述第二端面为朝向内部凹陷的内凹环面。
  4. 如权利要求3所述的基因测序仪，其特征在于：所述本体包括第一端部、第二端部及连接于所述第一端部及所述第二端部之间的连接部，所述第一端部与所述第二端部的直径大于所述连接部的直径，所述通孔贯穿所述第一端部、所述连接部及所述第二端部，所述第一端面为所述第一端部邻近所述基因测序芯片的表面，所述第二端面为所述第二端部邻近所述芯片连接模块的基体的表面。
  5. 如权利要求4所述的基因测序仪，其特征在于：所述第一端部还包括第一外侧面及第一底面，所述第一外侧面与所述第一端面之间具有倒角，所述第一底面连接于所述第一外侧面与所述连接部的外表 面之间，所述第二端部还包括第二外侧面及第二底面，所述第二外侧面与所述第二端面之间具有倒角，所述第二底面连接于所述第二外侧面与所述连接部的外表面之间。
  6. 如权利要求1所述的基因测序仪，其特征在于：所述密封与转接模块还包括盖板，所述盖板夹于所述基因测序芯片与所述芯片连接模块之间，所述盖板包括基板、及贯穿所述基板的第一固定孔，所述第一固定孔用于收容并固定所述弹性密封圈。
  7. 如权利要求6所述的基因测序仪，其特征在于：所述盖板还包括贯穿所述基板的第二固定孔，所述芯片连接模块还包括设置于所述基体上的与所述第二固定孔对应的锁孔，所述密封与转接模块还包括锁固件，所述锁固件穿过所述第二固定孔与所述锁孔锁固从而将所述密封与转接模块固定在所述芯片连接模块上。
  8. 如权利要求7所述的基因测序仪，其特征在于：所述锁固件及所述锁孔的数量为至少两个。
  9. 如权利要求7所述的基因测序仪，其特征在于：所述基板包括第一部分及与所述第一部分连接的第二部分，所述第一部分的厚度大于所述第二部分的厚度，所述第一固定孔设置于所述第一部分，所述第二固定孔设置于所述第二部分和/或所述第二部分与所述第一部分之间的连接处。
  10. 如权利要求9所述的基因测序仪，其特征在于：所述第一部分包括第一上表面、连接所述第二部分的连接面及位于所述第一上表面相背一侧的第一下表面，所述第一下表面还包括凹槽，所述弹性密封圈的邻近所述基因测序芯片的一端的至少部分设置于所述第一上表面上，所述弹性密封圈的邻近所述芯片连接模块的一端至少部分收容于所述凹槽中。
  11. 如权利要求10所述的基因测序仪，其特征在于：所述第二部分包括连接所述连接面的第二上表面及位于所述第二上表面相背一侧的第二下表面，所述第一下表面与所述第二下表面的至少部分平齐。
  12. 如权利要求11所述的基因测序仪，其特征在于：所述基体包括侧壁、上底面与下底面，所述溶液流入通道或所述溶液流出通道贯穿所述上底面及所述下底面或者贯穿所述上底面与所述侧壁。
  13. 如权利要求12所述的基因测序仪，其特征在于：所述上底面的预定区域朝向所述下底面一侧凹陷形成凹陷部，所述锁孔及所述溶液流入通道或所述溶液流出通道设置于所述凹陷部。
  14. 如权利要求1所述的基因测序仪，其特征在于：所述基体的数量为两个，其中一个基体上对应所述基因测序芯片的溶液入口设置且具有所述溶液流入通道，另外一个基体对应所述基因测序芯片的溶液出口设置且具有所述溶液流出通道，所述弹性密封圈的数量为两组，每组弹性密封圈具有至少一个弹性密封圈，其中一组弹性密封圈的通孔连接于所述溶液入口与所述溶液流入通道的出口之间，另外一组弹性密封圈的通孔连接于所述溶液出口与所述溶液流出通道的入口之间。
  15. 如权利要求14所述的基因测序仪，其特征在于：每组弹性密封圈包括多个弹性密封圈，所述基因测序芯片包括多个与弹性密封圈一一对应的溶液入口与溶液出口，每个弹性密封圈的通孔连接于对应的一个溶液入口与对应的一个溶液流入通道的出口之间或者连接于对应的一个溶液出口与对应的一个溶液流出通道的入口之间。
  16. 如权利要求14所述的基因测序仪，其特征在于：所述芯片平台包括还包括载台，所述两个基体分别位于所述载台的两侧。
  17. 如权利要求1所述的基因测序仪，其特征在于：所述弹性密封圈的材料包括硅胶或橡胶。
  18. 如权利要求1所述的基因测序仪，其特征在于：所述基因测序芯片包括芯片基体、设置于芯片基体一侧的顶板、位于所述顶板邻近所述芯片基体一侧的所述内部流道，所述芯片基体具有所述溶液入口与所述溶液出口，所述顶板盖设于所述芯片基体上使得所述溶液入口经由所述内部流道与所述溶液出口连通。
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