WO2023087179A1 - 检测芯片组件工装、注液装置、方法、电子设备和介质 - Google Patents

检测芯片组件工装、注液装置、方法、电子设备和介质 Download PDF

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Publication number
WO2023087179A1
WO2023087179A1 PCT/CN2021/131232 CN2021131232W WO2023087179A1 WO 2023087179 A1 WO2023087179 A1 WO 2023087179A1 CN 2021131232 W CN2021131232 W CN 2021131232W WO 2023087179 A1 WO2023087179 A1 WO 2023087179A1
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Prior art keywords
detection chip
liquid injection
vacuum
assembly
liquid
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PCT/CN2021/131232
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English (en)
French (fr)
Inventor
要军磊
张宇宁
王永
张萌萌
云全新
黎宇翔
董宇亮
章文蔚
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深圳华大生命科学研究院
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Priority to PCT/CN2021/131232 priority Critical patent/WO2023087179A1/zh
Publication of WO2023087179A1 publication Critical patent/WO2023087179A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers

Definitions

  • the present application relates to the technical field of gene detection, in particular to a microwell array detection chip component tooling, liquid injection device, method, electronic equipment and medium.
  • a detection chip such as a microwell array sequencing chip is: in a cavity filled with an electrochemical buffer, an insulating film with nanoscale pores (such as a phospholipid bilayer membrane, an artificial membrane, etc.) is used to divide the cavity into two Small chamber, when the voltage acts on the electrolyte chamber, ions or other small molecular substances can pass through the small holes, forming a stable and detectable ion current.
  • an insulating film with nanoscale pores such as a phospholipid bilayer membrane, an artificial membrane, etc.
  • the microwell array sequencing chip is mainly composed of thousands of microwells, and the inner wall of the microwell array is made of hydrophobic materials.
  • the filling of electrochemical buffer is an indispensable sequencing condition.
  • the buffer filling method of the currently commonly used microwell array sequencing chip is: use a pipette gun to disperse the buffer solution above the microwell array, then put it in a vacuum chamber, and vacuum until the liquid filling is completed.
  • the main purpose of the present application is to provide a detection chip component tooling, liquid injection device, method, electronic equipment and medium, so as to improve the above-mentioned defects in the prior art.
  • a detection chip component tooling is provided, which is used to install on a vacuum component
  • the detection chip assembly tooling includes:
  • the base is used to be installed on the detection chip.
  • the base is respectively provided with a reaction chamber for covering the detection chip and a fluid channel communicating with the reaction chamber.
  • the base is also provided with the The fluid channel is connected and used to inject the liquid inlet tank structure of the buffer solution;
  • the vacuum pumping assembly when the buffer solution is filled into the detection chip, the vacuum pumping assembly is started to discharge the air in the detection chip assembly tooling, and the pressure is released in response to the vacuum pumping of the vacuum pumping assembly.
  • the buffer in the lower liquid inlet structure flows into the reaction chamber along the fluid channel to fill the detection chip.
  • the base includes a cover plate and a bottom plate, and the cover plate is covered on the bottom plate;
  • a recessed area is provided on the cover, a hollowed out area is provided on the bottom plate, and the bottom of the recessed area and the hollowed out area form the reaction chamber;
  • a fluid groove is opened on the bottom plate, and the fluid channel is formed between the fluid groove and the bottom of the cover plate;
  • the liquid inlet tank structure is provided on the top of the cover plate.
  • an air storage tank is also opened on the bottom plate, and the air storage tank forms an air storage position with the bottom of the cover plate;
  • the air storage position communicates with the reaction chamber and is used for storing residual air pushed in by the buffer when the buffer is filled into the reaction chamber.
  • the detection chip assembly tooling also includes a fixed base
  • the detection chip is fixedly installed on the fixed base.
  • a liquid injection device for a detection chip including a liquid injection component, a vacuum component, a control module, and the above-mentioned detection chip component tooling;
  • the detection chip assembly tooling is installed on the vacuum assembly, and the liquid injection assembly is used to inject buffer into the liquid inlet tank structure;
  • the control module is configured to activate the vacuum assembly to discharge the air in the detection chip assembly tooling when filling the detection chip with buffer;
  • the control module is further configured to activate the liquid injection assembly to inject the buffer into the liquid inlet tank structure in response to detecting that a preset vacuum condition is formed in the detection chip assembly tooling, and control the pumping
  • the vacuum component releases pressure, and under the action of negative pressure, the buffer solution in the liquid inlet groove structure flows into the reaction chamber along the fluid channel groove to fill the detection chip.
  • the vacuum pumping assembly includes a chip assembly fixing plate, a vacuum tank body, a vacuum tank cover plate, an air pumping pipeline, a vacuum pump, and a vacuum valve;
  • the detection chip component tooling is installed on the chip component fixing plate;
  • the chip component fixing plate is fixedly arranged in the vacuum tank;
  • the vacuum tank cover plate is set on the vacuum tank body
  • One end of the air extraction pipeline is arranged in the vacuum tank;
  • the vacuum pump is arranged on the air extraction pipeline and is used to extract the air in the vacuum tank;
  • the vacuum valve is connected to the vacuum pump and communicated with the control module.
  • the vacuum assembly also includes a vacuum detection pressure gauge, a pressure relief speed regulating valve, and a gas filter;
  • the vacuum detection pressure gauge is connected in communication with the control module, and is used to detect the pressure in the vacuum tank;
  • the pressure relief speed regulating valve is connected with the vacuum valve, and is used for performing pressure relief and adjusting the pressure relief speed;
  • the gas filter is arranged on the suction pipeline.
  • the liquid injection assembly includes a liquid injection needle, a liquid injection needle holder, a liquid injection pump, a solenoid valve at the inlet of the liquid injection pump, a solenoid valve at the outlet of the liquid injection pump, and a connecting pipeline;
  • the liquid injection needle is fixedly arranged on the liquid injection needle holder, and is used to inject the buffer solution into the liquid inlet tank structure;
  • the liquid injection needle fixing part is arranged in the vacuum tank;
  • the liquid injection pump is connected to the liquid injection needle through the connecting pipeline, and is used to deliver buffer to the liquid injection needle;
  • the inlet solenoid valve of the infusion pump is connected to the inlet of the infusion pump, and communicated with the control module;
  • the solenoid valve at the outlet of the infusion pump is connected to the outlet of the infusion pump and communicated with the control module.
  • the liquid injection assembly also includes an adjusting screw and a guide rod;
  • the adjusting screw is arranged on the liquid injection needle fixing part, and is used to adjust the distance between the liquid injection needle and the liquid inlet groove structure;
  • the guide rod is arranged between the chip assembly fixing plate and the injection needle fixing part.
  • the liquid injection component also includes a buffer container
  • the buffer container is connected to the infusion pump through the connecting pipeline, and is used for containing the buffer.
  • a liquid injection method for a detection chip which is realized by using the above liquid injection device for a detection chip, and the liquid injection method includes:
  • the liquid injection assembly is activated to inject the buffer into the liquid inlet tank structure, and the vacuum pumping assembly is controlled to release the pressure. Under pressure, the buffer solution in the liquid inlet groove structure flows into the reaction chamber along the fluid channel groove to fill the detection chip.
  • an electronic device including a memory, a processor, and a computer program stored on the memory and operable on the processor.
  • the processor executes the computer program, the detection chip as described above is implemented. Injection method.
  • a computer-readable medium on which computer instructions are stored, and when the computer instructions are executed by a processor, the method for injecting liquid into a detection chip as described above is implemented.
  • This application effectively uses the method of vacuuming first and then automatically injecting liquid, so that the gas in the micropore array of the detection chip does not pass through the solution, thereby effectively avoiding the generation of gas-liquid mixture, and does not need manual operation with a pipette gun, one-key Realize automatic vacuuming, automatic liquid injection, automatic pressure relief, reduce labor costs, reduce the contact between staff and chemicals, and greatly improve the efficiency and accuracy of liquid injection of the detection chip.
  • Fig. 1a is a schematic diagram of a first assembly of a detection chip assembly tooling according to an embodiment of the present application.
  • Fig. 1b is a second assembly schematic diagram of the detection chip assembly tooling according to an embodiment of the present application.
  • Fig. 2a is a schematic structural diagram of a base and a detection chip of a detection chip assembly tooling according to an embodiment of the present application.
  • Fig. 2b is an assembly schematic diagram of the base of the testing chip assembly tool according to an embodiment of the present application.
  • Fig. 3 is a schematic structural diagram of a microwell array detection chip.
  • Fig. 4a is a schematic diagram of the gas inside the micropore of the detection chip after using the traditional liquid injection method.
  • FIG. 5 is a schematic diagram of a module structure of a liquid injection device for a detection chip according to another embodiment of the present application.
  • Fig. 6a is a schematic front view of a pump valve assembly of a liquid injection device for a detection chip according to another embodiment of the present application.
  • Fig. 6b is a schematic diagram of the back structure of the pump valve assembly of the liquid injection device for the detection chip according to another embodiment of the present application.
  • Fig. 7 is an assembly diagram of a vacuum assembly and a liquid injection assembly of a liquid injection device for a detection chip according to another embodiment of the present application.
  • FIG. 8 is a schematic diagram of an electronic control interface of a liquid injection device for a detection chip according to another embodiment of the content of the present application.
  • FIG. 9 is a schematic flowchart of a liquid injection method for a detection chip according to another embodiment of the present application.
  • FIG. 10 is a schematic structural diagram of an electronic device implementing a liquid injection method for a detection chip according to another embodiment of the present application.
  • Injection pump outlet solenoid valve 1 Injection pump inlet solenoid valve 2;
  • Vacuum valve 5 Electronic control board 6;
  • Injection needle 9 Injection needle 9; Injection needle holder 10;
  • Buffer container 24 Vacuum test pressure gauge 25;
  • references in the specification to "an embodiment,” “an alternative embodiment,” “another embodiment,” etc. indicate that the described embodiments may include a particular feature, structure, or characteristic, but each embodiment The specific feature, structure or characteristic may not necessarily be included. Moreover, such phrases are not necessarily referring to the same embodiment. Furthermore, when a particular feature, structure or characteristic is described in conjunction with an embodiment, it is within the purview of those skilled in the relevant arts to implement such feature, structure or characteristic in conjunction with other embodiments, whether or not explicitly described.
  • first and second are used for descriptive purposes only, and cannot be interpreted as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features. Thus, a feature defined as “first” and “second” may explicitly or implicitly include one or more of these features.
  • plural means two or more.
  • the term “comprise” and any variations thereof, are intended to cover a non-exclusive inclusion.
  • connection should be understood in a broad sense, for example, it can be a fixed connection or a flexible connection.
  • Detachable connection, or integral connection it can be mechanical connection or electrical connection; it can be direct connection or indirect connection through an intermediary, and it can be the internal communication of two components.
  • a detection chip such as a microwell array sequencing chip is mainly composed of thousands of microwells, and the inner wall of the microwell array is made of hydrophobic materials.
  • the filling of electrochemical buffer is an indispensable sequencing condition.
  • the method of first injecting liquid and then vacuuming is used to fill the buffer solution of the sequencing chip.
  • the microwell array is used to form a liquid storage tank with a sealing gasket or other methods, and the buffer solution is added to the surface of the microwell array, and the sealing device keeps the solution in the
  • the surface of the sequencing chip is then put into a vacuum tank to evacuate.
  • the air in the micropores needs to enter the surface buffer to form tiny bubbles. Due to the surface tension, some larger bubbles will burst due to pressure changes, while some tiny bubbles are suspended in the buffer and cannot be discharged, forming a gas-liquid mixture. After the pressure is released, the internal buffer of the microwell array is a gas-liquid mixture, which affects the working stability of the sequencing chip.
  • this embodiment provides a liquid injection device for a detection chip, including a liquid injection assembly, a vacuum assembly, a control module, and the detection chip assembly tooling as described above; the detection chip assembly tooling is installed on the vacuum assembly , the liquid injection component is used to inject the buffer solution into the liquid inlet tank structure; the control module is configured to start the vacuum pumping component to discharge the air in the detection chip assembly tooling when the buffer solution is filled into the detection chip; the control module is also configured to In response to the detection of the preset vacuum condition in the tooling of the detection chip component, the liquid injection component is activated to inject the buffer into the liquid inlet tank structure, and the vacuum pumping component is controlled to release the pressure, and the liquid inlet tank structure is under negative pressure The buffer solution flows into the reaction chamber along the fluid channel groove to fill the detection chip.
  • the detection chip is preferably a sequencing chip, but it is not limited to a sequencing chip, and can also be other biological or chemical detection chips, which can be adjusted or selected according to actual needs or possible needs.
  • the liquid injection device can also be used in various other fields such as protein analysis, single cell analysis, and drug screening. On the basis of realizing the above functions, it can also be combined with actual needs or possible needs Adjust or select accordingly.
  • the method of vacuuming first and then automatically injecting liquid is effectively used, so that the gas in the microwell array of the detection chip does not pass through the solution, thereby effectively avoiding the generation of gas-liquid mixture, and there is no need to manually use a pipette Operation, one-button automatic vacuuming, automatic liquid injection, automatic pressure relief, reducing labor costs, reducing the contact between staff and chemicals, and greatly improving the efficiency and accuracy of liquid injection of the detection chip.
  • the liquid injection device for the detection chip mainly includes a detection chip assembly tooling, a vacuum assembly, a liquid injection assembly and a control module.
  • the detection chip assembly tooling mainly includes a base 161 , several fastening screws 162 and a fixing base 163 .
  • the base 161 mainly includes a cover plate 1611 and a bottom plate 1612, wherein the cover plate 1611 covers the bottom plate 1612, the cover plate 1611 is provided with a recessed area 16111, the bottom plate 1612 is provided with a hollow area 16121, and the recessed area
  • the bottom of 16111 (that is, the bottom of the cover plate 1611) and the hollowed out area 16121 form a closed reaction chamber 164.
  • the bottom plate 1612 is provided with a fluid groove 16122.
  • the fluid groove 16122 forms a fluid channel with the bottom of the cover plate 1611.
  • a liquid inlet tank structure 163 is also provided on the top.
  • a gas storage tank 16123 is also provided on the bottom plate 1612, and the gas storage tank 16123 forms a closed gas storage position with the bottom of the cover plate 1611, and the gas storage position and the reaction chamber 164 connected.
  • the detection chip 17, the base 161 and the fixed base 163 are fixedly mounted together by several fastening screws 162 to form the chip assembly 14, wherein a closed reaction chamber is thus formed body 164, fluid passages and gas storage levels.
  • the number of fastening screws 162 or the way of fixing the detection chip are not specifically limited, as long as a corresponding fixing effect can be achieved, corresponding adjustments and selections can be made according to actual needs.
  • the vacuum assembly mainly includes a chip assembly fixing plate 13, a vacuum tank body 15, a vacuum tank cover plate 8, an air extraction pipeline (not shown in the figure), a vacuum pump 4 and a vacuum valve 5.
  • the chip component 14 is installed on the chip component fixing plate 13, the chip component fixing plate 13 is set in the vacuum tank body 15, the vacuum tank cover plate 8 is set on the vacuum tank body 15, and one end of the air extraction pipeline is set in the vacuum tank body 15
  • the vacuum pump 4 is arranged on the air extraction pipeline, and is used to extract the air in the vacuum tank body 15, the vacuum valve 5 is connected with the vacuum pump 4, and controls the start-up of the vacuum pump 4 by controlling the closing of the vacuum valve to extract the air in the vacuum tank body 15. air.
  • the vacuum assembly further includes a vacuum detection pressure gauge 25 , a pressure relief speed regulating valve 26 and at least two gas filters 27 .
  • the vacuum detection pressure gauge 25 is used to detect the pressure in the vacuum tank body 15; the pressure relief speed regulating valve 26 is connected with the vacuum valve 5, and is used to perform pressure relief and adjust the pressure relief speed.
  • Two gas filters 27 are respectively installed on the outlet of the vacuum pump 4 and the pressure relief port of the vacuum valve 5, respectively to prevent the experimental environment from being polluted by the volatilization of the electrochemical buffer solution, and to effectively prevent dust and impurities when the outside air enters the vacuum tank body 15. Entry into the vacuum valve 5 leads to failure and entry into the vacuum tank 15 causes buffer contamination.
  • the type of the vacuum assembly is not specifically limited, as long as the corresponding functions can be realized, other vacuum generators can be used instead of the vacuum pump.
  • the liquid injection assembly includes a liquid injection needle 9, a liquid injection needle holder 10, a liquid injection pump 3, an inlet solenoid valve 2 of the liquid injection pump, an outlet solenoid valve 1 of the liquid injection pump, Connect the pipeline, the adjusting screw 11, the guide rod 12 and the buffer container 24.
  • the liquid injection needle 9 is fixedly arranged on the liquid injection needle holder 10 , and is used for injecting buffer solution into the liquid inlet tank structure 1613 ; the liquid injection needle holder 10 is arranged in the vacuum tank 15 .
  • the injection pump 3 is connected to the injection needle 9 through a connecting pipeline, and is used for delivering buffer solution to the injection needle 9 .
  • the inlet solenoid valve 2 of the injection pump is connected to the inlet of the injection pump 3
  • the outlet solenoid valve 1 of the injection pump is connected to the outlet of the injection pump 3 .
  • the adjusting screw 11 is arranged on the liquid injection needle fixing part 10 and is used for adjusting the distance between the liquid injection needle 9 and the liquid inlet groove structure 1613 .
  • the guide rod 12 is arranged between the chip assembly fixing plate 13 and the liquid injection needle fixing member 10 to ensure the position accuracy of the liquid injection needle when it moves up and down.
  • the buffer container 24 is connected to the infusion pump 3 via a connecting line and is used for containing buffer.
  • the control module can communicate with the liquid injection pump outlet solenoid valve 1, the liquid injection pump inlet solenoid valve 2, the vacuum valve 5, the vacuum detection pressure gauge 25 and the pressure relief speed regulating valve 26 respectively.
  • liquid injection components As a preferred implementation mode, a total of four liquid injection components are designed.
  • the principles and materials of each liquid injection component are basically the same, and corresponding adjustments and selections can be made according to actual needs.
  • the fixing position adopts a ring design according to the chip structure, making full use of the plane space. Adjust the height of the liquid injection needle from the structure of the liquid inlet tank by adjusting the screw 11. The height above the liquid surface is preferably 3mm-5mm. If the distance is too high, it will cause splashing problems, and if the distance is too close, the liquid injection needle will easily touch the buffer. Causes crystallization problems, but the height is not specifically limited, and can be adjusted and selected according to actual needs.
  • control module may include an electronic control board 6 for controlling the valve body and a computer device (not shown) for performing calculation and control, wherein the liquid injection pump 3, the vacuum pump 4 and the Various valve bodies and electronic control boards 6 for controlling various pumps are installed on the mounting plate 7 to save installation space and facilitate management and maintenance.
  • the high-precision injection pump needs to be fixed vertically to allow air to escape.
  • control module is configured to start the vacuum assembly when the detection chip 17 needs to be filled with electrochemical buffer solution, that is, start the corresponding vacuum pump 4 to detect the air in the chip 17 (that is, the air in the entire chip assembly 14).
  • air discharge, specifically, the air in the reaction chamber 164 is discharged from the discharge hole of the liquid inlet tank structure 1613 along the fluid channel formed by the fluid tank 16122, wherein, the vacuum pressure gauge 25 is used to detect the vacuum tank body 15 in real time. The pressure inside is fed back to the control module.
  • the control module is also configured to respond to detecting that a preset vacuum condition is formed in the chip assembly 14, as an optional embodiment, responding to detecting that the pressure in the vacuum tank 15 reaches a preset value (can be set to reach After the maximum vacuum degree of the system), start the liquid injection component, that is, start the corresponding liquid injection pump 3 to inject the buffer solution into the liquid inlet tank structure, and control the vacuum pumping component to release the pressure, under the action of negative pressure, the liquid inlet tank structure
  • a preset value can be set to reach After the maximum vacuum degree of the system
  • start the liquid injection component that is, start the corresponding liquid injection pump 3 to inject the buffer solution into the liquid inlet tank structure
  • control the vacuum pumping component to release the pressure, under the action of negative pressure, the liquid inlet tank structure
  • the buffer solution flows into the reaction chamber along the fluid channel groove to fill the detection chip.
  • the air storage position is used to store the residual air pushed by the buffer when the buffer flows into the reaction cavity along the fluid channel, so as not to affect the working performance of the microwell array detection chip.
  • the gas storage position is designed at the end of the detection chip, which is a non-working area, and there is no need to fill it with buffer solution completely. When the buffer solution is injected from front to back, the residual air is gradually pushed into the gas storage position.
  • the detection chip assembly tooling makes the microhole array detection chip form a semi-closed cavity, uses the funnel-shaped exhaust port and liquid inlet tank structure, and starts the vacuum pump to pump the vacuum tank to -95KPa ⁇ -100KPa to discharge Detect the air in the micropore of the chip.
  • the liquid injection component is activated to inject liquid into the liquid inlet tank structure. Generation of air bubbles due to flow.
  • start the liquid injection component for liquid injection first open the solenoid valve at the inlet of the liquid injection pump. Open the solenoid valve at the outlet of the injection pump, and at this time, the injection pump injects the buffer solution into the liquid inlet tank structure through the injection needle. After injecting a preset amount (for example, 300ul) of buffer solution, stop the injection, and wait for a preset period of time (for example, 10s), then turn off the vacuum pump, open the pressure relief speed control valve, and release the pressure to connect to the atmospheric pressure. At this time, the buffer The liquid flows into the reaction chamber under the action of atmospheric pressure, thereby filling the detection chip, and the residual trace air during the filling process will be squeezed to the gas storage position.
  • a preset amount for example, 300ul
  • a preset period of time for example, 10s
  • the electrochemical buffer solution is placed in the buffer solution container without frequent human contact; the corresponding valve body can control the on-off of the liquid to ensure that the seal is formed during vacuuming and the liquid will not overflow; the high-precision liquid injection pump can precisely control the liquid injection The amount, injection speed and injection time; the injection needle ensures the accuracy of the liquid injection position and reduces the problem of hanging liquid.
  • the diameter of a single micropore 171 of the detection chip 17 is generally tens of microns to one hundred microns.
  • the traditional liquid injection method will result in the result shown in Figure 4a. It can be seen that the gas in the micropore 171 cannot be discharged (the unfilled part indicates gas, and the filled part indicates liquid), and the liquid cannot be filled; the filling situation of this embodiment is shown in Figure 4b. It can be seen that complete filling of micropores 171 can be achieved.
  • the control module can realize one-key control of the whole process by using the electronic control interface. After the chip component is placed inside the vacuum tank, click the electronic control interface to customize the operation to realize the automatic operation of the whole process . After running, take out the chip assembly, and the inside of the microwell has been filled with electrochemical buffer. At the same time, it can meet the requirements of individual control, and can individually control the opening or closing of each corresponding valve body, the operation of the plunger pump, etc.
  • each valve body of each type can be individually controlled, and joint operation can also be performed through an autonomous sequence to reduce manual participation.
  • Adopt the method of issuing logical instructions from the upper computer communicate with the electronic control board through high-speed data lines, and use handshake signal judgment, data verification, etc. to ensure the correctness of the issued instructions, and let the electronic control board control the corresponding components.
  • to realize automatic vacuuming, automatic liquid injection, automatic filling and other actions to ensure the accuracy and unmanned intervention of the whole process, so as to ensure that the electrochemical buffer solution completely enters the microwell array of the detection chip.
  • any single pump and valve can be controlled on the computer equipment, and the logic sequence can also be saved to run with one key.
  • the operation is flexible and convenient, and each parameter can be adjusted individually.
  • the vacuum environment can effectively discharge the air inside the micropore array of the detection chip, and the gas storage position can effectively avoid the situation where the air remains in the micropores due to the inability to achieve absolute vacuum, so as to realize the effective filling of the micropore array with the electrochemical buffer;
  • Each component of the liquid injection device in this embodiment can be electronically controlled by the control module, and one-key operation can be performed on the client side of the computer equipment through the electronic control interface, which is convenient and quick, and the liquid injection time, liquid injection speed, liquid injection The amount can be precisely controlled, thereby improving the overall stability and effectively avoiding human errors.
  • this embodiment provides a liquid injection method for a detection chip, which is implemented by using the liquid injection device for the detection chip described above, as shown in Figure 9, the liquid injection method mainly includes the following steps :
  • Step 201 receiving a detection chip filling buffer instruction
  • Step 202 start the vacuum assembly to extract the air in the chip assembly
  • Step 203 obtaining the pressure inside the vacuum tank
  • Step 204 in response to the pressure reaching a preset value, activate the injection component to fill the buffer into the detection chip.
  • step 201 when the electrochemical buffer needs to be filled into the detection chip, the assembled chip assembly is put into the vacuum tank, and the staff gives an instruction to fill the buffer through the electronic control interface.
  • step 202 start the vacuum assembly, that is, start the corresponding vacuum pump to exhaust the air in the chip assembly.
  • step 203 the pressure in the vacuum tank is detected in real time by a vacuum detection pressure gauge and fed back to the control module.
  • step 204 in response to detecting that the pressure in the vacuum tank reaches a preset value, the liquid injection component is activated to inject the buffer into the liquid inlet tank structure, and the vacuum component is controlled to release the pressure, and the process is performed under negative pressure.
  • the buffer solution in the liquid tank structure flows into the reaction chamber along the fluid channel tank to fill the detection chip.
  • the liquid injection method of the detection chip effectively uses the method of vacuuming first and then automatic liquid injection, so that the gas in the microhole array of the detection chip does not pass through the solution, thereby effectively avoiding the generation of gas-liquid mixture, and There is no need to manually use a pipette gun, one-button automatic vacuuming, automatic liquid injection, automatic pressure relief, reducing labor costs, reducing the contact between staff and chemicals, and greatly improving the efficiency and accuracy of liquid injection of the detection chip .
  • Fig. 10 is a schematic structural diagram of an electronic device provided according to this embodiment.
  • the electronic device includes a memory, a processor, and a computer program stored in the memory and executable on the processor. When the processor executes the program, the liquid injection method for the detection chip in the above embodiment is implemented.
  • the electronic device 30 shown in FIG. 10 is only an example, and should not limit the functions and application scope of the embodiment of the present application.
  • the electronic device 30 may be in the form of a general-purpose computing device, for example, it may be a server device.
  • Components of the electronic device 30 may include, but are not limited to: at least one processor 31 , at least one memory 32 , and a bus 33 connecting different system components (including the memory 32 and the processor 31 ).
  • the bus 33 includes a data bus, an address bus, and a control bus.
  • the memory 32 may include a volatile memory, such as a random access memory (RAM) 321 and/or a cache memory 322 , and may further include a read only memory (ROM) 323 .
  • RAM random access memory
  • ROM read only memory
  • Memory 32 may also include a program/utility tool 325 having a set (at least one) of program modules 324 including, but not limited to, an operating system, one or more application programs, other program modules, and program data, which Each or some combination of the examples may include the implementation of a network environment.
  • program/utility tool 325 having a set (at least one) of program modules 324 including, but not limited to, an operating system, one or more application programs, other program modules, and program data, which Each or some combination of the examples may include the implementation of a network environment.
  • the processor 31 executes various functional applications and data processing by executing the computer program stored in the memory 32 , such as the liquid injection method of the detection chip in the above embodiment of the present application.
  • Electronic device 30 may also communicate with one or more external devices 34 (eg, keyboards, pointing devices, etc.). Such communication may occur through input/output (I/O) interface 35 .
  • the model generation device 30 can also communicate with one or more networks (eg, a local area network (LAN), a wide area network (WAN) and/or a public network, such as the Internet) via a network adapter 36 .
  • network adapter 36 communicates with other modules of model generation device 30 via bus 33 .
  • model generating device 30 may be used in conjunction with the model generating device 30, including but not limited to: microcode, device drivers, redundant processors, external disk drive arrays, RAID (disk array) systems, tape drives, and data backup storage systems.
  • This embodiment also provides a computer-readable storage medium, on which a computer program is stored.
  • the program is executed by a processor, the steps in the liquid injection method for the detection chip in the above embodiment are implemented.
  • the readable storage medium may more specifically include but not limited to: portable disk, hard disk, random access memory, read-only memory, erasable programmable read-only memory, optical storage device, magnetic storage device or any of the above-mentioned the right combination.
  • the present application can also be implemented in the form of a program product, which includes program code.
  • the program product When the program product is executed on the terminal device, the program code is used to make the terminal device perform the detection in the above embodiment. Steps in the chip injection method.
  • the program code for executing the application can be written in any combination of one or more programming languages, and the program code can be completely executed on the user equipment, partially executed on the user equipment, as an independent software Package execution, partly on the user device and partly on the remote device, or entirely on the remote device.

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Abstract

本申请提供了一种检测芯片组件工装、注液装置、方法、电子设备和介质，该工装用于安装于抽真空组件；该工装包括：基座，用于安装于检测芯片上，基座分别设有覆盖所述检测芯片的反应腔体及与反应腔体连通的流体通道，基座还设有与流体通道连通并注入缓冲液的进液槽结构；当向检测芯片填充缓冲液时，启动抽真空组件以将检测芯片组件工装内的空气排出，响应于抽真空组件抽真空后进行泄压，在负压作用下进液槽结构内的缓冲液沿着流体通道流入至反应腔体以填充检测芯片。本申请有效地利用先抽真空再进行自动注液的方式，避免了气液混合物产生，而且无需人工使用移液枪操作，提升了检测芯片的注液效率及精度。

Description

检测芯片组件工装、注液装置、方法、电子设备和介质 技术领域
本申请涉及基因检测技术领域，特别涉及一种微孔阵列检测芯片组件工装、注液装置、方法、电子设备和介质。
背景技术
检测芯片例如微孔阵列测序芯片的工作原理是：在充满电化学缓冲液的腔内，利用带有纳米级小孔的绝缘薄膜(如磷脂双层膜、人工膜等)将腔体分成2个小室，当电压作用于电解液室，离子或其他小分子物质可穿过小孔，形成稳定的可检测的离子电流。掌握纳米孔的尺寸和表面特性、施加的电压及溶液条件，可检测不同类型的生物分子。
微孔阵列测序芯片主要由上千个微孔组成，而且微孔阵列内壁均为疏水性材料，电化学缓冲液的填充是其不可缺少的测序条件。
改变微孔阵列内壁的亲疏水性，使其达到亲水状态，可以使电化学缓冲液通过亲水性浸入微孔阵列内，然而材料表面改性方式较为复杂，成本较高，而且部分种类测序芯片要求微孔表面疏水，因而这种方式无法满足疏水性微孔阵列测序芯片缓冲液填充需求。
因此，目前一般使用的微孔阵列测序芯片的缓冲液填充方式为：使用移液枪将缓冲液分散于微孔阵列上方，然后放到真空室中，抽真空至液体填充完成。
但是，目前使用的上述填充方式具有以下缺陷：
1、使用移液枪注液，真空泵启停，均需人工操作，导致增加人工成本，而且会降低填充效率和精度；
2、由于先注液再抽气，导致微孔内部无法达到绝对真空，缓冲液无法完全填充；
3、抽真空时部分气泡会残留在缓冲液内，形成气液混合物，对后续测序造成影响。
发明内容
本申请的主要目的在于，提供一种检测芯片组件工装、注液装置、方法、电子设备和介质，以改善现有技术中存在的上述缺陷。
本申请是通过下述技术方案来解决上述技术问题：
作为本申请的一方面，提供一种检测芯片组件工装，用于安装于抽真空组件；
所述检测芯片组件工装，包括：
基座，用于安装于检测芯片上，所述基座分别设有用于覆盖所述检测芯片的反应腔 体以及与所述反应腔体连通的流体通道，所述基座还设有与所述流体通道连通并用于注入缓冲液的进液槽结构；
其中，当向所述检测芯片填充缓冲液时，启动所述抽真空组件以将所述检测芯片组件工装内的空气排出，响应于所述抽真空组件抽真空后进行泄压，在负压作用下所述进液槽结构内的所述缓冲液沿着所述流体通道流入至所述反应腔体以填充所述检测芯片。
作为可选实施方式，所述基座包括盖板及底板，所述盖板盖设于所述底板上；
所述盖板上设有凹陷区域，所述底板上设有镂空区域，所述凹陷区域的底部与所述镂空区域形成所述反应腔体；
所述底板上开设有流体槽，所述流体槽与所述盖板的底部形成所述流体通道；
所述盖板的顶部上设有所述进液槽结构。
作为可选实施方式，所述底板上还开设有储气槽，所述储气槽与所述盖板的底部形成储气位；
所述储气位与所述反应腔体连通，并且用于当所述缓冲液填充至所述反应腔体时储存被所述缓冲液推入的残余空气。
作为可选实施方式，所述检测芯片组件工装还包括固定底座；
所述检测芯片固定安装于所述固定底座上。
作为本申请的另一方面，提供一种检测芯片的注液装置，包括注液组件、抽真空组件、控制模块及如上述的检测芯片组件工装；
所述检测芯片组件工装安装于所述抽真空组件，所述注液组件用于向所述进液槽结构注入缓冲液；
所述控制模块被配置为当向所述检测芯片填充缓冲液时，启动所述抽真空组件以将所述检测芯片组件工装内的空气排出；
所述控制模块还被配置为响应于检测到所述检测芯片组件工装内形成预设真空条件后，启动所述注液组件以将缓冲液注入至所述进液槽结构，并且控制所述抽真空组件进行泄压，在负压作用下所述进液槽结构内的缓冲液沿着所述流体通道槽流入至所述反应腔体以填充所述检测芯片。
作为可选实施方式，所述抽真空组件包括芯片组件固定板、真空罐体、真空罐盖板、抽气管路、真空泵及真空阀；
所述检测芯片组件工装安装于所述芯片组件固定板上；
所述芯片组件固定板固定设置于所述真空罐体内；
所述真空罐盖板盖设于所述真空罐体上；
所述抽气管路的一端设置于所述真空罐体内；
所述真空泵设置于所述抽气管路上，并且用于抽取所述真空罐体内的空气；
所述真空阀与所述真空泵连接，并且与所述控制模块通信连接。
作为可选实施方式，所述抽真空组件还包括真空检测压力表、泄压调速阀及气体过滤器；
所述真空检测压力表与所述控制模块通信连接，并且用于检测所述真空罐体内的压强；
所述泄压调速阀与所述真空阀连接，并且用于进行泄压并调节泄压速度；
所述气体过滤器设置于所述抽气管路上。
作为可选实施方式，所述注液组件包括注液针、注液针固定件、注液泵、注液泵入口电磁阀、注液泵出口电磁阀及连接管路；
所述注液针固定设置于所述注液针固定件上，并且用于向所述进液槽结构注入所述缓冲液；
所述注液针固定件设置于所述真空罐体内；
所述注液泵通过所述连接管路与所述注液针连接，并且用于向所述注液针输送缓冲液；
所述注液泵入口电磁阀与所述注液泵的入口连接，并且与所述控制模块通信连接；
所述注液泵出口电磁阀与所述注液泵的出口连接，并且与所述控制模块通信连接。
作为可选实施方式，所述注液组件还包括调节螺杆及导向杆；
所述调节螺杆设置于所述注液针固定件上，并且用于调节所述注液针与所述进液槽结构之间的距离；
所述导向杆设置于所述芯片组件固定板与所述注液针固定件之间。
作为可选实施方式，所述注液组件还包括缓冲液容器；
所述缓冲液容器通过所述连接管路与所述注液泵连接，并且用于容纳所述缓冲液。
作为本申请的另一方面，提供一种检测芯片的注液方法，利用如上述的检测芯片的注液装置来实现，所述注液方法包括：
当向所述检测芯片填充缓冲液时，启动所述抽真空组件以将所述检测芯片组件工装内的空气排出；
响应于检测到所述检测芯片组件工装内形成预设真空条件后，启动所述注液组件以将缓冲液注入至所述进液槽结构，并且控制所述抽真空组件进行泄压，在负压作用下所述进液槽结构内的缓冲液沿着所述流体通道槽流入至所述反应腔体以填充所述检测芯片。
作为本申请的另一方面，提供一种电子设备，包括存储器、处理器及存储在存储器上并可在处理器上运行的计算机程序，所述处理器执行计算机程序时实现如上述的检测芯片的注液方法。
作为本申请的另一方面，提供一种计算机可读介质，其上存储有计算机指令，所述计算机指令在由处理器执行时实现如上述的检测芯片的注液方法。
根据本申请内容，本领域技术人员可以理解本申请内容的其它方面。
本申请的积极进步效果在于：
本申请有效地利用先抽真空再进行自动注液的方式，使得检测芯片微孔阵列内的气体不经过溶液，从而有效地避免了气液混合物产生，而且无需人工使用移液枪操作，一键实现自动抽真空，自动注液，自动泄压，减少了人工成本，减少了工作人员与化学品接触，进而极大地提升了检测芯片的注液效率及精度。
附图说明
在结合以下附图阅读本申请的实施例的详细描述之后，能够更好地理解本申请的所述特征和优点。在附图中，各组件不一定是按比例绘制，并且具有类似的相关特性或特征的组件可能具有相同或相近的附图标记。
图1a为根据本申请内容的一实施例的检测芯片组件工装的第一装配示意图。
图1b为根据本申请内容的一实施例的检测芯片组件工装的第二装配示意图。
图2a为根据本申请内容的一实施例的检测芯片组件工装的基座与检测芯片的结构示意图。
图2b为根据本申请内容的一实施例的检测芯片组件工装的基座的装配示意图。
图3为微孔阵列检测芯片的结构示意图。
图4a为利用传统注液方式后的检测芯片的微孔内部气体示意图。
图4b为利用本申请提供的检测芯片组件工装后的检测芯片的微孔内部气体示意图。
图5为根据本申请内容的另一实施例的检测芯片的注液装置的模块结构示意图。
图6a为根据本申请内容的另一实施例的检测芯片的注液装置的泵阀组件的正面结构示意图。
图6b为根据本申请内容的另一实施例的检测芯片的注液装置的泵阀组件的背面结构示意图。
图7为根据本申请内容的另一实施例的检测芯片的注液装置的抽真空组件和注液组件的装配示意图。
图8为根据本申请内容的另一实施例的检测芯片的注液装置的电子控制界面示意图。
图9为根据本申请内容的另一实施例的检测芯片的注液方法的流程示意图。
图10为根据本申请的另一实施例的实现检测芯片的注液方法的电子设备的结构示意图。
附图标记说明：
注液泵出口电磁阀       1；     注液泵入口电磁阀       2；
注液泵                 3；     真空泵                 4；
真空阀                 5；     电子控制板             6；
安装固定板             7；     真空罐盖板             8；
注液针                 9；     注液针固定件           10；
调节螺杆               11；    导向杆                 12；
芯片组件固定板         13；    芯片组件               14；
真空罐体               15；    基座                   161；
盖板                   1611；  凹陷区域               16111；
底板                   1612；  镂空区域               16121；
流体槽                 16122； 储气槽                 16123；
进液槽结构             1613；  紧固螺钉               162；
固定底座               163；   反应腔体               164；
检测芯片               17；    微孔                   171；
缓冲液容器             24；    真空检测压力表         25；
泄压调速阀             26；    气体过滤器             27。
具体实施方式
下面通过实施例的方式进一步说明本申请，但并不因此将本申请限制在所述的实施例范围之中。
应当注意，在说明书中对“一实施例”、“可选实施例”、“另一实施例”等的引用指示所描述的实施例可以包括特定的特征、结构或特性，但是每个实施例可能不一定包括该特定的特征、结构或特性。而且，这样的短语不一定指代相同的实施例。此外，当结合实施例描述特定特征、结构或特性时，无论是否被明确描述，结合其它实施例来实现这样的特征、结构或特性都在相关领域的技术人员的知识范围内。
在本申请内容的描述中，需要理解的是，术语“中心”、“横向”、“上”、“下”、“左”、 “右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本申请内容和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本申请内容的限制。此外，术语“第一”、“第二”仅用于描述目的，而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此，限定有“第一”、“第二”的特征可以明示或者隐含地包括一个或者更多个该特征。在本申请内容的描述中，除非另有说明，“多个”的含义是两个或两个以上。另外，术语“包括”及其任何变形，意图在于覆盖不排他的包含。
在本申请内容的描述中，需要说明的是，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本申请内容中的具体含义。
这里所使用的术语仅仅是为了描述具体实施例而不意图限制示例性实施例。除非上下文明确地另有所指，否则这里所使用的单数形式“一个”、“一项”还意图包括复数。还应当理解的是，这里所使用的术语“包括”和/或“包含”规定所陈述的特征、整数、步骤、操作、单元和/或组件的存在，而不排除存在或添加一个或更多其他特征、整数、步骤、操作、单元、组件和/或其组合。
检测芯片例如微孔阵列测序芯片主要由上千个微孔组成，而且微孔阵列内壁均为疏水性材料，电化学缓冲液的填充是其不可缺少的测序条件。
目前，使用先注液再抽真空的方式进行测序芯片的缓冲液填充，用密封垫或者其它方式使微孔阵列形成一个储液槽，在微孔阵列表面加入缓冲液，密封装置使溶液保持在测序芯片表面，然后放入真空罐内抽真空。此时，微孔阵列内部空气会随着真空罐内负压升高而被抽出，直至达到微孔内部与液体表面压力一致，但由于目前无法达到绝对真空，而且微孔阵列表面液体存在一定重力，即真空罐压力＝微孔内压力+液体重力，微孔阵列内部真空度小于真空罐内真空度，即有部分空气无法排出。另外，微孔内空气排出需要进入表面缓冲液内导致形成微小气泡，因表面张力作用部分较大气泡因压力变化会破裂，而部分微小气泡悬浮于缓冲液内无法排出，形成气液混合物，从而造成泄压后微孔阵列内部缓冲液为气液混合物，影响测序芯片工作稳定性。
为了克服目前存在的上述缺陷，本实施例提供一种检测芯片的注液装置，包括注液组件、抽真空组件、控制模块及如上述的检测芯片组件工装；检测芯片组件工装安装于 抽真空组件，注液组件用于向进液槽结构注入缓冲液；控制模块被配置为当向检测芯片填充缓冲液时，启动抽真空组件以将检测芯片组件工装内的空气排出；控制模块还被配置为响应于检测到检测芯片组件工装内形成预设真空条件后，启动注液组件以将缓冲液注入至进液槽结构，并且控制抽真空组件进行泄压，在负压作用下进液槽结构内的缓冲液沿着流体通道槽流入至反应腔体以填充检测芯片。
在本实施例中，检测芯片优选为测序芯片，但并不仅限于测序芯片，还可以为其他生物或化学检测芯片，可根据实际需求或可能出现的需求进行相应的调整或选择。该注液装置除了应用于测序领域，还可以应用于蛋白质分析、单细胞分析、药物筛选等其他不同的各个领域，在实现如上述的功能的基础上，还可结合实际需求或可能出现的需求进行相应的调整或选择。
在本实施例中，有效地利用先抽真空再进行自动注液的方式，使得检测芯片微孔阵列内的气体不经过溶液，从而有效地避免了气液混合物产生，而且无需人工使用移液枪操作，一键实现自动抽真空，自动注液，自动泄压，减少了人工成本，减少了工作人员与化学品接触，进而极大地提升了检测芯片的注液效率及精度。
作为一实施例，本实施例提供的检测芯片的注液装置主要包括检测芯片组件工装、抽真空组件、注液组件及控制模块。
如图1a及图1b所示，检测芯片组件工装主要包括基座161、若干个紧固螺钉162及固定底座163。
如图2b所示，基座161主要包括盖板1611及底板1612，其中，盖板1611盖设于底板1612，盖板1611上设有凹陷区域16111，底板1612上设有镂空区域16121，凹陷区域16111的底部(即盖板1611的底部)与镂空区域16121形成密闭的反应腔体164，底板1612上设有流体槽16122，流体槽16122与盖板1611的底部形成流体通道，盖板1611的顶部上还设有进液槽结构163。
作为可选实施方式，如图2a及2b所示，底板1612上还开设有储气槽16123，储气槽16123与盖板1611的底部形成密闭的储气位，储气位与反应腔体164连通。
参考图1a、图2a及图7所示，通过若干个紧固螺钉162将检测芯片17与基座161和固定底座163固定安装到一起，以形成芯片组件14，其中，从而形成密闭的反应腔体164、流体通道和储气位。
在本实施例中，并不具体限定紧固螺钉162的数量或固定检测芯片的方式，只要能够实现相应的固定效果，均可根据实际需求进行相应的调整及选择。
如图6b及图7所示，抽真空组件主要包括芯片组件固定板13、真空罐体15、真空 罐盖板8、抽气管路(图中未示出)、真空泵4及真空阀5。
芯片组件14安装于芯片组件固定板13上，芯片组件固定板13设置于真空罐体15内，真空罐盖板8盖设于真空罐体15上，抽气管路的一端设置于真空罐体15内，真空泵4设置于抽气管路上，并且用于抽取真空罐体15内的空气，真空阀5与真空泵4连接，并且通过控制真空阀的闭合来控制真空泵4的启动以抽取真空罐体15内的空气。
作为一优选实施方式，如图5所示，抽真空组件还包括真空检测压力表25、泄压调速阀26及至少两个气体过滤器27。
真空检测压力表25用于检测真空罐体15内的压强；泄压调速阀26与真空阀5连接，并且用于进行泄压并调节泄压速度。
两个气体过滤器27分别安装于真空泵4的出口和真空阀5的泄压口，分别防止电化学缓冲液的挥发造成实验环境污染，以及有效地防止了外界空气进入真空罐体15时灰尘杂质进入真空阀5导致故障和进入真空罐体15内造成缓冲液污染的情况。
在本实施例中，并不具体限定抽真空组件的类型，只要能够实现相应的功能，可利用其它真空发生器来替代真空泵。
如图5、6a、6b及图7所示，注液组件包括注液针9、注液针固定件10、注液泵3、注液泵入口电磁阀2、注液泵出口电磁阀1、连接管路、调节螺杆11、导向杆12及缓冲液容器24。
注液针9固定设置于注液针固定件10上，并且用于向进液槽结构1613注入缓冲液；注液针固定件10设置于真空罐体15内。
注液泵3通过连接管路与注液针9连接，并且用于向注液针9输送缓冲液。
注液泵入口电磁阀2与注液泵3的入口连接，注液泵出口电磁阀1与注液泵3的出口连接。
调节螺杆11设置于注液针固定件10上，并且用于调节注液针9与进液槽结构1613之间的距离。
导向杆12设置于芯片组件固定板13与注液针固定件10之间，以保证注液针上下运动时的位置精度。
缓冲液容器24通过连接管路与注液泵3连接，并且用于容纳缓冲液。
控制模块可分别与注液泵出口电磁阀1、注液泵入口电磁阀2、真空阀5、真空检测压力表25及泄压调速阀26通信连接。
在本实施例中，作为优选实施方式，共设计四路注液组件，每路注液组件的原理及物料基本相同，可根据实际需求进行相应的调整及选择。
在本实施例中，作为优选实施方式，设计同时处理四张微孔阵列检测芯片，将组装完成后的芯片组件放于芯片组件固定板13上，固定位根据芯片结构采用环形设计，充分利用平面空间。通过调节螺杆11调节注液针距离进液槽结构的高度，距离处于液面上方的高度优选为3mm-5mm，距离太高会造成溅液问题，距离太近容易造成注液针接触到缓冲液造成结晶问题，但并不具体限定该高度，可根据实际需求进行相应的调整及选择。
参考图6a及6b所示，控制模块可包括用于控制阀体的电子控制板6和用于执行计算和控制的计算机设备(图中未示出)，其中，注液泵3、真空泵4以及控制各类泵的各类阀体和电子控制板6均安装于安装固定板7，以节省安装空间并方便管理和维护。高精度注液泵需竖直固定，以便空气排出。
在本实施例中，控制模块被配置为当需要向检测芯片17填充电化学缓冲液时，启动抽真空组件，即启动相应的真空泵4以将检测芯片17内的空气(即整个芯片组件14的空气)排出，具体地，反应腔体164内的空气沿着由流体槽16122形成的流体通道从进液槽结构1613的排孔中排出，其中，利用真空检测压力表25实时检测真空罐体15内的压强并反馈至控制模块。
控制模块还被配置为响应于检测到芯片组件14内形成预设真空条件后，作为一可选实施方式，响应于检测到真空罐体15内的压强达到预设值后(可设定为达到系统最大真空度后)，启动注液组件，即启动相应的注液泵3以将缓冲液注入至进液槽结构，并且控制抽真空组件进行泄压，在负压作用下进液槽结构内的缓冲液沿着流体通道槽流入至反应腔体以填充检测芯片。
其中，储气位用于当缓冲液沿着流体通道流入至反应腔体时储存被缓冲液推入的残余空气，从而不影响微孔阵列检测芯片的工作性能。储气位设计在检测芯片末端，此处为非工作区，无需缓冲液完全填充，缓冲液从前往后注入时，残余空气被逐步推入储气位。
具体地，检测芯片组件工装使微孔阵列检测芯片形成一个半密闭容腔，利用漏斗型的排气口及进液槽结构，并启动真空泵将真空罐体抽至-95KPa～-100KPa，以排出检测芯片微孔内空气。当检测到真空罐体内达到预设真空条件后，启动注液组件向进液槽结构内进行注液，当启动注液组件时继续启动真空泵以保持抽取真空的状态，从而有效地防止由于注液流动导致的气泡的产生。
启动注液组件进行注液具体为：先开启注液泵入口电磁阀，此时注液泵会抽取缓冲液容器内的缓冲液，抽取一定量的缓冲液之后关闭注液泵入口电磁阀，再开启注液泵出口电磁阀，此时注液泵通过注液针将缓冲液注入至进液槽结构中。注入预设量(例如300ul) 的缓冲液后停止注液，并且等待预设时间段(例如可以为10s)，此后关闭真空泵，开启泄压调速阀，进行泄压以连通大气压，此时缓冲液在大气压的作用下流入至反应腔体，从而填充检测芯片，另外填充过程中的残留微量空气会被挤压至储气位。
电化学缓冲液放入缓冲液容器内，无需人为频繁接触；相应阀体可控制液体通断，保证在抽真空时形成密封，并保证液体不会溢出；高精度注液泵可精确控制注液量、注液速度及注液时间；注液针保证液体注液位置准确度，并减少挂液问题。
参考图3所示，检测芯片17的单个微孔171直径一般为几十微米至一百微米。传统注液方式会形成如图4a的结果，可以看出微孔171内气体无法排出(无填充部分表示气体，填充部分表示液体)，液体无法填充；本实施例填充情况如图4b所示，可以看出能够实现微孔171完全填充。
在本实施例中，参考图8所示，利用电子控制界面，控制模块能够实现全流程一键控制，芯片组件放于真空罐体内部后，点击电子控制界面定制运行便可实现全流程自动运行。运行后取出芯片组件，此时微孔内部已完成电化学缓冲液填充。同时可满足单体控制，可单独控制每个相应阀体的打开或关闭，柱塞泵运行等。
具体地，通过计算机设备(上位机)的电子控制界面与电子控制板6进行通信，可单独对每一个各类阀体进行单独的控制，也可以通过自主时序进行联合运行，减少人工参与，可自由选择控制通道数量，自行定义运行次数及循环方式，以实现全程自动化的控制手段。采用上位机下发逻辑指令的方式，通过高速数据线与电子控制板进行通信，并且利用握手信号判定、数据校验等方式，确保下发指令的正确性，让电子控制板控制相应元器件动作，以实现自动抽真空，自动注液，自动填充等动作，确保整个过程的准确性及无人干预性，从而确保电化学缓存液完全进入检测芯片微孔阵列内。
在本实施例中，可在计算机设备实现任何一个泵阀单体控制，也可以保存逻辑时序后一键运行，操作灵活方便，各参数可单独调整。
本实施例提供的检测芯片的注液装置，主要具有以下有益效果：
1、真空环境能有效排出检测芯片微孔阵列内部空气，储气位可有效地避免无法达到绝对真空造成空气残留微孔内的情况，从而能够实现电化学缓冲液对微孔阵列的有效填充；
2、无需人工使用移液枪操作，减少人工成本，减少工作人员与化学品接触；移液枪吸头为一次性耗材，本实施例无需使用吸头，从而节省了成本；
3、本实施例的注液装置的各元器件均可由控制模块电子控制，在计算机设备的客户端通过电子控制界面可进行一键操作，方便快捷，而且注液时间、注液速度、注液量均可 精确控制，从而提升了整体稳定性，可有效地避免人为误差。
作为另一实施例，本实施例提供一种检测芯片的注液方法，该注液方法利用如上述的检测芯片的注液装置来实现，如图9所示，该注液方法主要包括以下步骤：
步骤201、接收检测芯片填充缓冲液指令；
步骤202、启动抽真空组件以抽取芯片组件内的空气；
步骤203、获取真空罐体内的压强；
步骤204、响应于压强达到预设值，启动注液组件以将缓冲液填充至检测芯片。
具体地，在步骤201中，当需要向检测芯片填充电化学缓冲液时，将组装后的芯片组件放入至真空罐体内，并且工作人员通过电子控制界面下达填充缓冲液指令。
在步骤202中，启动抽真空组件，即启动相应的真空泵以将芯片组件内的空气排出。
在步骤203中，利用真空检测压力表实时检测真空罐体内的压强并反馈至控制模块。
在步骤204中，响应于检测到真空罐体内的压强达到预设值后，启动注液组件以将缓冲液注入至进液槽结构，并且控制抽真空组件进行泄压，在负压作用下进液槽结构内的缓冲液沿着流体通道槽流入至反应腔体以填充检测芯片。
本实施例提供的检测芯片的注液方法，有效地利用先抽真空再进行自动注液的方式，使得检测芯片微孔阵列内的气体不经过溶液，从而有效地避免了气液混合物产生，而且无需人工使用移液枪操作，一键实现自动抽真空，自动注液，自动泄压，减少了人工成本，减少了工作人员与化学品接触，进而极大地提升了检测芯片的注液效率及精度。
图10为根据本实施例提供的一种电子设备的结构示意图。电子设备包括存储器、处理器及存储在存储器上并可在处理器上执行的计算机程序，处理器执行程序时实现如上实施例中的检测芯片的注液方法。图10显示的电子设备30仅仅是一个示例，不应对本申请实施例的功能和使用范围带来任何限制。
如图10所示，电子设备30可以以通用计算设备的形式表现，例如其可以为服务器设备。电子设备30的组件可以包括但不限于：上述至少一个处理器31、上述至少一个存储器32、连接不同系统组件(包括存储器32和处理器31)的总线33。
总线33包括数据总线、地址总线和控制总线。
存储器32可以包括易失性存储器，例如随机存取存储器(RAM)321和/或高速缓存存储器322，还可以进一步包括只读存储器(ROM)323。
存储器32还可以包括具有一组(至少一个)程序模块324的程序/实用工具325，这样的程序模块324包括但不限于：操作系统、一个或者多个应用程序、其它程序模块以及程序数据，这些示例中的每一个或某种组合中可能包括网络环境的实现。
处理器31通过执行存储在存储器32中的计算机程序，从而执行各种功能应用以及数据处理，例如本申请如上实施例中的检测芯片的注液方法。
电子设备30也可以与一个或多个外部设备34(例如键盘、指向设备等)通信。这种通信可以通过输入/输出(I/O)接口35进行。并且，模型生成的设备30还可以通过网络适配器36与一个或者多个网络(例如局域网(LAN)，广域网(WAN)和/或公共网络，例如因特网)通信。如图10所示，网络适配器36通过总线33与模型生成的设备30的其它模块通信。应当明白，尽管图中未示出，可以结合模型生成的设备30使用其它硬件和/或软件模块，包括但不限于：微代码、设备驱动器、冗余处理器、外部磁盘驱动阵列、RAID(磁盘阵列)系统、磁带驱动器以及数据备份存储系统等。
应当注意，尽管在上文详细描述中提及了电子设备的若干单元/模块或子单元/模块，但是这种划分仅仅是示例性的并非强制性的。实际上，根据本申请的实施方式，上文描述的两个或更多单元/模块的特征和功能可以在一个单元/模块中具体化。反之，上文描述的一个单元/模块的特征和功能可以进一步划分为由多个单元/模块来具体化。
本实施例还提供了一种计算机可读存储介质，其上存储有计算机程序，程序被处理器执行时实现如上实施例中的检测芯片的注液方法中的步骤。
其中，可读存储介质可以采用的更具体可以包括但不限于：便携式盘、硬盘、随机存取存储器、只读存储器、可擦拭可编程只读存储器、光存储器件、磁存储器件或上述的任意合适的组合。
在可能的实施方式中，本申请还可以实现为一种程序产品的形式，其包括程序代码，当程序产品在终端设备上执行时，程序代码用于使终端设备执行实现如上实施例中的检测芯片的注液方法中的步骤。
其中，可以以一种或多种程序设计语言的任意组合来编写用于执行本申请的程序代码，程序代码可以完全地在用户设备上执行、部分地在用户设备上执行、作为一个独立的软件包执行、部分在用户设备上部分在远程设备上执行或完全在远程设备上执行。
虽然以上描述了本申请的具体实施方式，但是本领域的技术人员应当理解，这仅是举例说明，本申请的保护范围是由所附权利要求书限定的。本领域的技术人员在不背离本申请的原理和实质的前提下，可以对这些实施方式做出多种变更或修改，但这些变更和修改均落入本申请的保护范围。

Claims (13)

  1. 一种检测芯片组件工装，其特征在于，用于安装于抽真空组件；
    所述检测芯片组件工装，包括：
    基座，用于安装于检测芯片上，所述基座分别设有用于覆盖所述检测芯片的反应腔体以及与所述反应腔体连通的流体通道，所述基座还设有与所述流体通道连通并用于注入缓冲液的进液槽结构；
    其中，当向所述检测芯片填充缓冲液时，启动所述抽真空组件以将所述检测芯片组件工装内的空气排出，响应于所述抽真空组件抽真空后进行泄压，在负压作用下所述进液槽结构内的所述缓冲液沿着所述流体通道流入至所述反应腔体以填充所述检测芯片。
  2. 如权利要求1所述的检测芯片组件工装，所述基座包括盖板及底板，所述盖板盖设于所述底板上；
    所述盖板上设有凹陷区域，所述底板上设有镂空区域，所述凹陷区域的底部与所述镂空区域形成所述反应腔体；
    所述底板上开设有流体槽，所述流体槽与所述盖板的底部形成所述流体通道；
    所述盖板的顶部上设有所述进液槽结构。
  3. 如权利要求2所述的检测芯片组件工装，所述底板上还开设有储气槽，所述储气槽与所述盖板的底部形成储气位；
    所述储气位与所述反应腔体连通，并且用于当所述缓冲液填充至所述反应腔体时储存被所述缓冲液推入的残余空气。
  4. 如权利要求1～3中任意一项所述的检测芯片组件工装，所述检测芯片组件工装还包括固定底座；
    所述检测芯片固定安装于所述固定底座上。
  5. 一种检测芯片的注液装置，其特征在于，包括注液组件、抽真空组件、控制模块及如权利要求1～4中任意一项所述的检测芯片组件工装；
    所述检测芯片组件工装安装于所述抽真空组件，所述注液组件用于向所述进液槽结构注入缓冲液；
    所述控制模块被配置为当向所述检测芯片填充缓冲液时，启动所述抽真空组件以将所述检测芯片组件工装内的空气排出；
    所述控制模块还被配置为响应于检测到所述检测芯片组件工装内形成预设真空条件后，启动所述注液组件以将缓冲液注入至所述进液槽结构，并且控制所述抽真空组件进 行泄压，在负压作用下所述进液槽结构内的缓冲液沿着所述流体通道槽流入至所述反应腔体以填充所述检测芯片。
  6. 如权利要求5所述的检测芯片的注液装置，所述抽真空组件包括芯片组件固定板、真空罐体、真空罐盖板、抽气管路、真空泵及真空阀；
    所述检测芯片组件工装安装于所述芯片组件固定板上；
    所述芯片组件固定板固定设置于所述真空罐体内；
    所述真空罐盖板盖设于所述真空罐体上；
    所述抽气管路的一端设置于所述真空罐体内；
    所述真空泵设置于所述抽气管路上，并且用于抽取所述真空罐体内的空气；
    所述真空阀与所述真空泵连接，并且与所述控制模块通信连接。
  7. 如权利要求6所述的检测芯片的注液装置，所述抽真空组件还包括真空检测压力表、泄压调速阀及气体过滤器；
    所述真空检测压力表与所述控制模块通信连接，并且用于检测所述真空罐体内的压强；
    所述泄压调速阀与所述真空阀连接，并且用于进行泄压并调节泄压速度；
    所述气体过滤器设置于所述抽气管路上。
  8. 如权利要求6所述的检测芯片的注液装置，所述注液组件包括注液针、注液针固定件、注液泵、注液泵入口电磁阀、注液泵出口电磁阀及连接管路；
    所述注液针固定设置于所述注液针固定件上，并且用于向所述进液槽结构注入所述缓冲液；
    所述注液针固定件设置于所述真空罐体内；
    所述注液泵通过所述连接管路与所述注液针连接，并且用于向所述注液针输送缓冲液；
    所述注液泵入口电磁阀与所述注液泵的入口连接，并且与所述控制模块通信连接；
    所述注液泵出口电磁阀与所述注液泵的出口连接，并且与所述控制模块通信连接。
  9. 如权利要求8所述的检测芯片的注液装置，所述注液组件还包括调节螺杆及导向杆；
    所述调节螺杆设置于所述注液针固定件上，并且用于调节所述注液针与所述进液槽结构之间的距离；
    所述导向杆设置于所述芯片组件固定板与所述注液针固定件之间。
  10. 如权利要求8所述的检测芯片的注液装置，所述注液组件还包括缓冲液容器；
    所述缓冲液容器通过所述连接管路与所述注液泵连接，并且用于容纳所述缓冲液。
  11. 一种检测芯片的注液方法，其特征在于，利用如权利要求5～10中任意一项所述的检测芯片的注液装置来实现，所述注液方法包括：
    当向所述检测芯片填充缓冲液时，启动所述抽真空组件以将所述检测芯片组件工装内的空气排出；
    响应于检测到所述检测芯片组件工装内形成预设真空条件后，启动所述注液组件以将缓冲液注入至所述进液槽结构，并且控制所述抽真空组件进行泄压，在负压作用下所述进液槽结构内的缓冲液沿着所述流体通道槽流入至所述反应腔体以填充所述检测芯片。
  12. 一种电子设备，包括存储器、处理器及存储在存储器上并可在处理器上运行的计算机程序，其特征在于，所述处理器执行计算机程序时实现如权利要求11所述的检测芯片的注液方法。
  13. 一种计算机可读介质，其上存储有计算机指令，其特征在于，所述计算机指令在由处理器执行时实现如权利要求11所述的检测芯片的注液方法。
PCT/CN2021/131232 2021-11-17 2021-11-17 检测芯片组件工装、注液装置、方法、电子设备和介质 WO2023087179A1 (zh)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007107916A (ja) * 2005-10-11 2007-04-26 Shimadzu Corp マイクロチップへの分離バッファ液充填装置とそれを備えたマイクロチップ処理装置
JP2007212256A (ja) * 2006-02-08 2007-08-23 Matsushita Electric Ind Co Ltd 生体関連物質検出用反応装置
CN206215248U (zh) * 2016-11-07 2017-06-06 华南理工大学 一种负压引导的微流体自律运动的微流控芯片
CN107262169A (zh) * 2017-06-22 2017-10-20 浙江诺迦生物科技有限公司 负压驱动、涡旋混匀的微流控芯片机械式负压进样装置
CN207215838U (zh) * 2017-05-10 2018-04-10 王伟丽 一种宫颈癌hpv快速检测装置用试纸
CN113441197A (zh) * 2021-05-31 2021-09-28 昆明理工大学 赤泥中有价元素检测萃取并联型集成芯片及其设计方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007107916A (ja) * 2005-10-11 2007-04-26 Shimadzu Corp マイクロチップへの分離バッファ液充填装置とそれを備えたマイクロチップ処理装置
JP2007212256A (ja) * 2006-02-08 2007-08-23 Matsushita Electric Ind Co Ltd 生体関連物質検出用反応装置
CN206215248U (zh) * 2016-11-07 2017-06-06 华南理工大学 一种负压引导的微流体自律运动的微流控芯片
CN207215838U (zh) * 2017-05-10 2018-04-10 王伟丽 一种宫颈癌hpv快速检测装置用试纸
CN107262169A (zh) * 2017-06-22 2017-10-20 浙江诺迦生物科技有限公司 负压驱动、涡旋混匀的微流控芯片机械式负压进样装置
CN113441197A (zh) * 2021-05-31 2021-09-28 昆明理工大学 赤泥中有价元素检测萃取并联型集成芯片及其设计方法

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