WO2024073885A1 - 流体系统、流体运输方法、基因测序仪及生化检验方法 - Google Patents

流体系统、流体运输方法、基因测序仪及生化检验方法 Download PDF

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Publication number
WO2024073885A1
WO2024073885A1 PCT/CN2022/123789 CN2022123789W WO2024073885A1 WO 2024073885 A1 WO2024073885 A1 WO 2024073885A1 CN 2022123789 W CN2022123789 W CN 2022123789W WO 2024073885 A1 WO2024073885 A1 WO 2024073885A1
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WIPO (PCT)
Prior art keywords
fluid
box
chip
reagent
circulation pool
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PCT/CN2022/123789
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English (en)
French (fr)
Inventor
牛子华
陆灏
邢楚填
崔兴业
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深圳华大智造科技股份有限公司
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Priority to CN202280039405.9A priority Critical patent/CN117597426A/zh
Priority to PCT/CN2022/123789 priority patent/WO2024073885A1/zh
Publication of WO2024073885A1 publication Critical patent/WO2024073885A1/zh

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/36Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869Methods for sequencing

Definitions

  • the invention relates to a fluid system, a fluid transportation method, a gene sequencer and a biochemical testing method.
  • gene sequencing technology has been widely used in the field of medical health, such as infectious disease tracing, targeted tumor therapy, and whole genome testing. These different applications require gene sequencers to have higher and higher flexibility, especially in the types and quantities of samples that can be supported in each sequencing.
  • a gene sequencing chip is often designed to have multiple channels, each of which is loaded with different DNA samples.
  • the reagents used in the gene sequencing process are expensive, and the amount of reagents must be saved as much as possible. Therefore, there is usually only one pipeline connecting the sequencing chip and the reagent kit to compress the pipeline volume and reduce the loss of reagents in the pipeline.
  • the pipeline When the pipeline reaches the front end of the sequencing chip, it is divided into multiple branches and connected to multiple channels of the chip one by one. This leads to a contradiction, that is, different samples are bound to mix in the pipeline before reaching each channel of the chip, so that the demand for one sample for each channel cannot be met.
  • a fluid transport method comprising the following steps:
  • the pump valve assembly includes a fluid power assembly, which is configured to provide a positive pressure driving force or a negative pressure driving force for step a and step b;
  • step a) includes: a positive pressure driving step: generating the positive pressure driving force on the outlet side of the chip circulation pool so that the first fluid is input into the channel from the outlet; or a negative pressure driving step: generating the negative pressure driving force on the inlet side of the chip circulation pool so that the first fluid is input into the channel from the outlet.
  • the pump valve assembly further comprises a first fluid loading module, which is configured to be capable of switching at least between a first position for connecting the fluid power assembly to the fluid box fluid and a second position for connecting the fluid power assembly to the outlet fluid of the chip circulation pool; wherein, step a) comprises: first switching the first fluid loading module to the first position to generate the negative pressure driving force to draw the first fluid out of the fluid box, and then switching the first fluid loading module to the second position to perform the positive pressure driving step on the outlet side of the chip circulation pool.
  • the pump valve assembly further comprises a second fluid loading module, which is configured to be able to switch at least between a first position for connecting the inlet of the chip circulation pool with the fluid box fluid and a second position for connecting the inlet of the chip circulation pool with the fluid of the fluid power component fluid; the first fluid loading module is also configured to be able to switch between the first position, the second position and a third position for connecting the fluid box with the outlet fluid of the chip circulation pool; wherein the step a) comprises: first switching the first fluid loading module to the first position to generate the negative pressure driving force to draw out the first fluid in the fluid box, and then switching the first fluid loading module to the second position and switching the second fluid loading module to the first position to perform the positive pressure driving step on the outlet side of the chip circulation pool; or switching the first fluid loading module to the third position and switching the second fluid loading module to the second position to perform the negative pressure driving step on the inlet side of the chip circulation pool.
  • a) comprises: first switching the first fluid loading module to the first position to generate the negative pressure driving force
  • the fluid cartridge includes a sample cartridge and a first reagent cartridge that are arranged in parallel
  • the fluid transport method further includes: selectively performing fluid transport of the sample in the sample cartridge and the reagent in the first reagent cartridge.
  • a second reagent box is provided that is fluidly connected to the second fluid loading module, and the second fluid loading module is also configured to be switchable between the first position, the second position, and a third position for connecting the second reagent box with the inlet fluid of the chip circulation pool; the step b) includes: switching the first fluid loading module to the second position and switching the second fluid loading module to the third position to generate a negative pressure driving force on the outlet side of the chip circulation pool to input the reagent from the second reagent box from the inlet into the channel of the chip circulation pool.
  • a fluid drive control assembly is provided, and the fluid transport method further includes: controlling at least one of the fluid power assembly, the first fluid loading module, and the second fluid loading module through the fluid drive control assembly.
  • a sample box/reagent box recovery module is provided, and the fluid transport method further comprises: recovering the sample box and/or the first reagent box by the sample box/reagent box recovery module.
  • the fluid box also includes a cleaning module and a cleaning liquid/pure water storage module and a waste liquid storage module that are fluidically connected to the cleaning module
  • the fluid transport method also includes: using the cleaning module, the cleaning liquid/pure water storage module and the waste liquid storage module to perform cleaning of the channel of the chip circulation pool.
  • the cleaning module is arranged in parallel with the sample box and the first reagent box, and the fluid transport method also includes: selectively performing fluid transport of the sample in the sample box and the reagent in the first reagent box and cleaning the channel of the chip circulation pool; and when it is selected to perform cleaning of the channel of the chip circulation pool, the channel of the chip circulation pool is cleaned by the positive pressure driving step or the negative pressure driving step in step a) or step b).
  • a first mechanical motion platform, a second mechanical motion platform and a mechanical motion control component are provided, wherein at least the chip circulation pool is placed on the first mechanical motion platform, and at least the sample box, the first reagent kit and the cleaning module are placed on the second mechanical motion platform; the fluid transport method also includes: controlling the multi-axis movement of the first mechanical motion platform by the mechanical motion control component to connect the chip circulation pool to the fluid transport pipeline network; and controlling the multi-axis movement of the second mechanical motion platform by the mechanical motion control component to selectively connect the sample box, the first reagent kit and one of the cleaning modules to the fluid transport pipeline network.
  • the first fluid is different from the second fluid; the first fluid is any one of a sample, a reagent, a cleaning fluid or pure water, and the second fluid is any one of a reagent, a cleaning fluid or pure water.
  • a fluid system comprising:
  • a chip flow cell including multiple channels and inlets and outlets
  • a sample box and a first reagent box wherein the sample box is used to store samples, and the first reagent box is used to store reagents required for performing sequencing;
  • a fluid power component used to generate power to achieve the transportation of the sample or the reagent in the fluid system
  • the first fluid loading module is arranged on the outlet side of the chip circulation pool and is configured to be able to switch between at least a first position for connecting the fluid power component with the fluid box fluid, a second position for connecting the fluid power component with the outlet fluid of the chip circulation pool, and a third position for connecting the fluid box with the outlet fluid of the chip circulation pool.
  • the first fluid loading module includes: a first valve group consisting of a plurality of first valves, a second valve group consisting of a plurality of second valves, and a first straw assembly consisting of a plurality of first straws, wherein the plurality of first valves, the plurality of second valves and the plurality of first straws are respectively arranged to correspond one-to-one to the plurality of channels of the chip circulation pool; wherein each first valve is respectively connected to the fluid power component, a corresponding first straw and a corresponding channel of the chip circulation pool, and is configured to be at least capable of switching between a first position for connecting the fluid power component to the first straw fluid and a second position for connecting the fluid power component to the outlet fluid of a corresponding channel of the chip circulation pool; and wherein each second valve is respectively connected to the fluid power component, a corresponding first valve and a corresponding channel of the chip circulation pool, and is configured to be at least capable of switching between a first position for connecting the fluid power component to the
  • the first fluid loading module further comprises: a plurality of sensor components, each sensor component being respectively connected between the fluid power component and an outlet of a corresponding channel of the chip circulation pool and being configured to monitor fluid characteristics.
  • the fluid system also includes: a second fluid loading module, which is arranged on the inlet side of the chip circulation pool and is configured to be able to switch at least between a first position for connecting the inlet of the chip circulation pool with the fluid box fluid and a second position for connecting the inlet of the chip circulation pool with the fluid of the fluid power component.
  • a second fluid loading module which is arranged on the inlet side of the chip circulation pool and is configured to be able to switch at least between a first position for connecting the inlet of the chip circulation pool with the fluid box fluid and a second position for connecting the inlet of the chip circulation pool with the fluid of the fluid power component.
  • the fluid system further comprises: at least one second reagent box disposed on the inlet side of the multiple channels of the chip circulation pool; wherein the second fluid loading module is disposed between the inlet of the multiple channels of the chip circulation pool and the at least one second reagent box.
  • the second fluid loading module further includes: a solenoid valve, a third valve group consisting of a plurality of third valves, a second pipette assembly consisting of a plurality of second pipettes, and a manifold assembly; wherein the plurality of third valves and the plurality of second pipettes are arranged to correspond one-to-one to the plurality of channels of the chip circulation pool, the plurality of second pipettes are connected to the at least one second reagent box and are fluidly connected to the plurality of channels of the chip circulation pool via the manifold assembly; and wherein each third valve has a first port and a second port, the first port is connected to the manifold assembly, the second port is connected to a corresponding second pipette, and each third valve is configured to be switchable between a first position for closing the fluid connection between the manifold assembly and a corresponding second pipette and a second position for opening the fluid connection between the manifold assembly and a corresponding second pipette
  • the fluid system further comprises: a fluid drive control assembly configured to control at least one of the fluid power assembly, the first fluid loading module, and the second fluid loading module.
  • the fluid system further comprises: a sample cartridge/reagent cartridge recovery module, wherein the sample cartridge/reagent cartridge recovery module is configured to recover the sample cartridge and/or the first reagent cartridge.
  • the fluid system also includes: a cleaning module, which is arranged between the fluid power component and the first fluid loading module and is configured to perform cleaning of the multiple channels of the chip circulation pool; a cleaning liquid/pure water storage module, which is fluidly connected to the cleaning module and the second fluid loading module, respectively, and is configured to provide cleaning liquid and/or pure water when performing cleaning of the multiple channels of the chip circulation pool; and a waste liquid storage module, which is fluidly connected to the cleaning module and the fluid power component, respectively, and is configured to recover and/or discharge waste liquid.
  • a cleaning module which is arranged between the fluid power component and the first fluid loading module and is configured to perform cleaning of the multiple channels of the chip circulation pool
  • a cleaning liquid/pure water storage module which is fluidly connected to the cleaning module and the second fluid loading module, respectively, and is configured to provide cleaning liquid and/or pure water when performing cleaning of the multiple channels of the chip circulation pool
  • a waste liquid storage module which is fluidly connected to the cleaning module and the fluid power component, respectively, and is configured to recover and
  • the fluid power component includes: a syringe having multiple independent channels, and multiple reversing valves; wherein the multiple independent channels and the multiple reversing valves are configured to correspond one-to-one to the multiple channels of the chip circulation pool; and wherein each reversing valve is configured to be controllable individually or simultaneously.
  • the fluid system further includes: a first mechanical motion platform, a second mechanical motion platform, and a mechanical motion control component; wherein at least the chip circulation pool is placed on the first mechanical motion platform, and at least the sample box, the first reagent kit and the cleaning module are placed on the second mechanical motion platform; wherein the mechanical motion control component is configured to control the multi-axis movement of the first mechanical motion platform to selectively connect the chip circulation pool to the fluid transport pipeline network of the fluid system; and wherein the mechanical motion control component is also configured to control the multi-axis movement of the second mechanical motion platform to selectively connect one of the sample box, the first reagent kit and the cleaning module to the fluid transport pipeline network of the fluid system.
  • At least one of the first mechanical motion platform and the second mechanical motion platform is a three-dimensional motion platform or a rotary motion platform.
  • the plurality of first valves in the first valve group, the plurality of second valves in the second valve group, and the plurality of third valves in the third valve group are all solenoid valves.
  • the plurality of first valves in the first valve group are multi-way rotary valves
  • the plurality of second valves in the second valve group and the plurality of third valves in the third valve group are solenoid valves.
  • the multi-way rotary valve is a 2-position 8-way rotary valve or a 2-position 12-way rotary valve.
  • the fluid system further includes: a first rotary valve, which is disposed on the outlet side of the multiple channels of the chip circulation pool and is configured to selectively connect the sample box and one of the first reagent box to the fluid transport pipeline network of the fluid system; and a second rotary valve, which is disposed on the inlet side of the multiple channels of the chip circulation pool and is configured to selectively connect the sample box, one of the first reagent box and the second reagent box to the fluid transport pipeline network of the fluid system.
  • a first rotary valve which is disposed on the outlet side of the multiple channels of the chip circulation pool and is configured to selectively connect the sample box and one of the first reagent box to the fluid transport pipeline network of the fluid system.
  • the fluid system also includes: a sequencing platform, which is arranged between the first fluid loading module and the second fluid loading module; a loading platform, which is arranged between the sample box and the first reagent box and the fluid power component; and an automatic transfer device, which is configured to automatically transfer the chip circulation pool between the sequencing platform and the loading platform.
  • a gene sequencer comprising:
  • a chip flow cell including multiple channels and inlets and outlets
  • a sample box and a first reagent box wherein the sample box is used to store samples, and the first reagent box is used to store reagents required for performing sequencing;
  • a fluid power component used to generate power to achieve the transportation of the sample or the reagent in the fluid system
  • the first fluid loading module is arranged on the outlet side of the chip circulation pool and is configured to be able to switch between at least a first position for connecting the fluid power component with the sample box or the first reagent box fluid, a second position for connecting the fluid power component with the outlet fluid of the chip circulation pool, and a third position for connecting the sample box or the first reagent box with the outlet fluid of the chip circulation pool.
  • the first fluid loading module includes: a first valve group consisting of a plurality of first valves, a second valve group consisting of a plurality of second valves, and a first straw assembly consisting of a plurality of first straws, wherein the plurality of first valves, the plurality of second valves and the plurality of first straws are respectively arranged to correspond one-to-one to the plurality of channels of the chip circulation pool; wherein each first valve is respectively connected to the fluid power component, a corresponding first straw and a corresponding channel of the chip circulation pool, and is configured to be at least capable of switching between a first position for connecting the fluid power component to the first straw fluid and a second position for connecting the fluid power component to the outlet fluid of a corresponding channel of the chip circulation pool; and wherein each second valve is respectively connected to the fluid power component, a corresponding first valve and a corresponding channel of the chip circulation pool, and is configured to be at least capable of switching between a first position for connecting the fluid power component to the
  • the first fluid loading module further comprises: a plurality of sensor components, each sensor component being respectively connected between the fluid power component and an outlet of a corresponding channel of the chip circulation pool and being configured to monitor fluid characteristics.
  • the gene sequencer also includes: a second fluid loading module, which is arranged on the inlet side of the chip circulation pool and is configured to be able to switch at least between a first position for connecting the inlet of the chip circulation pool with the sample box or the first reagent box fluid and a second position for connecting the inlet of the chip circulation pool with the fluid of the fluid power component.
  • a second fluid loading module which is arranged on the inlet side of the chip circulation pool and is configured to be able to switch at least between a first position for connecting the inlet of the chip circulation pool with the sample box or the first reagent box fluid and a second position for connecting the inlet of the chip circulation pool with the fluid of the fluid power component.
  • the gene sequencer further includes: at least one second reagent box arranged on the inlet side of the multiple channels of the chip circulation pool; wherein the second fluid loading module is arranged between the inlet of the multiple channels of the chip circulation pool and the at least one second reagent box.
  • the gene sequencer also includes: the second fluid loading module further includes: a solenoid valve, a third valve group composed of a plurality of third valves, a second pipette assembly composed of a plurality of second pipettes, and a manifold assembly; wherein the plurality of third valves and the plurality of second pipettes are arranged to correspond one-to-one to the plurality of channels of the chip circulation pool, the plurality of second pipettes are connected to the at least one second reagent box and are fluidly connected to the plurality of channels of the chip circulation pool via the manifold assembly; and wherein each third valve has a first port and a second port, the first port is connected to the manifold assembly, the second port is connected to a corresponding second pipette, and each third valve is configured to be switchable between a first position for closing the fluid connection between the manifold assembly and a corresponding second pipette and a second position for opening the fluid connection between the manifold assembly and a corresponding
  • the gene sequencer further includes: a fluid drive control component, which is configured to control at least one of the fluid power component, the first fluid loading module, and the second fluid loading module.
  • the gene sequencer further includes: a sample box/reagent box recovery module, wherein the sample box/reagent box recovery module is configured to recover the sample box and/or the first reagent box.
  • the gene sequencer also includes: a cleaning module, which is arranged between the fluid power assembly and the first fluid loading module, and is configured to perform cleaning of the multiple channels of the chip circulation pool; a cleaning liquid/pure water storage module, which is fluidly connected to the cleaning module and the second fluid loading module, respectively, and is configured to provide cleaning liquid and/or pure water when performing cleaning of the multiple channels of the chip circulation pool; and a waste liquid storage module, which is fluidly connected to the cleaning module and the fluid power assembly, respectively, and is configured to recover and/or discharge waste liquid.
  • a cleaning module which is arranged between the fluid power assembly and the first fluid loading module, and is configured to perform cleaning of the multiple channels of the chip circulation pool
  • a cleaning liquid/pure water storage module which is fluidly connected to the cleaning module and the second fluid loading module, respectively, and is configured to provide cleaning liquid and/or pure water when performing cleaning of the multiple channels of the chip circulation pool
  • a waste liquid storage module which is fluidly connected to the cleaning module and the fluid power assembly, respectively, and is configured
  • the fluid power component includes: a syringe having multiple independent channels, and multiple reversing valves; wherein the multiple independent channels and the multiple reversing valves are configured to correspond one-to-one to the multiple channels of the chip circulation pool; and wherein each reversing valve is configured to be controllable individually or simultaneously.
  • the gene sequencer also includes: a first mechanical motion platform, a second mechanical motion platform, and a mechanical motion control component; wherein at least the chip circulation pool is placed on the first mechanical motion platform, and at least the sample box, the first reagent kit and the cleaning module are placed on the second mechanical motion platform; wherein the mechanical motion control component is configured to control the multi-axis movement of the first mechanical motion platform to selectively connect the chip circulation pool to the fluid transport pipeline network of the fluid system; and wherein the mechanical motion control component is also configured to control the multi-axis movement of the second mechanical motion platform to selectively connect one of the sample box, the first reagent kit and the cleaning module to the fluid transport pipeline network of the fluid system.
  • At least one of the first mechanical motion platform and the second mechanical motion platform is a three-dimensional motion platform or a rotary motion platform.
  • the plurality of first valves in the first valve group, the plurality of second valves in the second valve group, and the plurality of third valves in the third valve group are all solenoid valves.
  • the plurality of first valves in the first valve group are multi-way rotary valves
  • the plurality of second valves in the second valve group and the plurality of third valves in the third valve group are solenoid valves.
  • the multi-way rotary valve is a 2-position 8-way rotary valve or a 2-position 12-way rotary valve.
  • the gene sequencer further includes: a first rotary valve, which is disposed on the outlet side of the multiple channels of the chip circulation pool and is configured to selectively connect the sample box and one of the first reagent box to the fluid transport pipeline network of the fluid system; and a second rotary valve, which is disposed on the inlet side of the multiple channels of the chip circulation pool and is configured to selectively connect the sample box, one of the first reagent box and the second reagent box to the fluid transport pipeline network of the fluid system.
  • the gene sequencer also includes: a sequencing platform, which is arranged between the first fluid loading module and the second fluid loading module; a loading platform, which is arranged between the sample box and the first reagent box and the fluid power component; and an automatic transfer device, which is configured to automatically transfer the chip circulation pool between the sequencing platform and the loading platform.
  • a biochemical testing method comprising: loading a sample to be tested from the outlet side of a chip circulation pool into a channel of the chip circulation pool; and loading a reagent having a plurality of different reaction components into the channel of the chip circulation pool from the inlet side or the outlet side of the chip circulation pool to perform a biochemical reaction of the sample and the reagent;
  • the reaction component comprises at least one of a sample generating component or a sample analyzing component;
  • the biochemical reaction comprises generating a sample in the channel of the chip circulation pool, comprising causing different sample generating components to flow into the channel and controlling the reaction conditions of the channel to generate the sample; and the biochemical reaction comprises analyzing the sample in the channel, comprising causing a sample analyzing component to flow into the channel, the sample analyzing component reacting with the sample to provide a relevant detectable signal.
  • the biochemical reaction is a nucleic acid sequencing reaction
  • the sample to be tested is a nucleic acid sequencing library.
  • the detectable signal is an optical signal.
  • the biochemical testing method further includes: in a state where the reagent is loaded into the channel of the chip circulation pool from a first reagent box located on the outlet side of the chip circulation pool, the reagent is discharged to the first reagent box through the inlet of the chip circulation pool after the biochemical reaction is performed; or in a state where the reagent is loaded into the channel of the chip circulation pool from a second reagent box located on the inlet side of the chip circulation pool, the reagent is pushed back to the second reagent box through the inlet of the chip circulation pool after the biochemical reaction is performed.
  • the biochemical testing method also includes: loading cleaning liquid/pure water from the outlet side of the chip circulation pool into the channel of the chip circulation pool, and discharging the cleaning liquid/pure water to the first test kit or the second test kit or the waste liquid storage module through the inlet of the chip circulation pool; or loading the cleaning liquid/pure water from the inlet side of the chip circulation pool into the channel of the chip circulation pool, and pushing the cleaning liquid/pure water back to the second test kit or the waste liquid storage module through the inlet of the chip circulation pool.
  • a mechanical motion device for a fluid system wherein the fluid system at least includes a sample box, a reagent box, and a chip flow cell; the mechanical motion device includes:
  • a mechanical motion control component is configured to control the multi-axis motion of the first mechanical motion platform to connect the chip circulation pool to the fluid transport pipeline network of the fluid system, and to control the multi-axis motion of the second mechanical motion platform to selectively connect one of the sample box and the reagent box to the fluid transport pipeline network.
  • the fluid system also includes a cleaning module; wherein the cleaning module is placed on the second mechanical motion platform; the mechanical motion control component is also configured to control the multi-axis movement of the second mechanical motion platform to selectively connect the sample box, the reagent box and one of the cleaning modules to the fluid transport pipeline network.
  • At least one of the first mechanical motion platform and the second mechanical motion platform is a three-dimensional motion platform or a rotary motion platform.
  • samples or reagents are transported in reverse from the outlet to the inlet of the chip circulation pool, and the reversely loaded samples or reagents can eventually be directly returned to the sample box or test kit. Moreover, when the chip circulation pool channel and the fluid transport pipeline network are cleaned, the waste liquid after cleaning can flow directly into the test kit. It is also possible to load the same or different samples into different channels of the chip circulation pool, reduce the sequencing time, and increase the flexibility of sample/reagent loading.
  • sample loading system and the sequencer are integrated together by adopting a mechanical motion platform control method, so that the same or different samples can be loaded into different channels of the sequencing chip on the gene sequencer, and the loading of reagents can also be achieved at the same time, so as to reduce the sequencing steps and improve the efficiency of sequencing.
  • FIG1 is a schematic diagram of a fluid system provided according to an embodiment of the present invention.
  • FIG. 2 is a schematic diagram of a fluid system according to a first exemplary embodiment of the present invention.
  • FIG. 3 is a schematic diagram of a fluid system according to a second exemplary embodiment of the present invention.
  • FIGS. 4A and 4B are partial schematic diagrams of a fluid system according to a third exemplary embodiment of the present invention, respectively showing the states of the multi-way rotary valve in a first position and a second position;
  • FIG. 5 is a schematic diagram of a fluid system according to a first alternative embodiment of the present invention.
  • FIGS. 6A and 6B are partial schematic diagrams of a fluid system according to a first alternative embodiment of the present invention.
  • FIG. 7 is a schematic diagram of a fluid system according to a second alternative embodiment of the present invention.
  • the embodiments of the present invention mainly relate to a fluid system, a fluid transportation method, a gene sequencer and a biochemical testing method.
  • Fig. 1 shows the main functional modules of the fluid system provided according to an embodiment of the present invention and the coordination relationship between them. These functional modules and their functions and/or components are described below in conjunction with Fig. 1 .
  • Fluid drive control assembly 101 used to drive fluid devices. Specifically, the fluid drive control assembly 101 can drive multiple fluid devices such as pumps, valves, sensors, etc. in the fluid power assembly 109, the first fluid loading module 108, and the second fluid loading module 103, which will be described in detail below, either individually or simultaneously.
  • Mechanical motion control assembly 102 used to drive the first mechanical motion platform 104 and/or the second mechanical motion platform 105, which will be described in detail below, to achieve multi-axis motion of the first and/or second mechanical motion platforms.
  • the slide platform module 106 which will be described in detail below, is placed on the first mechanical motion platform 104, and some components in the first fluid loading module 108 can also be placed on the first mechanical motion platform 104; the sample box 113, the first reagent box 114, and the cleaning liquid/pure water storage module 111, which will be described in detail below, can be partially or completely placed on the second mechanical motion platform 105.
  • Fluid power assembly 109 used to generate power under the drive of fluid drive control assembly 101 to realize the movement of samples or reagents in the fluid system.
  • One form of the power is pressure, including negative pressure and positive pressure, depending on the direction required for fluid transportation.
  • a negative pressure drive method can be used to absorb the reagents in the second reagent box 117 to be described in detail below through the first fluid loading module 108 and the second fluid loading module 103 to each channel 107 of the chip circulation pool 115 to be described in detail below
  • a positive pressure drive method can also be used to push the reagents in the chip circulation pool 115 back into the second reagent box 117.
  • the fluid power assembly 109 has one or more fluid interfaces to realize the transportation of fluids in different channels.
  • the fluid power assembly 109 is in fluid communication with the first fluid loading module 108 and the second fluid loading module 103, and the transportation of samples and reagents can be realized.
  • the fluid power assembly 109 is in fluid communication with the cleaning module 112 to be described in detail below, which can provide power for cleaning the whole machine fluid system.
  • the fluid power component 109 is in fluid communication with the waste liquid storage module 110 described in detail below, so that the waste liquid can be discharged.
  • the fluid power component 109 can be a hydraulic unit in the form of a peristaltic pump, a plunger pump, a syringe pump, a gear pump or a diaphragm pump, or an air power unit in the form of a vacuum pump, a diaphragm pump or an air compressor.
  • the fluid power component 109 has a reversing valve, wherein the reversing valve can be a reversing device such as a solenoid valve, a rotary valve, a pneumatic reversing valve, an electro-hydraulic reversing valve, a manual reversing valve, a piezoelectric valve, a pinch valve, a rotary valve or a rotary cutting valve.
  • the first fluid loading module 108 and the second fluid loading module 103 are used to switch between different fluid pipelines so that the sample or reagent can be transported according to the set path, and also have a sensor component to detect the motion state of the fluid.
  • the first fluid loading module 108 has at least three interfaces, which can be connected to the fluid power component 109, the chip circulation pool 115 and the second mechanical motion platform 105 respectively.
  • the second fluid loading module 103 has at least 3 interfaces, which can be connected to the second reagent box 117, the chip circulation pool 115 and the fluid power component 109 respectively.
  • the first and second fluid loading modules can also include a pipette assembly, a reversing assembly, a manifold assembly and a sensor assembly respectively.
  • the pipette assembly has one or more interfaces, each pipette can be connected to the corresponding sample box, reagent box or cleaning module fluid, and can also be connected to the corresponding sample box, reagent box or cleaning module fluid in sequence through the transportation of the mechanical motion platform, and the interface opening connected to the sample box or reagent box can be vertically upward or vertically downward.
  • the reversing assembly has one or more fluid direction switching functions, which can be used to switch the flow path on and off or reverse.
  • the device for realizing the reversing function may be a reversing device such as a solenoid valve, a rotary valve, a pneumatic reversing valve, an electro-hydraulic reversing valve, a manual reversing valve, a piezoelectric valve, a pinch valve, a rotary valve or a rotary cutting valve.
  • the manifold assembly is a pipeline that can bring together multiple pipelines to realize the collection or diversion of samples/reagents.
  • the sensor assembly may be a pressure sensor, a flow sensor or a bubble sensor.
  • the wafer carrier platform module 106 is used to carry the chip circulation pool 115 and the interfaces 141 and 142 connected to the outside, and can drive the chip circulation pool 115 to perform multi-axis movement.
  • Chip flow cell 115 It is the place where the sequencing biochemical reaction is carried out, and has one or more channels 107.
  • the size of each channel can be exactly the same or different.
  • multiple channels can be combined into one channel at the outlet or inlet.
  • Waste liquid storage module 110 has one or more interfaces for storing or discharging all or part of the waste liquid of the liquid path system.
  • the waste liquid storage module can be inside or outside the instrument, or directly discharged to the laboratory waste liquid treatment system using the waste liquid interface.
  • the waste liquid storage module 110 may not include a container, or may include one or more containers.
  • the waste liquid storage module 110 may include a sensor for liquid detection, an air purification device, or a secondary overflow prevention device, etc.
  • Cleaning liquid/pure water storage module 111 used to store pure water or cleaning liquid required for cleaning the entire system. Cleaning liquid and pure water can be packaged separately or integrated together; they can be fixed on the second mechanical motion platform 105 or can be independently taken and placed. Furthermore, according to functional requirements, the cleaning liquid/pure water storage module 111 may include a liquid volume detection sensor, an air purification device, etc. Furthermore, the cleaning liquid/pure water storage module 111 can also be an interface directly connected to the outside of the instrument.
  • Sample box 113 used to store samples, and can be in fluid communication with the first fluid loading module 108.
  • the sample box 113 has one or more wells, which correspond to one or more channels 107 in the chip flow cell 115. Furthermore, the sample box 113 can receive recovered samples or reagents, and can also add one or more empty wells for recovery.
  • the first reagent kit 114 and the second reagent kit 117 are used to store reagents required by the system during sequencing.
  • the first reagent kit 114 may include one or more reagent kits located on the second mechanical motion platform 105, and reagents may be loaded from the first fluid loading module 108 into the chip circulation pool 115;
  • the second reagent kit 117 may be one or more reagent kits, and reagents may be loaded into the chip circulation pool 115 or the waste liquid storage module 110 through the second fluid loading module 103.
  • the sample box/reagent box recovery module 116 is used to store and recover the sample boxes and reagent boxes after use.
  • the flow of fluid in the chip flow cell 115 from right to left is defined as forward flow, and from left to right is defined as reverse flow.
  • the fluid transport methods according to the embodiments of the present invention can be generally classified into the following categories.
  • the fluid may be a sample, a reagent, or a cleaning fluid or pure water.
  • the sample/reagent may enter the chip circulation pool 115 for biochemical reaction, and the cleaning fluid/pure water may enter the chip circulation pool 115 and its upstream and downstream to clean the fluid system.
  • the first method is to use a positive pressure drive.
  • the first fluid loading module 108 Under the control of the first mechanical motion platform 104 or the second mechanical motion platform 105, the first fluid loading module 108 is switched to be in fluid communication with the sample box 113 and the fluid power component 109, and the fluid power component 109 provides negative pressure to extract the sample into the pipeline 136 for buffering; after the extraction is completed, the first fluid loading module 108 is switched to be in fluid communication with the fluid power component 109 and the chip circulation pool 115.
  • the fluid power component 109 is switched to provide positive pressure, and the sample buffered in the pipeline 136 is pushed into one or more channels 107 of the chip circulation pool 115 through the first fluid loading module 108. As needed, the excess fluid can be discharged to the sample box 113 or to the waste liquid storage module 110.
  • the second method is to use negative pressure drive.
  • the first fluid loading module 108 is switched to be in fluid communication with the sample box 113 and the chip circulation pool 115
  • the second fluid loading module 103 is switched to be in fluid communication with the fluid power component 109 and the chip circulation pool 115.
  • the fluid power component 109 provides negative pressure to directly extract samples into one or more channels 107 of the chip circulation pool 115. Excess fluid can be discharged to the sample box 113 or to the waste liquid storage module 110 as needed.
  • each chip circulation pool channel 107 is loaded with different samples, or the same samples.
  • the first fluid loading module 108 is switched to be in fluid communication with the fluid power assembly 109 and the chip circulation pool 115
  • the second fluid loading module 103 is switched to be in fluid communication with the second reagent box 117 and the chip circulation pool 115.
  • the fluid power assembly 109 provides power to extract the reagents in the second reagent box 117 into the chip circulation pool 115, and the excess reagents are discharged into the waste liquid storage module 110. This method can also realize the loading of the same sample or the cleaning of the entire liquid system.
  • FIG. 2 is a schematic diagram of a fluid system according to a first exemplary embodiment of the present invention.
  • the fluid power assembly 109 uses a syringe pump assembly including a syringe 127 and a reversing valve 128.
  • the syringe pump assembly has multiple independent channels, and the reversing valve 128 has multiple interfaces that can be switched to different pipelines. Each channel can be controlled individually or simultaneously.
  • the first fluid loading module 108 uses a first valve group 140, a second valve group 137, a pipette assembly 130, a bubble sensor assembly 133, and a pressure sensor assembly 135.
  • the first fluid loading module 108 corresponds to each channel 107 of the chip circulation pool 115 on the slide platform module 106.
  • a solenoid valve in the first valve group 140, a solenoid valve in the second valve group 137, a corresponding pipette in the pipette assembly 130, etc. all correspond to a corresponding channel of the channel 107.
  • Each solenoid valve in the first valve group 140 has at least three interfaces, which are respectively in fluid communication with the corresponding pipette assembly 130, pipeline 139, and pipeline 150.
  • Each solenoid valve in the second valve group 137 has at least three interfaces, which are respectively in fluid communication with pipeline 139, pipeline 136, and pipeline 138.
  • the bubble sensor 133 and the pressure sensor 135 are located between the syringe 127 and the channel 107 of the chip circulation pool.
  • the pressure sensor assembly 135 may be a flow sensor assembly or other sensing module capable of monitoring fluid characteristics.
  • the second fluid loading module 103 uses a third group of solenoid valves 148, a solenoid valve 146, a manifold assembly 144, and a pipette assembly 147.
  • the solenoid valve 148 and the solenoid valve 146 each have two ports and are connected in parallel.
  • the first ports of the solenoid valve 148 and the solenoid valve 146 are combined into a common pipeline 143, the second port of the solenoid valve 148 is in fluid communication with the pipette assembly 147, and the second port of the solenoid valve 146 is in fluid communication with the reagent pipeline 145.
  • the first port of the third valve group 148 and the common pipeline 143 can be combined in a stepped manner or in a centralized manner.
  • the sample connection interface is located between the syringe pump and the outlet of the chip circulation pool.
  • Two or more different reagents can be located between the syringe pump 127 and the outlet of the chip circulation pool 105 and at the inlet of the chip circulation pool 105.
  • the illustrated positions of the respective solenoid valves 140, 137, 148, 146 are defaulted to the first position and are switched to the second position as needed.
  • Fluid transport method 1 transport of samples/reagents (reverse transport).
  • the fluid transport method can realize the transport of samples or reagents.
  • the fluid transport method can realize different channels in the chip circulation pool to load different samples, and can also realize different channels in the chip circulation pool to load the same sample.
  • Step 1) The second mechanical motion platform 105 carries the sample box 113 to a position corresponding to the pipette assembly 130 in the first fluid loading module 108, an electromagnetic valve in the first valve group 140 is switched to the second position, and a corresponding pipette in the pipette assembly 130 is connected to the first sample fluid in the sample box 113.
  • Step 2) The reversing valve 128 in the fluid power assembly 109 is switched to be connected to the fluid of the pipeline 134, and the syringe 127 draws the first sample in the sample box 113 through a solenoid valve in the first valve group 140 and a corresponding pipette in the pipette assembly 130 to be cached in the pipeline 136.
  • Step 3) The solenoid valve 146 in the second fluid loading module 103 is switched to the second position, and one of the solenoid valves in the first valve group 140 is switched to the first position, and the pipette assembly 151 is in fluid communication with the sample box 113.
  • the syringe 127 pushes the sample in the pipeline 136 along one of the solenoid valves in the first valve group 140, the fluid pipeline 150, and the chip circulation pool interface 141 to a corresponding channel 107 of the chip circulation pool 115.
  • the sample/reagent in the pipeline 145 will be recovered into the sample box 113.
  • the pipette assembly 151 is in fluid communication with the waste liquid storage module 110, the sample/reagent in the pipeline 145 will be discharged to the waste liquid storage module.
  • the following is the transportation of reagents from the first reagent kit 114 , and the operation flow is substantially the same as the operation flow of the above-mentioned sample.
  • Step 5 The reversing valve 128 in the fluid power assembly 109 is switched to be connected to the fluid of the pipeline 134, and the syringe 127 draws the reagent in the first reagent box 114 through a solenoid valve in the first valve group 140 and a corresponding pipette in the pipette assembly 130 to be cached in the pipeline 136.
  • the syringe 127 pushes the reagent in the pipeline 136 along a solenoid valve in the first valve group 140, the fluid pipeline 150, and the chip circulation pool interface 141 to a corresponding channel 107 of the chip circulation pool 115.
  • the excess reagent in the pipeline 145 will be recovered into the first reagent box 114.
  • the pipette assembly 151 is in fluid communication with the waste liquid storage module 110, the sample/reagent in the fluid pipeline 145 will be discharged to the waste liquid storage module 110.
  • Fluid transport method 2 Transport of reagents (reagents used for sequencing are input from the front end of the chip circulation pool).
  • Step 1) Reagent injection process: A corresponding pipette in the pipette assembly 147 is in fluid communication with the corresponding first reagent in the second reagent box 117.
  • the solenoid valve 146, the solenoid valve 132, and one of the solenoid valves in the third valve group 148 are switched to the second position, the reversing valve 128 in the fluid power assembly 109 is switched to be in fluid communication with the manifold assembly 131, and the syringe 127 provides negative pressure to draw the first reagent in the second reagent box 117 into the manifold assembly 144 and the fluid pipeline 145.
  • the reversing valve 128 in the fluid power assembly 109 is switched to be in fluid communication with the fluid pipeline 129, and the syringe 127 provides positive pressure to discharge the reagent into the waste liquid storage module 110.
  • Step 2) Sequencing process: A corresponding pipette in the pipette assembly 147 is connected to the first reagent fluid in the second reagent box 117, a solenoid valve in the third valve group 148 is switched to the second position, and the reversing valve 128 in the fluid power assembly 109 is switched to be connected to the fluid of the pipeline 134.
  • the syringe 127 draws the first reagent and transports it along a corresponding pipette in the pipette assembly 147, a solenoid valve in the third valve group 148, the common pipeline 143, the channel 107 in the chip circulation pool 115, and the fluid pipeline 150.
  • the reversing valve 128 is switched to be connected to the fluid of the pipeline 129, and the syringe 127 discharges the reacted reagent into the waste liquid storage module 110.
  • Another corresponding pipette in the pipette assembly 147 is in fluid communication with the second reagent in the second reagent box 117, another solenoid valve in the third valve group 148 is switched to the second position, and the reversing valve 128 in the fluid power assembly 109 is switched to be in fluid communication with the pipeline 134.
  • the second valve group 137 is switched to the second position, and the syringe 127 draws the second reagent along the corresponding another pipette in the pipette assembly 147, another solenoid valve in the third valve group 148, the common pipeline 143, the channel 107 in the chip circulation pool 115, and the pipeline 150.
  • the reversing valve 128 is switched to be in fluid communication with the pipeline 129, and the syringe 127 discharges the reacted reagent into the waste liquid storage module 110.
  • Step 3) Sequencing reagent recovery:
  • a corresponding pipette in the pipette assembly 147 is in fluid communication with the first reagent in the second reagent box 117, a solenoid valve in the third valve group 148 is switched to the second position, and the reversing valve 128 in the fluid power assembly 109 is switched to fluid communication with the pipeline 134.
  • the syringe 127 draws the first reagent and transports it along a corresponding pipette in the pipette assembly 147, a solenoid valve in the third valve group 148, the common pipeline 143, the channel 107 in the chip circulation pool 115, and the pipeline 150.
  • the syringe 127 directly pushes the first reagent back to the corresponding hole position of the corresponding second reagent box 117.
  • Another corresponding straw in the straw assembly 147 is in fluid communication with the second reagent in the second reagent box 117, another solenoid valve in the third valve group 148 is switched to the second position, and the reversing valve 128 in the fluid power assembly 109 is switched to fluid communication with the pipeline 134.
  • the second valve group 137 is switched to the second position, and the syringe 127 draws the second reagent along the corresponding another straw in the straw assembly 147, another solenoid valve in the third valve group 148, the common pipeline 143, the channel 107 in the chip circulation pool 115, and the pipeline 150.
  • the syringe 127 directly pushes the second reagent back to the corresponding hole position of the corresponding second reagent box 117.
  • Fluid transportation method three pipeline cleaning.
  • Cleaning path one the cleaning liquid/pure water is sucked from the pipette assembly 130 and discharged to the waste liquid storage module 110 via the pipeline 129 or discharged to the second reagent box 117 via the pipeline 147 .
  • the second mechanical motion platform 105 carries the cleaning module 112 to a position corresponding to the straw assembly 130, the first valve group 140 switches to the second position, the reversing valve 128 switches to be fluidly connected to the pipeline 134, and the syringe 127 draws the cleaning liquid/pure water from the cleaning module 112 along the straw assembly 130, the first valve group 140, the second valve group 137, the pipeline 136, and the pipeline 134 into the syringe 127.
  • the first discharge cleaning method After the liquid extraction is completed, the reversing valve 128 is switched to be in fluid communication with the pipeline 129 , and the syringe 127 discharges the waste liquid into the waste liquid storage module 110 .
  • the fourth discharge and cleaning method After the liquid extraction is completed, the first valve group 140 is switched to the first position, the solenoid valve 146 is switched to the second position, and the syringe 127 discharges the waste liquid along the pipeline 134, the pipeline 150, the channel 107 in the chip circulation pool 115, and the straw assembly 151 into the first reagent box 114 or the second reagent box 117.
  • Cleaning path two suction from the pipette assembly 147, discharge from the pipeline 129 to the waste liquid storage module 110 or discharge from the pipette assembly 130 to the first reagent box 114.
  • the second mechanical motion platform 105 carries the cleaning module 112 to the position corresponding to the pipette assembly 147, and the third valve group 148 is switched to the second position.
  • the reversing valve 128 is switched to be in fluid communication with the pipeline 134, and the syringe 127 extracts the cleaning liquid/pure water from the cleaning module 112 through the channel 107 and the pipeline 150 in the chip circulation pool 115 to the syringe 127 for buffering.
  • the second valve group 137 is switched to the second position, the reagent extracted by the syringe can also be buffered in the syringe 127 through the channel 107 and the pipeline 138 in the chip circulation pool 115.
  • the first discharge cleaning method After the liquid extraction is completed, the reversing valve 128 is switched to be in fluid communication with the pipeline 129 , and the syringe 127 discharges the waste liquid into the waste liquid storage module 110 .
  • a gene sequencer comprises at least: a chip circulation pool 115, a sample box 113 and a first reagent box 114, a fluid power assembly 109, and a first fluid loading module 108.
  • the chip circulation pool 115 comprises a plurality of channels 107 and an inlet 142 and an outlet 141.
  • the sample box 113 is used to store samples
  • the first reagent box 114 is used to store reagents required for sequencing.
  • the fluid power assembly 109 is used to generate power to achieve the transportation of samples or reagents in the fluid system.
  • the first fluid loading module 108 is arranged on the outlet side of the chip circulation pool 115, and is configured to be able to switch between at least a first position for fluidly connecting the fluid power assembly 109 to the sample box 113 or the first reagent box 114, a second position for fluidly connecting the fluid power assembly 109 to the outlet 131 of the chip circulation pool 115, and a third position for fluidly connecting the sample box 113 or the first reagent box 114 to the outlet 141 of the chip circulation pool 115. More specifically, as shown in Fig. 2, the fluid power assembly 109 further includes: a syringe 127 having a plurality of independent channels, and a plurality of reversing valves 128.
  • the plurality of independent channels and the plurality of reversing valves 128 are arranged to correspond one-to-one with the plurality of channels 107 of the chip flow cell 115; and each reversing valve 128 is arranged to be controllable individually or simultaneously.
  • the first fluid loading module 108 may include: a first valve group consisting of a plurality of first valves 140, a second valve group consisting of a plurality of second valves 137, and a first pipette assembly consisting of a plurality of first suction pipes 130, wherein the plurality of first valves 140, the plurality of second valves 137, and the plurality of first suction pipes 130 are respectively arranged to correspond to the plurality of channels 107 of the chip circulation pool 115.
  • Each first valve 140 is respectively connected to the fluid power component 109, a corresponding first suction pipe 130, and a corresponding channel of the chip circulation pool 115, and is configured to be able to switch between at least a first position for fluidly connecting the fluid power component 109 with the first suction pipe 130 and a second position for fluidly connecting the fluid power component 109 with the outlet 141 of the corresponding channel 107 of the chip circulation pool 115.
  • Each second valve 137 is respectively connected to the fluid power assembly 109, a corresponding first valve 140 and a corresponding channel 107 of the chip circulation pool 115, and is configured to be able to switch between at least a first position for connecting the fluid power assembly 109 with a corresponding first valve 140 and a second position for directly connecting the fluid power assembly 109 with an outlet 141 of a corresponding channel 107 of the chip circulation pool 115.
  • the first fluid loading module 108 may also include: a plurality of sensor assemblies 133, 135. Each sensor assembly 133 or 135 is respectively connected between the fluid power assembly 109 and an outlet 141 of a corresponding channel 107 of the chip circulation pool 115, and is configured to monitor fluid properties.
  • the gene sequencer may further include: a second fluid loading module 103.
  • the second fluid loading module 103 is disposed at the inlet side of the chip circulation pool 115, and is configured to be able to switch between at least a first position for fluidly connecting the inlet 142 of the chip circulation pool 115 with the sample box 113 or the first reagent box 114 and a second position for fluidly connecting the inlet 142 of the chip circulation pool 115 with the fluid power component 109.
  • the gene sequencer may further include: at least one second reagent box 117 disposed at the inlet side of the multiple channels 107 of the chip circulation pool 115.
  • the second fluid loading module 108 is disposed between the inlet 142 of the multiple channels 107 of the chip circulation pool 115 and at least one second reagent box 117.
  • the second fluid loading module 103 may further include: a solenoid valve 146, a third valve group consisting of a plurality of third valves 148, a second pipette assembly consisting of a plurality of second pipettes 147, and a manifold assembly 144.
  • the plurality of third valves 148 and the plurality of second pipettes 147 are each arranged to correspond to the plurality of channels 107 of the chip flow cell 115, and the plurality of second pipettes 147 are connected to at least one second reagent cartridge 117 and are in fluid communication with the plurality of channels 107 of the chip flow cell 115 via the manifold assembly 144.
  • a solenoid valve 146 a third valve group consisting of a plurality of third valves 148, a second pipette assembly consisting of a plurality of second pipettes 147, and a manifold assembly 144.
  • the plurality of third valves 148 and the plurality of second pipettes 147 are each arranged to correspond
  • each of the third valves 148 has a first port and a second port, the first port being connected to the manifold assembly 144, the second port being connected to a corresponding one of the second pipettes 147, and each of the third valves 148 is configured to be switchable between a first position for closing the fluid communication between the manifold assembly 144 and the corresponding one of the second pipettes 147 and a second position for opening the fluid communication between the manifold assembly 144 and the corresponding one of the second pipettes 147.
  • the plurality of channels 107 of the chip circulation pool 115 are connected to the sample box 113 or the first reagent box 114 via the solenoid valve 146.
  • the plurality of first valves 140 in the first valve group, the plurality of second valves 137 in the second valve group, and the plurality of third valves 148 in the third valve group may all be solenoid valves.
  • the gene sequencer may further include: a fluid drive control component 101, a sample box/reagent box recovery module 116, a cleaning module 112, a cleaning liquid/pure water storage module 111, and a waste liquid storage module 110.
  • the fluid drive control component 101 is configured to control at least one of the fluid power component 109, the first fluid loading module 108, and the second fluid loading module 103.
  • the sample box/reagent box recovery module 116 is configured to recover the sample box 113 and/or the first reagent box 114.
  • the cleaning module 112 is disposed between the fluid power component 109 and the first fluid loading module 108, and is configured to perform cleaning of the plurality of channels 107 of the chip circulation pool 115.
  • the cleaning liquid/pure water storage module 111 is in fluid communication with the cleaning module 112 and the second fluid loading module 103, respectively, and is configured to provide cleaning liquid and/or pure water when performing cleaning of the plurality of channels 107 of the chip circulation pool 115.
  • the waste liquid storage module 110 is fluidically connected to the cleaning module 112 and the fluid power assembly 109, respectively, and is configured to recover and/or discharge waste liquid.
  • the gene sequencer may further include: a first mechanical motion platform 104, a second mechanical motion platform 105, and a mechanical motion control component 102.
  • a first mechanical motion platform 104 a second mechanical motion platform 105
  • a mechanical motion control component 102 a mechanical motion control component 102.
  • the chip circulation pool 115 is placed on the first mechanical motion platform 104
  • at least the sample box 113, the first reagent box 114, and the cleaning module 112 are placed on the second mechanical motion platform 105.
  • the mechanical motion control component 102 is configured to control the multi-axis motion of the first mechanical motion platform 104 to selectively connect the chip circulation pool 115 to the fluid transport pipeline network.
  • the mechanical motion control component 102 is also configured to control the multi-axis motion of the second mechanical motion platform 105 to selectively connect one of the sample box 113, the first reagent box 114, and the cleaning module 112 to the fluid transport pipeline network.
  • the first mechanical motion platform 104 and the second mechanical motion platform 105 adopts a three-dimensional motion platform or a rotary motion platform.
  • the embodiment of the present invention also provides a biochemical test method, which can be combined with the aforementioned fluid system or gene sequencer to perform gene sequencing.
  • the biochemical test method provided by the embodiment of the present invention mainly includes the following steps: loading the sample to be detected from the outlet side of the chip circulation pool into the channel of the chip circulation pool; and loading a reagent having a plurality of different reaction components from the inlet side or the outlet side of the chip circulation pool into the channel of the chip circulation pool to perform a biochemical reaction of the sample and the reagent.
  • the reaction component includes at least one of a sample generation component or a sample analysis component.
  • the biochemical reaction includes a generation step and/or a reaction step.
  • a sample is generated in the channel of the chip circulation pool; specifically, different sample generation components are made to flow into the channel and the reaction conditions of the channel are controlled to generate the sample.
  • the reaction step includes analyzing the sample in the channel; specifically, a sample analysis component is made to flow into the channel, and the sample analysis component reacts with the sample to provide a related detectable signal.
  • the detectable signal is preferably an optical signal.
  • the biochemical reaction is a nucleic acid sequencing reaction
  • the sample to be detected is a nucleic acid sequencing library.
  • the biochemical test method provided by the embodiment of the present invention may also include: in a state where the reagent is loaded from the first test kit located at the outlet side of the chip circulation pool into the channel of the chip circulation pool, after the biochemical reaction is performed, the reagent is discharged to the first test kit through the inlet of the chip circulation pool; or, in a state where the reagent is loaded from the second test kit located at the inlet side of the chip circulation pool into the channel of the chip circulation pool, after the biochemical reaction is performed, the reagent is pushed back to the second test kit through the inlet of the chip circulation pool.
  • the biochemical test method provided by the embodiment of the present invention may also include a cleaning step: loading cleaning liquid/pure water from the outlet side of the chip circulation pool into the channel of the chip circulation pool, and discharging the cleaning liquid/pure water through the inlet of the chip circulation pool to the first test kit or the second test kit or the waste liquid storage module; or, loading the cleaning liquid/pure water from the inlet side of the chip circulation pool into the channel of the chip circulation pool, and pushing the cleaning liquid/pure water back to the second test kit or the waste liquid storage module through the inlet of the chip circulation pool.
  • the sample or reagent is transported in the reverse direction from the outlet to the inlet of the chip circulation pool, and the reversely loaded sample or reagent can eventually be directly returned to the sample box or reagent box. Moreover, when the chip circulation pool channel and the fluid transport pipeline network are cleaned, the waste liquid after cleaning can flow directly into the reagent box. It is also possible to load the same or different samples into different channels of the chip circulation pool, reduce the sequencing time, and increase the flexibility of sample/reagent loading.
  • an embodiment of the present invention further provides a mechanical motion device for a fluid system.
  • the fluid system described herein includes at least a sample box 113, a reagent box 114, and a chip circulation pool 115, and may further include a cleaning module 112.
  • the mechanical motion device may include: a first mechanical motion platform 104, a second mechanical motion platform 105, and a mechanical motion control component 102. At least the chip circulation pool 115 is placed on the first mechanical motion platform 104, and at least the sample box 113 and the reagent box 114 are placed on the second mechanical motion platform 105.
  • the cleaning module 112 may also be placed on the second mechanical motion platform 105, and the mechanical motion control component 102 is also configured to control the multi-axis motion of the second mechanical motion platform 105 to selectively connect one of the sample box 113, the reagent box 114, and the cleaning module 112 to the fluid transport pipeline network.
  • the mechanical motion control component 102 is configured to control the multi-axis motion of the first mechanical motion platform 104 to connect the chip circulation pool 115 to the fluid transport pipeline network, and to control the multi-axis motion of the second mechanical motion platform 105 to selectively connect one of the sample box 113 and the reagent box 114 to the fluid transport pipeline network.
  • At least one of the first mechanical motion platform 104 and the second mechanical motion platform 105 can adopt a three-dimensional motion platform or a rotary motion platform.
  • the embodiment of the present invention integrates the sample loading system and the sequencer by means of mechanical motion platform control, so that the same or different samples can be loaded into different channels of the sequencing chip on the gene sequencer, and the loading of reagents can also be realized, so as to reduce the sequencing steps and improve the efficiency of sequencing.
  • the second exemplary embodiment and each exemplary embodiment and optional embodiment to be described below are based on the first exemplary embodiment described above, and the components/components/steps of the system/device/method mentioned in the first exemplary embodiment are added, deleted or replaced.
  • the same or similar components/components/steps are represented by the same or similar reference numerals.
  • Fig. 3 is a schematic diagram of a fluid system according to a second exemplary embodiment of the present invention.
  • a first rotary valve 250A and a second rotary valve 250B are respectively added to the outlet side and inlet side of multiple channels of the chip circulation pool.
  • the first rotary valve 250A is configured to selectively access the fluid transport pipeline network of the fluid system in the sample box and the first test kit
  • the second rotary valve 250B is configured to selectively access the fluid transport pipeline network of the fluid system in the sample box, the first test kit and the second test kit.
  • the sample from the sample box or the reagent from the first test kit can be loaded to the outlet side of the chip circulation pool channel through the interface 153 or 154 in the first rotary valve 250A.
  • the reagent from the first test kit can be loaded to the outlet side of the chip circulation pool channel through the interface 153 in the first rotary valve 250A
  • the reagent from the second test kit can be loaded to the inlet side of the chip circulation pool channel through the interface 156 in the second rotary valve 250B.
  • the pipeline 157 in the second rotary valve 250B may also be directly connected to the common pipeline 143 in the manifold assembly 144 without passing through the third valve group 148 .
  • the third valve in the third valve group adopts a multi-way rotary valve instead of a solenoid valve.
  • Figures 4A and 4B are partial schematic diagrams of the fluid system according to the third exemplary embodiment of the present invention, respectively showing the states of the multi-way rotary valve when it is in the first position and the second position.
  • the multi-way rotary valve takes a 2-position 12-way rotary valve as an example, but a 2-position 8-way rotary valve or a multi-position multi-way rotary valve may also be used.
  • the solenoid valve in the second valve group 137 When the rotary valve 140 is in the first position as shown in Figure 4A, the solenoid valve in the second valve group 137 is in fluid communication with the channel 107 of the chip circulation pool through the rotary valve 140. When the rotary valve 140 is in the second position as shown in Figure 4B, the solenoid valve in the second valve group 137 is in fluid communication with the core first straw assembly 130 through the rotary valve 140.
  • FIG. 5 is a schematic diagram of a fluid system according to the first optional embodiment of the present invention
  • Figures 6A and 6B are partial schematic diagrams of the fluid system according to the first optional embodiment of the present invention, showing the flow path of the loading platform 106A.
  • the dual-platform fluid system shown in FIG5 adopts a non-integrated chip circulation pool.
  • the chip circulation pool 115 is first placed on the loading platform 106A, and the sample box 113 and the first reagent box 114 can be connected to the chip circulation pool 115 interface in sequence through the control of the second mechanical motion platform 105.
  • the hole positions of the sample box 113 or the first reagent box 114 correspond to each channel 107 in the chip circulation pool 115.
  • the fluid power component 109 provides power to directly extract the sample or reagent in the sample box 113 or the reagent box 114 for loading, and the excess reagent is directly discharged into the waste liquid storage module 110.
  • the chip circulation pool 115 can be transferred to the slide platform module (in this embodiment, the sequencing platform) 106 by the automatic transfer device for the next biochemical reaction.
  • the automatic transfer device can be a manipulator or a mechanical claw.
  • the dual-platform fluid system provided in this embodiment can also use an integrated chip circulation pool.
  • an integrated chip circulation pool For the integrated chip circulation pool, as shown in Figures 6A and 6B, multiple channel interfaces at one end of the chip circulation pool 115 are gathered into a port (for example, the right port in Figure 6A and the left port in Figure 6B), and samples or reagents can be loaded by positive pressure or negative pressure.
  • the integrated chip circulation pool shown in Figure 6A uses positive pressure to load samples or reagents.
  • the sample box or the first reagent box can be fluidically connected to the pipette assembly 130 in turn through the control of the second mechanical motion platform 105, and the pipette assembly 130 corresponds to each channel 107 in the chip circulation pool 115.
  • the solenoid valve 137 is switched to be fluidically connected to the pipette assembly 130 and the fluid power assembly (including the syringe 127 and the reversing valve 128), and the fluid power assembly provides a negative pressure driving force to extract samples or reagents between the solenoid valve 137 and the fluid power assembly; after the aspiration is completed, the solenoid valve 137 is switched to make the chip circulation pool 115 and the fluid power assembly fluidly connected.
  • the fluid power assembly provides a positive pressure driving force to directly push the sample or reagent into the channel 107 of the chip circulation pool 115 for biochemical reaction, and the excess reagent enters the waste liquid storage module 110.
  • the integrated chip circulation pool shown in Figure 6B uses a negative pressure method to load samples or reagents.
  • the sample box 113 or the first reagent box 114 is directly fluidically connected to the chip circulation pool 115 located on the loading platform 106A, and the other end of the chip circulation pool 115 is fluidically connected to the fluid power assembly (including a syringe 127 and a reversing valve 128).
  • the negative pressure driving force is provided by the fluid power assembly to directly extract the sample or reagent into the channel 107 of the chip circulation pool 115 for biochemical reaction.
  • the reversing valve 128 in the fluid power assembly the excess reagent enters the waste liquid storage module 110.
  • the first fluid loading module 108 is provided at the outlet side of the chip circulation pool 115, and the second fluid loading module 103 is provided at the inlet side.
  • the first fluid loading module 108 is provided at the outlet side of the chip circulation pool, and no fluid loading module is provided at the inlet side.
  • FIG7 is a schematic diagram of a fluid system according to the second optional embodiment of the present invention.

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Abstract

流体系统、流体运输方法、基因测序仪及生化检验方法。一种流体运输方法,包括如下步骤:a)采用泵阀组件从流体盒吸取第一流体,将第一流体从芯片流通池(115)的出口(141)输入芯片流通池(115)的通道(107),并且使从芯片流通池(115)的入口(142)输出的第一流体返回至流体盒;和/或,b)采用泵阀组件从流体盒吸取第二流体,将第二流体从芯片流通池(115)的入口(142)输入芯片流通池(115)的通道(107),并且使从芯片流通池(115)的出口(141)输出的第二流体返回至流体盒。通过使样本或试剂从芯片流通池(115)的出口(141)向入口(142)反向输送,并且反向加载后的样本或试剂可以最终直接返回到样本盒(113)或试剂盒,可以减少测序的时间,增加了样本/试剂加载的灵活性,提高测序的效率。

Description

流体系统、流体运输方法、基因测序仪及生化检验方法 技术领域
本发明涉及一种流体系统、流体运输方法、基因测序仪及生化检验方法。
背景技术
基因测序技术经过过去数十年的发展,已经在医疗健康领域得到了广泛的应用,如传染病溯源、肿瘤靶向治疗、全基因组检测等。这些不同的应用促使基因测序仪需要具备越来越高的灵活度,尤其是在每次测序所能支持的样本类型和数量上。为了满足此需求,一张基因测序芯片往往被设计成具有多个通道,每个通道内加载不同的DNA样本。另一方面,基因测序过程中使用的试剂成本昂贵,必须尽可能的节省试剂用量。因此,测序芯片与试剂盒之间又通常只有一条管道相连,以压缩管道体积,减少试剂在管道中的损耗。该管道到达测序芯片前端时再分成多个支路,与芯片的多个通道一一相连。这就导致了一种矛盾,即不同的样本势必会在该管道中混合,然后才到达芯片的各个通道中,从而无法满足每个通道对应一种样本的需求。
为实现上述多个样本的加载,现有技术一般采取三种方式:
1)对不同的DNA样本作预处理,先连接上一段已知的碱基序列作为区分样本的“条形码”(barcode),混合在一起后统一加载到芯片的各个通道上,待测序结束后再对混合样本进行barcode的分拆识别;
2)通过机外(非测序仪)样本加载的方式,这种方式需要使用专门设计的自动化仪器,或者采用手动的方式实现,先将样本加载到芯片中,再将芯片转移到测序仪上进行后续的测序步骤;
3)通过测序仪上的流体系统反向加载样本来实现不同样本在不同芯片通道中的加载。
前述的现有三种方式的缺点为:
1)通过barcode的方式混合在一起上机,需要在测序的最后对barcode进行拆分识别,大幅增加了测序成本和测序时间。
2)通过在测序仪机外加载的方式,步骤多、效率低,同时也增加了测序时长和测序成本。
3)流体系统和反向加载样本的设计有待进一步优化。
发明内容
为了克服或者减轻上述现有使技术中存在的至少一个或多个技术问题,有必要 提供一种流体系统、流体运输方法、基因测序仪及生化检验方法。
根据本发明实施例的一个方面,提供了一种流体运输方法,包括如下步骤:
a)采用泵阀组件从流体盒吸取第一流体,将所述第一流体从芯片流通池的出口输入所述芯片流通池的通道,并且使从所述芯片流通池的入口输出的所述第一流体返回至所述流体盒;和/或
b)采用泵阀组件从流体盒吸取第二流体,将所述第二流体从所述芯片流通池的入口输入所述芯片流通池的通道,并且使从所述芯片流通池的出口输出的所述第二流体返回至所述流体盒。
在一些示例性实施例中,所述泵阀组件包括流体动力组件,所述流体动力组件被构造成为步骤a和步骤b提供正压驱动力或负压驱动力;所述步骤a)包括:正压驱动步骤:在所述芯片流通池的出口侧产生所述正压驱动力使所述第一流体从所述出口输入所述通道;或者负压驱动步骤:在所述芯片流通池的入口侧产生所述负压驱动力使所述第一流体从所述出口输入所述通道。
在一些示例性实施例中,所述泵阀组件还包括第一流体加载模块,所述第一流体加载模块被构造成至少能够在用于将所述流体动力组件与所述流体盒流体连通的第一位置与用于将所述流体动力组件与所述芯片流通池的出口流体连通的第二位置之间切换;其中,所述步骤a)包括:首先将所述第一流体加载模块切换至所述第一位置以产生所述负压驱动力将所述流体盒中的所述第一流体抽出,然后将所述第一流体加载模块切换至所述第二位置以在所述芯片流通池的出口侧执行所述正压驱动步骤。
在一些示例性实施例中,所述泵阀组件还包括第二流体加载模块,所述第二流体加载模块被构造成至少能够在用于将所述芯片流通池的入口与所述流体盒流体连通的第一位置与用于将所述芯片流通池的入口与所述流体动力组件流体连通的第二位置之间切换;所述第一流体加载模块还被构造成能够在所述第一位置、所述第二位置以及用于将所述流体盒与所述芯片流通池的出口流体连通的第三位置之间切换;其中,所述步骤a)包括:首先将所述第一流体加载模块切换至所述第一位置以产生所述负压驱动力将所述流体盒中的所述第一流体抽出,然后将所述第一流体加载模块切换至所述第二位置并且将所述第二流体加载模块切换至所述第一位置以在所述芯片流通池的出口侧执行所述正压驱动步骤;或者将所述第一流体加载模块切换至所述第三位置并且将所述第二流体加载模块切换至所述第二位置,以在所述芯片流通池的入口侧执行所述负压驱动步骤。
在一些示例性实施例中,所述流体盒包括并联设置的样本盒和第一试剂盒,所述流体运输方法还包括:选择性地执行所述样本盒中的样本和所述第一试剂盒中的试剂的流体运输。
在一些示例性实施例中,提供与所述第二流体加载模块流体连通的第二试剂 盒,所述第二流体加载模块还被构造成能够在所述第一位置、所述第二位置以及用于将所述第二试剂盒与所述芯片流通池的入口流体连通的第三位置之间切换;所述步骤b)包括:将所述第一流体加载模块切换至所述第二位置并且将所述第二流体加载模块切换成所述第三位置,以在所述芯片流通池的出口侧产生负压驱动力而将来自所述第二试剂盒的试剂从所述入口输入所述芯片流通池的通道。
在一些示例性实施例中,提供流体驱动控制组件,所述流体运输方法还包括:通过所述流体驱动控制组件控制所述流体动力组件、所述第一流体加载模块和所述第二流体加载模块中的至少一个。
在一些示例性实施例中,提供样品盒/试剂盒回收模块,所述流体运输方法还包括:通过所述样品盒/试剂盒回收模块回收所述样本盒和/或所述第一试剂盒。
在一些示例性实施例中,所述流体盒还包括清洗模块和与所述清洗模块流体连通的清洗液/纯水储存模块和废液储存模块,所述流体运输方法还包括:利用所述清洗模块、所述清洗液/纯水储存模块和所述废液储存模块执行对所述芯片流通池的通道的清洗。
在一些示例性实施例中,所述清洗模块与所述样本盒和所述第一试剂盒并联设置,所述流体运输方法还包括:选择性地执行所述样本盒中的样本和所述第一试剂盒中的试剂的流体运输以及对所述芯片流通池的通道的清洗;和当选择执行对所述芯片流通池的通道的清洗时,通过步骤a)中的正压驱动步骤或者负压驱动步骤或者步骤b)来执行对所述芯片流通池的通道的清洗。
在一些示例性实施例中,提供第一机械运动平台、第二机械运动平台和机械运动控制组件,其中,至少所述芯片流通池置于所述第一机械运动平台上,并且至少所述样本盒、所述第一试剂盒以及所述清洗模块置于所述第二机械运动平台上;所述流体运输方法还包括:通过所述机械运动控制组件控制所述第一机械运动平台的多轴运动以将所述芯片流通池接入流体运输管路网络;和通过所述机械运动控制组件控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述第一试剂盒以及所述清洗模块中的一个接入所述流体运输管路网络。
在一些示例性实施例中,所述第一流体与所述第二流体不同;所述第一流体为样本、试剂、清洗液或纯水中的任意一种,而所述第二流体为试剂、清洗液或纯水中的任意一种。
根据本发明实施例的另一方面,提供了一种流体系统,包括:
芯片流通池,包括多个通道以及入口和出口;
样本盒和第一试剂盒,所述样本盒用于存储样本,所述第一试剂盒用于存储执行测序所需的试剂;
流体动力组件,用于产生动力以实现所述样本或所述试剂在所述流体系统中的输送;以及
第一流体加载模块,设置在所述芯片流通池的出口侧,并且被构造成至少能够在用于将所述流体动力组件与所述流体盒流体连通的第一位置、用于将所述流体动力组件与所述芯片流通池的出口流体连通的第二位置以及用于将所述流体盒与所述芯片流通池的出口流体连通的第三位置之间切换。
在一些示例性实施例中,所述第一流体加载模块包括:由多个第一阀构成的第一阀组,由多个第二阀构成的第二阀组,以及,由多个第一吸管构成的第一吸管组件,其中,所述多个第一阀、所述多个第二阀和所述多个第一吸管分别设置成与所述芯片流通池的所述多个通道一一对应;其中,每一个第一阀分别联接至所述流体动力组件、对应的一个第一吸管以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述第一吸管流体连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口流体连通的第二位置之间切换;以及其中,每一个第二阀分别联接至所述流体动力组件、对应的一个第一阀以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述对应的一个第一阀连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口直接流体连通的第二位置之间切换。
在一些示例性实施例中,所述第一流体加载模块还包括:多组传感组件,每组传感组件分别联接在所述流体动力组件和所述芯片流通池的对应的一个通道的出口之间,并且被构造成用于监测流体特性。
在一些示例性实施例中,流体系统还包括:第二流体加载模块,设置在所述芯片流通池的入口侧,并且被构造成至少能够在用于将所述芯片流通池的入口与所述流体盒流体连通的第一位置与用于将所述芯片流通池的入口与所述流体动力组件流体连通的第二位置之间切换。
在一些示例性实施例中,流体系统还包括:设置在所述芯片流通池的所述多个通道的入口侧的至少一个第二试剂盒;其中,所述第二流体加载模块设置在所述芯片流通池的所述多个通道的入口和所述至少一个第二试剂盒之间。
在一些示例性实施例中,所述第二流体加载模块进一步包括:电磁阀,由多个第三阀构成的第三阀组,由多个第二吸管构成的第二吸管组件,以及,歧管组件;其中,所述多个第三阀和所述多个第二吸管均设置成与所述芯片流通池的所述多个通道一一对应,所述多个第二吸管联接至所述至少一个第二试剂盒并且经由所述歧管组件与所述芯片流通池的所述多个通道流体连通;以及其中,每一个第三阀具有第一端口和第二端口,所述第一端口联接至所述歧管组件,所述第二端口联接至对应的一个第二吸管,并且每一个第三阀被构造成能够在用于闭合所述歧管组件和对应的一个第二吸管之间的流体连通的第一位置与用于打开所述歧管组件和对应的一个第二吸管之间的流体连通的第二位置之间切换;以及其中,所述芯片流通池的 所述多个通道经由所述电磁阀联接至所述样本盒或所述第一试剂盒。
在一些示例性实施例中,流体系统还包括:流体驱动控制组件,所述流体驱动控制组件被构造成控制所述流体动力组件、所述第一流体加载模块和所述第二流体加载模块中的至少一个。
在一些示例性实施例中,流体系统还包括:样品盒/试剂盒回收模块,所述样品盒/试剂盒回收模块被构造成回收所述样本盒和/或所述第一试剂盒。
在一些示例性实施例中,流体系统还包括:清洗模块,所述清洗模块设置在所述流体动力组件和所述第一流体加载模块之间,并且被构造成用于执行对所述芯片流通池的所述多个通道的清洗;清洗液/纯水储存模块,所述清洗液/纯水储存模块分别与所述清洗模块和所述第二流体加载模块流体连通,并且被构造成用于在执行对所述芯片流通池的所述多个通道的清洗时提供清洗液和/或纯水;以及废液储存模块,所述废液储存模块分别与所述清洗模块和所述流体动力组件流体连通,并且被构造成用于回收和/或排放废液。
在一些示例性实施例中,所述流体动力组件包括:具有多个独立通道的注射器,以及多个换向阀;其中,所述多个独立通道和所述多个换向阀均设置成与所述芯片流通池的所述多个通道一一对应;以及其中,每个换向阀被设置成能够被单独或同时控制。
在一些示例性实施例中,流体系统还包括:第一机械运动平台,第二机械运动平台,以及机械运动控制组件;其中,至少所述芯片流通池置于所述第一机械运动平台上,并且至少所述样本盒、所述第一试剂盒以及所述清洗模块置于所述第二机械运动平台上;其中,所述机械运动控制组件被构造成用于控制所述第一机械运动平台的多轴运动以将所述芯片流通池选择性地接入所述流体系统的流体运输管路网络;以及其中,所述机械运动控制组件还被构造成控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述第一试剂盒以及所述清洗模块中的一个接入所述流体系统的流体运输管路网络。
在一些示例性实施例中,所述第一机械运动平台和所述第二机械运动平台中的至少一个采用三维运动平台或者旋转式运动平台。
在一些示例性实施例中,所述第一阀组中的多个第一阀、所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。
在另一些示例性实施例中,所述第一阀组中的多个第一阀为多通旋转阀,而所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。例如,所述多通旋转阀是2位8通旋转阀或者2位12通旋转阀。
在又一些示例性实施例中,流体系统还包括:第一旋转阀,所述第一旋转阀设置在所述芯片流通池的多个通道的出口侧,并且被构造成将所述样本盒和所述第一试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络;和第二旋转阀, 所述第二旋转阀设置在所述芯片流通池的多个通道的入口侧,并且被构造成将所述样本盒、所述第一试剂盒和所述第二试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络。
在一些可选实施例中,流体系统还包括:测序平台,所述测序平台设置在所述第一流体加载模块和所述第二流体加载模块之间;加载平台,所述加载平台设置在所述样本盒和所述第一试剂盒与所述流体动力组件之间;和自动转移装置,所述自动转移装置被构造成在所述测序平台和所述加载平台之间自动转移所述芯片流通池。
根据本发明实施例的另一方面,提供了一种基因测序仪,包括:
芯片流通池,包括多个通道以及入口和出口;
样本盒和第一试剂盒,所述样本盒用于存储样本,所述第一试剂盒用于存储执行测序所需的试剂;
流体动力组件,用于产生动力以实现所述样本或所述试剂在所述流体系统中的输送;以及
第一流体加载模块,设置在所述芯片流通池的出口侧,并且被构造成至少能够在用于将所述流体动力组件与所述样本盒或第一试剂盒流体连通的第一位置、用于将所述流体动力组件与所述芯片流通池的出口流体连通的第二位置以及用于将所述样本盒或第一试剂盒与所述芯片流通池的出口流体连通的第三位置之间切换。
在一些示例性实施例中,所述第一流体加载模块包括:由多个第一阀构成的第一阀组,由多个第二阀构成的第二阀组,以及,由多个第一吸管构成的第一吸管组件,其中,所述多个第一阀、所述多个第二阀和所述多个第一吸管分别设置成与所述芯片流通池的所述多个通道一一对应;其中,每一个第一阀分别联接至所述流体动力组件、对应的一个第一吸管以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述第一吸管流体连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口流体连通的第二位置之间切换;以及其中,每一个第二阀分别联接至所述流体动力组件、对应的一个第一阀以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述对应的一个第一阀连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口直接流体连通的第二位置之间切换。
在一些示例性实施例中,所述第一流体加载模块还包括:多组传感组件,每组传感组件分别联接在所述流体动力组件和所述芯片流通池的对应的一个通道的出口之间,并且被构造成用于监测流体特性。
在一些示例性实施例中,基因测序仪还包括:第二流体加载模块,设置在所述芯片流通池的入口侧,并且被构造成至少能够在用于将所述芯片流通池的入口与所 述样本盒或第一试剂盒流体连通的第一位置与用于将所述芯片流通池的入口与所述流体动力组件流体连通的第二位置之间切换。
在一些示例性实施例中,基因测序仪还包括:设置在所述芯片流通池的所述多个通道的入口侧的至少一个第二试剂盒;其中,所述第二流体加载模块设置在所述芯片流通池的所述多个通道的入口和所述至少一个第二试剂盒之间。
在一些示例性实施例中,基因测序仪还包括:所述第二流体加载模块进一步包括:电磁阀,由多个第三阀构成的第三阀组,由多个第二吸管构成的第二吸管组件,以及,歧管组件;其中,所述多个第三阀和所述多个第二吸管均设置成与所述芯片流通池的所述多个通道一一对应,所述多个第二吸管联接至所述至少一个第二试剂盒并且经由所述歧管组件与所述芯片流通池的所述多个通道流体连通;以及其中,每一个第三阀具有第一端口和第二端口,所述第一端口联接至所述歧管组件,所述第二端口联接至对应的一个第二吸管,并且每一个第三阀被构造成能够在用于闭合所述歧管组件和对应的一个第二吸管之间的流体连通的第一位置与用于打开所述歧管组件和对应的一个第二吸管之间的流体连通的第二位置之间切换;以及其中,所述芯片流通池的所述多个通道经由所述电磁阀联接至所述样本盒或所述第一试剂盒。
在一些示例性实施例中,基因测序仪还包括:流体驱动控制组件,所述流体驱动控制组件被构造成控制所述流体动力组件、所述第一流体加裁模块和所述第二流体加载模块中的至少一个。
在一些示例性实施例中,基因测序仪还包括:样品盒/试剂盒回收模块,所述样品盒/试剂盒回收模块被构造成回收所述样本盒和/或所述第一试剂盒。
在一些示例性实施例中,基因测序仪还包括:清洗模块,所述清洗模块设置在所述流体动力组件和所述第一流体加载模块之间,并且被构造成用于执行对所述芯片流通池的所述多个通道的清洗;清洗液/纯水储存模块,所述清洗液/纯水储存模块分别与所述清洗模块和所述第二流体加载模块流体连通,并且被构造成用于在执行对所述芯片流通池的所述多个通道的清洗时提供清洗液和/或纯水;以及废液储存模块,所述废液储存模块分别与所述清洗模块和所述流体动力组件流体连通,并且被构造成用于回收和/或排放废液。
在一些示例性实施例中,所述流体动力组件包括:具有多个独立通道的注射器,以及多个换向阀;其中,所述多个独立通道和所述多个换向阀均设置成与所述芯片流通池的所述多个通道一一对应;以及其中,每个换向阀被设置成能够被单独或同时控制。
在一些示例性实施例中,基因测序仪还包括:第一机械运动平台,第二机械运动平台,以及机械运动控制组件;其中,至少所述芯片流通池置于所述第一机械运动平台上,并且至少所述样本盒、所述第一试剂盒以及所述清洗模块置于所述第二 机械运动平台上;其中,所述机械运动控制组件被构造成用于控制所述第一机械运动平台的多轴运动以将所述芯片流通池选择性地接入所述流体系统的流体运输管路网络;以及其中,所述机械运动控制组件还被构造成控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述第一试剂盒以及所述清洗模块中的一个接入所述流体系统的流体运输管路网络。
在一些示例性实施例中,所述第一机械运动平台和所述第二机械运动平台中的至少一个采用三维运动平台或者旋转式运动平台。
在一些示例性实施例中,所述第一阀组中的多个第一阀、所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。
在另一些示例性实施例中,所述第一阀组中的多个第一阀为多通旋转阀,而所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。举例而言,所述多通旋转阀是2位8通旋转阀或者2位12通旋转阀。
在又一些示例性实施例中,基因测序仪还包括:第一旋转阀,所述第一旋转阀设置在所述芯片流通池的多个通道的出口侧,并且被构造成将所述样本盒和所述第一试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络;和第二旋转阀,所述第二旋转阀设置在所述芯片流通池的多个通道的入口侧,并且被构造成将所述样本盒、所述第一试剂盒和所述第二试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络。
在一些可选实施例中,基因测序仪还包括:测序平台,所述测序平台设置在所述第一流体加载模块和所述第二流体加载模块之间;加载平台,所述加载平台设置在所述样本盒和所述第一试剂盒与所述流体动力组件之间;和自动转移装置,所述自动转移装置被构造成在所述测序平台和所述加载平台之间自动转移所述芯片流通池。
根据本发明实施例的再一方面,提供了一种生化检验方法,包括:将待检测样本从芯片流通池的出口侧加载到所述芯片流通池的通道中;以及将具有多种不同反应成分的试剂从所述芯片流通池的入口侧或出口侧加载到所述芯片流通池的通道中,以执行所述样本和所述试剂的生化反应;所述反应成分包括样本生成成分或样本分析成分至少之一;任选的,所述生化反应包括在所述芯片流通池的通道中生成样本,包括使不同样本生成成分流入所述通道并控制所述通道的反应条件以生成所述样本;以及所述生化反应包括分析所述通道中的所述样本,包括使样本分析成分流入所述通道,所述样本分析成分与所述样本发生反应以提供相关可检测信号。
在一些示例性实施例中,所述生化检验方法中,所述生化反应为核酸测序反应,所述待检测样本为核酸测序文库。
在一些示例性实施例中,所述生化检验方法中,所述可检测信号为光学信号。
在一些示例性实施例中,生化检验方法还包括:在所述试剂从位于所述芯片流 通池的出口侧的第一试剂盒加载到所述芯片流通池的通道中的状态下,在执行生化反应后将所述试剂经由所述芯片流通池的入口排放至所述第一试剂盒;或者在所述试剂从位于所述芯片流通池的入口侧的第二试剂盒加载到所述芯片流通池的通道中的状态下,在执行生化反应后将所述试剂经由所述芯片流通池的入口回推至所述第二试剂盒。
在一些示例性实施例中,生化检验方法还包括:将清洗液/纯水从所述芯片流通池的出口侧加载至所述芯片流通池的通道中,并且将所述清洗液/纯水经由所述芯片流通池的入口排放至所述第一试剂盒或者所述第二试剂盒或者废液存储模块;或者将清洗液/纯水从所述芯片流通池的入口侧加载至所述芯片流通池的通道中,并且将所述清洗液/纯水经由所述芯片流通池的入口回推至所述第二试剂盒或者废液存储模块。
根据本发明实施例的还一方面,提供了一种用于流体系统的机械运动设备,所述流体系统至少包括样本盒、试剂盒和芯片流通池;所述机械运动设备包括:
第一机械运动平台,其中所述芯片流通池置于所述第一机械运动平台上;
第二机械运动平台,其中所述样本盒和所述试剂盒置于所述第二机械运动平台上;
机械运动控制组件,所述机械运动控制组件被构造成控制所述第一机械运动平台的多轴运动以将所述芯片流通池接入所述流体系统的流体运输管路网络,以及控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒和所述试剂盒中的一个接入所述流体运输管路网络。
在一些示例性实施例中,所述流体系统还包括清洗模块;其中,所述清洗模块置于所述第二机械运动平台上;所述机械运动控制组件还被构造成控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述试剂盒和所述清洗模块中的一个接入所述流体运输管路网络。
在一些示例性实施例中,所述第一机械运动平台和所述第二机械运动平台中的至少一个采用三维运动平台或者旋转式运动平台。
本发明上述各个方面和/或实施例提供的流体系统、流体运输方法、基因测序仪及生化检验方法,样本或试剂从芯片流通池的出口向入口反向输送,并且反向加载后的样本或试剂可以最终直接返回到样本盒或试剂盒。而且,执行对芯片流通池通道以及流体运输管路网络的清洗时,清洗后的废液可以直接流到试剂盒中。还可以实现芯片流通池的不同通道加载相同或不同的样本,减少测序的时间,增加了样本/试剂加载的灵活性。此外,采用机械运动平台控制的方式将样本加载系统和测序仪集成在一起,在基因测序仪上即可实现测序芯片不同通道加载相同或不同样本,同时也可以实现试剂的加载,以减少测序步骤,提高测序的效率。
通过下文中参照附图对本发明所作的描述,本发明的其它目的和优点将显而易 见,并可帮助对本发明有全面的理解。
附图说明
图1是根据本发明实施例提供的流体系统的示意图;
图2是根据本发明第一示例性实施例的流体系统的示意图;
图3是根据本发明第二示例性实施例的流体系统的示意图;
图4A和图4B是根据本发明第三示例性实施例的流体系统的局部示意图,分别显示了多通旋转阀处于第一位置和第二位置时的状态;
图5是根据本发明第一可选实施例的流体系统的示意图;
图6A和图6B是根据本发明第一可选实施例的流体系统的局部示意图;和
图7是根据本发明第二可选实施例的流体系统的示意图。
具体实施方式
下面通过实施例,并结合附图,对本发明的技术方案作进一步具体的说明。在说明书中,相同或相似的附图标号指示相同或相似的部件。下述参照附图对本发明实施方式的说明旨在对本发明的总体发明构思进行解释,而不应当理解为对本公开的一种限制。
另外,在下面的详细描述中,为便于解释,阐述了许多具体的细节以提供对本披露实施例的全面理解。然而明显地,一个或多个实施例在没有这些具体细节的情况下也可以被实施。在其他情况下,公知的结构和装置以图示的方式体现以简化附图。
本发明实施例主要涉及一种流体系统、流体运输方法、基因测序仪及生化检验方法。
【流体系统】
图1显示了根据本发明实施例提供的流体系统的主要功能模块以及它们之间的配合关系。以下结合图1描述这些功能模块以及它们的功能和/或组成部件。
流体驱动控制组件101:用于驱动流体器件。具体地,该流体驱动控制组件101可以单独或同时驱动将在下文中详细描述的流体动力组件109、第一流体加载模块108和第二流体加载模块103中的多个泵、阀、传感器等流体器件。
机械运动控制组件102:用于驱动将在下文中详细描述的第一机械运动平台104和/或第二机械运动平台105,以实现第一和/或第二机械运动平台的多轴运动。将在下文中详细描述的载片平台模块106置于第一机械运动平台104上,第一流体加载模块108中的部分器件也可置于第一机械运动平台104上;将在下文中详细描述的 样本盒113、第一试剂盒114、清洗液/纯水储存模块111可部分或全部置于第二机械运动平台105上。
流体动力组件109:用于在流体驱动控制组件101的驱动下产生动力,以实现样本或试剂在流体系统中的移动。所述动力的一种形式是压力,包括负压和正压,取决于流体运输所需的方向。例如,可以采用负压驱动方式通过第一流体加载模块108和第二流体加载模块103吸取将在下文中详细描述的第二试剂盒117中的试剂至将在下文中详细描述的芯片流通池115的各通道107中,也可以采取正压驱动方式将芯片流通池115中的试剂回推到第二试剂盒117中。流体动力组件109具有一个或多个流体接口,以实现不同通道流体的运输。例如,流体动力组件109与第一流体加载模块108和第二流体加载模块103流体连通,可以实现样本和试剂的运输。又例如,流体动力组件109与将在下文中详细描述的清洗模块112流体连通,可以为整机流体系统清洗提供动力。还例如,流体动力组件109与在下文中详细描述的废液存储模块110流体连通,可以实现废液的排放。进一步地,流体动力组件109可以是蠕动泵、柱塞泵、注射泵、齿轮泵或隔膜泵等形式的液压单元,也可以是真空泵、隔膜泵或空气压缩机等形式的空气动力单元。进一步地,流体动力组件109中具有换向阀,其中换向阀可以是电磁阀、旋转阀、气动换向阀、电液换向阀、手动换向阀、压电阀、夹管阀、旋转阀或旋切阀等换向装置。
第一流体加载模块108和第二流体加裁模块103:用于实现不同流体管道的切换,以使样本或试剂按照设定的路径运输,同时还具备传感组件以检测流体的运动状态。第一流体加载模块108至少具有三个接口,可分别与流体动力组件109、芯片流通池115和第二机械运动平台105连接。第二流体加载模块103至少具有3个接口,可分别与第二试剂盒117、芯片流通池115和流体动力组件109连接。第一和第二流体加载模块中还可以分别包括吸管组件、换向组件、歧管组件和传感组件。进一步地,吸管组件具有一个或多个接口,每根吸管可以与对应的样本盒、试剂盒或清洗模块流体连通,也可以通过机械运动平台的运输依次与对应的样本盒、试剂盒或清洗模块流体连通,与样本盒或试剂盒相连的接口开口可竖直向上或竖直向下。进一步地,换向组件具有一个或多个流体方向切换功能,可进行流路的通断或者换向。实现换向功能的器件可以是电磁阀、旋转阀、气动换向阀、电液换向阀、手动换向阀、压电阀、夹管阀、旋转阀或旋切阀等换向装置。进一步地,歧管组件是能将多个管道进行汇集的管道,以实现样本/试剂的汇集或分流。进一步地,传感组件可以是压力传感器、流量传感器或气泡传感器等。
载片平台模块106:用于承载芯片流通池115以及与外部连接的接口141、142,并能带动芯片流通池115进行多轴运动。
芯片流通池115:是测序进行生化反应的场所,具有一个或多个通道107。每个通道尺寸可以完全一样,也可以大小不一。进一步地,在出口或入口处多个通道 可汇集为一个通道。
废液存储模块110:具有一个或多个接口,用于存储或排放液路系统的全部或部分废液,废液存储模块可以是在仪器内部也可以是在仪器外部,或利用废液接口直接排放至实验室废液处理系统。进一步地,废液存储模块110可以不包括容器,也可以包括一个或多个容器。进一步地,根据功能需要,废液存储模块110可包括用于液体检测的传感器、空气净化装置或二次防溢设备等。
清洗液/纯水存储模块111:用于存储整机系统清洗所需的纯水或清洗液。清洗液和纯水可以单独分装,也可以集成在一起;可以是固定在第二机械运动平台105上,也可以独立取放。进一步地,根据功能需要,清洗液/纯水存储模块111可包括液量检测传感器、空气净化装置等。进一步地,清洗液/纯水存储模块111也可以是一个直接与仪器外部连接的接口。
样本盒113:用于存储样本,可与第一流体加载模块108流体连通。样本盒113具有一个或多个孔位,分别与芯片流通池115中的一个或多个通道107一一对应。进一步地,样本盒113可以接收回收的样本或试剂,还可以增加一个或多个空的孔位用于回收。
第一试剂盒114和第二试剂盒117:用于存储测序时系统所需的试剂。其中,第一试剂盒114可以包括位于第二机械运动平台105上的一个或多个试剂盒,可以从第一流体加载模块108加载试剂至芯片流通池115中;第二试剂盒117可以是一个或多个试剂盒,可以通过第二流体加载模块103加载试剂至芯片流通池115或废液存储模块110中。
样本盒/试剂盒回收模块116:用于存储回收使用后的样本盒和试剂盒。
【流体运输方法】
为了便于描述,在前述的图1以及将在下文中提及的各个附图中,将流体在芯片流通池115中从右向左流动定义为正向流动,从左向右为反向流动。
根据本发明实施例的流体运输方法总体上归纳为以下几种。
1、流体的反向加载运输
流体可以是样本、试剂也可以是清洗液或纯水。样本/试剂可进入芯片流通池115中进行生化反应,清洗液/纯水可进入芯片流通池115及其上下游,对流体系统进行清洗。
流体的反向加载运输有两种方式,为便于理解下面以样本的反向加载运输为例进行描述。
第一种是采用正压驱动的方式。在第一机械运动平台104或第二机械运动平台105的控制下,第一流体加载模块108切换至与样本盒113和流体动力组件109流体连通,由流体动力组件109提供负压将样本抽取到管道136中进行缓存;抽液完 成后第一流体加载模块108切换至与流体动力组件109和芯片流通池115流体连通。流体动力组件109切换成提供正压,将缓存在管道136中的样本经第一流体加载模块108推到芯片流通池115的一个或多个通道107中。根据需要,多余的流体可以排放至样本盒113,也可以排放至废液储存模块110中。
第二种是采用负压驱动的方式。在第一机械运动平台104或第二机械运动平台105的控制下,第一流体加载模块108切换至与样本盒113和芯片流通池115流体连通,第二流体加载模块103切换至与流体动力组件109和芯片流通池115流体连通。由流体动力组件109提供负压,直接抽取样本到芯片流通池115的一个或多个通道107中。根据需要,多余的流体可以排放至样本盒113,也可以排放至废液储存模块110中。
上述两种反向加载运输方式可以实现每个芯片流通池通道107加载不同的样本,也可以是相同的样本。
2、流体的正向加载运输
为便于理解,下面以试剂的正向加载运输为例进行描述。
第一流体加载模块108切换至与流体动力组件109和芯片流通池115流体连通,第二流体加载模块103切换至与第二试剂盒117和芯片流通池115流体连通。由流体动力组件109提供动力,抽取第二试剂盒117中的试剂进入芯片流通池115中,多余的试剂排放至废液储存模块110中。这种方式也可以实现相同样本的加载或对整机液路系统的清洗。
此外,第二流体加载模块103切换至与流体动力组件109和第二试剂盒117流体连通时,还可以实现对第二流体加载模块103的流体灌注和清洗。
【第一示例性实施例】
流体系统
图2是根据本发明第一示例性实施例的流体系统的示意图。
如图2所示,在本实施例中,流体动力组件109采用了包含注射器127和换向阀128的注射泵组件,注射泵组件具有多个独立的通道,换向阀128具有多个接口,可以切换至不同的管道。每个通道都可以单独或同时控制。
参见图2并结合图1可知,第一流体加载模块108采用了第一阀组140、第二阀组137、吸管组件130、气泡传感组件133、压力传感器组件135。第一流体加载模块108与载片平台模块106上的芯片流通池115的各个通道107一一对应。例如,第一阀组140中的一个电磁阀,第二阀组137中的一个电磁阀,吸管组件130中的对应的一个吸管等均对应通道107的对应的一个通道。第一阀组140中的每个电磁阀至少具有3个接口,分别与对应的吸管组件130、管道139和管道150流体连通。第二阀组137中的每个电磁阀至少具有3个接口,分别与管道139、管道136和管 道138流体连通。气泡传感器133和压力传感器135位于注射器127和芯片流通池的通道107之间。这里,压力传感器组件135可以是流量传感器组件等能够监测流体特性的传感模块。
第二流体加载模块103采用了第三组电磁阀148、电磁阀146、歧管组件144和吸管组件147。电磁阀148和电磁阀146均具有两个端口并采用了并联的方式,电磁阀148和电磁阀146的第一端口汇集成一条公共管道143,电磁阀148的第二端口与吸管组件147流体连通,电磁阀146的第二端口与试剂管道145流体连通。这里,第三阀组148的第一端口与公共管道143可以采用阶梯式汇集,也可以采用集中式汇集。
在本实施例中,样本连接接口位于注射泵和芯片流通池出口之间。两个或多个不同的试剂可分别位于注射泵127和芯片流通池105出口之间以及芯片流通池105入口处。在本实施例中,如图2所示,各个电磁阀140、137、148、146的图示位置默认为第一位置,并且根据需要被切换至第二位置。
流体运输方法
流体运输方法一:样本/试剂的运输(反向运输)。
本流体运输方法可实现样本或试剂的运输。在执行样本的运输时,本流体运输方法可实现芯片流通池中的不同通道加载不同样本,也可实现芯片流通池中的不同通道加载相同样本。
参见图2并结合图1,下面介绍本流体运输方法的流程和步骤。
步骤1):第二机械运动平台105携带样本盒113运动到与第一流体加载模块108中的吸管组件130对应的位置,第一阀组140中的一个电磁阀切换到第二位置,吸管组件130中的对应的一个吸管与样本盒113中的第一样本流体连通。
步骤2):流体动力组件109中的换向阀128切换至与管路134流体连通,由注射器127通过第一阀组140中的一个电磁阀和吸管组件130中的对应的一个吸管吸取样本盒113中的第一样本至管路136中缓存。
步骤3):第二流体加载模块103中的电磁阀146切换至第二位置,第一阀组140中的一个电磁阀切换至第一位置,同时吸管组件151与样本盒113流体连通。注射器127推动管路136中的样本沿第一阀组140中的一个电磁阀、流体管道150、芯片流通池接口141至芯片流通池115的对应的一个通道107中。管路145中的样本/试剂将会回收至样本盒113中。另一方面,如吸管组件151与废液储存模块110流体连通,则管道145中的样本/试剂将会排放至废液存储模块。
再次参见图2并结合图1,以下是来自第一试剂盒114的试剂的运输,操作流程和上述样本的操作流程基本相同。
步骤4):第二机械运动平台105携带第一试剂盒114运动到与第一流体加载 模块108中的吸管组件130对应的位置,第一阀组140中的一个电磁阀切换到第二位置,吸管组件130中的对应的一个吸管与试剂盒114中的第一试剂流体连通。
步骤5):流体动力组件109中的换向阀128切换至与管路134流体连通,由注射器127通过第一阀组140中的一个电磁阀和吸管组件130中的对应的一个吸管吸取第一试剂盒114中的试剂至管路136中缓存。
步骤6):第二流体加载模块103中的电磁阀146切换至第二位置,第一阀组140切换至第一位置,同时吸管组件151与第一试剂盒114流体连通。注射器127推动管路136中的试剂沿第一阀组140中的一个电磁阀、流体管道150、芯片流通池接口141至芯片流通池115的对应的一个通道107中。管路145中多余的试剂将会回收至第一试剂盒114中。另一方面,如吸管组件151与废液储存模块110流体连通,则流体管道145中的样本/试剂将会排放至废液存储模块110。
流体运输方法二:试剂的运输(用于测序的试剂从芯片流通池的前端输入)。
再次参见图2并结合图1,下面介绍本流体运输方法的流程和步骤。
步骤1)——试剂灌注流程:吸管组件147中的对应的一个吸管与第二试剂盒117中对应的第一试剂流体连通。电磁阀146、电磁阀132、和第三阀组148中的一个电磁阀切换至第二位置,流体动力组件109中的换向阀128切换至与歧管组件131流体连通,注射器127提供负压吸取第二试剂盒117中的第一试剂至歧管组件144和流体管道145中。流体动力组件109中的换向阀128切换至与流体管道129流体连通,注射器127提供正压将试剂排出到废液存储模块110中。
步骤2)——测序流程:吸管组件147中的对应的一个吸管与第二试剂盒117中的第一试剂流体连通,第三阀组148中的一个电磁阀切换至第二位置,流体动力组件109中的换向阀128切换至与管路134流体连通。注射器127吸取第一试剂沿吸管组件147中的对应的一个吸管、第三阀组148中的一个电磁阀、公共管道143、芯片流通池115中的通道107和流体管道150输送。待第一试剂在芯片流通池115中的通道107完成生化反应后,换向阀128切换至与管路129流体连通,注射器127将反应后的试剂排至废液存储模块110中。
吸管组件147中的对应的另一个吸管与第二试剂盒117中的第二试剂流体连通,第三阀组148中的另一个电磁阀切换至第二位置,流体动力组件109中的换向阀128切换至与管路134流体连通。第二阀组137切换至第二位置,注射器127吸取第二试剂沿吸管组件147中的对应的另一个吸管、第三阀组148中的另一个电磁阀、公共管道143、芯片流通池115中的通道107和管路150输送。待第二试剂在芯片流通池115中的通道107完成生化反应后,换向阀128切换至与管路129流体连通,注射器127将反应后的试剂排至废液存储模块110中。
步骤3)——测序试剂回收:吸管组件147中的对应的一个吸管与第二试剂盒117中的第一试剂流体连通,第三阀组148中的一个电磁阀切换至第二位置,流体 动力组件109中的换向阀128切换至与管路134流体连通。注射器127吸取第一试剂沿吸管组件147中的对应的一个吸管、第三阀组148中的一个电磁阀、公共管道143、芯片流通池115中的通道107和管路150输送。待第一试剂在芯片流通池115中的通道107完成生化反应后,注射器127直接回推第一试剂至对应的第二试剂盒117的对应孔位中。
吸管组件147中的对应的另一个吸管与第二试剂盒117中的第二试剂流体连通,第三阀组148中的另一个电磁阀切换至第二位置,流体动力组件109中的换向阀128切换至与管路134流体连通。第二阀组137切换至第二位置,注射器127吸取第二试剂沿吸管组件147中的对应的另一个吸管、第三阀组148中的另一个电磁阀、公共管道143、芯片流通池115中的通道107和管道150输送。待第二试剂在芯片流通池115中的通道107完成生化反应后,注射器127直接回推第二试剂至对应的第二试剂盒117的对应孔位中。
流体运输方法三:管路的清洗。
再次参见图2并结合图1,下面介绍管路清洗的路径和方式。
清洗路径一:清洗液/纯水从吸管组件130吸入,经由管路129排放至废液存储模块110或经由管路147排放至第二试剂盒117中。
具体地,第二机械运动平台105携带清洗模块112运动至与吸管组件130对应的位置,第一阀组140切换至第二位置,换向阀128切换至与管路134流体连通,注射器127从清洗模块112中将清洗液/纯水沿吸管组件130、第一阀组140、第二阀组137、管道136、管道134抽取至注射器127中。
A)第一种排放清洗方式:抽液完成后,换向阀128切换至与管路129流体连通,注射器127将废液排放至废液存储模块110中。
B)第二种排放清洗方式:抽液完成后,第一阀组140切换至第一位置,第三阀组148切换至第二位置,注射器127将废液沿管道134、管道150、芯片流通池115中的通道107、吸管组件147排放至第二试剂盒117中。
C)第三种排放清洗方式:抽液完成后,第二阀组137切换至第二位置,第三阀组148切换至第二位置,注射器127将废液沿管道134、管道138、芯片流通池115中的通道107、吸管组件147排放至第二试剂盒117中。
D)第四种排放清洗方式:抽液完成后,第一阀组140切换至第一位置,电磁阀146切换至第二位置,注射器127将废液沿管道134、管道150、芯片流通池115中的通道107、吸管组件151排放至第一试剂盒114或者第二试剂盒117中。
E)第五种排放清洗方式:抽液完成后,第二阀组137切换至第一位置,电磁阀146切换至第二位置,注射器127将废液沿管道134、管道138、芯片流通池115中的通道107、吸管组件151排放至第一试剂盒114或者第二试剂盒117中。
清洗路径二:从吸管组件147吸入,从管路129排放至废液存储模块110或从 吸管组件130排放至第一试剂盒114中。
具体地,第二机械运动平台105携带清洗模块112运动至吸管组件147对应的位置,第三阀组148切换至第二位置。换向阀128切换至与管路134流体连通,注射器127从清洗模块112中抽取清洗液/纯水经由芯片流通池115中的通道107和管路150至注射器127中缓存。本实施例中,如第二阀组137切换至第二位置,注射器抽取的试剂也可经由芯片流通池115中的通道107和管路138至注射器127中缓存。
A)第一种排放清洗方式:抽液完成后,换向阀128切换至与管路129流体连通,注射器127将废液排放至废液存储模块110中。
B)第二种排放清洗方式:抽液完成后,第一阀组140切换至第二位置,吸管组件130与第一试剂盒114流体连通,注射器127将废液排放至第一试剂盒114中。
基因测序仪
本发明实施例还提供了一种基因测序仪。如图1和图2所示,一种基因测序仪,至少包括:芯片流通池115,样本盒113和第一试剂盒114,流体动力组件109,以及第一流体加载模块108。具体地,芯片流通池115包括多个通道107以及入口142和出口141。样本盒113用于存储样本,第一试剂盒114用于存储执行测序所需的试剂。流体动力组件109用于产生动力以实现样本或试剂在流体系统中的输送。第一流体加载模块108,设置在芯片流通池115的出口侧,并且被构造成至少能够在用于将流体动力组件109与样本盒113或第一试剂盒114流体连通的第一位置、用于将流体动力组件109与芯片流通池115的出口131流体连通的第二位置以及用于将样本盒113或第一试剂盒114与芯片流通池115的出口141流体连通的第三位置之间切换。更具体地,如图2所示,流体动力组件109进一步包括:具有多个独立通道的注射器127,以及多个换向阀128。多个独立通道和多个换向阀128均设置成与芯片流通池115的多个通道107一一对应;并且每个换向阀128被设置成能够被单独或同时控制。
更具体地,如图1和图2所示,第一流体加载模块108可以包括:由多个第一阀140构成的第一阀组,由多个第二阀137构成的第二阀组,以及,由多个第一吸管130构成的第一吸管组件,其中,多个第一阀140、多个第二阀137和多个第一吸管130分别设置成与芯片流通池115的多个通道107一一对应。每一个第一阀140分别联接至流体动力组件109、对应的一个第一吸管130以及芯片流通池115的对应的一个通道,并且被构造成至少能够在用于将流体动力组件109与第一吸管130流体连通的第一位置与用于将流体动力组件109与芯片流通池115的对应的一个通道107的出口141流体连通的第二位置之间切换。每一个第二阀137分别联接至流体动力组件109、对应的一个第一阀140以及芯片流通池115的对应的一个通道107, 并且被构造成至少能够在用于将流体动力组件109与对应的一个第一阀140连通的第一位置与用于将流体动力组件109与芯片流通池115的对应的一个通道107的出口141直接流体连通的第二位置之间切换。此外,第一流体加载模块108还可以包括:多组传感组件133,135。每组传感组件133或135分别联接在流体动力组件109和芯片流通池115的对应的一个通道107的出口141之间,并且被构造成用于监测流体特性。
具体地,如图1和图2所示,基因测序仪还可以包括:第二流体加载模块103。第二流体加载模块103设置在芯片流通池115的入口侧,并且被构造成至少能够在用于将芯片流通池115的入口142与样本盒113或第一试剂盒114流体连通的第一位置与用于将芯片流通池115的入口142与流体动力组件109流体连通的第二位置之间切换。此外,基因测序仪还可以包括:设置在芯片流通池115的多个通道107的入口侧的至少一个第二试剂盒117。第二流体加载模块108设置在芯片流通池115的多个通道107的入口142和至少一个第二试剂盒117之间。
更具体地,如图1和图2所示,第二流体加载模块103可以进一步包括:电磁阀146,由多个第三阀148构成的第三阀组,由多个第二吸管147构成的第二吸管组件,以及,歧管组件144。多个第三阀148和多个第二吸管147均设置成与芯片流通池115的多个通道107一对应,多个第二吸管147联接至至少一个第二试剂盒117并且经由歧管组件144与芯片流通池115的多个通道107流体连通。如图2所示,每一个第三阀148具有第一端口和第二端口,第一端口联接至歧管组件144,第二端口联接至对应的一个第二吸管147,并且每一个第三阀148被构造成能够在用于闭合歧管组件144和对应的一个第二吸管147之间的流体连通的第一位置与用于打开歧管组件144和对应的一个第二吸管147之间的流体连通的第二位置之间切换。此外,芯片流通池115的多个通道107经由电磁阀146联接至样本盒113或第一试剂盒114。需要说明的是,在图2所示的实施例中,第一阀组中的多个第一阀140、第二阀组中的多个第二阀137以及第三阀组中的多个第三阀148可以均为电磁阀。
根据本发明实施例,基因测序仪还可以包括:流体驱动控制组件101、样品盒/试剂盒回收模块116、清洗模块112、清洗液/纯水储存模块111、以及废液储存模块110等。流体驱动控制组件101被构造成控制流体动力组件109、第一流体加载模块108和第二流体加载模块103中的至少一个。样品盒/试剂盒回收模块116被构造成回收样本盒113和/或第一试剂盒114。清洗模块112设置在流体动力组件109和第一流体加载模块108之间,并且被构造成用于执行对芯片流通池115的多个通道107的清洗。清洗液/纯水储存模块111分别与清洗模块112和第二流体加载模块103流体连通,并且被构造成用于在执行对芯片流通池115的多个通道107的清洗时提供清洗液和/或纯水。废液储存模块110分别与清洗模块112和流体动力组件 109流体连通,并且被构造成用于回收和/或排放废液。
根据本发明实施例,如图1和图2所示,基因测序仪还可以包括:第一机械运动平台104,第二机械运动平台105,以及机械运动控制组件102。具体地,至少芯片流通池115置于第一机械运动平台104上,并且至少样本盒113、第一试剂盒114以及清洗模块112置于第二机械运动平台105上。机械运动控制组件102被构造成用于控制第一机械运动平台104的多轴运动以将芯片流通池115选择性地接入流体运输管路网络。机械运动控制组件102还被构造成控制第二机械运动平台105的多轴运动以选择性地将样本盒113、第一试剂盒114以及清洗模块112中的一个接入流体运输管路网络。例如,第一机械运动平台104和第二机械运动平台105中的至少一个采用三维运动平台或者旋转式运动平台。
生化检验方法
本发明实施例还提供了一种生化检验方法,该方法可以结合前述的流体系统或基因测序仪来执行基因测序。本发明实施例提供的生化检验方法主要包括如下步骤:将待检测样本从芯片流通池的出口侧加载到所述芯片流通池的通道中;以及将具有多种不同反应成分的试剂从所述芯片流通池的入口侧或出口侧加载到所述芯片流通池的通道中,以执行所述样本和所述试剂的生化反应。所述反应成分包括样本生成成分或样本分析成分至少之一。所述生化反应包括生成步骤和/或反应步骤。生成步骤中,在所述芯片流通池的通道中生成样本;具体地,使不同样本生成成分流入所述通道并控制所述通道的反应条件以生成所述样本。反应步骤包括分析所述通道中的所述样本;具体地,使样本分析成分流入所述通道,所述样本分析成分与所述样本发生反应以提供相关可检测信号。所述可检测信号优选为光学信号。其中,所述生化反应为核酸测序反应,所述待检测样本为核酸测序文库。
进一步,本发明实施例提供的生化检验方法还可以包括:在试剂从位于芯片流通池的出口侧的第一试剂盒加载到芯片流通池的通道中的状态下,在执行生化反应后将试剂经由芯片流通池的入口排放至第一试剂盒;或者,在试剂从位于芯片流通池的入口侧的第二试剂盒加载到芯片流通池的通道中的状态下,在执行生化反应后将试剂经由芯片流通池的入口回推至第二试剂盒。此外,本发明实施例提供的生化检验方法还可以包括清洗步骤:将清洗液/纯水从芯片流通池的出口侧加载至芯片流通池的通道中,并且将清洗液/纯水经由芯片流通池的入口排放至第一试剂盒或者第二试剂盒或者废液存储模块;或者,将清洗液/纯水从芯片流通池的入口侧加载至芯片流通池的通道中,并且将清洗液/纯水经由芯片流通池的入口回推至第二试剂盒或者废液存储模块。
本发明实施例提供的生化检验方法,样本或试剂从芯片流通池的出口向入口反向输送,并且反向加载后的样本或试剂可以最终直接返回到样本盒或试剂盒。而且, 执行对芯片流通池通道以及流体运输管路网络的清洗时,清洗后的废液可以直接流到试剂盒中。还可以实现芯片流通池的不同通道加载相同或不同的样本,减少测序的时间,增加了样本/试剂加载的灵活性。
用于流体系统的机械运动设备
如图1所示,本发明实施例还提供了一种用于流体系统的机械运动设备。这里所描述的流体系统至少包括样本盒113、试剂盒114和芯片流通池115,进一步地还可以包括清洗模块112。机械运动设备可以包括:第一机械运动平台104、第二机械运动平台105以及机械运动控制组件102。至少芯片流通池115置于第一机械运动平台104上,至少样本盒113和试剂盒114置于第二机械运动平台105上。此外,清洗模块112也可置于第二机械运动平台105上,而机械运动控制组件102还被构造成控制第二机械运动平台105的多轴运动以选择性地将样本盒113、试剂盒114和清洗模块112中的一个接入流体运输管路网络。具体地,机械运动控制组件102被构造成控制第一机械运动平台104的多轴运动以将芯片流通池115接入流体运输管路网络,以及控制第二机械运动平台105的多轴运动以选择性地将样本盒113和试剂盒114中的一个接入流体运输管路网络。举例而言,第一机械运动平台104和第二机械运动平台105中的至少一个可以采用三维运动平台或者旋转式运动平台。这样,本发明实施例采用机械运动平台控制的方式将样本加载系统和测序仪集成在一起,在基因测序仪上即可实现测序芯片不同通道加载相同或不同样本,同时也可以实现试剂的加载,以减少测序步骤,提高测序的效率。
【第二示例性实施例】
需要说明的是,第二示例性实施例以及下文中将要描述的各个示例性实施例和可选实施例均以上文中所描述的第一示例性实施例为基础,并且在上述第一示例性实施例提及的系统/装置/方法等的组成/部件/步骤等的基础上进行组成/部件/步骤的增加或删减或替换。为了清楚的目的,下面仅描述第二示例性实施例以及下文中将要描述的各个示例性实施例与上述第一示例性实施例的不同之处。为此,相同或类似的组成/部件/步骤等采用相同或类似的附图标号表示。
图3是根据本发明第二示例性实施例的流体系统的示意图。参见图3,与第一示例性实施例不同的是,在第二示例性实施例中,在芯片流通池的多个通道的出口侧和入口侧分别增加一个第一旋转阀250A和一个第二旋转阀250B。第一旋转阀250A被构造成将样本盒和第一试剂盒中的一个选择性地接入流体系统的流体运输管路网络,第二旋转阀250B被构造成将样本盒、第一试剂盒和第二试剂盒中的一个选择性地接入流体系统的流体运输管路网络。例如,来自样本盒的样本或来自第一试剂盒的试剂可通过第一旋转阀250A中的接口153或154加载至芯片流通池通 道的出口侧。例如,来自第一试剂盒的试剂可通过第一旋转阀250A中的接口153加载至芯片流通池通道的出口侧,来自第二试剂盒的试剂可通过第二旋转阀250B中的接口156加载至芯片流通池通道的入口侧。此外,第二旋转阀250B中的管路157还可以不经第三阀组148直接与歧管组件144中的公共管路143汇集。
【第三示例性实施例】
与本发明第一示例性实施例不同的是,本发明第三示例性实施例提供的流体系统中,第三阀组中的第三阀采用多通旋转阀,而非电磁阀。图4A和图4B是根据本发明第三示例性实施例的流体系统的局部示意图,分别显示了多通旋转阀处于第一位置和第二位置时的状态。在图4A和图4B所示的示例性实施例中,多通旋转阀以2位12通旋转阀为例,但是也可以采用2位8通旋转阀或者多位多通旋转阀。当旋转阀140处于如图4A所示的第一位置时,第二阀组137中的电磁阀与芯片流通池的通道107通过旋转阀140流体连通。当旋转阀140处于如图4B所示的第二位置时,第二阀组137中的电磁阀与芯第一吸管组件130通过旋转阀140流体连通。
【第一可选实施例】
在上述本发明第一示例性实施例所描述的流体系统中,芯片流通池放置在载片平台模块上,直接进行样本/试剂的加载和测序工序,期间无需移动芯片流通池。与之不同地,图5以及图6A和图6B所示的第一可选实施例中显示了具有测序平台和加载平台两者的双平台流体系统。图5是根据本发明第一可选实施例的流体系统的示意图;图6A和图6B是根据本发明第一可选实施例的流体系统的局部示意图,显示了加载平台106A的流路。
图5中所示的双平台流体系统中采用非集成式芯片流通池。对于非集成式芯片流通池,如图5所示,芯片流通池115首先放置在加载平台106A上,样本盒113和第一试剂盒114通过第二机械运动平台105的控制可依次与芯片流通池115接口连接,样本盒113或第一试剂盒114的孔位与芯片流通池115内各通道107一一对应。由流体动力组件109提供动力,直接抽取样本盒113或试剂盒114中的样本或试剂进行加载,多余的试剂直接排放至废液存储模块110中。待反应完成后,可由自动转移装置将芯片流通池115转移到载片平台模块(在本实施例中为测序平台)106进行下一步生化反应。自动转移装置可以是机械手、也可以是机械拨爪。
本实施例提供的双平台流体系统也可以采用集成式芯片流通池。对于集成式芯片流通池,如图6A和图6B所示,位于芯片流通池115的一端的多个通道接口汇集成一个端口(例如图6A中的右侧端口和图6B中的左侧端口),可以采用正压或负压的方式加载样本或试剂。图6A所示的集成式芯片流通池采用正压方式加载样本或试剂。具体地,样本盒或第一试剂盒通过第二机械运动平台105的控制可依次与 吸管组件130流体连通,吸管组件130与芯片流通池115内的各通道107一一对应。电磁阀137切换至与吸管组件130和流体动力组件(包括注射器127和换向阀128)流体连通,由流体动力组件提供负压驱动力,抽取样本或试剂至电磁阀137与流体动力组件之间;吸液完成后,电磁阀137切换至使芯片流通池115和流体动力组件流体相通。流体动力组件提供正压驱动力,直接推动样本或试剂进入芯片流通池115的通道107进行生化反应,多余的试剂则进入废液存储模块110中。图6B所示的集成式芯片流通池采用负压方式加载样本或试剂。具体地,样本盒113或第一试剂盒114与位于加载平台106A上的芯片流通池115直接流体连通,芯片流通池115的另一端流体连通至流体动力组件(包括注射器127和换向阀128)。由流体动力组件提供负压驱动力,直接抽取样本或试剂进入芯片流通池115的通道107进行生化反应。此外,通过切换流体动力组件中的换向阀128,多余的试剂则进入废液存储模块110中。
【第二可选实施例】
在上述本发明第一示例性实施例所描述的流体系统中,芯片流通池115的出口侧设置第一流体加载模块108,而入口侧设置第二流体加载模块103。与之不同地,第二可选实施例中仅在芯片流通池的出口侧设置第一流体加载模块108,而在入口侧不设置流体加载模块。图7是根据本发明第二可选实施例的流体系统的示意图。
参见图7,由于芯片流通池115的入口侧没有设置流体控制器件,当样本或试剂在芯片流通池115的通道107完成生化反应后,多余的试剂从芯片流通池115入口侧的通道集成端口直接进入废液存储模块110中。
本领域的技术人员可以理解,上面所描述的实施例都是示例性的,并且本领域的技术人员可以对其进行改进,各种实施例中所描述的结构在不发生结构或者原理方面的冲突的情况下可以进行自由组合。
虽然结合附图对本发明进行了说明,但是附图中公开的实施例旨在对本发明实施方式进行示例性说明,而不能理解为对本发明的一种限制。
虽然本发明的一些实施例已被显示和说明,本领域普通技术人员将理解,在不背离本发明的原则和精神的情况下,可对这些实施例做出改变,本发明的范围以权利要求和它们的等同物限定。

Claims (54)

  1. 一种流体运输方法,包括如下步骤:
    a)采用泵阀组件从流体盒吸取第一流体,将所述第一流体从芯片流通池(115)的出口输入所述芯片流通池的通道,并且使从所述芯片流通池的入口输出的所述第一流体返回至所述流体盒;和/或
    b)采用泵阀组件从流体盒吸取第二流体,将所述第二流体从所述芯片流通池的入口输入所述芯片流通池的通道,并且使从所述芯片流通池的出口输出的所述第二流体返回至所述流体盒。
  2. 根据权利要求1所述的流体运输方法,其中,
    所述泵阀组件包括流体动力组件(109),所述流体动力组件被构造成为步骤a和步骤b提供正压驱动力或负压驱动力;
    所述步骤a)包括:
    正压驱动步骤:在所述芯片流通池的出口侧产生所述正压驱动力使所述第一流体从所述出口输入所述通道;或者
    负压驱动步骤:在所述芯片流通池的入口侧产生所述负压驱动力使所述第一流体从所述出口输入所述通道。
  3. 根据权利要求2所述的流体运输方法,其中,
    所述泵阀组件还包括第一流体加载模块(108),所述第一流体加载模块被构造成至少能够在用于将所述流体动力组件与所述流体盒流体连通的第一位置与用于将所述流体动力组件与所述芯片流通池的出口流体连通的第二位置之间切换;
    其中,所述步骤a)包括:
    首先将所述第一流体加载模块切换至所述第一位置以产生所述负压驱动力将所述流体盒中的所述第一流体抽出,然后将所述第一流体加载模块切换至所述第二位置以在所述芯片流通池的出口侧执行所述正压驱动步骤。
  4. 根据权利要求3所述的流体运输方法,其中,
    所述泵阀组件还包括第二流体加载模块(103),所述第二流体加载模块被构造成至少能够在用于将所述芯片流通池的入口与所述流体盒流体连通的第一位置与用于将所述芯片流通池的入口与所述流体动力组件流体连通的第二位置之间切换;所述第一流体加载模块还被构造成能够在所述第一位置、所述第二位置以及用于将所述流体盒与所述芯片流通池的出口流体连通的第三位置之间切换;
    其中,所述步骤a)包括:
    首先将所述第一流体加载模块切换至所述第一位置以产生所述负压驱动力将所述流体盒中的所述第一流体抽出,然后将所述第一流体加载模块切换至所述第二位置并且将所述第二流体加载模块切换至所述第一位置以在所述芯片流通池的出口侧执行所述正压驱动步骤;或者
    将所述第一流体加载模块切换至所述第三位置并且将所述第二流体加载模块切换至所述第二位置,以在所述芯片流通池的入口侧执行所述负压驱动步骤。
  5. 根据权利要求4所述的流体运输方法,其中,
    所述流体盒包括并联设置的样本盒(113)和第一试剂盒(114),所述流体运输方法还包括:
    选择性地执行所述样本盒中的样本和所述第一试剂盒中的试剂的流体运输。
  6. 根据权利要求5所述的流体运输方法,其中,
    提供与所述第二流体加载模块流体连通的第二试剂盒(117),所述第二流体加载模块还被构造成能够在所述第一位置、所述第二位置以及用于将所述第二试剂盒与所述芯片流通池的入口流体连通的第三位置之间切换;
    所述步骤b)包括:
    将所述第一流体加载模块切换至所述第二位置并且将所述第二流体加载模块切换成所述第三位置,以在所述芯片流通池的出口侧产生负压驱动力而将来自所述第二试剂盒的试剂从所述入口输入所述芯片流通池的通道。
  7. 根据权利要求6所述的流体运输方法,其中,
    提供流体驱动控制组件(101),所述流体运输方法还包括:
    通过所述流体驱动控制组件控制所述流体动力组件、所述第一流体加载模块和所述第二流体加载模块中的至少一个。
  8. 根据权利要求6所述的流体运输方法,其中,
    提供样品盒/试剂盒回收模块(116),所述流体运输方法还包括:
    通过所述样品盒/试剂盒回收模块回收所述样本盒和/或所述第一试剂盒。
  9. 根据权利要求6所述的流体运输方法,其中,
    所述流体盒还包括清洗模块(112)和与所述清洗模块流体连通的清洗液/纯水储存模块(111)和废液储存模块(110),所述流体运输方法还包括:
    利用所述清洗模块、所述清洗液/纯水储存模块和所述废液储存模块执行对所述 芯片流通池的通道的清洗。
  10. 根据权利要求9所述的流体运输方法,其中,
    所述清洗模块与所述样本盒和所述第一试剂盒并联设置,所述流体运输方法还包括:
    选择性地执行所述样本盒中的样本和所述第一试剂盒中的试剂的流体运输以及对所述芯片流通池的通道的清洗;和
    当选择执行对所述芯片流通池的通道的清洗时,通过步骤a)中的正压驱动步骤或者负压驱动步骤或者步骤b)来执行对所述芯片流通池的通道的清洗。
  11. 根据权利要求9所述的流体运输方法,其中,
    提供第一机械运动平台(104)、第二机械运动平台(105)和机械运动控制组件(102),其中,至少所述芯片流通池置于所述第一机械运动平台上,并且至少所述样本盒、所述第一试剂盒以及所述清洗模块置于所述第二机械运动平台上;
    所述流体运输方法还包括:
    通过所述机械运动控制组件控制所述第一机械运动平台的多轴运动以将所述芯片流通池接入流体运输管路网络;和
    通过所述机械运动控制组件控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述第一试剂盒以及所述清洗模块中的一个接入所述流体运输管路网络。
  12. 根据权利要求6所述的流体运输方法,其中,
    所述第一流体与所述第二流体不同;
    所述第一流体为样本、试剂、清洗液或纯水中的任意一种,而所述第二流体为试剂、清洗液或纯水中的任意一种。
  13. 一种流体系统,包括:
    芯片流通池(115),包括多个通道(107)以及入口(142)和出口(141);
    样本盒(113)和第一试剂盒(114),所述样本盒用于存储样本,所述第一试剂盒用于存储执行测序所需的试剂;
    流体动力组件(109),用于产生动力以实现所述样本或所述试剂在所述流体系统中的输送;以及
    第一流体加载模块(108),设置在所述芯片流通池的出口侧,并且被构造成至少能够在用于将所述流体动力组件与所述流体盒流体连通的第一位置、用于将所述流体动力组件与所述芯片流通池的出口流体连通的第二位置以及用于将所述流 体盒与所述芯片流通池的出口流体连通的第三位置之间切换。
  14. 如权利要求13所述的流体系统,其中,所述第一流体加载模块包括:
    由多个第一阀构成的第一阀组(140),由多个第二阀构成的第二阀组(137),以及,由多个第一吸管构成的第一吸管组件(130),
    其中,所述多个第一阀、所述多个第二阀和所述多个第一吸管分别设置成与所述芯片流通池的所述多个通道一一对应;
    其中,每一个第一阀分别联接至所述流体动力组件、对应的一个第一吸管以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述第一吸管流体连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口流体连通的第二位置之间切换;以及
    其中,每一个第二阀分别联接至所述流体动力组件、对应的一个第一阀以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述对应的一个第一阀连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口直接流体连通的第二位置之间切换。
  15. 如权利要求13所述的流体系统,其中,所述第一流体加载模块还包括:
    多组传感组件(133,135),每组传感组件分别联接在所述流体动力组件和所述芯片流通池的对应的一个通道的出口之间,并且被构造成用于监测流体特性。
  16. 如权利要求14所述的流体系统,还包括:
    第二流体加载模块(103),设置在所述芯片流通池的入口侧,并且被构造成至少能够在用于将所述芯片流通池的入口与所述流体盒流体连通的第一位置与用于将所述芯片流通池的入口与所述流体动力组件流体连通的第二位置之间切换。
  17. 根据权利要求16所述的流体系统,还包括:
    设置在所述芯片流通池的所述多个通道的入口侧的至少一个第二试剂盒(117);
    其中,所述第二流体加载模块设置在所述芯片流通池的所述多个通道的入口和所述至少一个第二试剂盒之间。
  18. 根据权利要求17所述的流体系统,其中,所述第二流体加载模块进一步包括:
    电磁阀(146),由多个第三阀构成的第三阀组(148),由多个第二吸管构成的第二吸管组件(147),以及,歧管组件(144);
    其中,所述多个第三阀和所述多个第二吸管均设置成与所述芯片流通池的所述多个通道一一对应,所述多个第二吸管联接至所述至少一个第二试剂盒并且经由所述歧管组件与所述芯片流通池的所述多个通道流体连通;以及
    其中,每一个第三阀具有第一端口和第二端口,所述第一端口联接至所述歧管组件,所述第二端口联接至对应的一个第二吸管,并且每一个第三阀被构造成能够在用于闭合所述歧管组件和对应的一个第二吸管之间的流体连通的第一位置与用于打开所述歧管组件和对应的一个第二吸管之间的流体连通的第二位置之间切换;以及
    其中,所述芯片流通池的所述多个通道经由所述电磁阀(146)联接至所述样本盒或所述第一试剂盒。
  19. 根据权利要求18所述的流体系统,还包括:
    流体驱动控制组件(101),所述流体驱动控制组件被构造成控制所述流体动力组件、所述第一流体加载模块和所述第二流体加载模块中的至少一个。
  20. 根据权利要求18所述的流体系统,还包括:
    样品盒/试剂盒回收模块(116),所述样品盒/试剂盒回收模块被构造成回收所述样本盒和/或所述第一试剂盒。
  21. 根据权利要求18所述的流体系统,还包括:
    清洗模块(112),所述清洗模块设置在所述流体动力组件和所述第一流体加载模块之间,并且被构造成用于执行对所述芯片流通池的所述多个通道的清洗;
    清洗液/纯水储存模块(111),所述清洗液/纯水储存模块分别与所述清洗模块和所述第二流体加载模块流体连通,并且被构造成用于在执行对所述芯片流通池的所述多个通道的清洗时提供清洗液和/或纯水;以及
    废液储存模块(110),所述废液储存模块分别与所述清洗模块和所述流体动力组件流体连通,并且被构造成用于回收和/或排放废液。
  22. 如权利要求21所述的流体系统,其中,所述流体动力组件包括:具有多个独立通道的注射器(127),以及多个换向阀(128);
    其中,所述多个独立通道和所述多个换向阀均设置成与所述芯片流通池的所述多个通道一一对应;以及
    其中,每个换向阀被设置成能够被单独或同时控制。
  23. 根据权利要求22所述的流体系统,还包括:
    第一机械运动平台(104),第二机械运动平台(105),以及机械运动控制组件(102);
    其中,至少所述芯片流通池置于所述第一机械运动平台上,并且至少所述样本盒、所述第一试剂盒以及所述清洗模块置于所述第二机械运动平台上;
    其中,所述机械运动控制组件被构造成用于控制所述第一机械运动平台的多轴运动以将所述芯片流通池选择性地接入所述流体系统的流体运输管路网络;以及
    其中,所述机械运动控制组件还被构造成控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述第一试剂盒以及所述清洗模块中的一个接入所述流体系统的流体运输管路网络。
  24. 根据权利要求23所述的流体系统,其中,
    所述第一机械运动平台和所述第二机械运动平台中的至少一个采用三维运动平台或者旋转式运动平台。
  25. 根据权利要求23所述的流体系统,其中,
    所述第一阀组中的多个第一阀、所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。
  26. 根据权利要求23所述的流体系统,其中,
    所述第一阀组中的多个第一阀为多通旋转阀,而所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。
  27. 根据权利要求26所述的流体系统,其中,
    所述多通旋转阀是2位8通旋转阀或者2位12通旋转阀。
  28. 根据权利要求23所述的流体系统,还包括:
    第一旋转阀(250A),所述第一旋转阀设置在所述芯片流通池的多个通道的出口侧,并且被构造成将所述样本盒和所述第一试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络;和
    第二旋转阀(250B),所述第二旋转阀设置在所述芯片流通池的多个通道的入口侧,并且被构造成将所述样本盒、所述第一试剂盒和所述第二试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络。
  29. 根据权利要求16所述的流体系统,还包括:
    测序平台(106),所述测序平台设置在所述第一流体加载模块和所述第二流 体加载模块之间;
    加载平台(106A),所述加载平台设置在所述样本盒和所述第一试剂盒与所述流体动力组件之间;和
    自动转移装置,所述自动转移装置被构造成在所述测序平台和所述加载平台之间自动转移所述芯片流通池。
  30. 一种基因测序仪,包括:
    芯片流通池(115),包括多个通道(107)以及入口(142)和出口(141);
    样本盒(113)和第一试剂盒(114),所述样本盒用于存储样本,所述第一试剂盒用于存储执行测序所需的试剂;
    流体动力组件(109),用于产生动力以实现所述样本或所述试剂在所述流体系统中的输送;以及
    第一流体加载模块(108),设置在所述芯片流通池的出口侧,并且被构造成至少能够在用于将所述流体动力组件与所述样本盒或第一试剂盒流体连通的第一位置、用于将所述流体动力组件与所述芯片流通池的出口流体连通的第二位置以及用于将所述样本盒或第一试剂盒与所述芯片流通池的出口流体连通的第三位置之间切换。
  31. 如权利要求30所述的基因测序仪,其中,所述第一流体加载模块包括:
    由多个第一阀构成的第一阀组(140),由多个第二阀构成的第二阀组(137),以及,由多个第一吸管构成的第一吸管组件(130),
    其中,所述多个第一阀、所述多个第二阀和所述多个第一吸管分别设置成与所述芯片流通池的所述多个通道一一对应;
    其中,每一个第一阀分别联接至所述流体动力组件、对应的一个第一吸管以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述第一吸管流体连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口流体连通的第二位置之间切换;以及
    其中,每一个第二阀分别联接至所述流体动力组件、对应的一个第一阀以及所述芯片流通池的对应的一个通道,并且被构造成至少能够在用于将所述流体动力组件与所述对应的一个第一阀连通的第一位置与用于将所述流体动力组件与所述芯片流通池的对应的一个通道的出口直接流体连通的第二位置之间切换。
  32. 如权利要求30所述的基因测序仪,其中,所述第一流体加载模块还包括:
    多组传感组件(133,135),每组传感组件分别联接在所述流体动力组件和所述芯片流通池的对应的一个通道的出口之间,并且被构造成用于监测流体特性。
  33. 如权利要求31所述的基因测序仪,还包括:
    第二流体加载模块(103),设置在所述芯片流通池的入口侧,并且被构造成至少能够在用于将所述芯片流通池的入口与所述样本盒或第一试剂盒流体连通的第一位置与用于将所述芯片流通池的入口与所述流体动力组件流体连通的第二位置之间切换。
  34. 如权利要求33所述的基因测序仪,还包括:
    设置在所述芯片流通池的所述多个通道的入口侧的至少一个第二试剂盒(117);
    其中,所述第二流体加载模块设置在所述芯片流通池的所述多个通道的入口和所述至少一个第二试剂盒之间。
  35. 如权利要求34所述的基因测序仪,所述第二流体加载模块进一步包括:
    电磁阀(146),由多个第三阀构成的第三阀组(148),由多个第二吸管构成的第二吸管组件(147),以及,歧管组件(144);
    其中,所述多个第三阀和所述多个第二吸管均设置成与所述芯片流通池的所述多个通道一一对应,所述多个第二吸管联接至所述至少一个第二试剂盒并且经由所述歧管组件与所述芯片流通池的所述多个通道流体连通;以及
    其中,每一个第三阀具有第一端口和第二端口,所述第一端口联接至所述歧管组件,所述第二端口联接至对应的一个第二吸管,并且每一个第三阀被构造成能够在用于闭合所述歧管组件和对应的一个第二吸管之间的流体连通的第一位置与用于打开所述歧管组件和对应的一个第二吸管之间的流体连通的第二位置之间切换;以及
    其中,所述芯片流通池的所述多个通道经由所述电磁阀(146)联接至所述样本盒或所述第一试剂盒。
  36. 如权利要求35所述的基因测序仪,还包括:
    流体驱动控制组件(101),所述流体驱动控制组件被构造成控制所述流体动力组件、所述第一流体加载模块和所述第二流体加载模块中的至少一个。
  37. 如权利要求35所述的基因测序仪,还包括:
    样品盒/试剂盒回收模块(116),所述样品盒/试剂盒回收模块被构造成回收所述样本盒和/或所述第一试剂盒。
  38. 如权利要求35所述的基因测序仪,还包括:
    清洗模块(112),所述清洗模块设置在所述流体动力组件和所述第一流体加载模块之间,并且被构造成用于执行对所述芯片流通池的所述多个通道的清洗;
    清洗液/纯水储存模块(111),所述清洗液/纯水储存模块分别与所述清洗模块和所述第二流体加载模块流体连通,并且被构造成用于在执行对所述芯片流通池的所述多个通道的清洗时提供清洗液和/或纯水;以及
    废液储存模块(110),所述废液储存模块分别与所述清洗模块和所述流体动力组件流体连通,并且被构造成用于回收和/或排放废液。
  39. 如权利要求38所述的基因测序仪,其中,所述流体动力组件包括:具有多个独立通道的注射器(127),以及多个换向阀(128);
    其中,所述多个独立通道和所述多个换向阀均设置成与所述芯片流通池的所述多个通道一一对应;以及
    其中,每个换向阀被设置成能够被单独或同时控制。
  40. 如权利要求39所述的基因测序仪,还包括:
    第一机械运动平台(104),第二机械运动平台(105),以及机械运动控制组件(102);
    其中,至少所述芯片流通池置于所述第一机械运动平台上,并且至少所述样本盒、所述第一试剂盒以及所述清洗模块置于所述第二机械运动平台上;
    其中,所述机械运动控制组件被构造成用于控制所述第一机械运动平台的多轴运动以将所述芯片流通池选择性地接入所述流体系统的流体运输管路网络;以及
    其中,所述机械运动控制组件还被构造成控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述第一试剂盒以及所述清洗模块中的一个接入所述流体系统的流体运输管路网络。
  41. 如权利要求40所述的基因测序仪,其中,
    所述第一机械运动平台和所述第二机械运动平台中的至少一个采用三维运动平台或者旋转式运动平台。
  42. 如权利要求40所述的基因测序仪,其中,
    所述第一阀组中的多个第一阀、所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。
  43. 根据权利要求40所述的基因测序仪,其中,
    所述第一阀组中的多个第一阀为多通旋转阀,而所述第二阀组中的多个第二阀以及所述第三阀组中的多个第三阀均为电磁阀。
  44. 根据权利要求43所述的基因测序仪,其中,
    所述多通旋转阀是2位8通旋转阀或者2位12通旋转阀。
  45. 根据权利要求40所述的基因测序仪,还包括:
    第一旋转阀(250A),所述第一旋转阀设置在所述芯片流通池的多个通道的出口侧,并且被构造成将所述样本盒和所述第一试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络;和
    第二旋转阀(250B),所述第二旋转阀设置在所述芯片流通池的多个通道的入口侧,并且被构造成将所述样本盒、所述第一试剂盒和所述第二试剂盒中的一个选择性地接入所述流体系统的流体运输管路网络。
  46. 根据权利要求33所述的基因测序仪,还包括:
    测序平台,所述测序平台设置在所述第一流体加载模块和所述第二流体加载模块之间;
    加载平台,所述加载平台设置在所述样本盒和所述第一试剂盒与所述流体动力组件之间;和
    自动转移装置,所述自动转移装置被构造成在所述测序平台和所述加载平台之间自动转移所述芯片流通池。
  47. 一种生化检验方法,包括:
    将待检测样本从芯片流通池的出口侧加载到所述芯片流通池的通道中;以及
    将具有多种不同反应成分的试剂从所述芯片流通池的入口侧或出口侧加载到所述芯片流通池的通道中,以执行所述样本和所述试剂的生化反应;
    所述反应成分包括样本生成成分或样本分析成分至少之一;
    任选的,所述生化反应包括在所述芯片流通池的通道中生成样本,包括使不同样本生成成分流入所述通道并控制所述通道的反应条件以生成所述样本;以及
    所述生化反应包括分析所述通道中的所述样本,包括使样本分析成分流入所述通道,所述样本分析成分与所述样本发生反应以提供相关可检测信号。
  48. 根据权利要求47所述的生化检验方法,其中,所述生化反应为核酸测序反应,所述待检测样本为核酸测序文库。
  49. 根据权利要求47所述的生化检验方法,其中,所述可检测信号为光学信号。
  50. 如权利要求47所述的生化检验方法,还包括:
    在所述试剂从位于所述芯片流通池的出口侧的第一试剂盒加载到所述芯片流通池的通道中的状态下,在执行生化反应后将所述试剂经由所述芯片流通池的入口排放至所述第一试剂盒;或者
    在所述试剂从位于所述芯片流通池的入口侧的第二试剂盒加载到所述芯片流通池的通道中的状态下,在执行生化反应后将所述试剂经由所述芯片流通池的入口回推至所述第二试剂盒。
  51. 如权利要求50所述的生化检验方法,还包括:
    将清洗液/纯水从所述芯片流通池的出口侧加载至所述芯片流通池的通道中,并且将所述清洗液/纯水经由所述芯片流通池的入口排放至所述第一试剂盒或者所述第二试剂盒或者废液存储模块;或者
    将清洗液/纯水从所述芯片流通池的入口侧加载至所述芯片流通池的通道中,并且将所述清洗液/纯水经由所述芯片流通池的入口回推至所述第二试剂盒或者废液存储模块。
  52. 一种用于流体系统的机械运动设备,所述流体系统至少包括样本盒(113)、试剂盒(114)和芯片流通池(115);所述机械运动设备包括:
    第一机械运动平台(104),其中所述芯片流通池置于所述第一机械运动平台上;
    第二机械运动平台(105),其中所述样本盒和所述试剂盒置于所述第二机械运动平台上;
    机械运动控制组件(102),所述机械运动控制组件被构造成控制所述第一机械运动平台的多轴运动以将所述芯片流通池接入所述流体系统的流体运输管路网络,以及控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒和所述试剂盒中的一个接入所述流体运输管路网络。
  53. 如权利要求52所述的机械运动设备,其中:
    所述流体系统还包括清洗模块(112);
    其中,所述清洗模块置于所述第二机械运动平台上;所述机械运动控制组件还被构造成控制所述第二机械运动平台的多轴运动以选择性地将所述样本盒、所述试剂盒和所述清洗模块中的一个接入所述流体运输管路网络。
  54. 如权利要求52所述的机械运动设备,其中:
    所述第一机械运动平台和所述第二机械运动平台中的至少一个采用三维运动平台或者旋转式运动平台。
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