Cell parallel reaction equipment

Abstract

The invention discloses a cell parallel reaction device, comprising: a reactor work station, which comprises at least one reactor capable of independently accommodating a plurality of reaction tanks; a pore plate placement area; a TIP head loading area; the pipetting system is configured to be capable of moving among the reactor workstation, the pore plate placing area and the TIP head loading area so as to pick up the TIP head, open and close the reaction tank, pick and place a micropore plate cover and a TIP head box cover, and suck and discharge liquid; a temperature control system; a gas path control system; a parameter detection system; and the control system is used for coordinating and controlling operation parameters of the reactor workstation, the pipetting system, the temperature control system, the gas circuit control system and the parameter detection system so as to realize automatic parallel culture of the cell parallel reaction equipment. According to the invention, systematic integration and collaborative design are realized, closed-loop automation of the whole process from culture, sampling to material supplement is realized, manual intervention is completely replaced, and experimental flux, consistency and sterile guarantee are greatly improved.

Description

Technical Field

[0001] This invention relates to the field of embryonic cell culture technology, and more specifically to a cell parallel reaction device. Background Technology

[0002] A parallel cell reactor is a bioreactor system used for the simultaneous and parallel culture and expansion of multiple cells. Its core objectives are to improve experimental efficiency, optimize process parameters, and ensure reproducibility and scalability.

[0003] Traditional bioreactors are mostly single-tank operations, and only one set of process parameters can be tested in a single experiment. This results in a long process development cycle, high costs, and difficulty in obtaining reliable and comparable experimental data due to batch-to-batch differences. In contrast, parallel bioreactor systems integrate multiple micro-reaction units to achieve simultaneous testing of multiple sets of culture conditions.

[0004] However, existing parallel reaction equipment has fragmented functional modules and insufficient integration and automation. For example, most systems only realize the physical parallel connection of reaction vessels and centralized control of basic parameters (such as stirring and temperature), but key cultivation operations (such as feeding, sampling, and waste removal) still require manual intervention or rely on external, separate, and cumbersome equipment. This operating mode not only easily introduces the risk of contamination, but also seriously restricts the experimental throughput and timeliness.

[0005] Therefore, it is necessary to provide a new approach to solve the aforementioned technical problems. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a cell parallel reaction device that achieves systematic integration and collaborative design, realizing closed-loop automation from culture and sampling to feeding, completely replacing manual intervention, and greatly improving experimental throughput, consistency, and aseptic assurance.

[0007] The technical solution of this invention is summarized as follows: The purpose of this invention is to provide a cell parallel reaction device, comprising: A reactor workstation, comprising at least one reactor capable of independently accommodating several reaction vessels; An orifice plate placement area, located beside the reactor workstation, is used to place at least one orifice plate; A TIP head loading area is provided next to the reactor workstation for placing at least two sizes of TIP heads; A pipetting system configured to move between the reactor workstation, the orifice plate placement area, and the TIP head loading area to pick up TIP heads, open and close the reaction vessel, pick up and place the microplate cover and TIP head box cover, and perform liquid aspiration and discharge. A temperature control system, which is connected to the reactor workstation and the orifice plate placement area, to provide independent temperature control for the reactor and the orifice plate placement area; A gas supply control system is provided for each of the aforementioned reaction vessels, which is used to independently deliver and regulate the culture gas into the corresponding reaction vessel. A parameter detection system, which is installed in the reactor workstation and corresponds to each of the reaction tanks, is used to detect the dissolved oxygen and / or pH value in the corresponding reaction tanks; The control system is used to coordinate and control the operating parameters of the reactor workstation, the pipetting system, the temperature control system, the gas path control system, and the parameter detection system to achieve automated parallel culture of the cell parallel reaction equipment.

[0008] Preferably, the working volume of the reaction vessel is 10-15 ml.

[0009] Preferably, the control system is configured to independently set, monitor, and adjust the temperature, pH value, dissolved oxygen concentration, and stirring speed in each of the reaction vessels.

[0010] Preferably, the reaction vessel is equipped with a magnetic stirring assembly; the reactor integrates several magnetic drive components. Each of the magnetic drive components is arranged around the periphery of a reaction vessel and is adapted to the position of the magnetic stirring component; Each of the magnetic drive components is configured to be independently controllable to drive the magnetic stirring components in the corresponding reaction vessel to rotate, and to achieve independent adjustment of the stirring speed of each reaction vessel.

[0011] Preferably, the temperature control system employs semiconductor refrigeration technology, and the temperature control system is configured to adjust the culture temperature of the reaction vessel within the reactor workstation within the range of 20°C to 40°C.

[0012] Preferably, the orifice plate placement area includes at least four independent placement stations, and at least one of the placement stations has a temperature control module integrated at its bottom. The temperature control module is connected to the temperature control system to regulate the temperature of the orifice plate placed thereon.

[0013] Preferably, the TIP head loading area includes at least two loading stations arranged side by side, each used to place TIP head plates of different volume specifications.

[0014] Preferably, the pipetting system includes: A pipetting stand is a support structure used to form a pipetting system. A drive unit, which is mounted on the pipetting rack; A pipetting device, which is mounted to and driven by the driving device; the pipetting device includes at least two sets of independent pipetting components and a liquid path control module that provides independent liquid path control for each set of pipetting components; A gripping device, which is mounted to and driven to move by the drive device; The pipetting assembly is configured to pick up at least two different sizes of TIP tips; the gripping device includes a gripper assembly for opening and closing the reaction vessel and / or a suction cup assembly for picking up and placing the microplate cover and the TIP tip box cover.

[0015] Preferably, it further includes: a TIP tip removal assembly, which includes a waste TIP tip collection box and a TIP tip removal block disposed on the waste TIP tip collection box; wherein the TIP tip removal block is configured to be adapted to TIP tips of different sizes to peel the TIP tip off the pipetting assembly and drop it into the waste TIP tip collection box.

[0016] Preferably, it further includes: an integrated consumables carrying area, which is configured to centrally hold purified water bottles, cleaning solution bottles, at least one culture medium bottle and waste liquid bottle, and each bottle is connected to the liquid circuit control module of the pipetting system through a pipeline.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides a parallel cell reaction apparatus. By systematically integrating and coordinating the reactor workstation, well plate placement area, TIP tip loading area, pipetting system, temperature control system, gas path control system, parameter detection system, and control system, it achieves fully closed-loop automation from culture and sampling to feeding. The pipetting system can autonomously move between the reactor workstation, well plate area, and TIP tip loading area, completing a full set of operations such as opening the lid, grasping, pipetting, and discarding tips, completely replacing manual intervention and greatly improving experimental throughput, consistency, and aseptic assurance. Furthermore, it provides independent multi-dimensional environmental parallel control capabilities, with an integrated temperature control system and an independently configured gas path control system for each reaction vessel, enabling stirring, Temperature, gas composition, and flow rate can all be controlled in parallel with high precision as independent variables. Combined with the parameter detection system, each reaction vessel is provided with independent online pH / DO monitoring, forming an independent sensing and control loop for each reaction unit. This ensures high precision and comparability of process conditions, enabling multi-task queue management, real-time data feedback, and process optimization. In particular, the reactor workstation and well plate placement area are equipped with independent temperature control systems, which not only provide a stable and independent culture temperature for each reaction vessel, but also ensure that reagents and samples in the well plates are always at the set temperature before and after processing. This avoids cell stress or reagent failure caused by temperature fluctuations, achieving completely independent and precise control of environmental parameters for each reaction unit. The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it according to the contents of the specification, the preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings. Specific embodiments of the present invention are given in detail below with reference to the accompanying drawings. Attached Figure Description

[0018] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this application, illustrate exemplary embodiments of the invention and, together with their description, serve to explain the invention and do not constitute an undue limitation thereof. In the drawings: Figure 1 This is a schematic diagram of the overall structure of the parallel cell reaction device in an embodiment of the present invention. Figure 1 ; Figure 2 This is a schematic diagram of the overall structure of the parallel cell reaction device in an embodiment of the present invention. Figure 2 ; Figure 3 This is a schematic diagram of the overall structure of the parallel cell reaction device in an embodiment of the present invention. Figure 3 ; Figure 4 This is a schematic diagram of the overall structure of the reactor workstation in an embodiment of the present invention; Figure 5 This is a schematic diagram of the installation structure of the reactor cover and the ventilation element in an embodiment of the present invention; Figure 6 This is a schematic diagram showing the arrangement of the heat insulation and ventilation plates in the reactor in an embodiment of the present invention; Figure 7 This is a schematic diagram of the operation of the reactor workstation in an embodiment of the present invention; Figure 8 This is a schematic diagram of the assembly of the reaction vessel in an embodiment of the present invention; Figure 9 This is a schematic diagram of the overall structure of the pipetting system in an embodiment of the present invention. Figure 1 ; Figure 10 This is a schematic diagram of the overall structure of the pipetting system in an embodiment of the present invention. Figure 2 ; Figure 11 This is a schematic diagram of the installation structure of the Y-axis moving unit, the Z-axis moving unit, and the pipetting assembly in an embodiment of the present invention; Figure 12 This is a schematic diagram of the structure of the Y-axis moving unit in an embodiment of the present invention; Figure 13 This is a schematic diagram showing the layout of the lifting drive motor in an embodiment of the present invention; Figure 14 This is a schematic diagram of the installation structure of the Z-axis moving unit and the pipetting assembly in an embodiment of the present invention. Figure 1 ; Figure 15 This is a schematic diagram of the installation structure of the Z-axis moving unit and the pipetting assembly in an embodiment of the present invention. Figure 2 ; Figure 16 This is an installation structure diagram of the ball spline pair, lifting module and pipetting assembly in an embodiment of the present invention; Figure 17 This is a schematic diagram of the pipetting assembly in an embodiment of the present invention; Figure 18 This is a diagram showing the assembly relationship between the pipette connector and the TIP tip in an embodiment of the present invention; Figure 19 This is the suction cup air path system in an embodiment of the present invention; Figure 20 This is a connection diagram of the liquid circuit control module in an embodiment of the present invention; Figure 21 This is a schematic diagram showing the connection between the orifice plate placement area and the temperature control system in an embodiment of the present invention; Figure 22 This is a schematic diagram of the structure of the perforated plate placement area in an embodiment of the present invention; Figure 23 This is a schematic diagram of the structure of the TIP header loading area in an embodiment of the present invention; Figure 24 This is a schematic diagram of the structure of the TIP header removal assembly in an embodiment of the present invention.

[0019] In the diagram: 1. Parallel cell reaction equipment; 10. Pipetting system; 11. Frame; 12. Drive unit; 121. X-axis moving unit; 1211. X-axis drive motor; 1212. X-axis synchronous belt drive mechanism; 1213. X-axis linear guide; 122. Y-axis moving unit; 1221. Y-axis moving bracket; 1222. Y-axis drive motor; 1223. Y-axis synchronous belt drive mechanism; 1224. Y-axis linear guide; 123. Z-axis moving unit; 1231. Lifting module; 12311. Gear; 12312. Rack; 1231 01. First lifting module; 123102. Second lifting module; 123103. Third lifting module; 1232. Z-axis moving bracket; 1233. Ball spline pair; 12331. Spline shaft; 12332. Spline sleeve; 123301. First ball spline pair; 123302. Second ball spline pair; 123303. Third ball spline pair; 1234. Lifting drive motor; 12341. First lifting drive motor; 12342. Second lifting drive motor; 12343. Third... Lifting drive motor; 1235, Z-axis linear guide; 12351, first Z-axis linear guide; 12352, first Z-axis linear guide; 12353, first Z-axis linear guide; 13, pipetting device; 131, pipetting assembly; 13101, first pipetting assembly; 13102, second pipetting assembly; 1311, pipetting connector; 13111, first connecting part; 13112, second connecting part; 13113, fluid connection end; 1312, pipetting mounting base; 13121, support frame; 13 13. Buffer structure; 13131. Connecting screw; 13132. Buffer spring; 132. Liquid circuit control module; 1321. Pipette pump assembly; 13211. Small capacity plunger pump; 13212. Large capacity plunger pump; 1322. Waste liquid removal pump assembly; 1323. Cleaning pump assembly; 1324. Gas purging pump assembly; 1325. Bubble sensor; 1326. Liquid level detection sensor; 14. Gripping device; 141. Gripper assembly; 142. Suction cup assembly; 15. Origin optocoupler; 16. Position optocoupler; 20. Reactor workstation; 21. Reactor; 2101. Receiving cavity; 211. Reactor seat; 2111. Connecting component; 212. Reactor cover plate; 213. Drive plate; 214. Cooling plate; 215. Ventilation element; 216. Quick-locking mechanism; 2161. Clamping device; 2162. Clamping port; 217. Heat insulation vent plate; 2171. Gas passage; 2172. Air inlet; 22. Reaction vessel; 221. Magnetic stirring assembly; 22 11. Stirring rotor; 2212. Stirring paddle; 22121. Stirring rod; 22122. Stirring blade; 222. Tank body; 2221. Protrusion; 223. Tank cover; 2231. Air inlet; 2232. Condensation chamber; 224. Vent column; 2241. Gas flow passage; 225. Exhaust structure; 2251. Air outlet; 2252. One-way valve; 226. Plunger; 23. Magnetic drive assembly; 231. Drive component; 232. Speed ​​sensor; 30. Orifice plate placement area; 31. Placement station; 311. Temperature control module; 322. Positioning structure; 3221. Positioning stop; 3222. Elastic positioning seat; 32. Orifice plate; 40. TIP head loading area; 41. Loading station; 411. TIP head plate locking block; 412. TIP head plate fixing post; 42. TIP head plate; 421. First TIP head plate; 422. Second TIP head plate; 50. Temperature control system; 51. Temperature control piping; 511. Reaction temperature control piping; 512. Drive temperature control piping; 513. Condensation temperature control piping; 514. Orifice plate temperature control piping; 52. Temperature control drive unit; 521. Reaction temperature control drive unit; 522. Drive temperature control drive unit; 523. Condensation temperature control drive unit; 524. Orifice plate temperature control drive unit; 5201. Semiconductor cooling chip; 5202. Heat transfer fluid transfer chamber; 5203. Heat dissipation module; 5204. Circulation pump; 60. Parameter detection system; 61. Detection optical fiber; 62. DO detection fluorescent membrane; 63. pH detection fluorescent membrane; 70. Gas circuit control system; 80. Control system; 90. TIP head removal assembly; 91. Waste TIP head collection box; 92. TIP head removal block; 921. First slot; 922. Second slot; 93. TIP head removal fixing plate; 100. Integrated consumables carrying area. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] In the accompanying drawings, shapes and dimensions may be enlarged for clarity, and the same reference numerals will be used in all figures to indicate the same or similar parts.

[0022] In the following description, terms such as center, thickness, height, length, front, back, rear, left, right, top, bottom, upper, and lower are defined relative to the structure shown in the accompanying drawings. In particular, "height" corresponds to the dimension from top to bottom, "width" corresponds to the dimension from left to right, and "depth" corresponds to the dimension from front to back. These are relative concepts and may vary depending on their location and usage. Therefore, these or other orientations should not be interpreted as restrictive terms.

[0023] Terms involving attachment, connection, etc. (e.g., “connection” and “attachment”) refer to the relationship in which these structures are directly or indirectly fixed or attached to each other through an intermediate structure, as well as movable or rigid attachments or relationships, unless otherwise explicitly stated. Example

[0024] This invention provides a cell parallel reaction device 1, combined with... Figures 1-24 As shown, it includes: Reactor workstation 20 includes at least one reactor 21 that can independently accommodate a plurality of reaction vessels 22; An orifice plate placement area 30 is provided on the side of the reactor workstation 20 for placing at least one orifice plate; TIP head loading area 40, which is located beside the reactor workstation 20, is used to place at least two sizes of TIP heads; The pipetting system 10 is configured to move between the reactor workstation 20, the orifice plate placement area 30, and the TIP head loading area 40 to pick up TIP heads, open and close the reaction vessel 22, pick up and place the microplate cover and the TIP head box cover, and perform liquid aspiration and discharge. Temperature control system 50, which is connected to the reactor workstation 20 and the orifice plate placement area 30, to provide independent temperature control for the reaction vessel 22 and the orifice plate placement area 30; A parameter detection system 60 is installed in the reactor workstation 20 and corresponds to each of the reaction tanks 22, for detecting the dissolved oxygen and / or pH value in the corresponding reaction tank 22. The gas path control system 70 is configured with an independent gas supply passage for each of the reaction vessels 22, for independently delivering and regulating the culture gas into the corresponding reaction vessel 22; The control system 80 is used to coordinate and control the operating parameters of the reactor workstation, the pipetting system, the temperature control system and the parameter detection system to realize automated parallel culture of the cell parallel reaction equipment.

[0025] This embodiment achieves closed-loop automation of the entire process from culture and sampling to feeding by systematically integrating and coordinating the reactor workstation, well plate placement area, TIP tip loading area, pipetting system, temperature control system, parameter detection system, and control system. The pipetting system can move autonomously between the reactor workstation, well plate area, and TIP tip loading area to complete a full set of operations such as opening the cap, grabbing, pipetting, and discarding the tip, completely replacing manual intervention and greatly improving experimental throughput, consistency, and aseptic assurance.

[0026] Furthermore, this embodiment provides independent multi-dimensional environmental parallel control capabilities, an integrated temperature control system, and a gas path control system independently configured for each reaction vessel. This allows stirring, temperature, gas composition, and flow rate to be controlled in parallel with high precision as independent variables. Combined with a parameter detection system, each reaction vessel is provided with independent online pH / DO monitoring, forming an independent sensing and control loop for each reaction unit. This ensures high precision and comparability of process conditions, enabling multi-task queue management, real-time data feedback, and process optimization.

[0027] The reactor workstation and well plate placement area are equipped with independent temperature control systems, which not only provide a stable and independent culture temperature for each reaction vessel, but also ensure that the reagents and samples in the well plates are always at the set temperature before and after processing, avoiding cell stress or reagent failure caused by temperature fluctuations, and achieving complete independent and precise control of the environmental parameters of each reaction unit.

[0028] In some embodiments, the working volume of the reaction vessel is 10-15 ml. This volume design not only fills the technological gap in the field of 15 ml-level high-throughput parallel cell reaction equipment in China, but also directly and significantly reduces the cost of using extremely expensive cell culture media and growth factors. That is, this embodiment can perfectly balance the miniaturization requirements of high-throughput parallel experiments with the volume requirements for obtaining sufficient analytical samples, so as to be able to screen up to 12 or 24 or even more parallel process conditions at the same time with extremely low cell and reagent consumption, shortening the traditional process development cycle that takes months and costs a lot to a few weeks, and significantly reducing the early research and development costs and risks.

[0029] Because the miniaturized reaction volume makes the culture system more sensitive to changes in environmental parameters such as temperature, pH, and dissolved oxygen, a more rapid and precise response from the control system is required. Therefore, in some embodiments, the control system is configured to independently set, monitor, and adjust the temperature, pH, dissolved oxygen concentration, and stirring speed within each reaction vessel. The independent high-precision temperature control system, magnetic stirring system, and parameter detection system integrated in this embodiment can achieve better control precision and uniformity than traditional large-volume reactors under these small volume conditions, providing a more stable, uniform, and controllable microenvironment for sensitive cells such as cells, and helping to obtain more reliable and reproducible experimental data.

[0030] In some preferred embodiments, combined with Figures 4-8 As shown, the reactor workstation 20 includes: Reactor 21, which has several accommodating cavities 2101 formed therein; A plurality of reaction vessels 22 are provided, and one reaction vessel 22 is correspondingly provided in each of the receiving cavities 2101; and a magnetic stirring assembly 221 is provided inside the reaction vessel 22. And a plurality of magnetic drive components 23 integrated in the reactor 21, each of the magnetic drive components 23 being arranged around a receiving cavity 2101 and adapted to the position of the magnetic stirring component 221; Each of the magnetic drive components 23 is configured to be independently controllable to drive the magnetic stirring component 221 in the corresponding reaction vessel 22 to rotate, and to achieve independent adjustment of the stirring speed of each reaction vessel 22.

[0031] In some preferred embodiments, the magnetic drive assembly 23 includes a drive element 231 and a speedometer 232.

[0032] In some preferred embodiments, the number of receiving cavities 2101 in the reactor 21 is 4-24; in this embodiment, two reactors 21 are provided, each reactor 21 has 12 receiving cavities 2101 arranged in an array, and each receiving cavity 2101 corresponds to a reaction vessel 22; that is, this embodiment includes 24 independently arranged reaction vessels 22.

[0033] This embodiment, by configuring each containment cavity 2101 with an independently controllable magnetic drive component 23, allows the stirring speed of each reaction vessel 22 to be independently set and adjusted in real time. This supports multiple parallel control experiments that require changing the stirring intensity as an experimental variable, improving experimental efficiency and data comparability. Furthermore, the arrangement of the magnetic drive component 23 around the containment cavity 2101 and its spatial adaptation to the magnetic stirring component 221 within the reaction vessel 22 generates a more uniform and stable three-dimensional rotating magnetic field, effectively improving the uniformity of culture medium mixing and avoiding mixing dead zones. This embodiment satisfies the parallelism requirements of high-throughput experiments while ensuring the independence and precise controllability of the culture conditions for each unit, providing a reliable technical foundation for the development of standardized and automated cell culture processes.

[0034] In some embodiments, the reactor 21 includes: The reactor base 211 is used to support the reaction vessel 22; specifically, the reactor base 211 is internally machined to form a plurality of receiving cavities 2101 to precisely support and position each reaction vessel 22. The reactor cover 212 is removably fitted over the reactor seat 211 to press the reaction vessel 22, ensuring that each reaction vessel 22 remains stably sealed during the cultivation process; A drive plate 213 and a cooling plate 214 are disposed between the reactor base 211 and the reactor cover 212; wherein... The magnetic drive component 23 is integrated within the drive plate 213; The cooling plate 214 is disposed above the drive plate 213 to fit against the top area of ​​the reaction vessel 22 to suppress evaporation of the culture medium and promote condensation reflux.

[0035] Specifically, the drive plate 213 serves as the core driving carrier, highly integrating each of the magnetic drive components 23 in a modular form. Each magnetic drive component 23 surrounds the upper part of the outer periphery of the reaction vessel 22 and corresponds one-to-one with the position of the magnetic stirring component 221 inside, thereby achieving non-contact magnetic coupling drive. The drive plate 213 is fixed to the reactor seat 211 via a connector 2111. The cooling plate 214 is arranged above the drive plate 213 and closely fits the lid 223 or upper wall area of ​​each reaction vessel 22. It can actively control the top temperature, reduce culture medium evaporation loss, and maintain the humidity and composition stability of the culture environment, making it suitable for long-duration and sensitive cell culture processes. This embodiment effectively improves the reliability, accuracy, and ease of operation in high-throughput parallel culture applications.

[0036] In some preferred embodiments, a quick-locking mechanism 216 is provided between the reactor cover 212 and the reactor seat 211. This mechanism can employ structures such as snap-fit, threaded locking, or magnetic locking to achieve rapid closing and opening between the reactor cover 212 and the reactor seat 211, while ensuring a stable and reliable sealing pressure during the cultivation process. In this embodiment, the quick-locking mechanism 216 includes a clamp 2161 disposed on the reactor cover 212 and a clamping port 2162 on the reactor seat 211, which is simple, reliable, and quick to operate.

[0037] In some preferred embodiments, the reactor cover 212 is equipped with a plurality of independent ventilation elements 215, each of the ventilation elements 215 being connected to the top of a reaction vessel 22 to form an independent gas flow path.

[0038] Furthermore, the reactor 21 also includes a heat-insulating vent plate 217, which is disposed between the drive plate 213 and the cooling plate 214, and the heat-insulating vent plate 217 is provided with a plurality of independent gas passages 2171. The side wall of the heat-insulating vent plate 217 is provided with an air inlet 2172 that communicates with the corresponding gas passage 2171 for connection to the gas path control system 70.

[0039] Specifically, the ventilation element 215 is detachably installed on the reactor cover plate 212, with one end extending to the top of the receiving cavity 2101 to communicate with the reaction vessel 22, and the other end communicating with the gas passage 2171 disposed in the heat insulation ventilation plate 217. Each gas passage 172 is connected to a corresponding ventilation element 215. That is, in this embodiment, the gas supply passage is constituted by the gas control system 70, the gas passage 2171, and the ventilation element 215.

[0040] Correspondingly, in this embodiment, 24 independent gas supply channels are configured through the gas path control system 70 to connect to each of the aforementioned reaction vessels 22 to achieve independent control of the gas supply. That is, the gas path control system 70 can achieve completely independent and precise control of the culture atmosphere of each reaction vessel 22. The proportions and ventilation rates of gases such as oxygen and carbon dioxide can be set individually for each reaction vessel 22 according to different cell types or experimental conditions, thereby further supporting multivariate parallel culture studies. At the same time, the ventilation element 215 in this embodiment avoids connecting multiple messy external gas paths, optimizes the overall structure, reduces the risk of cross-contamination, and improves the reliability and repeatability of high-throughput experiments.

[0041] In some embodiments, the temperature control system 50 includes at least three temperature control lines 51 and a temperature control drive unit 52 connected to each of the temperature control lines 51; wherein... At least one of the temperature control pipes 51 is installed inside the reactor base 211 to regulate the culture temperature of the reaction vessel 22; At least one of the temperature control pipes 51 is installed inside the drive plate 213 to regulate the operating temperature of the magnetic drive assembly 23; At least one of the temperature control pipes 51 is installed inside the cooling plate 214 to regulate the condensation temperature at the top of the reaction vessel 22.

[0042] Specifically, this embodiment includes two reaction temperature control pipelines 511 and a reaction temperature control drive unit 521 connected to the reaction temperature control pipelines 511, thereby regulating the culture temperature of the reaction vessel 22 to ensure cell growth in a suitable environment; a drive temperature control pipeline 512 and a drive temperature control drive unit 522 connected to the drive temperature control pipeline 512 are provided to regulate the operating temperature of the magnetic drive component 23 to ensure its long-term reliable operation; a condensation temperature control pipeline 513 and a condensation temperature control drive unit 523 connected to the condensation temperature control pipeline 513 are provided to regulate the condensation temperature at the top of the reaction vessel 22 to maintain the stability of the culture system and prevent evaporation loss. This embodiment, through three independent temperature control systems, achieves independent regional control of the culture environment temperature, the operating temperature of the drive component, and the top condensation temperature, improving the overall temperature control accuracy and stability of the system.

[0043] In some embodiments, the temperature control system 50 employs semiconductor refrigeration technology, and the temperature control system 50 is configured to adjust the culture temperature of the reaction vessel 22 within the reactor workstation 20 within the range of 20°C to 40°C.

[0044] Furthermore, each of the temperature control drive units 52 includes: The semiconductor cooling chip 5201, the heat transfer fluid transfer chamber 5202, and the heat dissipation module 5203; among them... The semiconductor cooling chip 5201 is connected to the heat transfer fluid transfer chamber 5202 and the heat dissipation module 5203 respectively; The heat transfer fluid transfer chamber 5202 is connected to the temperature control pipeline 51 to form a closed loop; When the heat transfer fluid circulates within the temperature control pipeline 51, it enables temperature control of the reactor base 211, drive plate 213, and cooling plate 214.

[0045] The process of temperature regulation by each of the temperature control drive units 52 includes at least the following: Temperature control of reaction vessel 22: When the heat transfer fluid flows from the heat transfer fluid transfer chamber 5202 into the reactor seat 211 through the reaction temperature control pipeline 511, it fully exchanges heat with the reactor seat 211 during the flow process, so as to achieve uniform and precise control of the culture temperature of the reaction vessel 22; by adjusting the power and polarity of the semiconductor cooling chip 5201, the temperature of the reactor seat 211 can be freely set within a temperature range of, for example, 20°C to 40°C to meet the needs of different cell types and culture stages.

[0046] Temperature control of drive board 213: When the heat transfer fluid flows from the heat transfer fluid transfer chamber 5202 into the drive board 213 through the drive temperature control pipeline 512, it continuously absorbs the heat generated when the magnetic drive coil is working, and the temperature of the drive board 213 is monitored in real time by the temperature sensor; the control system dynamically adjusts the output of the semiconductor cooling chip 5201 according to the feedback signal, so that the temperature of the drive board 213 is stabilized within the set target range, ensuring the long-term reliable operation of the drive component.

[0047] Temperature control of cooling plate 214: When the heat transfer fluid flows from the heat transfer fluid transfer chamber 5202 into the cooling plate 214 through the condensation temperature control pipeline 513, the heat transfer fluid cooled by the semiconductor cooling chip 5201 keeps the cooling plate 214 at a low temperature. The cooling plate 214 is in close contact with the top of the reaction vessel 22 to form a low-temperature condensation surface, which causes the water vapor evaporated in the reaction vessel 22 to condense on its surface and flow back to the culture medium, effectively maintaining the stability of the culture system.

[0048] In some preferred embodiments, the heat transfer fluid transfer chamber 5202 and the reactor seat 211 are both wrapped with heat insulation materials such as heat insulation cotton to significantly reduce heat exchange with the external environment, improve temperature control efficiency and accuracy, and reduce energy consumption.

[0049] In some embodiments, the reaction vessel 22 includes: Tank body 222; in some embodiments, the bottom of the tank body 222 is formed with at least one protrusion 2221 to reduce mixing dead zones; A can lid 223, which is detachably fitted onto the can body 222; A ventilation column 224 is formed inside the can lid 223 and extends into the can body 222, and a gas flow passage 2241 is formed inside the ventilation column 224 to deliver culture gas into the can. An exhaust structure 225 is installed with the can lid 223 and communicates with the can body 222 to allow gas inside the can to be discharged unidirectionally to the outside.

[0050] Specifically, the can lid 223 is provided with an air inlet 2231. One end of the air inlet 2231 is connected to the gas flow passage 2241, and the other end is connected to the ventilation element 215, so as to introduce gas from the outside of the can lid 223 into the culture medium or above the liquid surface.

[0051] Furthermore, the exhaust structure 225 includes an outlet 2251 disposed on the can cover 223 and a one-way valve 2252 connected to the outlet 2251, so as to allow the gas inside the can to be safely discharged when the pressure accumulates, while effectively preventing the backflow of external pollutants.

[0052] In some preferred embodiments, the can lid 223 also forms an outwardly protruding condensation chamber 2232, and the air outlet 2251 is disposed at the condensation chamber 2232; wherein, after the reaction tank 22 and the reactor 21 are assembled, the cooling plate 214 is attached to the condensation chamber 2232 of the reaction tank 22 for water vapor condensation and reflux at the air outlet 2251.

[0053] Furthermore, a plunger 226 is provided on the lid 223 to open and close the tank 222, facilitating the addition of culture medium or other materials to the tank 222. The plunger 226 is a silicone stopper.

[0054] In some preferred embodiments, the magnetic stirring assembly 221 is rotatably mounted on the venting column 224 and extends to the bottom region of the tank 222.

[0055] Further, the magnetic stirring assembly 221 includes: a stirring rotor 2211 and a stirring paddle 2212 mounted on the stirring rotor 2211; wherein, The stirring rotor 2211 is rotatably mounted to the vent column 224, and the stirring rotor 2211 has a built-in magnet; The stirring paddle 2212 includes a stirring rod 22121 extending toward the bottom of the tank 222 and a stirring blade 22122 disposed at the end of the stirring rod 22121; When the stirring rotor 2211 drives the stirring paddle 2212 to rotate to stir the culture medium, the stirring rotor 2211 is positioned above the surface of the culture medium.

[0056] Specifically, the stirring rotor 2211 can be rotatably connected to the venting column 224 through a bearing or a low-friction bushing, and a magnet is embedded inside it, which is magnetically coupled to the magnetic drive assembly 23. When in operation, the stirring rotor 2211 is completely above the surface of the culture medium, with only the stirring rod 22121 and the stirring blade 22122 immersed in the liquid to perform the stirring function.

[0057] This embodiment isolates the stirring rotor 2211 from the culture medium, completely avoiding direct contact between the magnet and the culture medium, eliminating potential biocompatibility risks and contamination hazards caused by the magnet material, and facilitating maintenance and cleaning. Furthermore, the top-mounted design of the stirring rotor 2211 reduces the resistance of the rotating components in the liquid, improving transmission efficiency. In addition, compared to existing structures that directly embed the magnet in the stirring blades 22122, this embodiment allows the stirring blades 22122 to be freed from the limitations of magnet shape and arrangement, thus enabling flexible optimization of the blade morphology, installation angle, and effective working area according to the culture characteristics of different cell types (such as shear stress sensitivity, mixing requirements, and flow field characteristics).

[0058] In some embodiments, the parameter detection system 60 includes a detection optical fiber 61 and an optical sensing film; the detection optical fiber 61 is installed on the reactor seat 211 and corresponds to each receiving cavity 2101, and the optical sensing film is disposed on the bottom inner wall of the reaction vessel 22; The end of the detection optical fiber 61 is optically coupled to the optical sensing film, and is used to detect the environmental parameters of the culture medium in the corresponding reaction vessel 22 in real time through fluorescence signals.

[0059] Furthermore, the optical sensing film includes a DO detection fluorescent film 62 for detecting dissolved oxygen and / or a pH detection fluorescent film 63 for detecting pH.

[0060] Specifically, the detection optical fiber 61 extends upward from the bottom of the corresponding accommodating cavity 2101 of the reactor seat 211, and two detection optical fibers 61 are installed at the bottom of each accommodating cavity 2101. Their ends are optically coupled to the DO detection fluorescent membrane 62 and the pH detection fluorescent membrane 63, respectively. By measuring the changes in the excitation-reception fluorescence signal, the dissolved oxygen and pH value in the culture medium are calculated in real time. Furthermore, the detection optical fiber 61 is connected to an external data acquisition module, which automatically adjusts the aeration rate in the reaction vessel 22 based on the dissolved oxygen and pH value detection results.

[0061] The cultivation process in this embodiment includes at least the following: The reaction vessel 22 is fitted into the cavity 2101 of the reactor seat 211 according to the shape of the cavity 2101; the temperature control function of the reactor seat 211 and the drive plate 213 is activated, and the reactor seat 211 reaches the target temperature and maintains stability; the clamp on the reactor cover 212 engages with the clamping port of the reactor seat 211; the venting element 215 connects the gas passage 2171 in the heat insulation venting plate 217 to the air inlet 2231 of the reaction vessel 22; the reactor cover 212 rests on the cooling plate 214 and is also attached to the lid 223 of the reaction vessel 22; the plunger 226 of the reaction vessel 22 is opened. Culture medium and other materials are added to reaction vessel 22; magnetic drive assembly 23 drives stirring rotor 2211 to rotate, causing stirring to rotate; culture gas is introduced into gas passage 2171 through air inlet 2172 of heat insulation vent plate 217, and then through venting element 215 from air inlet 2231 of reaction vessel 22 to venting column 224, and finally into and above the culture medium; detection fiber optic 61 detects dissolved oxygen and pH value in reaction vessel 22 through DO detection fluorescent membrane 62 and pH detection fluorescent membrane 63, and adjusts the ventilation rate; during this process, temperature control drive unit 52 controls the temperature of reactor seat 211, drive plate 213 and cooling plate 214.

[0062] In some embodiments, combined with Figure 21 and Figure 22 As shown, the orifice plate placement area 30 includes at least four independent placement stations 31. At least one of the placement stations 31 has a temperature control module 311 integrated at its bottom. The temperature control module 311 is connected to the temperature control system 50 to regulate the temperature of the orifice plate 32 placed thereon.

[0063] Furthermore, the temperature control system 50 also includes an orifice plate temperature control pipeline 514 connected to the temperature control module 311, and an orifice plate temperature control drive unit 524 connected to the orifice plate temperature control pipeline 514, thereby realizing the adjustment and control of the temperature of the orifice plate 32 placement area.

[0064] Furthermore, the temperature control module 311 is a water-cooled box with internal flow channels. The orifice plate temperature control drive unit 524, in conjunction with the orifice plate temperature control pipeline 514 and the circulating pump 5204, circulates the heat transfer fluid through the water-cooled box to achieve heating or cooling of the orifice plate 32.

[0065] When the perforated plate 32 needs to be heated, the control system 80 instructs the semiconductor cooling chip 5201 of the perforated plate temperature control drive unit 524 to operate in heating mode, heating the liquid in the heat transfer fluid transfer chamber 5202; the circulation pump 5204 pumps the heated heat transfer fluid into the flow channel of the water-cooled box through the perforated plate temperature control pipeline 514, and the heat is quickly conducted to the upper surface of the placement station 31 through the water-cooled box body, thereby uniformly heating the placed perforated plate 32.

[0066] When cooling of the orifice plate 32 is required, the control system 80 instructs the semiconductor cooling chip 5201 of the orifice plate temperature control drive unit 524 to operate in cooling mode, cooling the liquid in the heat transfer fluid transfer chamber 5202; the circulation pump 5204 pumps the cooled low-temperature liquid into the water-cooled box through the orifice plate temperature control pipeline 514, and the water-cooled box absorbs the heat of the orifice plate 32 and the sample inside the plate, realizing active cooling of the orifice plate 32.

[0067] This embodiment can precisely control the orifice plate temperature to the set value by adjusting the power of the semiconductor cooling chip 5201 and the flow rate of the circulating fluid, and has the characteristics of rapid heating and cooling and high stability.

[0068] Furthermore, in order to improve the versatility and ease of operation of the plate placement area 30, each placement station 31 is provided with a positioning structure 322 that can be adapted to various specifications of plate 32, so as to realize the rapid and accurate positioning and stable support of various specifications of plate 32 commonly used in the laboratory; for example, 12-well plates, 24-well plates, 96-well microplates, etc. can be placed.

[0069] Furthermore, the positioning structure 322 includes positioning blocks 3221 disposed on both sides adjacent to the placement station 31; wherein at least one positioning block 3221 is provided with an elastic positioning seat 3222 on the opposite side. Specifically, in this embodiment, the positioning blocks 3221 provide a rigid positioning reference for the orifice plate 32, and the elastic positioning seat 3222 provides an elastic clamping force to the orifice plate 32 pointing towards the positioning blocks 3221, thereby achieving fast and reliable clamping and improving work efficiency; it can also give the orifice plate 32 excellent vibration and impact resistance, ensuring its positional stability in the equipment row and eliminating the risk of pipetting failure or needle collision caused by displacement.

[0070] In some embodiments, combined with Figure 23 As shown, the TIP tip loading area 40 includes at least two loading stations 41 arranged side by side, each for placing TIP tip plates 42 of different volumes. In this embodiment, the TIP tip plate 42 includes at least a first TIP tip plate 421 for loading 1mTIP tips and a second TIP tip plate 422 for loading 5mTIP tips; further, each loading station 41 is provided with a TIP tip plate locking block 411 and a TIP tip plate fixing post 412 for positioning and fixing the TIP tip plate 42; wherein, the TIP tip plate 42 is provided with a TIP tip box cover that can be picked up by the suction cup assembly of the pipetting system.

[0071] In some embodiments, combined with Figures 9-20 As shown, the pipetting system 10 includes: The pipetting stand 11 is used to form a support structure for the pipetting system 10; Drive unit 12, which is mounted on the pipetting frame 11; A pipetting device 13 is mounted to and driven by the drive device 12; the pipetting device 13 includes at least two sets of independent pipetting components 131, and a liquid path control module 132 that provides independent liquid path control for each set of pipetting components 131. The driving device 12 is configured to drive the pipetting device 13 to move in a horizontal plane and independently drive each pipetting component 131 to perform lifting and lowering movements. The liquid circuit control module 132 individually controls the liquid aspiration and dispensing operations of each of the pipetting components 131, so as to enable each of the pipetting components 131 to perform pipetting work independently or synchronously.

[0072] This embodiment configures at least two sets of pipetting components 131 with independent lifting and independent liquid path control capabilities, enabling each pipetting component 131 to simultaneously or according to any logical sequence independently perform actions such as descent, aspiration or dispensing, and ascent. It can independently or synchronously perform pipetting operations on different targets, effectively increasing the throughput per unit time and meeting the experimental requirements of high throughput and real-time monitoring. Moreover, this design simplifies the mechanical structure, reduces manufacturing costs, and optimizes the overall layout while ensuring the independence of lifting and liquid path control.

[0073] Furthermore, the pipetting assembly 131 is configured to pick up at least two different sizes of TIP tips; for example, in this embodiment, the pipetting assembly 131 is configured to pick up 1ml TIP tips and 5ml TIP tips; when a micro-pipette operation is required, the control system 80 drives the pipetting assembly 131 to move above the loading station 41 in the TIP tip loading area 40 where the 1ml TIP tip plate (first TIP tip plate 421) is stored; the pipetting assembly 131 descends and assembles with the 1ml TIP tip to complete the pickup. When a large volume liquid transfer is required, the control system 80 drives the pipetting assembly 131 to move to the loading station 41 where the 5ml TIP tip plate (second TIP tip plate 422) is stored; the pipetting assembly 131 descends in the same manner and assembles with the 5ml TIP tip to achieve pickup.

[0074] In some embodiments, combined with Figure 9 As shown, the driving device 12 includes: X-axis moving unit 121 is fixedly installed with the pipette frame 11; Y-axis moving unit 122 is connected to the power output end of X-axis moving unit 121; Z-axis moving unit 123 is connected to the power output end of Y-axis moving unit 122; Among them, the Z-axis moving unit 123 includes at least two independently driven lifting modules 1231, and the pipetting component 131 is correspondingly installed on the lifting module 1231.

[0075] Specifically, the Y-axis moving unit 122 is driven by the X-axis moving unit 121 to move along the X-axis direction, and the Z-axis moving unit 123 is driven by the Y-axis moving unit 122 to move along the Y-axis direction; the pipetting component 131 is driven by the lifting module 1231 to move up and down along the Z-axis direction.

[0076] To endow the pipetting system 1 with more functions, in some preferred embodiments, it further includes: a grasping device 14, which is installed with the driving device 12 and is driven by the driving device 12 to move; and the grasping device 14 can independently perform lifting movement under the control of the driving device 12.

[0077] Furthermore, in combination Figure 14 and Figure 15 as shown, the grasping device 14 includes a jaw component 141 for opening and closing the reaction tank 22 and / or a suction cup component 142 for picking and placing the cover of the microplate and the cover of the TIP head box. Among them, the jaw component 141 is used to clamp and place the plunger 226 of the reaction tank 22 to open and close the reaction tank 22; the suction cup component 142 is used to suck and place the cover of the microplate to open and close the microplate and / or the cover of the TIP head box. Specifically, when picking up the TIP head, the suction cup sucks the cover of the TIP head box, and the pipetting component 131 picks up the TIP head. After the operation is completed, the suction cup returns the cover of the TIP head box to avoid contamination of the TIP head; when it is necessary to pick up the culture medium, the suction cup sucks the cover of the well plate. After the operation is completed, the suction cup returns the cover of the well plate to avoid contamination of the culture medium.

[0078] Among them, a suction cup gas circuit system配套 with the suction cup component 142 is also provided, which is used to realize the suction and placement of flat objects such as the cover of the microplate and the cover of the TIP head box. In combination Figure 19 as shown, the suction cup gas circuit system mainly includes: a diaphragm air pump, two two-way three-way solenoid valves, and two three-way connectors; among them, the diaphragm air pump is used as a gas source power device to provide positive pressure / negative pressure air flow; the two-way three-way solenoid valve is used to switch the on / off of the gas circuit and the air flow direction; the two three-way connectors are respectively connected to the diaphragm air pump, the two-way three-way solenoid valve and the gas circuit branch to realize the splitting and confluence of the air flow.

[0079] The working process of the suction cup air circuit in this embodiment includes at least the following: suction operation: controlling one of the two-position three-way solenoid valves to switch directions, so that a negative pressure air circuit is formed between the diaphragm air pump and the suction cup, and a vacuum suction force is generated in the suction cup, thereby adsorbing the orifice plate cover or TIP head box cover; placement operation: controlling the other two-position three-way solenoid valve to switch directions, so that the diaphragm air pump provides a positive pressure airflow to the suction cup, breaking the vacuum state in the suction cup, and the orifice plate cover or TIP head box cover is released under the action of positive pressure and its own gravity; through the suction cup air circuit system, the picking and placing of the orifice plate cover and TIP head box cover in the pipetting system can be completed quickly and stably.

[0080] In some alternative embodiments, the suction cup assembly 142 is fixedly mounted to the gripper assembly 141 so as to move synchronously with the gripper assembly 141 under the control of the drive device 12.

[0081] In some alternative embodiments, the gripper assembly 141 and the suction cup assembly 142 can perform independent lifting and lowering movements under the control of the drive device 12. Specifically, the Z-axis moving unit 123 includes multiple independently driven lifting modules 1231. Each pipetting assembly 131, gripper assembly 141, and suction cup assembly 142 is installed with its corresponding lifting module 1231 to perform independent lifting and lowering movements under the drive of the lifting module 1231. That is, in this embodiment, the gripper assembly 141, suction cup assembly 142, and pipetting assembly 131 can all perform independent lifting and lowering movements under the control of the drive device 12.

[0082] In some preferred embodiments, combined with Figures 9-10 As shown, the X-axis moving unit 121 includes: X-axis drive motor 1211; X-axis synchronous belt transmission mechanism 1212 driven by the X-axis drive motor 1211; And the X-axis linear guide 1213 fixedly installed on the pipette frame 11; The Y-axis moving unit 122 is mounted on the slider of the X-axis linear guide 1213 and connected to the X-axis synchronous belt transmission mechanism 1212, so as to move along the X-axis linear guide 1213 under the drive of the X-axis drive motor 1211.

[0083] This embodiment employs a high-precision linear motion scheme that combines a motor-driven synchronous belt transmission mechanism with an X-axis linear guide rail 1213 fixed to the pipetting frame 11 to provide guiding support. This achieves stable movement capabilities with a wide range and high speed in the X-axis direction of the horizontal plane, enabling rapid and accurate positioning along the X-axis. Its structure is stable and reliable, with high transmission efficiency and low maintenance costs, laying the foundation for flexible and efficient operation of the entire pipetting device in the horizontal plane.

[0084] In some preferred embodiments, combined with Figure 9 , Figures 11-12 As shown, the Y-axis movement unit 122 includes: The Y-axis moving bracket 1221 is connected to the power output end of the X-axis moving unit 121. Specifically, the Y-axis moving bracket 1221 is mounted on the slider of the X-axis linear guide 1213 and connected to the X-axis synchronous belt transmission mechanism 1212 so as to move along the X-axis linear guide 1213 under the drive of the X-axis drive motor 1211. Y-axis drive motor 1222 is installed on the Y-axis moving bracket 1221; Y-axis synchronous belt transmission mechanism 1223 driven by the Y-axis drive motor 1222; And a Y-axis linear guide 1224 fixedly installed with the Y-axis moving bracket 1221; The Z-axis moving unit 123 is mounted on the slider of the Y-axis linear guide 1224 and connected to the Y-axis synchronous belt transmission mechanism 1223, so as to move along the Y-axis linear guide 1224 under the drive of the Y-axis drive motor 1222.

[0085] This embodiment effectively ensures the smoothness and positioning accuracy of the pipetting assembly in the Y-axis direction, and provides high rigidity support for the Z-axis moving unit 123. Its structure is stable and reliable, with high transmission efficiency and low maintenance cost.

[0086] In some preferred embodiments, combined with Figure 9 , Figures 11-16 As shown, the Z-axis movement unit 123 further includes: Z-axis moving bracket 1232 is connected to the power output end of Y-axis moving unit 122; specifically, Z-axis moving bracket 1232 is mounted on the slider of Y-axis linear guide 1224 and connected to Y-axis synchronous belt transmission mechanism 1223, so as to move along Y-axis linear guide 1224 under the drive of Y-axis drive motor 1222; A plurality of ball spline pairs 1233 are mounted to the Y-axis moving unit 122, and the Z-axis moving bracket 1232 is assembled with the ball spline pairs 1233; A plurality of lifting drive motors 1234, each of the lifting drive motors 1234 being assembled with a corresponding ball spline pair 1233; And a plurality of Z-axis linear guides 1235 mounted to the Z-axis moving bracket 1232; Each of the lifting modules 1231 is mounted on the slider of the corresponding Z-axis linear guide 1235 and assembled with the corresponding ball spline pair 1233; the lifting drive motor 1234 drives the ball spline pair 1233 to rotate, so as to drive the lifting module 1231 to move up and down along the extension direction of the Z-axis linear guide 1235.

[0087] Furthermore, each of the ball spline pairs 1233 includes a spline shaft 12331 and a spline sleeve 12332; wherein, the spline shaft 12331 extends along the Y-axis direction and is rotatably mounted with the Y-axis moving bracket 1221, and one end of the spline shaft 12331 is assembled with the power output end of the lifting drive motor 1234; the spline sleeve 12332 is assembled with the spline shaft 12331 through a ball assembly, so that the spline sleeve 12332 can slide with low friction relative to the spline shaft 12331 along the Y-axis direction, or can be combined with the spline shaft 12331 to rotate synchronously under the drive of the lifting drive motor 1234.

[0088] Furthermore, the lifting module 1231 is a gear and rack structure; that is, the lifting module 1231 includes a gear 12311 installed with the spline sleeve 12332 and a rack 12312 meshing with the gear 12311, wherein the rack 12312 is installed with the slider of the Z-axis linear guide 1235, and the end of the rack 12312 is used to fix it to the pipetting assembly 131.

[0089] During operation, when the pipetting assembly 131 is controlled to move along the Y-axis, the Z-axis moving bracket 1232, driven by the Y-axis moving unit 122, drives the spline sleeve 12332 to slide with low friction relative to the spline shaft 12331 along the Y-axis, thereby forming a more precise guide. When the pipetting assembly 131 is controlled to move up and down along the Z-axis, the lifting drive motor 1234 drives the spline shaft 12331 to rotate, which in turn drives the spline sleeve 12332 connected to the spline shaft 12331 to rotate synchronously. At this time, the gear 12311 installed on the spline sleeve 12332 rotates synchronously with the spline sleeve 12332. Through the meshing transmission between the gear 12311 and the rack 12312, the rack moves up and down to drive the pipetting assembly to move up and down.

[0090] This embodiment creatively integrates Y-axis sliding and Z-axis driving functions into a single component through a unique combination of spline shaft 12331 and spline sleeve 12332. During operation, spline sleeve 12332 serves as a key interface: during Y-axis movement, it forms a low-friction sliding pair with spline shaft 12331, providing precise guidance; during Z-axis lifting, it locks with spline shaft 12331 and transmits torque, efficiently converting rotational motion into linear lifting. This design eliminates redundant transmission components in traditional designs, minimizing the power transmission path. It not only results in an extremely compact structure but also significantly improves the transmission stiffness, response speed, and positioning accuracy of Z-axis motion, facilitating high-speed, high-precision independent lifting of the pipetting assembly 131.

[0091] In some preferred embodiments, several of the lifting drive motors 1234 are mounted on the Y-axis moving bracket 1221 and positioned close to the X-axis linear guide rail 1213.

[0092] For example, such as Figure 11 , Figure 12 , Figure 14 and Figure 15 As shown, the device includes a first pipetting assembly 13101, a second pipetting assembly 13102, and a gripping device 14. Correspondingly: to control the lifting and lowering of the first pipetting assembly 13101, a first ball spline joint 123301, a first lifting drive motor 12341, a first Z-axis linear guide 12351, and a first lifting module 123101 are provided; to control the lifting and lowering of the second pipetting assembly 13101, a second ball spline joint 123302, a second Z-axis linear guide 12352, a second lifting drive motor 12342, and a second lifting module 123102 are provided; to control the lifting and lowering of the gripping device 14, a third ball spline joint 123303, a third lifting drive motor 12343, a third Z-axis linear guide 12353, and a third lifting module 123103 are provided.

[0093] The first lifting drive motor 12341, the second lifting drive motor 12342, and the third lifting drive motor 12343 are all installed in the same area of ​​the Y-axis moving bracket 1221, and transmit rotational power to their respective spline sleeves 12332 through their corresponding spline shafts 12331, thereby driving the corresponding lifting modules 1231 to move. On the one hand, this centralized layout facilitates wiring; on the other hand, it allows for centralized and controllable mass distribution of the moving parts, which helps reduce the system's moment of inertia, thereby improving the dynamic response and positioning stability during high-speed Y-axis movement, and increasing the overall system reliability and rigidity.

[0094] In some preferred embodiments, such as Figure 2As shown, it also includes: an origin optical coupler 15, which is disposed on the pipetting frame 11 to define the zero point position of motion, so as to ensure precise control and positioning of the motion of each axis.

[0095] In some preferred embodiments, such as Figure 10 As shown, it also includes: a position optocoupler 16, which is disposed on the pipetting frame 11, for detecting whether the drive motor has lost steps.

[0096] In some embodiments, combined with Figures 14-18 As shown, the pipetting assembly 131 includes a pipetting connector 1311 and a pipetting mounting base 1312; wherein, The pipetting mounting base 1312 is installed with the lifting module 1231; The pipetting connector 1311 is fixed to the pipetting mounting base 1312 and communicates with the liquid circuit control module 132; and the pipetting connector 1311 includes at least two connecting parts to adapt to TIP tips of different sizes.

[0097] In this embodiment, the pipette connector 1311 includes a first connecting part 13111 and a second connecting part 13112. The first connecting part 13111 is adapted to a 5ml TIP tip, and the second connecting part 13112 is adapted to a 1ml TIP tip, so as to facilitate the use of the corresponding TIP tip according to different pipetting needs. For example, when adding culture medium to the reaction vessel at the beginning, a 5ml TIP tip is used for sample addition. During the culture process, when extracting culture waste liquid from the reaction vessel or adding culture medium, a 1ml TIP tip is used for operation.

[0098] In some preferred embodiments, a buffer structure 1313 is provided between the pipetting mounting base 1312 and the lifting module 1231 to ensure reliability during the TIP tip removal process.

[0099] Furthermore, the buffer structure 1313 includes a connecting screw 13131 and a buffer spring 13132 sleeved on the connecting screw 13131. The connecting screw 13131 passes through the bottom through hole of the pipetting mounting base 1312 to be fixed to the bottom of the rack 12312 of the lifting module 1231. The two ends of the buffer spring 13132 are in contact with the bottom of the rack 12312 and the pipetting mounting base 1312, respectively.

[0100] Furthermore, the pipetting mounting base 1312 also includes a support frame 13121, which is used to fix the pipetting connector 1311 and allow the liquid flow connection end 13113 of the pipetting connector 1311 to extend out to connect with the liquid circuit control module 132.

[0101] In some preferred embodiments, combined with Figure 9and Figure 20 As shown, the liquid circuit control module 132 includes: a pipetting pump assembly 1321, a waste liquid removal pump assembly 1322, and a cleaning pump assembly 1323, all connected to the pipetting component 131; wherein, The pipetting pump assembly 1321 is used to perform the aspiration and expulsion of nutrient solution; The waste liquid removal pump set 1322 is used to perform the rapid removal of nutrient solution waste liquid from the reaction tank; The cleaning pump assembly 1323 is used to clean the fluid lines of the liquid control module 132 and fill the pipette pump assembly 1321 with purified water.

[0102] Furthermore, the pipetting pump assembly 1321 includes a small-capacity plunger pump 13211 and a large-capacity plunger pump 13212 connected in series; the outlet of the small-capacity plunger pump 13211 and the inlet of the large-capacity plunger pump 13212 are connected to the pipetting connector 1311 through a valve assembly, so that the small-capacity plunger pump 13211 and the large-capacity plunger pump 13212 can be selectively connected in series according to pipetting needs; in this embodiment, the small-capacity plunger pump 13211 is a 1ml plunger pump and the large-capacity plunger pump 13212 is a 10ml plunger pump.

[0103] In some preferred embodiments, the waste liquid removal pump assembly 1322 includes a peristaltic pump; the peristaltic pump can be connected to the fluid pipeline of the pipetting assembly 131 and the waste liquid collection container through a valve assembly; during operation, the control system opens the corresponding valve and starts the peristaltic pump, which can directly and quickly draw the culture waste liquid in the reaction tank into the waste liquid bottle to complete the waste liquid removal operation.

[0104] In some preferred embodiments, the cleaning pump assembly 1323 includes a diaphragm fluid pump.

[0105] Furthermore, the cleaning pump assembly 1323 is configured to fill the pump chamber of the pipetting pump assembly 1321 (i.e., the pump chamber of the small-capacity plunger pump and / or the large-capacity plunger pump) with purified water.

[0106] In this embodiment, the inlet of the diaphragm pump is connected to the cleaning solution source and the purified water source respectively through corresponding valve groups, and the outlet is connected to the fluid pipeline of the pipetting assembly 131 and the pump chamber of the plunger pump through corresponding valve groups. During operation, the control system can switch valve groups to drive the diaphragm pump to pump the cleaning solution or purified water into the designated pipeline or pump chamber, realizing online cleaning of the fluid pipeline and liquid filling and replacement of the plunger pump chamber; specifically, filling the plunger pump with purified water reduces the volume of the fluid pipeline, improves pipetting accuracy and precision, and lubricates the moving parts of the plunger pump.

[0107] In some preferred embodiments, combined with Figure 9 and Figure 20As shown, the liquid circuit control module 132 also includes a gas purge pump group 1324, which is configured to introduce gas into the fluid pipeline of the liquid circuit control module 132 to purge residual liquid.

[0108] Furthermore, the gas purging pump assembly 1324 is a diaphragm air pump; the diaphragm air pump is configured to introduce clean, dry gas into the fluid pipeline after completing the cleaning or liquid transfer operation, so as to avoid reagent dilution, cross-contamination or microbial growth caused by liquid residue, and provide a clean starting point for the next high-precision operation.

[0109] In some preferred embodiments, combined with Figure 9 and Figure 20 As shown, the liquid circuit control module 132 also includes a bubble sensor 1325 installed in the fluid pipeline to monitor in real time whether the liquid flowing through the pipeline contains bubbles, thereby realizing real-time, online quality monitoring of the liquid transmission process.

[0110] In some preferred embodiments, combined with Figure 9 and Figure 20 As shown, the liquid circuit control module 132 also includes a liquid level detection sensor 1326 disposed in the fluid pipeline; the liquid level detection sensor 1326 can be a pressure sensing type. When the pipetting assembly 131 descends and its tip approaches the liquid surface in the container, the liquid level detection sensor 1326 can sensitively detect the slight change in pressure between the liquid surface and the tip, thereby accurately locating the liquid level height and feeding the signal back to the control system.

[0111] In this embodiment, taking the pipetting channel 1 (i.e., the first pipetting component 13101) as an example, combined with... Figure 20 The control logic of the liquid circuit control module is described in detail in Table 1 below: Table 1 It should be understood that the pipetting channel 2 (i.e., the second pipetting component 13102) and its associated liquid circuit control module provided in this embodiment correspond to the aforementioned detailed description of the pipetting channel 1 (the first pipetting component 13101) in terms of structure, connection relationship, and control logic. For the sake of brevity, the pipetting channel 2 will not be described again here. Based on the above description of the pipetting channel 1, those skilled in the art can understand and implement the relevant technical solutions of the pipetting channel 2 without any doubt.

[0112] In some embodiments, combined with Figure 24As shown, it also includes: a TIP tip removal assembly 90, which includes a waste TIP tip collection box 91 and a TIP tip removal block 92 disposed on the waste TIP tip collection box 91; wherein, the TIP tip removal block 92 is configured to adapt to TIP tips of different sizes, so as to peel the TIP tip off the pipetting assembly 131 and let it fall into the waste TIP tip collection box 91; wherein, each TIP tip removal block can simultaneously accommodate the removal of 1ml TIP tips and 5ml TIP tips.

[0113] In this embodiment, the TIP tip ejection assembly 90 includes two TIP tip ejection blocks 92. The two TIP tip ejection blocks 92 are disposed on opposite sides of the waste TIP tip collection box 91 via a TIP tip ejection fixing plate 93 to accommodate two sets of pipetting assemblies 131. In this embodiment, each TIP tip ejection block 92 is provided with a first slot portion 921 and a second slot portion 922. The first slot portion 921 is adapted to a 1ml TIP tip, and the second slot portion 922 is adapted to a 5ml TIP tip.

[0114] After the pipetting system 10 completes the liquid operation, the pipetting assembly 131 carrying the used tip moves above the waste tip collection box 91 and descends, so that the shoulder of the tip abuts against the corresponding slot in the tip retraction block 92; then the pipetting assembly 131 rises, and since the tip is stuck by the tip retraction block 92, while the pipetting assembly 131 continues to move upward, the two generate relative displacement, thereby smoothly scraping the tip off and letting it fall into the waste tip collection box 91 below.

[0115] In some embodiments, combined with Figure 1 , Figure 20 As shown, the cell parallel reaction device 1 also includes an integrated consumables carrying area 100, which is configured to centrally hold purified water bottles, cleaning solution bottles, at least one culture medium bottle and waste liquid bottle, and each bottle is connected to the liquid circuit control module 132 of the pipetting system 10 through a pipeline.

[0116] In this embodiment, the main functional steps of the cell parallel reaction device 1 include at least the following: Preparations in advance: The reaction vessel 22 has been placed in the corresponding reactor seat 211; the 24 microplates containing culture medium (each microplate has a capacity of 10 ml) have been placed in the corresponding plate placement area 30; the TIP head plate 42 has been placed in the TIP head loading area 40.

[0117] Feeding (adding culture medium to reaction vessel 22): The pipetting assembly 131 moves to the TIP tip loading area 40 (for large-volume replenishment, it moves to the 5ml TIP tip area; for small-volume replenishment, it moves to the 1ml TIP tip area) → The pipetting assembly 131 (pipette connector 1311) picks up the TIP tip → The suction cup assembly 142 of the gripping device 14 removes the microplate cover from the microplate and places it in the microplate cover position → The pipetting assembly 131 aspirates the corresponding culture medium from the microplate → The gripper assembly 141 of the gripping device 14 removes the plunger 226 from the cap 223 of the reaction vessel 22 → The pipetting assembly 131 places the TIP tip into the reaction vessel 22 and discharges the culture medium into the reaction vessel 22 → The gripper assembly 141 returns the plunger 226 → The pipetting assembly 131 retracts the TIP tip into the waste TIP tip collection box 91 → The suction cup assembly 142 places the microplate cover back onto the microplate.

[0118] sampling: The pipetting assembly 131 moves to the 1ml TIP head area → the pipetting assembly 131 (pipette connector 1311) takes the TIP head → the gripper assembly 141 removes the plunger 226 from the cap 223 of the reaction vessel 22 → the pipetting assembly 131 places the TIP head into the reaction vessel 22 and aspirates the amount of cell culture medium in the reaction vessel 22 to be tested (the agitator 2212 of the reaction vessel 22 must be stopped during aspiration, and the sampling position can be precisely controlled by the liquid level detection function) → the gripper assembly 141 puts the plunger 226 back → the pipetting assembly 131 places the sample into the corresponding microplate → the pipetting assembly 131 retracts the TIP head into the waste TIP head collection box 91.

[0119] Waste liquid removal from reaction vessel 22: The pipetting assembly 131 moves to the 1ml TIP head area → the pipetting assembly 131 (pipette connector 1311) takes the TIP head → the gripper assembly 141 removes the plunger 226 from the cap 223 of the reaction vessel 22 → the pipetting assembly 131 places the TIP head into the reaction vessel 22, starts the peristaltic pump, and coordinates with the corresponding valve action to remove the waste liquid in the reaction vessel 22 (during aspiration, the agitator 2212 of the reaction vessel 22 must be stopped and remain still for a period of time, and the cell culture medium in the reaction vessel 22 is in a layered state; combined with the liquid level detection function, the position of the removed waste liquid can be accurately controlled) into the waste liquid bottle → the gripper assembly 141 puts the plunger 226 back → the pipetting assembly 131 retracts the TIP head into the waste TIP head collection box 91.

[0120] Although embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the specification and embodiments. They can be applied to various fields suitable for the present invention. For those skilled in the art, other modifications can be easily made. Therefore, without departing from the general concept defined by the claims and their equivalents, the present invention is not limited to the specific details and illustrations shown and described herein.

Claims

1. A cell parallel reaction device, characterized in that, include: A reactor workstation, comprising at least one reactor capable of independently accommodating several reaction vessels; An orifice plate placement area, located beside the reactor workstation, is used to place at least one orifice plate; A TIP head loading area is provided next to the reactor workstation for placing at least two sizes of TIP heads; A pipetting system configured to move between the reactor workstation, the orifice plate placement area, and the TIP head loading area to pick up TIP heads, open and close the reaction vessel, pick up and place the microplate cover and TIP head box cover, and perform liquid aspiration and discharge. A temperature control system, which is connected to the reactor workstation and the orifice plate placement area, to provide independent temperature control for the reactor and the orifice plate placement area; A gas supply control system is provided for each of the aforementioned reaction vessels, which is used to independently deliver and regulate the culture gas into the corresponding reaction vessel. A parameter detection system, which is installed in the reactor workstation and corresponds to each of the reaction tanks, is used to detect the dissolved oxygen and / or pH value in the corresponding reaction tanks; The control system is used to coordinate and control the operating parameters of the reactor workstation, the pipetting system, the temperature control system, the gas path control system, and the parameter detection system to achieve automated parallel culture of the cell parallel reaction equipment.

2. The cell parallel reaction apparatus as described in claim 1, characterized in that: The working volume of the reaction vessel is 10-15 ml.

3. The cell parallel reaction apparatus as described in claim 1, characterized in that: The control system is configured to independently set, monitor, and adjust the temperature, pH value, dissolved oxygen concentration, and stirring speed within each of the reaction vessels.

4. The cell parallel reaction apparatus as described in claim 1, characterized in that: The reaction vessel is equipped with a magnetic stirring assembly; the reactor integrates several magnetic drive components. Each of the magnetic drive components is arranged around the periphery of a reaction vessel and is adapted to the position of the magnetic stirring component; Each of the magnetic drive components is configured to be independently controllable to drive the magnetic stirring components in the corresponding reaction vessel to rotate, and to achieve independent adjustment of the stirring speed of each reaction vessel.

5. The cell parallel reaction apparatus as described in claim 1, characterized in that: The temperature control system employs semiconductor refrigeration technology and is configured to adjust the culture temperature of the reaction vessel within the reactor workstation within the range of 20°C to 40°C.

6. The cell parallel reaction apparatus as described in claim 1, characterized in that: The orifice plate placement area includes at least four independent placement stations, and at least one of the placement stations has a temperature control module integrated at its bottom. The temperature control module is connected to the temperature control system to regulate the temperature of the orifice plate placed thereon.

7. The cell parallel reaction apparatus as described in claim 1, characterized in that: The TIP head loading area includes at least two loading stations arranged side by side, each used to place TIP head plates of different volume specifications.

8. The cell parallel reaction apparatus as described in claim 1, characterized in that: The pipetting system includes: A pipetting stand is a support structure used to form a pipetting system. A drive unit, which is mounted on the pipetting rack; A pipetting device, which is mounted to and driven by the driving device; the pipetting device includes at least two sets of independent pipetting components and a liquid path control module that provides independent liquid path control for each set of pipetting components; A gripping device, which is mounted to and driven to move by the drive device; The pipetting assembly is configured to pick up at least two different sizes of TIP tips; the gripping device includes a gripper assembly for opening and closing the reaction vessel and / or a suction cup assembly for picking up and placing the microplate cover and the TIP tip box cover.

9. The cell parallel reaction apparatus as described in claim 1, characterized in that, Also includes: A tip removal assembly includes a waste tip collection box and a tip removal block disposed on the waste tip collection box; wherein the tip removal block is configured to adapt to tip removal of different sizes to detach the tip from the pipetting assembly and allow it to fall into the waste tip collection box.

10. The cell parallel reaction apparatus as described in claim 1, characterized in that, Also includes: An integrated consumables carrying area is configured to centrally hold purified water bottles, cleaning solution bottles, at least one culture medium bottle, and waste liquid bottles, and each bottle is connected to the liquid circuit control module of the pipetting system through a pipeline.

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