WO2023065747A1 - 用于大分子抽提的系统 - Google Patents

用于大分子抽提的系统 Download PDF

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Publication number
WO2023065747A1
WO2023065747A1 PCT/CN2022/107404 CN2022107404W WO2023065747A1 WO 2023065747 A1 WO2023065747 A1 WO 2023065747A1 CN 2022107404 W CN2022107404 W CN 2022107404W WO 2023065747 A1 WO2023065747 A1 WO 2023065747A1
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WIPO (PCT)
Prior art keywords
unit
sample
incubator
macromolecules according
centrifuge tube
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PCT/CN2022/107404
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English (en)
French (fr)
Inventor
陈皓
杨开琳
郅岩
陈晓悦
Original Assignee
英诺维尔智能科技（苏州）有限公司
上海药明生物技术有限公司
药明生物技术爱尔兰有限公司
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Application filed by 英诺维尔智能科技（苏州）有限公司, 上海药明生物技术有限公司, 药明生物技术爱尔兰有限公司 filed Critical 英诺维尔智能科技（苏州）有限公司
Publication of WO2023065747A1 publication Critical patent/WO2023065747A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices

Definitions

  • the present disclosure relates generally to the technical field of macromolecules. More particularly, the present disclosure relates to systems for the extraction of macromolecules.
  • the biopharmaceutical industry is in a period of rapid development, and macromolecular biopharmaceuticals are put into large-scale use.
  • the research and development of new drugs, especially the selection of effective target products in the early stage, has become the key to the sustainable competitiveness of the company's product pipeline.
  • the traditional manual production method is difficult to meet the large-scale production and target product selection of the upcoming macromolecular biopharmaceuticals in the research and development stage.
  • the traditional manual production method is suitable for single batch and small batch pharmaceutical production.
  • Realizing industrial scale production with traditional manual production methods requires: 1) a large number of qualified operators, 2) manual operation of various instruments and equipment, and 3) a large area of clean space.
  • One of the aims of the present disclosure is to solve one or more of the above problems and to achieve other additional advantages.
  • a system for extraction of macromolecules comprising: at least one incubator for culturing biological samples to provide basic samples for the extraction of macromolecules
  • the sample operating system the sample operating system is used to perform predetermined operations on the biological samples cultivated in the incubator, so as to extract macromolecules from the basic samples;
  • the transport platform the transport platform is used for Transporting the biological sample between a box and the sample handling system.
  • the transfer platform includes a robot.
  • the robot is arranged on a ground rail or an aerial rail.
  • the transfer platform includes a transfer slide
  • the robot can transfer the biological sample from the incubator to the transfer slide
  • the transfer slide is configured to transfer the biological sample to the sample operating system
  • the transfer slide can transfer biological samples in batches.
  • multiple incubators are provided, and the multiple incubators are arranged on both sides of the transfer platform.
  • the incubator includes a housing and a culture component accommodated in the housing, and the culture component is arranged on an automatic sliding table element, so that the culture component can be controlled from the slides out of or into the housing.
  • the incubator is configured to automatically control the temperature and humidity of the biological sample, wherein the internal temperature of the incubator is controlled at 15-40° C., and its humidity is controlled by Control at 70-95% for expansion culture.
  • the incubator includes a heating film, and the heating film automatically heats the incubator to control its internal temperature at 15-40°C.
  • the incubator includes a humidification unit, the humidification unit includes an automatic water supply unit and an atomizer, the automatic water supply unit is configured to supply water to the incubator in a controlled manner, and the mist A nebulizer is configured to control the humidity of the incubator by atomizing the water from the automatic water supply unit.
  • the incubator includes a refrigeration compressor, and the refrigeration compressor is configured to control the temperature of the biological sample at 2-8°C when sedimentation and enrichment of the biological sample is required.
  • a part of the incubators in the incubators are configured to carry out amplified culture of the biological samples, while another part of the incubators in the incubators are configured to perform amplification of the biological samples at the same time. Sedimentation enrichment.
  • the sample operating system is arranged in a controlled laminar flow environment such that the internal environment of the sample operating system is isolated from its external environment.
  • the sample operating system is provided with a laminar flow unit configured to use a pressure difference to form the laminar flow environment inside the sample operating system.
  • the laminar flow unit includes a laminar flow air supply unit and a laminar flow return air unit, the laminar flow air supply unit is arranged on the top of the sample operating system, and the laminar flow return air unit The unit is arranged at the bottom of the sample operating system.
  • the sample operating system includes an operation table, and two sets of sample operation components are installed on the operation table.
  • the central axis is arranged mirror-symmetrically, and the two sets of sample manipulation assemblies are configured to be able to perform both independent operations and parallel operations.
  • the sample operation component includes at least one of the following devices: a code scanning unit, a centrifuge tube shaking unit, a shaker bottle shaker unit, a centrifuge tube cap uncapping unit, a shaker bottle cap uncapping unit, Magnetic bead sorting unit, centrifuge unit, pipetting stage, and multi-degree-of-freedom robot.
  • a pipetting unit and a cryotube uncapping unit are further installed on the operation table, and the pipetting unit and the cryotube uncap unit are arranged on the central axis of the operation table.
  • the sample operating system is configured to perform at least one of the following operations: code scanning, cap opening, shaking, centrifugal separation, magnetic bead sorting, pipetting, pumping and heating.
  • the multi-freedom robot is installed on a linear motor module, and the linear motor module includes a beam extending along the horizontal direction and a beam installed on the beam and along the beam.
  • the extension direction drives the linear motor of the multi-freedom robot, and the multi-freedom robot can move on the beam, so that the operating range of the multi-freedom robot can basically cover the operation area of each device of the sample operation assembly.
  • the sample operating system further includes a pumping unit, and the pumping unit includes a liquid storage unit for storing liquid required in the process, and a pump body for selecting a liquid pumping channel A panel, a pumping actuator module for pumping fluid into the consumable, and a motion module for moving the pumping actuator module.
  • the pumping unit includes a liquid storage unit for storing liquid required in the process, and a pump body for selecting a liquid pumping channel A panel, a pumping actuator module for pumping fluid into the consumable, and a motion module for moving the pumping actuator module.
  • the pump body panel is configured to select a liquid pumping channel among a plurality of liquid pumping channels, and the liquid pumping execution module can move to different positions through the movement module and utilize the The selected liquid pumping channel performs the liquid pumping operation.
  • the liquid storage unit includes at least one liquid storage container.
  • a weighing unit can be installed under the liquid storage container, through which the remaining liquid in the liquid storage container can be weighed.
  • the liquid pumping execution module is configured as a centrifuge tube pumping device or a shaker flask pumping device.
  • the centrifuge tube oscillating and turning unit is configured to rotate the centrifuge tube at an angle of 0° to 360° for mixing, and at least one of the following parameters can be controlled during the mixing process: rotation Speed, number of rotation cycles, and direction of rotation.
  • the centrifuge tube uncapping unit includes a centrifuge tube feeding linear module and a working head of a centrifuge tube uncapping machine, and the centrifuge tube feeding linear module is configured for the multi-degree-of-freedom robot to carry After the centrifuge tube carrier plate of the centrifuge tube is placed on the centrifuge tube feeding linear module, the centrifuge tube carrier plate is transferred to the lower part of the working head of the centrifuge tube capping machine.
  • the centrifuge tube feeding linear module is equipped with a centrifuge tube automatic positioning and alignment mechanism, and the centrifuge tube automatic positioning and alignment mechanism is configured to position and clamp the centrifuge tube carrier tray.
  • the magnetic bead sorting unit includes a magnetic bead sorting rack for magnetic bead adsorption and a magnetic bead pouring rack for dumping waste supernatant.
  • the magnetic bead adsorption operation and the waste supernatant dumping operation can be performed simultaneously.
  • the cryopreservation tube uncapping unit includes a cryopreservation tube feeding linear module and a working head of a cryopreservation tube uncapping machine, and the cryopreservation tube feeding linear module is configured for multiple degrees of freedom
  • the robot places the cryopreservation tube tray on the cryopreservation tube feeding linear module, and then transfers the cryopreservation tube tray to the working head of the cryopreservation tube uncapping machine.
  • the cryopreservation tube feeding linear module is equipped with a cryopreservation tube automatic positioning and alignment mechanism, and the cryopreservation tube automatic positioning and alignment mechanism is configured to position and clamp the cryopreservation tube load. plate.
  • the pipetting unit is configured to transfer the liquid required in the process to the consumables placed on the pipetting platform, so as to perform corresponding operations.
  • the pipetting unit includes a pipetting robot and a pipetting module, and the pipetting module is configured to be able to move independently along the Z axis in the pipetting unit, wherein the Z The axis is perpendicular to the horizontal plane.
  • the pipetting robot is configured as a SCARA robot.
  • the sample operating system further includes an operating platform and a consumable carrier sliding table for carrying the operating platform, and the consumable carrier sliding table is configured to be able to slide out and in in a controlled manner
  • the sample operating system facilitates loading or unloading consumables on the operating platform.
  • the operation table and the sample operation components installed on the operation table are arranged in the middle bin body.
  • the liquid storage unit and the pump body panel are arranged in the bottom compartment.
  • the system for extracting macromolecules further includes an automatic control system configured to control the incubator, the sample operating system, and the transfer platform operation.
  • an automated production system suitable for macromolecule extraction including a top chamber body, a middle chamber body, a bottom chamber body, a temperature-controlled incubator, a robot and a track, a sample operating system and electrical control system, the top chamber includes laminar air intake and robot guide rails, and the middle chamber includes code scanning, cover opening, shaking, centrifuge, magnetic bead sorting, pipetting, pump liquid storage and pump body unit, For heating, electric door and manual door modules, the bottom chamber includes a liquid storage chamber, a centrifugal equipment storage chamber, a pump valve control chamber, a return air fan and a cable liquid circuit.
  • the inside of the temperature-controlled incubator is provided with an equipment frame unit, and the inner lower side of the temperature-controlled incubator is provided with a shaking table mechanism drive unit, and the inside of the temperature-controlled incubator is located
  • the upper side of the bed mechanism drive unit is provided with an automatic slide unit
  • the upper side of the automatic slide unit is provided with a shaker plate unit
  • the upper side of the temperature-controlled incubator is provided with an equipment lighting/purification/disinfection unit
  • the right rear side of the temperature-controlled incubator is provided with an intelligent comprehensive control unit
  • the right side of the temperature-controlled incubator is provided with an equipment operation and display area
  • the right side of the end of the temperature-controlled incubator is provided with Self-sealing door unit.
  • the sample operating system includes a loading slide, a liquid transfer platform, a cryotube cap opener unit, a liquid pipette robot and a module, a centrifuge tube cap opener unit, a centrifuge, a magnetic bead Sorting unit, centrifugal turning unit, centrifuge tube oscillation unit, manual loading table, handling robot, automatic loading table shake bottle cap.
  • the pump liquid storage and pump body unit includes a large-capacity liquid storage, a multi-channel pump body panel, a pump liquid execution unit linear motion module, and a pump liquid execution module.
  • both the frozen tube capping machine unit and the centrifuge tube capping machine unit include a feeding linear module, a capping machine working head, and an automatic positioning and alignment mechanism.
  • the Z-axis independent motion pipetting unit of the robot is installed on the SCARA robot platform.
  • the electrical control system includes a temperature sensor, a weight sensor, a differential pressure sensor, a photoelectric sensor, a camera, a code reader, an I/O acquisition module, an industrial computer and a drive module.
  • FIG. 1 is a front view of the basic structure of a system for macromolecule extraction according to an embodiment of the present disclosure
  • FIG. 2 is a schematic diagram of a fully automatic incubator unit according to an embodiment of the present disclosure
  • Figure 3 is a system diagram of an array of incubators and operating a sample transport robot according to one embodiment of the present disclosure
  • FIG. 4 is a top view of the connection between the incubator array and the sample operating system according to an embodiment of the present disclosure
  • FIG. 5 is a plane layout diagram of a sample operating system according to an embodiment of the present disclosure.
  • Fig. 6 is a schematic diagram of a pump fluid storage and pump body unit array according to an embodiment of the present disclosure
  • FIG. 7 is a schematic diagram of a centrifuge tube oscillation and turnover unit according to an embodiment of the present disclosure.
  • FIG. 8 is a schematic diagram of a centrifuge cover opening unit according to an embodiment of the present disclosure.
  • FIG. 9 is a schematic diagram of a magnetic bead sorting unit according to an embodiment of the present disclosure.
  • Fig. 10 is a schematic diagram of a cryotube uncapping unit according to an embodiment of the present disclosure.
  • Figure 11 is a schematic diagram of a pipetting unit according to an embodiment of the present disclosure.
  • FIG. 12 is a perspective view of the basic structure of a sample operating system according to an embodiment of the present disclosure.
  • FIG. 13 is another perspective view of the basic structure of a sample operating system according to an embodiment of the present disclosure.
  • FIG. 14 is a schematic diagram of a sample operation process according to an embodiment of the present disclosure.
  • FIG. 15 is a schematic diagram of a basic automatic control architecture according to an embodiment of the present disclosure.
  • Fig. 16 is a schematic diagram of the software architecture of the intelligent macromolecule extraction system according to an embodiment of the present disclosure.
  • the system 10 may include: at least one incubator 1, the incubator 1 is used for culturing biological samples to provide basic samples for the extraction of the macromolecules; a sample operating system 3, the sample operating system 3 is used for The biological samples cultivated in the above-mentioned incubator 1 perform predetermined operations (such as operations related to the extraction of macromolecules, such as uncapping, shaking, centrifugation, magnetic bead sorting, pipetting, pumping, etc.), to It is used to extract macromolecules from basic samples; and a transfer platform 2 is used to transfer the biological samples between the incubator 1 and the sample operating system 3 .
  • predetermined operations such as operations related to the extraction of macromolecules, such as uncapping, shaking, centrifugation, magnetic bead sorting, pipetting, pumping, etc.
  • the transfer platform 2 can be configured as a culture material transfer platform, which is used to transfer cultured biological samples between the incubator 1 and the sample operating system 3 .
  • the culture material transfer platform can transfer the biological samples cultivated in the incubator 1 to the sample operating system 3 for the corresponding operation of the sample operating system 3, and can also transfer the biological samples from the sample operating system 3 back to the incubator 1, to continue cultivating.
  • a plurality of incubators 1 may be configured as an array of incubators.
  • the transfer platform 2 may include a robot 210 (also referred to as a robotic arm), and the robot 210 may be used to transfer biological samples between the incubator 1 and the sample operating system 3 .
  • the robot 210 may be set on a ground rail or an aerial rail.
  • the robot 210 can move on the ground guide rail and/or the aerial guide rail, so as to transfer biological samples in a wider range.
  • the incubator 1, the sample operating system 3 and the transfer platform 2 of the system 10 will be described in detail below.
  • the incubator 1 may include a housing 100 and culture components accommodated in the housing 100 .
  • the culture assembly may include one or more shake flasks 109 for holding biological samples.
  • the one or more shake flasks 109 may be placed on the shake flask carrier plate assembly 105 .
  • the shake bottle carrier plate assembly 105 can be placed on the automatic slide unit 104, so that the shake bottle carrier plate assembly 105 and the shake bottle 109 it carries can slide out or slide in from the housing 100 in a controlled manner when needed.
  • the shaker plate assembly 105 and the automated slide unit 104 may be located within the frame unit 103 .
  • An oscillating unit (for example, a shaker mechanism or a shaker mechanism drive unit) 102 may be provided below the frame unit 103, so that the shaker bottle carrier plate assembly 105 and the shaker flask 109 it carries can be oscillated when needed.
  • the interior of the incubator 1 may also be provided with an equipment lighting/purification/disinfection unit 101 .
  • the equipment lighting/purification/disinfection unit 101 can be arranged in the upper side of the incubator 1 inside the incubator 1 .
  • a suitable device lighting/decontamination/disinfection unit 101 may be an ultraviolet light irradiation unit.
  • the incubator 1 may be an intelligent incubator.
  • the incubator 1 is provided with an intelligent comprehensive control system 107 to realize intelligent control of the incubator 1 .
  • the integrated control system 107 can control the real-time oscillation of the oscillation unit 102, the sliding in and out of the automatic slide unit 104, the opening and closing of the equipment lighting/purification/disinfection unit, and so on.
  • the incubator 1 may also include an equipment operation and display area 106 .
  • the device operation and display area 106 may include input/output components such as a touch screen to provide a human-computer interaction interface.
  • the incubator 1 may further include a self-sealing door unit 108 .
  • the self-sealing door unit 108 can be automatically opened or closed under the control of the integrated control system 107 to open or close the incubator 1 . These all contribute to the automatic docking of the incubator 1 and the culture material transfer platform.
  • intelligent network units can also be used to transmit instructions to the integrated control system 107 via software installed on remote terminals (such as computers, smart phones or other controllers, etc.), so as to realize the control of the incubator 1 remote control.
  • the incubator 1 can be configured to be able to perform automatic temperature-controlled and humidity-controlled cultivation of biological samples.
  • the incubator 1 can realize temperature control of 15-40° C. and/or humidity control of 70-95%.
  • the temperature control of the incubator 1 can be realized by using heating film and insulation material.
  • the heating film can be made of thin film heating material, which is used to automatically heat the incubator 1 so that it is in a predetermined temperature range, and the thermal insulation material can be used to reduce the distance between the inner space of the incubator 1 and the outside world. temperature transfer.
  • the incubator 1 may include a humidification unit.
  • the humidification unit may include an automatic water supply unit and a nebulizer.
  • the atomizer can control the humidity of the incubator 1 by atomizing the water from the automatic water supply unit. This is in contrast to traditional incubators, which require an operator to position a volume of water inside to maintain humidity.
  • the nebulizer can be configured as an ultrasonic nebulizer. The atomizer can be started or stopped as required under the control of the integrated control system 107 to effectively control the humidity in the incubator 1 .
  • the incubator 1 can also be configured to be able to perform automatic low-temperature sedimentation enrichment on biological samples.
  • Refrigeration compressors can be arranged in the incubator 1 .
  • the refrigerating compressor is configured to control the temperature of the biological sample at 2-8°C when the biological sample needs to be sedimented and enriched, so as to realize the low-temperature sedimentation of the biological sample.
  • FIG. 3 and FIG. 4 it shows a system diagram of the incubator array and the operating sample transfer robot, and a top view of the connection between the incubator array and the sample operating system 3 .
  • the transfer platform 2 can transfer the biological samples cultivated in the incubator 1 to the sample operating system 3 and can also transfer the biological samples from the sample operating system 3 back to the incubator 1 .
  • the transfer platform 2 transfers the biological sample from the incubator 1 to the sample operating system 3 , firstly, under the control of the integrated control system 107 , the automatic sealing door unit 108 is automatically opened. Then the automatic slide unit 104 slides out, so that the shaker flask carrier assembly 105 and the shaker flasks 109 carried thereon slide out from the housing 100 of the incubator 1 . Then the robot 210 (for example, a mechanical arm) used for transfer transfers the shaker bottle tray assembly 105 carrying the shaker flasks to the transfer platform 2 .
  • the robot 210 for example, a mechanical arm
  • the shake bottle carrier assembly 105 can be transferred from the robot to the transfer platform 220 of the transfer platform 2 for temporary storage or intermediate storage of the shake bottle carrier assembly 105 .
  • the transfer transport platform 220 can assume the role of the temporary storage.
  • the robot 210 transfers the shake bottle carrier plate assembly 105 from the transfer transport platform 220 to the sample operating system 3 .
  • the shaker plate assembly 105 can also be transferred to the transfer platform 2 via the robot 210 after sliding out from the housing 100 of the incubator 1 , and directly transferred from the transfer platform 2 to the sample operating system 3 .
  • the biological samples can be transferred to the sample operating system 3 in batches through the transfer platform 2 , so as to complete the loading into the sample operating system 3 .
  • the sample operating system 3 performs sample operations on biological samples, and completes data collection and analysis.
  • the biological sample can be transferred from the sample operating system 3 to the transfer platform 2 again.
  • the robot 210 can be used to transfer the shake bottle carrier plate assembly 105 to the transfer transport platform 220 in for temporary storage.
  • the robot 210 can be used to transfer the shaker flask carrier assembly 105 from the transfer platform 220 of the transfer platform 2 to an available incubator 1 .
  • the shake flask carrier plate assembly 105 can also be directly transferred to the transfer platform 2 after coming out of the sample operating system 3 .
  • the shake bottle tray assembly 105 is transferred from the transfer platform 2 to the automated slide unit 104. Under the control of the integrated control system 107, the self-sealing door unit 108 is automatically opened. Then the automatic slide unit 104 slides in, so that the shaker flask carrier plate assembly 105 is transferred into the incubator 1 again.
  • the incubator array After the incubator array acquires culture consumables (such as shake flasks, etc.), they are first placed in batches on the transfer slide, and after a single batch is placed, they are transferred to the sample operating system 3 in batches, which can greatly improve the transfer efficiency. After the rehydration/replacement operation of the shake flask is completed, the batches are transferred to the slide table, and then transferred back to the incubator array uniformly.
  • culture consumables such as shake flasks, etc.
  • the multiple incubators 1 can be arranged on both sides of the transfer platform 2 .
  • the multiple incubators 1 may be respectively arranged on both sides of the transfer platform 2 .
  • Some of the incubators 1 in the plurality of incubators can be configured to carry out amplified culture of the biological samples, while another part of the incubators 1 in the plurality of incubators can be configured to perform amplification and cultivation of the biological samples at the same time. Sedimentation enrichment. Therefore, in the case where multiple incubators 1 are arranged, each incubator 1 can undertake the tasks of expansion culture and sedimentation enrichment respectively according to needs.
  • the sample operating system 3 can be arranged entirely in a controlled laminar flow environment, which effectively isolates the internal environment of the sample operating system 3 from its external environment (eg, the laboratory environment in which the sample operating system 3 is arranged).
  • the sample operating system 3 may be provided with a laminar flow unit.
  • the laminar flow unit can be configured to form a laminar flow environment inside the sample handling system 3 by utilizing a pressure difference.
  • the laminar flow unit may comprise a laminar air supply unit.
  • the laminar air supply unit can be arranged on the top of the sample operating system 3 .
  • the laminar flow air supply unit may include air supply equipment such as a blower or a centrifugal fan, which can send gas from the environment or a dedicated gas source into the interior of the sample operating system 3 in the form of laminar flow.
  • the laminar flow unit may also include a laminar return air unit.
  • the laminar return air unit can be arranged at the bottom of the sample operating system 3 .
  • the laminar return air unit can circulate and filter the laminar gas in the sample operating system 3 and circulate it back to the inside of the sample operating system 3, so as to effectively protect the safety of personnel, samples, and the surrounding environment during operation. safety.
  • the laminar flow air supply unit and the laminar flow return air unit may be equipped with corresponding filter units respectively.
  • the laminar flow air supply unit and the laminar flow return air unit By arranging the laminar flow air supply unit and the laminar flow return air unit according to the present disclosure, it can ensure that the flow field in the operation area is uniform, the flow velocity complies with regulations, and the safety of production samples can be ensured.
  • the system 10 according to the present disclosure can provide a debugging function, so that the working mode and the fast exhaust mode can be realized according to the requirements, and the requirements related to the wind speed and manifold required in national standards such as biological safety cabinets can be guaranteed.
  • sample operating system 3 according to an embodiment of the present disclosure will be described in detail below with reference to FIGS. 5 to 13 .
  • the sample operating system 3 includes an operation table 310 on which two sets of sample operation components 300 can be installed.
  • the two groups of sample manipulation assemblies 300 may have the same arrangement and structure, so as to realize exactly the same function. As shown in FIG. 5 , two groups of sample operation components 300 can be arranged on both sides of the operation surface 310, respectively. In this embodiment, the two sample operation assemblies 300 may be arranged mirror-symmetrically with respect to the central axis of the operation surface 310 .
  • the two two-group sample manipulation assemblies 300 may be configured to be able to implement both independent operations and parallel operations, that is, the two two-group sample manipulation assemblies 300 may be configured not only to be able to operate independently of each other, but also to operate in parallel.
  • each sample manipulation assembly 300 may include at least one of the following devices: a code scanning unit, a centrifuge tube shaking unit 330 , a shaking bottle shaking unit, and a centrifuge tube uncapping unit. unit 340 , shaker bottle capping unit 3110 , magnetic bead sorting unit 360 , centrifuge unit 3100 , liquid transfer stage 371 , and multi-degree-of-freedom robot 311 .
  • a pipetting unit 370 and a cryotube cap opening unit 350 are also installed on the operating table 310 .
  • the pipetting unit 370 and the cryotube cap opening unit 350 may be arranged on the central axis of the operating table 310 .
  • the operation table 310 together with the sample operation assembly 300 installed on the operation table 310 may be arranged in the middle bin body.
  • the sample operating system 3 can perform various operations for extracting macromolecules, including but not limited to: code scanning, cap opening, shaking, centrifugation, magnetic bead sorting, pipetting , Pumping and heating etc.
  • each device in the sample operating system 3 is arranged according to an island layout, and the following advantages can be achieved through the island layout: 1) It is possible to realize the aggregation operation of each process flow link, and it is not necessary to use biological equipment for specific operations.
  • Laminar flow air supply units and laminar flow return air units can be arranged around each device arranged in an island layout, so as to ensure a clean operating environment.
  • a multi-degree-of-freedom robot 311 may also be arranged on the operating table 310 of the sample operating system 3 .
  • the multi-degree-of-freedom robot 311 can move with multiple degrees of freedom (eg, horizontal movement, vertical movement, rotation around its own central axis, deflection around the horizontal axis and vertical axis, etc.).
  • the multi-degree-of-freedom robot 311 can be installed on the linear motor module 312 .
  • the linear motor module 312 may include a beam 313 extending along the horizontal direction and a linear motor mounted on the beam 313 and driving the multi-degree-of-freedom robot 311 along the extending direction of the beam 313 .
  • the multi-degree-of-freedom robot 311 can move in the direction of the arrow.
  • the multi-degree-of-freedom robot 311 can also move in the direction opposite to the direction of the arrow.
  • the multi-degree-of-freedom robot 311 can move within the predetermined range of the sample operating system 3, thereby helping it to automatically transfer consumables and biological samples within the predetermined range.
  • the scope of action of the multi-freedom robot 311 can basically cover the operation area of each device of the sample operation assembly 300 .
  • the arrangement of the multi-degree-of-freedom robot 311 helps to enhance the intelligence and automation level of the system 10 according to the present disclosure.
  • a corresponding multi-degree-of-freedom robot 311 can be provided respectively.
  • a high-throughput and highly flexible transfer and operation unit can be obtained, which can achieve the following advantages: 1) Different materials can be efficiently transported and transferred between different stations; 2) Different materials can be adjusted and controlled and 3) can perform anthropomorphic operations, such as dumping waste liquid, etc.;
  • the code scanning unit can be configured to identify the identification code or label element set on the consumables, so as to realize the recording and automatic management of the materials of the whole machine, and realize the unified management of materials in the database.
  • the identification code can be configured as a barcode or a two-dimensional code.
  • the tag identification element can be designed as an RFID tag.
  • the sample operating system 3 may further include a liquid pump unit 320, and the liquid pump unit 320 includes a liquid storage unit 321 for storing the liquid required in the process.
  • the pump body panel 322 for selecting the liquid pumping channel, the pump liquid execution module 323 for pumping the liquid into the consumables, and the movement module 324 for moving the liquid pump execution module 323 .
  • the liquid can reach the liquid pump execution module 323 from the liquid storage unit 321 through the pump body panel 322 .
  • the pump liquid execution module can be configured as a centrifuge tube pumping device or a shaker flask pumping device.
  • the pumping execution module 323 may be mounted on a motion module 324 configured as a linear module.
  • the movement module 324 may also include a beam extending along the horizontal direction and a linear motor installed on the beam and driving the pumping actuator module 323 along the extending direction of the beam.
  • the liquid pump execution module 323 can move within a predetermined range of the sample operating system 3 to perform liquid replenishment operations on shake flasks or consumables.
  • the liquid storage unit 321 can be partially arranged in the lower area of the sample operating system 3 below the operating table 310 , for example, in the bottom chamber, and partially arranged on the operating table 310 areas, such as in the intermediate compartment.
  • the liquid storage unit 321 can also be completely arranged in the lower area of the sample operating system 3 below the operating table 310 , or in the area above the operating table 310 .
  • the liquid storage unit 321 may include at least one liquid storage container 325, such as a liquid storage bottle or a liquid storage box.
  • a weighing unit can be installed below the liquid storage container 325 , by means of which the remaining liquid in the liquid storage container 325 can be weighed. When the remaining liquid in the liquid storage container 325 is lower than a specific threshold, the weighing unit can detect this situation and automatically notify the superior equipment to replenish the liquid storage container 325 .
  • a liquid level sensor can be arranged in the liquid storage container 325, by means of which the remaining liquid level can be monitored.
  • the liquid storage container 325 can have a temperature adjustment device, and the temperature adjustment device can adjust the temperature of the liquid stored in the liquid storage container 325, such as heating, cooling or heat preservation, so that the stored liquid can have different required temperature. liquid temperature.
  • the pump body panel 322 can be arranged in the lower area of the sample handling system 3 below the operating table 310 .
  • the pump body panel 322 may be disposed adjacent to the liquid storage unit 321 .
  • the pump body panel 322 may have a plurality of liquid pumping channels and be configured to select a liquid pumping channel among the plurality of liquid pumping channels.
  • the plurality of liquid pumping passages can be respectively fluidly connected with a plurality of corresponding liquid storage containers 325, thereby forming a plurality of corresponding pump liquid supply pipelines. These pump fluid supply lines are independent of each other.
  • the pump body panel 322 may also have a single liquid pumping channel.
  • the liquid pumping execution module 323 can move to different positions through the movement module 324 and use the selected liquid pumping channel to perform liquid pumping operation.
  • the liquid pump unit 320 itself can have a liquid circuit cleaning function, which can realize the functions of quick cleaning, deep cleaning, reverse disinfection, and disinfection and cleaning of the inner and outer walls of the steel needle according to the use requirements of the process liquid.
  • the pump liquid unit 320 is equipped with a pump liquid heating unit, and the pump liquid heating unit can heat the process fluid.
  • the heating may be instant heating. In this way, the process and cleaning requirements can be realized.
  • the pumping unit 320 of the present disclosure the following advantages can be achieved: 1) The addition of a large dose of solution in the production process can realize pumping of dozens to hundreds of liquids at most, and each liquid uses an independent pumping tube 2) Ensure the cleanliness of the entire liquid operating circuit; 3) Monitor and alarm the liquid volume; 4) Control the liquid stored in the liquid storage unit 321 at low temperature, normal temperature, and high temperature.
  • the centrifuge tube shaking unit 330 may be configured as a centrifuge tube shaking and turning unit, which may include a turning unit 331 and a centrifuge tube shaking unit 332 .
  • the centrifuge tube shaking and turning unit can be configured to rotate the centrifuge tube at an angle of 0° to 360° for mixing. At least one of the following parameters can be controlled during mixing: rotation speed, number of rotation cycles, and rotation direction.
  • the inverting unit 331 can be inverted in a positive or negative direction, or clockwise or counterclockwise.
  • the shaker flask shaker unit is similar in structure to the centrifuge tube shaker unit 330 . By setting the centrifuge tube shaking unit 330 and the shaker bottle shaking unit, automatic shaking of samples during the production process can be realized.
  • the centrifuge tube uncapping unit 340 may include a centrifuge tube feeding linear module 341 and a working head 342 of the centrifuge tube uncapping machine.
  • the centrifuge tube feeding linear module 341 may be equipped with an automatic positioning and alignment mechanism for centrifuge tubes.
  • the centrifuge tube feeding linear module 341 is configured to transfer the centrifuge tube carrier to the working head of the centrifuge tube uncapping machine after the multi-degree-of-freedom robot places the centrifuge tube carrier with the centrifuge tube on the centrifuge tube feeding linear module 341 342 below.
  • the centrifuge tube automatic positioning and alignment mechanism is configured to position and clamp the centrifuge tube carrier plate arranged in the centrifuge tube feeding linear module 341 .
  • the freezing tube capping unit 350 includes a freezing tube loading linear module 351 and a working head 352 of the freezing tube capping machine.
  • the linear module 351 for feeding frozen storage tubes is equipped with an automatic positioning and alignment mechanism for frozen storage tubes.
  • the freezing tube loading linear module 351 is configured to transfer the freezing tube loading plate to the working head of the freezing tube opening machine after the multi-degree-of-freedom robot places the freezing tube loading plate on the freezing tube loading linear module 351 352 below.
  • the automatic positioning and alignment mechanism for cryopreservation tubes is configured to position and clamp the cryopreservation tube carrier set on the cryopreservation tube feeding linear module 351 .
  • the structure of the shaker bottle automatic uncapping unit is similar to the centrifuge tube uncapping unit 340 or the freezing tube uncapping unit 350 .
  • the cryotube cap opening unit 350, the centrifuge tube cap opening unit 340 and the shaker bottle self-capping unit By setting the cryotube cap opening unit 350, the centrifuge tube cap opening unit 340 and the shaker bottle self-capping unit, the automatic opening and closing of various consumables can be realized.
  • the caps are stored using special tooling placed upwards to avoid crossing materials.
  • the magnetic bead sorting unit 360 may include a magnetic bead sorting rack 361 for magnetic bead adsorption and a magnetic bead pouring liquid for dumping the discarded supernatant.
  • Rack 362 The magnetic bead adsorption operation and the waste supernatant dumping operation can be performed simultaneously.
  • the magnetic bead sorting unit 360 may be equipped with a corresponding magnetic bead liquid shaking unit.
  • the magnetic bead solution shaking unit is configured to automatically shake the magnetic bead solution, so as to realize the automatic shaking of the magnetic beads (sorting operation, etc.) before sample loading.
  • the centrifuge unit 3100 may be configured as a temperature-controlled centrifuge unit 3100 .
  • the temperature-controlled centrifuge unit 3100 can work together with the corresponding material transfer unit to perform automatic low-temperature/normal-temperature/high-temperature centrifugation and material transfer of samples, so as to achieve effective mixing of samples and collection of effective products during the production process.
  • the pipetting unit 370 can be configured to transfer the liquid required in the process to the consumables placed on the pipetting platform 371 to perform corresponding operations .
  • the pipetting unit 370 may include a pipetting robot 372 and a pipetting module 373 .
  • the pipetting module 373 is configured to be able to move independently along the Z-axis in the pipetting unit 370 , wherein the Z-axis is perpendicular to the horizontal plane.
  • the pipetting robot 372 can be configured as a SCARA robot.
  • liquid pipetting unit 370 By setting the liquid pipetting unit 370 that moves independently on the Z axis and installing the liquid pipetting module 373 on the SCARA robot platform, compared with the traditional X-Y-Z linear motor liquid pipetting platform, a wider range of liquid pipetting operations can be achieved, and the operation time is greatly improved. flexibility in the process. In addition, the addition of small doses of medicaments and the harvesting and packaging of final products can be realized through the pipetting unit 370 .
  • the sample operating system 3 may further include an operation platform and a consumables carrier slide 381 for carrying the operation platform, and the consumables carrier slide 381 is configured to slide in a controlled manner. Out and slide into the sample operating system 3, so as to load or unload consumables on the operating platform.
  • a manual loading platform 391 in addition to automatic loading, can also be provided, through which manual loading can be performed.
  • the manual loading table 391 is equipped with a corresponding transfer robot 392, through which the transfer robot 392 can transfer the manually loaded consumables into the automatic operation route.
  • Fig. 14 is a schematic diagram of the sample operation process of the present invention.
  • the seed solution can first be added to consumables (such as shake flasks). Then, the consumables with the seed liquid are subjected to amplified culture in the incubator 1 to form an amplified and cultured biological sample. Then, in the incubator 1, the amplified and cultured biological samples are enriched by low-temperature sedimentation. The expansion culture and low-temperature precipitation enrichment can be carried out in the same incubator 1, or in different incubators 1 in the incubator array.
  • the biological sample is then transferred from the incubator 1 to the sample handling system 3 via the transfer platform 2 . Corresponding operations are performed on biological samples in the sample operating system 3 . Intermediate products can be obtained after centrifugation and enrichment of biological samples.
  • rehydration can be performed again, and the rehydrated biological sample is transferred from the sample operating system 3 to the incubator 1 via the transfer platform 2, and the expansion culture and low-temperature sedimentation enrichment are performed again.
  • the product can be subjected to magnetic bead separation.
  • DNA washing can then be performed, for example, by centrifugation, and the DNA washing can be performed in multiple rounds. Finally, DNA encapsulation is performed to complete all steps of macromolecular extraction.
  • the system 10 can be configured as an automated and intelligent system, each module in the system 10 (such as the incubator 1, the sample operating system 3, the transfer platform 2, etc.) All operations can be completed automatically under the control of the automatic control system.
  • Fig. 15 shows the architecture of the automatic control system 6 according to one embodiment of the present disclosure.
  • the automatic control system 6 may include an industrial computer, an input/output data acquisition module, and a driving module.
  • various collection devices can be installed in the system 10, including but not limited to: temperature sensors, weight sensors, differential pressure sensors, photoelectric sensors, cameras, code readers, etc. Wherein, temperature sensors, weight sensors, differential pressure sensors, photoelectric sensors, cameras, etc.
  • the drive module is used to control the operation of each component or module in the system 10, including but not limited to the operation of the following components or modules: electrothermal film, robot (transfer, pipetting, etc.), pump (pump liquid, drain liquid, etc.), electromagnetic Valves, centrifuges, electric slides, drive motors (for example, drive motors for incubator doors and shakers), centrifugal fans, etc.
  • Fig. 16 shows the complete whole process control software of the system according to an embodiment of the present disclosure.
  • process editing functions include: editing and management of the whole process process list; provision of standardized process templates; and real-time process control and adjustment.
  • Equipment operation monitoring and operation functions include: sample liquid operation history data; sample magnetic bead operation history data; sample centrifugation operation history data; sample incubation operation history data; sample transfer operation history data; Status monitoring; sample loading management of solid consumables; sample loading management of liquid materials; storage management of consumables in the storage center; replenishment management of consumables in the storage center; Equipment debugging work (manual operation mode) includes: calibration and correction of each motion module in the system; calibration and correction of each liquid unit in the system; log prompt function; recording operator login information; material feeding information; recording equipment failure information during operation; recording Device warning information during operation; and record device operation information during operation.
  • the setting function includes: personnel authority setting; parameter setting of each module of the system; liquid pipeline type configuration; and liquid capacity configuration.
  • An automatic production system suitable for macromolecule extraction including top chamber, middle chamber, bottom chamber, temperature-controlled incubator, robot and track, core operating system and electrical control system, and the top chamber includes laminar air inlet and robot guide rails, the middle warehouse includes modules for scanning code, opening cover, shaking, centrifuge, magnetic bead sorting, pipetting, pump liquid storage and pump body unit, heating, electric door and manual door, and the bottom warehouse Including liquid storage bin, centrifugal equipment storage bin, pump valve control bin, return air fan and cable liquid circuit.
  • the inside of the temperature-controlled incubator is provided with an equipment frame unit, the inner lower side of the temperature-controlled incubator is provided with a shaking table mechanism drive unit, and the inside of the temperature-controlled incubator is located on the upper side of the shaker mechanism drive unit.
  • An automatic slide unit the upper side of the automatic slide unit is provided with a shaker plate unit, and the upper side of the temperature-controlled incubator is provided with an equipment lighting/purification/disinfection unit, and the right side of the temperature-controlled incubator
  • the rear side is provided with an intelligent comprehensive control unit, the right side of the temperature-controlled incubator is provided with an equipment operation and display area, and the right side of the end of the temperature-controlled incubator is provided with an automatic sealing door unit.
  • the core operating system includes a loading slide, a pipetting platform, a cryotube cap opening unit, a liquid pipetting robot and modules, a centrifuge tube cap opening unit, a centrifuge, a magnetic bead sorting unit, a centrifugal flipping unit, and a centrifuge.
  • Tube oscillating unit manual loading table, handling robot, automatic feeding table shake bottle cap.
  • the pump liquid storage and pump body unit includes a large-capacity liquid storage, a multi-channel pump body panel, a pump liquid execution unit linear motion module, and a pump liquid execution module.
  • Both the freezing tube capping machine unit and the centrifuge tube capping machine unit include a feeding linear module, a capping machine working head, and an automatic positioning and alignment mechanism.
  • the robot Z-axis independently moves the pipetting unit and is installed on the SCARA robot platform.
  • the electrical control system includes a temperature sensor, a weight sensor, a differential pressure sensor, a photoelectric sensor, a camera, a code reader, an I/O acquisition module, an industrial computer and a drive module.
  • Embodiment a) core operating system: based on a multi-robot system and a fully automated module, the manual operation replacement of the whole process of macromolecule extraction is realized;
  • the effective sedimentation and enrichment of carrier cells is realized, which is convenient for the operation of replenishing and changing liquid in the core operating system;
  • the robot and supporting guide rail system realize the efficient transfer of samples between the core operating system and the incubator array;
  • the intelligent network unit realizes the remote control of the incubator array by the factory software
  • the incubator array After the incubator array acquires culture consumables (such as shake flasks, etc.), they are first placed on the transfer slide in batches. After a single batch is placed, they are transferred to the core liquid operating system in batches, which can greatly improve the transfer efficiency; complete the rehydration in the shake flasks / After changing the medium, batches are transferred to the slide table, and transferred back to the incubator array in a unified manner;
  • culture consumables such as shake flasks, etc.
  • Step1 The door of the incubator opens automatically, the slide table slides out, and the transfer robot transfers the culture sample (shake flask) to the transfer platform;
  • Step2 The transfer platform transfers the culture samples to the core operating system in batches, and completes the feeding to the core operating system;
  • Step3 The core operating system performs sample operations, and completes data collection and analysis during the process;
  • Step4 The culture sample is transferred from the core operating system to the slide table;
  • Step5. The door of the incubator opens automatically, the slide table slides out, and the robot loads materials to the incubator to resume cultivation;
  • Each work unit is arranged in an island layout, and each process link is concentrated and operated to improve the single-step operation throughput;
  • Laminar air intake and return air circuits are arranged around the islands of each working unit to ensure a clean operating environment
  • the core operating system contains the core modules:
  • High-degree-of-freedom flexible robot unit (including linear guide rail), used for handling and anthropomorphic operations of various types of materials;
  • the pumping operation of the selected channel can be performed at any position under the linear motion module; under each liquid storage bottle, a weighing unit is installed for automatic notification of liquid rehydration;
  • the centrifuge tube oscillation and turning unit is used for mixing the samples in the centrifuge tube;
  • Centrifuge tube cap opening unit including: feeding linear module, working head of cap uncapping machine, automatic positioning and alignment mechanism; after the robot transfers the centrifuge tube disk to the linear module, the positioning mechanism performs automatic clamping and alignment operations;
  • Magnetic bead sorting unit while magnetic beads are being adsorbed, the waste supernatant is automatically dumped;
  • Cap opening unit for cryopreservation tubes including: feeding linear module, working head of the cap opening machine, automatic positioning and alignment mechanism; after the robot transfers the centrifuge tube disk to the linear module, the positioning mechanism performs automatic clamping and alignment operations ;
  • the scale of the incubator array can be adjusted based on the actual process needs to increase or decrease the number
  • the core operating system can increase the number based on the actual process requirements and connect with the fully automated cultivation system;

Abstract

一种用于大分子的抽提的系统，包括：一个或多个培养箱，所述培养箱用于培养生物样本，以为所述大分子的检测筛选提供基础样本；样本操作系统，所述样本操作系统用于对所述培养箱培养的生物样本实施预定的操作；样本检测平台，所述样本检测平台用于对所述生物样本进行检测以便于筛选；和转运平台，所述转运平台用于在所述培养箱和所述样本操作系统之间和/或在所述样本操作系统和所述样本检测平台之间转运所述生物样本。

Description

用于大分子抽提的系统 技术领域
本公开总体上涉及大分子的技术领域。更特别地，本公开涉及用于大分子抽提的系统。
背景技术
生物药品行业处在快速发展期，大分子生物药品投入大规模的使用。新型药品的研发，特别是在初期有效目标产物的挑选，成为企业产品管线持续竞争力的关键。传统的手工生产方式难以满足即将到来的大分子生物药品在研发阶段的大规模生产与目标产物挑选。
传统的手工生产方式，适用于单个批次，小批量药品生产。用传统手工生产方式实现工业化规模生产，需要：1)数量众多的合格操作人员，2)种类众多的各类仪器设备手动操作，3)大面积的洁净空间。存在以下问题：1)设备与洁净空间的利用率低，2)产品的质量受操作人员的技术水平影响，3)灵活性低，难以实现快速工艺迭代和规模扩展，4)生产及目标产物挑选效率低下，较难实现大规模潜在样本中有效产物的合成、生产、挑选。
发明内容
本公开的目的之一是解决以上问题中的一个或多个并实现其它额外的优点。
在本公开的第一方面，提供了一种用于大分子的抽提的系统，包括：至少一个培养箱，所述培养箱用于培养生物样本，以为所述大分子的抽提提供基础样本；样本操作系统，所述样本操作系统用于对所述培养箱培养的生物样本实施预定的操作，以用于从基础样本抽提大分子；转运平台，所述转运平台用于在所述培养箱和所述样本操作系统之间转运所述生物样本。
根据本公开的一个实施例，所述转运平台包括机器人。
根据本公开的一个实施例，所述机器人设置在地面导轨或空中导轨上。
根据本公开的一个实施例，所述转运平台包括中转滑台，所述机器人能够将生物样本从所述培养箱转移到中转滑台上，所述中转滑台构造用于将生物样本转运到样本操作系统。
根据本公开的一个实施例，所述中转滑台能够批量地转运生物样本。
根据本公开的一个实施例，设置有多个培养箱，所述多个培养箱布置在转运平台两侧。
根据本公开的一个实施例，所述培养箱包括壳体和容纳在所述壳体内的培养组件，所述培养组件设置在自动滑台元件上，以使得所述培养组件能够受控地从所述壳体内滑出或者滑入到所述壳体内。
根据本公开的一个实施例，所述培养箱被构造成对所述生物样本进行自动的温度控制和湿度控制，其中，所述培养箱的内部温度被控制在15～40℃、而其湿度被控制在70～95％，以进行扩增培养。
根据本公开的一个实施例，所述培养箱包括加热膜，所述加热膜对所述培养箱进行自动加热而将其内部温度控制在15～40℃。
根据本公开的一个实施例，所述培养箱包括加湿单元，所述加湿单元包括自动供水单元和雾化器，所述自动供水单元构造成受控地对所述培养箱供水，而所述雾化器构造成将来自所述自动供水单元的水雾化而控制所述培养箱的湿度。
根据本公开的一个实施例，所述培养箱包括制冷压缩机，所述制冷压缩机构造成在需要对所述生物样本进行沉降富集时将所述生物样本的温度控制在2～8℃。
根据本公开的一个实施例，所述培养箱中的一部分培养箱构造成进行对所述生物样本进行扩增培养，而所述培养箱中的另一部分培养箱构造成同时对所述生物样本进行沉降富集。
根据本公开的一个实施例，所述样本操作系统被布置在受控的层流环境中，以使得所述样本操作系统的内部环境与其外部环境隔离开。
根据本公开的一个实施例，所述样本操作系统设置有层流单元，所述层流单元构造成利用压差在所述样本操作系统的内部形成所述层流环境。
根据本公开的一个实施例，所述层流单元包括层流送风单元和层流回风单元，所述层流送风单元布置在所述样本操作系统的顶部，而所述层流回风单元布置在所述样本操作系统的底部。
根据本公开的一个实施例，所述样本操作系统包括操作台面，所述操作台面上安装有两组样本操作组件，所述两组样本操作组件分别在所述操作台面的两侧关于操作台面的中心轴线镜像对称地布置，并且所述两个两组样本操作组件被构造成能够实施独立操作和并行操作这两者。
根据本公开的一个实施例，所述样本操作组件包括以下设备中的至少一种：扫码单元、离心管摇匀单元、摇瓶摇匀单元、离心管开盖单元、摇瓶开盖单元、磁珠分选单元、离心机单元、移液载台、和多自由度机器人。
根据本公开的一个实施例，在所述操作台面上还安装有移液单元和冻存管开盖单元，所述移液单元和冻存管开盖单元布置在操作台面的中心轴线上。
根据本公开的一个实施例，所述样本操作系统被构造成执行以下操作中的至少一种：扫码、开盖、摇匀、离心分离、磁珠分选、移液、泵液和加热。
根据本公开的一个实施例，所述多自由机器人被安装在直线电机模组上，所述直线电机模组包括沿着水平方向延伸的横梁以及安装在所述横梁上并沿着所述横梁的延伸方向驱动所述多自由机器人的直线电机，所述多自由机器人能够在所述横梁上移动，使得所述多自由机器人的作用范围能够基本上覆盖所述样本操作组件的各设备的操作区域。
根据本公开的一个实施例，所述样本操作系统还包括泵液单元，所述泵液单元包括用于存放工艺过程中所需的液体的液体存放单元、用于选择液体泵送通道的泵体面板、用于将液体泵入到耗材中的泵液执行模组以及用于使泵液执行模组运动的运动模组。
根据本公开的一个实施例，所述泵体面板构造用于在多个液体泵送通道中选定一个液体泵送通道，泵液执行模组能够通过运动模组运动到不同的位置并且利用所选定的液体泵送通道进行液体泵入操作。
根据本公开的一个实施例，所述液体存放单元包括至少一个储液容器。
根据本公开的一个实施例，在储液容器下能够安装有称重单元，通过该称重单元能够称量在储液容器中剩余的液体。
根据本公开的一个实施例，所述泵液执行模组构造为离心管泵送装置或摇瓶泵送装置。
根据本公开的一个实施例，所述离心管振荡与翻转单元构造用于使离心管以0度至360度的角度旋转混匀，在混匀过程中能够控制以下参数中的至少一项：旋转速度、旋转循环数量、和旋转方向。
根据本公开的一个实施例，所述离心管开盖单元包括离心管上料直线模块和离心管开盖机工作头，所述离心管上料直线模块构造用于在多自由度机器人将带有离心管的离心管载盘放置到离心管上料直线模块上之后将离心管载盘传送到离心管开盖机 工作头下方。
根据本公开的一个实施例，所述离心管上料直线模块配设有离心管自动定位对准机构，所述离心管自动定位对准机构构造用于定位和夹紧离心管载盘。
根据本公开的一个实施例，所述磁珠分选单元包括用于进行磁珠吸附的磁珠分选架和用于倾倒废弃上清液的磁珠倒液架。
根据本公开的一个实施例，磁珠吸附操作和废弃上清液倾倒操作能够同时进行。
根据本公开的一个实施例，所述冻存管开盖单元包括冻存管上料直线模块和冻存管开盖机工作头，所述冻存管上料直线模块构造用于在多自由度机器人将冻存管载盘放置到冻存管上料直线模块上之后将冻存管载盘传送到冻存管开盖机工作头下方。
根据本公开的一个实施例，所述冻存管上料直线模块配设有冻存管自动定位对准机构，所述冻存管自动定位对准机构构造用于定位和夹紧冻存管载盘。
根据本公开的一个实施例，所述，所述移液单元构造成将工艺过程中所需的液体转移到放置在移液载台上的耗材中，以执行相应的操作。
根据本公开的一个实施例，所述移液单元包括移液机器人以及移液模块，所述移液模块构造成能够在所述移液单元内独立地沿着Z轴运动，其中，所述Z轴与水平平面垂直。
根据本公开的一个实施例，所述移液机器人构造为SCARA机器人。
根据本公开的一个实施例，所述样本操作系统还包括操作载台和用于承载操作载台的耗材载台滑台，所述耗材载台滑台构造成能够受控地滑出和滑入所述样本操作系统，以便于在所述操作载台上加载或卸载耗材。
根据本公开的一个实施例，所述操作台面连同安装在操作台面上的样本操作组件布置在中间仓体中。
根据本公开的一个实施例，所述液体存放单元和所述泵体面板布置在底部仓体中。
根据本公开的一个实施例，所述用于大分子的抽提的系统还包括自动控制系统，所述自动控制系统构造成控制所述培养箱、所述样本操作系统、和所述转运平台中的操作。
在本公开的第二方面，提供了一种适用于大分子抽提自动化生产系统，包括顶部仓体、中间仓体、底部仓体、温控培养箱、机器人及轨道、样本操作系统和电气控制系统，所述顶部仓体包括层流进风和机器人导轨，所述中间仓体包括扫码、开盖、摇 匀、离心机、磁珠分选、移液、泵液存储与泵体单元、加热、电动门及手动门模块，所述底部仓体包括液体储存仓、离心设备存放仓、泵阀控制仓、回风风机和线缆液路。
作为本发明优选的方案，所述温控培养箱的内部设置有设备框架单元，所述温控培养箱的内部下侧设置有摇床机构驱动单元，所述温控培养箱的内部且位于摇床机构驱动单元的上侧设置有自动滑台单元，所述自动滑台单元的上侧设置有摇瓶载盘单元，所述温控培养箱的内部上侧设置有设备照明/净化/消毒单元，所述温控培养箱的右后侧设置有智能化综合控制单元，所述温控培养箱的右侧面设置有设备操作与显示区域，所述温控培养箱的端部右侧设置有自动密封门单元。
作为本发明优选的方案，所述样本操作系统包括上料滑台、移液载台、冻存管开盖机单元、移液机器人及模组、离心管开盖机单元、离心机、磁珠分选单元、离心翻转单元、离心管振荡单元、手动上料台、搬运机器人、自动上料台摇瓶开盖。
作为本发明优选的方案，所述泵液存储与泵体单元包括大容量液体存储、多通道泵体面板、泵液执行单元直线运动模组、泵液执行模组。
作为本发明优选的方案，所述冻存管开盖机单元和离心管开盖机单元均包括上料直线模组、开盖机工作头、自动定位对准机构。
作为本发明优选的方案，所述机器人Z轴独立运动移液单元，安装在SCARA机器人平台上。
作为本发明优选的方案，所述电气控制系统包括温度传感器、重量传感器、压差传感器、光电传感器、摄像头、读码器、I/O采集模块、工控机和驱动模块。
本公开的附加和/或其他方面和优点将在下文的描述中阐述，或者从描述中显而易见或者可以通过本公开的实践来学习。本公开的各种技术特征可以任意组合，只要它们不相互矛盾即可。
附图说明
结合附图，参考下面对本公开的具体实施方式的详细描述，本公开的上面提到的特征和优点和其他特征和优点、以及实现它们的方式将会变得更加显而易见。在附图中：
图1是根据本公开的一个实施例的用于大分子抽提的系统的基本结构前视图；
图2是根据本公开的一个实施例的全自动培养箱单元示意图；
图3是根据本公开的一个实施例的培养箱阵列以及操作样本转运机器人的系统 图；
图4是根据本公开的一个实施例的培养箱阵列与样本操作系统的连接俯视图；
图5是根据本公开的一个实施例的样本操作系统平面布局图；
图6是根据本公开的一个实施例的泵液存储与泵体单元阵列示意图；
图7是根据本公开的一个实施例的离心管振荡与翻转单元示意图；
图8是根据本公开的一个实施例的离心机开盖单元示意图；
图9是根据本公开的一个实施例的磁珠分选单元示意图；
图10是根据本公开的一个实施例的冻存管开盖单元示意图；
图11是根据本公开的一个实施例的移液单元示意图；
图12是根据本公开的一个实施例的样本操作系统基本结构的透视图；
图13是根据本公开的一个实施例的样本操作系统基本结构的另一个透视图；
图14是根据本公开的一个实施例的样本操作流程的示意图；
图15是根据本公开的一个实施例的基本自动控制架构示意图；
图16是根据本公开的一个实施例的智能大分子抽提系统软件架构示意图。
在附图中，相应的附图标记表示相应的部件。这里描述的示例用于阐述本公开的示例性方面，这些示例不应被解释为以任何方式限制本公开的范围。
具体实施方式
以下将参考附图描述本公开，其中的附图示出了本公开的若干实施例。然而应当理解的是，本公开可以以多种不同的方式呈现出来，并不局限于下文描述的实施例；事实上，下文描述的实施例旨在使本公开的公开更为完整，并向本领域技术人员充分说明本公开的保护范围。还应当理解的是，本文公开的实施例能够以各种方式进行组合，从而提供更多额外的实施例。
出于描述的目的，术语“上”、“下”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“横向”、“纵向”以及它们的派生词均与本公开的附图中的取向有关。然而应该理解的是，本公开可以采用各种替代性的变型，除非明确相反地说明。例如，在附图中的装置倒转时，原先描述为在其它特征“下方”的特征，此时可以描述为在其它特征的“上方”。装置还可以以其它方式定向(旋转90度或在其它方位)，此时将相应地解释相对空间关系。
说明书使用的单数形式“一”、“所述”和“该”除非清楚指明，均包含复数形式。说 明书使用的用辞“包括”、“包含”和“含有”表示存在所声称的特征，但并不排斥存在一个或多个其它特征。说明书使用的用辞“和/或”包括相关列出项中的一个或多个的任意和全部组合。
在说明书中，称一个元件位于另一元件“上”、“附接”至另一元件、“连接”至另一元件、“联接”至另一元件、或“接触”另一元件等时，该元件可以直接位于另一元件上、附接至另一元件、连接至另一元件、联接至另一元件或接触另一元件，或者可以存在中间元件。相对照的是，称一个元件“直接”位于另一元件“上”、“直接附接”至另一元件、“直接连接”至另一元件、“直接联接”至另一元件或、或“直接接触”另一元件时，将不存在中间元件。在说明书中，一个特征布置成与另一特征“相邻”，可以指一个特征具有与相邻特征重叠的部分或者位于相邻特征上方或下方的部分。
首先参照图1，示出了根据本公开的一个实施例的用于大分子的抽提的系统。该系统10可以包括：至少一个培养箱1，所述培养箱1用于培养生物样本，以为所述大分子的抽提提供基础样本；样本操作系统3，所述样本操作系统3用于对所述培养箱1培养的生物样本实施预定的操作(比如，与用于大分子的抽提相关的操作，例如开盖、摇匀、离心、磁珠分选、移液、泵液等)，以用于从基础样本抽提大分子；以及转运平台2，所述转运平台2用于在所述培养箱1和所述样本操作系统3之间转运所述生物样本。在根据本公开的一个实施例中，转运平台2可以构造为培养物料转运平台，该培养物料转运平台用于在培养箱1和样本操作系统3之间转运所培养的生物样本。比如，培养物料转运平台可以将培养箱1所培养的生物样本转运至样本操作系统3以供样本操作系统3进行相应的操作，并且还可以将生物样本从样本操作系统3转运回培养箱1，以继续进行培养。多个培养箱1可以构造成培养箱阵列。
在根据本公开的一个实施例中，转运平台2可以包括机器人210(也称为机械臂)，可以利用机器人210来实现生物样本在培养箱1和样本操作系统3之间的转运。在根据本公开的一个实施例中，所述机器人210可以设置在地面导轨或空中导轨上。由此，机器人210可以在地面导轨和/或空中导轨上移动，以在更大范围内进行生物样本的转运。通过使用高速、高自由度机器人自动物料搬运模块，可以实现多种工艺物料(摇瓶、离心管、离心管载架、冻存管盘、96孔板、Tip盒、磁珠载架、工装等)的上下料、转移等，实现培养箱阵列与样本操作系统3之间的高效连接与转移。
下文将分别对系统10的培养箱1和样本操作系统3以及转运平台2进行详细描述。
参照图2，示出了根据本公开的一个实施例的培养箱1的具体结构。培养箱1可以包括壳体100以及容纳在壳体100内的培养组件。培养组件可以包括用于盛放生物样本的一个或多个摇瓶109。所述一个或多个摇瓶109可以放在摇瓶载盘组件105上。摇瓶载盘组件105可以放在自动滑台单元104上，以使得摇瓶载盘组件105及其所承载的摇瓶109在需要时可以受控地从壳体100内滑出或者滑入到壳体100内。摇瓶载盘组件105和自动滑台单元104可以位于框架单元103内。在框架单元103的下方可以设置振荡单元(比如，摇床机构或摇床机构式驱动单元)102，以使摇瓶载盘组件105及其所承载的摇瓶109在需要时可以被振荡。培养箱1的内部还可以设置有设备照明/净化/消毒单元101。设备照明/净化/消毒单元101可以在培养箱1的内部设置在培养箱的上侧位置。合适的设备照明/净化/消毒单元101可以是紫外光照射单元。
在根据本公开的一个实施例中，培养箱1可以是智能培养箱。为此，培养箱1设置有智能化综合控制系统107，以实现对培养箱1的智能化控制。比如，综合控制系统107可以控制振荡单元102的实时振荡、自动滑台单元104的滑入滑出、设备照明/净化/消毒单元的开闭、等等。为了便于操作智能化综合控制系统107，培养箱1还可以包括设备操作与显示区域106。设备操作与显示区域106可以包括诸如触摸屏之类的输入/输出部件，以提供人机交互接口。在根据本公开的一个实施例中，培养箱1还可以包括自动密封门单元108。自动密封门单元108可以在综合控制系统107的控制下自动打开或关闭，以打开或关闭培养箱1。这些均有助于培养箱1与培养物料转运平台的自动化对接。在根据本公开的一个实施例中，还可以利用智能网络单元经由安装在远程终端(比如，电脑、智能手机或其它控制器等)软件向综合控制系统107传输指令，以实现对培养箱1的远程控制。
在根据本公开的一个实施例中，培养箱1可以被构造成能够对生物样本进行自动化控温控湿培养。比如，培养箱1可以实现15～40℃的温度控制和/或70～95％的湿度控制。可以利用加热膜和保温材料来实现培养箱1的温度控制。在该实施例中，加热膜可以由薄膜加热材料制成，用于对培养箱1进行自动加热以使其处于预定的温度范围，而保温材料可以用于减少培养箱1的内部空间与外界的温度传递。为了实现湿度控制，培养箱1可以包括加湿单元。加湿单元可以包括自动供水单元和雾化器。雾化器可以将来自自动供水单元的水雾化而控制培养箱1的湿度。这与传统的培养箱形成对比，传统的培养箱需要操作员定位在其内部放入一定量的水来保持湿度。雾化器可以构造成超声雾化器。雾化器能够在综合控制系统107的控制下根据需要启动或停止， 以有效控制培养箱1内的湿度。
在根据本公开的一个实施例中，培养箱1还可以被构造成能够对生物样本进行自动化的低温沉降富集。培养箱1内可以设置制冷压缩机。制冷压缩机构造成在需要对生物样本进行沉降富集时将生物样本的温度控制在2～8℃，从而实现生物样本的低温沉降。
参见图3和图4，示出了培养箱阵列以及操作样本转运机器人的系统图以及培养箱阵列与样本操作系统3的连接俯视图。
如上所述，转运平台2可以将培养箱1所培养的生物样本转运至样本操作系统3并且还可以将生物样本从样本操作系统3转运回培养箱1。在转运平台2将生物样本从培养箱1转运至样本操作系统3时，首先在综合控制系统107的控制下，自动密封门单元108自动打开。然后自动滑台单元104滑出，以使摇瓶载盘组件105及其所承载的摇瓶109从培养箱1的壳体100内滑出。接着用于转运的机器人210(比如机械臂)将承载有摇瓶的摇瓶载盘组件105转移到转运平台2上。在根据本公开的一个实施例中，摇瓶载盘组件105可以通过机器人从转移到转运平台2的中转运输台220中，以对摇瓶载盘组件105进行临时存储或者说中间存储。当样本操作系统3中所有可进行操作的设备都被占用时，必要时需要对待操作的摇瓶载盘组件105进行临时存储，此时中转运输台220可以承担该临时存储的作用。在样本操作系统3对于待操作的摇瓶载盘组件105再次可用时，再由机器人210将摇瓶载盘组件105从中转运输台220转运到样本操作系统3中。在根据本公开的一个实施例中，在样本操作系统3可用的情况下，摇瓶载盘组件105也可以在从培养箱1的壳体100内滑出之后经由机器人210转移到转运平台2上，并且直接由转运平台2转运到样本操作系统3中。由此，通过转运平台2可以将生物样本批量转运到样本操作系统3，以完成到样本操作系统3内部的上料。在样本操作系统3中，样本操作系统3对生物样本进行样本操作，并完成数据采集与分析。在需要对生物样本再进行培养时，可以将生物样本从样本操作系统3又转运到转运平台2中。在根据本公开的一个实施例中，摇瓶载盘组件105在从样本操作系统3中出来之后，如果没有培养箱1可用，则可以利用机器人210将摇瓶载盘组件105转移中转运输台220中以进行临时存储。在有培养箱1可用时，可以利用机器人210再将摇瓶载盘组件105从转运平台2的中转运输台220转移到可用的培养箱1中。在根据本公开的一个实施例中，摇瓶载盘组件105在从样本操作系统3中出来之后也可以直接被转移到转运平台2中。摇瓶载盘组件105被从转运平台2转移到 自动滑台单元104上。在综合控制系统107的控制下，自动密封门单元108自动打开。然后自动滑台单元104滑入，以使摇瓶载盘组件105再次转运到培养箱1中。
培养箱阵列获取培养耗材(如摇瓶等)后，先批量放置在中转滑台上，待单批次放置完毕后，批量转移至样本操作系统3，可大大提高转运效率。在摇瓶完成补液/换液操作后，批量转移至滑台，统一转运回培养箱阵列。
如图4所示，在设置有多个培养箱1的情况下，所述多个培养箱1可以布置在转运平台2两侧。比如，在设置有四个培养箱1的情况下，在转运平台2的两侧可以分别布置有两个培养箱1。所述多个培养箱中的一部分培养箱1可以构造成进行对所述生物样本进行扩增培养，而所述多个培养箱中的另一部分培养箱1可以构造成同时对所述生物样本进行沉降富集。因此，在布置有多个培养箱1的情况下，各个培养箱1可以分别根据需要承担扩增培养和沉降富集的任务。
样本操作系统3可以整体布置在受控的层流环境中，这使得样本操作系统3的内部环境与其外部环境(比如，样本操作系统3布置于其中的实验室环境)有效隔离开。例如，如图1所示，样本操作系统3可以设置有层流单元。在根据本公开的一个实施例中，层流单元可以构造成利用压差在样本操作系统3的内部形成层流环境。层流单元可以包括层流送风单元。层流送风单元可以设置在样本操作系统3的顶部。层流送风单元可以包括诸如鼓风机或离心风机之类的送风设备，其可以将来自环境或专用气体源的气体以层流的形式送入样本操作系统3的内部。层流单元还可以包括层流回风单元。层流回风单元可以设置在样本操作系统3的底部。层流回风单元可以对样本操作系统3内的层流气体进行循环过滤并将其循环送回到样本操作系统3的内部，从而在操作过程中能够有效地保障人员、样本、和周围环境的安全性。层流送风单元和层流回风单元可以分别配设有相应的过滤单元。通过设置根据本公开的层流送风单元和层流回风单元，可以保证操作区域流场均匀一致，流速合规，保证生产样本的安全。同时，根据本公开的系统10可以提供调试功能，从而可按需求实现工作模式及快速排风模式，保障满足生物安全柜等国家标准中要求的风速与流形相关要求。
下面参照图5至图13对根据本公开的一个实施例的样本操作系统3进行详细描述。
在根据本公开的实施例中，样本操作系统3包括操作台面310，在操作台面310上可以安装有两组样本操作组件300。所述两组样本操作组件300可以具有相同的布置和构造，从而能够实现完全相同的功能。如图5所述，两组样本操作组件300可以 分别布置在操作台面310的两侧。在该实施例中，所述两个样本操作组件300可以关于操作台面310的中心轴线镜像对称地布置。所述两个两组样本操作组件300可以被构造成能够实施独立操作和并行操作这两者，亦即所述两个两组样本操作组件300可以构造成不仅能够彼此独立地操作，而且还能够并行操作。通过布置这样的两组样本操作组件300，可以实现以下优点：1)能够实现不同工艺、不同规格需求的样本的并行操作，提供工艺的适应性；2)能够倍数级地提高根据本公开的系统10的整体操作通量；3)由于设置了两个样本操作组件300，因此，对于系统10中的一些关键操作来说，其具备冗余设计，这使得在两个样本操作组件300中的任意一个产生故障时，仍然能够使用另外一个样本操作组件300来执行相应的关键操作，从而避免了整个系统10的宕机、保障了整个系统10的自动化操作的高可靠性。
参照图5，在根据本公开的一个实施例中，各样本操作组件300可以包括以下设备中的至少一种：扫码单元、离心管摇匀单元330、摇瓶摇匀单元、离心管开盖单元340、摇瓶开盖单元3110、磁珠分选单元360、离心机单元3100、移液载台371、和多自由度机器人311。此外，在操作台面310上还安装有移液单元370和冻存管开盖单元350。移液单元370和冻存管开盖单元350可以布置在操作台面310的中心轴线上。操作台面310连同安装在操作台面310上的样本操作组件300可以布置在中间仓体中。在根据本公开的实施例中，样本操作系统3可以执行用于抽提大分子的各种操作，包括但不限于：扫码、开盖、摇匀、离心分离、磁珠分选、移液、泵液和加热等等。在该实施例中，样本操作系统3中的各个设备按照岛式布局进行布置，通过岛式布局这种可以实现以下优点：1)能够实现各工艺流程环节集聚操作，针对特定操作不需要使生物样本在多个不同的部件之间进行来回转移，而是可以在同一个设备的范围内完成相应的操作，由此提高样本操作效率；2)能够倍数级地提高根据本公开的系统10的单体操作通量。在按照岛式布局布置的各个设备的四周可以布置有层流送风单元和层流回风单元，从而可以确保操作环境洁净。
在根据本公开的一个实施例中，为了实现耗材和生物样本在样本操作系统3内的自动化转运和操作，在样本操作系统3的操作台面310上还可以设置有多自由度机器人311。多自由度机器人311能够以多个自由度(比如，水平移动、竖直移动、围绕自身中心轴线旋转、围绕水平轴线和竖直轴线偏转等)运动。在图13所示的实施例中，多自由度机器人311可以被安装在直线电机模组312上。直线电机模组312可以包括沿着水平方向延伸的横梁313以及安装在横梁313上并沿着横梁313的延伸方向 驱动多自由度机器人311的直线电机。如图12所示，多自由度机器人311可以沿箭头方向移动。当然，多自由度机器人311也可以沿与箭头方向相反的方向移动。由此，多自由度机器人311能够在样本操作系统3的预定范围内移动，从而有助于其在预定范围内自动转运耗材和生物样本。多自由机器人311的作用范围能够基本上覆盖所述样本操作组件300的各设备的操作区域。多自由度机器人311的设置有助于增强根据本公开的系统10的智能化和自动化水平。如图13所示，对于每个样本操作组件300，可以分别设置一个相配设的多自由度机器人311。通过设置多自由度机器人，可以得到高通量高柔性的转移与操作单元，由此可以实现以下优点：1)不同物料能够在不同工位间的高效搬运转移；2)能够调整与控制不同物料的姿态；以及3)能够进行拟人化操作，比如废液倾倒等；
根据本公开的一个实施例中，扫码单元可以构造为对设置在耗材上的识别码或者标签元件进行识别，以实现整机物料的记录和自动管理，实现数据库物料统一管理。该识别码可以构造为条形码或二维码。该标签识别元件可以构造为RFID标签。
在根据本公开的一个实施例中，如图6所示，样本操作系统3还可以包括泵液单元320，泵液单元320包括用于存放工艺过程中所需的液体的液体存放单元321、用于选择液体泵送通道的泵体面板322、用于将液体泵入到耗材中的泵液执行模组323以及用于使泵液执行模组323运动的运动模组324。液体可以从液体存放单元321中经由泵体面板322到达泵液执行模组323。泵液执行模块可以构造为离心管泵送装置或摇瓶泵送装置。泵液执行模组323可以被安装在构造为直线模组的运动模组324上。运动模组324也可以包括沿着水平方向延伸的横梁以及安装在横梁上并沿着横梁的延伸方向驱动泵液执行模组323的直线电机。由此，泵液执行模组323能够在样本操作系统3的预定范围内移动，以对摇瓶或者说耗材进行液体补液操作。液体存放单元321可以在如图6所示的一个实施例中部分地布置在样本操作系统3的位于操作台面310下方的下部区域、例如底部仓体中，部分地布置在位于操作台面310之上的区域、例如中间仓体中。在另一个实施例中，液体存放单元321也可以完全布置在样本操作系统3的位于操作台面310下方的下部区域中，或完全布置在位于操作台面310之上的区域中。液体存放单元321可以包括至少一个储液容器325、比如储液瓶或液体存放箱。在储液容器325下能够安装有称重单元，通过该称重单元能够称量在储液容器325中剩余的液体。在储液容器325中剩余液体低于特定的阈值时，可以通过称重单元检测出这一情况并且自动通知上级设备对储液容器325进行补液。备选地或附加地，在 储液容器325中可以设置有液位传感器，通过该液位传感器可以实现对剩余液位的监测。当称重单元或液位传感器检测到剩余液体不足时，可以发出报警，以提醒对储液容器325进行补液。此外，储液容器325可以具有调温装置，该调温装置可以对存放在储液容器325中的液体进行调温、例如加热、冷却或保温，使得所存放的液体可以具有所需要的不同的液体温度。泵体面板322可以布置在样本操作系统3的位于操作台面310下方的下部区域中。泵体面板322可以邻接于液体存放单元321布置。泵体面板322可以具有多个液体泵送通道，并且构造用于在多个液体泵送通道中选定一个液体泵送通道。所述多个液体泵送通过可以分别与多个相应的储液容器325流体连接，从而形成多个相应的泵液供应管路。这些泵液供应管路彼此间相互独立。在另一个实施例中，泵体面板322也可以具有一个单个的液体泵送通道。泵液执行模组323能够通过运动模组324运动到不同的位置并且利用所选定的液体泵送通道进行液体泵入操作。泵液单元320自身可以具有液体回路清洁功能，其可按工艺液体的使用需求实现快速清洗、深度清洗、反向消毒及钢针内外壁的消毒清洗功能。此外，泵液单元320配设有泵液加热单元，该泵液加热单元可以对工艺流体进行加热。所述加热可以是即时加热。由此可以实现工艺与清洁洁净需求。根据本公开的泵液单元320可以实现以下优点：1)实现生产过程中大剂量溶液的添加，最多可实现数十路至上百路液体的泵液，每一种液体都使用独立的泵液管路，无交叉；2)保障整个液体操作回路的洁净；3)能够对液量进行监测报警；4)能够对存储在液体存放单元321中的液体实现低温、常温、高温温度控制。
在根据本公开的一个实施例中，如图7所示，离心管摇匀单元330可以构造为离心管振荡与翻转单元，其可以包括翻转单元331和离心管振荡单元332。离心管振荡与翻转单元可以构造用于使离心管以0度至360度的角度旋转混匀。在混匀过程中能够控制以下参数中的至少一项：旋转速度、旋转循环数量、和旋转方向。例如，在混匀过程中可以使得翻转单元331沿正方向或负方向翻转，或者说沿顺时针方向或沿逆时针方向翻转。摇瓶摇匀单元在结构上类似于离心管摇匀单元330。通过设置离心管摇匀单元330以及摇瓶摇匀单元，可以实现生产过程中样本的自动摇匀。
在根据本公开的一个实施例中，如图8所示，离心管开盖单元340可以包括离心管上料直线模块341和离心管开盖机工作头342。此外，离心管上料直线模块341可以配设有离心管自动定位对准机构。离心管上料直线模块341构造用于在多自由度机器人将带有离心管的离心管载盘放置到离心管上料直线模块341上之后将离心管载盘 传送到离心管开盖机工作头342下方。离心管自动定位对准机构构造用于对设置在离心管上料直线模块341的离心管载盘进行定位和夹紧。如图10所示，冻存管开盖单元350包括冻存管上料直线模块351和冻存管开盖机工作头352。此外，冻存管上料直线模块351配设有冻存管自动定位对准机构。冻存管上料直线模块351构造用于在多自由度机器人将冻存管载盘放置到冻存管上料直线模块351上之后将冻存管载盘传送到冻存管开盖机工作头352下方。冻存管自动定位对准机构构造用于对设置在冻存管上料直线模块351上的冻存管载盘进行定位和夹紧。摇瓶自动开盖单元的结构类似于离心管开盖单元340或冻存管开盖单元350。通过设置冻存管开盖单元350、离心管开盖单元340以及摇瓶自开盖单元，可以实现各种耗材的自动开关盖，盖子的存放采用向上放置的专用工装，避免交叉物料。
在根据本公开的一个实施例中，如图9所示，磁珠分选单元360可以包括用于进行磁珠吸附的磁珠分选架361和用于倾倒废弃上清液的磁珠倒液架362。磁珠吸附操作和废弃上清液倾倒操作能够同时进行。通过自动的磁珠分选单元360，可以实现样本液自动分选、自动上清液回收、分选磁珠回收以及废液自动排出。磁珠分选单元360可以配设有相应的磁珠液摇匀单元。该磁珠液摇匀单元构造用于对磁珠液进行自动摇匀，从而实现磁珠(分选操作等)上样前的自动摇匀。
在根据本公开的一个实施例中，离心机单元3100可以构造为温控式离心机单元3100。该温控式离心机单元3100可以与相应的物料转运单元共同作用，以进行样本的自动低温/常温/高温离心功能和物料转运，以实现生产过程中样本的有效混匀及有效产物的收集。
在根据本公开的一个实施例中，如图11所示，移液单元370可以构造成将工艺过程中所需的液体转移到放置在移液载台371上的耗材中，以执行相应的操作。移液单元370可以包括移液机器人372以及移液模块373。移液模块373构造成能够在所述移液单元370内独立地沿着Z轴运动，其中，所述Z轴与水平平面垂直。移液机器人372可以构造为SCARA机器人。通过设置Z轴独立运动的移液单元370，并且将移液模块373安装在SCARA机器人平台上，相对于传统X-Y-Z直线电机移液平台，可以实现更大范围的移液操作，并大大提高在操作过程中的灵活性。此外，通过该移液单元370可以实现小剂量药剂的添加以及最终产品的收获封装等。
在根据本公开的一个实施例中，样本操作系统3还可以包括操作载台和用于承载操作载台的耗材载台滑台381，所述耗材载台滑台381构造成能够受控地滑出和滑入 所述样本操作系统3，以便于在所述操作载台上加载或卸载耗材。
在根据本公开的一个实施例中，除了自动上料之外，还可以设置有手动上料台391，通过该手动上料台391可以进行手动上料。手动上料台391配设有相应的搬运机器人392，通过该搬运机器人392可以将手动上料后的耗材转移进入到自动操作路线中。
图14为本发明的样本操作流程的示意图。首先可以将种子液加入到耗材中(比如摇瓶)中。然后使带有种子液的耗材在培养箱1中进行扩增培养，形成经扩增培养的生物样本。接着在培养箱1中对经扩增培养的生物样本进行低温沉降富集。扩增培养和低温沉降富集可以在同一个培养箱1中进行，也可以在培养箱阵列中的不同的培养箱1中进行。然后经由转运平台2将生物样本从培养箱1转移到样本操作系统3中。在样本操作系统3对生物样本进行相应的操作。在对生物样本进行离心分离和富集之后，可以得到中间产物。为了获得足够量的中间产物，可以再进行补液，并将经补液后的生物样本经由转运平台2从样本操作系统3转移到培养箱1中，并再次进行扩增培养和低温沉降富集。在完成了所需的中间产物的离心富集之后，可以对产物进行磁珠分选。接着可以进行DNA清洗，例如通过离心法进行DNA清洗，该DNA清洗可以多轮操作。最后进行DNA封装，从而完成大分子抽提的所有步骤。
如上文所述，在根据本公开的实施例中，系统10可以被构造成自动化和智能化的系统，系统10中的各模块(比如，培养箱1、样本操作系统3、转运平台2等)的所有操作均可以在自动控制系统的控制下自动完成。图15示出了根据本公开的一个实施例的自动控制系统6的架构。如图15所示，根据本公开的自动控制系统6可以包括工控机、输入/输出数据采集模块、和驱动模块。为了进行数据采集，可以在系统10内设置各种采集设备，包括但不限于：温度传感器、重量传感器、压差传感器、光电传感器、摄像头、读码器等。其中，温度传感器、重量传感器、压差传感器、光电传感器、摄像头等可以根据需要布置在系统10内的适当位置。驱动模块用于控制系统10内的各个部件或模块的操作，包括但不限于以下部件或模块的操作：电热膜、机器人(转运、移液等)、泵(泵液、排液等)、电磁阀、离心机、滑台电缸、驱动电机(比如，培养箱的门和摇床的驱动电机)、离心风机、等等。
图16示出了根据本公开的一个实施例的系统配套完整的全流程控制软件。在本公开的系统10中通过控制软件可以实现以下功能中的至少一项：流程编辑功能、设备运行监控与操作功能(针对全自动运行模式)、设备调试工作功能(针对手动操作 模式)、日志提示功能以及设置功能。流程编辑功能包括：全流程工艺清单编辑与管理；标准化工艺模板提供；以及实时工艺管控与调整。设备运行监控与操作功能包括：样本液体操作历史数据；样本磁珠操作历史数据；样本离心操作历史数据；样本孵育操作历史数据；样本转运操作历史数据；各工位物料状态管理；各设备模块运行状态监控；固体耗材上样管理；液体物料上样管理；存储中心耗材存储管理；存储中心耗材补充管理；以及培养整列摇瓶状态管理。设备调试工作(手动操作模式)包括：系统内各运动模块校准校正；系统内各液体单元校准校正；日志提示功能；记录操作人员登录信息；物料上料信息；记录运行过程中设备故障信息；记录运行过程中设备警告信息；以及记录运行过程中设备操作信息。设置功能包括：人员权限设置；系统各模块参数设置；液体管路类型配置；以及液体容量配置。
通过本公开的系统，可以得到以下优点：
1)实现人工操作在研发生产阶段难以企及的通量，实现两个数量级的通量提升。配置全流程智能调度系统，将设备与设施通量发挥到最大，消除过程中的等待浪费；
2)有效避免规模化生产过程中不同批次样本在培养过程中的交叉污染。持续保持生产过程中样本及环境高洁净度；
3)全流程拟人化操作并匹配分子抽提常见工艺模块，高柔性匹配不同工艺操作需求；
4)灵活的工艺编辑能力，并在系统软件内保存常见工艺流程，实现研发阶段工艺高速切换；
5)过程中持续收集、存储、分析工艺参数与工艺结果，实现工艺在线优化；
6)可灵活调整不同的生产规模。
7)使用高通量全自动化温控培养箱阵列，实现种子菌液的大规模培养，并提供扩展接口，可快速扩展规模。
8)实现单日百级/千级/万级不同序列设计质粒培养载体细胞的培养。
下文公开了本公开的其它实施例。
请参阅图1-16本发明提供一种技术方案：
一种适用于大分子抽提自动化生产系统，包括顶部仓体、中间仓体、底部仓体、温控培养箱、机器人及轨道、核心操作系统和电气控制系统，顶部仓体包括层流进风和机器人导轨，所述中间仓体包括扫码、开盖、摇匀、离心机、磁珠分选、移液、泵液存储与泵体单元、加热、电动门及手动门模块，底部仓体包括液体储存仓、离心设备存放仓、泵阀控制仓、回风风机和线缆液路。
温控培养箱的内部设置有设备框架单元，所述温控培养箱的内部下侧设置有摇床机构驱动单元，所述温控培养箱的内部且位于摇床机构驱动单元的上侧设置有自动滑台单元，所述自动滑台单元的上侧设置有摇瓶载盘单元，所述温控培养箱的内部上侧设置有设备照明/净化/消毒单元，所述温控培养箱的右后侧设置有智能化综合控制单元，所述温控培养箱的右侧面设置有设备操作与显示区域，所述温控培养箱的端部右侧设置有自动密封门单元。
核心操作系统包括上料滑台、移液载台、冻存管开盖机单元、移液机器人及模组、离心管开盖机单元、离心机、磁珠分选单元、离心翻转单元、离心管振荡单元、手动上料台、搬运机器人、自动上料台摇瓶开盖。
泵液存储与泵体单元包括大容量液体存储、多通道泵体面板、泵液执行单元直线运动模组、泵液执行模组。
冻存管开盖机单元和离心管开盖机单元均包括上料直线模组、开盖机工作头、自动定位对准机构。
机器人Z轴独立运动移液单元，安装在SCARA机器人平台上。
电气控制系统包括温度传感器、重量传感器、压差传感器、光电传感器、摄像头、读码器、I/O采集模块、工控机和驱动模块。
实施例：a)核心操作系统：基于多机器人系统与全自动化模块，实现大分子抽提全流程的人工操作替代；
1～2个数量级提升大分子抽提工艺环节的生产效率(人工团队20～30样本/日处理通量，自动化系统数百到千级样本/日处理通量)；整个操作过程密封在层流结构中，隔离环境对样本的污染风险，同时隔离系统内样本对安装环境潜在的生物污染风险；
b)大规模温控摇床培养箱阵列：
-在加温培养箱内实现质粒培养载体细胞的扩增；
-在低温培养箱内，实现载体细胞有效的沉降富集，便于核心操作系统内的补液换液操作；
c)转运单元：
-机器人及配套导轨系统，实现样本在核心操作系统与培养箱阵列间的高效转移；
全自动培养箱单元：
1)实现全自动控温控湿培养(25～38C的温度控制，70～95％湿度控制)；
2)实现全自动的低温样本沉降富集(2C～8C温度控制，实现样本沉降)；
3)实现样本全自动的滑入滑出操作，与全自动机器人转运系统对接；
4)实现培养箱门体全自动开关，与全自动机器人转运系统对接；
5)智能网络单元，实现厂务软件对培养箱阵列的远端控制；
培养箱阵列获取培养耗材(如摇瓶等)后，先批量放置在中转滑台上，待单批次放置完毕后，批量转移至核心液体操作系统，可大大提高转运效率；在摇瓶完成补液/换液操作后，批量转移至滑台，统一转运回培养箱阵列；
系统完整的操作流程示例:
Step1.培养箱门自动打开，滑台滑出，转运机器人将培养样本(摇瓶)转移到转运平台上；
Step2.转运平台将培养样本批量转运到核心操作系统，完成到核心操作系统内部的上料；
Step3.核心操作系统进行样本操作，并完成过程中的数据采集与分析；
Step4.培养样本从核心操作系统转运到滑台；
Step5.培养箱门自动打开，滑台滑出，机器人上料到培养箱恢复培养；
核心操作系统：
1)系统左右两侧进行镜像布置，左右两侧并行运行，提高整体操作通量，便于应急冗余备份；
2)各工作单元进行岛式布局，各工艺流程环节集聚操作，提高单步操作通量；
3)各工作单元岛四周布置层流进风与回风回路，保障操作环境洁净；
核心操作系统包含核心模块：
1)自动上料平台，上料暂存及操作盘组盘；
2)高自由度柔性机器人单元(含直线导轨)，用于各类型物料的搬运与拟人操作；
3)泵液单元，用于大容量液体的泵入及管路的全自动清洁；
泵液存储与泵体单元阵列
包括：大容量液体存储、多通道泵体面板、泵液执行单元直线运动模组、泵液执行模组；
可在直线运动模组下任意位置执行选定通道的泵液操作；每个储液瓶下，安装称重单元，进行液体补液自动通知；
4)离心管振荡与翻转单元，用于离心管内样本混合；
实现离心管阵列0～360度的高效旋转混匀，混匀过程中可控制旋转速度、旋转循环数 量、正反方向；
5)离心管开盖单元：包含：上料直线模组、开盖机工作头、自动定位对准机构；机器人将离心管盘传送到直线模组后，定位机构执行自动夹紧对准操作；
6)磁珠分选单元：在进行磁珠吸附的同时，自动倾倒废弃上清液；
7)冻存管开盖单元：包含：上料直线模组、开盖机工作头、自动定位对准机构；机器人将离心管盘传送到直线模组后，定位机构执行自动夹紧对准操作；
8)温控离心机单元；
9)移液平台；
10)移液单元；Z轴独立运动移液单元，安装在SCARA机器人平台上；相对于传统X-Y-Z直线电机移液平台，实现更大范围的移液操作，并大大提高在操作过程中的灵活性；
11)核心操作系统基本结构侧视图，工作台面进行优化，实现接近于单向的物料流通，进一步提高生产流水线的通量与效率；
1.培养箱阵列的规模可基于实际工艺需要，进行数量增加与减少的调整；
2.可更换位反应器阵列等其他培养方式；
3.核心操作系统，可基于实际工艺需求，进行数量的增加，并与全自动化培养系统进行衔接；
4.基于实际工艺需求，可调整核心液体操作系统内机器人单元、各个类型耗材开盖机单元、磁珠操作单元、离心机单元、泵液单元、移液单元等的类型、数量可做对应调整；
5.基于实际工艺要求，进行核心系统内部布局调整；
一个完整的分子抽提的示例流程：如图14，核心操作系统配置完整的电气控制系统，实现全流程的自动化操作：如图15，系统配套完整的全流程控制软件：如图16。
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。

Claims (39)

  1. 一种用于大分子的抽提的系统，包括：
    至少一个培养箱，所述培养箱用于培养生物样本，以为所述大分子的抽提提供基础样本；
    样本操作系统，所述样本操作系统用于对所述培养箱培养的生物样本实施预定的操作，以用于从基础样本抽提大分子；
    转运平台，所述转运平台用于在所述培养箱和所述样本操作系统之间转运所述生物样本。
  2. 根据权利要求1所述的用于大分子的抽提的系统，其中，所述转运平台包括机器人。
  3. 根据权利要求2所述的用于大分子的抽提的系统，其中，所述机器人设置在地面导轨或空中导轨上。
  4. 根据权利要求2所述的用于大分子的抽提的系统，其中，所述转运平台包括中转滑台，所述机器人能够将生物样本从所述培养箱转移到中转滑台上，所述中转滑台构造用于将生物样本转运到样本操作系统。
  5. 根据权利要求2所述的用于大分子的抽提的系统，其中，所述中转滑台能够批量地转运生物样本。
  6. 根据权利要求1所述的用于大分子的抽提的系统，其中，设置有多个培养箱，所述多个培养箱布置在转运平台两侧。
  7. 根据权利要求1所述的用于大分子的抽提的系统，其中，所述培养箱包括壳体和容纳在所述壳体内的培养组件，所述培养组件设置在自动滑台元件上，以使得所述培养组件能够受控地从所述壳体内滑出或者滑入到所述壳体内。
  8. 根据权利要求7所述的用于大分子的抽提的系统，其中，所述培养箱被构造成对所述生物样本进行自动的温度控制和湿度控制，其中，所述培养箱的内部温度被控制在15～40℃、而其湿度被控制在70～95％，以进行扩增培养。
  9. 根据权利要求8所述的用于大分子的抽提的系统，其中，所述培养箱包括加热膜，所述加热膜对所述培养箱进行自动加热而将其内部温度控制在15～40℃。
  10. 根据权利要求8所述的用于大分子的抽提的系统，其中，所述培养箱包括加湿单元，所述加湿单元包括自动供水单元和雾化器，所述自动供水单元构造成受控地 对所述培养箱供水，而所述雾化器构造成将来自所述自动供水单元的水雾化而控制所述培养箱的湿度。
  11. 根据权利要求7所述的用于大分子的抽提的系统，其中，所述培养箱包括制冷压缩机，所述制冷压缩机构造成在需要对所述生物样本进行沉降富集时将所述生物样本的温度控制在2～8℃。
  12. 根据权利要求7所述的用于大分子的抽提的系统，其中，所述培养箱中的一部分培养箱构造成进行对所述生物样本进行扩增培养，而所述培养箱中的另一部分培养箱构造成同时对所述生物样本进行沉降富集。
  13. 根据权利要求1所述的用于大分子的抽提的系统，其中，所述样本操作系统被布置在受控的层流环境中，以使得所述样本操作系统的内部环境与其外部环境隔离开。
  14. 根据权利要求13所述的用于大分子的抽提的系统，其中，所述样本操作系统设置有层流单元，所述层流单元构造成利用压差在所述样本操作系统的内部形成所述层流环境。
  15. 根据权利要求14所述的用于大分子的抽提的系统，其中，所述层流单元包括层流送风单元和层流回风单元，所述层流送风单元布置在所述样本操作系统的顶部，而所述层流回风单元布置在所述样本操作系统的底部。
  16. 根据权利要求1所述的用于大分子的抽提的系统，其中，所述样本操作系统包括操作台面，所述操作台面上安装有两组样本操作组件，所述两组样本操作组件分别在所述操作台面的两侧关于操作台面的中心轴线镜像对称地布置，并且所述两个两组样本操作组件被构造成能够实施独立操作和并行操作这两者。
  17. 根据权利要求16所述的用于大分子的抽提的系统，其中，所述样本操作组件包括以下设备中的至少一种：扫码单元、离心管摇匀单元、摇瓶摇匀单元、离心管开盖单元、摇瓶开盖单元、磁珠分选单元、离心机单元、移液载台、和多自由度机器人。
  18. 根据权利要求17所述的用于大分子的抽提的系统，其中，在所述操作台面上还安装有移液单元和冻存管开盖单元，所述移液单元和冻存管开盖单元布置在操作台面的中心轴线上。
  19. 根据权利要求16所述的用于大分子的抽提的系统，其中，所述样本操作系统被构造成执行以下操作中的至少一种：扫码、开盖、摇匀、离心分离、磁珠分选、 移液、泵液和加热。
  20. 根据权利要求17所述的用于大分子的抽提的系统，其中，所述多自由机器人被安装在直线电机模组上，所述直线电机模组包括沿着水平方向延伸的横梁以及安装在所述横梁上并沿着所述横梁的延伸方向驱动所述多自由机器人的直线电机，所述多自由机器人能够在所述横梁上移动，使得所述多自由机器人的作用范围能够基本上覆盖所述样本操作组件的各设备的操作区域。
  21. 根据权利要求16所述的用于大分子的抽提的系统，其中，所述样本操作系统还包括泵液单元，所述泵液单元包括用于存放工艺过程中所需的液体的液体存放单元、用于选择液体泵送通道的泵体面板、用于将液体泵入到耗材中的泵液执行模组以及用于使泵液执行模组运动的运动模组。
  22. 根据权利要求21所述的用于大分子的抽提的系统，其中，所述泵体面板构造用于在多个液体泵送通道中选定一个液体泵送通道，泵液执行模组能够通过运动模组运动到不同的位置并且利用所选定的液体泵送通道进行液体泵入操作。
  23. 根据权利要求21所述的用于大分子的抽提的系统，其中，所述液体存放单元包括至少一个储液容器。
  24. 根据权利要求23所述的用于大分子的抽提的系统，其中，在储液容器下能够安装有称重单元，通过该称重单元能够称量在储液容器中剩余的液体。
  25. 根据权利要求21所述的用于大分子的抽提的系统，其中，所述泵液执行模组构造为离心管泵送装置或摇瓶泵送装置。
  26. 根据权利要求17所述的用于大分子的抽提的系统，其中，所述离心管摇匀单元构造为离心管振荡与翻转单元，该离心管振荡与翻转单元构造用于使离心管以0度至360度的角度旋转混匀，在混匀过程中能够控制以下参数中的至少一项：旋转速度、旋转循环数量、和旋转方向。
  27. 根据权利要求17所述的用于大分子的抽提的系统，其中，所述离心管开盖单元包括离心管上料直线模块和离心管开盖机工作头，所述离心管上料直线模块构造用于在多自由度机器人将带有离心管的离心管载盘放置到离心管上料直线模块上之后将离心管载盘传送到离心管开盖机工作头下方。
  28. 根据权利要求27所述的用于大分子的抽提的系统，其中，所述离心管上料直线模块配设有离心管自动定位对准机构，所述离心管自动定位对准机构构造用于定位和夹紧离心管载盘。
  29. 根据权利要求17所述的用于大分子的抽提的系统，其中，所述磁珠分选单元包括用于进行磁珠吸附的磁珠分选架和用于倾倒废弃上清液的磁珠倒液架。
  30. 根据权利要求29所述的用于大分子的抽提的系统，其中，磁珠吸附操作和废弃上清液倾倒操作能够同时进行。
  31. 根据权利要求18所述的用于大分子的抽提的系统，其中，所述冻存管开盖单元包括冻存管上料直线模块和冻存管开盖机工作头，所述冻存管上料直线模块构造用于在多自由度机器人将冻存管载盘放置到冻存管上料直线模块上之后将冻存管载盘传送到冻存管开盖机工作头下方。
  32. 根据权利要求31所述的用于大分子的抽提的系统，其中，所述冻存管上料直线模块配设有冻存管自动定位对准机构，所述冻存管自动定位对准机构构造用于定位和夹紧冻存管载盘。
  33. 根据权利要求18所述的用于大分子的抽提的系统，其中，所述，所述移液单元构造成将工艺过程中所需的液体转移到放置在移液载台上的耗材中，以执行相应的操作。
  34. 根据权利要求33所述的用于大分子的抽提的系统，其中，所述移液单元包括移液机器人以及移液模块，所述移液模块构造成能够在所述移液单元内独立地沿着Z轴运动，其中，所述Z轴与水平平面垂直。
  35. 根据权利要求34所述的用于大分子的抽提的系统，其中，所述移液机器人构造为SCARA机器人。
  36. 根据权利要求16所述的用于大分子的抽提的系统，其中，所述样本操作系统还包括操作载台和用于承载操作载台的耗材载台滑台，所述耗材载台滑台构造成能够受控地滑出和滑入所述样本操作系统，以便于在所述操作载台上加载或卸载耗材。
  37. 根据权利要求16所述的用于大分子的抽提的系统，其中，所述操作台面连同安装在操作台面上的样本操作组件布置在中间仓体中。
  38. 根据权利要求21所述的用于大分子的抽提的系统，其中，所述液体存放单元和所述泵体面板布置在底部仓体中。
  39. 根据权利要求1所述的用于大分子的抽提的系统，其中，所述用于大分子的抽提的系统还包括自动控制系统，所述自动控制系统构造成控制所述培养箱、所述样本操作系统、和所述转运平台中的操作。
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