WO2024065292A1 - 芯片处理装置、基因测序仪和进行生化检测的方法 - Google Patents

芯片处理装置、基因测序仪和进行生化检测的方法 Download PDF

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Publication number
WO2024065292A1
WO2024065292A1 PCT/CN2022/122191 CN2022122191W WO2024065292A1 WO 2024065292 A1 WO2024065292 A1 WO 2024065292A1 CN 2022122191 W CN2022122191 W CN 2022122191W WO 2024065292 A1 WO2024065292 A1 WO 2024065292A1
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WIPO (PCT)
Prior art keywords
chip
fluid
processing device
platform
drainage
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PCT/CN2022/122191
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English (en)
French (fr)
Inventor
陈泽华
陆灏
王佳
孙磊林
邢楚填
Original Assignee
深圳华大智造科技股份有限公司
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Priority to PCT/CN2022/122191 priority Critical patent/WO2024065292A1/zh
Publication of WO2024065292A1 publication Critical patent/WO2024065292A1/zh

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/34Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/36Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers

Definitions

  • the present disclosure relates to the technical field of sequencing, and in particular to a chip processing device integrated with a reagent kit, a gene sequencer, a gene sequencing equipment, and a method for performing biochemical detection.
  • a pipe joint is usually used to guide the reagents to the core for biochemical reactions or optical photography, and the reagent kit and its reagent needle are independent of the chip platform and connected by a pipe joint; the existing valve assembly is usually independent of the chip installation platform and connected by a pipe joint; and the flow path connection between each functional module produces many pipelines, and the existing chip installation platform and reagent kit platform are two independent platforms, not an integrated assembly or combination.
  • each cycle needs to be biochemically reacted.
  • the reagents required for the biochemical reaction are provided by the reagent needle set on the reagent kit.
  • a selector valve such as a rotary valve are used to pump the reagent from the corresponding reagent needle into the chip to perform a biochemical reaction.
  • reagent kits usually plays the role of accommodating and supplying different reagents
  • the reagent needle plays the role of inserting the reagent kit and deriving different reagents from the reagent kit
  • the selector valve usually acts as a key component in the flow path arrangement, and plays the function of controlling the fluid path of different reagents and cleaning fluids.
  • the existing discrete component design requires a larger reagent cartridge stroke and a longer fluid path within a limited space, which requires a larger horizontal displacement and lifting stroke to achieve the delivery of fluids such as reagents from the reagent needle to the sequencing chip.
  • fluids such as reagents from the reagent needle to the sequencing chip.
  • the purpose of the present disclosure is to provide a chip processing device integrated with a reagent kit, a gene sequencer, a gene sequencing equipment, and a method for using a gene sequencer.
  • a chip processing device integrated with a reagent kit comprising a substrate extending along a first direction, and a reagent kit platform and a chip platform assembled on the substrate side by side and adjacently along a second direction transverse to the first direction, the top plate of the chip platform on the side facing away from the substrate is provided with a chip receiving area for accommodating a chip carrying a sample to be detected by fluid, the reagent kit platform is formed with a hollow accommodating chamber, and the reagent kit is received in the accommodating chamber; the reagent kit platform has a first fluid transport structure located at a side thereof facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located at a side of the chip platform facing the reagent kit platform along the second direction and configured to at least partially overlap and communicate with the first fluid transport structure when the reagent kit platform and the chip platform are assembled, the first fluid transport structure being fluidically connected to the chip via the second fluid transport structure.
  • the accommodating bin is connected to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position lower than the drainage position, and the drainage position and the non-drainage position are distributed corresponding to a state in which the first fluid transporting structure and the second fluid transporting structure are fluidically connected, and a state in which they are not fluidly connected; and the chip processing device is configured to: in response to the accommodating bin rising away from the substrate to the drainage position, connect the first fluid transporting structure and the second fluid transporting structure to each other to be fluidically connected; and in response to the accommodating bin descending toward the substrate to the non-drainage position, separate the first fluid transporting structure and the second fluid transporting structure from each other.
  • the top plate of the chip platform at a side away from the substrate has a flange protruding toward the reagent kit platform along the second direction, and the reagent kit platform is partially embedded and assembled between the outwardly protruding flange of the top plate and the substrate.
  • the first fluid transport structure includes a plurality of reagent grooves and a plurality of guide grooves arranged in the reagent kit in a one-to-one correspondence, and a connecting channel in which the fluid is connected between the bottom of each guide groove and the bottom of the corresponding reagent groove, each reagent groove is at least partially filled with fluid and has a first opening open upward toward the flange, and a first pierceable structure covering the first opening, and each guide groove has a second opening open upward toward the flange, and a second pierceable structure covering the second opening.
  • the second fluid transport structure includes a fluid supply device, which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed on the top plate and in fluid communication with the flow path network.
  • the selector valve includes: a valve seat, the selector valve is fixed to the top plate via the valve seat; a valve body, extending from the valve seat in a direction away from the top plate, and formed with a fluid inlet configured to guide the fluid to flow into the inside of the valve body and a fluid outlet configured to guide the fluid to flow outward from the inside of the valve body.
  • the flow path network includes: a plurality of drainage needle ports, located on the side of the top plate opposite to the chip receiving area; a plurality of inlet ports, arranged to be spaced apart from the plurality of drainage needle ports in a one-to-one correspondence; a plurality of branch flow channels, each branch flow channel is connected between each drainage needle port and the corresponding inlet port, and is configured to guide the fluid input from each drainage needle port to the corresponding inlet port; an outlet port, arranged to be spaced apart from the plurality of inlet ports and not connected to the plurality of branch flow channels; and a common flow channel, connected between the outlet port and the chip receiving area, and configured to guide the fluid output from the outlet port to the chip receiving area.
  • the selector valve is arranged so that the fluid outlet is fluidly connected to the outlet port, and the fluid inlet is fluidly connected to at least one of the multiple inlet ports, and is configured to switch the selective connection between at least one of the multiple inlet ports corresponding to the multiple branch flow channels and the outlet port via the fluid inlet and the fluid outlet.
  • the plurality of drainage needle ports are formed through-through in a convex portion at an edge of the top plate, protruding toward a side of the top plate that is away from the chip receiving area.
  • the second fluid delivery structure further includes a flow guide component protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide component including: a plurality of membrane puncturing needles and a plurality of drainage needles, respectively protruding from the side of the top plate opposite to the chip receiving area toward the reagent kit platform, each membrane puncturing needle having a first end aligned with a corresponding first pierceable structure, and each drainage needle having a second end aligned with a corresponding second pierceable structure.
  • Each membrane puncturing needle is not connected to the flow path network, and is configured to pierce the first pierceable structure with its first end in response to the accommodating bin reaching the drainage position, and then insert the reagent tank to expose the reagent tank to change the air pressure in the reagent tank.
  • each drainage needle is constructed as a hollow needle, and is in fluid communication with a corresponding branch flow channel in the plurality of branch flow channels in a one-to-one correspondence, and is configured to pierce the second pierceable structure with its second end in response to the accommodating bin reaching the drainage position, and then insert the guide groove to fluidically connect to the guide groove to draw the fluid in the guide groove.
  • the free end of each of the plurality of drainage needles is higher than the inner wall at the bottom of the reagent tank.
  • each guide groove is configured as a groove having a circular cross section with a first inner diameter
  • each guide groove is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter
  • the first pierceable structure is a metal foil; and the second pierceable structure is a flexible seal such that a liquid-tight seal is maintained after being pierced by a corresponding drainage needle of the plurality of drainage needles.
  • the plurality of drainage needles are arranged in a straight line with a spacing from each other, and the plurality of membrane rupture needles are arranged in a straight line with a spacing from each other; and the plurality of drainage needles and the plurality of membrane rupture needles are arranged parallel to each other.
  • a corresponding membrane-breaking needle is arranged one-to-one on the side of each of the plurality of drainage needles, and each drainage needle is adjacent to but spaced apart from the corresponding single membrane-breaking needle in pairs.
  • each drainage needle includes a hollow and elongated straight tubular needle body, and a through tip having a tapered longitudinal cross-sectional shape.
  • the plurality of drainage needles are mounted to the plurality of drainage needle ports in a threaded connection manner.
  • the guide assembly also includes: at least two guide pins, which protrude outward from the side of the top plate opposite to the chip receiving area and are arranged in a straight line spaced apart from each other, and are constructed to match the alignment features on the reagent box in shape.
  • the plurality of drainage needle ports are arranged linearly aligned with each other.
  • the plurality of drainage needle ports are arranged to be separated from each other at uniform intervals.
  • the selector valve is a rotary valve, and the rotary valve is configured to be rotatable around its axis to switch the selective connection between at least one of the multiple inlet ports corresponding to the multiple branch flow channels and the outlet port via the fluid inlet and the fluid outlet.
  • each of the inlet port and the outlet port is parallel to the axis
  • the inlet port is disposed to be offset from the axis
  • the outlet port is disposed coaxially with the axis.
  • the selector valve is mounted to the back side of the top plate away from the chip receiving area via the valve seat, and wherein the multiple inlet ports are configured to be arranged in a ring around the axis, the multiple inlet ports and the outlet ports are both open to the back side of the top plate, and at least one of the multiple inlet ports is selectively connected to the fluid inlet of the valve body, the outlet port is connected to the fluid outlet of the valve body, and the center distance between each of the multiple inlet ports and the outlet port is equal.
  • the plurality of branch flow channels are arranged to diverge radially around the rotary valve and turn to communicate with the plurality of drainage needle ports in a one-to-one correspondence.
  • the top plate includes: a top layer, the chip receiving area is formed in the top layer; and a supporting layer, the supporting layer and the top layer are stacked and located between the top layer and the selector valve; and the plurality of branch flow channels and the common flow channel are formed on a side of the supporting layer facing the top layer, and the plurality of inlet ports, the outlet ports and the plurality of drainage needle ports extend through the supporting layer.
  • a through accommodating hole is formed in the chip receiving area of the top layer, and a recessed portion is recessed from a side of the top layer away from the supporting layer and arranged around the accommodating hole.
  • the top plate also includes a chip adsorption component, which is arranged to be partially fixed in the accommodating hole and protrude from the accommodating hole away from the supporting layer, and is configured to accommodate and adsorb the chip, including: a pipe joint connected to a negative pressure source; an adsorption platform, which is partially disposed in the accommodating hole, and the edge of its top surface protrudes outward to define an adsorption groove in the top layer that is recessed toward the supporting layer and between the edge and the top surface, the adsorption groove is constructed as a closed groove extending along the edge and in the form of a closed loop, and is shaped and sized to be suitable for surrounding and fixing the edge of the chip; and a negative pressure channel, which is formed through the adsorption platform and connected between the pipe joint and the adsorption groove.
  • a chip adsorption component which is arranged to be partially fixed in the accommodating hole and protrude from the accommodating hole away from the supporting layer, and is configured to accommodate and adsorb the chip, including
  • the top layer is formed with a supply port and a discharge port extending therethrough and to the recess, the supply port being fluidly connected to the outlet port of the valve body via the common flow channel, and the discharge port being spaced apart from the supply port.
  • the common flow channel is linearly coupled between the outlet port and the supply port.
  • the plurality of branch flow channels are arranged not to intersect each other and to avoid the common flow channel.
  • the ends of the exhaust port and the supply port and the end of the support layer respectively extend to the recess; and, when the chip is received and adsorbed on the adsorption platform, a first liquid-tight sealing surface is jointly defined between the adsorption platform and the chip, and the chip forms a sealed fluid connection with the supply port and the exhaust port respectively at the first liquid-tight sealing surface.
  • the support layer is formed with a discharge channel which passes therethrough and is fluidically connected from the discharge port to the outside of the top plate.
  • the multiple inlet ports and the outlet ports extend through the support layer to the back side of the top plate, the back side and the valve seat jointly define a second liquid-tight sealing surface, and the multiple inlet ports and the outlet ports respectively form a sealed fluid connection with the fluid inlet and the fluid outlet of the valve body at the second liquid-tight sealing surface.
  • the chip processing device also includes a driving member arranged inside the chip processing device and at least one guide rail assembly connected between the storage bin and the substrate.
  • the storage bin can be moved in a direction orthogonal to the substrate by the driving member through the transmission of the at least one guide rail assembly so that the guide assembly is inserted and the fluid is connected to the test kit.
  • the driving member includes: a driving source, including one of a stepping motor and a piezoelectric driver; and a lead screw drivingly connected between the driving source and the at least one guide rail assembly.
  • each guide rail assembly includes two sets of spaced-apart cross roller guide rails, each set of cross roller guide rails includes a fixed rail fixed to the chip platform, a movable rail connected to the accommodating bin, and a plurality of rollers held between the fixed rail and the movable rail.
  • the fixed rail is fixed to the chip platform in a manner orthogonal to the substrate
  • the movable rail is fixed to the accommodating bin in a manner orthogonal to the substrate.
  • the lead screw is coupled to the movable rails of each of the two sets of cross roller guides in the at least one guide assembly.
  • the chip processing device also includes a positioning device, which includes: a groove, which is recessed in the top inner wall of the accommodating bin; an elastic component, which is arranged in the groove; and a positioning bead, which is arranged at one end of the elastic component facing the substrate and is configured as follows: in response to the test kit not reaching the positioning bead in the accommodating bin, the elastic component is in an initial state where it is not subject to the force applied by the test kit and the positioning bead at least partially protrudes from the top inner wall of the accommodating bin toward the substrate; and in response to the test kit being inserted into the accommodating bin and squeezing the positioning bead, the elastic component is pushed toward the groove via the positioning bead, and then the elastic component is at least partially retracted into the groove.
  • a positioning device which includes: a groove, which is recessed in the top inner wall of the accommodating bin; an elastic component, which is arranged in the groove; and a positioning bead, which is arranged at one end of the elastic component facing the
  • the test kit has a protrusion protruding toward the top inner wall of the accommodating bin, and a positioning groove recessed from the protrusion, and in response to the test kit being inserted into the accommodating bin and squeezing the positioning bead, the positioning bead is clamped between the positioning groove and the elastic component.
  • the chip processing device also includes an in-place detector arranged inside the accommodating bin, the in-place detector includes an optical coupling component and a shielding member, the optical coupling component includes an infrared transmitter and an infrared receiver, and is configured to determine that the reagent kit is in place in the accommodating bin in response to the situation that when the reagent kit is inserted into the accommodating bin and in place, the shielding member is displaced or deformed by the force exerted by the reagent kit and blocks the infrared receiver from receiving infrared rays from the infrared transmitter.
  • the in-place detector includes an optical coupling component and a shielding member
  • the optical coupling component includes an infrared transmitter and an infrared receiver
  • the chip processing device also includes a clamping device formed at the top of the reagent kit platform, the top of the reagent kit platform is formed with a through opening to at least partially expose the reagent kit inserted into the accommodating bin
  • the clamping device includes: a pressing plate, one side of which is fixed to the reagent kit platform; a pin extending through the pressing plate at a free side opposite to the one side; a pair of arms, one end of each arm being pivotally connected to a corresponding end of the pin; and a pair of elastic members, each elastic member being elastically connected between a corresponding arm of the pair of arms and the reagent kit platform.
  • the chip processing device also includes a first tilt adjustment mechanism arranged between the bottom of the reagent cartridge platform and the substrate, the first tilt adjustment mechanism including a first distance head arranged non-linearly and two first thread pairs that can be screwed and adjusted relative to the substrate.
  • the chip processing device also includes a second tilt adjustment mechanism arranged between the bottom of the chip platform and the substrate, and the second tilt adjustment mechanism includes a second distance head arranged non-linearly and two second thread pairs that can be screwed and adjusted relative to the substrate.
  • the chip processing device also includes a limit device, which includes: a sensing plate, which is arranged on the corresponding movable rail of at least one group of cross-roller guide rails in at least one guide rail assembly; and an upper limit optical coupler and a lower limit optical coupler, which are respectively arranged at the positions corresponding to the upper and lower ends of the stroke of the corresponding movable rail at both ends of the corresponding fixed rail of the at least one group of cross-roller guide rails, and are respectively configured to stop the driving source in response to detecting that the sensing plate blocks the upper limit optical coupler to determine that the movable rail rises to the upper limit position, and to stop the driving source in response to detecting that the sensing plate blocks the lower limit optical coupler to determine that the movable rail descends to the lower limit position.
  • a limit device which includes: a sensing plate, which is arranged on the corresponding movable rail of at least one group of cross-roller guide rails in at least one guide rail assembly; and an upper limit optical
  • the chip processing device further includes a power component, which is arranged to be in fluid communication with the flow path network and configured to drive the fluid to flow toward the supply port through the flow path network.
  • the power assembly includes a pump in communication with the chip receiving area, and the pump is configured to provide negative pressure to the chip receiving area.
  • the chip processing device also includes a temperature control component, which is arranged on a side of the top plate opposite to the chip receiving area and is configured to adjust the temperature of the fluid supplied from the flow guide component to the chip receiving area.
  • the temperature control component includes a first temperature regulating device, which is arranged to be adjacent to the selector valve on the same side of the top plate; and the fluid guiding device also includes an adapter bracket fixed to the top plate at a side opposite to the chip receiving area, which is constructed in the form of a frame, and the adapter bracket is formed with two recesses arranged in parallel and recessed from the opposite sides of the adapter bracket away from the top plate and toward the top plate, respectively, for accommodating and fixing the selector valve and the first temperature regulating device therein, respectively.
  • the first temperature regulating device includes: a heat sink, which is accommodated and installed in one of the two recesses of the adapter bracket that is recessed from the side facing the top plate, and is fixed to the side opposite to the chip receiving area via the heat insulation fixing member, and includes: at least one of an active heat sink and a passive heat sink; and a temperature control module, which is installed to the heat sink and is configured to cut off the power component when the temperature at the heat sink exceeds a threshold temperature.
  • the temperature control assembly further includes: a heat conducting member inserted between the top plate and the first temperature regulating device.
  • the heat conducting member includes a phase change material.
  • the active heat dissipation element includes a thermoelectric cooler; or the passive heat dissipation element includes one of the following: a single heat sink, a heat sink array.
  • the temperature control assembly further includes a second temperature regulating device, which is fixed to a side of the adapter bracket facing away from the top plate and is arranged in parallel with the rotary valve and is arranged to be aligned with the first temperature regulating device.
  • the second temperature regulating device includes a fan, the fan including: a hollow first shell, the interior of which defines a cavity for airflow, the first shell is arranged so that the cavity is aligned with the first temperature regulating device and is open toward the first temperature regulating device, so as to connect the cavity fluid between the first temperature regulating device and the outside of the fluid guiding device; and a fan assembly, which is accommodated in the first shell.
  • the fan assembly includes: a second shell, which is constructed as a hollow cylindrical body fixedly mounted in the first shell; a rotating shaft, which is rotatably mounted in the second shell; and a plurality of fan blades, which are coaxially fixed to the rotating shaft in the second shell and can rotate relative to the second shell with the rotating shaft.
  • the adapter bracket is also formed with a gas channel that runs through the interior thereof and is open at opposite ends toward the cavities of the first temperature regulating device and the second temperature regulating device, respectively, and the cavity is connected to the first temperature regulating device via the gas channel.
  • the second temperature regulating device also includes a vibration damping device, which includes: a first-stage vibration damping structure, which is constructed as a gasket inserted between the adapter bracket and the first shell of the fan; and a second-stage vibration damping structure, which is arranged in the first shell of the fan and between the first shell and the second shell of the fan assembly, and includes a plurality of vibration damping members that are respectively snapped into the inner wall of the first shell and are spaced apart from each other, and the second shell of the fan assembly is connected to the first shell via the plurality of vibration damping members.
  • a vibration damping device which includes: a first-stage vibration damping structure, which is constructed as a gasket inserted between the adapter bracket and the first shell of the fan; and a second-stage vibration damping structure, which is arranged in the first shell of the fan and between the first shell and the second shell of the fan assembly, and includes a plurality of vibration damping members that are respectively snapped into the inner wall of the first shell and are spaced apart from
  • At least one of the first-stage vibration reduction structure and the second-stage vibration reduction structure is a vibration compensation device, and the vibration compensation device is an elastic member or a damping member.
  • the first shell of the fan is fixed to the adapter bracket via a flexible vibration-absorbing material screw, and the first-stage vibration reduction structure is pressed tightly between the adapter bracket and the first shell via the screw.
  • the selector valve is fixed to the top plate at its valve seat via a threaded connection, and the selector valve is connected to the adapter bracket via an adjustable pressing device, the adjustable pressing device comprising: a plurality of fixed-distance screws, each of which passes through the adapter bracket in a screwable manner and presses the valve body of the selector valve; and a plurality of springs, each of which elastically presses the plurality of fixed-distance screws toward the top plate in a one-to-one corresponding manner.
  • a gene sequencer comprising: a chip, the chip carrying a sample to be detected by fluid; and a chip processing device, the chip processing device comprising a substrate extending in a first direction, and a reagent kit platform and a chip platform assembled on the substrate side by side and adjacently in a second direction transverse to the first direction, the top plate of the chip platform at the side away from the substrate is provided with a chip receiving area for accommodating the chip, the reagent kit platform is formed with a hollow accommodating chamber, the reagent kit is received in the accommodating chamber, and the interior is at least partially filled with the fluid.
  • the reagent kit has a first fluid transport structure located at one side of the reagent kit facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located at one side of the chip platform facing the reagent kit platform along the second direction and configured to overlap and communicate with the first fluid transport structure at least partially when the reagent kit platform and the chip platform are assembled, and the reagent kit is inserted into the accommodating chamber of the chip processing device in a removable manner, and the fluid in the reagent kit is fluidly connected to the sample carried on the chip via the first fluid transport structure and the second fluid transport structure. Since it includes the aforementioned chip processing device, it has similar advantages and will not be described in detail here.
  • the accommodating bin is connected to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position lower than the drainage position, and the drainage position and the non-drainage position are distributed corresponding to a state in which the first fluid transporting structure and the second fluid transporting structure are fluidically connected, and a state in which they are not fluidly connected; and the chip processing device is configured to: in response to the accommodating bin rising away from the substrate to the drainage position, connect the first fluid transporting structure and the second fluid transporting structure to each other to be fluidically connected; and in response to the accommodating bin descending toward the substrate to the non-drainage position, separate the first fluid transporting structure and the second fluid transporting structure from each other.
  • the top plate of the chip platform at a side away from the substrate has a flange protruding toward the reagent kit platform along the second direction, and the reagent kit platform is partially embedded and assembled between the flange of the top plate and the substrate.
  • the first fluid transport structure includes a plurality of reagent grooves and a plurality of guide grooves arranged in a one-to-one correspondence within the reagent kit, and a fluid connecting channel between the bottom of each guide groove and the bottom of the corresponding reagent groove, each reagent groove is at least partially filled with fluid and has a first opening open upward toward the flange, and a first pierceable structure covering the first opening, and each guide groove has a second opening open upward toward the flange, and a second pierceable structure covering the second opening.
  • the second fluid transport structure includes a fluid supply device, which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed on the top plate and in fluid communication with the flow path network.
  • the selector valve includes: a valve seat, the selector valve is fixed to the top plate via the valve seat; a valve body, extending from the valve seat in a direction away from the top plate, and formed with a fluid inlet configured to guide the fluid to flow into the inside of the valve body and a fluid outlet configured to guide the fluid to flow outward from the inside of the valve body.
  • the flow path network includes: a plurality of drainage needle ports, located on the side of the top plate opposite to the chip receiving area; a plurality of inlet ports, arranged to be spaced apart from the plurality of drainage needle ports in a one-to-one correspondence; a plurality of branch flow channels, each branch flow channel is connected between each drainage needle port and the corresponding inlet port, and is configured to guide the fluid input from each drainage needle port to the corresponding inlet port; an outlet port, arranged to be spaced apart from the plurality of inlet ports and not connected to the plurality of branch flow channels; and a common flow channel, connected between the outlet port and the chip receiving area, and configured to guide the fluid output from the outlet port to the chip receiving area.
  • the selector valve is arranged so that the fluid outlet is fluidly connected to the outlet port, and the fluid inlet is fluidly connected to at least one of the multiple inlet ports, and is configured to switch the selective connection between at least one of the multiple inlet ports corresponding to the multiple branch flow channels and the outlet port via the fluid inlet and the fluid outlet.
  • the plurality of drainage needle ports are formed through-through in a convex portion at an edge of the top plate, protruding toward a side of the top plate that is away from the chip receiving area.
  • the second fluid delivery structure also includes a flow guide component protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide component including: a plurality of membrane rupture needles and a plurality of drainage needles, respectively protruding from the side of the top plate opposite to the chip receiving area toward the reagent kit platform, each membrane rupture needle having a first end aligned with the corresponding first pierceable structure, and each drainage needle having a second end aligned with the corresponding second pierceable structure, each membrane rupture needle is not connected to the flow path network, and is configured to pierce the first pierceable structure with its first end in response to the accommodating chamber reaching the drainage position, and then insert into the reagent tank to expose the reagent tank to change the air pressure in the reagent tank; and each drainage needle is constructed as a hollow needle, and is fluidically connected to a corresponding branch flow channel among the multiple branch flow channels in a one-to-one correspondence, and is
  • the free end of each of the plurality of drainage needles is higher than the inner wall at the bottom of the reagent tank.
  • each guide groove is configured as a groove having a circular cross section with a first inner diameter
  • each guide groove is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter
  • the first pierceable structure is a metal foil; and the second pierceable structure is a flexible seal such that a liquid-tight seal is maintained after being pierced by a corresponding drainage needle of the plurality of drainage needles.
  • a gene sequencing device comprising: a chip carrying a sample to be detected by fluid; and at least two chip processing devices, each chip processing device comprising a substrate extending along a first direction, and a reagent kit platform and a chip platform assembled on the substrate side by side and adjacently along a second direction transverse to the first direction, a chip receiving area for accommodating the chip is provided on a top plate of the chip platform at a side away from the substrate, and the reagent kit platform forms a hollow accommodating chamber, the reagent kit is received in the accommodating chamber, and the interior is at least partially filled with the fluid.
  • the test kit has a first fluid transport structure located at one side of the test kit along the second direction toward the chip platform, and the chip platform has a second fluid transport structure located at one side of the chip platform along the second direction toward the test kit platform and configured to at least partially overlap and communicate with the first fluid transport structure when the test kit platform and the chip platform are assembled; the test kit is removably inserted into the containing chamber, and the fluid in the test kit is fluidly connected to the sample carried on the chip via the first fluid transport structure and the second fluid transport structure; and the at least two chip processing devices are symmetrically arranged with their respective chip platforms adjacent to each other.
  • the at least two chip processing devices include at least one pair of chip processing devices arranged in mirror symmetry with each other and with respective chip platforms adjacent to each other. Since it includes the aforementioned chip processing device, it has similar advantages and is not described in detail here.
  • the accommodating chamber is connected to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position lower than the drainage position, and the drainage position and the non-drainage position correspond to a state in which the first fluid transport structure and the second fluid transport structure are in fluid communication and a state in which they are not in fluid communication.
  • the chip processing device is configured to: in response to the accommodating chamber rising away from the substrate to the drainage position, the first fluid transport structure and the second fluid transport structure are connected to each other to form fluid communication; and in response to the accommodating chamber descending toward the substrate to the non-drainage position, the first fluid transport structure and the second fluid transport structure are separated from each other.
  • the top plate of the chip platform at a side away from the substrate has a flange protruding toward the reagent kit platform along the second direction, and the reagent kit platform is partially embedded and assembled between the flange of the top plate and the substrate.
  • the first fluid transport structure includes a plurality of reagent grooves and a plurality of guide grooves arranged in a one-to-one correspondence within the reagent kit, and a fluid connecting channel between the bottom of each guide groove and the bottom of the corresponding reagent groove, each reagent groove is at least partially filled with fluid and has a first opening open upward toward the flange, and a first pierceable structure covering the first opening, and each guide groove has a second opening open upward toward the flange, and a second pierceable structure covering the second opening.
  • the second fluid transport structure includes a fluid supply device, which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed on the top plate and in fluid communication with the flow path network.
  • the selector valve includes: a valve seat, the selector valve is fixed to the top plate via the valve seat; a valve body, extending from the valve seat in a direction away from the top plate, and formed with a fluid inlet configured to guide the fluid to flow into the inside of the valve body and a fluid outlet configured to guide the fluid to flow outward from the inside of the valve body.
  • the flow path network includes: a plurality of drainage needle ports, located on the side of the top plate opposite to the chip receiving area; a plurality of inlet ports, arranged to be spaced apart from the plurality of drainage needle ports in a one-to-one correspondence; a plurality of branch flow channels, each branch flow channel is connected between each drainage needle port and a corresponding inlet port, and is configured to guide the fluid input from each drainage needle port to the corresponding inlet port; an outlet port, arranged to be spaced apart from the plurality of inlet ports and not connected to the plurality of branch flow channels; and a common flow channel, connected between the outlet port and the chip receiving area, and configured to guide the fluid output from the outlet port to the chip receiving area.
  • the selector valve is arranged so that the fluid outlet is fluidly connected to the outlet port, and the fluid inlet is fluidly connected to at least one of the multiple inlet ports, and is configured to switch the selective connection between at least one of the multiple inlet ports corresponding to the multiple branch flow channels and the outlet port via the fluid inlet and the fluid outlet.
  • the plurality of drainage needle ports are formed through-through in a convex portion at an edge of the top plate, protruding toward a side of the top plate that is away from the chip receiving area.
  • the second fluid delivery structure further includes a flow guide component protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide component including: a plurality of membrane puncturing needles and a plurality of drainage needles, respectively protruding from the side of the top plate opposite to the chip receiving area toward the reagent kit platform, each membrane puncturing needle having a first end aligned with a corresponding first pierceable structure, and each drainage needle having a second end aligned with a corresponding second pierceable structure.
  • Each membrane puncturing needle is not connected to the flow path network, and is configured to pierce the first pierceable structure with its first end in response to the accommodating bin reaching the drainage position, and then insert the reagent tank to expose the reagent tank to change the gas pressure in the reagent tank; and each drainage needle is constructed as a hollow needle, and is in fluid communication with a corresponding branch flow channel in the plurality of branch flow channels in a one-to-one correspondence, and is configured to pierce the second pierceable structure with its second end in response to the accommodating bin reaching the drainage position, and then insert the guide groove to be fluidically connected to the guide groove to draw the fluid in the guide groove.
  • the free end of each of the plurality of drainage needles is higher than the inner wall at the bottom of the reagent tank.
  • each guide groove is configured as a groove having a circular cross section with a first inner diameter
  • each guide groove is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter
  • the first pierceable structure is a metal foil; and the second pierceable structure is a flexible seal so that a liquid-tight seal is maintained after being pierced by a corresponding drainage needle among the multiple drainage needles.
  • a method for performing biochemical detection comprising: establishing a fluid connection between a chip having a sample to be detected and a test kit having a plurality of different reaction components, the reaction components comprising at least one of a sample generation component or a sample analysis component; optionally, generating a sample on the chip in a generation operation, the generation operation comprising allowing different sample generation components to flow into the chip and controlling the reaction conditions of the chip to generate the sample; and analyzing the sample on the chip in an analysis operation, the analysis operation comprising allowing sample analysis components to flow into the chip, the sample analysis components reacting with the sample to provide a relevant detectable signal; the test kit and the chip are integrated in a chip processing device, and the fluid in the test kit is fluidly connected to the chip via a first fluid transport structure and a second fluid transport structure separated from each other in the chip processing device.
  • the first fluid transport structure is integrated into the reagent kit
  • the second fluid transport structure is integrated into a carrier supporting the chip
  • the carrier is integrated into the chip processing device.
  • the reagent box moves relative to the carrier through a movable bracket integrated in the chip processing device, thereby achieving communication between the first fluid transport structure and the second fluid transport structure.
  • the biochemical reaction is a nucleic acid sequencing reaction
  • the sample to be detected is a nucleic acid sequencing library.
  • the biochemical reaction is a specific binding reaction
  • the sample to be detected is a biological tissue or a tissue section.
  • the specific binding reaction can be a binding reaction between an antigen and an antibody, or a binding reaction between biotin and streptavidin, etc.
  • the detectable signal is an optical signal.
  • connection between the first fluid transport structure and the second fluid transport structure includes: the first fluid transport structure is connected to the external air pressure of the chip processing device to drive the fluid in the reagent kit to flow into the second circulation transport structure; and the chip is selectively connected to the fluid in the second circulation transport structure.
  • the second flow transport structure has a plurality of branch flow channels
  • the selective connection between the chip and the fluid includes: utilizing a selector valve integrated in the chip processing device to control the selective connection between different branch flow channels and the chip.
  • the chip processing device, gene sequencer, gene sequencing equipment and method of using the gene sequencer implemented by the embodiments of the present disclosure can realize an integrated pipeline-free fluid delivery structure through the above settings, which has a reduced flow channel length, a more reliable leveling and tightening effect on the test kit, and a higher positioning accuracy.
  • the setting of aspirating from the top of the test kit combined with the use of a syringe pump is adopted, which avoids long-stroke translation and lifting movements and also avoids the need to insert the reagent needle into the bottom of the test kit as in conventional operations.
  • the fixation, positioning, stroke, etc. of the fluid delivery structure can be improved while improving the integration and thus the space utilization, and the design expectations can be achieved with a more compact structure.
  • this compact structure minimizes the space occupancy, and the simple structure and connection relationship facilitate assembly and disassembly.
  • FIG1(a) schematically shows a three-dimensional structural view of a chip processing device according to an embodiment of the present disclosure
  • FIG1(b) is an exploded schematic diagram of FIG1(a)
  • FIG1(c) shows a top view of a portion of the structure of FIG1(a)
  • FIG1(d) is a cross-sectional schematic diagram of FIG1(c) along the P-P line
  • FIG1(e) is a cross-sectional schematic diagram of the structure shown in FIG1(e) at the same position after the reagent chamber 110 is removed
  • FIG1(f) is a three-dimensional schematic diagram of the structure shown in FIG1(a) after the reagent chamber 110 is removed;
  • Fig. 2(a) to Fig. 2(e) schematically show views of the chip processing device shown in Fig. 1 from different angles
  • Fig. 2(a) is a schematic stereoscopic view with the panel of the chip platform and the internal cross roller guide removed
  • Fig. 2(b) is a front view with the panel of the chip platform and the internal cross roller guide removed
  • Fig. 2(c) is a schematic stereoscopic view from another angle with the panel of the chip platform and the internal V-shaped support arranged on the outside removed
  • Fig. 2(d) is a front view with the panel of the chip platform
  • Fig. 2(e) is a top view
  • Fig. 2(f) schematically shows an assembly diagram of the selector valve and the adapter bracket
  • FIG3( a ) shows a schematic diagram of the structure of a reagent box as a liquid reservoir
  • FIG3( b ) shows a top view of the reagent box of FIG3( a ) after removing the top panel
  • Fig. 4 shows a view cut along the line F-F in Fig. 2(e), which shows the specific arrangement of the reagent tank and the guide groove inside the reagent kit;
  • FIG. 5( a ) schematically shows a specific structure for conveying fluid in the top plate of the chip platform in the chip processing device of FIG. 1 , so as to serve as a fluid supply device;
  • FIG. 5( b ) schematically shows the assembly relationship between the top plate serving as a carrier and the selector valve;
  • FIG6(a) shows a schematic three-dimensional view of a carrier, wherein the carrier has a chip adsorption assembly installed in a chip receiving area;
  • FIG6(b) to FIG6(c) schematically show exploded views of the carrier of FIG6(a) from a top view angle and a bottom view angle, respectively, wherein the chip adsorption assembly is removed for simplicity;
  • FIG7 shows a schematic structural diagram of a chip adsorption assembly
  • FIG8 schematically shows a cross-sectional view of a top plate serving as a carrier along a common flow channel
  • Figures 9(a) to 9(f) respectively show the fluid guiding device in the chip platform in the chip processing device of Figure 1, especially its flow guiding component, from different angles.
  • Figures 9(a) and 9(b) are schematic stereoscopic views of the fluid guiding device from different angles;
  • Figures 9(c) to 9(f) are the front view, right view, rear view, and top view of the fluid guiding device, respectively;
  • FIG10 illustrates a cross-sectional view of the chip processing device shown in the top view of FIG2(e) along the line E-E, showing the internal positioning device and the position detector for detecting that the liquid reservoir is inserted into the receiving chamber;
  • FIG11 is a schematic diagram of the explosion of FIG9( b );
  • Fig. 12 is a schematic cross-sectional view along line A-A in Fig. 9(f);
  • FIG. 13( a ) is a schematic diagram of an explosion of the second temperature adjustment device in FIG. 11 ;
  • FIG. 13( b) to FIG. 13( c) are schematic three-dimensional views respectively showing the structure of the device observed after cutting along the lines C-C and D-D in FIG. 9( f);
  • FIG14 schematically illustrates a gene sequencer according to an embodiment of the present disclosure, which includes the chip processing device shown in FIG1 and a liquid reservoir removably inserted into a receiving compartment of a reagent cartridge platform of the chip processing device, and a sequencing chip removably inserted into a chip receiving area on a top plate of the chip platform;
  • FIG15 illustrates a gene sequencing device according to an embodiment of the present disclosure, comprising a pair of the aforementioned gene sequencers that are mirror-symmetrical and arranged adjacent to each other;
  • FIG. 16 illustrates a schematic flow chart of a method for biochemical detection using gene sequencing shown in FIG. 14 according to an embodiment of the present disclosure.
  • FIG. 17 schematically shows more specific steps in the method of the flowchart of FIG. 16 .
  • Figure 1(a) schematically shows a three-dimensional structural view of a chip processing device according to an embodiment of the present disclosure
  • Figure 1(b) is an exploded schematic diagram of Figure 1(a)
  • Figure 1(c) shows a top view of a portion of the structure of Figure 1(a)
  • Figure 1(d) is a cross-sectional schematic diagram of Figure 1(c) along the P-P line.
  • a chip processing device 1 integrated with a reagent kit is provided, which is used to supply fluid from a fluid reservoir 2 (e.g., a reagent kit) containing fluid to a chip 3 (e.g., a gene sequencing chip 3), and the chip processing device 1 includes a substrate 10 extending along a first direction, and a reagent kit platform 11 and a chip platform 12 assembled and arranged side by side and adjacently on the substrate 10 along a second direction transverse to the first direction.
  • a fluid reservoir 2 e.g., a reagent kit
  • a chip 3 e.g., a gene sequencing chip 3
  • the chip platform 12 is provided with a top plate 120 located at the top thereof, and the top plate 120 serves as a carrier for supporting the chip and carrying a fluid transport structure. More specifically, the top plate 120 of the chip platform 12 on the side away from the substrate is provided with a chip receiving area 121a for accommodating a chip 3 carrying a sample to be detected by fluid; more specifically, for example, the shape and size of the chip receiving area 121a are determined to be suitable for accommodating the chip 3, so that the chip 3 is accommodated in the chip receiving area 121a on the top plate 120 of the chip platform 12.
  • a hollow containing chamber 110 is formed in the reagent kit platform 11, and the reagent kit is received in the containing chamber.
  • the reagent kit platform 11 has a containing chamber 110 which is open to the outside (for example, open to the outside on its lateral side as shown in FIG. 1) and is suitable for receiving a fluid reservoir 2 (such as a reagent kit) containing a fluid.
  • the reagent kit platform has a first fluid transport structure located at one side of the chip platform along the second direction inside the reagent kit platform, and the chip platform has a second fluid transport structure located at one side of the chip platform along the second direction toward the reagent kit platform and configured to at least partially overlap and communicate with the first fluid transport structure when the reagent kit platform and the chip platform are assembled, and the first fluid transport structure is fluidically connected to the chip via the second fluid transport structure.
  • the accommodating chamber is connected to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position lower than the drainage position, and the drainage position and the non-drainage position are distributed corresponding to a state in which the first fluid transport structure and the second fluid transport structure are in fluid communication and a state in which they are not in fluid communication; and the chip processing device is configured such that in response to the accommodating chamber rising away from the substrate to the drainage position, the first fluid transport structure and the second fluid transport structure are engaged with each other to form fluid communication; and in response to the accommodating chamber descending toward the substrate to the non-drainage position, the first fluid transport structure and the second fluid transport structure are separated from each other.
  • a chip processing device integrated with a liftable reagent box it is convenient to realize the switching between the fluid communication state and the non-communication state between the first fluid transport structure in the reagent box platform and the second fluid transport structure in the chip platform.
  • the top plate at the side of the chip platform facing away from the substrate has a flange protruding toward the reagent kit platform along the second direction
  • the top plate at the side of the chip platform facing away from the substrate has a flange protruding toward the reagent kit platform along the second direction
  • the reagent kit platform 11 is partially embedded and assembled between the outwardly protruding flange 1201 of the top plate 120 and the substrate 10.
  • Figures 2(a) to 2(e) schematically show views of the chip processing device 1 shown in Figure 1 at different angles
  • Figure 2(a) is a schematic stereoscopic view with the panel of the chip platform 12 and the internal cross-roller guide 130 removed
  • Figure 2(b) is a front view with the panel of the chip platform 12 and the internal cross-roller guide 130 removed
  • Figure 2(c) is a schematic stereoscopic view from another angle with the panel of the chip platform 12 and the V-shaped support 133 arranged on the outside removed
  • Figure 2(d) is a front view with the panel of the chip platform 12
  • Figure 2(e) is a top view.
  • Figure 3(a) shows a schematic diagram of the structure of the reagent box from the reservoir;
  • Figure 3(b) shows a top view of the reagent box of Figure 3(a) after the top panel is removed.
  • Figure 4 shows a view cut along the line F-F in Figure 2(e), which shows the specific arrangement of the reagent tank and the guide groove inside the reagent box;
  • the first fluid transport structure includes a plurality of reagent grooves 20a and a plurality of guide grooves 20b arranged in a one-to-one correspondence in the reagent kit, and a connecting channel 20c in which the fluid is connected between the bottom of each guide groove 20b and the bottom of the corresponding reagent groove 20a, each reagent groove 20a is at least partially filled with fluid and has a first opening 21 open upward toward the flange, and a first pierceable structure 210 covering the first opening 21, and each guide groove 20b has a second opening 22 open upward toward the flange, and a second pierceable structure 220 covering the second opening 22.
  • Figure 5(a) schematically shows the specific structure for conveying fluid in the top plate of the chip platform in the chip processing device of Figure 1 to serve as a fluid supply device;
  • Figure 5(b) schematically shows the assembly relationship between the top plate serving as a carrier and the selector valve.
  • FIG6(a) shows a schematic three-dimensional view of a carrier, wherein the carrier has a chip adsorption assembly installed in a chip receiving area;
  • FIG6(b) to FIG6(c) schematically show exploded views of the carrier of FIG6(a) from a top view and a bottom view, respectively, wherein the chip adsorption assembly is removed for simplicity.
  • FIG7 shows a schematic structural diagram of the chip adsorption assembly.
  • FIG8 schematically shows a cross-sectional view of the top plate 120 serving as a carrier along the L-L line where the common flow channel is located in FIG6(a).
  • FIG9(a) to FIG9(f) respectively show the fluid guiding device in the chip platform in the chip processing device of FIG1, especially its flow guiding component, from different angles.
  • FIG9(a) and FIG9(b) are schematic stereoscopic views of the fluid guiding device shown at different angles;
  • FIG9(c) to FIG9(f) are respectively the front view, right view, rear view, and top view of the fluid guiding device.
  • the second fluid delivery structure includes a fluid supply device
  • the fluid supply device 150 includes: a flow network 125, formed in the top plate of the chip platform and connected between the first fluid delivery structure and the chip, and a selector valve 126, installed on the top plate and fluidically connected to the flow network.
  • the selector valve includes: a valve seat 1261, and the selector valve is fixed to the top plate via the valve seat 1261; a valve body 1262, extending from the valve seat 1261 in a direction away from the top plate and forming a fluid inlet 126a configured to guide the fluid to flow into the interior of the valve body 1262 and a fluid outlet 126b configured to guide the fluid to flow outward from the interior of the valve body 1262, and a drive motor 1263 for at least driving the valve seat to rotate to achieve communication with different branch flow channels of the fluid network, and the drive motor 1263 is preferably a stepping motor.
  • the flow path network includes: a plurality of drainage needle ports 1250, located on the side of the top plate opposite to the chip receiving area; a plurality of inlet ports 1254, arranged to be spaced apart from the plurality of drainage needle ports in a one-to-one correspondence; a plurality of branch flow channels 1252, each branch flow channel being connected between each drainage needle port and the corresponding inlet port, and being configured to guide the fluid input from each drainage needle port to the corresponding inlet port; an outlet port 1255, arranged to be spaced apart from the plurality of inlet ports and not connected to the plurality of branch flow channels; and a common flow channel 1253, being connected between the outlet port and the chip receiving area, and being configured to guide the fluid output from the outlet port to the chip receiving area.
  • the selector valve is arranged so that the fluid outlet 126b is fluidly connected to the outlet port, and the fluid inlet 126a is fluidly connected to at least one of the multiple inlet ports, and is configured to switch the selective connection between at least one of the multiple inlet ports 1254 corresponding to the multiple branch flow channels and the outlet port via the fluid inlet 126a and the fluid outlet 126b.
  • the fluid inlet 126a represents the interface of the valve body connected to the upper surface of the valve seat 1261 and the branch flow channel of the top plate for selective connection
  • the fluid outlet 126b represents the interface of the valve body connected to the upper surface of the valve seat 1261 and the outlet port 1255.
  • the plurality of drainage needle ports are formed through-through in a protrusion at an edge of the top plate that protrudes toward a side of the top plate that is away from the chip receiving area.
  • the second fluid delivery structure further includes a flow guide component 123 protruding from the flange 1201 toward the reagent kit platform 11 and connected to the chip receiving area 121a
  • the flow guide component 123 includes: a plurality of membrane rupture needles 123b and a plurality of drainage needles 123a, respectively protruding from the side of the top plate opposite to the chip receiving area toward the reagent kit platform, each membrane rupture needle having a first end aligned with a corresponding first pierceable structure 210, and each drainage needle having a second end aligned with a corresponding second pierceable structure 220.
  • each membrane rupture needle is not connected to the flow path network, and is configured to pierce the first pierceable structure 210 with its first end in response to the accommodating chamber reaching the drainage position, and then insert into the reagent tank 20a to expose the reagent tank 20a to change the air pressure in the reagent tank 20a.
  • each drainage needle is constructed as a hollow needle and is fluidically connected to a corresponding branch channel among the multiple branch channels in a one-to-one correspondence, and is configured to pierce the second pierceable structure 220 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove 20b to be fluidically connected to the guide groove 20b to draw the fluid in the guide groove 20b.
  • the free ends of the plurality of drainage needles are higher than the inner wall at the bottom of the reagent tank 20 a .
  • the membrane rupture needle 123b pierces the first pierceable structure 210 covering the first opening 21 and enters the reagent tank 20a, so that the atmospheric pressure enters the reagent tank 20a from the pierced first pierceable structure 210 through the first opening 21, thereby further pressing the reagent into the guide groove 20b through the connecting channel 20c at the bottom.
  • the drainage needle 123a also synchronously pierces the second pierceable structure 220 covering the second opening 22 and enters the guide groove 20b. Therefore, through the above arrangement, it is convenient for the drainage needle at least partially inserted into the guide groove to still achieve the suction of the reagent liquid even if it is far away from the reagent page in the reagent box.
  • each guide groove 20b is configured as a groove having a circular cross-section with a first inner diameter
  • each guide groove 20b is configured as a groove having a circular cross-section with a second inner diameter smaller than the first inner diameter
  • the first pierceable structure is, for example, a metal foil.
  • the second pierceable structure is a flexible seal such that a fluid-tight seal is maintained after being pierced by a corresponding drainage needle of the plurality of drainage needles.
  • the plurality of drainage needles are arranged in a straight line spaced apart from each other, and the plurality of membrane rupture needles are arranged in a straight line spaced apart from each other; and the plurality of drainage needles and the plurality of membrane rupture needles are both arranged parallel to each other.
  • the plurality of drainage needles 123a are spaced apart from each other at a uniform spacing.
  • the plurality of reagent dispensing ports are also spaced apart from each other at the spacing.
  • the plurality of drainage needles 123a are evenly distributed at the aforementioned single edge of the carrier 120, effectively avoiding mutual interference and being conducive to local thermal balance.
  • multiple drainage needles 123a arranged linearly and evenly spaced and concentrated at a single edge of the carrier 120 are utilized as reagent needles, thereby realizing a uniformly distributed structure for aspirating liquid from the liquid reservoir with optimized space utilization, and facilitating the subsequent distribution of multiple fluid paths (for example, in the form of multiple manifold branches) from the drainage needles 123a to the selector valve 126, effectively avoiding mutual interference between different reagent paths and being beneficial to regional thermal balance distribution.
  • a corresponding membrane rupture needle is arranged one-to-one on the side of each of the plurality of drainage needles, and each drainage needle is adjacent to but spaced apart from the corresponding single membrane rupture needle in pairs.
  • each drainage needle comprises a hollow and elongated straight tubular needle body and a through top with a tapered longitudinal cross-sectional shape.
  • the plurality of drainage needles are installed to the plurality of drainage needle ports in a threaded connection manner.
  • the guide assembly also includes: at least two guide pins, which protrude outward from the side of the top plate opposite to the chip receiving area and are arranged in a straight line spaced apart from each other, and are constructed to be shaped to match the alignment features on the reagent kit.
  • the at least two guide pins 123c are two guide pins 123c arranged colinearly with the plurality of drainage needles 123a and respectively located outside two drainage needles 123a at both ends of the plurality of drainage needles 123a.
  • the two guide pins 123c and the corresponding alignment features on the reservoir are aligned with each other and in positive fit, thereby serving as guides for accurately positioning all drainage needles 123a relative to the corresponding reagent dispensing ports in the reservoir; in other words, once the two guide pins 123c at both ends are correctly aligned and fit into the alignment features on the reservoir, all drainage needles 123a are aligned and positioned relative to their respective corresponding reagent dispensing ports.
  • the plurality of drainage needle ports are arranged to be aligned with each other in a straight line. In a more specific embodiment, as an example, the plurality of drainage needle ports are arranged to be separated from each other at a uniform spacing.
  • the selector valve is a rotary valve, and the rotary valve is configured to be able to rotate around its axis to switch the selective connection between at least one of the multiple inlet ports corresponding to the multiple branch flow channels and the outlet port via the fluid inlet 126a and the fluid outlet 126b.
  • the inlet port and the outlet port are each axially parallel to the axis, and the inlet port is arranged to be offset from the axis, and the outlet port is arranged coaxially with the axis.
  • the selector valve is mounted to the back side of the top plate away from the chip receiving area via the valve seat 1261, and the multiple inlet ports are configured to be arranged in a ring around the axis, the multiple inlet ports and the outlet ports are both open to the back side of the top plate, and at least one of the multiple inlet ports is selectively connected to the fluid inlet 126a of the valve body 1262, and the outlet port is connected to the fluid outlet 126b of the valve body 1262, and the center distance between each of the multiple inlet ports and the outlet port is equal.
  • the plurality of branch flow channels are arranged to diverge radially around the rotary valve and turn to communicate with the plurality of drainage needle ports in a one-to-one correspondence.
  • the rotary valve 126 is utilized to act as the selector valve 126, and a plurality of inlet ports 1254 (preferably, for example, a plurality of inlet ports 1254 spaced apart from each other circumferentially at the same angle) are arranged along the circumference of the rotary valve 126 as outlets of the branch flow channels 1252, and correspondingly, the plurality of branch flow channels 1252 are radially diverged outward from the corresponding inlet ports 1254, for example, diverging outward in a substantially radial direction around the axis AX of the rotary valve 126 at uniform angular intervals, thereby realizing a substantially uniformly spaced distribution of manifolds in the surrounding area adjacent to the rotary valve 126, facilitating the uniform arrangement of the flow path network 125 in the entire area between the rotary valve 126 and the drainage needle port 1250, and effectively controlling the overall flow channel length by planning and arranging the manifold, thereby avoiding redundant fluid path length and reducing reagent loss, and also
  • the flow network 125 also realizes centralized fluid supply on the area between the selector valve 126 and the chip receiving area 121a (for accommodating the chip) of the carrier 120 by means of a single pipeline, thereby simplifying the liquid supply arrangement in the final stage of supplying fluids such as reagents to the chip.
  • the top plate includes: a top layer 120a, in which the chip receiving area is formed; and a support layer 120b, which is stacked with the top layer 120a and located between the top layer 120a and the selector valve.
  • the plurality of branch flow channels and the common flow channel are formed on a side of the support layer 120b facing the top layer 120a, and the plurality of inlet ports, the outlet port, and the plurality of drainage needle ports extend through the support layer 120b.
  • a through accommodating hole 1202 is formed in the chip receiving area of the top layer 120a, and a recess 1203 is recessed from the side of the top layer 120a facing away from the supporting layer 120b and is arranged around the accommodating hole 1202.
  • the top plate also includes a chip adsorption component 120c, which is arranged to be partially fixed in the accommodating hole 1202 and protrude from the accommodating hole 1202 away from the supporting layer 120b, and is configured to accommodate and adsorb the chip, including: a pipe joint 1204 connected to a negative pressure source; an adsorption platform 1205, which is partially disposed in the accommodating hole 1202, and the edge of its top surface protrudes outward to define an adsorption groove 1206 in the top layer 120a that is recessed toward the supporting layer 120b and between the edge and the top surface, the adsorption groove 1206 being constructed as a closed groove extending along the edge and in the form of a closed loop, and is shaped and sized to be suitable for surrounding and fixing the edge of the chip; and a negative pressure channel 1207, which is formed through the adsorption platform 1205 and connected between the pipe joint 1204 and the adsorption groove 1206.
  • a chip adsorption component 120c which is arranged to be partially fixed in the accommodating
  • the top layer 120a is formed with a supply port and a discharge port extending therethrough and extending to the recess 1203, the supply port being fluidically connected to the selector valve via the common flow channel, and the discharge port being spaced apart from the supply port.
  • the common flow channel is linearly connected between the outlet port and the supply port.
  • the plurality of branch flow passages are arranged not to intersect each other and to avoid the common flow passage.
  • the ends of the exhaust port and the supply port respectively connected to the support layer 120b extend to the recess 1203.
  • the adsorption platform 1205 and the chip jointly define a chip liquid-tight sealing surface P1 serving as a first liquid-tight sealing surface, and the chip forms a sealed fluid connection with the supply port and the exhaust port at the first liquid-tight sealing surface.
  • the support layer 120b is formed with a discharge channel that runs through it and is fluidly connected from the discharge port to the outside of the top plate.
  • the multiple inlet ports and the outlet ports extend through the support layer 120b to the back side of the top plate, and the back side and the valve seat 1261 jointly define a valve liquid-tight sealing surface P2 that acts as a second liquid-tight sealing surface, and the multiple inlet ports and the outlet ports form a sealed fluid connection with the fluid inlet 126a and the fluid outlet 126b of the valve body 1262 at the second liquid-tight sealing surface.
  • the chip liquid-tight sealing surface P1 and the valve liquid-tight sealing surface P2 are respectively located at the upper and lower sides of the flow channel inside the switch valve. This arrangement simplifies the arrangement of the sealing surface, and by defining two sealing surfaces at different positions in the carrier 120, easy fluid isolation and liquid-tight sealing at the chip and the valve are achieved.
  • the chip platform 12 has a driving member 122 disposed therein
  • the chip processing device 1 for example, also includes at least one rail assembly 13 connected between the accommodating chamber 110 and the substrate, and the accommodating chamber 110 can be moved in a direction orthogonal to the substrate 10 by the driving member 122 via the at least one rail assembly 13, and the flow guide assembly 123 is inserted and fluid is connected to the liquid reservoir 2.
  • the chip processing device 1 includes two rail assemblies 13 arranged in parallel.
  • the drainage position is, for example, any position value in a certain range of multiple positions (referred to as a first position range); more specifically, once the accommodating chamber 110 rises to reach a first threshold position in the first position range (for example, the lowest position in the first position range), the first fluid transport structure in the reagent kit platform 11 engages with the second fluid transport structure in the chip platform 12, thereby establishing fluid connection between the first fluid transport structure and the second fluid transport structure.
  • a first position range for example, any position value in a certain range of multiple positions
  • the non-drainage position is, for example, any position value in another certain range of multiple positions (referred to as a second position range); more specifically, once the accommodating chamber 110 descends to reach a second threshold position in the second position range (for example, the highest position in the second position range), the first fluid transport structure in the reagent cartridge platform 11 and the second fluid transport structure in the chip platform 12 are disengaged from each other and thereby the first fluid transport structure and the second fluid transport structure are separated from each other so that there is no longer fluid connection between the two.
  • a second position range for example, the highest position in the second position range
  • the first threshold position is higher than the second threshold position.
  • the first position range and the second position range do not overlap with each other at all.
  • the driving member 122 includes: a driving source, including one of a stepping motor and a piezoelectric driver; and a lead screw in a transmission connection between the driving source and the at least one guide rail assembly 13. More specifically, as an example, the lead screw is further connected to the at least one guide rail assembly 13 via a coupling located upstream thereof and in a transmission connection with the output shaft of the driving source, thereby facilitating the reciprocating movement of the accommodating bin 110 orthogonal to the substrate 10 by the driving member 122 via the transmission of the at least one guide rail assembly 13, that is, realizing the lifting and lowering action of the accommodating bin 110.
  • a driving source including one of a stepping motor and a piezoelectric driver
  • the lead screw is further connected to the at least one guide rail assembly 13 via a coupling located upstream thereof and in a transmission connection with the output shaft of the driving source, thereby facilitating the reciprocating movement of the accommodating bin 110 orthogonal to the substrate 10 by the driving member 122 via the transmission of the at least one guide rail assembly 13,
  • each guide rail assembly 13 includes two spaced-apart groups of cross roller guide rails 130, each group of cross roller guide rails 130 includes a fixed rail 131 fixed to the chip platform 12, a movable rail 132 connected to the storage bin 110, and a plurality of rolling elements 135 held between the fixed rail 131 and the movable rail 132, the plurality of rolling elements being, for example, a plurality of balls (in this case, the cross ball guide acts as each group of cross roller guide rails 130), or a plurality of rollers arranged orthogonally in an alternating manner (in this case, the cross roller guide acts as each group of cross roller guide rails 130), thereby facilitating the bearing of loads in a plurality of different directions.
  • the cross ball guide acts as each group of cross roller guide rails 130
  • the cross roller guide acts as each group of cross roller guide rails 130
  • the fixed rail 131 is fixed to the chip platform 12 in a manner orthogonal to the substrate 10
  • the movable rail 132 is fixed to the storage bin 110 in a manner orthogonal to the substrate 10.
  • each group of cross rollers in the at least one guide rail assembly 13 works together to act as a guiding device for the movement of the accommodating bin 110 in a direction orthogonal to the substrate 10, thereby achieving accurate guidance of the lifting and lowering action of the accommodating bin 110.
  • the lead screw is connected to the movable rails 132 of the two groups of cross roller guides 130 in the at least one guide assembly 13.
  • the two groups of cross roller guides 130 spaced apart from each other in the same guide assembly 13 are synchronously guided for the lifting and lowering of the accommodating bin 110, and at the same time, it is also convenient to maintain the integrated support for the bottom of the accommodating bin 110 during the lifting and lowering of the accommodating bin 110.
  • the first fluid delivery structure of the reagent cartridge platform 11 includes a reservoir 2, such as a reagent cartridge.
  • the chip platform 12 further includes a V-shaped support 133 for fixing the selector valve 126.
  • the selector valve 126 is inserted into the adapter bracket 127.
  • the adapter bracket 127 is fixed to the fixed bracket 12a.
  • the V-shaped support 133 is connected between the bottom of the adapter bracket 127 and the selector valve 126.
  • the V-shaped support 133 includes two legs 1330 and a connecting portion 1332 connecting the two legs 1330. The two legs are respectively connected to the bottom of the adapter bracket 127 by a screw thread pair that can be screwed and adjusted, and the connecting portion 1332 can be fixed to the selector valve 126 by a similar screw thread structure. In this way, the selector valve is stably installed in the chip platform 12.
  • Figure 5(a) schematically shows a specific structure for conveying fluid in the top plate 120 of the chip platform 12 in the chip processing device 1 of Figure 1, such as a second fluid conveying structure;
  • Figure 5(b) schematically shows the assembly relationship between the top plate acting as a carrier and the selector valve.
  • the second fluid transport structure of the chip platform 12 is, for example, the fluid guiding device 160 to be described below, and the fluid guiding device more specifically includes a fluid supply device 150 and a flow guiding component 123; and the fluid supply device includes the aforementioned top plate 120 (which acts as a carrier for carrying the sequencing chip), as well as a flow path network 125 and a selector valve 126, whereby the top plate 120, the flow path network 125 and the selector valve 126 together form a fluid supply device 150 for supplying fluid to the chip; and further, the fluid supply device 150 works in conjunction with the flow guiding component 123 to jointly define the fluid guiding device 160 that acts as the second fluid transport structure.
  • the fluid supply device includes the aforementioned top plate 120 (which acts as a carrier for carrying the sequencing chip), as well as a flow path network 125 and a selector valve 126, whereby the top plate 120, the flow path network 125 and the selector valve 126 together form a fluid supply device 150 for supplying fluid to the chip; and further,
  • the chip processing device 1 also includes a flow network 125 formed in the top plate 120 of the chip platform 12, and a selector valve 126 installed to the top plate 120 and fluidically connected to the flow network
  • the flow network 125 more specifically includes: a plurality of drainage needle ports 1250, which are aligned in a straight line and spaced apart from each other; a plurality of branch flow channels 1252, one end of each branch flow channel 1252 is connected to a corresponding drainage needle port 1250 among the plurality of drainage needle ports 1250, and the other end passes through a side of the top plate 120 close to the selector valve 126 and is selectively connected to a fluid inlet 126a of the selector valve; and a single common flow channel 1253, which is fluidically connected between the fluid outlet 126b of the selector valve 126 and the chip receiving area 121a, and the selector valve 126 is operable
  • the aforementioned top plate 120 serves as a carrier for carrying the sequencing chip, and is combined with the flow path network 125 and the selector valve 126 as described above, and the three together form a fluid supply device 150 for supplying fluid to the chip.
  • a flow channel is provided mainly in the top plate 120 of the chip platform 12, which facilitates the shortening of the flow channel length, reduces the substitution ratio and the amount of reagents used, and reduces the sequencing cost.
  • the selector valve 126 is a rotary valve, and the rotary valve is configured to be rotatable around its axis AX so that the fluid inlet 126a switches alignment and fluid communication with one of the multiple branch flow channels 1252.
  • each of the fluid inlet 126a and the fluid outlet 126b is parallel to the axis AX, and the fluid inlet 126a is arranged to be offset from the axis AX, and the fluid outlet 126b is arranged coaxially with the axis AX.
  • the corresponding other end of the multiple branch flow channels 1252 connected to the fluid inlet 126a is constructed as a plurality of inlet ports 1254 arranged in a ring around the axis AX, and the center distance between each inlet port 1254 and the fluid outlet 126b is equal to the center distance between the fluid inlet 126a and the fluid outlet 126b.
  • the fluid inlet 126a of the valve can be conveniently and selectively switched to align with the outlet of a desired branch flow channel 1252 among the multiple branch flow channels 1252 and to be fluidically connected to each other by simply rotating the valve body of the rotary valve.
  • FIG. 8 schematically shows a cross-sectional view of a top plate serving as a carrier, cut along a common flow channel.
  • the fluid inlet 126a and the fluid outlet 126b share a first sealing surface P1
  • the multiple inlet ports 1254 share a second sealing surface P2
  • the first sealing surface P1 and the second sealing surface P2 are respectively located on the upper and lower sides of the flow channel inside the switch valve.
  • the setting of the sealing surface is simplified, and easy fluid isolation is achieved by only defining two non-overlapping sealing surfaces at different side flow channels in the valve body, which facilitates effective liquid-tight sealing and flow channel blocking when the inlet port 1254 of the branch flow channel 1252 is not aligned with the fluid inlet 126a of the rotary valve 126, and/or the inlet of the downstream common flow channel 1253 is not aligned with the fluid outlet 126b of the rotary valve 126, ensuring timely opening and closing of the flow channel at the rotary valve 126, and effective sealing when the rotary valve 126 is switched to off to avoid unwanted mixing between reagents.
  • Figures 9(a) to 9(f) respectively show the fluid guiding device in the chip platform in the chip processing device of Figure 1, especially its flow guiding component, from different angles.
  • Figures 9(a) and 9(b) are schematic stereoscopic views of the fluid guiding device from different angles;
  • Figures 9(c) to 9(f) are the front view, right view, rear view, and top view of the fluid guiding device, respectively.
  • the multiple drainage needle ports 1250 are arranged at a substantially longitudinal single edge 1208 of the top plate 120, and the multiple branch flow channels 1252 are arranged to radially diverge around the selector valve 126 and turn toward the edge 1208 to be connected to the multiple drainage needle ports 1250 one by one.
  • the selector valve 126 e.g., a rotary valve
  • the selector valve 126 typically at uniform angular intervals and circumferentially radiating radially
  • the flow guide component 123 includes a plurality of drainage needles 123a which are fluidically connected to the plurality of branch flow channels 1252 in a one-to-one correspondence, and the plurality of drainage needles 123a protrude from the lower side of the aforementioned single edge 1208 of the top plate 120 of the chip platform 12 toward the reagent cartridge platform 11, and are spaced apart from each other (for example, spaced apart from each other at a uniform interval) and arranged in a straight line, and each drainage needle 123a is constructed as a hollow needle.
  • the plurality of drainage needle ports 1250 are formed through the convex portion 121b protruding from the edge 1208 of the top plate 120 toward the side of the top plate 120 away from the chip receiving area 121a accommodating the chip 3.
  • the plurality of drainage needles 123a are installed to the plurality of drainage needle ports 1250 in a threaded connection manner and are in one-to-one fluid communication with the plurality of branch flow channels 1252.
  • the plurality of drainage needle ports 1250 are also correspondingly arranged in the same manner as the plurality of drainage needles 123a, specifically, for example, spaced apart from each other (e.g., spaced apart from each other at the same uniform spacing as the drainage needles) and arranged in a straight line at the single edge 1208 of the top plate 120.
  • the plurality of drainage needles 123a are also configured, for example, to puncture the sealing pad covered above the corresponding reagent extraction part of the liquid reservoir 2 (e.g., reagent box) in the storage bin 110 once the storage bin 110 rises to the upper limit position in the reagent box platform 11, thereby achieving that the plurality of drainage needles 123a are respectively connected to the corresponding reagent extraction parts in the liquid reservoir 2 in a one-to-one correspondence.
  • the upper limit position is, for example, the aforementioned drainage position, and in particular, for example, the highest position in the first position range serving as the drainage position.
  • both a secure mechanical connection and direct fluid communication between the drainage needle 123a, which serves as a reagent needle (for aspirating liquid from the reagent cartridge), and the flow path network 125 are achieved in a simple installation manner.
  • the common flow channel 1253 is connected between the fluid outlet 126b and the chip receiving area 121a in a straight line.
  • the plurality of branch flow channels 1252 are arranged so as not to intersect each other and avoid the common flow channel 1253.
  • the flow guide component 123 also includes a plurality of membrane-breaking needles 123b, which protrude outward from the lower side of the edge 1208 of the top plate 120 and are arranged in a straight line spaced apart from each other, and each membrane-breaking needle 123b is constructed as a solid needle.
  • the plurality of drainage needles 123a for example, are arranged parallel to each other with the plurality of membrane-breaking needles 123b.
  • the sides of the plurality of drainage needles 123a are arranged one by one with corresponding membrane-breaking needles 123b, and the membrane-breaking needles 123b are configured to puncture the film for covering the sealing pad on the corresponding reagent extraction part of the reservoir 2 (e.g., the reagent box) in the accommodating bin 110 once the accommodating bin 110 rises to the upper limit position in the reagent box platform 11.
  • each drainage needle 123a is adjacent to the corresponding single membrane-breaking needle 123b in pairs but spaced apart.
  • the guide assembly 123 further includes, for example: at least two guide pins 123c, which protrude outward from the lower side of the edge 1208 of the top plate 120 and are arranged in a straight line spaced apart from each other, and are configured to be in shape matching with the alignment features on the reservoir 2. After the guide pins 123c and the alignment features are aligned with each other, the guide pins 123c are inserted into the alignment features (such as alignment holes or alignment recesses) to achieve the assembly of the reservoir 2 and the guide assembly 123.
  • the alignment features such as alignment holes or alignment recesses
  • the at least two guide pins 123c are two guide pins 123c arranged in line with the plurality of drainage needles 123a and located respectively on the outside of two drainage needles 123a at both ends of the plurality of drainage needles 123a.
  • the flow network 125 further includes an outlet pipeline for discharging waste liquid and a return pipeline for returning the injected reagent, which are respectively connected to the chip receiving area 121a.
  • the flow guiding component 123 and the aforementioned fluid supply device 150 together define a fluid guiding device 160, and the fluid guiding device 160 is configured to guide a plurality of reagent fluids from a fluid reservoir (such as a reagent kit 2) to the sequencing chip 3.
  • Figure 10 illustrates a cross-sectional view along the E-E line of the chip processing device 1 shown in the top view of Figure 2(e), which shows the internal positioning device 111 and the position detector 112 for detecting that the liquid reservoir 2 is inserted into the accommodating chamber 110.
  • the chip processing device 1 shown also includes a positioning device 111, and the positioning device 111 is, for example, arranged in the reagent box platform 11, and includes: a groove 1110, which is recessed in the top inner wall of the accommodating chamber 110; an elastic component, which is arranged in the groove 1110; and a positioning bead 111b, which is arranged at one end of the elastic component facing the substrate, and is configured as follows: in response to the reagent box not reaching the positioning bead in the accommodating chamber, the elastic component is in an initial state where it is not subject to the force applied by the reagent box and the positioning bead at least partially protrudes from the top inner wall of the accommodating chamber toward the substrate; and in response to the liquid reservoir 2 being inserted into the accommodating chamber 110 and squeezing the positioning bead, the elastic component is pushed toward the groove via the positioning bead, and then the elastic component is at least partially retracted into the groove 1110.
  • the positioning device 111 When a liquid reservoir 2 such as a test kit is inserted into the accommodating chamber 110, the liquid reservoir 2 gradually pushes the positioning beads 111b of the elastic component exposed from the groove 1110 into the groove 1110 until the liquid reservoir 2 is inserted into the accommodating chamber 110 and is in place. At this time, the positioning beads 111b are pressed outwardly against the surface of the liquid reservoir 2 by the elastic restoring force of the spring 111a in a compressed state, thereby achieving firm positioning of the liquid reservoir 2 to keep the liquid reservoir 2 in place in the accommodating chamber 110.
  • the reagent box top wall 25 has a protrusion 23 protruding toward the top inner wall of the storage chamber, and a positioning groove 24 recessed from the protrusion 23, and in response to the reagent box being inserted into the storage chamber and squeezing the positioning bead, the positioning bead is clamped between the positioning groove 24 and the elastic component.
  • At least one recess is formed on the surface of the liquid reservoir 2 corresponding to the position of the positioning bead 111b when the liquid reservoir 2 is in place in the storage chamber 110, and the shape and size of the recess are determined to be suitable for receiving the positioning bead 111b, so that when the liquid reservoir 2 is inserted in place, the positioning bead 111b is pushed outward by the elastic restoring force of the compressed spring 111a to cooperate with the recess, thereby locking the liquid reservoir 2 in place in an elastic manner.
  • This elastic locking does not affect the removal of the reagent box from the storage chamber 110 after the sequencing work is completed.
  • the chip processing device 1 further includes a position detector 112 disposed inside the accommodation chamber 110, the position detector 112 includes an optical coupling component and a shielding member, the shielding member is, for example, disposed on the liquid reservoir 2 or connected to the liquid reservoir 2;
  • the optical coupling component includes an infrared transmitter and an infrared receiver, the optical coupling components are, for example, both disposed in the reagent box platform 11 and spaced apart from each other, and configured to respond to the situation that when the liquid reservoir 2 is inserted into the accommodation chamber 110 and in position, the shielding member is displaced or deformed by the force applied by the liquid reservoir 2 and blocks the infrared receiver from receiving infrared rays from the infrared transmitter, thereby determining that the liquid reservoir 2 is in position in the accommodation chamber 110.
  • a shielding member carried by the liquid reservoir 2 it is convenient to realize the event detection of whether the liquid reservoir 2 is in position in the accommodation chamber 110 and to determine that it is in
  • the chip processing device 1 further includes a positioning feature provided on the outer surface of the liquid reservoir 2, and a position sensor provided inside the accommodation chamber 110, wherein the positioning feature is aligned with the position sensor when the liquid reservoir 2 is inserted into the accommodation chamber 110 and is in position, and the position sensor is configured to determine that the liquid reservoir 2 is in position in the accommodation chamber 110 by detecting the pushing action applied by the positioning feature.
  • the position sensor is a force sensor.
  • the chip processing device 1 further includes a clamping device 113 formed at the top of the reagent kit platform 11, the top of the reagent kit platform 11 is formed with a through opening to at least partially expose the liquid reservoir 2 inserted into the accommodating chamber 110, the clamping device 113 includes: a pressing plate 1130, one side of which is relatively fixed to the base plate 10; a pin 1131 extending through the pressing plate 1130 at a free side opposite to the one side; a pair of arms 1132, one end of each arm 1132 being pivotally connected to a corresponding end of the pin 1131; and a pair of elastic members 1133, each elastic member 1133 (e.g., a torsion spring) being elastically connected between a corresponding arm 1132 in the pair of arms 1132 and the reagent kit platform 11.
  • a pressing plate 1130 one side of which is relatively fixed to the base plate 10
  • a pin 1131 extending through the pressing plate 1130 at a free side opposite to the one side
  • a pair of arms 1132 one end
  • the pair of arms 1132 can be triggered to further pivot around the pin 1131 under the action of the elastic force of the pair of connected springs, thereby utilizing the pressure plate 1130 to tightly press the top of the accommodating chamber 110 and the liquid reservoir 2, thereby further pressing the accommodating chamber 110 together with the liquid reservoir 2 downward in a substantially vertical direction.
  • the chip platform 12 includes a fixed bracket 12a, which is supported and fixed between the top plate 120 and the base plate 10, and partially extends between the reagent kit platform and the base plate 10 and leaves a gap between the reagent kit platform 11.
  • the fixed bracket 12a extends from one side edge of the reagent kit platform 11 corresponding to the fixed bracket 12a, and is fixed to the pressure plate 1130, and the reagent kit platform 11 is located between the extension plate 12b and the selector valve.
  • the reagent kit platform 11 includes a movable bracket 11a, and the reagent chamber 110 is suspended and supported by the movable bracket 11a.
  • the movable bracket 11a is fixed to the movable rail 132 and is movably connected to the fixed rail 135 via the movable rail 132.
  • the movable bracket 11a is L-shaped.
  • the chip processing device 1 further includes a first tilt adjustment mechanism 114 disposed between the fixed support 12a and the substrate 10 and located on one side of the reagent reagent platform 11, wherein the first tilt adjustment mechanism 114 includes a first distance head arranged non-linearly and two first thread pairs 1140 capable of being screwed and adjusted relative to the substrate 10.
  • the chip processing device 1 further includes a second tilt adjustment mechanism 124 disposed between the fixed support 12a and the substrate 10 and located on one side of the chip platform 12, wherein the second tilt adjustment mechanism 124 includes a second distance head arranged non-linearly and two second thread pairs 1240 capable of being screwed and adjusted relative to the substrate 10.
  • first distance head and the two adjustable first thread pairs 1140 in the first tilt adjustment structure jointly define a three-point support structure, stable support is achieved once the reagent box platform 11 is leveled by adjusting the first thread pairs 1140; similarly, since the second distance head and the two adjustable second thread pairs 1240 in the second tilt adjustment structure jointly define another three-point support structure, stable support is achieved once the chip platform 12 is leveled by adjusting the second thread pairs 1240.
  • the chip processing device 1 further includes a limit device 14, the limit device 14 including: a sensing sheet 140, arranged on a corresponding movable rail 132 of at least one group of cross-roller guide rails 130 in at least one guide rail assembly 13; and an upper limit optical coupler 141 and a lower limit optical coupler 142, respectively arranged at the two ends of the corresponding fixed rail 131 of the at least one group of cross-roller guide rails 130 at positions corresponding to the upper end and the lower end of the stroke of the corresponding movable rail 132, and respectively configured to stop the driving source in response to detecting that the sensing sheet 140 blocks the upper limit optical coupler 141 to determine that the movable rail 132 rises to the upper limit position, and to stop the driving source in response to detecting that the sensing sheet 140 blocks the lower limit optical coupler 142 to determine that the movable rail 132 drops to the lower limit position
  • the upper limit position and the lower limit position of the accommodating bin 110 can be detected and determined during the lifting and lowering movement of the accommodating bin 110 carrying the liquid reservoir 2 inserted therein within the reagent kit platform 11, and the power supply of the driving source can be cut off once the accommodating bin 110 reaches such an upper limit position or a lower limit position, thereby realizing the limit position detection and limiting in an electrically controlled manner.
  • the limiting device further comprises two limiting blocks respectively arranged at both ends of the fixed rail 131 of at least one set of cross ball guide rails, and each limiting block is at least partially aligned with the corresponding movable rail 132.
  • the limiting blocks realize auxiliary limiting in a mechanical manner.
  • a power component 129 is also provided, wherein the power component 129 is arranged to be fluidically connected to the flow path network and configured to drive the fluid to flow through the flow path network toward the supply port.
  • the power assembly includes a pump connected to the chip receiving area, and the pump is configured to provide negative pressure to the chip receiving area.
  • the pump is a syringe pump disposed at least at one of the upstream and downstream of the selector valve 126, and the syringe pump is configured to provide negative pressure to the chip receiving area 121a.
  • the negative pressure provided by the syringe pump is used to suck the fluid, thereby eliminating the need to insert the drainage needle 123a into the bottom of the reservoir 2 to achieve suction of the fluid (more specifically, the reagent in the reagent kit), thereby providing aspiration and liquid supply for the fluid to be transported from the reagent kit to the sequencing chip 3.
  • FIG11 shows the assembly relationship of the temperature control assembly relative to the carrier via the adapter bracket in an exploded view.
  • FIG12(a) shows a cross-sectional view along line A-A as in FIG9(f)
  • FIG12(b) shows a cross-sectional view along line B-B as in FIG9(f)
  • FIG13(b) to FIG13(c) respectively show cross-sectional views along lines C-C and D-D as in FIG9(f), and particularly show the assembly relationship between the selector valve and the top plate connected by screws S1.
  • the fluid guiding device 160 is additionally integrated with a temperature control component 128, which is disposed on a side of the top plate opposite to the chip receiving area and configured to adjust the temperature of the fluid supplied from the flow guiding component to the chip receiving area.
  • the temperature control component 128 is arranged below the top plate 120 (more specifically, on the opposite side surface of the chip receiving area 121a for receiving the chip 3), and is configured to adjust the temperature of the fluid supplied from the flow guide component 123 to the chip receiving area 121a.
  • the temperature control assembly 128 includes a first temperature regulating device 128a, which is arranged to be adjacent to the selector valve on the same side of the top plate.
  • the fluid guiding device also includes an adapter bracket 127 fixed to the top plate at a side opposite to the chip receiving area, which is constructed in the form of a frame, and the adapter bracket 127 is formed with two recesses 1270, 1271 arranged in parallel and recessed from the opposite sides of the adapter bracket 127 away from the top plate and toward the top plate respectively, so as to accommodate and fix the selector valve and the first temperature regulating device therein, respectively.
  • This arrangement further ensures that the selector valve is reliably fixed relative to the carrier, and also realizes an assembly relationship in which the first temperature regulating device is fixed relative to the carrier 120 via the adapter bracket 127 .
  • the first temperature regulating device 128a includes: a heat sink, which is accommodated and installed in one of the two recesses 1270, 1271 of the adapter bracket 127 and is recessed from the side facing the top plate, and includes at least one of an active heat sink and a passive heat sink; and a temperature control module 1282, which is installed to the heat sink and is configured to cut off the power component 129 when the temperature at the heat sink exceeds a threshold temperature.
  • the temperature control assembly further includes a heat conducting member 128b (also shown as being built inside the adapter bracket 127) inserted between the carrier and the first temperature regulating device.
  • the heat conducting member 128b includes a phase change material.
  • the active heat sink includes a thermoelectric cooler (e.g., a thermoelectric cooler (TEC) such as a Peltier effect device, a fan, etc.); or the passive heat sink includes a heat sink, such as a fin heat sink, formed as a single heat sink or a heat sink array.
  • TEC thermoelectric cooler
  • the passive heat sink includes a heat sink, such as a fin heat sink, formed as a single heat sink or a heat sink array.
  • the temperature control assembly 128 also includes a second temperature regulating device 128c, which is fixed to a side of the adapter bracket 127 away from the top plate and is arranged in parallel with the rotary valve and arranged to be aligned with the first temperature regulating device.
  • the second temperature regulating device includes a fan 1280.
  • the fan 1280 includes: a hollow first shell 1281, the interior of which defines a cavity for airflow, the first shell 1281 is arranged so that the cavity is aligned with the first temperature regulating device and is open toward the first temperature regulating device, so that the cavity fluid is connected between the first temperature regulating device and the outside of the fluid guiding device; and a fan assembly, which is accommodated in the first shell 1281.
  • the fan assembly includes: a second shell 1283, which is constructed to be a hollow cylindrical body fixedly mounted in the first shell 1281; a rotating shaft 1284, which is rotatably installed in the second shell 1283; and a plurality of fan blades 1285, which are coaxially fixed to the rotating shaft 1284 in the second shell 1283 and can rotate relative to the second shell 1283 with the rotating shaft 1284.
  • the adapter bracket 127 is also formed with a gas channel 1286 that runs through the interior thereof and is open at opposite ends toward the cavities of the first temperature regulating device and the second temperature regulating device respectively, and the cavity is connected to the first temperature regulating device via the gas channel 1286.
  • the fan is located on the side of the heat sink of the first temperature regulating device away from the carrier 120, which facilitates the acceleration of airflow exchange, thereby improving the heat exchange speed and efficiency of the heat sink.
  • the temperature control module 1282 is a temperature control switch, and the temperature control switch 1282 is configured to cut off the power supply of the power component 129 when the temperature at the heat sink exceeds a threshold temperature.
  • the second temperature adjustment device 128c further includes a vibration reduction device, and the vibration reduction device includes: a gasket located between the adapter bracket 127 and the first housing 1281 of the fan 1280; and
  • the second-stage vibration-damping structure is arranged in the first shell 1281 of the fan 1280 and between the first shell 1281 and the second shell 1283 of the fan assembly, and includes a plurality of vibration-damping members that are respectively snapped into the inner wall of the first shell 1281 and are spaced apart from each other.
  • the second shell 1283 of the fan assembly is connected to the first shell 1281 via the plurality of vibration-damping members.
  • the first shell of the fan is fixed to the adapter bracket via a flexible vibration-absorbing material screw member 1281a, the first shell 1281 is protrudingly formed with an ear 1281b for installing the screw member 1281a, and the first-stage vibration reduction structure is pushed tightly between the adapter bracket 127 and the first shell 1281 via the screw member 1281a.
  • At least one of the first-stage vibration reduction structure 128d and the second-stage vibration reduction structure 128e is a vibration compensation device, and the vibration compensation device is an elastic member or a damping member.
  • the first shell 1281 of the fan 1280 is fixed to the adapter bracket 127 via a flexible vibration-absorbing material screw, for example, and the first-stage vibration reduction structure is pushed tightly between the adapter bracket 127 and the first shell 1281 via the screw.
  • a vibration reduction structure in a sandwich arrangement (for example, the two-stage vibration reduction structure shown in the figure and arranged separately from each other) is further adopted, and the second temperature regulating device 128c is inserted between the first-stage vibration reduction structure 128d and the second-stage vibration reduction structure 128e, thereby realizing a sandwich-type multi-stage vibration reduction structure, which can effectively offset, or at least partially dissipate and block the vibration caused by, for example, the fan 128c for providing forced air cooling, and avoid the vibration from the temperature control component 128, especially the aforementioned second temperature regulating device 128c including the fan 128c, to other parts of, for example, the fluid guiding device 160 (such as but not limited to the branch flow channel 1252 and the common flow channel 1253 of the flow network 125, and the selector valve 126).
  • the fluid guiding device 160 such as but not limited to the branch flow channel 1252 and the common flow channel 1253 of the flow network 125, and the selector valve 126.
  • the selector valve 126 is fixed to the carrier at its valve seat 1261 via a threaded connection, and the selector valve is connected to the adapter bracket 127 via an adjustable pressing device 161, and the adjustable pressing device 161 includes: a plurality of fixed-distance screws 1611, which respectively penetrate the adapter bracket 127 in a screwable manner and press the valve body 1262 of the selector valve; and a plurality of springs 1612, which elastically press the plurality of fixed-distance screws toward the top plate in a one-to-one corresponding manner.
  • the selector valve 126 is supported to the carrier 120 in a manner similar to suspension and floating, and the spring 1612 forms a structure similar to an elastic suspension, which works in combination with the distance screw 1611 to support the selector valve 126, and the spring 1612 in the adjustable pressure device 161 also plays an auxiliary role in filtering vibrations from vibration sources directly or indirectly connected to it (such as fans 128c and active heat sinks).
  • FIG14 schematically illustrates a gene sequencer 4 according to an embodiment of the present disclosure, which includes: a chip carrying a sample to be detected using a fluid; and the aforementioned chip processing device.
  • a gene sequencer 4 is provided, wherein the chip processing device comprises a substrate extending in a first direction, and a reagent kit platform and a chip platform assembled on the substrate side by side and adjacently in a second direction transverse to the first direction, the top plate of the chip platform at the side away from the substrate is provided with a chip receiving area for accommodating the chip, the reagent kit platform is formed with a hollow accommodating chamber, the reagent kit is received in the accommodating chamber, and the inside is at least partially filled with the fluid.
  • the reagent kit has a first fluid transport structure located at one side of the reagent kit facing the chip platform along the second direction
  • the chip platform has a second fluid transport structure located at one side of the chip platform facing the reagent kit platform along the second direction and configured to overlap and communicate with the first fluid transport structure at least partially when the reagent kit platform and the chip platform are assembled
  • the reagent kit is inserted into the accommodating chamber in a removable manner, and the fluid in the reagent kit is fluidly connected to the sample carried on the chip via the first fluid transport structure and the second fluid transport structure.
  • the accommodating bin is connected to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position lower than the drainage position, and the drainage position and the non-drainage position are distributed corresponding to a state in which the first fluid transporting structure and the second fluid transporting structure are fluidically connected, and a state in which they are not fluidly connected; and the chip processing device is configured to: in response to the accommodating bin rising away from the substrate to the drainage position, connect the first fluid transporting structure and the second fluid transporting structure to each other to be fluidically connected; and in response to the accommodating bin descending toward the substrate to the non-drainage position, separate the first fluid transporting structure and the second fluid transporting structure from each other.
  • the top plate of the chip platform at a side away from the substrate has a flange protruding toward the reagent kit platform along the second direction, and the reagent kit platform is partially embedded and assembled between the flange of the top plate and the substrate.
  • the first fluid transport structure includes a plurality of reagent grooves 20a and a plurality of guide grooves 20b arranged in a one-to-one correspondence in the reagent kit, and a connecting channel 20c that fluidly connects the bottom of each guide groove 20b with the bottom of the corresponding reagent groove 20a
  • each reagent groove 20a is at least partially filled with fluid and has a first opening 21 that opens upward toward the flange, and a first pierceable structure 210 covering the first opening 21, and each guide groove 20b has a second opening 22 that opens upward toward the flange, and a second pierceable structure 220 covering the second opening 22.
  • the second fluid transport structure includes a fluid supply device, which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed to the top plate and in fluid communication with the flow path network.
  • a fluid supply device which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed to the top plate and in fluid communication with the flow path network.
  • the selector valve includes: a valve seat 1261, and the selector valve is fixed to the top plate via the valve seat 1261; a valve body 1262, which extends from the valve seat 1261 in a direction away from the top plate and is formed with a fluid inlet 126a configured to guide the fluid to flow into the interior of the valve body 1262 and a fluid outlet 126b configured to guide the fluid to flow outward from the interior of the valve body 1262.
  • the flow path network includes: a plurality of drainage needle ports, located on the side of the top plate opposite to the chip receiving area; a plurality of inlet ports, arranged to be spaced apart from the plurality of drainage needle ports in a one-to-one correspondence; a plurality of branch flow channels, each branch flow channel is connected between each drainage needle port and a corresponding inlet port, and is configured to guide the fluid input from each drainage needle port to the corresponding inlet port; an outlet port, arranged to be spaced apart from the plurality of inlet ports and not connected to the plurality of branch flow channels; and a common flow channel, connected between the outlet port and the chip receiving area, and configured to guide the fluid output from the outlet port to the chip receiving area.
  • the selector valve is arranged so that the fluid outlet 126b is in fluid communication with the outlet port, and the fluid inlet 126a is in fluid communication with at least one of the plurality of inlet ports, and is configured to switch the selective communication between at least one of the plurality of inlet ports corresponding to the plurality of branch flow channels and the outlet port via the fluid inlet 126a and the fluid outlet 126b.
  • the plurality of drainage needle ports are formed through-through in a convex portion at an edge of the top plate, protruding toward a side of the top plate that is away from the chip receiving area.
  • the second fluid delivery structure also includes a guide component protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the guide component including: a plurality of membrane rupture needles and a plurality of drainage needles, respectively protruding from the side of the top plate opposite to the chip receiving area toward the reagent kit platform, each membrane rupture needle having a first end aligned with the corresponding first pierceable structure 210, and each drainage needle having a second end aligned with the corresponding second pierceable structure 220.
  • each membrane rupturing needle is not connected to the flow path network, and is configured to pierce the first pierceable structure 210 with its first end in response to the accommodating chamber reaching the drainage position, and then insert into the reagent tank 20a to expose the reagent tank 20a to change the air pressure in the reagent tank 20a; and each drainage needle is constructed as a hollow needle, and is fluidically connected to the corresponding branch flow channels in the multiple branch flow channels in a one-to-one correspondence, and is configured to pierce the second pierceable structure 220 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove 20b to be fluidically connected to the guide groove 20b to draw the fluid in the guide groove 20b.
  • the free end of each of the plurality of drainage needles is higher than the inner wall at the bottom of the reagent tank 20 a .
  • each guide groove 20b is configured as a groove having a circular cross section with a first inner diameter
  • each guide groove 20b is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter
  • the first pierceable structure is a metal foil; and the second pierceable structure is a flexible seal such that a liquid-tight seal is maintained after being pierced by a corresponding drainage needle of the plurality of drainage needles.
  • the gene sequencer 4 includes the aforementioned chip processing device 1, it also correspondingly possesses all the advantages of the chip processing device 1, which will not be elaborated here.
  • FIG. 15 illustrates a gene sequencing device 5 according to an embodiment of the present disclosure, comprising a pair of the aforementioned gene sequencers 4 that are mirror-symmetrical and arranged adjacent to each other.
  • a gene sequencing device 5 comprising: a chip, the chip carrying a sample to be detected by fluid; and at least two aforementioned chip processing devices, each chip processing device comprising a substrate extending along a first direction, and a reagent kit platform and a chip platform assembled on the substrate side by side and adjacently along a second direction transverse to the first direction, the top plate of the chip platform on the side away from the substrate is provided with a chip receiving area for accommodating the chip, the reagent kit platform is formed with a hollow accommodating chamber, the reagent kit is received in the accommodating chamber, and the interior is at least partially filled with the fluid.
  • the reagent kit has a first fluid transport structure located at one side of the reagent kit facing the chip platform along the second direction
  • the chip platform has a second fluid transport structure located at one side of the chip platform facing the reagent kit platform along the second direction, and is configured to at least partially overlap and communicate with the first fluid transport structure when the reagent kit platform and the chip platform are assembled.
  • the reagent box is inserted into the storage compartment in a removable manner, and the fluid in the reagent box is fluidly connected to the sample carried on the chip via the first fluid delivery structure and the second fluid delivery structure.
  • the at least two chip processing devices are symmetrically arranged with their respective chip platforms arranged adjacent to each other.
  • the at least two chip processing devices include at least one pair of chip processing devices which are arranged in a mirror-symmetrical manner to each other and whose respective chip platforms are arranged adjacent to each other.
  • the accommodating chamber is connected to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position lower than the drainage position, and the drainage position and the non-drainage position are distributed corresponding to a state in which the first fluid transport structure and the second fluid transport structure are in fluid communication and a state in which they are not in fluid communication.
  • the chip processing device is configured to: in response to the accommodating chamber rising away from the substrate to the drainage position, the first fluid transport structure and the second fluid transport structure are connected to each other in fluid communication; and in response to the accommodating chamber descending toward the substrate to the non-drainage position, the first fluid transport structure and the second fluid transport structure are separated from each other.
  • the top plate of the chip platform at a side away from the substrate has a flange protruding toward the reagent kit platform along the second direction, and the reagent kit platform is partially embedded and assembled between the flange of the top plate and the substrate.
  • the first fluid transport structure includes a plurality of reagent grooves 20a and a plurality of guide grooves 20b arranged in a one-to-one correspondence in the reagent kit, and a connecting channel 20c that fluidly connects the bottom of each guide groove 20b with the bottom of the corresponding reagent groove 20a
  • each reagent groove 20a is at least partially filled with fluid and has a first opening 21 that opens upward toward the flange, and a first pierceable structure 210 covering the first opening 21, and each guide groove 20b has a second opening 22 that opens upward toward the flange, and a second pierceable structure 220 covering the second opening 22.
  • the second fluid transport structure includes a fluid supply device, which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed to the top plate and in fluid communication with the flow path network.
  • a fluid supply device which includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid transport structure and the chip, and a selector valve installed to the top plate and in fluid communication with the flow path network.
  • the selector valve includes: a valve seat 1261, and the selector valve is fixed to the top plate via the valve seat 1261; a valve body 1262, which extends from the valve seat 1261 in a direction away from the top plate and is formed with a fluid inlet 126a configured to guide the fluid to flow into the interior of the valve body 1262 and a fluid outlet 126b configured to guide the fluid to flow outward from the interior of the valve body 1262.
  • the flow path network includes: a plurality of drainage needle ports, located on the side of the top plate opposite to the chip receiving area; a plurality of inlet ports, arranged to be spaced apart from the plurality of drainage needle ports in a one-to-one correspondence; a plurality of branch flow channels, each branch flow channel is connected between each drainage needle port and a corresponding inlet port, and is configured to guide the fluid input from each drainage needle port to the corresponding inlet port; an outlet port, arranged to be spaced apart from the plurality of inlet ports and not connected to the plurality of branch flow channels; and a common flow channel, connected between the outlet port and the chip receiving area, and configured to guide the fluid output from the outlet port to the chip receiving area.
  • the selector valve is arranged so that the fluid outlet 126b is in fluid communication with the outlet port, and the fluid inlet 126a is in fluid communication with at least one of the plurality of inlet ports, and is configured to switch the selective communication between at least one of the plurality of inlet ports corresponding to the plurality of branch flow channels and the outlet port via the fluid inlet 126a and the fluid outlet 126b.
  • the plurality of drainage needle ports are formed through-through in a convex portion at an edge of the top plate, protruding toward a side of the top plate that is away from the chip receiving area.
  • the second fluid delivery structure further includes a flow guide component protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide component including: a plurality of membrane puncturing needles and a plurality of drainage needles, respectively protruding from the side of the top plate opposite to the chip receiving area toward the reagent kit platform, each membrane puncturing needle having a first end aligned with a corresponding first pierceable structure 210, and each drainage needle having a second end aligned with a corresponding second pierceable structure 220.
  • each membrane puncturing needle is not connected to the flow path network, and is configured to pierce the first pierceable structure 210 with its first end in response to the accommodating chamber reaching the drainage position, and then insert into the reagent tank 20a to expose the reagent tank 20a to change the air pressure in the reagent tank 20a.
  • each drainage needle is constructed as a hollow needle and is fluidically connected to the corresponding branch flow channels among the multiple branch flow channels in a one-to-one correspondence, and is configured to pierce the second pierceable structure 220 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove 20b to be fluidically connected to the guide groove 20b to draw the fluid in the guide groove 20b.
  • the free end of each of the plurality of drainage needles is higher than the inner wall at the bottom of the reagent tank 20 a .
  • each guide groove 20b is configured as a groove having a circular cross section with a first inner diameter
  • each guide groove 20b is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter
  • the first pierceable structure is a metal foil; and the second pierceable structure is a flexible seal such that a liquid-tight seal is maintained after being pierced by a corresponding drainage needle of the plurality of drainage needles.
  • the gene sequencing device 5 includes the aforementioned chip processing device 1 and the aforementioned gene sequencer 4, and thus has all the advantages of the aforementioned chip processing device 1, which will not be described in detail here.
  • the two aforementioned gene sequencers 4 that are mirror images of each other, it is possible to simultaneously load two chips 3 with the distance between them minimized, greatly reducing the moving distance of the switching chip 3, and correspondingly shortening the test time interval.
  • Fig. 16 is a schematic flowchart of a biochemical detection method according to an embodiment of the present disclosure using the gene sequencer 4 shown in Fig. 14.
  • Fig. 17 schematically shows more specific steps in the method as shown in the flowchart of Fig. 16 .
  • a biochemical detection method using the aforementioned gene sequencer 4 is also provided.
  • the gene sequencer includes: a chip, the chip carries a sample to be detected by fluid; and a chip processing device, the chip processing device includes a substrate extending along a first direction, and a reagent kit platform and a chip platform assembled on the substrate side by side and adjacently along a second direction transverse to the first direction, the top plate of the chip platform on the side away from the substrate is provided with a chip receiving area for accommodating the chip, and the reagent kit platform is formed with a hollow accommodating chamber, the reagent kit is received in the accommodating chamber, and the interior is at least partially filled with the fluid.
  • the reagent kit has a first fluid transport structure located at one side of the reagent kit along the second direction toward the chip platform, and the chip platform has a second fluid transport structure located at one side of the chip platform along the second direction toward the reagent kit platform and is configured to overlap and communicate with the first fluid transport structure at least partially when the reagent kit platform and the chip platform are assembled.
  • the reagent kit is removably inserted into the containing chamber, and the fluid in the reagent kit is fluidically connected to the sample carried on the chip via the first fluid transport structure and the second fluid transport structure.
  • the biochemical detection method includes: S1: establishing a fluid connection between a chip having a sample to be detected and a reagent box having a plurality of different reaction components, wherein the reaction components include at least one of a sample generation component or a sample analysis component. S2: performing a generation operation and/or an analysis operation.
  • the reagent box and the chip are integrated into the chip processing device described in the above embodiment, and the fluid in the reagent box is fluidly connected to the chip via a first fluid transport structure and a second fluid transport structure separated from each other in the chip processing device.
  • a sample to be detected is generated on the chip, and the generation operation includes flowing different sample generation components into the chip and controlling the reaction conditions of the chip to generate the sample.
  • the sample on the chip is analyzed, and the analysis operation includes flowing sample analysis components into the chip, and the sample analysis components react with the sample to provide a relevant detectable signal.
  • the biochemical reaction can be a nucleic acid sequencing reaction or an antigen-antibody binding reaction
  • the sample to be detected can be a nucleic acid sequencing library or a biological tissue slice
  • the detectable signal is preferably an optical signal.
  • the first fluid delivery structure is connected to the external air pressure of the chip processing device to drive the fluid in the reagent box to flow into the second flow delivery structure; and selectively connect the chip with the fluid.
  • the second flow delivery structure has the above-mentioned multiple branch flow channels, and the above-mentioned selector valve 126 integrated in the chip processing device is used to control the selective connection between different multiple branch flow channels and the chip.
  • establishing a fluid connection between the chip and the reagent kit in step S1 includes: inserting the reagent kit (having a similar structure to the liquid reservoir 2 described in the above embodiment) into the receiving chamber 110 through the open opening of the receiving chamber 110, and using the aforementioned in-position detector 112 arranged inside the receiving chamber 110 to detect whether the reagent kit is in place in the receiving chamber 110, and using the positioning bead 111b of the aforementioned positioning device 111 in the receiving chamber 110 to tightly press the reagent kit under the elastic pushing action of the spring 111a to keep the reagent kit in place.
  • the storage bin is moved in the chip processing device through a movable bracket (equivalent to the above-mentioned movable bracket 11a), and is connected to the substrate in a manner that can be linearly moved within a range between the highest drainage position and the non-drainage position below the drainage position, and the drainage position and the non-drainage position correspond to the state of fluid communication between the first fluid delivery structure and the second fluid delivery structure, and the state of no fluid communication.
  • a movable bracket equivalent to the above-mentioned movable bracket 11a
  • the chip processing device is configured to: in response to the storage bin rising away from the substrate to the drainage position, the first fluid delivery structure and the second fluid delivery structure are connected to each other to form fluid communication; and in response to the storage bin descending toward the substrate to the non-drainage position, the first fluid delivery structure and the second fluid delivery structure are separated from each other.
  • the method also includes: after the reagent kit is inserted into the storage bin and placed in place, the storage bin is raised to the drainage position, thereby triggering the subsequent fluid communication of the reagent kit to the carrier supporting the chip (having a similar structure to the top plate 120 in the above-mentioned embodiment).
  • the top plate at the side of the chip platform away from the substrate has a flange protruding toward the reagent kit platform along the second direction, and the reagent kit platform is partially embedded and assembled between the flange of the top plate and the substrate.
  • the first fluid delivery structure includes a plurality of reagent tanks 20a and a plurality of guide grooves 20b arranged in a one-to-one correspondence in the reagent kit, and a connecting channel 20c that is fluidly connected between the bottom of each guide groove 20b and the bottom of the corresponding reagent tank 20a, each reagent tank 20a is at least partially filled with fluid and has a first opening 21 that opens upward toward the flange, and a first pierceable structure 210 covering the first opening 21, and each guide groove 20b has a second opening 22 that opens upward toward the flange, and a second pierceable structure 220 covering the second opening 22.
  • the second fluid delivery structure includes a flow guide component, which includes: a plurality of membrane puncturing needles and a plurality of drainage needles, which protrude from the side of the top plate opposite to the chip receiving area toward the reagent reagent platform, respectively, each membrane puncturing needle has a first end aligned with the corresponding first pierceable structure 210, and each drainage needle has a second end aligned with the corresponding second pierceable structure 220, each membrane puncturing needle is configured to pierce the first pierceable structure 210 with its first end in response to the accommodating chamber reaching the drainage position, and then insert into the reagent tank 20a to expose the reagent tank 20a to change the air pressure in the reagent tank 20a, and each drainage needle is constructed as a hollow needle and is selectively fluidically connected to the sample carried on the chip, and is configured to pierce the second pierceable structure 220 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove 20
  • the method further includes lowering and returning the accommodating chamber 110. Specifically, after raising the accommodating chamber to the drainage position, the fluid connection between the first fluid delivery structure and the second fluid delivery structure is established by driving the corresponding first end of each membrane rupture needle to pierce the first pierceable structure 210, and driving the corresponding second end of each drainage needle to pierce the second pierceable structure 220; and after lowering and resetting the accommodating chamber from the drainage position to the non-drainage position, the fluid connection between the first fluid delivery structure and the second fluid delivery structure is cut off by driving the corresponding first end of each membrane rupture needle to detach from the first pierceable structure 210, and driving the corresponding second end of each drainage needle to detach from the second pierceable structure 220.
  • step S1 further includes respectively raising and adjusting the adjustable threaded pairs of the aforementioned first tilt adjustment mechanism 114 and the aforementioned second tilt adjustment mechanism 124 to level the reagent kit platform 11 and the chip platform 12.
  • the reagent kit platform 11 is leveled and stably supported by adjusting the three-point support structure defined by the first distance head and the two adjustable first threaded pairs 1140 in the first tilt adjustment structure
  • the chip platform 12 is leveled and stably supported by adjusting the other three-point support structure defined by the second distance head and the two adjustable second threaded pairs 1240 in the second tilt adjustment structure.
  • step S1 also includes utilizing the aforementioned clamping device 113 formed at the top of the reagent reagent platform 11, by slightly pushing one of the pair of arms 1132 around the pin 1131, thereby triggering the pair of arms 1132 to further pivot around the pin 1131 under the elastic force of the connected pair of springs 111a, thereby achieving the use of the pressure plate 1130 to tightly press the top of the accommodating bin 110 and the liquid reservoir 2, thereby further achieving the accommodating bin 110 together with the liquid reservoir 2 being pressed downward in a substantially vertical direction.
  • step S1 also includes: the aforementioned driving source drives the accommodating bin 110 to perform an upward movement from an initial lower position via the guidance of each group of cross roller guide rails 130 in the at least one guide rail assembly 13 .
  • step S1 further includes: the aforementioned limiting device 14 stops the driving source in response to the accommodating bin 110 rising to the upper limit position.
  • step S1 also includes: utilizing the guide needle in the aforementioned guide assembly 123 to puncture into the fluid reservoir 2, and then utilizing the aforementioned selector valve 126 (e.g., a rotary valve) to switch to fluid connection with the desired branch flow channel 1252, thereby allowing the desired branch flow channel 1252 leading to the fluid reservoir 2 (e.g., a test kit) to flow through the single common flow channel 1253 via the selector valve 126 to be fluidically connected to the sequencing chip 3.
  • the aforementioned selector valve 126 e.g., a rotary valve
  • step S1 also includes: placing the chip 3 (for example, a gene sequencing chip 3) in a chip receiving area 121a formed on a carrier (top plate 120) of the chip platform 12 of the chip processing device 1, and holding the chip 3 in place in the chip receiving area 121a, for example, via pressure at the side walls of the chip receiving area 121a and adsorption at the bottom of the chip receiving area 121a (for example, achieved by an adsorption force generated by an adsorption device, such as a negative air pressure adsorption device or a magnetic adsorption device).
  • an adsorption device such as a negative air pressure adsorption device or a magnetic adsorption device.
  • step S1 includes: contacting the reagent with the sample and performing the above-mentioned analysis and/or generation operations by introducing the reagent fluid from the selector valve 126 and the single common flow channel 1253 into the chip receiving area 121a accommodating the chip 3.
  • the method further includes “removing the chip 3 from the chip handling device 1 ”, for example, taking out the chip 3 from the chip handling device 1 by disabling/canceling the adsorption force and then removing the chip 3 from the chip receiving area 121 a .
  • the method further includes: the aforementioned driving source drives the accommodating bin 110 to perform a descending movement through the guidance of each group of cross roller guide rails 130 in the at least one guide rail assembly 13 until it is reset to an initial lower position.
  • the liquid reservoir 2 is released from the accommodation bin 110 , for example, by first pivoting the pressing device 113 in the opposite direction, and then the liquid reservoir 2 is moved out from the open opening of the accommodation bin 110 .
  • the method of applying the aforementioned gene sequencer 4 adopts the aforementioned chip processing device 1 and the aforementioned gene sequencer 4, thereby having all the advantages of the aforementioned chip processing device 1, which will not be repeated here.
  • the chip processing device, gene sequencer, gene sequencing equipment, and method using the gene sequencer disclosed in the embodiments of the present disclosure have the following superior technical effects compared with the related art in the field:
  • the chip processing device, gene sequencer, gene sequencing equipment and biochemical detection method implemented by the embodiments of the present disclosure can realize an integrated pipeline-free fluid delivery structure through the above settings, which has a reduced flow path length, a more reliable leveling and tightening effect on the test kit, and a higher positioning accuracy.
  • the setting of aspirating from the top of the test kit combined with the use of a syringe pump is adopted, which avoids long-stroke translation and lifting movements and also avoids the need to insert the reagent needle into the bottom of the test kit as in conventional operations.
  • the fixation, positioning, stroke, etc. of the fluid delivery structure can be improved while improving the integration and thus the space utilization, and the design expectations can be achieved with a more compact structure.
  • this compact structure minimizes space occupancy, and the simple structure and connection relationship facilitate assembly and disassembly.

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Abstract

一种集成有试剂盒的芯片处理装置、基因测序仪、基因测序设备、以及进行生化检测的方法,该芯片处理装置包括沿第一方向延伸的基板、和沿横向于该第一方向的第二方向并排且毗邻地组装于该基板上的试剂盒平台和芯片平台,该芯片平台具备用于容置芯片的芯片接纳区,该试剂盒平台形成有容置仓,该试剂盒接纳于容置仓;该试剂盒具有第一流体输送结构,且该芯片平台中具有位于该芯片平台的与该第一流体输送结构至少部分地交叠且连通的第二流体输送结构;该第一流体输送结构经由该第二流体输送结构流体连通至该芯片。

Description

芯片处理装置、基因测序仪和进行生化检测的方法 技术领域
本公开涉及测序技术领域,具体涉及一种集成有试剂盒的芯片处理装置、一种基因测序仪、一种基因测序设备、以及一种进行生化检测的方法。
背景技术
在现有的用于将试剂引入至芯片以进行生化反应或用于光学拍摄成像的芯片平台中,例如在基因测序仪中,通常利用管道接头将试剂引导至芯以供进行生化反应或光学拍照,并且试剂盒及其试剂针独立于芯片平台之外,通过管道接头连接;现有的阀组件通常独立于芯片的安装平台之外,通过管道接头连接;且各个功能模块之间的流路连接产生很多管道,且现有的芯片的安装平台和试剂盒平台是两个彼此独立的平台,并非集成一体的装配件或组合。在基因测序过程中,每一个循环都需要进行生化反应。通常生化反应所需的试剂由设置在试剂盒上的试剂针所提供。具体是利用注射泵和诸如旋转阀这样的选择器阀将试剂从对应的试剂针泵入到芯片内从而进行生化反应。
并且,通常在所述芯片平台以外离散地设置单独的试剂盒、试剂针、和选择器阀,这种各种零部件的分立设置导致较低的集成度和空间利用率,并且相应导致流道布置复杂且流道长度难以缩小。并且具体地,试剂盒通常起到容置和供应不同试剂的作用,试剂针起到插入所述试剂盒且从所述试剂盒导出不同试剂的作用,而选择器阀通常充当流路布置中的关键零部件,起到控制不同的试剂和清洗液的流体通路的功能。通过选择器阀切换不同的流体通路,接通试剂盒与芯片之间的流路,从而选择性实现试剂以及清洗液的进出。这样的具备较多离散零部件的常规布置通常需要众多管道接头和歧管流路,需要在有限的安装空间内合理设计歧管流路的布置以实现避免彼此交叉且最小化相互走线干扰,并且也需要在设计时考虑到实现在所述选择器阀处的多条歧管流路的出口与阀端口之间的对接、切换和密封。并且,现有的离散零部件设计需要在有限的空间内实现较大的试剂盒行程和较长的流体路径,即由此需要较大行程的水平移位和升降以实现从试剂针到测序芯片的流体诸如试剂的输送。并且需要和在不同流体路径之间的切换以及在各次切换之间对于残留流体的清洗,以及对于试剂盒和芯片的牢固固定和精细调平、以及试剂盒的精确定位,这些要求相互之间存在冲突。
发明内容
为了解决现有技术中存在的上述问题和缺陷的至少一个方面,本公开的目的在于提供一种集成有试剂盒的芯片处理装置、一种基因测序仪、一种基因测序设备、以及一种应用基因测序仪的方法。
为了实现上述目的,本公开的技术方案通过以下方式来实现:
根据本公开的第一方面,提供一种集成有试剂盒的芯片处理装置,包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置载有待利用流体检测的样品的芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内;所述试剂盒平台具有位于其内部的沿所述第二方向朝向所述芯片平台的一侧处的第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构,所述第一流体输送结构经由所述第二流体输送结构流体连通至所述芯片。
在根据本公开的实施例中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及所述芯片处理装置配置成:响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
在根据本公开的实施例中,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入地装配于所述顶板的向外伸出的凸缘与所述基板之间。
在根据本公开的实施例中,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽和多个引导槽,以及流体连通于每个引导槽的底部与相应试剂槽的底部之间的连通通道,每个试剂槽中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口、和覆盖于所述第一开口上的第一可刺穿结构,且每个引导槽具备向上朝向所述凸缘敞开的第二开口、和覆盖于所述第二开口上的第二可刺穿结 构。
在根据本公开的实施例中,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和选择器阀,安装至所述顶板且与所述流路网路成流体连通。
在根据本公开的实施例中,所述选择器阀包括:阀座,所述选择器阀经由所述阀座固定至所述顶板;阀体,从所述阀座沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体内部的流体入口和被配置成引导流体从所述阀体内部向外流动的流体出口。并且,所述流路网络包括:多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区。所述选择器阀布置成使得所述流体出口与所述出口端口成流体连通,且所述流体入口与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的选择性连通。
在根据本公开的实施例中,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
在根据本公开的实施例中,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构对准的第一末端、且每个引流针具有与相应第二可刺穿结构对准的第二末端。每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构、继而插入所述试剂槽以暴露所述试剂槽来改变所述试剂槽内的气压。以及每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构、继而插入所述引导槽以流体连通至所述引导槽来汲取所 述引导槽中的流体。
在根据本公开的实施例中,在所述多个引流针插入所述引导槽的情况下,所述多个引流针各自的自由端高于所述试剂槽的底部处的内壁。
在根据本公开的实施例中,每个引导槽被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
在根据本公开的实施例中,所述第一可刺破结构是金属箔;以及所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
在根据本公开的实施例中,所述多个引流针彼此间隔开地呈直线布置,且所述多个破膜针彼此间隔开地呈直线布置;以及所述多个引流针与所述多个破膜针两者彼此平行布置。
在根据本公开的实施例中,所述多个引流针中每个的旁侧一一对应地布置有相应破膜针,且每个引流针与相应的单个破膜针成对地毗邻但间隔开设置。
在根据本公开的实施例中,每个引流针包括中空且伸长的空心直管状针主体、和具备锥形渐缩的纵向截面形状的贯通的顶端。
在根据本公开的实施例中,所述多个引流针以螺纹连接方式安装至所述多个引流针端口。
在根据本公开的实施例中,所述导流组件还包括:至少两个导向销,从所述顶板的与所述芯片接纳区相反的一侧向外突伸且彼此间隔开地呈直线布置,且被构造成与所述试剂盒上的对准特征呈形状配合。
在根据本公开的实施例中,所述多个引流针端口布置呈直线地彼此对准。
在根据本公开的实施例中,所述多个引流针端口布置成以均一的间距彼此分离。
在根据本公开的实施例中,所述选择器阀是旋转阀,且所述旋转阀被配置成能够围绕其轴线旋转以使得切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的的选择性连通。
在根据本公开的实施例中,所述入口端口和所述出口端口各自的轴向平行于所述轴线,且所述入口端口设置成与所述轴线偏离,且所述出口端口与所述轴线同轴设置。
在根据本公开的实施例中,所述选择器阀经由所述阀座而被安装至所述顶板的与所述芯片接纳区背离的背侧面,以及其中,所述多个入口端口被构造成绕所述轴线呈环形布置,所述多个入口端口和所述出口端口均向所述顶板的所述背侧面敞开,且所述多个入口端口中的至少一个选择性连通至所述阀体的所述流体入口、所述出口端口 连通至所述阀体的所述流体出口,且所述多个入口端口中的每个与所述出口端口之间的中心距是相等的。
在根据本公开的实施例中,所述多个分支流道被布设成围绕所述旋转阀呈放射状发散且转向至分别与所述多个引流针端口一一对应地连通。
在根据本公开的实施例中,所述顶板包括:顶层,所述芯片接纳区形成于所述顶层中;和支撑层,所述支撑层与所述顶层呈层叠设置,且位于所述顶层与所述选择器阀之间;并且,所述多个分支流道和所述公共流道形成于所述支撑层的朝向所述顶层的一侧,且所述多个入口端口、所述出口端口以及所述多个引流针端口延伸贯穿所述支撑层。
在根据本公开的实施例中,所述顶层的所述芯片接纳区中形成有贯通的容置孔,以及从所述顶层的背离所述支撑层的一侧凹入的、且围绕所述容置孔设置的凹部。
在根据本公开的实施例中,所述顶板还包括芯片吸附组件,所述芯片吸附组件被布置成部分地固定于所述容置孔内并且从所述容置孔背离所述支撑层突伸出,且被配置成容置并且吸附芯片,包括:与负压源连通的管接头;吸附台,部分地安置于所述容置孔中,其顶表面的边缘向外突伸以限定所述顶层中的朝向所述支撑层凹入的、介于所述边缘与所述顶表面之间的吸附槽,所述吸附槽被构造呈沿所述边缘延伸且闭合回路形式的闭合槽、且被确定形状和大小为适于围绕且固定所述芯片的边缘;以及负压通道,贯通地形成于所述吸附台内并且连通于所述管接头与所述吸附槽之间。
在根据本公开的实施例中,所述顶层形成有贯穿其中且延伸至所述凹部的供应端口以及排出端口,所述供应端口经由所述公共流道与所述阀体的所述出口端口成流体连通,且所述排出端口与所述供应端口间隔开。
在根据本公开的实施例中,所述公共流道呈直线地联接于所述出口端口与所述供应端口之间。
在根据本公开的实施例中,所述多个分支流道被布置成彼此不交叉且避开所述公共流道。
在根据本公开的实施例中,所述排出端口和所述供应端口各自的与所述支撑层的端部分别延伸至所述凹部;并且,在所述芯片被接纳且吸附于所述吸附台上的情况下,所述吸附台与所述芯片之间共同限定第一液密密封面,且所述芯片在所述第一液密密封面处分别与所述供应端口和所述排出端口形成密封的流体连通。
在根据本公开的实施例中,所述支撑层形成有贯通其中且从所述排出端口流体连 通至所述顶板外部的排出通道。
在根据本公开的实施例中,所述多个入口端口和所述出口端口延伸贯穿所述支撑层至所述顶板的背侧面,所述背侧面与所述阀座之间共同限定第二液密密封面,并且所述多个入口端口和所述出口端口在所述第二液密密封面处分别与所述阀体的所述流体入口和所述流体出口形成密封的流体连通。
在根据本公开的实施例中,所述芯片处理装置还包括设于其内部的驱动件、联接于所述容置仓与所述基板之间的至少一个导轨组件,所述容置仓能够由所述驱动件经由所述至少一个导轨组件的传动沿与所述基板正交的方向移动且使得所述导流组件插入且流体联通至所述试剂盒。
在根据本公开的实施例中,所述驱动件包括:驱动源,包括步进电机、压电驱动器之一;以及在所述驱动源与所述至少一个导轨组件之间成传动联接的丝杠。
在根据本公开的实施例中,每个导轨组件包括间隔开的两组交叉滚子导轨,每组交叉滚子导轨包括固定至所述芯片平台的固定轨、联接至所述容置仓的可动轨、和保持于所述固定轨与所述可动轨之间的多个滚动件。
在根据本公开的实施例中,每组交叉滚子导轨中,所述固定轨以与所述基板正交的方式固定至所述芯片平台,且所述可动轨以与所述基板正交的方式固定至所述容置仓。
在根据本公开的实施例中,所述丝杠与所述至少一个导轨组件中的的两组交叉滚子导轨各自的可动轨联接。
在根据本公开的实施例中,所述芯片处理装置还包括定位装置,所述定位装置包括:凹槽,凹入地形成于所述容置仓的顶侧内壁中;弹性组件,设置于所述凹槽内;和定位珠,所述定位珠设置于所述弹性组件的朝向所述基板的一端处,且被配置成:响应于所述试剂盒没有达到所述容置仓内的所述定位珠处的情况,所述弹性组件处于不受试剂盒所施加力的初始状态且所述定位珠从所述容置仓的所述顶侧内壁至少部分地朝向所述基板凸出;和响应于在所述试剂盒插入于所述容置仓内并且挤压所述定位珠的情况,所述弹性组件经由所述定位珠被朝向所述凹槽内推压、继而使所述弹性组件至少部分缩回至所述凹槽内。
在根据本公开的实施例中,所述试剂盒具备朝向所述容置仓的顶侧内壁突伸的突出部、以及从所述突出部凹入的定位槽,并且响应于在所述试剂盒插入于所述容置仓内并且挤压所述定位珠的情况,所述定位珠被夹持于所述定位槽与所述弹性组件之间。
在根据本公开的实施例中,所述芯片处理装置还包括设置于所述容置仓内部的就位检测器,所述就位检测器包括光耦组件和遮蔽件,所述光耦组件包括红外发射器和红外接收器,且配置成响应于当所述试剂盒插入到所述容置仓内部就位时所述遮蔽件受所述试剂盒所施加的力发生移位或变形并且阻挡由所述红外接收器接收来自红外发射器的红外线的情况而确定所述试剂盒已在所述容置仓内就位。
在根据本公开的实施例中,所述芯片处理装置还包括形成于所述试剂盒平台的顶部处的压紧装置,所述试剂盒平台的顶部形成有贯通开口以至少部分地暴露插入于所述容置仓内的所述试剂盒,所述压紧装置包括:压板,其一侧被固定至所述试剂盒平台;销,延伸贯穿所述压板的与所述一侧相反的自由侧处;一对臂,每个臂的一端以能够枢转的方式联接至所述销的两端中的相应端;和一对弹性件,每个弹性件弹性地联接于所述一对臂中相应臂与所述试剂盒平台之间。
在根据本公开的实施例中,所述芯片处理装置还包括设置于所述试剂盒平台的底部与所述基板之间的第一倾斜调节机构,所述第一倾斜调节机构包括非直线布置的第一定距头和两个能够相对于所述基板旋拧调节的第一螺纹副。
在根据本公开的实施例中,所述芯片处理装置还包括设置于所述芯片平台的底部与所述基板之间的第二倾斜调节机构,所述第二倾斜调节机构包括非直线布置的第二定距头和和两个能够相对于所述基板旋拧调节的第二螺纹副。
在根据本公开的实施例中,所述芯片处理装置还包括限位装置,所述限位装置包括:感应片,设置于至少一个导轨组件中的至少一组交叉滚子导轨的相应可动轨上;和上限位光耦和下限位光耦,分别设置于所述至少一组交叉滚子导轨的相应固定轨两端的与所述相应可动轨的行程的上末端和下末端对应的部位处,且分别被配置成响应于通过检测到感应片遮挡所述上限位光耦确定所述可动轨上升至上极限位置来停止驱动源、且通过响应于检测到感应片遮挡所述下限位光耦确定所述可动轨下降至下极限位置来停止驱动源。
在根据本公开的实施例中,所述芯片处理装置还包括动力组件,所述动力组件被布置成与所述流路网络成流体连通,且配置成驱动流体经过所述流路网络朝向所述供应端口流动。
在根据本公开的实施例中,所述动力组件包括与所述芯片接纳区连通的泵,所述泵被配置成向所述芯片接纳区提供负压。
在根据本公开的实施例中,所述芯片处理装置还包括温控组件,所述温控组件设 置于所述顶板的与所述芯片接纳区相反的一侧,且配置成调节从所述导流组件供应至所述芯片接纳区的流体的温度。
在根据本公开的实施例中,所述温控组件包括第一温度调节装置,所述第一温度调节装置布置成与所述选择器阀在所述顶板的同侧彼此毗邻设置;并且,所述流体引导装置还包括固定至所述顶板的与所述芯片接纳区相反的一侧处的适配器支架,被构造呈框架形式,且所述适配器支架形成有并列设置的、且分别从所述适配器支架的背离所述顶板以及朝向所述顶板的相反两侧凹入的两个凹窝以供在其中分别容置和固定所述选择器阀和所述第一温度调节装置。
在根据本公开的实施例中,所述第一温度调节装置包括:散热件,被容置于且安装入所述适配器支架的所述两个凹窝中的从朝向所述顶板的一侧凹入的一个凹窝内,经由所述隔热固定件而固定至所述与所述芯片接纳区相反的一侧,且包括:主动式散热件和被动式散热件中的至少一种;和温控模块,安装至所述散热件且配置成在所述散热件处的温度超过阈值温度的情况下切断所述动力组件。
在根据本公开的实施例中,所述温控组件还包括:插置于所述顶板与所述第一温度调节装置之间的导热件。
在根据本公开的实施例中,所述导热件包括相变材料。
在根据本公开的实施例中,所述主动式散热件包括热电制冷器;或所述被动式散热件包括如下之一:单个散热片、散热片阵列。
在根据本公开的实施例中,所述温控组件还包括第二温度调节装置,所述第二温度调节装置固定至所述适配器支架的背离所述顶板的一侧且与所述旋转阀并列设置、且布置成与所述第一温度调节装置对准。
在根据本公开的实施例中,所述第二温度调节装置包括风扇,所述风扇包括:中空的第一壳体,其内部限定腔体以供气流流动,所述第一壳体布置成使得所述腔体对准所述第一温度调节装置、且朝向所述第一温度调节装置敞开,以将所述腔体流体连通于所述第一温度调节装置与所述流体引导装置的外部之间;以及扇组件,容置于所述第一壳体内。所述扇组件包括:第二壳体,被构造呈固定地套设于所述第一壳体内的中空的筒状体;转轴,以能够旋转的方式安装至所述第二壳体内;和多个扇叶,所述多个扇叶在所述第二壳体内同轴地固定至所述转轴、且能够随所述转轴相对于所述第二壳体旋转。
在根据本公开的实施例中,所述适配器支架还形成有贯穿其内部的、且在相反两 端分别朝向所述第一温度调节装置和所述第二温度调节装置的腔体敞开的气体通道,所述腔体经由所述气体通道连通至所述第一温度调节装置。
在根据本公开的实施例中,所述第二温度调节装置还包括减振装置,所述减振装置包括:第一级减振结构,被构造呈插置于所述适配器支架与所述风扇的所述第一壳体之间的垫片;和第二级减振结构,设置于所述风扇的所述第一壳体内、位于所述第一壳体与所述扇组件的所述第二壳体之间,包括分别卡入配合到所述第一壳体的内壁处、且彼此间隔开设置的多个减振件,所述扇组件的所述第二壳体经由所述多个减振件而联接至所述第一壳体。
在根据本公开的实施例中,所述第一级减振结构与所述第二级减振结构中的至少一个为振动补偿装置,所述振动补偿装置为弹性件或阻尼件。
在根据本公开的实施例中,所述风扇的所述第一壳体经由柔性吸振材质螺纹件而固定至所述适配器支架,且所述第一级减振结构经由所述螺纹件而被推压抵紧于所述适配器支架与所述第一壳体之间。
在根据本公开的实施例中,所述选择器阀在其阀座处经由螺纹连接而固定至所述顶板,并且所述选择器阀经由可调式抵压装置而联接至所述适配器支架,所述可调式抵压装置包括:多个定距螺钉,分别以能够旋拧的方式贯穿所述适配器支架且抵压选择器阀的所述阀体;和多个弹簧,分别以一一对应的方式弹性地朝向所述顶板抵压所述多个定距螺钉。
根据本公开的第二方面,又提供一种基因测序仪,包括:芯片,所述芯片载有待利用流体检测的样品;和芯片处理装置,所述芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体。所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构,以及所述试剂盒以能够移除的方式插入所述芯片处理装置的容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品。由于其包括前述芯片处理装置,从而具 有类似优点,在此不再赘述。
在根据本公开的实施例中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及所述芯片处理装置配置成:响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
在根据本公开的实施例中,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
在根据本公开的实施例中,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽和多个引导槽,以及流体连通于每个引导槽的底部与相应试剂槽的底部之间的连通通道,每个试剂槽中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口、和覆盖于所述第一开口上的第一可刺穿结构,且每个引导槽具备向上朝向所述凸缘敞开的第二开口、和覆盖于所述第二开口上的第二可刺穿结构。
在根据本公开的实施例中,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和选择器阀,安装至所述顶板且与所述流路网路成流体连通。
在根据本公开的实施例中,所述选择器阀包括:阀座,所述选择器阀经由所述阀座固定至所述顶板;阀体,从所述阀座沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体内部的流体入口和被配置成引导流体从所述阀体内部向外流动的流体出口。所述流路网络包括:多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区。 所述选择器阀布置成使得所述流体出口与所述出口端口成流体连通,且所述流体入口与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的选择性连通。
在根据本公开的实施例中,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
在根据本公开的实施例中,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构对准的第一末端、且每个引流针具有与相应第二可刺穿结构对准的第二末端,每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构、继而插入所述试剂槽以暴露所述试剂槽来改变所述试剂槽内的气压;以及每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构、继而插入所述引导槽以流体连通至所述引导槽来汲取所述引导槽中的流体。
在根据本公开的实施例中,在所述多个引流针插入所述引导槽的情况下,所述多个引流针各自的自由端高于所述试剂槽的底部处的内壁。
在根据本公开的实施例中,每个引导槽被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
在根据本公开的实施例中,所述第一可刺破结构是金属箔;以及所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
根据本公开的第三方面,再提供一种基因测序设备,包括:芯片,所述芯片载有待利用流体检测的样品;和至少两个芯片处理装置,每个芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体。所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中 具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构;所述试剂盒以能够移除的方式插入所述容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品;以及所述至少两个芯片处理装置相互对称设置且各自的芯片平台彼此毗邻设置。
在根据本公开的实施例中,所述至少两个芯片处理装置包括彼此呈镜像对称布置且各自的芯片平台彼此邻接设置的至少一对芯片处理装置。由于其包括前述芯片处理装置,从而具有类似优点,在此不再赘述。
在根据本公开的实施例中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态。以及所述芯片处理装置配置成:响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
在根据本公开的实施例中,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
在根据本公开的实施例中,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽和多个引导槽,以及流体连通于每个引导槽的底部与相应试剂槽的底部之间的连通通道,每个试剂槽中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口、和覆盖于所述第一开口上的第一可刺穿结构,且每个引导槽具备向上朝向所述凸缘敞开的第二开口、和覆盖于所述第二开口上的第二可刺穿结构。
在根据本公开的实施例中,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和选择器阀,安装至所述顶板且与所述流路网路成流体连通。
在根据本公开的实施例中,所述选择器阀包括:阀座,所述选择器阀经由所述阀 座固定至所述顶板;阀体,从所述阀座沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体内部的流体入口和被配置成引导流体从所述阀体内部向外流动的流体出口。所述流路网络包括:多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区。所述选择器阀布置成使得所述流体出口与所述出口端口成流体连通,且所述流体入口与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的选择性连通。
在根据本公开的实施例中,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
在根据本公开的实施例中,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构对准的第一末端、且每个引流针具有与相应第二可刺穿结构对准的第二末端。每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构、继而插入所述试剂槽以暴露所述试剂槽来改变所述试剂槽内的气压;以及每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构、继而插入所述引导槽以流体连通至所述引导槽来汲取所述引导槽中的流体。
在根据本公开的实施例中,在所述多个引流针插入所述引导槽的情况下,所述多个引流针各自的自由端高于所述试剂槽的底部处的内壁。
在根据本公开的实施例中,每个引导槽被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
在根据本公开的实施例中,所述第一可刺破结构是金属箔;以及所述第二可刺破 结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
根据本公开的第四方面,还提供一种进行生化检测的方法,所述方法包括:在具有待检测样品的芯片和具有多种不同反应成分的试剂盒之间建立流体连接,所述反应成分包括样本生成成分或样本分析成分至少之一;任选的,在生成操作中在所述芯片生成样本,所述生成操作包括使不同样本生成成分流入所述芯片并控制所述芯片的反应条件以生成所述样本;以及在分析操作中分析所述芯片的所述样本,所述分析操作包括使样本分析成分流入所述芯片,所述样本分析成分与所述样本发生反应以提供相关可检测信号;所述试剂盒和芯片集成于芯片处理装置,且所述试剂盒中的所述流体经由所述芯片处理装置中且相互分离的第一流体输送结构和第二流体输送结构流体连通至所述芯片。
在根据本公开的实施例中,所述第一流体输送结构集成于所述试剂盒中,所述第二流体输送结构集成于支撑所述芯片的载台中,所述载台集成于所述芯片处理装置。
在根据本公开的实施例中,所述试剂盒通过集成于所述芯片处理装置的可移动支架相对所述载台运动,实现所述第一流体输送结构与所述第二流体输送结构的连通。
在根据本公开的实施例中,所述生化反应为核酸测序反应,所述待检测样本为核酸测序文库。
在根据本公开的实施例中,所述生化反应为特异性结合反应,所述待检测样本为生物组织或组织切片。其中,上述特异性结合反应可以为抗原和抗体的结合反应,或生物素与链霉亲和素的结合反应等。
在根据本公开的实施例中,所述可检测信号为光学信号。
在根据本公开的实施例中,所述第一流体输送结构与所述第二流体输送结构的连通包括:第一流体输送结构与所述芯片处理装置的外部气压连通以驱动所述试剂盒中的所述流体流入所述第二流通输送结构;以及将所述芯片与所述第二流通输送结构中的所述流体选择性连通。
在根据本公开的实施例中,所述第二流通输结构具有多个分支流道,所述芯片与所述流体选择性连通包括:利用集成在所述芯片处理装置的选择器阀控制不同所述多个分支流道与所述芯片的选择性连通。
本公开提供的技术方案具备以下优点:本公开的实施例所实现的芯片处理装置、基因测序仪、基因测序设备和使用基因测序仪的方法,特别是芯片处理装置,能够通过如上的设置,实现一体化的无管道式流体输送结构,其具备减少的流道长度,对于 试剂盒的更可靠的调平和紧固作用、以及更高的定位精度。并且采用了从试剂盒顶部吸液结合注射泵的使用的设置,避免了长行程的平移和升降运动且也避免了如常规操作中般必需将试剂针插入到试剂盒底部。由此,能够在改善集成度从而提高空间利用率的同时改善流体输送结构的固定、定位、行程等等,并且以更紧凑的构造实现设计预期。且这种紧凑的结构使得空间占用最小化,且简单的构造和联接关系便利了装配和拆卸。
附图说明
图1(a)示意性示出根据本公开的一种实施例的芯片处理装置的立体结构视图,图1(b)为图1(a)的爆炸示意图,图1(c)示出了图1(a)部分结构的俯视图;图1(d)为图1(c)沿P-P线的剖视示意图;图1(e)为图1(e)所示结构去除试剂仓110后的相同位置的剖视示意图;图1(f)为图1(a)所示结构去除试剂仓110后的立体示意图;
图2(a)至图2(e)示意性示出图1所示的芯片处理装置的不同角度的视图,图2(a)为示意性立体图且移除芯片平台的面板和内部的交叉滚子导轨,图2(b)为正视图且移除芯片平台的面板和内部的交叉滚子导轨,图2(c)为另一角度的示意性立体图且移除芯片平台的面板、内部靠外侧布置的V形支撑件,图2(d)为正视图且芯片平台的面板,图2(e)为俯视图;图2(f)示意性示出了选择器阀与适配器支架的装配示意图;
图3(a)示出从当储液器的试剂盒的结构示意图;图3(b)示出图3(a)的试剂盒移除顶部面板之后的俯视图;
图4示出沿图2(e)中的线F-F剖切的视图,其中示出了试剂盒内部的试剂槽和引导槽的具体布置;
图5(a)示意性示出了图1的芯片处理装置中所述芯片平台的顶板中的用于输送流体的具体结构,以充当流体供应装置;图5(b)示意性示出充当载台的顶板与选择器阀之间的装配关系;
图6(a)示出载台的示意性立体图,其中所述载台带有安装于芯片接纳区中的芯片吸附组件;图6(b)至图6(c)分别以俯视角度和仰视角度示意性示出图6(a)的载台的爆炸视图,其中为简单起见移除了芯片吸附组件;
图7示出了芯片吸附组件的结构示意图;
图8示意性示出了沿着公共流道剖切充当载台的顶板的剖视图;
图9(a)至图9(f)分别以不同角度视图示出图1的芯片处理装置中的所述芯片平台中的流体引导装置,特别是其导流组件。其中,图9(a)和图9(b)分别是以不同角度展示的所述流体引导装置的示意性立体图;图9(c)至图9(f)分别是所述流体引导装置的正视图、右视图、后视图、俯视图;
图10图示了图2(e)俯视图所示的芯片处理装置沿着E-E线的剖视图,其示出内部的定位装置和用于探测储液器在容置仓内插入就位的就位检测器;
图11为图9(b)的爆炸示意图;
图12为图9(f)中沿线A-A的剖视示意图;
图13(a)为图11中的第二温度调节装置的爆炸示意图;
图13(b)至图13(c)分别示出如图9(f)中沿线C-C、以及线D-D剖切之后观察到的示意性立体视图;
图14示意性地图示了根据本公开实施例的基因测序仪,其包括图1所示的芯片处理装置和以能够移除的方式插入芯片处理装置的试剂盒平台的容置仓中的储液器、以及以能够移除的方式插入芯片平台的顶板芯片接纳区中的测序芯片;
图15图示了根据本公开实施例的基因测序设备,包括呈镜像对称且相互邻接设置的一对前述的基因测序仪;以及
图16图示了根据本公开实施例的应用图14所示的基因测序的生化检测的方法,的示意性流程图。
图17示意性示出了如图16的流程图的方法中的更具体步骤。
具体实施方式
下面通过实施例并结合附图对本公开的技术方案作进一步具体的说明。在说明书中,相同或相似的附图标号表示功能相同或相似的部件。下述参照附图对本公开实施方式的说明旨在对本公开的总体构思进行解释,而不应当理解为对本公开的一种限制。另外,在下面的详细描述中,为便于解释,阐述了许多具体的细节以提供对本披露实施例的全面理解。然而明显地,一个或更多个实施例在没有这些具体细节的情况下也可以被实施。
图1(a)示意性示出根据本公开的一种实施例的芯片处理装置的立体结构视图,图1(b)为图1(a)的爆炸示意图,图1(c)示出了图1(a)部分结构的俯视图;图 1(d)为图1(c)沿P-P线的剖视示意图。
根据本公开实施例的一个总体技术构思,例如,如图1(a)-图(d)所示,提供了集成有试剂盒的芯片处理装置1,用于从包含流体的储液器2(例如试剂盒)供应流体至芯片3(例如基因测序芯片3),所述芯片处理装置1包括沿第一方向延伸的基板10、和沿横向于所述第一方向的第二方向并排且毗邻地组装设置于所述基板10上的试剂盒平台11和芯片平台12。其中,所述芯片平台12具备位于其顶部处的顶板120,所述顶板120充当用于支撑所述芯片并且承载流体输送结构的载台。并且更具体地,所述芯片平台12的背离所述基板一侧处的所述顶板120上具备用于容置载有待利用流体检测的样品的芯片3的芯片接纳区121a;更具体地,例如,所述芯片接纳区121a的形状和尺寸例如被确定为适于容纳所述芯片3,使得所述芯片3被容置在所述芯片平台12的顶板120上的芯片接纳区121a中。所述试剂盒平台11中形成有中空的容置仓110,所述试剂盒接纳于所述容置仓内。并且,例如,所述试剂盒平台11内具有向外敞开(例如如图1所示为在其横向侧上向外敞开)且适于接纳包含流体的储液器2(诸如试剂盒)的容置仓110。进一步地,作为示例,所述试剂盒平台中具有位于其内部的沿所述第二方向朝向所述芯片平台的一侧处的第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构,所述第一流体输送结构经由所述第二流体输送结构流体连通至所述芯片。并且,作为示例,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及所述芯片处理装置配置成响应于所述容置仓背离所述基板上升至引流位置,所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;且响应于所述容置仓朝向所述基板下降至非引流位置,所述第一流体输送结构与所述第二流体输送结构彼此分离。由此,在集成有可升降式试剂盒的芯片处理装置内,便利于实现了所述试剂盒平台中的所述第一流体输送结构与所述芯片平台中的所述第二流体输送结构之间的流体连通状态与非连通状态之间的切换。
并且,在具体实施例中,作为示例,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述芯片平台的背离所 述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台11部分嵌入地装配于所述顶板120的向外伸出的所述凸缘1201与所述基板10之间。
图2(a)至图2(e)示意性示出图1所示的芯片处理装置1的不同角度的视图,图2(a)为示意性立体图且移除芯片平台12的面板和内部的交叉滚子导轨130,图2(b)为正视图且移除芯片平台12的面板和内部的交叉滚子导轨130,图2(c)为另一角度的示意性立体图且移除芯片平台12的面板、内部靠外侧布置的V形支撑件133,图2(d)为正视图且芯片平台12的面板,图2(e)为俯视图。
图3(a)示出从当储液器的试剂盒的结构示意图;图3(b)示出图3(a)的试剂盒移除顶部面板之后的俯视图。图4示出沿图2(e)中的线F-F剖切的视图,其中示出了试剂盒内部的试剂槽和引导槽的具体布置;
在根据本公开的实施例中,例如如图所示,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽20a和多个引导槽20b,以及流体连通于每个引导槽20b的底部与相应试剂槽20a的底部之间的连通通道20c,每个试剂槽20a中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口21、和覆盖于所述第一开口21上的第一可刺穿结构210,且每个引导槽20b具备向上朝向所述凸缘敞开的第二开口22、和覆盖于所述第二开口22上的第二可刺穿结构220。
图5(a)示意性示出了图1的芯片处理装置中所述芯片平台的顶板中的用于输送流体的具体结构,以充当流体供应装置;图5(b)示意性示出充当载台的顶板与选择器阀之间的装配关系。
图6(a)示出载台的示意性立体图,其中所述载台带有安装于芯片接纳区中的芯片吸附组件;图6(b)至图6(c)分别以俯视角度和仰视角度示意性示出图6(a)的载台的爆炸视图,其中为简单起见移除了芯片吸附组件。图7示出了芯片吸附组件的结构示意图。
图8示意性示出了沿着图6(a)中公共流道所在的L-L线剖切充当载台的顶板120的剖视图。图9(a)至图9(f)分别以不同角度视图示出图1的芯片处理装置中的所述芯片平台中的流体引导装置,特别是其导流组件。其中,图9(a)和图9(b)分别是以不同角度展示的所述流体引导装置的示意性立体图;图9(c)至图9(f)分别是所述流体引导装置的正视图、右视图、后视图、俯视图。
在进一步的实施例中,如图所示,所述第二流体输送结构包括流体供应装置,所 述流体供应装置150包括:流路网络125,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和选择器阀126,安装至所述顶板且与所述流路网路成流体连通。
在更进一步的实施例中,如图所示,所述选择器阀包括:阀座1261,所述选择器阀经由所述阀座1261固定至所述顶板;阀体1262,从所述阀座1261沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体1262内部的流体入口126a和被配置成引导流体从所述阀体1262内部向外流动的流体出口126b、以及至少驱动阀座旋转实现与流体网络的不同分支流道连通的驱动电机1263,驱动电机1263优选为步进电机。并且,所述流路网络包括:多个引流针端口1250,位于所述顶板的与所述芯片接纳区相反的一侧;多个入口端口1254,布置成以一一对应关系与所述多个引流针端口间隔开;多个分支流道1252,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;出口端口1255,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和公共流道1253,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区。例如,所述选择器阀布置成使得所述流体出口126b与所述出口端口成流体连通,且所述流体入口126a与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口1254中的至少一个与所述出口端口之间的、经由所述流体入口126a和所述流体出口126b的选择性连通,如图9(f)及图12(a)所示,流体入口126a表示阀体连通至阀座1261上表面与顶板的分支流道选择性连通的接口,流体出口126b表示阀体连通至阀座1261上表面与出口端口1255连通的接口。
在再更进一步的实施例中,例如,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
并且,如图1和图2(a)至图2(e)所示,在根据本公开的实施例中,例如,所述芯片平台12中,所述第二流体输送结构还包括从所述凸缘1201向所述试剂盒平台11突伸且连至所述芯片接纳区121a的导流组件123,并且,进一步地,如图所述导流组件123包括:多个破膜针123b和多个引流针123a,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构210对准的第一末端、且每个引流针具有与相应第二可刺穿结构220对准的第二末端。作为示例,每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所 述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构210、继而插入所述试剂槽20a以暴露所述试剂槽20a来改变所述试剂槽20a内的气压。并且,作为示例,每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构220、继而插入所述引导槽20b以流体连通至所述引导槽20b来汲取所述引导槽20b中的流体。
在一种示例性实施例中,例如,在所述多个引流针插入所述引导槽20b的情况下,所述多个引流针各自的自由端高于所述试剂槽20a的底部处的内壁。
通过上述设置,当试剂盒随着容置仓上升至引流位置,则破膜针123b刺破覆盖于所述第一开口21上的所述第一可刺穿结构210从而进入试剂槽20a内,使得大气压从被刺破的所述第一可刺穿结构210经过所述第一开口21而进入所述试剂槽20a,由此将试剂经由底部的连通通道20c而进一步压入引导槽20b。同时,引流针123a也同步地刺破覆盖于所述第二开口22上的所述第二可刺穿结构220从而进入引导槽20b内。由此,通过上述布置,便利了至少部分地插入引导槽内的引流针即便距离试剂盒内的试剂页面很远仍旧可以实现对试剂液体的抽吸。
在具体的实施例中,作为示例,每个引导槽20b被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽20b被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。通过这种设置,更进一步便利了引流针将试剂槽中的试剂液体经由底部的连通通道吸取至引导槽内。
在具体的实施例中,作为示例,所述第一可刺破结构是金属箔。并且,例如,所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
在具体的实施例中,作为示例,所述多个引流针彼此间隔开地呈直线布置,且所述多个破膜针彼此间隔开地呈直线布置;以及所述多个引流针与所述多个破膜针两者彼此平行布置。
在更具体的实施例中,作为示例,所述多个引流针123a以均一的间距彼此间隔开。对应地,所述多个试剂分配端口也以所述间距彼此间隔开。由此,实现了多个引流针123a在所述载台120的前述单个边缘处的均分分布,有效避免了相互干扰且有利于局部热平衡。
通过上述设置,其利用在所述载台120的单个边缘处集中布设的均匀间隔分布的 线性布置的多个引流针123a充当试剂针,由此以优化的空间利用率实现了均匀分布的从储液器吸液的结构,也便利了后续布设从引流针123a至选择器阀126的多个流体路径(例如呈多个歧管分支的形式)的分布,有效地避免了不同试剂路径之间的相互干扰且有利于区域热平衡分布。
在本公开的进一步实施例中,如图所示,例如,所述多个引流针中每个的旁侧一一对应地布置有相应破膜针,且每个引流针与相应的单个破膜针成对地毗邻但间隔开设置。
在具体的实施例中,作为示例,每个引流针包括中空且伸长的空心直管状针主体、和具备锥形渐缩的纵向截面形状的贯通的顶端。例如,所述多个引流针以螺纹连接方式安装至所述多个引流针端口。
在本公开的其他的实施例中,如图所示,例如,所述导流组件还包括:至少两个导向销,从所述顶板的与所述芯片接纳区相反的一侧向外突伸且彼此间隔开地呈直线布置,且被构造成与所述试剂盒上的对准特征呈形状配合。
在更具体地实施例中,如图所示,作为示例,所述至少两个导向销123c是与所述多个引流针123a共线布置且分别位于所述多个引流针123a的两端处的两个引流针123a外侧的两个导向销123c。
通过这种设置,例如,所述两个导向销123c与所述储液器上地相应地对准特征例如凹坑彼此对准且呈形状配合(in positive fit),由此可充当所有引流针123a相对于所述储液器中的相应试剂分配端口准确定位的导向件;换言之,一旦两端处的所述两个导向销123c正确地对准且适配入所述储液器上的对准特征,则所有引流针123a相对于各自相应的试剂分配端口对准地定位。
在具体的实施例中,作为示例,对应地,所述多个引流针端口布置呈直线地彼此对准。在更具体的实施例中,作为示例,所述多个引流针端口布置成以均一的间距彼此分离。
另外,在本公开的实施例中,例如,如图所示,所述选择器阀是旋转阀,且所述旋转阀被配置成能够围绕其轴线旋转以使得切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口126a和所述流体出口126b的选择性连通。
在进一步的实施例中,优选地作为示例,所述入口端口和所述出口端口各自的轴向平行于所述轴线,且所述入口端口设置成与所述轴线偏离,且所述出口端口与所述 轴线同轴设置。
在具体的实施例中,例如,所述选择器阀经由所述阀座1261而被安装至所述顶板的与所述芯片接纳区背离的背侧面,并且,所述多个入口端口被构造成绕所述轴线呈环形布置,所述多个入口端口和所述出口端口均向所述顶板的所述背侧面敞开,且所述多个入口端口中的至少一个选择性连通至所述阀体1262的所述流体入口126a、所述出口端口连通至所述阀体1262的所述流体出口126b,且所述多个入口端口中的每个与所述出口端口之间的中心距是相等的。
在更进一步的实施例中,例如,所述多个分支流道被布设成围绕所述旋转阀呈放射状发散且转向至分别与所述多个引流针端口一一对应地连通。
通过这些具体设置,利用旋转阀126充当选择器阀126,并且沿旋转阀126的周向设置作为分支流道1252的出口的多个入口端口1254(优选地例如以相同角度沿周向彼此间隔开设置的多个入口端口1254),并且对应地使得所述多个分支流道1252从相应的入口端口1254放射状地向外发散,例如以均匀的角向间隔绕旋转阀126的轴线AX沿大致径向向外发散,实现了在毗邻于所述旋转阀126的周围区域的实质上均一间隔开分布的歧管,便利于流路网络125的在介于所述旋转阀126与所述引流针端口1250之间的整个区域上的均匀布设,通过规划布设歧管来有效地控制了总体流道长度,避免了冗余的流体路径长度,减少了试剂损耗,同时也有利于整个流体供应装置1上的温控和温度均衡。
并且,在本公开的实施例中,如图所示,流路网络125也实现了在所述载台120的介于选择器阀126与芯片接纳区121a(用于容置芯片)之间的区域上的凭借单一管线的集中流体供应,简化了向芯片供应流体例如试剂的最终阶段的供液布置。
在本公开的更具体的实施例中,例如,所述顶板包括:顶层120a,所述芯片接纳区形成于所述顶层120a中;和支撑层120b,所述支撑层120b与所述顶层120a呈层叠设置,且位于所述顶层120a与所述选择器阀之间。并且,所述多个分支流道和所述公共流道形成于所述支撑层120b的朝向所述顶层120a的一侧,且所述多个入口端口、所述出口端口以及所述多个引流针端口延伸贯穿所述支撑层120b。
更具体地,如图6(a)至6(c)所示,例如,所述顶层120a的所述芯片接纳区中形成有贯通的容置孔1202,以及从所述顶层120a的背离所述支撑层120b的一侧凹入的、且围绕所述容置孔1202设置的凹部1203。
并且,如图7所示,例如,所述顶板还包括芯片吸附组件120c,所述芯片吸附组 件120c被布置成部分地固定于所述容置孔1202内并且从所述容置孔1202背离所述支撑层120b突伸出,且被配置成容置并且吸附芯片,包括:与负压源连通的管接头1204;吸附台1205,部分地安置于所述容置孔1202中,其顶表面的边缘向外突伸以限定所述顶层120a中的朝向所述支撑层120b凹入的、介于所述边缘与所述顶表面之间的吸附槽1206,所述吸附槽1206被构造呈沿所述边缘延伸且闭合回路形式的闭合槽、且被确定形状和大小为适于围绕且固定所述芯片的边缘;以及负压通道1207,贯通地形成于所述吸附台1205内并且连通于所述管接头1204与所述吸附槽1206之间。
在本公开的实施例中,例如,所述顶层120a形成有贯穿其中且延伸至所述凹部1203的供应端口以及排出端口,所述供应端口经由所述公共流道与所述选择器阀成流体连通,且所述排出端口与所述供应端口间隔开。
进一步地,例如,所述公共流道呈直线地联接于所述出口端口与所述供应端口之间。
并且,例如,所述多个分支流道被布置成彼此不交叉且避开所述公共流道。
在具体的实施例中,例如,如图所示,所述排出端口和所述供应端口各自的与所述支撑层120b的端部分别延伸至所述凹部1203。并且,作为示例,如图8所示,在所述芯片被接纳且吸附于所述吸附台1205上的情况下,所述吸附台1205与所述芯片之间共同限定芯片液密密封面P1充当第一液密密封面,且所述芯片在所述第一液密密封面处分别与所述供应端口和所述排出端口形成密封的流体连通。
在具体的实施例中,例如,如图所示,所述支撑层120b形成有贯通其中且从所述排出端口流体连通至所述顶板外部的排出通道。并且,作为示例,如图8所示,所述多个入口端口和所述出口端口延伸贯穿所述支撑层120b至所述顶板的背侧面,所述背侧面与所述阀座1261之间共同限定阀液密密封面P2充当第二液密密封面,并且所述多个入口端口和所述出口端口在所述第二液密密封面处分别与所述阀体1262的所述流体入口126a和所述流体出口126b形成密封的流体连通。
所述芯片液密密封面P1和所述阀液密密封面P2分别位于所述切换器阀内部的流道的上下两侧。通过这种设置,简化了密封面的设置,并且通过载台120内限定不同位置处的两种密封面,实现了容易的流体隔离以及分别在芯片处和阀处的不漏液的密封。
进一步地,如图所示,例如,所述芯片平台12具备设于其内部的驱动件122,且所述芯片处理装置1例如还包括联接于所述容置仓110与所述基板之间的至少一个导 轨组件13,所述容置仓110能够由所述驱动件122经由所述至少一个导轨组件13的传动沿与所述基板10正交的方向移动且使得所述导流组件123插入且流体联通至所述储液器2。作为示例,例如如图1(c)所示,所述芯片处理装置1包括并列布置的两个导轨组件13。
在本公开的具体实施例中,所述引流位置例如是一定范围的多个位置(称为第一位置范围)中的任一位置值;更具体地,所述容置仓110一旦上升达到所述第一位置范围中的第一阈值位置(例如所述第一位置范围中的最低位置)则实现所述试剂盒平台11中的所述第一流体输送结构接合所述芯片平台12中的所述第二流体输送结构、由此建立所述第一流体输送结构与所述第二流体输送结构之间的流体连通。
而且,在本公开的具体实施例中,所述非引流位置例如也是另外的一定范围的多个位置(称为第二位置范围)中的任一位置值;更具体地,所述容置仓110一旦下降达到所述第二位置范围中的第二阈值位置(例如所述第二位置范围中的最高位置)则实现所述试剂盒平台11中的所述第一流体输送结构与所述芯片平台12中的所述第二流体输送结构相互脱离接合且由此实现了所述第一流体输送结构与所述第二流体输送结构彼此分离从而在两者之间不再存在流体连通。
并且,通常地,作为示例,所述第一阈值位置高于所述第二阈值位置。由此,所述第一位置范围与所述第二位置范围彼此完全不交叠。
在具体的实施例中,例如,所述驱动件122包括:驱动源,包括步进电机、压电驱动器之一;以及在所述驱动源与所述至少一个导轨组件13之间成传动联接的丝杠。更具体地,作为示例,所述丝杠经由位于其上游且与所述驱动源的输出轴成传动联接的联轴器而进一步联接至所述至少一个导轨组件13,由此,便利了由所述驱动件122经由所述至少一个导轨组件13的传动来正交于所述基板10往复移动所述容置仓110,即实现了容置仓110的升降动作。
在具体的实施例中,例如,每个导轨组件13包括间隔开的两组交叉滚子导轨130,每组交叉滚子导轨130包括固定至所述芯片平台12的固定轨131、联接至所述容置仓110的可动轨132、和保持于所述固定轨131与所述可动轨132之间的多个滚动件135,所述多个滚动件例如多个滚珠(在此情况下由交叉滚珠导轨充当每组交叉滚子导轨130)、或交替地正交布置的多个滚柱(在此情况下由交叉滚柱导轨充当每组交叉滚子导轨130),由此便利了承载沿多个不同方向的负荷。并且,在进一步的实施例中给,例如如图所示,每组交叉滚子导轨130中,所述固定轨131以与所述基板10正交的方 式固定至所述芯片平台12,且所述可动轨132以与所述基板10正交的方式固定至所述容置仓110。
由此,如图所示的所述至少一个导轨组件13(图示为并排布置的两个导轨组件13)中的各组交叉滚子协同工作以充当所述容置仓110沿着与所述基板10正交的方向运动的导向装置,由此实现了对于容置仓110的升降动作的准确导向。
在进一步的实施例中,作为示例,所述丝杠与所述至少一个导轨组件13中的两组交叉滚子导轨130各自的可动轨132联接。通过互联于每个导轨组件13中的不同组交叉滚子导轨130的各自可动轨132之间的这种设置,实现了同一个导轨组件13中的彼此间隔开设置的两组交叉滚子导轨130的对于容置仓110升降动作的同步导向,并且同时也便利了在容置仓110的升降期间维持对于容置仓110下方的一体化的支撑。
作为示例,所述试剂盒平台11的所述第一流体输送结构包括储液器2,例如试剂盒。
如图2(f)所示,芯片平台12还包括固定选择器阀126的V形支撑件133,选择器阀126穿设于适配器支架127,适配器支架127与固定支架12a固定,V形支撑件133连接在适配器支架127底部与选择器阀126之间,且所述V形支撑件133包括两个支腿1330以及连接两支腿1330的连接部1332,两支腿分别例如由可旋拧调节的螺纹副与适配器支架127底部连接,连接部1332可通过相似的螺纹结构与选择器阀126固定。由此实现选择器阀在芯片平台12中的稳定安装。
图5(a)示意性示出了图1的芯片处理装置1中所述芯片平台12的顶板120中的用于输送流体的具体结构,例如第二流体输送结构;图5(b)示意性示出充当载台的顶板与选择器阀之间的装配关系。
作为示例,所述芯片平台12的所述第二流体输送结构例如将在下文中阐述的流体引导装置160,所述流体引导装置更具体地包括流体供应装置150和导流组件123;并且所述流体供应装置包括前述的顶板120(其充当用于承载测序芯片的载台),以及流路网络125和选择器阀126,由此,所述顶板120、所述流路网络125和所述选择器阀126三者共同形成了向该芯片供应流体的流体供应装置150;且进而,所述流体供应装置150与所述导流组件123协同工作以共同限定充当所述第二流体输送结构的流体引导装置160。
进一步地,在本公开的实施例中披露了所述流体输送装置的用于输送流体的具体结构。作为示例,如图所示,所述芯片处理装置1还包括形成于所述芯片平台12的所 述顶板120中的流路网络125,和安装至所述顶板120且与所述流路网路成流体连通的选择器阀126,所述流路网络125更具体地包括:多个引流针端口1250,呈直线地对准且彼此间隔开;多个分支流道1252,每个分支流道1252的一端连通至所述多个引流针端口1250中的相应引流针端口1250、且另一端贯穿顶板120靠近选择器阀126的一侧并与所述选择器阀的流体入口126a选择性连通;和单一的公共流道1253,流体连通于所述选择器阀126的流体出口126b与所述芯片接纳区121a之间,且所述选择器阀126可操作以切换所述多个分支流道1252之一的相应另一端与所述流体入口126a的对准以及连通。所述多个分支流道1252共同形成歧管段1251。
并且,前述的顶板120充当用于承载测序芯片的载台,并且与如上所述的流路网络125和选择器阀126相结合,三者共同形成了向该芯片供应流体的流体供应装置150。由此,利用如上所述设置于所述芯片平台12的顶板120中的输送流体的具体结构,提供主要在所述芯片平台12的顶板120中布设流道,便利了实现流道长度的缩短,降低了替代比及试剂用量,降低了测序成本。
并且,在本公开的实施例中,如图所示,作为示例,所述选择器阀126是旋转阀,且所述旋转阀被配置成能够围绕其轴线AX旋转以使得所述流体入口126a切换与所述多个分支流道1252之一的对准和流体连通。
在进一步的实施例中,例如如图所示,所述流体入口126a和所述流体出口126b各自的轴向平行于所述轴线AX,且所述流体入口126a设置成与所述轴线AX偏离,且所述流体出口126b与所述轴线AX同轴设置。
在更具体的实施例中,如图所示,作为示例,所述多个分支流道1252的与所述流体入口126a相联接的相应的另一端被构造成绕所述轴线AX呈环形布置的多个入口端口1254,且每个入口端口1254与所述流体出口126b之间的中心距等于所述流体入口126a与所述流体出口126b之间的中心距。
由此,利用旋转阀充当选择器阀126,利用简单的对旋转阀的阀体进行旋转的方式即可便利地选择性地将该阀的流体入口126a切换成与所述多个分支流道1252中的一个期望分支流道1252的出口对准且彼此呈流体连通。
图8示意性示出了沿着公共流道剖切充当载台的顶板的剖视图。
并且,在本公开的另外实施例中,如图所示,在所述旋转阀126内,所述流体入口126a和所述流体出口126b共用第一密封面P1,且所述多个入口端口1254共用第二密封面P2,所述第一密封面P1和所述第二密封面P2分别位于所述切换器阀内部的 流道的上下两侧。
通过这种设置,简化了密封面的设置,并且通过在阀体内仅需限定不同侧流道处的两种不叠合的密封面,实现了容易的流体隔离,便利于在分支流道1252的入口端口1254不与旋转阀126的流体入口126a对准、和/或下游的公共流道1253的入口不与旋转阀126的流体出口126b对准时的有效的液密密封和流道阻断,确保了在旋转阀126处及时打开与关断流道,以及在旋转阀126切换为关断时的有效密封以避免试剂之间的不期望的混合。
图9(a)至图9(f)分别以不同角度视图示出图1的芯片处理装置中的所述芯片平台中的流体引导装置,特别是其导流组件。其中,图9(a)和图9(b)分别是以不同角度展示的所述流体引导装置的示意性立体图;图9(c)至图9(f)分别是所述流体引导装置的正视图、右视图、后视图、俯视图。
此外,在本公开的实施例中,如图所示,作为示例,所述多个引流针端口1250设置于所述顶板120的实质上纵向的单个边缘1208处,且所述多个分支流道1252被布设成围绕所述选择器阀126呈放射状发散且朝向所述边缘1208转向至分别与所述多个引流针端口1250一一对应地连通。
通过这种将分支流道1252的末端围绕选择器阀126(例如旋转阀)的周向布置,典型地例如以均匀的角度间隔而周向布置呈各自沿径向呈辐射状发散,能够实现在选择器阀126的毗邻的周边区域均匀的布设分支流道1252,由此也便于实现对跨越所述顶板120中的分布所述多个分支流道1252的整个区域的均一温度控制和的流道之间以均匀间隔的布置。
并且,在本公开的实施例中,例如如图所示,所述导流组件123包括分别与所述多个分支流道1252以一一对应关系成流体连通的多个引流针123a,所述多个引流针123a从所述芯片平台12的所述顶板120的前述单一的边缘1208的下侧朝向所述试剂盒平台11突伸、且彼此间隔开地(例如以均一的间距彼此间隔开)呈直线布置,每个引流针123a被构造为中空的针状。
更具体地,例如,所述多个引流针端口1250贯穿地形成于从所述顶板120的所述边缘1208处朝向所述顶板120的背离容置所述芯片3的芯片接纳区121a的一侧突伸的凸部121b中。并且,对应地,作为示例,所述多个引流针123a以螺纹连接方式安装至所述多个引流针端口1250并且与所述多个分支流道1252成一一对应的流体连通。由此,所述多个引流针端口1250也对应地呈与所述多个引流针123a相同的布置,具 体地例如,彼此间隔开地(例如以与引流针相同的均一的间距彼此间隔开)呈直线布置于所述顶板120的该单个边缘1208处。
所述多个引流针123a还例如被配置成在一旦所述容置仓110在所述试剂盒平台11中上升到上极限位置时穿刺所述容置仓110中的所述储液器2(例如试剂盒)的对应的试剂引出部位上方所覆盖的密封垫,由此实现所述多个引流针123a分别以一一对应关系流体连通至所述储液器2中的对应的试剂引出部位。所述上极限位置例如为前述的引流位置,特别地例如是充当所述引流位置的所述第一位置范围中的最高位置。
由此以简易的安装方式实现了对于充当试剂针(起到从试剂盒吸液作用)的引流针123a与流路网络125的稳固机械联接和直接流体连通两者。
此外,在本公开的实施例中,如图所示,作为示例,所述公共流道1253呈直线地联接于所述流体出口126b与所述芯片接纳区121a之间。并且,作为示例,所述多个分支流道1252被布置成彼此不交叉且被避开所述公共流道1253。由此,实现了对于选择器阀126而言,进入其的流道与从其输出的流道有效地彼此分离,且选择性地连通的各个分支流道1252也有效地彼此间隔开布置。
此外,在本公开的实施例中,如图所示,所述导流组件123例如还包括多个破膜针123b,从所述顶板120的所述边缘1208的下侧向外突伸且彼此间隔开地呈直线布置,每个破膜针123b被构造为实心的针状。继而,在更具体地实施例中,所述多个引流针123a例如与所述多个破膜针123b两者彼此平行布置。并且,在进一步的实施例中,作为示例,所述多个引流针123a的旁侧一一对应地布置有相应破膜针123b,破膜针123b被配置成一旦所述容置仓110在所述试剂盒平台11中上升到上极限位置时穿刺所述容置仓110中的所述储液器2(例如试剂盒)的对应的试剂引出部位上所覆盖的用于覆盖密封垫的膜。且更具体地,例如,每个引流针123a与相应的单个破膜针123b成对地毗邻但间隔开设置。
此外,在本公开的另外实施例中,所述导流组件123例如还包括:至少两个导向销123c,从所述顶板120的所述边缘1208的下侧向外突伸且彼此间隔开地呈直线布置,且被构造成与所述储液器2上的对准特征呈形状配合。所述导向销123c与所述对准特征彼此对准之后通过所述导向销123c插入所述对准特征(例如对准孔或对准凹部)来实现所述储液器2与所述导流组件123的装配就位。在更具体地实施例中,例如,所述至少两个导向销123c是与所述多个引流针123a共线布置且分别位于所述多个引流针123a的两端处的两个引流针123a外侧的两个导向销123c。
并且,在本公开的另外实施例中,作为示例,所述流路网络125还包括分别联通至所述芯片接纳区121a的用于排出废液的出口管线、和用于返回注入试剂的返液管线。
利用如上所述的芯片处理装置1的用于输送流体的具体结构,实现了从作为储液器2的试剂盒至测序芯片3之间的无管道化流体路径;并且,根据本公开实施例的上述具体结构,实现了从试剂盒顶部吸液,由此也避免了长行程的试剂盒平移和升降运动、以及避免了试剂针插入到试剂盒底部。同时,结合所述芯片处理装置1的其他结构实现了对于试剂盒的精确定位。
由此,所述导流组件123与前述的流体供应装置150(所述流体供应装置150包括前述的顶板120(充当用于承载测序芯片的载台)、流路网络125和选择器阀126)共同限定了一种流体引导装置160,所述流体引导装置160被配置成将来自储液器(诸如试剂盒2)的多种试剂流体引导至所述测序芯片3。
另外,图10图示了图2(e)俯视图所示的芯片处理装置1沿着E-E线的剖视图,其示出内部的定位装置111和用于探测储液器2在容置仓110内插入就位的就位检测器112。
如图所示,在根据本公开的实施例中,例如,所示芯片处理装置1还包括定位装置111,所述定位装置111例如设置于所述试剂盒平台11内,且包括:凹槽1110,凹入地形成于所述容置仓110的顶侧内壁中;弹性组件,设置于所述凹槽1110内;和定位珠111b,所述定位珠111b设置于所述弹性组件的朝向所述基板的一端处,且被配置成:响应于所述试剂盒没有达到所述容置仓内的所述定位珠处的情况,所述弹性组件处于不受试剂盒所施加力的初始状态且所述定位珠从所述容置仓的所述顶侧内壁至少部分地朝向所述基板凸出;和响应于在所述储液器2插入于所述容置仓110内并且挤压所述定位珠的情况,所述弹性组件经由所述定位珠被朝向所述凹槽内推压、继而使所述弹性组件至少部分缩回至所述凹槽1110内。通过定位装置111的这种设置,当诸如试剂盒之类的储液器2被插入到所述容置仓110内时,所述储液器2逐步将所述弹性组件的从凹槽1110暴露的定位珠111b向凹槽1110内推抵,直至所述储液器2被插入到所述容置仓110内部就位时,所述定位珠111b受处于压缩状态的弹簧111a的弹性恢复力作用向外抵紧所述储液器2的表面,由此实现对储液器2的牢固定位以将所述储液器2保持就位于所述容置仓110内。
在更具体的实施例中,例如,所述试剂盒顶壁25具备朝向所述容置仓的顶侧内壁突伸的突出部23、以及从所述突出部23凹入的定位槽24,并且响应于在所述试剂盒 插入于所述容置仓内并且挤压所述定位珠的情况,所述定位珠被夹持于所述定位槽24与所述弹性组件之间。换言之,所述储液器2的表面上还形成有与储液器2在容置仓110内处于就位状态情况下所述定位珠111b的部位对应设置的至少一个凹穴,且所述凹穴的形状和大小被确定为适于接纳所述定位珠111b,由此,当储液器2插入就位时,所述定位珠111b被受压缩的弹簧111a的弹性恢复力向外推压成与所述凹穴配合,由此将储液器2以弹性方式锁定就位。这种弹性的锁定不会影响后续完成测序工作之后试剂盒从容置仓110被移除。
在根据本公开的实施例中,作为示例,所述芯片处理装置1还包括设置于所述容置仓110内部的就位检测器112,所述就位检测器112包括光耦组件和遮蔽件,所述遮蔽件例如设置于所述储液器2上或与所述储液器2相联接;所述光耦组件包括红外发射器和红外接收器,所述光耦组件例如均设置于所述试剂盒平台11内且彼此间隔开设置、且配置成响应于当所述储液器2插入到所述容置仓110内部就位时所述遮蔽件受所述储液器2所施加的力发生移位或变形并且阻挡由所述红外接收器接收来自红外发射器的红外线的情况而确定所述储液器2已在所述容置仓110内就位。利用这种由所述储液器2携载的遮蔽件,便利了实现储液器2在容置仓110内的就位与否的事件检测和确定已就位。
在本公开的替代实施例中,作为示例,所述芯片处理装置1还包括设置于所述储液器2的外表面的定位特征、以及设置于所述容置仓110内部的就位传感器,所述定位特征在所述储液器2插入到所述容置仓110内部就位的情况下与所述就位传感器对准,且所述就位传感器配置成通过检测由所述定位特征施加的推抵作用来确定所述储液器2已在所述容置仓110内就位。进一步地,例如,所述就位传感器是力传感器。通过这样的替代设置,利用力传感器基于接触力实现了所述储液器2插入于容置仓110内的就位检测。
在根据本公开的实施例中,返回参见图1,作为示例,所述芯片处理装置1还包括形成于所述试剂盒平台11的顶部处的压紧装置113,所述试剂盒平台11的顶部形成有贯通开口以至少部分地暴露插入于所述容置仓110内的储液器2,所述压紧装置113包括:压板1130,其一侧与基板10保持相对固定;销1131,延伸贯穿所述压板1130的与所述一侧相反的自由侧处;一对臂1132,每个臂1132的一端以能够枢转的方式联接至所述销1131的两端中的相应端;和一对弹性件1133,每个弹性件1133(例如扭簧)弹性地联接于所述一对臂1132中相应臂1132与所述试剂盒平台11之间。利用 这种压紧装置113的设置,一旦所述储液器2在所述容置仓110内被插入就位,则例如通过绕所述销1131略微推动所述一对臂1132之一,可以触发所述一对臂1132在所联接的一对弹簧的弹性力的作用下绕销1131的进一步枢转,实现利用压板1130紧密抵压所述容置仓110和储液器2的顶部,由此实现进一步在大致竖直方向将所述容置仓110连同所述储液器2向下压紧。
在根据本公开的实施例中,返回参见图1,进一步地,例如设置额外的倾斜调节结构以促成对于试剂盒平台11和芯片平台12的调平。更具体地,如图1(d)-(f)所示,作为示例,芯片平台12包括固定支架12a,固定支架12a支撑并固定在顶板120与基板10之间,且部分延伸至试剂盒平台与所述基板10之间并与所述试剂盒平台11之间留有间隙。固定支架12a对应所述试剂盒平台11的一侧边缘延伸有与压板1130固定的延伸板12b,试剂盒平台11位于延伸板12b与选择器阀之间。试剂盒平台11包括活动支架11a,试剂仓110由活动支架11a悬置支撑。活动支架11a与可动轨132固定并经可动轨132与固定轨135活动连接。优选地,活动支架11a呈L形。
所述芯片处理装置1还包括设置于固定支架12a与所述基板10之间并位于所述试剂盒平台11一侧的第一倾斜调节机构114,所述第一倾斜调节机构114包括非直线布置的第一定距头和两个能够相对于所述基板10旋拧调节的第一螺纹副1140。另外,作为示例,所述芯片处理装置1还包括固定支架12a与所述基板10之间并位于所述芯片平台12一侧的第二倾斜调节机构124,所述第二倾斜调节机构124包括非直线布置的第二定距头和和两个能够相对于所述基板10旋拧调节的第二螺纹副1240。由于所述第一倾斜调节结构中的第一定距头和两个可调的第一螺纹副1140共同限定了三点式支撑结构,因此实现了一旦利用调节所述第一螺纹副1140对于所述试剂盒平台11的调平之后的稳定支撑;类似地,由于所述第二倾斜调节结构中的第二定距头和两个可调的第二螺纹副1240共同限定了另一个三点式支撑结构,因此实现了一旦利用调节所述第二螺纹副1240对于所述芯片平台12的调平之后的稳定支撑。
在本公开的实施例中,返回参见图2(b)和图2(d),例如,所述芯片处理装置1还包括限位装置14,所述限位装置14包括:感应片140,设置于至少一个导轨组件13中的至少一组交叉滚子导轨130的相应可动轨132上;以及上限位光耦141和下限位光耦142,分别设置于所述至少一组交叉滚子导轨130的相应固定轨131两端的与所述相应可动轨132的行程的上末端和下末端对应的部位处,且分别被配置成响应于通过检测到感应片140遮挡所述上限位光耦141确定所述可动轨132上升至上极限位 置来停止驱动源、且通过响应于检测到感应片140遮挡所述下限位光耦142确定所述可动轨132下降至下极限位置来停止驱动源。所述下极限位置例如为前述的非引流位置,特别地例如是充当所述非引流位置的所述第二位置范围中的最低位置。
通过所述限位装置14的上述具体设置,实现了在所述容置仓110携带插入其内部的储液器2在所述试剂盒平台11内的升降运动期间对于容置仓110的上极限位置与下极限位置的检测和确定,并且实现了所述容置仓110一旦达到这种上极限位置或下极限位置时切断驱动源的动力供应,由此实现了以电控方式的极限位置检测和限位。
并且,额外地,作为本公开的拓展实施例,所述限位装例如还包括分别设置于至少一组交叉滚珠导轨的所述固定轨131两端处的两个限位块,每个限位块至少部分地与相应的可动轨132匹配地对准。由此,一旦所述容置仓110被升高至上极限位置或降低至下极限位置,则限位块实现了以机械方式的辅助限位。
并且,在所述芯片处理装置1中,与上述用于输送流体的具体结构相协同,还设置有动力组件129,所述动力组件129被布置成与所述流路网络成流体连通,且配置成驱动流体经过所述流路网络朝向所述供应端口流动。
作为示例,所示动力组件包括与所述芯片接纳区连通的泵,所述泵被配置成向所述芯片接纳区提供负压。例如,所示泵为至少设置于所述选择器阀126上游和下游中至少一处的注射泵,所述注射泵被配置成向所述芯片接纳区121a提供负压。由此,通过注射泵提供的负压进行对于流体的抽吸,由此无需将引流针123a插入至所述储液器2的底部即可实现对于流体(更具体地例如试剂盒内的试剂)的抽吸,进而提供了流体从试剂盒输送至测序芯片3的吸液和液体供应。
图11以分解图示出温控组件经由适配器支架相对于载台的组装关系。图12(a)示出如图9(f)中沿线A-A的剖视图,图12(b)示出如图9(f)中沿B-B线的剖视图,特别地示出了温控组件的构造及其装配关系,温控组件通过螺钉与顶板组装配合。图13(b)至图13(c)分别示出如图9(f)中沿线C-C、以及线D-D的剖视图,特别地示出了选择器阀与顶板之间通过螺钉S1连接的装配关系。
作为示例,所述流体引导装置160还例如额外地集成有温控组件128,所述温控组件设置于所述顶板的与所述芯片接纳区相反的一侧,且配置成调节从所述导流组件供应至所述芯片接纳区的流体的温度。
另外,在本公开的实施例中,作为示例,所述的温控组件128设置于所述顶板120下方(更具体地在用于接纳所述芯片3的芯片接纳区121a的相反侧表面处),且被配 置成调节从所述导流组件123供应至所述芯片接纳区121a的流体的温度。
在本公开的具体实施例中,例如,所述温控组件128包括第一温度调节装置128a,所述第一温度调节装置128a布置成与所述选择器阀在所述顶板的同侧彼此毗邻设置。并且,作为示例,如图所示,所述流体引导装置还包括固定至所述顶板的与所述芯片接纳区相反的一侧处的适配器支架127,被构造呈框架形式,且所述适配器支架127形成有并列设置的、且分别从所述适配器支架127的背离所述顶板以及朝向所述顶板的相反两侧凹入的两个凹窝1270,1271以供在其中分别容置和固定所述选择器阀和所述第一温度调节装置。
通过这种设置,进一步确保了所述选择器阀相对于载台可靠地固定,并且也实现了所述第一温度调节装置经由所述适配器支架127相对于载台120固定的组装关系。
作为示例,如图所示,所述第一温度调节装置128a包括:散热件,被容置于且安装入所述适配器支架127的所述两个凹窝1270,1271中的从朝向所述顶板的一侧凹入的一个凹窝1271内,且包括主动式散热件和被动式散热件中的至少一种;和温控模块1282,所述温控模块被安装至所述散热件且配置成在所述散热件处的温度超过阈值温度的情况下切断所述动力组件129。
并且,作为示例,所述温控组件还包括插置于所述载台与所述第一温度调节装置之间的导热件128b(也图示为内置于所示适配器支架127内部)。更具体地,例如,所述导热件128b包括相变材料。
在更具体地实施例中,例如,所述主动式散热件包括热电制冷器(例如,诸如帕尔贴效应器件之类的热电制冷器(TEC)、风扇之类);或所述被动式散热件包括散热片,诸如鳍片散热件,形成为单个散热片或散热片阵列。
在本公开的额外的实施例中,作为示例,所述温控组件128还包括第二温度调节装置128c,所述第二温度调节装置固定至所述适配器支架127的背离所述顶板的一侧且与所述旋转阀并列设置、且布置成与所述第一温度调节装置对准。
结合图13(a),在根据本公开的实施例中,所述第二温度调节装置包括风扇1280。所述风扇1280包括:中空的第一壳体1281,其内部限定腔体以供气流流动,所述第一壳体1281布置成使得所述腔体对准所述第一温度调节装置、且朝向所述第一温度调节装置敞开,以将所述腔体流体连通于所述第一温度调节装置与所述流体引导装置的外部之间;以及扇组件,容置于所述第一壳体1281内。
在更进一步的实施例中,例如,所述扇组件包括:第二壳体1283,被构造呈固定 地套设于所述第一壳体1281内的中空的筒状体;转轴1284,以能够旋转的方式安装至所述第二壳体1283内;和多个扇叶1285,所述多个扇叶1285在所述第二壳体1283内同轴地固定至所述转轴1284、且能够随所述转轴1284相对于所述第二壳体1283旋转。
在根据本公开的实施例中,所述适配器支架127还形成有贯穿其内部的、且在相反两端分别朝向所述第一温度调节装置和所述第二温度调节装置的腔体敞开的气体通道1286,所述腔体经由所述气体通道1286连通至所述第一温度调节装置。
由此,所述风扇位于所述第一温度调节装置的所述散热件的远离载台120的一侧,便利了加速气流交换,由此提升所述散热件的热交换速度和效率。
并且,在本公开的实施例中,例如,所述温控模块1282是温控开关,所述温控开关1282被配置成在所述散热件处的温度超过阈值温度的情况下切断所述动力组件129的电源供应。
通过上述设置,便利了实现对于芯片接纳区121a特别是选择器阀126周围的有效温度控制。
并且,在本公开的实施例中,作为示例,所述第二温度调节装置128c还包括减振装置,所述减振装置包括:位于适配器支架127与风扇1280的所述第一壳体1281之间的垫片;和
第二级减振结构,设置于所述风扇1280的所述第一壳体1281内、位于所述第一壳体1281与所述扇组件的所述第二壳体1283之间,包括分别卡入配合到所述第一壳体1281的内壁处、且彼此间隔开设置的多个减振件,所述扇组件的所述第二壳体1283经由所述多个减振件而联接至所述第一壳体1281。
并且,更具体地,作为示例,所述风扇的所述第一壳体经由柔性吸振材质螺纹件1281a而固定至所述适配器支架,第一壳体1281凸设形成有安装所述螺纹件1281a的凸耳1281b,且所述第一级减振结构经由所述螺纹件1281a被推压抵紧于所述适配器支架127与所述第一壳体1281之间。
在进一步的实施例中,例如,所述第一级减振结构128d与所述第二级减振结构128e中的至少一个为振动补偿装置,所述振动补偿装置为弹性件或阻尼件。
在更具体实施例中,所述风扇1280的所述第一壳体1281例如经由柔性吸振材质螺纹件而固定所述适配器支架127,且所述第一级减振结构经由所述螺纹件而被推压 抵紧于所述适配器支架127与所述第一壳体1281之间。
由此,通过上述设置,对于包括用于提供强制风冷的例如风扇的第二温度调节装置128c,进一步采用了呈夹层布置的减振结构(例如图示的彼此分离设置的两级式减振结构),通过使得所述第二温度调节装置128c被插置于所述第一级减振结构128d与所述第二级减振结构128e之间,由此实现了一种三明治式的多级减振构造,能够有效地抵消、或者至少部分地耗散以及阻隔来自用于提供强制风冷的例如风扇128c带来的振动,避免振动从温控组件128特别是包括风扇128c的前述第二温度调节装置128c传递至例如流体引导装置160的其他部位(诸如但不限于流路网络125的分支流道1252和公共流道1253、以及选择器阀126)。
另外,在本公开的实施例中,如图13(b)至图13(c)所示,例如,在本公开的实施例中,如图所示,例如,所述选择器阀126在其阀座1261处经由螺纹连接而固定至所述载台,并且所述选择器阀经由可调式抵压装置161而联接至所述适配器支架127,所述可调式抵压装置161包括:多个定距螺钉1611,分别以能够旋拧的方式贯穿所述适配器支架127且抵压所述选择器阀的所述阀体1262;和多个弹簧1612,分别以一一对应的方式弹性地朝向所述顶板抵压所述多个定距螺钉。
由此,实现了所述选择器阀126例如以类似悬置且浮动的方式被支撑至所述载台120,且弹簧1612形成类似于弹性悬挂结构,与定距螺钉1611相组合工作共同起到承载所述选择器阀126的作用,并且,可调式抵压装置161内的所述弹簧1612还同时辅助地起到过滤来自直接或间接地联接至的振动源(诸如风扇128c和主动式散热件)的振动的作用。
图14示意性地图示了根据本公开实施例的基因测序仪4,其包括:芯片,所述芯片载有待利用流体检测的样品;和前述芯片处理装置。
根据本公开实施例的另一方面,基于本公开实施例的总体技术构思,例如,如图14所示,又提供了一种基因测序仪4,所述芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体。并且,例如,所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中具 有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构;以及,所述试剂盒以能够移除的方式插入所述容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品。
在更具体实施例中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及所述芯片处理装置配置成:响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
作为示例,更具体地,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
作为示例,更具体地,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽20a和多个引导槽20b,以及流体连通于每个引导槽20b的底部与相应试剂槽20a的底部之间的连通通道20c,每个试剂槽20a中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口21、和覆盖于所述第一开口21上的第一可刺穿结构210,且每个引导槽20b具备向上朝向所述凸缘敞开的第二开口22、和覆盖于所述第二开口22上的第二可刺穿结构220。
作为示例,更具体地,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和选择器阀,安装至所述顶板且与所述流路网路成流体连通。
作为示例,更具体地,所述选择器阀包括:阀座1261,所述选择器阀经由所述阀座1261固定至所述顶板;阀体1262,从所述阀座1261沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体1262内部的流体入口126a和被配置成引导流体从所述阀体1262内部向外流动的流体出口126b。并且,作为示例,所述流路网络包括:多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;多个分支流道,每个分支流道 连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区。例如,所述选择器阀布置成使得所述流体出口126b与所述出口端口成流体连通,且所述流体入口126a与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口126a和所述流体出口126b的选择性连通。
作为示例,更具体地,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
作为示例,更具体地,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构210对准的第一末端、且每个引流针具有与相应第二可刺穿结构220对准的第二末端。例如,每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构210、继而插入所述试剂槽20a以暴露所述试剂槽20a来改变所述试剂槽20a内的气压;以及每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构220、继而插入所述引导槽20b以流体连通至所述引导槽20b来汲取所述引导槽20b中的流体。
作为示例,更具体地,在所述多个引流针插入所述引导槽20b的情况下,所述多个引流针各自的自由端高于所述试剂槽20a的底部处的内壁。
作为示例,更具体地,每个引导槽20b被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽20b被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
作为示例,更具体地,所述第一可刺破结构是金属箔;以及所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
所述基因测序仪4由于包括前述的芯片处理装置1,因此也相应地具备所述芯片 处理装置1的所有优点,在此不再赘述。
图15图示了根据本公开实施例的基因测序设备5,包括呈镜像对称且相互邻接设置的一对前述的基因测序仪4。
根据本公开实施例的另一方面,基于本公开实施例的总体技术构思,例如,如图15所示,也提供了一种基因测序设备5,包括:芯片,所述芯片载有待利用流体检测的样品;和至少两个前述芯片处理装置,每个芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体。例如,所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构。并且,例如,所述试剂盒以能够移除的方式插入所述容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品。特别地,例如如图所示,所述至少两个芯片处理装置相互对称设置且各自的芯片平台彼此毗邻设置。
作为示例,更具体地,所述至少两个芯片处理装置包括彼此呈镜像对称布置且各自的芯片平台彼此邻接设置的至少一对芯片处理装置。
作为示例,更具体地,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态。并且,例如,所述芯片处理装置配置成:响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
作为示例,更具体地,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
作为示例,更具体地,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽20a和多个引导槽20b,以及流体连通于每个引导槽20b的底部与相应试剂槽20a的底部之间的连通通道20c,每个试剂槽20a中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口21、和覆盖于所述第一开口21上的第一可刺穿结构210,且每个引导槽20b具备向上朝向所述凸缘敞开的第二开口22、和覆盖于所述第二开口22上的第二可刺穿结构220。
作为示例,更具体地,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和选择器阀,安装至所述顶板且与所述流路网路成流体连通。
作为示例,更具体地,所述选择器阀包括:阀座1261,所述选择器阀经由所述阀座1261固定至所述顶板;阀体1262,从所述阀座1261沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体1262内部的流体入口126a和被配置成引导流体从所述阀体1262内部向外流动的流体出口126b。并且,作为示例,所述流路网络包括:多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区。并且例如,所述选择器阀布置成使得所述流体出口126b与所述出口端口成流体连通,且所述流体入口126a与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口126a和所述流体出口126b的选择性连通。
作为示例,更具体地,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
作为示例,更具体地,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构210对准的第一末端、且每个引流针具有与相应第二可刺穿结构220对准的第二末端。并且,例如,每个破膜针不连接至所述流路 网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构210、继而插入所述试剂槽20a以暴露所述试剂槽20a来改变所述试剂槽20a内的气压。并且,例如,每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构220、继而插入所述引导槽20b以流体连通至所述引导槽20b来汲取所述引导槽20b中的流体。
作为示例,更具体地,在所述多个引流针插入所述引导槽20b的情况下,所述多个引流针各自的自由端高于所述试剂槽20a的底部处的内壁。
作为示例,更具体地,每个引导槽20b被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽20b被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
作为示例,更具体地,所述第一可刺破结构是金属箔;以及所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
所述基因测序设备5包括前述芯片处理装置1和前述基因测序仪4,由此具有前述芯片处理装置1的所有优点,在此不再赘述。并且,通过彼此镜像设置的两个前述基因测序仪4,能够实现两张芯片3同时上机且它们间距最小化,极大地缩小了切换芯片3的移动距离,相应地缩短了测试的时间间隔。
图16图示了根据本公开实施例的应用图14所示的基因测序仪4的生化检测方法的示意性流程图。图17示意性示出了如图16的流程图的方法中的更具体步骤。
根据本公开实施例的另一方面,基于本公开实施例的总体技术构思,例如,如图16所示,还提供了一种应用根据前述的基因测序仪4的生化检测方法。所述基因测序仪包括:芯片,所述芯片载有待利用流体检测的样品;和芯片处理装置,所述芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体。并且,例如,所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所 述第一流体输送结构至少部分地交叠且连通的第二流体输送结构。并且,例如,所述试剂盒以能够移除的方式插入所述容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品。
作为示例,所述生化检测方法包括:S1:在具有待检测样品的芯片和具有多种不同反应成分的试剂盒之间建立流体连接,所述反应成分包括样本生成成分或样本分析成分至少之一。S2:执行生成操作和/或分析操作。其中所述试剂盒和芯片集成于上述实施例中所述的芯片处理装置,且所述试剂盒中的所述流体经由所述芯片处理装置中且相互分离的第一流体输送结构和第二流体输送结构流体连通至所述芯片。
可选地,在生成操作中在所述芯片生成待检测样本,所述生成操作包括使不同样本生成成分流入所述芯片并控制所述芯片的反应条件以生成所述样本。在分析操作中分析所述芯片的所述样本,所述分析操作包括使样本分析成分流入所述芯片,所述样本分析成分与所述样本发生反应以提供相关可检测信号。其中,所述生化反应可以是核酸测序反应或抗原抗体结合反应,所述待检测样本可以为核酸测序文库或生物组织切片;所述可检测信号优选为光学信号。
第一流体输送结构与所述芯片处理装置的外部气压连通以驱动所述试剂盒中的所述流体流入所述第二流通输送结构;以及将所述芯片与所述流体选择性连通。例如,所述第二流通输结构具有上述多个分支流道,利用集成在所述芯片处理装置的上述选择器阀126控制不同所述多个分支流道与所述芯片的选择性连通。
并且,为使本领域技术人员能够更清楚明白地理解本发明,以下结合图17所示,示出了图16所示方法的更具体步骤。
在本公开的更具体的实施例中,例如,步骤S1中在芯片和试剂盒之间建立流体连接包括:将试剂盒(与上述实施例中描述的储液器2具有相似结构)穿过容置仓110的敞开开口而插入到容置仓110内,和利用设置于所述容置仓110内部的前述就位检测器112来检测所述试剂盒是否在容置仓110中就位,以及利用容置仓110中的前述定位装置111的定位珠111b在弹簧111a的弹性推抵作用下紧密抵压所述试剂盒以将试剂盒保持就位。
在具体的实施例中,例如,所述容置仓通过一可移动支架(相当于上述活动支架11a)实现在芯片处理装置中的移动、以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的 状态、以及不成流体连通的状态。并且,作为示例,所述芯片处理装置配置成:响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。在此设置下,进一步地,所述方法还包括:将所述试剂盒插入所述容置仓中就位之后,升高所述容置仓至所述引流位置,由此触发随后的所述试剂盒流体连通至支撑芯片的载台(与上述实施例中的顶板120具有相似结构)。
在具体的实施例中,例如,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。并且,作为示例,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽20a和多个引导槽20b,以及流体连通于每个引导槽20b的底部与相应试剂槽20a的底部之间的连通通道20c,每个试剂槽20a中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口21、和覆盖于所述第一开口21上的第一可刺穿结构210,且每个引导槽20b具备向上朝向所述凸缘敞开的第二开口22、和覆盖于所述第二开口22上的第二可刺穿结构220。并且,作为示例,所述第二流体输送结构包括导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构210对准的第一末端、且每个引流针具有与相应第二可刺穿结构220对准的第二末端,每个破膜针被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构210、继而插入所述试剂槽20a以暴露所述试剂槽20a来改变所述试剂槽20a内的气压,且每个引流针被构造为中空的针状、且与所述芯片上载有的所述样品成选择性的流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构220、继而插入所述引导槽20b以流体连通至所述引导槽20b来汲取所述引导槽20b中的流体。由此,所述方法还包括容置仓110下降返回。具体地,在升高所述容置仓至所述引流位置之后,通过带动每个破膜针的相应第一末端刺穿所述第一可刺穿结构210,以及带动每个引流针的相应第二末端刺穿所述第二可刺穿结构220,建立所述第一流体输送结构与所述第二流体输送结构之间的流体连通;以及在将所述容置仓从所述引流位置向非引流位置降低复位之后,通过带动每个破膜针的相应第一末端脱离所述第一可刺穿结构210,以及带动每个引流针的相应第二末端脱离所述第二 可刺穿结构220,切断所述第一流体输送结构与所述第二流体输送结构之间的流体连通。
在进一步的实施例中,作为示例,步骤S1还包括分别提高对前述第一倾斜调节机构114和前述第二倾斜调节机构124各自的可调螺纹副进行调节来调平所述试剂盒平台11和所述芯片平台12。具体地,分别通过调节由所述第一倾斜调节结构中的第一定距头和两个可调的第一螺纹副1140共同限定的三点式支撑结构来调平和稳定支撑所述试剂盒平台11,并且通过调节由所述第二倾斜调节结构中的第二定距头和两个可调的第二螺纹副1240共同限定的另一个三点式支撑结构来调平和稳定支撑所述芯片平台12。
在进一步的另一实施例中,作为示例,步骤S1还包括利用形成于所述试剂盒平台11的顶部处的前述压紧装置113,通过绕所述销1131略微推动所述一对臂1132之一,由此触发所述一对臂1132在所联接的一对弹簧111a的弹性力的作用下绕销1131的进一步枢转,实现利用压板1130紧密抵压所述容置仓110和储液器2的顶部,由此实现进一步在大致竖直方向将所述容置仓110连同所述储液器2向下压紧。
在本公开的更具体的实施例中,例如,步骤S1还包括:由前述驱动源经由所述至少一个导轨组件13中的各组交叉滚子导轨130的导向来驱动所述容置仓110从初始的较低位置开始执行上升运动。
在进一步的实施例中,作为示例,步骤S1还包括:由前述的限位装置14响应于所述容置仓110上升达到上极限位置的情况来停止所述驱动源。
在本公开的更具体的实施例中,例如,步骤S1还包括:利用前述的导流组件123中的导流针穿刺入储液器2,并且随后利用前述的选择器阀126(例如,旋转阀)切换至与期望的分支流道1252成流体连通,由此将通往所述储液器2(例如试剂盒)的期望的分支流道1252经由所述选择器阀126进而流经所述单一的公共流道1253来与所述测序芯片3成流体连通。
在本公开的更具体的实施例中,例如,步骤S1还包括:将芯片3(例如基因测序芯片3)置于形成于所述芯片处理装置1的所述芯片平台12的载台(顶板120)上的芯片接纳区121a中,并且例如经由所述芯片接纳区121a侧壁处的抵压和所述芯片接纳区121a底部处的吸附(例如由吸附装置,诸如负气压吸附装置或磁性吸附装置所产生的吸附力而实现)而将所述芯片3在所述芯片接纳区121a中保持就位。
在本公开的更具体的实施例中,例如,步骤S1包括:通过将来自选择器阀126和所述单一的公共流道1253的试剂流体引入至容纳所述芯片3的芯片接纳区121a,实现试剂与样本的接触并执行上述分析和/或生成操作。
在本公开的更具体的实施例中,例如,所述方法还包括“将芯片3从芯片处理装置1移除”,例如通过禁用/取消吸附力并且随后从芯片接纳区121a移除所述芯片3来从芯片处理装置1取出所述芯片3。
在本公开的更具体的实施例中,例如,所述方法还包括:由前述驱动源经由所述至少一个导轨组件13中的各组交叉滚子导轨130的导向来驱动所述容置仓110执行下降运动直至复位至初始的较低位置。
在本公开的更具体的实施例中,例如通过首先反向枢转所述压紧装置113来将所述储液器2从所述容置仓110释放,并且随后将所述储液器2从所述容置仓110的敞开开口移出。
所述应用前述基因测序仪4的方法采用前述芯片处理装置1和前述基因测序仪4,由此具有前述芯片处理装置1的所有优点,在此不再赘述。
由此,本公开的实施例所披露的芯片处理装置、基因测序仪、基因测序设备、以及应用所述基因测序仪的方法相比于本领域的相关技术,具备如下优越的技术效果:
本公开的实施例所实现的芯片处理装置、基因测序仪、基因测序设备和生化检测方法,特别是芯片处理装置,能够通过如上的设置,实现一体化的无管道式流体输送结构,其具备减少的流道长度,对于试剂盒的更可靠的调平和紧固作用、以及更高的定位精度。并且采用了从试剂盒顶部吸液结合注射泵的使用的设置,避免了长行程的平移和升降运动且也避免了如常规操作中般必需将试剂针插入到试剂盒底部。由此,能够在改善集成度从而提高空间利用率的同时改善流体输送结构的固定、定位、行程等等,并且以更紧凑的构造实现设计预期。且这种紧凑的结构使得空间占用最小化,且简单的构造和联接关系便利了装配和拆卸。
在本说明书的描述中,参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中,对上述术语的示意性表述不必须针对的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或示例中以合适的方式结合。此外,在不相互 矛盾的情况下,本领域的技术人员可以将本说明书中描述的不同实施例或示例以及不同实施例或示例的特征进行结合和组合。
虽然结合附图对本公开进行了说明,但是附图中公开的实施例旨在对本公开优选实施方式进行示例性说明,而不能理解为对本公开的一种限制。
虽然本公开总体构思的一些实施例已被显示和说明,本领域普通技术人员将理解,在不背离本总体构思的原则和精神的情况下,可对这些实施例做出改变,本公开的范围以权利要求和它们的等同物限定。

Claims (89)

  1. 一种集成有试剂盒的芯片处理装置,包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置载有待利用流体检测的样品的芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内;
    其中,所述试剂盒具有位于其内部的沿所述第二方向朝向所述芯片平台的一侧处的第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构,所述第一流体输送结构经由所述第二流体输送结构流体连通至所述芯片。
  2. 根据权利要求1所述的芯片处理装置,其中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及
    所述芯片处理装置配置成:
    响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和
    响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
  3. 根据权利要求2所述的芯片处理装置,其中,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
  4. 根据权利要求3所述的芯片处理装置,其中,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽和多个引导槽,以及流体连通于每个引导槽的底部与相应试剂槽的底部之间的连通通道,每个试剂槽中至少部分地填充有流 体并且具备向上朝向所述凸缘敞开的第一开口、和覆盖于所述第一开口上的第一可刺穿结构,且每个引导槽具备向上朝向所述凸缘敞开的第二开口、和覆盖于所述第二开口上的第二可刺穿结构。
  5. 根据权利要求4所述的芯片处理装置,其中,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:
    流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和
    选择器阀,安装至所述顶板且与所述流路网路成流体连通。
  6. 根据权利要求5所述的芯片处理装置,其中,
    所述选择器阀包括:
    阀座,所述选择器阀经由所述阀座固定至所述顶板;
    阀体,从所述阀座沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体内部的流体入口和被配置成引导流体从所述阀体内部向外流动的流体出口;以及
    所述流路网络包括:
    多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;
    多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;
    多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;
    出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和
    公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区,
    其中,所述选择器阀布置成使得所述流体出口与所述出口端口成流体连通,且所述流体入口与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的选择性连通。
  7. 根据权利要求6所述的芯片处理装置,其中,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
  8. 根据权利要求6所述的芯片处理装置,其中,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构对准的第一末端、且每个引流针具有与相应第二可刺穿结构对准的第二末端,
    其中,每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构、继而插入所述试剂槽以暴露所述试剂槽来改变所述试剂槽内的气压;以及
    每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构、继而插入所述引导槽以流体连通至所述引导槽来汲取所述引导槽中的流体。
  9. 根据权利要求8所述的芯片处理装置,其中,在所述多个引流针插入所述引导槽的情况下,所述多个引流针各自的自由端高于所述试剂槽的底部处的内壁。
  10. 根据权利要求9所述的芯片处理装置,其中,每个引导槽被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
  11. 根据权利要求8所述的芯片处理装置,其中,所述第一可刺破结构是金属箔;以及
    所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
  12. 根据权利要求8所述的芯片处理装置,其中,所述多个引流针彼此间隔开地呈直线布置,且所述多个破膜针彼此间隔开地呈直线布置;以及
    所述多个引流针与所述多个破膜针两者彼此平行布置。
  13. 根据权利要求12所述的芯片处理装置,其中,所述多个引流针中每个的旁侧一一对应地布置有相应破膜针,且每个引流针与相应的单个破膜针成对地毗邻但间隔开设置。
  14. 根据权利要求8所述的芯片处理装置,其中,每个引流针包括中空且伸长的空心直管状针主体、和具备锥形渐缩的纵向截面形状的贯通的顶端。
  15. 根据权利要求8所述的芯片处理装置,其中,所述多个引流针以螺纹连接方式安装至所述多个引流针端口。
  16. 根据权利要求8所述的芯片处理装置,其中,所述导流组件还包括:至少两个导向销,从所述顶板的与所述芯片接纳区相反的一侧向外突伸且彼此间隔开地呈直线布置,且被构造成与所述试剂盒上的对准特征呈形状配合。
  17. 根据权利要求6所述的芯片处理装置,其中,所述多个引流针端口布置呈直线地彼此对准。
  18. 根据权利要求17所述的芯片处理装置,其中,所述多个引流针端口布置成以均一的间距彼此分离。
  19. 根据权利要求6所述的芯片处理装置,其中,所述选择器阀是旋转阀,且所述旋转阀被配置成能够围绕其轴线旋转以使得切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的的选择性连通。
  20. 根据权利要求19所述的芯片处理装置,其中,所述入口端口和所述出口端口各自的轴向平行于所述轴线,且所述入口端口设置成与所述轴线偏离,且所述出口端口与所述轴线同轴设置。
  21. 根据权利要求20所述的芯片处理装置,其中,所述选择器阀经由所述阀座而被安装至所述顶板的与所述芯片接纳区背离的背侧面,以及
    其中,所述多个入口端口被构造成绕所述轴线呈环形布置,所述多个入口端口和所述出口端口均向所述顶板的所述背侧面敞开,且所述多个入口端口中的至少一个选择性连通至所述阀体的所述流体入口、所述出口端口连通至所述阀体的所述流体出口,且所述多个入口端口中的每个与所述出口端口之间的中心距是相等的。
  22. 根据权利要求19所述的芯片处理装置,其中,所述多个分支流道被布设成围绕所述旋转阀呈放射状发散且转向至分别与所述多个引流针端口一一对应地连通。
  23. 根据权利要求6所述的芯片处理装置,其中,所述顶板包括:顶层,所述芯片接纳区形成于所述顶层中;和支撑层,所述支撑层与所述顶层呈层叠设置,且位于所述顶层与所述选择器阀之间,以及
    其中,所述多个分支流道和所述公共流道形成于所述支撑层的朝向所述顶层的一侧,且所述多个入口端口、所述出口端口以及所述多个引流针端口延伸贯穿所述支撑层。
  24. 根据权利要求23所述的芯片处理装置,其中,所述顶层的所述芯片接纳区中形成有贯通的容置孔,以及从所述顶层的背离所述支撑层的一侧凹入的、且围绕所述容置孔设置的凹部。
  25. 根据权利要求24所述的芯片处理装置,其中,所述顶板还包括芯片吸附组件,所述芯片吸附组件被布置成部分地固定于所述容置孔内并且从所述容置孔背离所述支撑层突伸出,且被配置成容置并且吸附芯片,包括:
    与负压源连通的管接头;
    吸附台,部分地安置于所述容置孔中,其顶表面的边缘向外突伸以限定所述顶层中的朝向所述支撑层凹入的、介于所述边缘与所述顶表面之间的吸附槽,所述吸附槽被构造呈沿所述边缘延伸且闭合回路形式的闭合槽、且被确定形状和大小为适于围绕且固定所述芯片的边缘;以及
    负压通道,贯通地形成于所述吸附台内并且连通于所述管接头与所述吸附槽之间。
  26. 根据权利要求24所述的芯片处理装置,其中,所述顶层形成有贯穿其中且延伸至所述凹部的供应端口以及排出端口,所述供应端口经由所述公共流道与所述阀体的所述出口端口成流体连通,且所述排出端口与所述供应端口间隔开。
  27. 根据权利要求26所述的芯片处理装置,其中,所述公共流道呈直线地联接于所述出口端口与所述供应端口之间。
  28. 根据权利要求27所述的芯片处理装置,其中,所述多个分支流道被布置成彼此不交叉且避开所述公共流道。
  29. 根据权利要求26所述的芯片处理装置,其中,所述排出端口和所述供应端口各自的与所述支撑层的端部分别延伸至所述凹部;以及
    其中,在所述芯片被接纳且吸附于所述吸附台上的情况下,所述吸附台与所述芯片之间共同限定第一液密密封面,且所述芯片在所述第一液密密封面处分别与所述供应端口和所述排出端口形成密封的流体连通。
  30. 根据权利要求26所述的芯片处理装置,其中,所述支撑层形成有贯通其中且从所述排出端口流体连通至所述顶板外部的排出通道。
  31. 根据权利要求23所述的芯片处理装置,其中,所述多个入口端口和所述出口端口延伸贯穿所述支撑层至所述顶板的背侧面,所述背侧面与所述阀座之间共同限定第二液密密封面,并且所述多个入口端口和所述出口端口在所述第二液密密封面处分别与所述阀体的所述流体入口和所述流体出口形成密封的流体连通。
  32. 根据权利要求8所述的芯片处理装置,其中,所述芯片处理装置还包括设于其内部的驱动件、联接于所述容置仓与所述基板之间的至少一个导轨组件,所述容置仓能够由所述驱动件经由所述至少一个导轨组件的传动沿与所述基板正交的方向移动且使得所述导流组件插入且流体联通至所述试剂盒。
  33. 根据权利要求32所述的芯片处理装置,其中,所述驱动件包括:驱动源,包括步进电机、压电驱动器之一;以及在所述驱动源与所述至少一个导轨组件之间成传动联接的丝杠。
  34. 根据权利要求33所述的芯片处理装置,其中,每个导轨组件包括间隔开的两组交叉滚子导轨,每组交叉滚子导轨包括固定至所述芯片平台的固定轨、联接至所述容置仓的可动轨、和保持于所述固定轨与所述可动轨之间的多个滚动件。
  35. 根据权利要求34所述的芯片处理装置,其中,每组交叉滚子导轨中,所述固定轨以与所述基板正交的方式固定至所述芯片平台,且所述可动轨以与所述基板正交的方式固定至所述容置仓。
  36. 根据权利要求35所述的芯片处理装置,其中,所述丝杠与所述至少一个导轨组件中的两组交叉滚子导轨各自的可动轨联接。
  37. 根据权利要求1所述的芯片处理装置,还包括定位装置,所述定位装置包括:
    凹槽,凹入地形成于所述容置仓的顶侧内壁中;
    弹性组件,设置于所述凹槽内,以及
    定位珠,所述定位珠设置于所述弹性组件的朝向所述基板的一端处,且被配置成:
    响应于所述试剂盒没有达到所述容置仓内的所述定位珠处的情况,所述弹性组件处于不受试剂盒所施加力的初始状态且所述定位珠从所述容置仓的所述顶侧内壁至少部分地朝向所述基板凸出;和
    响应于在所述试剂盒插入于所述容置仓内并且挤压所述定位珠的情况,所述弹性组件经由所述定位珠被朝向所述凹槽内推压、继而使所述弹性组件至少部分缩回至所述凹槽内。
  38. 根据权利要求37所述的芯片处理装置,其中,所述试剂盒具备朝向所述容置仓的顶侧内壁突伸的突出部、以及从所述突出部凹入的定位槽,并且
    响应于在所述试剂盒插入于所述容置仓内并且挤压所述定位珠的情况,所述定位 珠被夹持于所述定位槽与所述弹性组件之间。
  39. 根据权利要求1或37所述的芯片处理装置,还包括设置于所述容置仓内部的就位检测器,所述就位检测器包括光耦组件和遮蔽件,所述光耦组件包括红外发射器和红外接收器,且配置成响应于当所述试剂盒插入到所述容置仓内部就位时所述遮蔽件受所述试剂盒所施加的力发生移位或变形并且阻挡由所述红外接收器接收来自红外发射器的红外线的情况而确定所述试剂盒已在所述容置仓内就位。
  40. 根据权利要求1所述的芯片处理装置,还包括形成于所述试剂盒平台的顶部处的压紧装置,所述试剂盒平台的顶部形成有贯通开口以至少部分地暴露插入于所述容置仓内的所述试剂盒,所述压紧装置包括:
    压板,其一侧被固定至所述试剂盒平台;
    销,延伸贯穿所述压板的与所述一侧相反的自由侧处;
    一对臂,每个臂的一端以能够枢转的方式联接至所述销的两端中的相应端;和
    一对弹性件,每个弹性件弹性地联接于所述一对臂中相应臂与所述试剂盒平台之间。
  41. 根据权利要求1所述的芯片处理装置,还包括设置于所述试剂盒平台的底部与所述基板之间的第一倾斜调节机构,所述第一倾斜调节机构包括非直线布置的第一定距头和两个能够相对于所述基板旋拧调节的第一螺纹副。
  42. 根据权利要求1所述的芯片处理装置,还包括设置于所述芯片平台的底部与所述基板之间的第二倾斜调节机构,所述第二倾斜调节机构包括非直线布置的第二定距头和和两个能够相对于所述基板旋拧调节的第二螺纹副。
  43. 根据权利要求34所述的芯片处理装置,还包括限位装置,所述限位装置包括:
    感应片,设置于至少一个导轨组件中的至少一组交叉滚子导轨的相应可动轨上;和
    上限位光耦和下限位光耦,分别设置于所述至少一组交叉滚子导轨的相应固定轨两端的与所述相应可动轨的行程的上末端和下末端对应的部位处,且分别被配置成响 应于通过检测到感应片遮挡所述上限位光耦确定所述可动轨上升至上极限位置来停止驱动源、且通过响应于检测到感应片遮挡所述下限位光耦确定所述可动轨下降至下极限位置来停止驱动源。
  44. 根据权利要求8至16中任一项所述的芯片处理装置,还包括动力组件,所述动力组件被布置成与所述流路网络成流体连通,且配置成驱动流体经过所述流路网络朝向所述供应端口流动。
  45. 根据权利要求44所述的芯片处理装置,其中,所述动力组件包括与所述芯片接纳区连通的泵,所述泵被配置成向所述芯片接纳区提供负压。
  46. 根据权利要求44所述的芯片处理装置,其中,还包括温控组件,所述温控组件设置于所述顶板的与所述芯片接纳区相反的一侧,且配置成调节从所述导流组件供应至所述芯片接纳区的流体的温度。
  47. 根据权利要求46所述的芯片处理装置,其中,所述温控组件包括第一温度调节装置,所述第一温度调节装置布置成与所述选择器阀在所述顶板的同侧彼此毗邻设置,且
    其中,所述流体引导装置还包括固定至所述顶板的与所述芯片接纳区相反的一侧处的适配器支架,被构造呈框架形式,且所述适配器支架形成有并列设置的、且分别从所述适配器支架的背离所述顶板以及朝向所述顶板的相反两侧凹入的两个凹窝以供在其中分别容置和固定所述选择器阀和所述第一温度调节装置。
  48. 根据权利要求47所述的芯片处理装置,其中,所述第一温度调节装置包括:
    散热件,被容置于且安装入所述适配器支架的所述两个凹窝中的从朝向所述顶板的一侧凹入的一个凹窝内,且包括:主动式散热件和被动式散热件中的至少一种;和
    温控模块,安装至所述散热件且配置成在所述散热件处的温度超过阈值温度的情况下切断所述动力组件。
  49. 根据权利要求47所述的芯片处理装置,其中,所述温控组件还包括:插置于 所述顶板与所述第一温度调节装置之间的导热件。
  50. 根据权利要求49所述的芯片处理装置,其中,所述导热件包括相变材料。
  51. 根据权利要求48所述的芯片处理装置,其中,所述主动式散热件包括热电制冷器;或
    所述被动式散热件包括如下之一:单个散热片、散热片阵列。
  52. 根据权利要求47所述的芯片处理装置,其中,所述温控组件还包括第二温度调节装置,所述第二温度调节装置固定至所述适配器支架的背离所述顶板的一侧且与所述选择器阀并列设置、且布置成与所述第一温度调节装置对准。
  53. 根据权利要求52所述的芯片处理装置,其中,所述第二温度调节装置包括风扇,所述风扇包括:
    中空的第一壳体,其内部限定腔体以供气流流动,所述第一壳体布置成使得所述腔体对准所述第一温度调节装置、且朝向所述第一温度调节装置敞开,以将所述腔体流体连通于所述第一温度调节装置与所述流体引导装置的外部之间;以及
    扇组件,容置于所述第一壳体内,所述扇组件包括:
    第二壳体,被构造呈固定地套设于所述第一壳体内的中空的筒状体;
    转轴,以能够旋转的方式安装至所述第二壳体内;和
    多个扇叶,所述多个扇叶在所述第二壳体内同轴地固定至所述转轴、且能够随所述转轴相对于所述第二壳体旋转。
  54. 根据权利要求53所述的芯片处理装置,其中,所述适配器支架还形成有贯穿其内部的、且在相反两端分别朝向所述第一温度调节装置和所述第二温度调节装置的腔体敞开的气体通道,所述腔体经由所述气体通道连通至所述第一温度调节装置。
  55. 根据权利要求53所述的芯片处理装置,其中,所述第二温度调节装置还包括减振装置,所述减振装置包括:
    第一级减振结构,被构造呈插置于所述适配器支架与所述风扇的所述第一壳体之 间的垫片;和
    第二级减振结构,设置于所述风扇的所述第一壳体内、位于所述第一壳体与所述扇组件的所述第二壳体之间,包括分别卡入配合到所述第一壳体的内壁处、且彼此间隔开设置的多个减振件,所述扇组件的所述第二壳体经由所述多个减振件而联接至所述第一壳体。
  56. 根据权利要求55所述的芯片处理装置,其中,所述第一级减振结构与所述第二级减振结构中的至少一个为振动补偿装置,所述振动补偿装置为弹性件或阻尼件。
  57. 根据权利要求55所述的芯片处理装置,其中,所述风扇的所述第一壳体经由柔性吸振材质螺纹件而固定至所述适配器支架,且所述第一级减振结构经由所述螺纹件而被推压抵紧于所述适配器支架与所述第一壳体之间。
  58. 根据权利要求47或57所述的芯片处理装置,其中,所述选择器阀在其阀座处经由螺纹连接而固定至所述顶板,并且所述选择器阀经由可调式抵压装置而联接至所述适配器支架,所述可调式抵压装置包括:
    多个定距螺钉,分别以能够旋拧的方式贯穿所述适配器支架且抵压所述选择器阀的所述阀体;和
    多个弹簧,分别以一一对应的方式弹性地朝向所述顶板抵压所述多个定距螺钉。
  59. 一种基因测序仪,包括:
    芯片,所述芯片载有待利用流体检测的样品;和
    芯片处理装置,所述芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体,
    其中,所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装 情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构,以及
    所述试剂盒以能够移除的方式插入所述容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品。
  60. 根据权利要求59所述的基因测序仪,其中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及
    所述芯片处理装置配置成:
    响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和
    响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
  61. 根据权利要求60所述的基因测序仪,其中,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
  62. 根据权利要求61所述的基因测序仪,其中,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽和多个引导槽,以及流体连通于每个引导槽的底部与相应试剂槽的底部之间的连通通道,每个试剂槽中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口、和覆盖于所述第一开口上的第一可刺穿结构,且每个引导槽具备向上朝向所述凸缘敞开的第二开口、和覆盖于所述第二开口上的第二可刺穿结构。
  63. 根据权利要求62所述的基因测序仪,其中,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:
    流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和
    选择器阀,安装至所述顶板且与所述流路网路成流体连通。
  64. 根据权利要求63所述的基因测序仪,其中,
    所述选择器阀包括:
    阀座,所述选择器阀经由所述阀座固定至所述顶板;
    阀体,从所述阀座沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体内部的流体入口和被配置成引导流体从所述阀体内部向外流动的流体出口;以及
    所述流路网络包括:
    多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;
    多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;
    多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;
    出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和
    公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区,
    其中,所述选择器阀布置成使得所述流体出口与所述出口端口成流体连通,且所述流体入口与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的选择性连通。
  65. 根据权利要求64所述的基因测序仪,其中,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
  66. 根据权利要求64所述的基因测序仪,其中,所述第二流体输送结构还包括从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构对准的第一末端、且每个引流针具有与相应第二可刺穿结构对准的第二末端,
    其中,每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构、继而插入所述试剂槽以暴露所述试剂槽来改变所述试剂槽内的气压;以及
    每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构、继而插入所述引导槽以流体连通至所述引导槽来汲取所述引导槽中的流体。
  67. 根据权利要求66所述的基因测序仪,其中,在所述多个引流针插入所述引导槽的情况下,所述多个引流针各自的自由端高于所述试剂槽的底部处的内壁。
  68. 根据权利要求67所述的基因测序仪,其中,每个引导槽被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
  69. 根据权利要求66所述的基因测序仪,其中,所述第一可刺破结构是金属箔;以及
    所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
  70. 一种基因测序设备,包括:
    芯片,所述芯片载有待利用流体检测的样品;和
    至少两个芯片处理装置,每个芯片处理装置包括沿第一方向延伸的基板、和沿横向于所述第一方向的第二方向并排且毗邻地组装于所述基板上的试剂盒平台和芯片平台,所述芯片平台的背离所述基板一侧处的顶板上具备用于容置所述芯片的芯片接纳区,所述试剂盒平台形成有中空的容置仓,所述试剂盒接纳于所述容置仓内、且内部至少部分地填充有所述流体,
    其中,所述试剂盒具有位于所述试剂盒的沿所述第二方向朝向所述芯片平台的一侧处第一流体输送结构,且所述芯片平台中具有位于所述芯片平台的沿所述第二方向朝向所述试剂盒平台的一侧处的、且被构造成在所述试剂盒平台与所述芯片平台组装 情况下与所述第一流体输送结构至少部分地交叠且连通的第二流体输送结构;
    所述试剂盒以能够移除的方式插入所述容置仓内,且所述试剂盒中的所述流体经由所述第一流体输送结构和所述第二流体输送结构流体连通至所述芯片上载有的所述样品;以及
    所述至少两个芯片处理装置相互对称设置且各自的芯片平台彼此毗邻设置。
  71. 根据权利要求70所述的基因测序设备,其中,所述至少两个芯片处理装置包括彼此呈镜像对称布置且各自的芯片平台彼此邻接设置的至少一对芯片处理装置。
  72. 根据权利要求70所述的基因测序设备,其中,所述容置仓以能够在最高的引流位置与低于所述引流位置的非引流位置之间的范围内线性移动的方式联接至所述基板,所述引流位置和所述非引流位置分布对应于所述第一流体输送结构与所述第二流体输送结构之间成流体连通的状态、以及不成流体连通的状态;以及
    所述芯片处理装置配置成:
    响应于所述容置仓背离所述基板上升至引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此接合成流体连通;和
    响应于所述容置仓朝向所述基板下降至非引流位置,将所述第一流体输送结构与所述第二流体输送结构彼此分离。
  73. 根据权利要求72所述的基因测序设备,其中,所述芯片平台的背离所述基板一侧处的所述顶板具备沿所述第二方向朝向所述试剂盒平台突伸的凸缘,且所述试剂盒平台部分嵌入装配于所述顶板的所述凸缘与所述基板之间。
  74. 根据权利要求73所述的基因测序设备,其中,所述第一流体输送结构包括以一一对应关系设置于所述试剂盒内的多个试剂槽和多个引导槽,以及流体连通于每个引导槽的底部与相应试剂槽的底部之间的连通通道,每个试剂槽中至少部分地填充有流体并且具备向上朝向所述凸缘敞开的第一开口、和覆盖于所述第一开口上的第一可刺穿结构,且每个引导槽具备向上朝向所述凸缘敞开的第二开口、和覆盖于所述第二开口上的第二可刺穿结构。
  75. 根据权利要求74所述的基因测序设备,其中,所述第二流体输送结构包括流体供应装置,所述流体供应装置包括:
    流路网络,形成于所述芯片平台的所述顶板中且连通于所述第一流体输送结构与所述芯片之间,和
    选择器阀,安装至所述顶板且与所述流路网路成流体连通。
  76. 根据权利要求75所述的基因测序设备,其中,
    所述选择器阀包括:
    阀座,所述选择器阀经由所述阀座固定至所述顶板;
    阀体,从所述阀座沿背离所述顶板的方向延伸、且形成有被配置成引导流体流入阀体内部的流体入口和被配置成引导流体从所述阀体内部向外流动的流体出口;以及
    所述流路网络包括:
    多个引流针端口,位于所述顶板的与所述芯片接纳区相反的一侧;
    多个入口端口,布置成以一一对应关系与所述多个引流针端口间隔开;
    多个分支流道,每个分支流道连通于每个引流针端口与相应的入口端口之间,且配置成从每个引流针端口输入的流体引导至相应的入口端口;
    出口端口,布置成与所述多个入口端口间隔开且不与所述多个分支流道连通;和
    公共流道,连通于所述出口端口与所述芯片接纳区之间,且配置成将所述出口端口输出的流体引导至所述芯片接纳区,
    其中,所述选择器阀布置成使得所述流体出口与所述出口端口成流体连通,且所述流体入口与所述多个入口端口中的至少一个成流体连通,且被配置成切换与所述多个分支流道对应的所述多个入口端口中的至少一个与所述出口端口之间的、经由所述流体入口和所述流体出口的选择性连通。
  77. 根据权利要求76所述的基因测序设备,其中,所述多个引流针端口贯穿地形成于所述顶板的边缘处、朝向所述顶板的背离所述芯片接纳区的一侧突伸的凸部中。
  78. 根据权利要求76所述的基因测序设备,其中,所述第二流体输送结构还包括 从所述凸缘向所述试剂盒平台突伸且连通至所述芯片接纳区的导流组件,所述导流组件包括:多个破膜针和多个引流针,分别从所述顶板的与所述芯片接纳区相反的一侧朝向所述试剂盒平台突伸,每个破膜针具有与相应第一可刺穿结构对准的第一末端、且每个引流针具有与相应第二可刺穿结构对准的第二末端,
    其中,每个破膜针不连接至所述流路网络,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第一末端刺穿所述第一可刺穿结构、继而插入所述试剂槽以暴露所述试剂槽来改变所述试剂槽内的气压;以及
    每个引流针被构造为中空的针状、且与所述多个分支流道中的相应分支流道以一一对应关系成流体连通,且被配置成响应于所述容置仓达到所述引流位置的情况以其所述第二末端刺穿所述第二可刺穿结构、继而插入所述引导槽以流体连通至所述引导槽来汲取所述引导槽中的流体。
  79. 根据权利要求78所述的基因测序设备,其中,在所述多个引流针插入所述引导槽的情况下,所述多个引流针各自的自由端高于所述试剂槽的底部处的内壁。
  80. 根据权利要求79所述的基因测序设备,其中,每个引导槽被构造呈具有具备第一内径的圆形横截面的槽,且每个引导槽被构造呈具有具备小于第一内径的第二内径的圆形横截面的槽。
  81. 根据权利要求78所述的基因测序设备,其中,所述第一可刺破结构是金属箔;以及
    所述第二可刺破结构是柔性密封件,使得由所述多个引流针中的相应引流针刺穿之后保持液密密封。
  82. 一种进行生化检测的方法,所述方法包括:
    在具有待检测样品的芯片和具有多种不同反应成分的试剂盒之间建立流体连接,所述反应成分包括样本生成成分或样本分析成分至少之一;
    任选的,在生成操作中在所述芯片生成样本,所述生成操作包括使不同样本生成成分流入所述芯片并控制所述芯片的反应条件以生成所述样本;以及
    在分析操作中分析所述芯片的所述样本,所述分析操作包括使样本分析成分流入 所述芯片,所述样本分析成分与所述样本发生反应以提供相关可检测信号;
    其中所述试剂盒和芯片集成于芯片处理装置,且所述试剂盒中的所述流体经由所述芯片处理装置中且相互分离的第一流体输送结构和第二流体输送结构流体连通至所述芯片。
  83. 根据权利要求82所述的方法,其中,所述第一流体输送结构集成于所述试剂盒中,所述第二流体输送结构集成于支撑所述芯片的载台中,所述载台集成于所述芯片处理装置。
  84. 根据权力要求83所述的方法,其中,所述试剂盒通过集成于所述芯片处理装置的可移动支架相对所述载台运动,实现所述第一流体输送结构与所述第二流体输送结构的连通。
  85. 根据权利要求82所述的方法,其中,所述生化反应为核酸测序反应,所述待检测样本为核酸测序文库。
  86. 根据权利要求82所述的方法,其中,所述待检测样本为组织样本,所述生化反应为特异性结合反应。
  87. 根据权力要求82所述的方法,其中,所述可检测信号为光学信号。
  88. 根据权利要求84所述的方法,其中,所述第一流体输送结构与所述第二流体输送结构的连通包括:第一流体输送结构与所述芯片处理装置的外部气压连通以驱动所述试剂盒中的所述流体流入所述第二流通输送结构;以及将所述芯片与所述第二流通输送结构中的所述流体选择性连通。
  89. 根据权利要求88所述的方法,其中,所述第二流通输结构具有多个分支流道,所述芯片与所述流体选择性连通包括:利用集成在所述芯片处理装置的选择器阀控制不同所述多个分支流道与所述芯片的选择性连通。
PCT/CN2022/122191 2022-09-28 2022-09-28 芯片处理装置、基因测序仪和进行生化检测的方法 WO2024065292A1 (zh)

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