CN115074231A - High-throughput automation equipment for monoclonal selection - Google Patents

High-throughput automation equipment for monoclonal selection Download PDF

Info

Publication number
CN115074231A
CN115074231A CN202210637601.8A CN202210637601A CN115074231A CN 115074231 A CN115074231 A CN 115074231A CN 202210637601 A CN202210637601 A CN 202210637601A CN 115074231 A CN115074231 A CN 115074231A
Authority
CN
China
Prior art keywords
channel
picking head
picking
assembly
head
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202210637601.8A
Other languages
Chinese (zh)
Inventor
陈皓
杨开琳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Innovel Intelligent Technology Suzhou Co Ltd
Original Assignee
Innovel Intelligent Technology Suzhou Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Innovel Intelligent Technology Suzhou Co Ltd filed Critical Innovel Intelligent Technology Suzhou Co Ltd
Priority to CN202210637601.8A priority Critical patent/CN115074231A/en
Publication of CN115074231A publication Critical patent/CN115074231A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48Automatic or computerized control
    • 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
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/02Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by impregnation, e.g. using swabs or loops
    • 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
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/08Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by vibration
    • 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
    • C12M39/00Means for cleaning the apparatus or avoiding unwanted deposits of microorganisms
    • 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Computer Hardware Design (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention relates to the technical field of biological pharmacy, in particular to high-throughput automatic equipment for monoclonal selection, which comprises an operation table and a control computer, wherein an X-Y linear motor portal frame is arranged at the top of the operation table, a 96-channel picking head assembly is arranged on the left side of the X-Y linear motor portal frame, a picking head sterilizing and cleaning assembly is arranged at the top of the operation table and below the 96-channel picking head assembly, a channel pipetting assembly is arranged on the right side of the X-Y linear motor portal frame, and a shaking-uniform coating assembly is arranged at the top of the operation table and below the channel pipetting assembly, the online collection of mass data is realized, and the comprehensive efficiency of data collection, arrangement, analysis and mining in the research and development process is effectively improved.

Description

High-throughput automation equipment for monoclonal selection
Technical Field
The invention relates to the technical field, in particular to high-throughput automatic equipment for monoclonal selection.
Background
The application of biological medicines, synthetic organisms and the like is in the rapid development stage, the monoclonal selection is taken as an important link of research and development and production, the application of the method is more and more extensive, after the carrier cells and bacteria are cultured, the carrier cells and bacteria are required to be subjected to monoclonal selection, the cells and bacteria are suitable for continuous amplification of subsequent processes, ten thousand-level selection quantity is required every day for selecting suitable target bacteria and cells, however, a single person for manual operation can only achieve hundred-level selection quantity every day, the requirement of high-speed large-scale research and development production is difficult to meet, a large staff team and a large-scale field are required in the traditional manual operation mode, a specially trained high-skilled person is required at the first line, and therefore research institutions or enterprises need to bear higher manpower resource cost, meanwhile, the operation of different personnel can bring about the problems of unstable and complicated process and the like, and the unified and stable operation standard is difficult to form.
Disclosure of Invention
The present invention is directed to an automated apparatus for single clone selection with high throughput, which solves the above-mentioned problems of the background art.
In order to achieve the purpose, the invention provides the following technical scheme:
the utility model provides a high flux is used for automation equipment that monoclonal was selected, includes operation panel and control computer, the top of operation panel is provided with X-Y linear electric motor portal frame, the left side of X-Y linear electric motor portal frame is provided with 96 passageway components of picking head, the top of operation panel and be provided with the sterilization of picking head and wash the subassembly in 96 passageway components of picking head's below, the right side of X-Y linear electric motor portal frame is provided with the passageway and moves the liquid subassembly, the top of operation panel and the below of passageway move the liquid subassembly be provided with shake even coating module the top of operation panel and be provided with LED orifice plate ware of shooing in the front of picking head sterilization and wash the subassembly, the top center department of operation panel installs consumptive material carrier sliding table matrix, the top of operation panel and all be provided with the conveyer belt in the both sides of consumptive material carrier sliding table matrix, the top of operation panel and be provided with pump liquid cabin in the top of shaking even coating module, the device comprises an operation table, and is characterized in that a laminar flow air inlet static pressure box is arranged at the top of the operation table, an air exhaust and air collection box body is arranged at the bottom of the operation table, a laminar flow air exhaust static pressure box is arranged at the bottom of the air exhaust and air collection box body, a liquid storage tank is arranged at the bottom of the operation table and on the left side of the laminar flow air exhaust static pressure box, a solid waste collecting tank is arranged at the bottom of the operation table and on the right side of the laminar flow air exhaust static pressure box, and a pore plate clamping jaw robot is arranged on the outer wall of the X-Y linear motor portal frame and on the left side of a channel liquid transfer assembly;
96 passageway is picked first subassembly including installing the Z axle motor on X-Y linear electric motor portal frame, the support is installed in making of Z axle motor, the internally mounted of support has collection dress gas circuit switch valves, the inside of support and be provided with pneumatic flexible subassembly in collection dress gas circuit switch valves's below, pneumatic flexible subassembly is connected with the ram through picking the first connecting piece, distance sensor and camera are installed from left to right in proper order in the front of support, the outer wall of support and be provided with the distribution valve piece in collection dress gas circuit switch valves's top, the air supply control valve is just installed in collection dress gas circuit switch valves's front to the outer wall of support.
As a preferable scheme of the invention, the picking head sterilizing and cleaning assembly comprises a picking head drying groove arranged at the top of an operation table, a heating array is arranged on the inner wall of the picking head drying groove, a cooling fan is arranged on the inner wall of the picking head drying groove and at a position close to the heating array, an air outlet is formed in the bottom of the inner wall of the picking head drying groove, and a first alcohol cleaning groove, a second alcohol cleaning groove and a hydrogen peroxide ultrasonic cleaning groove are sequentially arranged at the top of the operation table and in the front of the picking head drying groove from left to right.
According to the preferable scheme of the invention, the shaking and coating assembly comprises a driving motor arranged at the top of the operating platform, a cam oscillating mechanism is arranged at the top end of an output shaft of the driving motor, a clamping mechanism is arranged at the top of the cam oscillating mechanism, and an in-situ sensor is arranged on the outer wall of the cam oscillating mechanism.
As a preferred scheme of the present invention, the specific work flow of the 96-channel picking head assembly is as follows: firstly, a 96-channel picker assembly is transferred to a target hole plate position by an X-Y linear motor portal frame to finish primary aiming, the X-Y linear motor portal frame continues to drive the 96-channel picker assembly to move, a distance sensor finishes planeness scanning of a selecting plate and calibrates a height distance, meanwhile, a camera carries out real-time picture shooting to finish real-time position calculation of target bacteria or cells, a computer is controlled to finish selecting sequence scheduling, then, the position of the target bacteria or cells is selected, the X-Y linear motor portal frame moves to an accurate aiming position, the position is quickly confirmed by the camera, a Z-axis motor micro-motion is adjusted to match the local height of the selecting position, a single-channel air valve in an air channel switch valve group moves to finish up-and-down movement of the single-channel picker to realize selecting operation, the next single-clone selecting target is selected, and the operation of the previous step is repeated, until the 96-well plate completed the elution of the whole plate monoclonal picked product.
As a preferred scheme of the invention, the tail end of the picking head is specially designed for achieving the best picking effect and transfer safety and preventing the picking head from falling off in the carrying process, the picking head is made of a material meeting GMP requirements, the guide part of the picking head is made of a wear-resistant material meeting FDA (food and drug administration) certification, the picking head is in floating connection with the picking head connecting piece, the processing and assembling difficulty is reduced on the premise of ensuring the precision of the multi-channel picking head, the head driving unit and the control element thereof are in modular design, the integration of the random flux from a single channel to 96 channels can be realized, the tail end of the multi-channel picking head is unified to be hard limited, the descending distance of the picking head is accurate due to the plane formed in one step, and the support is provided with the mounting hole of the picking head formed in one step.
As a preferred scheme of the present invention, the specific work flow of the picking head sterilization cleaning assembly is as follows: the picking head is sequentially sent into the hydrogen peroxide ultrasonic cleaning tank, the second alcohol cleaning tank and the first alcohol cleaning tank for circular cleaning, after the circular cleaning is finished, the picking head is sent into the picking head drying tank for heat source irradiation drying, and the picking head is cooled by the cooling fan.
As a preferable scheme of the invention, the air outlet is connected with the exhaust gas collecting box body through a pipeline, the heating array is made of a plurality of groups of infrared heating pipes, two groups of heating arrays are arranged, and the two groups of heating arrays are symmetrically arranged on the inner wall of the picking head drying groove.
As a preferable scheme of the invention, the specific working flow of the shaking coating component is as follows: the agar plate for coating is transferred into the shaking-up coating assembly, the 96-channel pick-head assembly fills process liquid into each hole of the agar plate, the driving motor drives the agar plate to vibrate through the cam vibration mechanism based on a set rotating speed, so that the process liquid is uniformly coated on the surface of the agar plate, the 96-channel pick-head assembly fills bacteria or cell solution onto the surface of the agar plate, and the driving motor drives the agar plate to vibrate through the cam vibration mechanism based on the set rotating speed, so that the bacteria or cell solution is uniformly coated on the surface of the agar plate.
As a preferred scheme of the present invention, the control computer is internally installed with integrated software, which ensures that the whole system operates fully automatically, and realizes the integrated collection, storage and analysis functions of data in the operation process, and the integrated software comprises a process editing module having the functions of editing and managing a full-process list, providing a standardized process template, and managing, controlling and adjusting a real-time process; the device operation monitoring and operating module is used for recording sample liquid operation historical data, sample coating operation historical data, sample monoclonal selection historical data and sample transfer operation historical data, and monitoring the operation state of each device module, solid consumable material sample loading management and liquid material sample loading management; the device debugging working module has the functions of calibrating and correcting each motion module in the system, calibrating and correcting each liquid unit in the system, intelligently selecting and teaching a monoclonal sample and teaching a sample coating process; the data storage module has the function of singly selecting and storing original image data; the log prompting module has the functions of recording login information of operators, material loading information, equipment fault information in the running process, equipment warning information in the running process and equipment operation information in the running process; the setting module has the functions of personnel permission setting, parameter setting of each module of the system, liquid pipeline type configuration, liquid capacity configuration, liquid unit operation parameter configuration, monoclonal sample intelligent image identification configuration and coating motion parameter configuration.
Compared with the prior art, the invention has the beneficial effects that:
1. in the invention, the processing flux can be improved by more than two orders of magnitude by comparing with manual work, the full-automatic processing of the high-flux sample is realized, the scale benefit is effectively generated by amplification, the production cost of a single sample can be optimized by orders of magnitude, the site requirement is reduced by orders of magnitude, the infrastructure cost is greatly reduced, the standardized operation is realized, the uniformity, the stability and the reproducibility of the process flow are greatly improved, after the standardized operation, the multi-site and multi-scene deployment is convenient, the biological safety of personnel, samples and installation environment in the process operation process is ensured, the data collection, the storage and the comprehensive application of the whole process flow are realized with high efficiency, the cross contamination of different batches of samples in the culture process in the scale production process is effectively avoided, the high cleanliness of the samples and the environment in the production process is continuously maintained, the humanized operation of the whole process flow is realized, and the different process operation requirements are highly matched, flexible process editing capacity, common process flows stored in system software, high-speed process switching in a research and development stage, full-flow data collection and storage analysis, and avoidance of a large amount of manual case work.
Drawings
FIG. 1 is a schematic perspective view of the present invention;
FIG. 2 is a schematic top view of the basic structure of the present invention;
FIG. 3 is a schematic axial-side perspective view of a 96-channel picker assembly of the present invention;
FIG. 4 is a schematic perspective view of a single pick-up head channel and a 96-channel module according to the present invention;
FIG. 5 is a basic flow chart of the present invention for single clone selection;
FIG. 6 is a perspective view of the oscillation coating unit according to the present invention;
FIG. 7 is a flow chart of the inventive oscillatory coating process;
FIG. 8 is a top view of the picking head cleaning array of the monoclonal picking unit of the present invention;
FIG. 9 is a schematic view of a three-dimensional structure formed by the picking head cleaning and drying tank of the monoclonal picking unit of the present invention;
FIG. 10 is a basic flow chart of the present invention for the cleaning of the pick head;
FIG. 11 is a basic schematic diagram of laminar flow in the apparatus of the present invention;
FIG. 12 is a diagram of the basic architecture of the electrical system of the present invention;
FIG. 13 is a block diagram of the integrated software architecture of the present invention.
In the figure: 1. an operation table; 2. x, Y gantry of linear motor; 3. a 96-channel picker assembly; 4. a picking head sterilization cleaning component; 5. a channel pipetting assembly; 6. shaking up the coating component; 7. an LED orifice plate camera; 8. a consumable carrier sliding table matrix; 9. a conveyor belt; 10. a pump liquid tank; 11. a control computer; 12. synthesizing software; 13. a hole plate gripper robot; 101. a laminar air inlet plenum box; 102. an exhaust gas collection box body; 103. a laminar flow exhaust plenum box; 104. a liquid storage tank; 105. a solid waste collection tank; 121. a flow editing module; 122. a monitoring and operating module; 123. debugging a working module; 124 a data storage module; 125. a log prompting module; 126. setting a module; 301. a Z-axis motor; 302. a support; 303. assembling a gas circuit switch valve group; 304. a pneumatic telescoping assembly; 305. a ram connecting piece; 306. picking a head; 307. a distance sensor; 308. a camera; 309. a distribution valve block; 310. a gas source control valve; 401. a ram drying groove; 402. heating the array; 403. a cooling fan; 404. an air outlet; 405. a first alcohol cleaning tank; 406. a second alcohol cleaning tank; 407. a hydrogen peroxide ultrasonic cleaning tank; 601. a drive motor; 602. a cam oscillating mechanism; 603. a chucking mechanism; 604. an in-situ sensor.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments, and all other embodiments obtained by a person of ordinary skill in the art without any creative work based on the embodiments of the present invention belong to the protection scope of the present invention.
While several embodiments of the present invention will be described more fully hereinafter with reference to the accompanying drawings, in order to facilitate an understanding of the invention, the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather should be construed to provide a more complete disclosure of the invention.
It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present, that when an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present, and that the terms "vertical", "horizontal", "left", "right" and the like are used herein for descriptive purposes only.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, and the terms used herein in the specification of the present invention are for the purpose of describing particular embodiments only and are not intended to limit the present invention, and the term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Referring to fig. 1-13, the present invention provides a technical solution:
a high-throughput automation device for monoclonal selection comprises an operation table 1 and a control computer 11, wherein an X-Y linear motor portal frame 2 is arranged at the top of the operation table 1, a 96-channel picking head assembly 3 is arranged on the left side of the X-Y linear motor portal frame 2, a picking head sterilizing and cleaning assembly 4 is arranged at the top of the operation table 1 and below the 96-channel picking head assembly 3, a channel pipetting assembly 5 is arranged on the right side of the X-Y linear motor portal frame 2, a shaking uniform coating assembly 6 is arranged at the top of the operation table 1 and below the channel pipetting assembly 5, an LED orifice plate photographing device 7 is arranged at the top of the operation table 1 and on the front side of the picking head sterilizing and cleaning assembly 4, a consumable carrier matrix 8 is arranged at the center of the top of the operation table 1, conveyor belts 9 are arranged at the top of the operation table 1 and on two sides of the consumable carrier matrix 8, a liquid pumping cabin 10 is arranged at the top of the operating platform 1 and above the shaking coating assembly 6, a laminar flow air inlet static pressure box 101 is arranged at the top of the operating platform 1, an air exhaust and air collection box body 102 is arranged at the bottom of the operating platform 1, a laminar flow air exhaust static pressure box 103 is arranged at the bottom of the air exhaust and air collection box body 102, a liquid storage tank 104 is arranged at the bottom of the operating platform 1 and on the left side of the laminar flow air exhaust static pressure box 103, a solid waste collecting tank 105 is arranged at the bottom of the operating platform 1 and on the right side of the laminar flow air exhaust static pressure box 103, and a pore plate clamping jaw robot 13 is arranged on the outer wall of the X-Y linear motor portal frame 2 and on the left side of the channel liquid moving assembly 5;
the 96-channel pick head assembly 3 comprises a Z-axis motor 301 installed on an X-Y linear motor portal frame 2, a support 302 is installed on the Z-axis motor 301, an integrated air circuit switch valve group 303 is installed inside the support 302, a pneumatic telescopic assembly 304 is arranged inside the support 302 and below the integrated air circuit switch valve group 303, the pneumatic telescopic assembly 304 is connected with a pick head 306 through a pick head connecting piece 305, a distance sensor 307 and a camera 308 are sequentially installed on the front surface of the support 302 from left to right, a distribution valve block 309 is arranged on the outer wall of the support 302 and above the integrated air circuit switch valve group 303, and an air source control valve 310 is installed on the outer wall of the support 302 and on the front surface of the integrated air circuit switch valve group 303.
Further, the picking head sterilizing and cleaning assembly 4 comprises a picking head drying groove 401 arranged at the top of the operating platform 1, a heating array 402 is arranged on the inner wall of the picking head drying groove 401, a cooling fan 403 is arranged on the inner wall of the picking head drying groove 401 and at a position close to the heating array 402, an air outlet 404 is formed in the bottom of the inner wall of the picking head drying groove 401, and a first alcohol cleaning groove 405, a second alcohol cleaning groove 406 and a hydrogen peroxide ultrasonic cleaning groove 407 are sequentially arranged at the top of the operating platform 1 and in the front of the picking head drying groove 401 from left to right.
Further, the shaking coating assembly 6 comprises a driving motor 601 installed at the top of the operation table 1, a cam oscillating mechanism 602 is installed at the top end of an output shaft of the driving motor 601, a clamping mechanism 603 is installed at the top of the cam oscillating mechanism 602, and an in-situ sensor 604 is installed on the outer wall of the cam oscillating mechanism 602.
Further, the specific work flow of the 96-channel picking head assembly 3 is as follows: firstly, the 96-channel picker assembly 3 is transferred to a target hole plate position by the X-Y linear motor portal frame 2 to finish primary aiming, the X-Y linear motor portal frame 2 continuously drives the 96-channel picker assembly 3 to move, the flatness scanning of a selected plate and the height distance calibration are finished by the distance sensor 307, meanwhile, the camera 308 carries out real-time picture shooting to finish the calculation of the real-time position of target bacteria or cells, the computer 11 is controlled to finish the selection sequence scheduling, then, the position of the target bacteria or cells is selected, the X-Y linear motor portal frame 2 moves to an accurate aiming position, the camera 308 quickly confirms the position, the Z-axis motor 301 is micro-regulated to match the local height of the selected position, the single-channel air valve in the air channel switch valve group 303 is assembled to move, the single-channel picker 306 moves up and down to realize the selection operation, and the next single-clone selected target, the above procedure was repeated until the 96-well plate was finished with elution of the whole plate monoclonal picked product.
Furthermore, the tail end of the picking head 306 is specially designed for achieving the best selecting effect and transferring safety and preventing the picking head from falling in the carrying process, the picking head 306 is made of a material meeting GMP requirements, the guide part of the picking head 306 is made of a wear-resistant material meeting FDA certification, the picking head 306 is in floating connection with the picking head connecting piece 305, machining and assembling difficulty is reduced on the premise of ensuring multichannel picking head precision, the head driving unit and the control element of the head driving unit are in modular design, single-channel to 96-channel random flux integration can be achieved, the tail end of the multichannel picking head 306 is unified and hard to limit, the precision of the dropping distance of the picking head is guaranteed on the plane formed in one-step machining mode, and the support 302 is provided with a mounting hole of the picking head 306 formed in one-step machining mode.
Further, the specific work flow of the picking head sterilizing and cleaning assembly 4 is as follows: the picking head 306 is sequentially sent to the hydrogen peroxide ultrasonic cleaning tank 407, the second alcohol cleaning tank 406 and the first alcohol cleaning tank 405 to be circularly cleaned, after the circular cleaning is finished, the picking head 306 is sent to the picking head drying tank 401 to be subjected to heat source irradiation drying, and the picking head 306 is cooled by the cooling fan 403.
Further, the exhaust outlet 404 is connected with the exhaust gas collection box body 102 through a pipeline, the heating arrays 402 are made of a plurality of groups of infrared heating pipes, two groups of heating arrays 402 are arranged, and the two groups of heating arrays 402 are symmetrically arranged on the inner wall of the picking head drying groove 401.
Further, the specific working flow of the shaking coating component 6 is as follows: the agar plate for coating is transferred into the shaking-up coating component 6, the 96-channel pick-head component 3 fills process liquid into each hole position of the agar plate, the drive motor 601 drives the agar plate to vibrate through the cam vibration mechanism 602 based on the set rotating speed, so that the process liquid is uniformly coated on the surface of the agar plate, the 96-channel pick-head component 3 fills bacteria or cell solution onto the surface of the agar plate, and the drive motor 601 drives the agar plate to vibrate through the cam vibration mechanism 602 based on the set rotating speed, so that the bacteria or cell solution is uniformly coated on the surface of the agar plate.
Furthermore, the control computer 11 is internally provided with integrated software 12, which ensures the whole system to operate fully automatically and realizes the integrated collection, storage and analysis functions of data in the operation process, and the integrated software 12 comprises a process editing module 121 with the functions of editing and managing a full-process list, providing a standardized process template and controlling and adjusting a real-time process; the equipment operation monitoring and operating module 122 is used for recording sample liquid operation historical data, sample coating operation historical data, sample monoclonal selection historical data and sample transfer operation historical data, and monitoring the operation state of each equipment module, sample loading management of solid consumables and sample loading management of liquid materials; an equipment debugging working module 123 with the functions of calibrating and correcting each motion module in the system, calibrating and correcting each liquid unit in the system, intelligently selecting and teaching a monoclonal sample and teaching a sample coating process; a data storage module 124 having a function of storing original image data selected by a single clone; a log prompt module 125 having functions of recording operator login information, material loading information, equipment failure information in the running process, equipment warning information in the running process, and equipment operation information in the running process; and the setting module 126 has the functions of personnel permission setting, parameter setting of each module of the system, liquid pipeline type configuration, liquid capacity configuration, liquid unit operation parameter configuration, monoclonal sample intelligent image identification configuration and coating motion parameter configuration.
The working process of the invention is as follows: firstly, the 96-channel picker assembly 3 is transferred to a target hole plate position by the X-Y linear motor portal frame 2 to finish primary aiming, the X-Y linear motor portal frame 2 continuously drives the 96-channel picker assembly 3 to move, the flatness scanning of a selected plate and the height distance calibration are finished by the distance sensor 307, meanwhile, the camera 308 carries out real-time picture shooting to finish the calculation of the real-time position of target bacteria or cells, the computer 11 is controlled to finish the selection sequence scheduling, then, the position of the target bacteria or cells is selected, the X-Y linear motor portal frame 2 moves to an accurate aiming position, the camera 308 quickly confirms the position, the Z-axis motor 301 is micro-regulated to match the local height of the selected position, the single-channel air valve in the air channel switch valve group 303 is assembled to move, the single-channel picker 306 moves up and down to realize the selection operation, and the next single-clone selected target, repeating the operation of the previous step until the elution of the monoclonal picked product of the whole plate is completed by a 96-well plate;
transferring the agar plate for coating into the shaking-up coating component 6, filling the process liquid into each hole position of the agar plate by the 96-channel pick-up head component 3, driving the agar plate to vibrate by the cam vibration mechanism 602 based on the set rotating speed by the driving motor 601, realizing the uniform coating of the process liquid on the surface of the agar plate, filling the bacteria or cell solution onto the surface of the agar plate by the 96-channel pick-up head component 3, driving the agar plate to vibrate by the cam vibration mechanism 602 based on the set rotating speed by the driving motor 601, and realizing the uniform coating of the bacteria or cell solution on the surface of the agar plate;
the picking head 306 is sequentially sent to the hydrogen peroxide ultrasonic cleaning tank 407, the second alcohol cleaning tank 406 and the first alcohol cleaning tank 405 to be circularly cleaned, after the circular cleaning is finished, the picking head 306 is sent to the picking head drying tank 401 to be subjected to heat source irradiation drying, and the picking head 306 is cooled by the cooling fan 403.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims (9)

1. A high throughput automated device for monoclonal selection comprising an operating console (1) and a control computer (11), characterized in that: the top of the operation table (1) is provided with an X-Y linear motor portal frame (2), the left side of the X-Y linear motor portal frame (2) is provided with a 96-channel picking assembly (3), the top of the operation table (1) is provided with a picking sterilizing and cleaning assembly (4) below the 96-channel picking assembly (3), the right side of the X-Y linear motor portal frame (2) is provided with a channel pipetting assembly (5), the top of the operation table (1) is provided with a shaking uniformly coating assembly (6) below the channel pipetting assembly (5), the top of the operation table (1) is provided with an LED orifice plate photographing device (7) in the front of the picking sterilizing and cleaning assembly (4), the top center of the operation table (1) is provided with a consumable carrier sliding table matrix (8), the top of the operation table (1) is provided with conveyor belts (9) on both sides of the consumable carrier sliding table matrix (8), a liquid pumping cabin (10) is arranged at the top of the operating platform (1) and above the shaking coating assembly (6), a laminar flow air inlet static pressure box (101) is arranged at the top of the operating platform (1), an air exhaust and air collection box body (102) is arranged at the bottom of the operating platform (1), a laminar flow air exhaust static pressure box (103) is arranged at the bottom of the air exhaust and air collection box body (102), a liquid storage tank (104) is arranged at the bottom of the operating platform (1) and on the left side of the laminar flow air exhaust static pressure box (103), a solid waste collecting tank (105) is arranged at the bottom of the operating platform (1) and on the right side of the laminar flow air exhaust static pressure box (103), and a pore plate clamping jaw robot (13) is arranged on the outer wall of the X-Y linear motor portal frame (2) and on the left side of the channel liquid moving assembly (5);
the 96-channel pick-up head assembly (3) comprises a Z-axis motor (301) arranged on an X-Y linear motor portal frame (2), a bracket (302) is installed on the Z-axis motor (301), a packaging air path switch valve group (303) is installed inside the bracket (302), a pneumatic telescopic component (304) is arranged in the bracket (302) and below the integrated air path switch valve group (303), the pneumatic telescopic component (304) is connected with a picking head (306) through a picking head connecting piece (305), the front surface of the bracket (302) is sequentially provided with a distance sensor (307) and a camera (308) from left to right, a distribution valve block (309) is arranged on the outer wall of the bracket (302) and above the integrated gas circuit switch valve group (303), and an air source control valve (310) is arranged on the outer wall of the bracket (302) and on the front surface of the integrated air path switch valve group (303).
2. A high throughput automated apparatus for monoclonal selection according to claim 1, wherein: pick first sterilization cleaning assembly (4) including setting up at the first drying tank (401) of picking at operation panel (1) top, the inner wall of picking first drying tank (401) is provided with heating array (402), pick the inner wall of first drying tank (401) and install cooling fan (403) in the position department that is close to heating array (402), pick the bottom of first drying tank (401) inner wall and seted up air exit (404), the top of operation panel (1) and the front of picking first drying tank (401) set gradually first alcohol washing tank (405), second alcohol washing tank (406) and hydrogen peroxide ultrasonic cleaning tank (407) from a left side to the right side.
3. A high throughput automated apparatus for monoclonal selection according to claim 1, wherein: shake even coating unit (6) including installing driving motor (601) at operation panel (1) top, cam oscillation mechanism (602) is installed on the top of driving motor (601) output shaft, chucking mechanism (603) are installed at the top of cam oscillation mechanism (602), normal position sensor (604) are installed to the outer wall of cam oscillation mechanism (602).
4. A high throughput automated apparatus for monoclonal selection according to claim 1, wherein: the specific working process of the 96-channel picking assembly (3) is as follows: firstly, a 96-channel picker component (3) is transferred to a target hole plate position by an X-Y linear motor portal frame (2) to finish primary aiming, the X-Y linear motor portal frame (2) continuously drives the 96-channel picker component (3) to move, a distance sensor (307) finishes flatness scanning of a selected plate and calibrates a height distance, meanwhile, a camera (308) carries out real-time picture shooting to finish real-time position calculation of target bacteria or cells, a computer (11) is controlled to finish selection sequence, then, the position of the target bacteria or cells is selected, the X-Y linear motor portal frame (2) moves to an accurate aiming position, the camera (308) quickly confirms the position, a Z-axis motor (301) is micro-regulated to match and select local height of the position, and a single-channel air valve in an air channel switch valve group (303) is assembled to finish the up-and-down movement of the single-channel picker (306), and (4) realizing the selection operation, selecting the next monoclonal selection target, and repeating the operation of the previous step until the elution of the whole plate of monoclonal selection products is completed by the 96-well plate.
5. A high throughput automated apparatus for monoclonal selection according to claim 1, wherein: the tail end of the picking head (306) is specially designed for achieving the best selecting effect and transferring safety and preventing the carrying process from dropping, the picking head (306) is made of a material meeting GMP requirements, the guide part of the picking head (306) is made of a wear-resistant material meeting FDA (food and drug administration) certification, the picking head (306) is connected with the picking head connecting piece (305) in a floating mode, machining and assembling difficulty is reduced on the premise that multichannel picking head precision is guaranteed, the head driving unit and a control element of the head driving unit are designed in a modularized mode, single-channel to 96-channel random flux integration can be achieved, the tail end of the multichannel picking head (306) is unified in use and is hard in limit, the plane formed in one-step machining mode guarantees accuracy of the descending distance of the picking head, and the support (302) is provided with a mounting hole of the one-step machining formed picking head (306).
6. A high throughput automated apparatus for monoclonal selection according to claim 2, wherein: the specific working process of the picking head sterilizing and cleaning assembly (4) is as follows: the picking head (306) is sequentially sent into a hydrogen peroxide ultrasonic cleaning tank (407), a second alcohol cleaning tank (406) and a first alcohol cleaning tank (405) for cyclic cleaning, after the cyclic cleaning is finished, the picking head (306) is sent into a picking head drying tank (401) for heat source irradiation drying, and a cooling fan (403) cools the picking head (306).
7. A high throughput automated apparatus for monoclonal selection according to claim 2, wherein: the exhaust port (404) is connected with the exhaust gas collection box body (102) through a pipeline, the heating arrays (402) are made of a plurality of groups of infrared heating pipes, two groups of heating arrays (402) are arranged, and the two groups of heating arrays (402) are symmetrically arranged on the inner wall of the picking head drying groove (401).
8. A high throughput automated apparatus for monoclonal selection according to claim 3, wherein: the specific working flow of the shaking coating component (6) is as follows: the agar plate for coating is transferred into the shaking-up coating component (6), the 96-channel pick-head component (3) fills the process liquid into each hole of the agar plate, the drive motor (601) drives the agar plate to vibrate through the cam vibration mechanism (602) based on the set rotating speed, so that the process liquid is uniformly coated on the surface of the agar plate, the 96-channel pick-head component (3) fills the bacteria or cell solution onto the surface of the agar plate, the drive motor (601) drives the agar plate to vibrate through the cam vibration mechanism (602) based on the set rotating speed, so that the bacteria or cell solution is uniformly coated on the surface of the agar plate.
9. A high throughput automated apparatus for monoclonal selection according to claim 1, wherein: the control computer (11) is internally provided with integrated software (12) which ensures the whole system to operate fully automatically and realizes the functions of integrated collection, storage and analysis of data in the operation process, and the integrated software (12) comprises a process editing module (121) which has the functions of full-process list editing and management, standardized process template provision and real-time process control and adjustment; the device operation monitoring and operating module (122) is used for recording sample liquid operation historical data, sample coating operation historical data, sample monoclonal selection historical data and sample transfer operation historical data, and monitoring the operation state of each device module, solid consumable material sample loading management and liquid material sample loading management; the equipment debugging working module (123) has the functions of calibrating and correcting each motion module in the system, calibrating and correcting each liquid unit in the system, intelligently selecting and teaching a monoclonal sample and teaching a sample coating process; a data storage module (124) with the function of singly selecting the original image data; the log prompting module (125) has the functions of recording login information of operators, material loading information, equipment fault information in the running process, equipment warning information in the running process and equipment operation information in the running process; and the setting module (126) has the functions of personnel permission setting, parameter setting of each module of the system, liquid pipeline type configuration, liquid capacity configuration, liquid unit operation parameter configuration, monoclonal sample intelligent image recognition configuration and coating motion parameter configuration.
CN202210637601.8A 2022-06-08 2022-06-08 High-throughput automation equipment for monoclonal selection Pending CN115074231A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210637601.8A CN115074231A (en) 2022-06-08 2022-06-08 High-throughput automation equipment for monoclonal selection

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210637601.8A CN115074231A (en) 2022-06-08 2022-06-08 High-throughput automation equipment for monoclonal selection

Publications (1)

Publication Number Publication Date
CN115074231A true CN115074231A (en) 2022-09-20

Family

ID=83251826

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210637601.8A Pending CN115074231A (en) 2022-06-08 2022-06-08 High-throughput automation equipment for monoclonal selection

Country Status (1)

Country Link
CN (1) CN115074231A (en)

Similar Documents

Publication Publication Date Title
US7074246B2 (en) Modular semiconductor workpiece processing tool
JP5286354B2 (en) Vertical transport and processing system for plating a workpiece and a slack method for transporting the workpiece
US11679933B2 (en) Robotic processing system
US20030215357A1 (en) Automated processing system and method of using same
JP2004528531A (en) Automated laboratory system and method
US20060257999A1 (en) Compound profiling devices, systems, and related methods
US20120034596A1 (en) Device for automatically cultivating cells in parallel
WO2009093585A1 (en) Culture apparatus
JP7441967B2 (en) Compact clinical diagnostic system using planar sample transport
CN113514652A (en) Intelligent system for biological medicine expression purification and detection screening
TW201934295A (en) Resin molding mold and resin molding method efficiently supplies the film and the molded resin and shorten the manufacturing time
CN115074231A (en) High-throughput automation equipment for monoclonal selection
CN218290934U (en) High-throughput automation equipment for monoclonal selection
JP2009131908A (en) Automatic manufacturing system
WO2023065747A1 (en) System for macromolecule extraction
CN213529686U (en) Automatic screening and sorting device for bacterial colonies
WO2023083311A1 (en) Intelligent gene synthesis and monoclonal selection system
CN209821227U (en) Quick-replacement multi-channel automatic titration device
CN112974276A (en) Material removing and supplementing control method of intelligent production line system of liquid transfer head
CN219951065U (en) Full-automatic cell strain construction laboratory
CN114015554A (en) High-flux monoclonal automatic selection module
WO2023005842A1 (en) System for expression, purification, and detection and screening of biological drugs
CN218996661U (en) Full-automatic semiconductor wafer planting and film pasting integrated machine
CN217587262U (en) Multi-degree-of-freedom optical detection and operation platform
CN219016836U (en) Whole-flow integrated medicine research and development workstation

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination