Chip processing device, gene sequencer and biochemical detection method
Patent Information
- Application Number
- CN202280098740.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2022-09-28
- Publication Date
- 2025-03-14
AI Technical Summary
In existing gene sequencers, the kit and chip platform are independent, resulting in complex flow path connections, difficulty in reducing the length of the flow channel, and low space utilization. In addition, the stroke and fluid path of the kit require large strokes and lifting movements, which affects the degree of integration. and positioning accuracy.
Design a chip processing device with an integrated reagent kit. By assembling the reagent kit and chip platform side by side on the substrate, a pipelineless fluid transport structure is adopted, and the selector valve and flow guide assembly are used to achieve fluid communication and switching to avoid long strokes. Translation and lifting movements simplify the fixation and positioning of fluid transport structures.
The length of the flow channel is shortened, the leveling and tightening effect of the kit is improved, the positioning accuracy and space utilization are improved, the assembly and disassembly process is simplified, and the structure is compact and the space occupied is minimized.
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Figure CN119630780A_ABST
Abstract
Description
Chip processing device, gene sequencer and biochemical detection method Technical Field
[0001] The present disclosure relates to the field of sequencing technology, and in particular to a chip processing device integrated with a reagent kit, a gene sequencer, a gene sequencing device, and a method for performing biochemical detection. Background Art
[0002] In existing chip platforms for introducing reagents into chips for biochemical reactions or for optical imaging, such as in gene sequencers, pipe joints are usually used to guide 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 pipe joints; the existing valve assembly is usually independent of the chip installation platform and connected by pipe joints; and the flow path connection between each functional module produces many pipes, and the existing chip installation platform and reagent kit platform are two independent platforms, not an integrated assembly or combination. In the gene sequencing process, a biochemical reaction is required for each cycle. Usually, the reagents required for the biochemical reaction are provided by a reagent needle provided on the reagent kit. Specifically, a syringe pump and a selector valve such as a rotary valve are used to pump the reagents from the corresponding reagent needle into the chip to perform the biochemical reaction.
[0003] Moreover, separate reagent kits, reagent needles, and selector valves are usually discretely arranged outside the chip platform. The discrete arrangement of various components leads to lower integration and space utilization, and accordingly causes the flow path layout to be complicated and the flow path length to be difficult to reduce. In particular, the reagent kit usually plays the role of accommodating and supplying different reagents, the reagent needle plays the role of inserting the reagent kit and extracting different reagents from the reagent kit, and the selector valve usually acts as a key component in the flow path layout, playing the function of controlling the fluid paths of different reagents and cleaning solutions. Different fluid paths are switched by the selector valve to connect the flow path between the reagent kit and the chip, thereby selectively realizing the entry and exit of reagents and cleaning solutions. Such a conventional arrangement with more discrete components usually requires numerous pipe joints and manifold flow paths, and it is necessary to rationally design the layout of the manifold flow paths within a limited installation space to avoid crossing each other and minimize mutual wiring interference, and it is also necessary to take into account the docking, switching and sealing between the outlets of the multiple manifold flow paths at the selector valve and the valve ports during design. Furthermore, existing discrete component designs require a large reagent cartridge travel and a long fluid path within a limited space. This necessitates large-scale horizontal displacement and lifting to deliver fluids, such as reagents, from the reagent needle to the sequencing chip. Furthermore, these requirements conflict with the switching between different fluid paths, the cleaning of residual fluids between switches, the secure fixing and precise leveling of the reagent cartridge and chip, and the precise positioning of the reagent cartridge.
[0004] Summary of the Invention
[0005] In order to solve at least one aspect of the above-mentioned problems and defects in the prior art, 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.
[0006] In order to achieve the above objectives, the technical solution of the present disclosure is implemented in the following ways:
[0007] According to a first aspect of the present disclosure, a chip processing device integrated with a reagent kit is provided, 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, wherein a top plate of the chip platform on a 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, and the reagent kit platform is formed with a hollow accommodating chamber, in which the reagent kit is received; 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, and the first fluid transport structure is fluidically connected to the chip via the second fluid transport structure.
[0008] In an embodiment according to the present disclosure, 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 transport structure and the second fluid transport structure are fluidically connected, and a state in which they are not fluidically 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 transport structure and the second fluid transport structure to each other to form fluid communication; and in response to the accommodating bin descending toward the substrate to the non-drainage position, separate the first fluid transport structure and the second fluid transport structure from each other.
[0009] In an embodiment of the present disclosure, the top plate of the chip platform at a side facing away from the base plate has a flange protruding toward the reagent cartridge platform along the second direction, and the reagent cartridge platform is partially embedded and assembled between the outwardly protruding flange of the top plate and the base plate.
[0010] In an embodiment according to the present disclosure, the first fluid delivery structure includes a plurality of reagent tanks and a plurality of guide tanks arranged in a one-to-one correspondence within the reagent kit, and a communication channel in which the fluid is connected between the bottom of each guide tank and the bottom of the corresponding reagent tank, each reagent tank 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 tank has a second opening open upward toward the flange, and a second pierceable structure covering the second opening.
[0011] In an embodiment according to the present disclosure, 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.
[0012] In an embodiment of the present disclosure, the selector valve includes: a valve seat, the selector valve being 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 having a fluid inlet configured to guide fluid into the valve body and a fluid outlet configured to guide fluid outward from the valve body. Furthermore, the flow network includes: a plurality of drainage needle ports located on a 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 being connected between each drainage needle port and a corresponding inlet port and configured to guide fluid input from each drainage needle port to the corresponding inlet port; an outlet port being 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 fluid output from the outlet port to the chip receiving area. The selector valve is arranged so that the fluid outlet is in fluid communication with the outlet port, and the fluid inlet is in fluid communication with at least one of the multiple inlet ports, and is configured to switch the selective communication 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.
[0013] In an embodiment according to the present disclosure, the plurality of drainage needle ports are formed through an edge of the top plate in a protrusion protruding toward a side of the top plate away from the chip receiving area.
[0014] In an embodiment of the present disclosure, the second fluid delivery structure further includes a flow guide assembly protruding from the flange toward the reagent cartridge platform and connected to the chip receiving area, the flow guide assembly comprising: a plurality of membrane puncturing needles and a plurality of drainage needles, each protruding from a side of the top plate opposite the chip receiving area toward the reagent cartridge 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, in response to the accommodating chamber reaching the drainage position, pierce the first pierceable structure with its first end, then insert into the reagent reservoir to expose the reagent reservoir and change the air pressure within the reagent reservoir. Each drainage needle is constructed in a hollow needle shape and is in fluid communication with a corresponding branch flow channel of the plurality of branch flow channels in a one-to-one correspondence, and is configured to, in response to the accommodating chamber reaching the drainage position, pierce the second pierceable structure with its second end, then insert into the guide groove to fluidically connect to the guide groove and draw fluid from the guide groove.
[0015] In an embodiment according to the present disclosure, when the plurality of drainage needles are inserted into 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.
[0016] In an embodiment according to the present disclosure, each guide groove is configured as a groove having a circular cross section with a first inner diameter, and each guide groove is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter.
[0017] In an embodiment according to the present disclosure, the first pierceable structure is a metal foil; and 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.
[0018] In an embodiment according to the present disclosure, the plurality of drainage needles are spaced apart from each other and arranged in a straight line, and the plurality of membrane rupture needles are spaced apart from each other and arranged in a straight line; and the plurality of drainage needles and the plurality of membrane rupture needles are both arranged parallel to each other.
[0019] In an embodiment according to the present disclosure, a corresponding membrane rupture needle is arranged on the side of each of the plurality of drainage needles in a one-to-one correspondence, and each drainage needle is adjacent to but spaced apart from the corresponding single membrane rupture needle in pairs.
[0020] In an embodiment according to the present disclosure, each drainage needle includes a hollow and elongated straight tubular needle body and a through tip having a tapered longitudinal cross-sectional shape.
[0021] In an embodiment according to the present disclosure, the plurality of drainage needles are mounted to the plurality of drainage needle ports in a threaded connection manner.
[0022] In an embodiment according to the present disclosure, the guide assembly further 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 configured to be shaped to fit with the alignment features on the reagent kit.
[0023] In an embodiment according to the present disclosure, the plurality of drainage needle ports are arranged in a straight line aligned with each other.
[0024] In an embodiment according to the present disclosure, the plurality of drainage needle ports are arranged to be separated from each other at uniform intervals.
[0025] In an embodiment according to the present disclosure, the selector valve is a rotary valve, and the rotary valve is configured to be rotatable around its axis so as to switch the selective communication 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.
[0026] In an embodiment according to the present disclosure, the axial directions of the inlet port and the outlet port are respectively parallel to the axis, the inlet port is arranged to be offset from the axis, and the outlet port is arranged coaxially with the axis.
[0027] In an embodiment according to the present disclosure, 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 all 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, and 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.
[0028] In an embodiment according to the present disclosure, 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.
[0029] In an embodiment according to the present disclosure, the top plate includes: a top layer, in which the chip receiving area is formed; and a supporting layer, which is stacked with the top layer and located between the top layer and the selector valve; and the multiple branch flow channels and the common flow channel are formed on a side of the supporting layer facing the top layer, and the multiple inlet ports, the outlet ports and the multiple drainage needle ports extend through the supporting layer.
[0030] In an embodiment of the present disclosure, 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.
[0031] In an embodiment according to the present disclosure, the top plate also includes a chip adsorption assembly, 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, partially disposed in the accommodating hole, the edge of its top surface protruding 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 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, which is formed through the adsorption platform and connected between the pipe joint and the adsorption groove.
[0032] In an embodiment according to the present disclosure, the top layer is formed with a supply port and a discharge port extending therethrough and to the recess, the supply port being fluidically 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.
[0033] In an embodiment according to the present disclosure, the common flow channel is linearly coupled between the outlet port and the supply port.
[0034] In an embodiment according to the present disclosure, the plurality of branch flow channels are arranged so as not to intersect with each other and to avoid the common flow channel.
[0035] In an embodiment according to the present disclosure, the ends of the exhaust port and the supply port and 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.
[0036] In an embodiment according to the present disclosure, the support layer is formed with a discharge channel therethrough and fluidically connected from the discharge port to the outside of the top plate.
[0037] In an embodiment according to the present disclosure, 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.
[0038] In an embodiment according to the present disclosure, the chip processing device also includes a driving member arranged inside it and at least one guide rail assembly connected between the accommodating bin and the substrate. The accommodating 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.
[0039] In an embodiment according to the present disclosure, the driving member includes: a driving source including one of a stepping motor and a piezoelectric driver; and a lead screw drivingly coupled between the driving source and the at least one guide rail assembly.
[0040] In an embodiment according to the present disclosure, each guide rail assembly includes two spaced-apart sets of 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 rolling elements held between the fixed rail and the movable rail.
[0041] In an embodiment according to the present disclosure, in each set of cross roller guide rails, the fixed rail is fixed to the chip platform in a manner orthogonal to the substrate, and the movable rail is fixed to the accommodating bin in a manner orthogonal to the substrate.
[0042] In an embodiment according to the present disclosure, the lead screw is coupled to the movable rails of each of the two sets of cross roller guide rails in the at least one guide rail assembly.
[0043] In an embodiment according to the present disclosure, the chip processing device also includes a positioning device, which includes: a groove, which is recessed in the top inner wall of the accommodating chamber; 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 chamber, the elastic component is in an initial state without being subjected to the force applied by the test kit and the positioning bead protrudes at least partially toward the substrate from the top inner wall of the accommodating chamber; and in response to the test kit being inserted into the accommodating chamber 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.
[0044] In an embodiment according to the present disclosure, the test kit has a protrusion protruding toward the top inner wall of the accommodating chamber, and a positioning groove recessed from the protrusion, and in response to the test kit being inserted into the accommodating chamber and squeezing the positioning bead, the positioning bead is clamped between the positioning groove and the elastic component.
[0045] In an embodiment according to the present disclosure, 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 shielding member being displaced or deformed by the force exerted by the reagent kit when the reagent kit is inserted into the accommodating bin and is in place, and blocking the infrared receiver from receiving infrared rays from the infrared transmitter.
[0046] In an embodiment according to the present disclosure, the chip processing device also includes a clamping device formed at the top of the reagent reagent platform, the top of the reagent reagent platform is formed with a through opening to at least partially expose the reagent reagent inserted in the accommodating chamber, and the clamping device includes: a pressure plate, one side of which is fixed to the reagent reagent platform; a pin, extending through the free side of the pressure plate opposite to the one side; a pair of arms, one end of each arm is pivotally connected to the corresponding end of the pin; and a pair of elastic members, each elastic member is elastically connected between the corresponding arm of the pair of arms and the reagent reagent platform.
[0047] In an embodiment according to the present disclosure, the chip processing device also includes a first tilt adjustment mechanism arranged between the bottom of the reagent cartridge platform and the base plate, 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 base plate.
[0048] In an embodiment according to the present disclosure, 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.
[0049] In an embodiment according to the present disclosure, 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 end and lower end 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.
[0050] In an embodiment according to the present disclosure, the chip processing device further includes a power component, which is arranged to be in fluid communication with the flow network and configured to drive the fluid to flow through the flow network toward the supply port.
[0051] In an embodiment according to the present disclosure, 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.
[0052] In an embodiment of the present disclosure, the chip processing device further includes a temperature control component, 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 guide component to the chip receiving area.
[0053] In an embodiment according to the present disclosure, the temperature control assembly includes a first temperature regulating device, which is arranged 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 adapter bracket away from the top plate and on opposite sides of the top plate, respectively, for accommodating and fixing the selector valve and the first temperature regulating device therein, respectively.
[0054] In an embodiment according to the present disclosure, 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 configured to cut off the power component when the temperature at the heat sink exceeds a threshold temperature.
[0055] In an embodiment according to the present disclosure, the temperature control assembly further includes: a heat conducting member inserted between the top plate and the first temperature regulating device.
[0056] In an embodiment according to the present disclosure, the heat conducting member includes a phase change material.
[0057] In an embodiment of the present disclosure, the active heat dissipation element includes a thermoelectric cooler; or the passive heat dissipation element includes one of the following: a single heat sink, or a heat sink array.
[0058] In an embodiment according to the present disclosure, 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 arranged to be aligned with the first temperature regulating device.
[0059] In an embodiment of the present disclosure, the second temperature regulating device includes a fan, the fan comprising: a hollow first housing, the interior of which defines a cavity for airflow, the first housing being 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 exterior of the fluid guiding device; and a fan assembly housed within the first housing. The fan assembly comprises: a second housing, configured as a hollow cylindrical body fixedly mounted within the first housing; a rotating shaft rotatably mounted within the second housing; and a plurality of fan blades, the plurality of fan blades being coaxially fixed to the rotating shaft within the second housing and being rotatable relative to the second housing along with the rotating shaft.
[0060] In an embodiment of the present disclosure, the adapter bracket is further formed with a gas channel running through its interior and 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.
[0061] In an embodiment according to the present disclosure, 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 located 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. The second shell of the fan assembly is connected to the first shell via the plurality of vibration damping members.
[0062] In an embodiment according to the present disclosure, at least one of the first-stage vibration damping structure and the second-stage vibration damping structure is a vibration compensation device, and the vibration compensation device is an elastic member or a damping member.
[0063] In an embodiment of the present disclosure, 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 pushed tightly between the adapter bracket and the first shell via the screw.
[0064] In an embodiment according to the present disclosure, 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 including: a plurality of 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 distance screws toward the top plate in a one-to-one correspondence.
[0065] According to a second aspect of the present disclosure, a gene sequencer is provided, comprising: a chip carrying a sample to be detected using a fluid; and a chip processing device, the chip processing device comprising a substrate extending along a first direction, and a reagent cartridge platform and a chip platform assembled side by side and adjacent to each other on the substrate along a second direction transverse to the first direction, the chip platform having a chip receiving area on a top plate on a side facing away from the substrate for accommodating the chip, the reagent cartridge platform forming a hollow accommodating chamber, the reagent cartridge being received in the accommodating chamber and at least partially filled with the fluid, the reagent cartridge having a first fluid transport structure located on a side of the reagent cartridge facing the chip platform along the second direction, the chip platform having a second fluid transport structure located on a side of the chip platform facing the reagent cartridge platform along the second direction and configured to at least partially overlap and communicate with the first fluid transport structure when the reagent cartridge platform and the chip platform are assembled, and the reagent cartridge is removably inserted into the accommodating chamber of the chip processing device, and the fluid in the reagent cartridge is fluidically connected to the sample carried on the chip via the first and second fluid transport structures. Since it includes the aforementioned chip processing device, it has similar advantages and will not be described in detail here.
[0066] In an embodiment according to the present disclosure, 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 transport structure and the second fluid transport structure are fluidically connected, and a state in which they are not fluidically 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 transport structure and the second fluid transport structure to each other to form fluid communication; and in response to the accommodating bin descending toward the substrate to the non-drainage position, separate the first fluid transport structure and the second fluid transport structure from each other.
[0067] In an embodiment of the present disclosure, the top plate of the chip platform at a side away from the base plate has a flange protruding toward the reagent cartridge platform along the second direction, and the reagent cartridge platform is partially embedded and assembled between the flange of the top plate and the base plate.
[0068] In an embodiment according to the present disclosure, the first fluid delivery structure includes a plurality of reagent tanks and a plurality of guide tanks arranged in a one-to-one correspondence within the reagent kit, and a communication channel in which the fluid is connected between the bottom of each guide tank and the bottom of the corresponding reagent tank, each reagent tank 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 tank has a second opening open upward toward the flange, and a second pierceable structure covering the second opening.
[0069] In an embodiment according to the present disclosure, 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.
[0070] In an embodiment according to the present disclosure, 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 forming a fluid inlet configured to guide fluid into the valve body and a fluid outlet configured to guide fluid from the valve body to the outside. The flow path network includes: a plurality of drainage needle ports, located on a 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 connected between each drainage needle port and a corresponding inlet port, and configured to guide 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 fluid output from the outlet port to the chip receiving area. The selector valve is arranged so that the fluid outlet is in fluid communication with the outlet port, and the fluid inlet is in fluid communication with at least one of the multiple inlet ports, and is configured to switch the selective communication 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.
[0071] In an embodiment according to the present disclosure, the plurality of drainage needle ports are formed through an edge of the top plate in a protrusion protruding toward a side of the top plate away from the chip receiving area.
[0072] In an embodiment according to the present disclosure, 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 configured to pierce the second pierceable structure with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove to be fluidically connected to the guide groove to draw fluid from the guide groove.
[0073] In an embodiment according to the present disclosure, when the plurality of drainage needles are inserted into 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.
[0074] In an embodiment according to the present disclosure, each guide groove is configured as a groove having a circular cross section with a first inner diameter, and each guide groove is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter.
[0075] In an embodiment according to the present disclosure, the first pierceable structure is a metal foil; and 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.
[0076] According to a third aspect of the present disclosure, a gene sequencing device is provided, comprising: a chip carrying a sample to be detected using a fluid; and at least two chip processing devices, each chip processing device comprising a substrate extending along a first direction, and a reagent reagent platform and a chip platform assembled side by side and adjacently on the substrate along a second direction transverse to the first direction, a chip receiving area for accommodating the chip being provided on a top plate of the chip platform on a side facing away from the substrate, and a hollow accommodating chamber formed on the reagent reagent platform, the reagent reagent being received in the accommodating chamber, and the interior of the chamber being at least partially filled with the fluid. The reagent kit has a first fluid transport structure located at a 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 a side of the chip platform along the second direction toward the reagent kit platform, 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 kit is inserted into the containing 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; and the at least two chip processing devices are symmetrically arranged with their respective chip platforms arranged adjacent to each other.
[0077] In an embodiment of the present disclosure, 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 devices, it has similar advantages and will not be described in detail here.
[0078] In an embodiment of the present disclosure, the housing is coupled to the substrate in a manner capable of linear movement between a highest drainage position and a non-drainage position below the drainage position, wherein 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. Furthermore, the chip handling device is configured to: in response to the housing rising away from the substrate to the drainage position, engage the first fluid transport structure and the second fluid transport structure to establish fluid communication with each other; and in response to the housing descending toward the substrate to the non-drainage position, separate the first fluid transport structure and the second fluid transport structure from each other.
[0079] In an embodiment of the present disclosure, the top plate of the chip platform at a side away from the base plate has a flange protruding toward the reagent cartridge platform along the second direction, and the reagent cartridge platform is partially embedded and assembled between the flange of the top plate and the base plate.
[0080] In an embodiment according to the present disclosure, the first fluid delivery structure includes a plurality of reagent tanks and a plurality of guide tanks arranged in a one-to-one correspondence within the reagent kit, and a communication channel in which the fluid is connected between the bottom of each guide tank and the bottom of the corresponding reagent tank, each reagent tank 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 tank has a second opening open upward toward the flange, and a second pierceable structure covering the second opening.
[0081] In an embodiment according to the present disclosure, 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.
[0082] In an embodiment according to the present disclosure, 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 forming a fluid inlet configured to guide fluid into the valve body and a fluid outlet configured to guide fluid from the valve body to the outside. The flow path network includes: a plurality of drainage needle ports, located on a 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 connected between each drainage needle port and a corresponding inlet port, and configured to guide 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 fluid output from the outlet port to the chip receiving area. The selector valve is arranged so that the fluid outlet is in fluid communication with the outlet port, and the fluid inlet is in fluid communication with at least one of the multiple inlet ports, and is configured to switch the selective communication 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.
[0083] In an embodiment according to the present disclosure, the plurality of drainage needle ports are formed through an edge of the top plate in a protrusion protruding toward a side of the top plate away from the chip receiving area.
[0084] In an embodiment of the present disclosure, the second fluid delivery structure further includes a flow guide assembly protruding from the flange toward the reagent cartridge platform and connected to the chip receiving area, the flow guide assembly comprising: a plurality of membrane puncturing needles and a plurality of drainage needles, each protruding from a side of the top plate opposite the chip receiving area toward the reagent cartridge 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, in response to the accommodating chamber reaching the drainage position, pierce the first pierceable structure with its first end and then insert into the reagent reservoir to expose the reagent reservoir and thereby change the air pressure within the reagent reservoir; and each drainage needle is constructed in a hollow needle shape and is in fluid communication with a corresponding branch flow channel of the plurality of branch flow channels in a one-to-one correspondence, and is configured to, in response to the accommodating chamber reaching the drainage position, pierce the second pierceable structure with its second end and then insert into the guide groove to fluidically connect to the guide groove and draw fluid from the guide groove.
[0085] In an embodiment according to the present disclosure, when the plurality of drainage needles are inserted into 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.
[0086] In an embodiment according to the present disclosure, each guide groove is configured as a groove having a circular cross section with a first inner diameter, and each guide groove is configured as a groove having a circular cross section with a second inner diameter smaller than the first inner diameter.
[0087] In an embodiment according to the present disclosure, the first pierceable structure is a metal foil; and 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.
[0088] According to the fourth aspect of the present disclosure, a method for performing biochemical detection is also provided, the method comprising: establishing a fluid connection between a chip having a sample to be detected and a reagent 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 reagent kit and the chip are integrated in a chip processing device, and the fluid in the reagent 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.
[0089] In an embodiment according to the present disclosure, the first fluid transport structure is integrated into the reagent kit, the second fluid transport structure is integrated into a carrier supporting the chip, and the carrier is integrated into the chip processing device.
[0090] In an embodiment of the present disclosure, the reagent kit is moved relative to the carrier by a movable bracket integrated in the chip processing device, thereby achieving communication between the first fluid transport structure and the second fluid transport structure.
[0091] In an embodiment according to the present disclosure, the biochemical reaction is a nucleic acid sequencing reaction, and the sample to be detected is a nucleic acid sequencing library.
[0092] In an embodiment of the present disclosure, the biochemical reaction is a specific binding reaction, and the sample to be detected is a biological tissue or 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.
[0093] In an embodiment according to the present disclosure, the detectable signal is an optical signal.
[0094] In an embodiment according to the present disclosure, the 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.
[0095] In an embodiment according to the present disclosure, the second flow transmission structure has a plurality of branch flow channels, and the selective communication between the chip and the fluid includes: using a selector valve integrated in the chip processing device to control the selective communication between different branch flow channels and the chip.
[0096] The technical solution provided by the present disclosure has the following advantages: the chip processing device, gene sequencer, gene sequencing equipment and method of using the gene sequencer implemented by the embodiments of the present disclosure, especially the chip processing device, can realize an integrated pipeline-free fluid delivery structure through the above-mentioned setting, which has a reduced flow channel length, a more reliable leveling and tightening effect on the test kit, and a higher positioning accuracy. And 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. As a result, 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. And this compact structure minimizes space occupancy, and the simple structure and connection relationship facilitate assembly and disassembly. BRIEF DESCRIPTION OF THE DRAWINGS
[0097] FIG1(a) schematically illustrates 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), and FIG1(c) illustrates a top view of a portion of the structure of FIG1(a); FIG1(d) is a cross-sectional schematic diagram of FIG1(c) along line PP; FIG1(e) is a cross-sectional schematic diagram of the structure shown in FIG1(e) with the reagent chamber 110 removed; and FIG1(f) is a three-dimensional schematic diagram of the structure shown in FIG1(a) with the reagent chamber 110 removed.
[0098] Figures 2(a) to 2(e) schematically illustrate views of the chip processing device shown in Figure 1 from different angles, wherein Figure 2(a) is a schematic three-dimensional view with the panel of the chip platform and the internal cross roller guide removed, Figure 2(b) is a front view with the panel of the chip platform and the internal cross roller guide removed, Figure 2(c) is a schematic three-dimensional view from another angle with the panel of the chip platform and the internal V-shaped support members arranged on the outside removed, Figure 2(d) is a front view with the panel of the chip platform, and Figure 2(e) is a top view; Figure 2(f) schematically illustrates an assembly diagram of a selector valve and an adapter bracket;
[0099] FIG3( a ) shows a schematic diagram of the structure of the reagent box with the liquid reservoir; FIG3( b ) shows a top view of the reagent box of FIG3( a ) after the top panel is removed;
[0100] FIG4 shows a view taken along line FF in FIG2( e), showing the specific arrangement of the reagent tank and the guide groove inside the reagent kit;
[0101] FIG5(a) schematically illustrates a specific structure for conveying fluid in the top plate of the chip platform in the chip processing device of FIG1 , so as to serve as a fluid supply device; FIG5(b) schematically illustrates the assembly relationship between the top plate serving as the carrier and the selector valve;
[0102] FIG6( a ) is a schematic perspective view of a carrier with a chip suction assembly mounted in a chip receiving area; FIG6( b ) to FIG6( c ) are schematic exploded views of the carrier of FIG6( a ) from top and bottom perspectives, respectively, with the chip suction assembly removed for simplicity;
[0103] FIG7 shows a schematic structural diagram of a chip adsorption assembly;
[0104] FIG8 schematically shows a cross-sectional view of a top plate serving as a carrier along a common flow channel;
[0105] Figures 9(a) to 9(f) illustrate the fluid guiding device, particularly its flow guiding assembly, in the chip platform of the chip processing device of Figure 1 from different angles. Figures 9(a) and 9(b) are schematic perspective views of the fluid guiding device from different angles; Figures 9(c) to 9(f) are front, right, rear, and top views of the fluid guiding device, respectively.
[0106] FIG10 illustrates a cross-sectional view of the chip processing device shown in the top view of FIG2(e) along line EE, showing an internal positioning device and a seat detector for detecting that the liquid reservoir is inserted into the receiving chamber;
[0107] FIG11 is a schematic diagram of the explosion of FIG9( b );
[0108] FIG12 is a schematic cross-sectional view along line AA in FIG9( f);
[0109] FIG13( a ) is a schematic diagram of an explosion of the second temperature adjustment device in FIG11 ;
[0110] 13( b ) to 13 ( c ) are schematic perspective views respectively showing the cross-section along lines CC and DD in FIG. 9 ( f );
[0111] FIG14 schematically illustrates a gene sequencer according to an embodiment of the present disclosure, which includes the chip processing device shown in FIG1 , 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;
[0112] FIG15 illustrates a gene sequencing device according to an embodiment of the present disclosure, comprising a pair of the aforementioned gene sequencers arranged adjacent to each other in a mirror-symmetrical manner; and
[0113] FIG16 illustrates a schematic flow chart of a method for biochemical detection using gene sequencing shown in FIG14 according to an embodiment of the present disclosure.
[0114] FIG. 17 schematically illustrates more specific steps in the method as shown in the flowchart of FIG. 16 . DETAILED DESCRIPTION
[0115] The technical solution of the present disclosure is further specifically described below through examples and in conjunction with the accompanying drawings. In the specification, the same or similar figure numerals represent components with the same or similar functions. The following description of the embodiments of the present disclosure with reference to the accompanying drawings is intended to explain the overall concept of the present disclosure and should not be construed as a limitation of the present disclosure. In addition, in the detailed description below, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of the embodiments of the present disclosure. However, it is obvious that one or more embodiments can also be implemented without these specific details.
[0116] 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); and Figure 1(d) is a cross-sectional schematic diagram of Figure 1(c) along the PP line.
[0117] According to a general technical concept of an embodiment of the present disclosure, for example, as shown in Figures 1(a) to 1(d), a chip processing device 1 integrated with a reagent kit is provided for supplying fluid from a fluid reservoir 2 (e.g., a reagent kit) to a chip 3 (e.g., a gene sequencing chip 3). 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 adjacent to each other on the substrate 10 along a second direction transverse to the first direction. The chip platform 12 has a top plate 120 located at its top, which 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 a side facing away from the substrate, has a chip receiving area 121a for accommodating a chip 3 carrying a sample to be detected using a 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 storage chamber 110 is formed in the reagent kit platform 11, and the reagent kit is received in the storage chamber. Moreover, for example, the reagent kit platform 11 has a storage chamber 110 that is open to the outside (for example, open to the outside on its lateral side as shown in FIG1 ) and is suitable for receiving a fluid reservoir 2 (such as a reagent kit) containing a fluid. Further, as an example, the reagent kit platform has a first fluid transport structure located at one side thereof 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 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. Furthermore, as an example, the accommodating chamber is coupled to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position below the drainage position, wherein 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; and the chip processing device is configured such that, in response to the accommodating chamber being raised 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 being lowered toward the substrate to the non-drainage position, the first fluid transport structure and the second fluid transport structure are separated from each other. Thus, within a chip processing device integrated with a liftable reagent cartridge, switching between a fluid communication state and a non-communication state between the first fluid transport structure in the reagent cartridge platform and the second fluid transport structure in the chip platform is facilitated.
[0118] Furthermore, in a specific embodiment, as an example, the top plate at the side of the chip platform facing away from the substrate has a flange protruding along the second direction toward the reagent reagent platform, and the top plate at the side of the chip platform facing away from the substrate has a flange protruding along the second direction toward the reagent reagent platform, and the reagent reagent platform 11 is partially embedded and assembled between the outwardly protruding flange 1201 of the top plate 120 and the substrate 10.
[0119] Figures 2(a) to 2(e) schematically show views of the chip processing device 1 shown in Figure 1 from 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 internal 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.
[0120] Figure 3(a) shows a schematic diagram of the structure of the reagent box with the liquid 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 taken along line FF in Figure 2(e), which shows the specific arrangement of the reagent tank and guide groove inside the reagent box;
[0121] In an embodiment according to the present disclosure, for example, as shown in the figure, 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 in which the fluid is 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 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.
[0122] 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, so as 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.
[0123] Figure 6(a) shows a schematic perspective view of a carrier with a chip suction assembly mounted in a chip receiving area. Figures 6(b) and 6(c) show exploded views of the carrier of Figure 6(a) from top and bottom perspectives, respectively, with the chip suction assembly removed for simplicity. Figure 7 shows a schematic structural diagram of the chip suction assembly.
[0124] Figure 8 schematically illustrates a cross-sectional view of the top plate 120, which serves as a carrier, along line LL, where the common flow channel is located, in Figure 6(a). Figures 9(a) to 9(f) illustrate the fluid guiding device, particularly its flow guiding components, in the chip platform of the chip processing device of Figure 1 from different angles. Figures 9(a) and 9(b) are schematic perspective views of the fluid guiding device from different angles, respectively; Figures 9(c) to 9(f) are the front view, right side view, rear view, and top view of the fluid guiding device, respectively.
[0125] In a further embodiment, as shown in the figure, the second fluid delivery structure includes a fluid supply device, and 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, mounted to the top plate and in fluid communication with the flow network.
[0126] In a further embodiment, as shown in the figure, 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. The drive motor 1263 is preferably a stepping motor. Furthermore, 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. For example, the selector valve is arranged so that the fluid outlet 126b is fluidically connected to the outlet port, and the fluid inlet 126a is fluidically 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. As shown in Figures 9(f) and 12(a), 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, and 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.
[0127] In yet a further embodiment, for example, 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.
[0128] Furthermore, as shown in Figures 1 and 2(a) to 2(e), in an embodiment according to the present disclosure, for example, in the chip platform 12, the second fluid delivery structure further includes a flow guide assembly 123 protruding from the flange 1201 toward the reagent cartridge platform 11 and connected to the chip receiving area 121a. Furthermore, as shown in the figure, the flow guide assembly 123 includes: a plurality of membrane rupture needles 123b and a plurality of drainage needles 123a, each protruding from a side of the top plate opposite the chip receiving area toward the reagent cartridge 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. As an example, each membrane rupture needle is not connected to the fluid path network and is configured to, in response to the accommodating chamber reaching the drainage position, pierce the first pierceable structure 210 with its first end and then insert into the reagent reservoir 20a to expose the reagent reservoir 20a, thereby changing the air pressure within the reagent reservoir 20a. And, as an example, 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.
[0129] In an exemplary embodiment, for example, when the plurality of drainage needles are inserted into the guide groove 20 b , 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 .
[0130] Through the above arrangement, when the reagent kit rises to the drainage position along with the storage compartment, the membrane rupture needle 123b pierces the first pierceable structure 210 covering the first opening 21 and enters the reagent tank 20a, allowing atmospheric pressure to enter the reagent tank 20a from the punctured 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. At the same time, 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 that is at least partially inserted into the guide groove to aspirate the reagent liquid even if it is far away from the reagent page in the reagent kit.
[0131] In a specific embodiment, for example, each guide groove 20b is configured as a groove having a circular cross-section with a first inner diameter, and 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. This configuration further facilitates the drainage needle to draw the reagent liquid from the reagent tank into the guide groove via the connecting channel at the bottom.
[0132] In a specific embodiment, the first pierceable structure is, for example, a metal foil, and the second pierceable structure is, for example, 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.
[0133] In a specific embodiment, as an example, the plurality of drainage needles are spaced apart from each other and arranged in a straight line, and the plurality of membrane rupture needles are spaced apart from each other and arranged in a straight line; and the plurality of drainage needles and the plurality of membrane rupture needles are both arranged parallel to each other.
[0134] In a more specific embodiment, for example, the plurality of drainage needles 123a are spaced apart at uniform intervals. Correspondingly, the plurality of reagent dispensing ports are also spaced apart at the aforementioned intervals. This achieves an even distribution of the plurality of drainage needles 123a at the aforementioned single edge of the carrier 120, effectively avoiding mutual interference and promoting local thermal equilibrium.
[0135] Through the above-mentioned arrangement, a plurality of linearly arranged drainage needles 123a that are 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.
[0136] In a further embodiment of the present disclosure, as shown in the figure, for example, a corresponding membrane rupture needle is arranged one-to-one beside each of the multiple drainage needles, and each drainage needle is adjacent to but spaced apart from the corresponding single membrane rupture needle in pairs.
[0137] In a specific embodiment, as an example, each drainage needle comprises a hollow and elongated straight tubular needle body and a through-top with a tapered longitudinal cross-section. For example, the plurality of drainage needles are mounted to the plurality of drainage needle ports in a threaded connection manner.
[0138] In other embodiments of the present disclosure, as shown in the figures, for example, the guide assembly further 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 configured to be shaped to fit with the alignment features on the reagent kit.
[0139] In a more specific embodiment, as shown in the figure, as an example, the at least two guide pins 123c are two guide pins 123c arranged colinearly with the multiple drainage needles 123a and respectively located outside two drainage needles 123a at both ends of the multiple drainage needles 123a.
[0140] Through this arrangement, for example, the two guide pins 123c are aligned with the corresponding alignment features, such as pits, on the liquid reservoir and are in positive fit, thereby serving as guides for accurately positioning all drainage needles 123a relative to the corresponding reagent dispensing ports in the liquid reservoir; in other words, once the two guide pins 123c at both ends are correctly aligned and fit into the alignment features on the liquid reservoir, all drainage needles 123a are aligned and positioned relative to their respective corresponding reagent dispensing ports.
[0141] In a specific embodiment, as an example, 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 uniform intervals.
[0142] In addition, in an embodiment of the present disclosure, for example, as shown in the figure, 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.
[0143] In a further embodiment, preferably as an example, the inlet port and the outlet port are each axially parallel to the axis, the inlet port is arranged offset from the axis, and the outlet port is arranged coaxially with the axis.
[0144] In a specific embodiment, for example, 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 all 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.
[0145] In a further embodiment, for example, 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.
[0146] Through these specific settings, the rotary valve 126 is utilized 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 layout of the flow 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 manifolds, avoiding redundant fluid path length, reducing reagent loss, and also facilitating temperature control and temperature balance on the entire fluid supply device 1.
[0147] Furthermore, in an embodiment of the present disclosure, as shown in the figure, the flow network 125 also realizes the 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.
[0148] In a more specific embodiment of the present disclosure, for example, 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. Furthermore, the multiple 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 multiple inlet ports, the outlet port, and the multiple drainage needle ports extend through the support layer 120b.
[0149] More specifically, as shown in Figures 6(a) to 6(c), for example, 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 away from the supporting layer 120b and arranged around the accommodating hole 1202.
[0150] Furthermore, as shown in FIG7 , for example, the top plate further includes a chip adsorption assembly 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, which is recessed toward the supporting layer 120b and is 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.
[0151] In an embodiment of the present disclosure, for example, the top layer 120a is formed with a supply port and a discharge port extending therethrough and 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.
[0152] Further, for example, the common flow channel is linearly connected between the outlet port and the supply port.
[0153] Also, for example, the plurality of branch flow channels are arranged so as not to intersect with each other and to avoid the common flow channel.
[0154] In a specific embodiment, for example, as shown in the figure, the ends of the exhaust port and the supply port, which are adjacent to the support layer 120b, extend to the recessed portion 1203. Furthermore, as an example, as shown in FIG8 , when the chip is received and adsorbed on the adsorption platform 1205, the adsorption platform 1205 and the chip jointly define a chip liquid-tight sealing surface P1, which serves as a first liquid-tight sealing surface, and the chip forms sealed fluid communication with the supply port and the exhaust port, respectively, at the first liquid-tight sealing surface.
[0155] In a specific embodiment, for example, as shown in the figure, the support layer 120b is formed with a discharge channel extending therethrough and communicating fluid from the discharge port to the exterior of the top plate. Furthermore, as an example, as shown in FIG8 , the multiple inlet ports and the outlet port extend through the support layer 120b to the back side of the top plate. The back side and the valve seat 1261 together define a valve liquid-tight sealing surface P2, which serves as a second liquid-tight sealing surface. Furthermore, the multiple inlet ports and the outlet port are in sealed fluid communication with the fluid inlet 126a and the fluid outlet 126b of the valve body 1262, respectively, at the second liquid-tight sealing surface.
[0156] The chip liquid-tight sealing surface P1 and the valve liquid-tight sealing surface P2 are located on the upper and lower sides of the flow channel inside the switch valve, respectively. This configuration simplifies the configuration of the sealing surfaces, and by defining two sealing surfaces at different positions within the carrier 120, easy fluid isolation and a liquid-tight seal at the chip and valve are achieved.
[0157] Furthermore, as shown in the figure, for example, the chip platform 12 has a driving member 122 disposed therein, and the chip processing device 1 also includes, for example, at least one guide rail assembly 13 coupled between the accommodating chamber 110 and the base plate. The accommodating chamber 110 can be moved in a direction perpendicular to the base plate 10 by the driving member 122 via the at least one guide rail assembly 13, so that the guide assembly 123 is inserted and fluidically connected to the liquid reservoir 2. As an example, as shown in FIG1(c), for example, the chip processing device 1 includes two guide rail assemblies 13 arranged in parallel.
[0158] In a specific embodiment of the present disclosure, 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 the 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 is engaged with the second fluid transport structure in the chip platform 12, thereby establishing fluid communication between the first fluid transport structure and the second fluid transport structure.
[0159] Moreover, in a specific embodiment of the present disclosure, 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 the 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 kit platform 11 and the second fluid transport structure in the chip platform 12 are disengaged from each other and the first fluid transport structure and the second fluid transport structure are separated from each other so that there is no longer fluid communication between the two.
[0160] And, generally, as an example, the first threshold position is higher than the second threshold position. Thus, the first position range and the second position range do not overlap with each other at all.
[0161] In a specific embodiment, for example, the driving member 122 includes: a driving source, including one of a stepper motor and a piezoelectric driver; and a lead screw drivingly coupled between the driving source and the at least one guide rail assembly 13. More specifically, as an example, the lead screw is further coupled to the at least one guide rail assembly 13 via a coupling located upstream thereof and drivingly coupled to an output shaft of the driving source. This facilitates the reciprocating movement of the accommodating bin 110 orthogonal to the base plate 10 by the driving member 122 via the at least one guide rail assembly 13, thereby achieving a lifting motion of the accommodating bin 110.
[0162] In a specific embodiment, for example, each guide rail assembly 13 includes two spaced-apart sets of cross roller guide rails 130, each set of cross roller guide rails 130 including 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, a cross ball guide serves as each set of cross roller guide rails 130), or a plurality of rollers arranged alternately and orthogonally (in this case, a cross roller guide serves as each set of cross roller guide rails 130), thereby facilitating the bearing of loads in multiple different directions. Furthermore, in a further embodiment, for example, as shown in the figure, in each set 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, and the movable rail 132 is fixed to the storage bin 110 in a manner orthogonal to the substrate 10.
[0163] Therefore, as shown in the figure, each group of cross rollers in the at least one guide rail assembly 13 (shown as two guide rail assemblies 13 arranged side by side) works together to act as a guiding device for the accommodating bin 110 to move in a direction orthogonal to the substrate 10, thereby achieving accurate guidance of the lifting and lowering action of the accommodating bin 110.
[0164] In a further embodiment, as an example, the lead screw is coupled to the movable rails 132 of each of the two sets of cross roller guide rails 130 in the at least one guide rail assembly 13. By interconnecting the movable rails 132 of the different sets of cross roller guide rails 130 in each guide rail assembly 13, the two sets of cross roller guide rails 130 spaced apart from each other in the same guide rail assembly 13 are synchronized in guiding the lifting and lowering of the accommodating bin 110, and at the same time, it is facilitated to maintain an integrated support for the bottom of the accommodating bin 110 during the lifting and lowering of the accommodating bin 110.
[0165] As an example, the first fluid delivery structure of the reagent cartridge platform 11 includes a reservoir 2 , such as a reagent cartridge.
[0166] As shown in FIG2( f ), the chip platform 12 further includes a V-shaped support 133 for fixing the selector valve 126. The selector valve 126 is provided through the adapter bracket 127, which 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, for example, a screw thread pair that can be screwed and adjusted. The connecting portion 1332 can be fixed to the selector valve 126 by a similar screw thread structure. This achieves a stable installation of the selector valve in the chip platform 12.
[0167] Figure 5(a) schematically shows the 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 the second fluid conveying structure; Figure 5(b) schematically shows the assembly relationship between the top plate acting as a carrier and the selector valve.
[0168] As an example, 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 guide component 123; and the fluid supply device includes the aforementioned top plate 120 (which serves 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 furthermore, the fluid supply device 150 works in conjunction with the flow guide component 123 to jointly define the fluid guiding device 160 that serves as the second fluid transport structure.
[0169] Furthermore, the specific structure of the fluid delivery device for delivering fluid is disclosed in the embodiments of the present disclosure. As an example, as shown in the figure, 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 mounted to the top plate 120 and fluidically connected to the flow network, the flow network 125 more specifically including: 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 the 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 to switch the alignment and connection between the corresponding other end of one of the plurality of branch flow channels 1252 and the fluid inlet 126a. The plurality of branch flow channels 1252 together form a manifold segment 1251 .
[0170] Furthermore, the aforementioned top plate 120 serves as a carrier for the sequencing chip and, in combination with the aforementioned fluid network 125 and selector valve 126, forms a fluid supply device 150 for supplying fluid to the chip. Thus, utilizing the specific structure for delivering fluid disposed within the top plate 120 of the chip platform 12 as described above, a flow channel is primarily arranged within the top plate 120 of the chip platform 12, facilitating the shortening of the flow channel length, reducing the substitution ratio and reagent usage, and lowering sequencing costs.
[0171] Also, in an embodiment of the present disclosure, as shown in the figure, as an example, 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.
[0172] In further embodiments, for example, as shown in the figure, the fluid inlet 126a and the fluid outlet 126b are each axially parallel to the axis AX, the fluid inlet 126a is disposed offset from the axis AX, and the fluid outlet 126b is disposed coaxially with the axis AX.
[0173] In a more specific embodiment, as shown in the figure, as an example, the corresponding other ends of the multiple branch flow channels 1252 connected to the fluid inlet 126a are constructed as multiple 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.
[0174] Thus, by utilizing a rotary valve as a selector valve 126, 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.
[0175] FIG8 schematically shows a cross-sectional view of a top plate serving as a carrier, taken along a common flow channel.
[0176] Furthermore, in another embodiment of the present disclosure, as shown in the figure, in the rotary valve 126, the fluid inlet 126a and the fluid outlet 126b share a first sealing surface P1, and the multiple inlet ports 1254 share a second sealing surface P2, and 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 switcher valve.
[0177] Through this arrangement, the setting of the sealing surface is simplified, and by only defining two non-overlapping sealing surfaces at different side flow channels in the valve body, easy fluid isolation is achieved, 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.
[0178] Figures 9(a) to 9(f) illustrate, from different angles, the fluid guiding device, specifically its flow guiding components, within the chip platform of the chip processing device of Figure 1 . Figures 9(a) and 9(b) are schematic perspective views of the fluid guiding device, shown from different angles; Figures 9(c) to 9(f) are front, right, rear, and top views of the fluid guiding device, respectively.
[0179] In addition, in an embodiment of the present disclosure, as shown in the figure, as an example, 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 diverge radially around the selector valve 126 and turn toward the edge 1208 to communicate with the multiple drainage needle ports 1250 one by one.
[0180] By arranging the ends of the branch channels 1252 circumferentially around the selector valve 126 (e.g., a rotary valve), typically, for example, at uniform angular intervals and circumferentially radiating radially, it is possible to evenly distribute the branch channels 1252 in the adjacent peripheral areas of the selector valve 126, thereby facilitating uniform temperature control of the entire area across which the multiple branch channels 1252 are distributed in the top plate 120 and an evenly spaced arrangement between the channels.
[0181] Furthermore, in an embodiment of the present disclosure, for example, as shown in the figure, the flow guide component 123 includes a plurality of drainage needles 123a respectively connected to the plurality of branch flow channels 1252 in a one-to-one correspondence in fluid communication, 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 reagent 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.
[0182] More specifically, for example, the plurality of drainage needle ports 1250 are formed through a protrusion 121b that protrudes from the edge 1208 of the top plate 120 toward a side of the top plate 120 that faces away from the chip receiving area 121a that accommodates the chip 3. Furthermore, correspondingly, as an example, the plurality of drainage needles 123a are threadedly mounted to the plurality of drainage needle ports 1250 and are in one-to-one fluid communication with the plurality of branch flow channels 1252. Thus, the plurality of drainage needle ports 1250 also have the same arrangement 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.
[0183] The plurality of drainage needles 123a are further configured, for example, to puncture the sealing gasket covering the corresponding reagent extraction portion of the liquid reservoir 2 (e.g., a reagent cartridge) in the storage compartment 110 once the storage compartment 110 rises to the upper limit position in the reagent cartridge platform 11, thereby achieving one-to-one fluid communication between the plurality of drainage needles 123a and the corresponding reagent extraction portion in the liquid reservoir 2. The upper limit position is, for example, the aforementioned drainage position, and in particular, the highest position in the first position range serving as the drainage position.
[0184] Thus, 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.
[0185] Furthermore, in the embodiments of the present disclosure, as shown in the figures, the common flow channel 1253 is linearly coupled between the fluid outlet 126b and the chip receiving area 121a. Furthermore, the plurality of branch flow channels 1252 are arranged so as not to intersect with each other and to avoid the common flow channel 1253. This effectively separates the flow channel entering the selector valve 126 from the flow channel exiting the selector valve 126, and the selectively connected branch flow channels 1252 are also effectively spaced apart from each other.
[0186] In addition, in an embodiment of the present disclosure, as shown in the figure, the diversion assembly 123, for example, further includes a plurality of membrane rupture needles 123b, which protrude outward from the lower side of the edge 1208 of the top plate 120 and are spaced apart from each other in a straight line, and each membrane rupture needle 123b is constructed as a solid needle. Then, in a more specific embodiment, the plurality of drainage needles 123a are, for example, arranged parallel to each other with the plurality of membrane rupture needles 123b. And, in a further embodiment, as an example, corresponding membrane rupture needles 123b are arranged one-to-one on the sides of the plurality of drainage needles 123a, and the membrane rupture needles 123b are configured to puncture the film covering the sealing gasket on the corresponding reagent outlet portion of the liquid reservoir 2 (e.g., the reagent kit) in the accommodating chamber 110 once the accommodating chamber 110 rises to the upper limit position in the reagent kit platform 11. More specifically, for example, each drainage needle 123a is adjacent to but spaced apart from a corresponding single membrane rupture needle 123b in pair.
[0187] Furthermore, in another embodiment of the present disclosure, the guide assembly 123 further includes, for example, at least two guide pins 123c, which protrude outward from the underside of the edge 1208 of the top plate 120 and are spaced apart from each other in a straight line. The guide pins 123c are configured to form a positive fit with alignment features on the reservoir 2. After the guide pins 123c are aligned with the alignment features, the guide pins 123c are inserted into the alignment features (e.g., alignment holes or alignment recesses) to achieve the assembly of the reservoir 2 and the guide assembly 123. In a more specific embodiment, for example, the at least two guide pins 123c are arranged colinearly with the plurality of drainage needles 123a and are located outside two drainage needles 123a at either end of the plurality of drainage needles 123a.
[0188] Furthermore, in another embodiment of the present disclosure, as an example, the flow network 125 further includes an outlet pipeline for discharging waste liquid and a return pipeline for returning the injected reagent, both of which are connected to the chip receiving area 121 a.
[0189] The specific structure of the chip processing device 1 for fluid delivery, as described above, achieves a pipeline-free fluid path from the reagent cartridge, serving as the liquid reservoir 2, to the sequencing chip 3. Furthermore, according to the specific structure of the disclosed embodiment, liquid aspiration from the top of the reagent cartridge is achieved, thereby avoiding long-stroke translation and lifting of the reagent cartridge and preventing the reagent needle from being inserted into the bottom of the cartridge. Furthermore, in combination with other structures of the chip processing device 1, precise positioning of the reagent cartridge is achieved.
[0190] Thus, the flow guide component 123 and the aforementioned fluid supply device 150 (the fluid supply device 150 includes the aforementioned top plate 120 (acting as a carrier for carrying the sequencing chip), the flow network 125 and the selector valve 126) together define a fluid guiding device 160, which is configured to guide a plurality of reagent fluids from a fluid reservoir (such as a reagent kit 2) to the sequencing chip 3.
[0191] In addition, FIG10 illustrates a cross-sectional view of the chip processing device 1 shown in the top view of FIG2(e) along line EE, 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.
[0192] As shown in the figure, in an embodiment according to the present disclosure, for example, the chip processing device 1 shown also includes a positioning device 111, which is, for example, arranged in the reagent chamber platform 11 and includes: a groove 1110, recessed in the top inner wall of the accommodating chamber 110; an elastic component, 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 to: in response to the reagent chamber not reaching the positioning bead in the accommodating chamber, the elastic component is in an initial state without being subjected to the force applied by the reagent chamber and the positioning bead protrudes at least partially toward the substrate from the top inner wall of the accommodating chamber; 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. Through this setting of 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 bead 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. The positioning bead 111b is pressed outward 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.
[0193] In a more specific embodiment, for example, the top wall 25 of the reagent box 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. In other words, 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 into place, the positioning bead 111b is pushed outward by the elastic restoring force of the compressed spring 111a to cooperate with the recess, thereby elastically locking the liquid reservoir 2 in place. This elastic locking does not affect the subsequent removal of the reagent box from the storage chamber 110 after the sequencing work is completed.
[0194] In an embodiment of the present disclosure, as an example, the chip processing device 1 further includes a position detector 112 disposed within the storage compartment 110. The position detector 112 includes an optical coupling assembly and a shielding member. The shielding member is, for example, disposed on or connected to the liquid reservoir 2. The optical coupling assembly includes an infrared emitter and an infrared receiver. The optical coupling assemblies are, for example, both disposed within the reagent reagent platform 11 and spaced apart from each other. The optical coupling assemblies are configured to determine that the liquid reservoir 2 is in place within the storage compartment 110 in response to the shielding member being displaced or deformed by the force exerted by the liquid reservoir 2 when the liquid reservoir 2 is inserted into the storage compartment 110 and in place, thereby blocking the infrared receiver from receiving infrared rays from the infrared emitter. Utilizing such a shielding member carried by the liquid reservoir 2 facilitates detection of whether the liquid reservoir 2 is in place within the storage compartment 110 and determination of its position.
[0195] In an alternative embodiment of the present disclosure, as an example, 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. The positioning feature aligns with the position sensor when the liquid reservoir 2 is inserted into the accommodation chamber 110 and is in place, and the position sensor is configured to determine that the liquid reservoir 2 is in place within the accommodation chamber 110 by detecting the pushing action exerted by the positioning feature. Furthermore, for example, the position sensor is a force sensor. Through such an alternative configuration, the force sensor is used to detect the position of the liquid reservoir 2 inserted into the accommodation chamber 110 based on contact force.
[0196] In an embodiment according to the present disclosure, referring back to Figure 1, as an example, the chip processing device 1 also includes a clamping device 113 formed at the top of the reagent reagent platform 11, and the top of the reagent reagent platform 11 is formed with a through opening to at least partially expose the liquid reservoir 2 inserted into the accommodating chamber 110, and 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 free side of the pressing plate 1130 opposite to the one side; a pair of arms 1132, one end of each arm 1132 is pivotally connected to the corresponding end of the pin 1131; and a pair of elastic members 1133, each elastic member 1133 (such as a torsion spring) is elastically connected between the corresponding arm 1132 in the pair of arms 1132 and the reagent reagent platform 11. By utilizing the setting of this clamping device 113, once the liquid reservoir 2 is inserted into place in the accommodating chamber 110, for example, by slightly pushing one of the pair of arms 1132 around the pin 1131, 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 roughly vertical direction.
[0197] In an embodiment according to the present disclosure, referring back to FIG1 , further, for example, an additional tilt adjustment structure is provided to facilitate the leveling of the reagent reagent platform 11 and the chip platform 12. More specifically, as shown in FIG1( d)-(f), as an example, the chip platform 12 includes a fixed bracket 12a, which supports and is fixed between the top plate 120 and the base plate 10, and partially extends between the reagent reagent platform and the base plate 10 and leaves a gap between the reagent reagent platform 11. An extension plate 12b fixed to the pressure plate 1130 extends from the fixed bracket 12a corresponding to one side edge of the reagent reagent platform 11, and the reagent reagent platform 11 is located between the extension plate 12b and the selector valve. The reagent reagent 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. Preferably, the movable bracket 11a is L-shaped.
[0198] The chip processing device 1 further includes a first tilt adjustment mechanism 114 disposed between the fixed bracket 12a and the base plate 10 and located on one side of the reagent reagent platform 11. The first tilt adjustment mechanism 114 includes a non-linear first distance head and two first thread pairs 1140 capable of being screwed and adjusted relative to the base plate 10. Furthermore, as an example, the chip processing device 1 further includes a second tilt adjustment mechanism 124 disposed between the fixed bracket 12a and the base plate 10 and located on one side of the chip platform 12. The second tilt adjustment mechanism 124 includes a non-linear second distance head and two second thread pairs 1240 capable of being screwed and adjusted relative to the base plate 10. Since the 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 reagent 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.
[0199] In an embodiment of the present disclosure, referring back to Figure 2(b) and Figure 2(d), for example, the chip processing device 1 also includes a limit device 14, and the limit device 14 includes: a sensing plate 140, which is arranged on the 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, which are respectively arranged at the upper and lower ends of the stroke of the corresponding movable rail 132 at both ends of the corresponding fixed rail 131 of the at least one group of cross-roller guide rails 130, and are respectively configured to stop the driving source in response to detecting that the sensing plate 140 blocks the upper limit optical coupler 141 and determines that the movable rail 132 rises to the upper limit position, and to stop the driving source in response to detecting that the sensing plate 140 blocks the lower limit optical coupler 142 and determines that the movable rail 132 drops to the lower limit position. The lower limit position is, for example, the aforementioned non-drainage position, and in particular, is, for example, the lowest position in the second position range serving as the non-drainage position.
[0200] Through the above-mentioned specific setting of the limiting device 14, the upper limit position and the lower limit position of the accommodating bin 110 can be detected and determined during the lifting movement of the accommodating bin 110 carrying the liquid reservoir 2 inserted therein within the reagent reagent 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 lower limit position, thereby realizing the limit position detection and limiting in an electronically controlled manner.
[0201] Furthermore, as an expanded embodiment of the present disclosure, the position limiting device may further include two position limiting blocks, respectively provided at both ends of the fixed rail 131 of at least one set of cross ball guide rails, with each position limiting block at least partially aligned with a corresponding movable rail 132. Thus, once the accommodating bin 110 is raised to the upper limit position or lowered to the lower limit position, the position limiting blocks mechanically assist in position limiting.
[0202] Furthermore, in the chip processing device 1, in conjunction with the above-mentioned specific structure for conveying fluid, a power component 129 is also provided. The power component 129 is arranged to be fluidically connected to the flow network and configured to drive the fluid to flow through the flow network toward the supply port.
[0203] As an example, 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. For example, the pump is a syringe pump disposed at least at one location upstream and downstream of the selector valve 126, and the syringe pump is configured to provide negative pressure to the chip receiving area 121a. Thus, the negative pressure provided by the syringe pump is used to aspirate the fluid, thereby achieving aspiration of the fluid (more specifically, the reagent in the reagent kit) without inserting the drainage needle 123a into the bottom of the reservoir 2, thereby providing aspiration and liquid supply for the fluid to be transported from the reagent kit to the sequencing chip 3.
[0204] Figure 11 illustrates, in exploded view, the assembly relationship of the temperature control assembly relative to the carrier via the adapter bracket. Figure 12(a) shows a cross-sectional view along line AA as in Figure 9(f), and Figure 12(b) shows a cross-sectional view along line BB as in Figure 9(f), specifically illustrating the structure and assembly relationship of the temperature control assembly, which is assembled to the top plate via screws. Figures 13(b) to 13(c) respectively show cross-sectional views along lines CC and DD as in Figure 9(f), specifically illustrating the assembly relationship between the selector valve and the top plate via screw S1.
[0205] As an example, the fluid guiding device 160 is additionally integrated with a temperature control component 128, which is arranged on the side of the top plate opposite to the chip receiving area and is configured to adjust the temperature of the fluid supplied from the guide component to the chip receiving area.
[0206] In addition, in an embodiment of the present disclosure, as an example, 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 regulate the temperature of the fluid supplied from the flow guide component 123 to the chip receiving area 121a.
[0207] In a specific embodiment of the present disclosure, for example, the temperature control assembly 128 includes a first temperature regulating device 128a, which is arranged adjacent to the selector valve on the same side of the top plate. Furthermore, as shown in the figure, the fluid guiding device further includes an adapter bracket 127 fixed to the side of the top plate opposite the chip receiving area. The adapter bracket 127 is constructed in the form of a frame, and the adapter bracket 127 is formed with two recesses 1270 and 1271 arranged in parallel and recessed from the adapter bracket 127 on opposite sides facing away from the top plate and toward the top plate, respectively, for accommodating and securing the selector valve and the first temperature regulating device therein, respectively.
[0208] This arrangement further ensures that the selector valve is reliably fixed relative to the carrier, and also achieves an assembly relationship in which the first temperature adjustment device is fixed relative to the carrier 120 via the adapter bracket 127 .
[0209] As an example, as shown in the figure, 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, which 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.
[0210] Furthermore, as an example, the temperature control assembly further includes a heat conducting member 128b interposed between the carrier and the first temperature regulating device (also shown as being built into the adapter bracket 127). More specifically, for example, the heat conducting member 128b includes a phase change material.
[0211] In a more specific embodiment, for example, the active heat sink includes a thermoelectric cooler (e.g., a thermoelectric cooler (TEC) such as a Peltier effect device, a fan, or the like); 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.
[0212] In an additional embodiment of the present disclosure, as an example, the temperature control assembly 128 further includes a second temperature regulating device 128c, which is fixed to a side of the adapter bracket 127 facing 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.
[0213] 13( a ), in an embodiment of the present disclosure, the second temperature regulating device includes a fan 1280. The fan 1280 includes: a hollow first housing 1281, the interior of which defines a cavity for airflow; the first housing 1281 is arranged such that the cavity is aligned with and open toward the first temperature regulating device, thereby fluidically connecting the cavity between the first temperature regulating device and the exterior of the flow guiding device; and a fan assembly housed within the first housing 1281.
[0214] In a further embodiment, for example, the fan assembly includes: a second shell 1283, which is constructed as 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.
[0215] In an embodiment of the present disclosure, the adapter bracket 127 is also formed with a gas channel 1286 that runs through its interior 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.
[0216] Therefore, 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 air flow exchange, thereby improving the heat exchange speed and efficiency of the heat sink.
[0217] Furthermore, in an embodiment of the present disclosure, for example, 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.
[0218] The above arrangement facilitates effective temperature control of the chip receiving area 121 a , especially around the selector valve 126 .
[0219] Furthermore, in an embodiment of the present disclosure, as an example, 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
[0220] 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. It includes a plurality of vibration-damping parts that are respectively snapped into the inner wall of the first shell 1281 and 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 parts.
[0221] And, more specifically, as an example, the first shell of the fan is fixed to the adapter bracket via a flexible vibration-absorbing material screw 1281a, the first shell 1281 is protruded with a lug 1281b for installing the screw 1281a, and the first-stage vibration reduction structure is pushed tightly between the adapter bracket 127 and the first shell 1281 via the screw 1281a.
[0222] In a further embodiment, for example, 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.
[0223] In a more specific embodiment, the first shell 1281 of the fan 1280 is fixed to the adapter bracket 127 via a flexible vibration-absorbing material screw, and the first-stage vibration reduction structure is pushed tightly between the adapter bracket 127 and the first shell 1281 via the screw.
[0224] Therefore, through the above-mentioned arrangement, for the second temperature regulating device 128c including a fan for providing forced air cooling, a vibration reduction structure arranged in a sandwich manner (for example, the two-stage vibration reduction structure shown in the figure and arranged separately from each other) is further adopted. By inserting the second temperature regulating device 128c between the first-stage vibration reduction structure 128d and the second-stage vibration reduction structure 128e, a sandwich-type multi-stage vibration reduction structure is realized, 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 the fluid guiding device 160, for example (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).
[0225] In addition, in an embodiment of the present disclosure, as shown in Figures 13(b) to 13(c), for example, in an embodiment of the present disclosure, as shown in the figure, for example, 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 pass through 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.
[0226] In this way, 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. In addition, 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).
[0227] 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.
[0228] According to another aspect of the embodiments of the present disclosure, based on the overall technical concept of the embodiments of the present disclosure, for example, as shown in FIG14 , a gene sequencer 4 is provided, wherein the chip processing device includes a substrate extending along a first direction, and a reagent cartridge platform and a chip platform assembled side by side and adjacent to each other on the substrate along a second direction transverse to the first direction, wherein the top plate of the chip platform on a side facing away from the substrate is provided with a chip receiving area for accommodating the chip, and the reagent cartridge platform is formed with a hollow accommodating chamber, wherein the reagent cartridge is received in the accommodating chamber and is at least partially filled with the fluid. Furthermore, for example, the reagent cartridge has a first fluid transport structure located on a side of the reagent cartridge facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located on a side of the chip platform facing the reagent cartridge platform along the second direction and configured to at least partially overlap and communicate with the first fluid transport structure when the reagent cartridge platform and the chip platform are assembled; and the reagent cartridge is removably inserted into the accommodating chamber, and the fluid in the reagent cartridge is fluidically connected to the sample loaded on the chip via the first and second fluid transport structures.
[0229] In a more specific embodiment, 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 fluidically connected, and a state in which they are not fluidically connected; and the chip processing device is configured to: in response to the accommodating chamber rising away from the substrate to the drainage position, connect the first fluid transport structure and the second fluid transport structure to each other to form fluid communication; and in response to the accommodating chamber descending toward the substrate to the non-drainage position, separate the first fluid transport structure and the second fluid transport structure from each other.
[0230] As an example, more specifically, the top plate of the chip platform at the side away from the base plate 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 base plate.
[0231] As an example, more specifically, the first fluid transport 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 in which the fluid is 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 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.
[0232] As an example, more specifically, 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 mounted to the top plate and in fluid communication with the flow path network.
[0233] As an example, more specifically, the selector valve includes: a valve seat 1261, via which the selector valve is fixed to the top plate; 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. Furthermore, as an example, the flow path network includes: a plurality of drainage needle ports located on a 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 communicating between each drainage needle port and a corresponding inlet port and configured to guide 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 communicating with the plurality of branch flow channels; and a common flow channel communicating between the outlet port and the chip receiving area and configured to guide fluid output from the outlet port to the chip receiving area. For example, 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 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.
[0234] As an example, more specifically, the plurality of drainage needle ports are formed through the edge of the top plate in a protrusion protruding toward a side of the top plate away from the chip receiving area.
[0235] As an example, more specifically, 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. For example, 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.
[0236] As an example, more specifically, when the plurality of drainage needles are inserted into the guide groove 20 b , 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 .
[0237] As an example, more specifically, each guide groove 20b is configured as a groove having a circular cross section with a first inner diameter, and 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.
[0238] As an example, more specifically, the first pierceable structure is a metal foil; and 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.
[0239] Since 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 described in detail here.
[0240] FIG15 illustrates a gene sequencing device 5 according to an embodiment of the present disclosure, comprising a pair of the aforementioned gene sequencers 4 arranged in a mirror-symmetrical manner and adjacent to each other.
[0241] According to another aspect of the embodiments of the present disclosure, based on the overall technical concept of the embodiments of the present disclosure, for example, as shown in FIG15 , a gene sequencing device 5 is also provided, comprising: a chip carrying a sample to be detected using a fluid; and at least two aforementioned chip processing devices, each chip processing device comprising a substrate extending along a first direction, and a reagent cartridge platform and a chip platform assembled side by side and adjacently on the substrate along a second direction transverse to the first direction, the top plate of the chip platform on the side facing away from the substrate being provided with a chip receiving area for accommodating the chip, the reagent cartridge platform being formed with a hollow accommodating chamber, the reagent cartridge being received in the accommodating chamber and at least partially filled with the fluid. For example, the reagent cartridge has a first fluid transport structure located on a side of the reagent cartridge facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located on a side of the chip platform facing the reagent cartridge platform along the second direction and being configured to at least partially overlap and communicate with the first fluid transport structure when the reagent cartridge platform and the chip platform are assembled. Furthermore, for example, the reagent kit is removably inserted into the storage compartment, and the fluid in the reagent kit is fluidically connected to the sample loaded on the chip via the first fluid delivery structure and the second fluid delivery structure. Specifically, for example, as shown in the figure, the at least two chip processing devices are symmetrically arranged with their respective chip platforms adjacent to each other.
[0242] As an example, more specifically, the at least two chip processing devices include at least one pair of chip processing devices that are arranged in a mirror-symmetrical manner with each other and whose respective chip platforms are adjacent to each other.
[0243] As an example, more specifically, the accommodating chamber is coupled to the substrate in a manner capable of linear movement within a range between a highest drainage position and a non-drainage position below the drainage position, wherein 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. Furthermore, for example, the chip handling device is configured to: in response to the accommodating chamber being raised away from the substrate to the drainage position, the first fluid transport structure and the second fluid transport structure are engaged and fluidically connected with each other; and in response to the accommodating chamber being lowered toward the substrate to the non-drainage position, the first fluid transport structure and the second fluid transport structure are separated from each other.
[0244] As an example, more specifically, the top plate of the chip platform at the side away from the base plate 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 base plate.
[0245] As an example, more specifically, the first fluid transport 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 in which the fluid is 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 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.
[0246] As an example, more specifically, 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 mounted to the top plate and in fluid communication with the flow path network.
[0247] As an example, more specifically, the selector valve includes: a valve seat 1261, via which the selector valve is fixed to the top plate; 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. Furthermore, as an example, the fluid path network includes: a plurality of drainage needle ports located on a 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 communicating between each drainage needle port and a corresponding inlet port and configured to guide 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 communicating with the plurality of branch flow channels; and a common flow channel communicating between the outlet port and the chip receiving area and configured to guide fluid output from the outlet port to the chip receiving area. Furthermore, for example, 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 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.
[0248] As an example, more specifically, the plurality of drainage needle ports are formed through the edge of the top plate in a protrusion protruding toward a side of the top plate away from the chip receiving area.
[0249] As an example, more specifically, the second fluid delivery structure further includes a flow guide assembly protruding from the flange toward the reagent cartridge platform and connected to the chip receiving area, the flow guide assembly including: a plurality of membrane rupture needles and a plurality of drainage needles, each protruding from a side of the top plate opposite to the chip receiving area toward the reagent cartridge 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. Furthermore, for example, each membrane rupture needle is not connected to the flow path network and is configured to puncture 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 reservoir 20a to expose the reagent reservoir 20a and change the air pressure within the reagent reservoir 20a. And, for example, 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.
[0250] As an example, more specifically, when the plurality of drainage needles are inserted into the guide groove 20 b , 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 .
[0251] As an example, more specifically, each guide groove 20b is configured as a groove having a circular cross section with a first inner diameter, and 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.
[0252] As an example, more specifically, the first pierceable structure is a metal foil; and 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.
[0253] The gene sequencing device 5 comprises the aforementioned chip processing device 1 and the aforementioned gene sequencer 4, thereby possessing all the advantages of the aforementioned chip processing device 1, which will not be further elaborated here. Furthermore, by using two mirror-image gene sequencers 4, two chips 3 can be loaded simultaneously with minimal spacing between them, significantly reducing the travel distance required to switch chips 3 and, consequently, shortening the test interval.
[0254] Figure 16 is a schematic flow chart of a biochemical detection method according to an embodiment of the present disclosure using the gene sequencer 4 shown in Figure 14. Figure 17 schematically illustrates more specific steps in the method shown in the flow chart of Figure 16.
[0255] According to another aspect of the embodiments of the present disclosure, based on the overall technical concept of the embodiments of the present disclosure, for example, as shown in FIG16 , a biochemical detection method using the aforementioned gene sequencer 4 is also provided. The gene sequencer includes: a chip, the chip carrying a sample to be detected using a fluid; and a chip processing device, the chip processing device including a substrate extending along a first direction, and a reagent cartridge platform and a chip platform assembled side by side and adjacent to each other on the substrate along a second direction transverse to the first direction, the top plate of the chip platform on the side facing away from the substrate having a chip receiving area for accommodating the chip, the reagent cartridge platform forming a hollow accommodating chamber, the reagent cartridge being received in the accommodating chamber and at least partially filled with the fluid. Furthermore, for example, the reagent cartridge has a first fluid transport structure located on the side of the reagent cartridge facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located on the side of the chip platform facing the reagent cartridge platform along the second direction and configured to at least partially overlap and communicate with the first fluid transport structure when the reagent cartridge platform and the chip platform are assembled. Furthermore, for example, the reagent kit is removably inserted into the storage 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.
[0256] As an example, the biochemical detection method includes: S1: establishing a fluid connection between a chip having a sample to be detected and a reagent kit having multiple different reaction components, wherein the reaction components include at least one of a sample generation component and a sample analysis component. S2: performing a generation operation and / or an analysis operation. The reagent kit and chip are integrated into the chip processing device described in the above embodiments, and the fluid in the reagent kit is fluidically connected to the chip via a first fluid transport structure and a second fluid transport structure that are separate from each other in the chip processing device.
[0257] Optionally, a sample to be detected is generated on the chip during a generation operation, the generation operation comprising flowing different sample generation components into the chip and controlling reaction conditions on the chip to generate the sample. The sample on the chip is analyzed during an analysis operation, the analysis operation comprising flowing sample analysis components into the chip, the sample analysis components reacting with the sample to provide a relevant detectable signal. The biochemical reaction may be a nucleic acid sequencing reaction or an antigen-antibody binding reaction, the sample to be detected may be a nucleic acid sequencing library or a biological tissue slice, and the detectable signal is preferably an optical signal.
[0258] The first fluid delivery structure is connected to the external air pressure of the chip handling device to drive the fluid in the reagent cartridge into the second flow delivery structure, and selectively connects the chip to the fluid. For example, the second flow delivery structure includes the aforementioned multiple branch flow channels, and the selector valve 126 integrated in the chip handling device controls the selective connection between different branch flow channels and the chip.
[0259] Furthermore, in order to enable those skilled in the art to understand the present invention more clearly, more specific steps of the method shown in FIG. 16 are shown below in conjunction with FIG. 17 .
[0260] In a more specific embodiment of the present disclosure, for example, 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 storage chamber 110 through the open opening of the storage chamber 110, and using the aforementioned in-position detector 112 provided inside the storage chamber 110 to detect whether the reagent kit is in place in the storage chamber 110, and using the positioning bead 111b of the aforementioned positioning device 111 in the storage chamber 110 to tightly press the reagent kit under the elastic pushing action of the spring 111a to keep the reagent kit in place.
[0261] In a specific embodiment, for example, the storage chamber is movable within the chip processing device via a movable bracket (equivalent to the above-mentioned movable bracket 11a) and 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 below the drainage position, wherein 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. Furthermore, as an example, the chip processing device is configured to: in response to the storage chamber being raised 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 storage chamber being lowered toward the substrate to the non-drainage position, the first fluid transport structure and the second fluid transport structure are separated from each other. In this configuration, the method further includes: after inserting the reagent kit into the storage chamber and placing it in position, raising the storage chamber to the drainage position, thereby triggering the subsequent fluid communication of the reagent kit to the chip supporting platform (having a similar structure to the top plate 120 in the above-mentioned embodiment).
[0262] In a specific embodiment, for example, the top plate of the chip platform on the side facing away from the base plate 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 base plate. In addition, as an example, the first fluid delivery structure includes a plurality of reagent reservoirs 20a and a plurality of guide grooves 20b arranged in a one-to-one correspondence within the reagent kit, and a communication channel 20c fluidically connected between the bottom of each guide groove 20b and the bottom of the corresponding reagent reservoir 20a, each reagent reservoir 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. Furthermore, as an example, the second fluid delivery structure includes a flow guide component, which includes: a plurality of membrane rupturing 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 rupturing 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 rupturing 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 20b to be fluidically connected to the guide groove 20b to draw the fluid in the guide groove 20b. Thus, the method further includes lowering and returning the accommodating chamber 110. Specifically, after raising the accommodating chamber to the drainage position, the corresponding first end of each membrane rupture needle is driven to pierce the first pierceable structure 210, and the corresponding second end of each drainage needle is driven to pierce the second pierceable structure 220, thereby establishing fluid communication between the first fluid delivery structure and the second fluid delivery structure; and after lowering and resetting the accommodating chamber from the drainage position to the non-drainage position, the corresponding first end of each membrane rupture needle is driven to detach from the first pierceable structure 210, and the corresponding second end of each drainage needle is driven to detach from the second pierceable structure 220, thereby cutting off fluid communication between the first fluid delivery structure and the second fluid delivery structure.
[0263] In a further embodiment, as an example, step S1 further includes adjusting the adjustable thread pairs of the first tilt adjustment mechanism 114 and the second tilt adjustment mechanism 124 to level the reagent reagent platform 11 and the chip platform 12. Specifically, the reagent reagent platform 11 is leveled and stably supported by adjusting a three-point support structure defined by a first distance head and two adjustable first thread pairs 1140 in the first tilt adjustment structure, and the chip platform 12 is leveled and stably supported by adjusting another three-point support structure defined by a second distance head and two adjustable second thread pairs 1240 in the second tilt adjustment structure.
[0264] In a further embodiment, as an example, 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 action of the elastic force of the connected pair of springs 111a, thereby realizing the use of the pressure plate 1130 to tightly press the top of the accommodating chamber 110 and the liquid reservoir 2, thereby further realizing the accommodating chamber 110 together with the liquid reservoir 2 being pressed downward in a substantially vertical direction.
[0265] In a more specific embodiment of the present disclosure, for example, step S1 further 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.
[0266] In a further embodiment, as an example, step S1 further includes: the aforementioned limiting device 14 stops the driving source in response to the situation that the accommodating bin 110 rises to the upper limit position.
[0267] In a more specific embodiment of the present disclosure, for example, step S1 also includes: using the guide needle in the aforementioned guide assembly 123 to puncture the liquid reservoir 2, and then using the aforementioned selector valve 126 (for example, 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 liquid reservoir 2 (for example, 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.
[0268] In a more specific embodiment of the present disclosure, for example, 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, for example, maintaining the chip 3 in place in the chip receiving area 121a 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).
[0269] In a more specific embodiment of the present disclosure, for example, step S1 includes: 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, thereby achieving contact between the reagent and the sample and performing the above-mentioned analysis and / or generation operations.
[0270] In a more specific embodiment of the present disclosure, for example, the method further includes “removing the chip 3 from the chip handling device 1 ”, for example, taking the chip 3 out of the chip handling device 1 by disabling / canceling the adsorption force and then removing the chip 3 from the chip receiving area 121 a .
[0271] In a more specific embodiment of the present disclosure, for example, 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 the initial lower position.
[0272] In a more specific embodiment of the present disclosure, 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 .
[0273] The method of applying the aforementioned gene sequencer 4 uses 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.
[0274] Therefore, 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 to related technologies in the field:
[0275] The chip processing device, gene sequencer, gene sequencing equipment and biochemical detection method implemented by the embodiments of the present disclosure, especially the chip processing device, can realize an integrated pipeline-free fluid delivery structure through the above-mentioned settings, which has a reduced flow channel length, a more reliable leveling and tightening effect on the test kit, and a higher positioning accuracy. And 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. Thus, it is possible to improve the fixation, positioning, stroke, etc. of the fluid delivery structure while improving the integration and thus the space utilization, and realize the design expectations with a more compact structure. And this compact structure minimizes the space occupied, and the simple structure and connection relationship facilitate assembly and disassembly.
[0276] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.
[0277] Although the present disclosure is described in conjunction with the accompanying drawings, the embodiments disclosed in the drawings are intended to exemplify the preferred embodiments of the present disclosure and should not be construed as limiting the present disclosure.
[0278] Although some embodiments of the present general inventive concept have been shown and described, it will be appreciated by those skilled in the art that changes may be made to these embodiments without departing from the principles and spirit of the present general inventive concept, the scope of which is defined in the claims and their equivalents.
Claims
1. A chip processing device integrated with a reagent cartridge, comprising a base plate extending in a first direction, and a reagent cartridge platform and a chip platform assembled side by side and adjacent to each other on the base plate in a second direction transverse to the first direction, wherein a top plate of the chip platform, facing away from the base plate, is provided with a chip receiving area for accommodating a chip carrying a sample to be tested using a fluid, and the reagent cartridge platform is formed with a hollow receiving chamber, wherein the reagent cartridge is received in the receiving chamber; in, The reagent kit has a first fluid transport structure located inside the reagent kit at a side thereof facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located on 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, and the first fluid transport structure is fluidically connected to the chip via the second fluid transport structure.
2. The chip processing device according to claim 1, wherein: The accommodating chamber is coupled to the base plate 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, wherein the drainage position and the non-drainage position correspond to a state in which the first fluid conveying structure and the second fluid conveying structure are in fluid communication and a state in which the fluid is not in fluid communication; and The chip processing device is configured to: In response to the accommodating chamber rising away from the substrate to a drainage position, the first fluid delivery structure and the second fluid delivery structure are coupled to each other to achieve fluid communication; and In response to the accommodating chamber descending toward the substrate to a non-draining position, the first fluid delivery structure and the second fluid delivery structure are separated from each other.
3. The chip processing device according to claim 2, wherein: The top plate on the side of the chip platform facing away from the base plate 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 base plate.
4. The chip processing device according to claim 3, wherein: The first fluid delivery structure includes a plurality of reagent reservoirs and a plurality of guide reservoirs arranged in a one-to-one correspondence within the reagent cartridge, and a communication channel in which the bottom of each guide reservoir is fluidically connected to the bottom of the corresponding reagent reservoir, each reagent reservoir being at least partially filled with fluid and having a first opening opening upwardly toward the flange and a first pierceable structure covering the first opening, and each guide reservoir having a second opening opening upwardly toward the flange and a second pierceable structure covering the second opening.
5. The chip processing device according to claim 4, wherein: The second fluid delivery structure includes a fluid supply device, and the fluid supply device includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid delivery structure and the chip, and A selector valve is mounted to the top plate and is in fluid communication with the flow network.
6. The chip processing device according to claim 5, wherein: The selector valve comprises: a valve seat, via which the selector valve is fixed to the top plate; a valve body extending from the valve seat in a direction away from the top plate and forming a fluid inlet configured to guide fluid into the interior of the valve body and a fluid outlet configured to guide fluid to flow outward from the interior of the valve body; and The flow path network includes: a plurality of drainage needle ports located on a 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 being connected between each drainage needle port and a corresponding inlet port and configured to guide 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 in communication with the plurality of branch flow channels; and a common flow channel communicating 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; Wherein, the selector valve is arranged so that the fluid outlet is fluidically connected to the outlet port, and the fluid inlet is fluidically 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.
7. The chip processing device according to claim 6, wherein: The plurality of drainage needle ports are formed through a convex portion at an edge of the top plate and protruding toward a side of the top plate away from the chip receiving area.
8. The chip processing device according to claim 6, wherein: The second fluid delivery structure further includes a flow guide assembly protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide assembly including: a plurality of membrane rupture needles and a plurality of drainage needles, each protruding from a 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, and each drainage needle having a second end aligned with a corresponding second pierceable structure, wherein each membrane rupturing needle is not connected to the flow network and is configured to, in response to the accommodating chamber reaching the drainage position, pierce the first pierceable structure with its first end and then insert into 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 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 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove to be fluidically connected to the guide groove to draw fluid in the guide groove.
9. The chip processing device according to claim 8, wherein: When the plurality of drainage needles are inserted into 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.
10. The chip processing device according to claim 9, wherein: Each guide groove is configured as a groove having a circular cross-section with a first inner diameter, and each guide groove is configured as a groove having a circular cross-section with a second inner diameter smaller than the first inner diameter.
11. The chip processing device according to claim 8, wherein: The first pierceable structure is a metal foil; and The second pierceable structure is a flexible seal such that a fluid-tight seal is maintained after being pierced by a corresponding drain needle of the plurality of drain needles.
12. The chip processing device according to claim 8, wherein: The plurality of drainage needles are spaced apart from each other and arranged in a straight line, and the plurality of membrane rupture needles are spaced apart from each other and arranged in a straight line; and The plurality of drainage needles and the plurality of membrane rupture needles are arranged parallel to each other.
13. The chip processing device according to claim 12, wherein: A corresponding membrane-breaking needle is arranged on the side of each of the plurality of drainage needles in a one-to-one correspondence, and each drainage needle is adjacent to the corresponding single membrane-breaking needle in pairs but spaced apart.
14. The chip processing device according to claim 8, wherein: Each drainage needle includes a hollow and elongated straight tubular needle body and a through-top with a tapered longitudinal cross-sectional shape.
15. The chip processing device according to claim 8, wherein: The plurality of drainage needles are mounted to the plurality of drainage needle ports in a threaded connection manner.
16. The chip processing device according to claim 8, wherein: The guide assembly further includes: at least two guide pins protruding outward from a side of the top plate opposite to the chip receiving area and spaced apart from each other in a straight line, and configured to form a shape fit with alignment features on the reagent cartridge.
17. The chip processing device according to claim 6, wherein: The plurality of drainage needle ports are arranged in a straight line aligned with each other.
18. The chip processing device according to claim 17, wherein: The plurality of drainage needle ports are arranged to be separated from each other at uniform intervals.
19. The chip processing device according to claim 6, wherein: The selector valve is a rotary valve configured to be rotatable about its axis so as to switch 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 and the fluid outlet.
20. The chip processing device according to claim 19, wherein: The inlet port and the outlet port each have an axial direction parallel to the axis, the inlet port is disposed offset from the axis, and the outlet port is disposed coaxially with the axis.
21. The chip processing device according to claim 20, wherein: The selector valve is mounted via the valve seat to a back side of the top plate facing away from the chip receiving area, and The plurality of inlet ports are configured to be arranged in a ring around the axis, the plurality of inlet ports and the outlet port are both open to the back side of the top plate, at least one of the plurality of inlet ports is selectively connected to the fluid inlet of the valve body, and the outlet port is connected to the fluid outlet of the valve body, and the center distance between each of the plurality of inlet ports and the outlet port is equal.
22. The chip processing device according to claim 19, wherein: 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.
23. The chip processing device according to claim 6, wherein: The top plate includes: a top layer in which the chip receiving area is formed; and a support layer, the support 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 support layer facing the top layer, and the plurality of inlet ports, the outlet ports and the plurality of drainage needle ports extend through the support layer.
24. The chip processing device according to claim 23, wherein: 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 is arranged around the accommodating hole.
25. The chip processing device according to claim 24, wherein: The top plate further 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, partially disposed in the receiving hole, with an edge of a top surface thereof protruding outward to define an adsorption groove in the top layer that is recessed toward the support layer and is located between the edge and the top surface, wherein the adsorption groove is configured as a closed groove extending along the edge and in a closed loop, and is shaped and sized to surround and secure the edge of the chip; and A negative pressure channel is formed through the adsorption platform and communicates between the pipe joint and the adsorption tank.
26. The chip processing device according to claim 24, wherein: The top layer is formed with a supply port and a discharge port extending therethrough and to the recess, the supply port being in fluid communication with the outlet port of the valve body via the common flow passage, and the discharge port being spaced apart from the supply port.
27. The chip processing device according to claim 26, wherein: The common flow channel is linearly connected between the outlet port and the supply port.
28. The chip processing device according to claim 27, wherein: The plurality of branch flow channels are arranged so as not to intersect with each other and to avoid the common flow channel.
29. The chip processing device according to claim 26, wherein: The ends of the exhaust port and the supply port and the support layer extend to the recessed portion, respectively; 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 discharge port respectively at the first liquid-tight sealing surface.
30. The chip processing device according to claim 26, wherein: The support layer is formed with a discharge channel therethrough that is fluidically connected from the discharge port to the outside of the top plate.
31. The chip processing device according to claim 23, wherein: The multiple inlet ports and the outlet ports extend through the support layer to the back side of the top plate, and the back side and the valve seat jointly define a second liquid-tight sealing surface. The multiple inlet ports and the outlet ports respectively form sealed fluid communication with the fluid inlet and the fluid outlet of the valve body at the second liquid-tight sealing surface.
32. The chip processing device according to claim 8, wherein: The chip processing device also includes a driving member arranged inside it and at least one guide rail assembly connected between the storage bin and the base plate. The storage bin can be moved in a direction orthogonal to the base plate 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.
33. The chip processing device according to claim 32, wherein: The driving member 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.
34. The chip processing device according to claim 33, wherein: Each guide rail assembly includes two spaced-apart sets of 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 containing bin, and a plurality of rolling elements held between the fixed rail and the movable rail.
35. The chip processing device according to claim 34, wherein: In each set of cross roller guide rails, the fixed rail is fixed to the chip platform in a manner perpendicular to the substrate, and the movable rail is fixed to the accommodating bin in a manner perpendicular to the substrate.
36. The chip processing device according to claim 35, wherein: The lead screw is coupled to the movable rails of each of the two sets of cross roller guide rails in the at least one guide rail assembly.
37. The chip processing device according to claim 1, further comprising a positioning device, wherein the positioning device comprises: a groove, concavely formed in the top inner wall of the accommodating bin; an elastic component disposed in the groove, and A positioning bead is provided 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 without being subjected to a 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 base plate; and In response to the reagent box being inserted into the accommodating compartment and squeezing the positioning beads, the elastic component is pushed toward the groove via the positioning beads, and then the elastic component is at least partially retracted into the groove.
38. The chip processing device according to claim 37, wherein: The reagent kit includes a protrusion protruding toward the top inner wall of the accommodating chamber and a positioning groove recessed from the protrusion, and In response to the reagent box being inserted into the accommodating compartment and squeezing the positioning bead, the positioning bead is clamped between the positioning groove and the elastic component.
39. The chip processing device according to claim 1 or 37 further includes a position detector arranged inside the storage bin, the position 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 storage bin in response to the shielding member being displaced or deformed by the force exerted by the reagent kit when the reagent kit is inserted into the storage bin and is in place, and blocking the infrared receiver from receiving infrared rays from the infrared transmitter.
40. The chip processing device according to claim 1 , further comprising a pressing device formed at a top of the reagent cartridge platform, wherein a through opening is formed at the top of the reagent cartridge platform to at least partially expose the reagent cartridge inserted into the accommodating chamber, the pressing device comprising: a pressing plate, one side of which is fixed to the reagent cartridge platform; a pin extending through the pressure plate at a free side opposite the one side; a pair of arms, each arm having one end pivotally coupled to a corresponding one of the ends of the pin; and A pair of elastic members, each elastic member is elastically coupled between a corresponding arm of the pair of arms and the reagent reagent platform.
41. The chip processing device according to claim 1 further includes a first tilt adjustment mechanism arranged between the bottom of the reagent cartridge platform and the base plate, 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 base plate.
42. The chip processing device according to claim 1 further includes a second tilt adjustment mechanism arranged between the bottom of the chip platform and the substrate, the second tilt adjustment mechanism including a second distance head arranged non-linearly and two second thread pairs that can be screwed and adjusted relative to the substrate.
43. The chip processing device according to claim 34, further comprising a limiting device, wherein the limiting device comprises: an induction plate, disposed on a corresponding movable rail of at least one set of cross roller guide rails in at least one guide rail assembly; and The upper limit optical coupler and the lower limit optical coupler are respectively arranged at the positions corresponding to the upper end and the lower end 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 sensor sheet blocks the upper limit optical coupler and determines that the movable rail rises to the upper limit position, and to stop the driving source in response to detecting that the sensor sheet blocks the lower limit optical coupler and determines that the movable rail descends to the lower limit position.
44. The chip processing device according to any one of claims 8 to 16, further comprising a power component, wherein the power component is arranged to be in fluid communication with the flow network and configured to drive the fluid to flow through the flow network toward the supply port.
45. The chip processing device according to claim 44, wherein: The power assembly includes a pump in communication with the chip receiving area, the pump being configured to provide negative pressure to the chip receiving area.
46. The chip processing device according to claim 44, wherein: The device further includes a temperature control component, 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 guide component to the chip receiving area.
47. The chip processing device according to claim 46, wherein: The temperature control assembly includes a first temperature regulating device, which is arranged adjacent to the selector valve on the same side of the top plate, and The fluid guiding device further comprises an adapter bracket fixed to a side of the top plate opposite to the chip receiving area, the adapter bracket being constructed in the form of a frame, and the adapter bracket being formed with two recesses arranged in parallel and recessed from opposite sides of the adapter bracket facing 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.
48. The chip processing device according to claim 47, wherein: The first temperature regulating device comprises: a heat sink, housed in and mounted in one of the two recesses of the adapter bracket that is recessed from the side facing the top plate, and comprising: at least one of an active heat sink and a passive heat sink; and A temperature control module is mounted to the heat sink and is configured to cut off the power assembly when the temperature at the heat sink exceeds a threshold temperature.
49. The chip processing device according to claim 47, wherein: The temperature control assembly further includes: a heat conducting member inserted between the top plate and the first temperature regulating device.
50. The chip processing device according to claim 49, wherein: The heat conducting member includes a phase change material.
51. The chip processing device according to claim 48, wherein: The active heat sink comprises a thermoelectric cooler; or The passive heat sink includes one of the following: a single heat sink, a heat sink array.
52. The chip processing device according to claim 47, wherein: The temperature control assembly further includes a second temperature regulating device fixed to a side of the adapter bracket facing away from the top plate, arranged in parallel with the selector valve, and arranged to be aligned with the first temperature regulating device.
53. The chip processing device according to claim 52, wherein: The second temperature regulating device includes a fan, and the fan includes: a hollow first housing defining a cavity therein for airflow, the first housing being arranged such 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 fluidically between the first temperature regulating device and the exterior of the flow guiding device; and A fan assembly is accommodated in the first housing, and the fan assembly includes: The second shell is constructed as a hollow cylindrical body fixedly mounted in the first shell; a rotating shaft rotatably mounted in the second housing; and A plurality of fan blades are coaxially fixed to the rotating shaft in the second housing and are rotatable relative to the second housing along with the rotating shaft.
54. The chip processing device according to claim 53, wherein: The adapter bracket further has a gas passage running through it and opening at opposite ends thereof toward the cavities of the first temperature regulating device and the second temperature regulating device, respectively. The cavity is connected to the first temperature regulating device via the gas passage.
55. The chip processing device according to claim 53, wherein: The second temperature regulating device further includes a vibration damping device, and the vibration damping device includes: a first-stage vibration-damping structure configured as a spacer interposed between the adapter bracket and the first housing of the fan; and The second-stage vibration damping structure is arranged in the first shell of the fan and is located between the first shell and the second shell of the fan assembly. It includes a plurality of vibration damping parts that are respectively snapped into the inner wall of the first shell and spaced apart from each other. The second shell of the fan assembly is connected to the first shell via the plurality of vibration damping parts.
56. The chip processing device according to claim 55, wherein: At least one of the first-stage vibration damping structure and the second-stage vibration damping structure is a vibration compensation device, and the vibration compensation device is an elastic member or a damping member.
57. The chip processing device according to claim 55, wherein: 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.
58. The chip processing device according to claim 47 or 57, wherein: The selector valve is fixed to the top plate at its valve seat via a threaded connection, and the selector valve is coupled to the adapter bracket via an adjustable pressing device, the adjustable pressing device comprising: a plurality of distance screws, each of which is threadably inserted through the adapter bracket and presses against the valve body of the selector valve; and A plurality of springs elastically press the plurality of distance screws toward the top plate in a one-to-one correspondence.
59. A gene sequencer comprising: a chip carrying a sample to be detected using a fluid; and A chip processing device, comprising a substrate extending along a first direction, and a reagent reagent platform and a chip platform assembled side by side and adjacent to each other on the substrate along a second direction transverse to the first direction, wherein a chip receiving area for accommodating the chip is provided on a top plate of the chip platform on a side facing away from the substrate, and a hollow accommodating chamber is formed on the reagent reagent platform, wherein the reagent reagent 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 on a side of the reagent kit facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located on 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 reagent kit is removably inserted into the storage 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.
60. The gene sequencer according to claim 59, wherein: The accommodating chamber is coupled to the base plate 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, wherein the drainage position and the non-drainage position correspond to a state in which the first fluid conveying structure and the second fluid conveying structure are in fluid communication and a state in which the fluid is not in fluid communication; and The chip processing device is configured to: In response to the accommodating chamber rising away from the substrate to a drainage position, the first fluid delivery structure and the second fluid delivery structure are coupled to each other to achieve fluid communication; and In response to the accommodating chamber descending toward the substrate to a non-draining position, the first fluid delivery structure and the second fluid delivery structure are separated from each other.
61. The gene sequencer according to claim 60, wherein: The top plate on the side of the chip platform facing away from the base plate 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 base plate.
62. The gene sequencer according to claim 61, wherein: The first fluid delivery structure includes a plurality of reagent reservoirs and a plurality of guide reservoirs arranged in a one-to-one correspondence within the reagent cartridge, and a communication channel in which the bottom of each guide reservoir is fluidically connected to the bottom of the corresponding reagent reservoir, each reagent reservoir being at least partially filled with fluid and having a first opening opening upwardly toward the flange and a first pierceable structure covering the first opening, and each guide reservoir having a second opening opening upwardly toward the flange and a second pierceable structure covering the second opening.
63. The gene sequencer according to claim 62, wherein: The second fluid delivery structure includes a fluid supply device, and the fluid supply device includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid delivery structure and the chip, and A selector valve is mounted to the top plate and is in fluid communication with the flow network.
64. The gene sequencer according to claim 63, wherein: The selector valve comprises: a valve seat, via which the selector valve is fixed to the top plate; a valve body extending from the valve seat in a direction away from the top plate and forming a fluid inlet configured to guide fluid into the interior of the valve body and a fluid outlet configured to guide fluid to flow outward from the interior of the valve body; and The flow path network includes: a plurality of drainage needle ports located on a 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 being connected between each drainage needle port and a corresponding inlet port and configured to guide 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 in communication with the plurality of branch flow channels; and a common flow channel communicating 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; Wherein, the selector valve is arranged so that the fluid outlet is fluidically connected to the outlet port, and the fluid inlet is fluidically 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.
65. The gene sequencer according to claim 64, wherein: The plurality of drainage needle ports are formed through a convex portion at an edge of the top plate and protruding toward a side of the top plate away from the chip receiving area.
66. The gene sequencer according to claim 64, wherein: The second fluid delivery structure further includes a flow guide assembly protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide assembly including: a plurality of membrane rupture needles and a plurality of drainage needles, each protruding from a 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, and each drainage needle having a second end aligned with a corresponding second pierceable structure, wherein each membrane rupturing needle is not connected to the flow network and is configured to, in response to the accommodating chamber reaching the drainage position, pierce the first pierceable structure with its first end and then insert into 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 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 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove to be fluidically connected to the guide groove to draw fluid in the guide groove.
67. The gene sequencer according to claim 66, wherein: When the plurality of drainage needles are inserted into 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.
68. The gene sequencer according to claim 67, wherein: Each guide groove is configured as a groove having a circular cross-section with a first inner diameter, and each guide groove is configured as a groove having a circular cross-section with a second inner diameter smaller than the first inner diameter.
69. The gene sequencer according to claim 66, wherein: The first pierceable structure is a metal foil; and The second pierceable structure is a flexible seal such that a fluid-tight seal is maintained after being pierced by a corresponding drain needle of the plurality of drain needles.
70. A gene sequencing device comprising: a chip carrying a sample to be detected using a fluid; and At least two chip processing devices, each chip processing device includes a base plate extending along a first direction, and a reagent reagent platform and a chip platform assembled side by side and adjacent to each other on the base plate 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 on a side facing away from the base plate, and a hollow accommodating chamber is formed on the reagent reagent platform, the reagent reagent is received in the accommodating chamber, and the interior of the chamber is at least partially filled with the fluid, The reagent kit has a first fluid transport structure located on a side of the reagent kit facing the chip platform along the second direction, and the chip platform has a second fluid transport structure located on 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 reagent kit is removably inserted into the storage compartment, 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; as well as The at least two chip processing devices are symmetrically arranged with respect to each other, and their respective chip platforms are arranged adjacent to each other.
71. The gene sequencing device according to claim 70, wherein: The at least two chip processing devices include at least one pair of chip processing devices that are arranged in a mirror-symmetrical manner with respect to each other and whose respective chip platforms are adjacent to each other.
72. The gene sequencing device according to claim 70, wherein: The accommodating chamber is coupled to the base plate 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, wherein the drainage position and the non-drainage position correspond to a state in which the first fluid conveying structure and the second fluid conveying structure are in fluid communication and a state in which the fluid is not in fluid communication; and The chip processing device is configured to: In response to the accommodating chamber rising away from the substrate to a drainage position, the first fluid delivery structure and the second fluid delivery structure are coupled to each other to achieve fluid communication; and In response to the accommodating chamber descending toward the substrate to a non-draining position, the first fluid delivery structure and the second fluid delivery structure are separated from each other.
73. The gene sequencing device according to claim 72, wherein: The top plate on the side of the chip platform facing away from the base plate 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 base plate.
74. The gene sequencing device according to claim 73, wherein: The first fluid delivery structure includes a plurality of reagent reservoirs and a plurality of guide reservoirs arranged in a one-to-one correspondence within the reagent cartridge, and a communication channel in which the bottom of each guide reservoir is fluidically connected to the bottom of the corresponding reagent reservoir, each reagent reservoir being at least partially filled with fluid and having a first opening opening upwardly toward the flange and a first pierceable structure covering the first opening, and each guide reservoir having a second opening opening upwardly toward the flange and a second pierceable structure covering the second opening.
75. The gene sequencing device according to claim 74, wherein: The second fluid delivery structure includes a fluid supply device, and the fluid supply device includes: a flow path network formed in the top plate of the chip platform and connected between the first fluid delivery structure and the chip, and A selector valve is mounted to the top plate and is in fluid communication with the flow network.
76. The gene sequencing device according to claim 75, wherein: The selector valve comprises: a valve seat, via which the selector valve is fixed to the top plate; a valve body extending from the valve seat in a direction away from the top plate and forming a fluid inlet configured to guide fluid into the interior of the valve body and a fluid outlet configured to guide fluid to flow outward from the interior of the valve body; and The flow path network includes: a plurality of drainage needle ports located on a 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 being connected between each drainage needle port and a corresponding inlet port and configured to guide 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 in communication with the plurality of branch flow channels; and a common flow channel communicating 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; Wherein, the selector valve is arranged so that the fluid outlet is fluidically connected to the outlet port, and the fluid inlet is fluidically 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.
77. The gene sequencing device according to claim 76, wherein: The plurality of drainage needle ports are formed through a convex portion at an edge of the top plate and protruding toward a side of the top plate away from the chip receiving area.
78. The gene sequencing device according to claim 76, wherein: The second fluid delivery structure further includes a flow guide assembly protruding from the flange toward the reagent kit platform and connected to the chip receiving area, the flow guide assembly including: a plurality of membrane rupture needles and a plurality of drainage needles, each protruding from a 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, and each drainage needle having a second end aligned with a corresponding second pierceable structure, wherein each membrane rupturing needle is not connected to the flow network and is configured to, in response to the accommodating chamber reaching the drainage position, pierce the first pierceable structure with its first end and then insert into 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 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 with its second end in response to the accommodating chamber reaching the drainage position, and then insert into the guide groove to be fluidically connected to the guide groove to draw fluid in the guide groove.
79. The gene sequencing device according to claim 78, wherein: When the plurality of drainage needles are inserted into 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.
80. The gene sequencing device according to claim 79, wherein: Each guide groove is configured as a groove having a circular cross-section with a first inner diameter, and each guide groove is configured as a groove having a circular cross-section with a second inner diameter smaller than the first inner diameter.
81. The gene sequencing device according to claim 78, wherein: The first pierceable structure is a metal foil; and The second pierceable structure is a flexible seal such that a fluid-tight seal is maintained after being pierced by a corresponding drain needle of the plurality of drain needles.
82. A method for performing a biochemical assay, the method comprising: Establishing a fluid connection between a chip having a sample to be detected and a reagent cartridge having a plurality of different reaction components, the reaction components including at least one of a sample generation component or a sample analysis component; Optionally, generating a sample on the chip in a generating operation, the generating operation comprising flowing different sample generating components into the chip and controlling reaction conditions of the chip to generate the sample; as well as Analyzing the sample on the chip in an analysis operation, the analysis operation comprising flowing a sample analysis component into the chip, the sample analysis component reacting with the sample to provide a related detectable signal; The reagent kit and the chip are integrated into a chip processing device, and the fluid in the reagent kit is fluidically connected to the chip via a first fluid transport structure and a second fluid transport structure that are separated from each other and are in the chip processing device.
83. The method of claim 82, wherein The first fluid delivery structure is integrated into the reagent kit, the second fluid delivery structure is integrated into a carrier supporting the chip, and the carrier is integrated into the chip processing device.
84. The method of claim 83, wherein: The reagent box is moved relative to the carrier through a movable bracket integrated in the chip processing device, thereby achieving communication between the first fluid delivery structure and the second fluid delivery structure.
85. The method of claim 82, wherein The biochemical reaction is a nucleic acid sequencing reaction, and the sample to be detected is a nucleic acid sequencing library.
86. The method of claim 82, wherein The sample to be detected is a tissue sample, and the biochemical reaction is a specific binding reaction.
87. The method of claim 82, wherein: The detectable signal is an optical signal.
88. The method of claim 84, wherein The 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 selectively connecting the chip with the fluid in the second circulation transport structure.
89. The method according to claim 88, wherein the second flow transport structure has a plurality of branch flow channels, and the chip selectively communicating with the fluid comprises: A selector valve integrated in the chip processing device is used to control the selective communication between different branch flow channels and the chip.