Multifunctional cell treatment equipment

Abstract

The invention relates to the technical field of biological engineering, and particularly discloses multifunctional cell treatment equipment, which comprises a super clean bench, a pipetting mechanism, a cover opening mechanism, a centrifugal mechanism, a pipe cap opener, a first feeding and discharging device and a cell counting and morphological observation all-in-one machine, the first feeding and discharging device comprises a transfer mechanism and a bearing conveying belt, the transfer mechanism and the cell counting and form observing all-in-one machine are both located outside the super clean bench, and the transfer mechanism takes and places a culture dish / pore plate / counting plate on the bearing conveying belt; the cell counting and form observing all-in-one machine is provided with a pushing mechanism, and the pushing mechanism is used for transferring the culture dishes / counting plates between the bearing conveying belt and the objective table of the cell counting and form observing all-in-one machine. The scheme is used for solving the problem that existing automatic cell treatment equipment is mostly designed for single functions such as passage and split charging. At present, the equipment does not have the functions of passage and planking at the same time, and the super clean bench is small in size and low in maintenance cost.

Description

Technical Field

[0001] The present invention relates to the technical field of bioengineering, and in particular to a multifunctional cell processing device. Background Art

[0002] In laboratory cell processing, there are operations such as cell passaging, cell plating, and cell packaging. For large-scale production of passaging, plating, and packaging, there are currently automated equipment that improves operational efficiency.

[0003] For example, patent publication number CN217868908U is a cell intelligent passaging device, patent publication number CN116286344A is a cell passaging culture workstation and cell passaging culture method, and patent publication number CN110124763B is a fully automatic stem cell solution packaging method. These devices are all specific and suitable for a certain type of cell processing. They are suitable for factory production or large laboratories or hospitals for highly repetitive cell processing operations.

[0004] There are also many systems in the prior art that take into account operations such as pipetting and centrifugation. However, these systems often make the entire equipment very cumbersome to take into account various operations, or still require semi-automated coordination with a high degree of human participation. For example, the intelligent cell culture system and method proposed in Patent Publication No. CN117778184A is too general and occupies a large area, which is not conducive to its use in small laboratories with high costs. For example, Patent Publication No. CN117511697A describes an intelligent cell pipetting workstation. This workstation integrates core functions such as pipetting mechanism, centrifuge, lid opener, culture dish / culture bottle / test tube storage area / sample storage area into a closed ultra-clean environment. However, because the workstation needs to accommodate multiple independent functional modules at the same time, some functional modules are designed to be bulky during use, but only partially utilized. For example, the large centrifuge module has the same structure as a single centrifuge and can centrifuge multiple test tubes simultaneously. For example, the corresponding storage areas for culture dishes, reagent tubes, and consumables also take up a lot of space. This "big and comprehensive" design concept results in a large overall size of the workstation, which not only significantly increases the cost of integrated clean room construction and air purification systems, but also limits its deployment in laboratory scenarios with limited space (such as university scientific research platforms).

[0005] Furthermore, large, integrated equipment is complex and difficult to maintain. Some consumables, such as culture dishes, well plates, test tubes, and pipette tips, often sit idle due to a low number of experiments. These issues combine to prevent existing automated workstations from theoretically replacing manual labor. However, their high purchase costs (often exceeding one million yuan) and limited adaptability to specific scenarios severely restrict their adoption in small and medium-sized research institutions. Summary of the Invention

[0006] The present invention aims to provide a multifunctional cell processing device to address the problem that existing automated cell processing equipment is mostly designed for single functions such as cell culture and packaging. Currently, such equipment lacks the ability to simultaneously perform cell culture and plating, and lacks the compact size and low maintenance costs of clean benches.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions: A multifunctional cell processing equipment includes an ultra-clean bench and a pipetting mechanism, a cover opening mechanism, a centrifugal mechanism and a tube cap opener located in the ultra-clean bench. The pipetting mechanism is used to pipet the opened culture dish / well plate / test tube, the centrifugal mechanism is used to centrifuge the substance in the test tube, and the tube cap opener is used to open and close the test tube cap and transfer the test tube between the test tube placement position and the centrifugal position of the centrifugal mechanism. It also includes a first loading and unloading device and a cell counting and morphology observation integrated machine. The first loading and unloading device includes a transfer mechanism and a receiving conveyor belt. The receiving conveyor belt is located below the pipetting mechanism and the receiving conveyor belt is located in the ultra-clean bench. The transfer mechanism and the cell counting and morphology observation integrated machine are both located outside the ultra-clean bench. The transfer mechanism takes and places the culture dish / well plate / counting plate on the receiving conveyor belt through a channel provided on the ultra-clean bench; the cell counting and morphology observation integrated machine is used to realize cell morphology observation and cell counting. The cell counting and morphology observation integrated machine is provided with a pushing mechanism. The pushing mechanism is used to transfer the culture dish / counting plate between the receiving conveyor belt and the loading platform of the cell counting and morphology observation integrated machine.

[0008] The principles and advantages of this solution are: when adopting this solution, since this solution integrates the pipetting mechanism, the cover opening mechanism, the centrifugal mechanism, the tube cap opener, the first feeding and discharging device, and the cell counting and morphology observation all-in-one machine, the same set of cell processing equipment can be used for cell passage. When using culture dishes for cell passage, the first feeding and discharging device sends the culture dishes / counting plates / well plates used to the receiving conveyor belt in the clean bench, the cover opening mechanism opens the culture dish cover / well plate cover, and the pipetting mechanism performs pipetting; the culture dishes / counting plates are sent to the loading platform of the cell counting and morphology observation all-in-one machine through the receiving conveyor belt and the pushing mechanism for cell morphology observation or cell counting. The culture dishes / counting plates on the loading platform that have completed cell morphology observation / cell counting are sent back to the receiving conveyor belt from the channel connecting the clean bench to the outside under the pushing mechanism. For test tubes that need to be opened during the pipetting process, the cap opener opens the test tube in the test tube position, facilitating pipetting by the pipette mechanism. The cap opener is used to cap the test tube and transfer the test tube to the centrifuge mechanism for centrifugation. After centrifugation, the test tube is returned to the test tube position and the cap of the centrifuged test tube is opened again, facilitating pipetting by the pipette mechanism to resuspend the cells. All operating functions can meet the needs of cell passaging, cell plating, and packaging operations, and are suitable for a variety of biological experiments in the laboratory, with strong applicability.

[0009] In addition, in this solution, because the first material loading and unloading device and the integrated cell counting and morphological observation equipment are set outside the clean bench, the culture dishes / well plates / counting plates that occupy a large area are only sent into the clean bench when needed, and can be sent out of the clean bench when they are no longer needed, so there is no need to set up culture dish placement areas, well plate placement areas, and counting plate placement areas in the clean bench, which helps to reduce the size of the clean bench and make the clean bench more miniaturized. When the clean bench is smaller in size, the cost is naturally reduced. At the same time, the structure inside the clean bench is simpler and maintenance is more convenient. The first material loading and unloading device can be maintained separately outside the clean bench, which also reduces the maintenance cost of the entire equipment.

[0010] In addition, the use of an all-in-one cell counting and morphology observation machine to take into account both cell morphology observation and cell counting can help reduce equipment costs and floor space costs.

[0011] Preferably, as an improvement, the transfer mechanism includes a culture dish transfer mechanism and a well plate transfer mechanism. The culture dish transfer mechanism is located outside the clean bench and includes a storage rack and a transfer robot. The transfer robot is used to transfer the culture dish or a counting plate with the same outer contour as the culture dish between the receiving conveyor belt and the storage rack. The well plate transfer mechanism is used to send the well plate into or out of the receiving conveyor belt.

[0012] Beneficial effects: When this solution is adopted, the transfer robot can transfer both the culture dish and the counting plate with the same outer contour as the culture dish in the same way, which facilitates the transfer of the culture dish and the counting plate in the same way, reduces equipment costs and helps to automate cell processing operations.

[0013] Preferably, as an improvement, the transfer mechanism also includes an inlet and outlet turntable, which includes a fixedly mounted tray and a rotatable turntable, the tray is provided with a through hole for avoiding air to receive the conveyor belt, the turntable is located above the tray, and the turntable is provided with at least two kinds of air avoidance holes, one of which can cooperate with the culture dish, and the other can cooperate with the orifice plate, and after the turntable rotates, the culture dish / counting plate / orifice plate can be transferred between the receiving conveyor belt and the tray.

[0014] Beneficial effects: The culture dish / well plate / counting plate with the same outer contour as the culture dish can be placed on the inlet and outlet turntable for transfer. Under the shared design structure, the culture dish transfer mechanism and the well plate transfer mechanism can be set in different positions, and both can facilitate material loading and unloading.

[0015] Preferably, as an improvement, the orifice plate transfer mechanism includes an orifice plate conveyor belt, an orifice plate pusher, an orifice plate lifting platform, an orifice plate storage conveyor belt and an orifice plate pusher. The orifice plate conveyor belt passes through a channel provided on the clean bench, and the orifice plate pusher, the orifice plate lifting platform, the orifice plate pusher and the orifice plate storage conveyor belt are all outside the clean bench; the orifice plate conveyor belt is perpendicular to the orifice plate storage conveyor belt, and the two ends of the conveying direction of the orifice plate conveyor belt are respectively the orifice plate lifting platform and the feed and discharge turntable. The orifice plate pusher is used to push the orifice plate at the top of the orifice plate lifting platform onto the orifice plate conveyor belt, the orifice plate conveyor belt is used to send the orifice plate into / out of the feed and discharge turntable, and the orifice plate pusher is used to push the orifice plate from the orifice plate conveyor belt to the orifice plate storage conveyor belt.

[0016] Beneficial effects: When this solution is adopted, the setting of the well plate conveyor, well plate pusher, and well plate lifting platform facilitates the automatic pushing of stacked well plates, making it convenient to send the well plates into the clean bench; and through the setting of the well plate storage conveyor and the well plate pusher, it is convenient to send the well plates that have been plated to the well plate storage conveyor through the well plate pusher for storage, so that multiple well plates can be placed on the well plate storage conveyor in sequence after plating, which facilitates the plating operations of different cells in sequence.

[0017] Preferably, as an improvement, the pipetting mechanism includes a space mover and a pipetting assembly installed at the output end of the space mover, the space mover is used to drive the pipetting assembly to move in space, the pipetting assembly includes a presser, a rotating seat and multiple pipette guns, the rotating seat and the presser are both installed at the output end of the space mover, the multiple pipette guns are distributed circumferentially on the rotating seat, the rotating seat is used to rotate the pipette gun to the working position, the presser is used to press the pressing head of the pipette gun located in the working position to absorb or discharge liquid, and the presser is used to press the push head rod after aligning the push head rod of the pipette gun to replace the gun head.

[0018] Beneficial effect: Beneficial effect: When adopting this scheme, taking cell passaging as an example, when cell passaging is required, the liquid raw materials required for cell passaging, such as PBS, digestion solution, stop solution, and complete culture medium, are first packed in test tubes with tube caps, and new test tubes required for centrifugation are prepared. These test tubes are placed on the test tube placement position. Each time the pipetting mechanism needs to take the corresponding liquid, the culture dish is opened by the cover opener, and the cap of the test tube is opened by the tube cap opener, so as to facilitate the pipette gun located in the working position of the pipetting mechanism to perform pumping and drainage actions, such as aspirating the liquid in the culture dish / aspirating the liquid in the test tube / discharging the aspirated liquid into the waste container placed in the clean bench / filling the aspirated liquid into the culture dish / new test tube, etc.; when the pipetting mechanism is in action, since multiple pipette guns can be installed on the rotating seat of the pipetting mechanism, the choice of these pipette guns can be selected with different ranges according to operational requirements, ensuring that the pumping and drainage operations of different aspiration amounts can be met, thereby improving applicability.

[0019] Moreover, in this solution, although there are multiple pipettes in the pipette assembly, each pipette needs to rotate the rotating seat to the working position before the pipetting operation can be performed, that is, multiple pipettes share a presser, thereby simplifying the structure of the pipette assembly and also simplifying the difficulty of operating the pipette assembly.

[0020] In addition, the presser on the pipette assembly can not only press the pressing head of the pipette, thereby facilitating the extraction of liquid by pressing, but also, with the cooperation of the rotating seat, after driving the pipette to rotate an angle, the presser can be aligned with the push rod of the pipette to replace the tip and press the push rod to automatically push out the pipette tip. The pipette mechanism then drives the pipette to align with the required tip on the tip set placed in the clean bench and inserts it downwards onto the new tip, thus completing the assembly of the new tip. This solution makes the entire cell processing highly automated and has a wide range of applications. In addition, the pipette mechanism has a simple structure and low control difficulty.

[0021] Preferably, as an improvement, the pipetting mechanism also includes a waste container placed on the clean bench and a gun tip group containing multiple gun tips of different specifications. The pipette can be inserted into the gun tip of the gun tip group to assemble a new gun tip, and the gun tip or waste liquid pushed out of the pipette can be received by the waste container.

[0022] Preferably, as an improvement, the presser includes a reciprocating pressure rod, a rotator and a pressing block, the reciprocating pressure rod is used to drive the pressing block away from or close to the pressing head of the pipette, the pressing block and the pressing head can fit together in a concave and convex manner, and the rotator is used to drive the pressing block to rotate; a plurality of suction volume data acquisition modules are provided on the rotating seat, and each suction volume data acquisition module is used to collect the range on a corresponding pipette.

[0023] Beneficial effects: This solution adjusts the aspiration volume of the pipette by acting on the pressing block through the rotator, and then rotating the pressing head through the pressing block. In addition, through the setting of the aspiration volume data acquisition module, it is convenient to automatically adjust the range of different pipetting processes according to different biological treatment experiments. For example, the range of a pipette is 20-200ul. When 100ul is needed, the aspiration volume of the pipette is adjusted through the rotator and the pressing block. The adjusted aspiration volume value can be directly displayed on the display of the pipette. The displayed value is collected by the aspiration volume data acquisition module. When the aspiration volume value is displayed as 100ul, the rotator is controlled by the control system to stop rotating the pressing block, thereby ensuring that the aspiration volume is automatically adjusted under different usage requirements, further improving the degree of automation.

[0024] Preferably, as an improvement, the receiving conveyor belt includes a first conveying section and a second conveying section that are parallel and arranged along the conveying direction, the first conveying section is arranged at the through-hole position of the tray, the second conveying section is immediately connected to the end of the first conveying section, the second conveying section includes two parallel, equal-height and synchronized conveyor belts, a tilting mechanism is arranged between the two conveyor belts of the second conveying section, the tilting mechanism includes a pusher and a push rod and a baffle fixed at the output end of the pusher, the pusher drives the push rod and the baffle to rise and fall synchronously along the Z axis, the push rod is used to push the culture dish, the distance between the push rod and the baffle is greater than the radius of the culture dish and smaller than the diameter of the culture dish, the baffle is used to tilt the culture dish against the baffle when the push rod eccentrically pushes the culture dish, so as to facilitate the pipette gun to absorb the liquid in the culture dish.

[0025] Preferably, as an improvement, the baffle is an arc-shaped plate, and the arc-shaped plate matches the arc structure of the culture dish.

[0026] Preferably, as an improvement, the push rod is an elastic push rod.

[0027] Preferably, as an improvement, the centrifuge mechanism includes a rotatable centrifuge frame, which is provided with a counterweight and a placement hole symmetrical about the centrifuge frame's rotation axis. This solution makes the centrifuge mechanism very simple in structure and very small in size, so the space occupied by the clean bench is also very small. In addition, the setting of the counterweight ensures that even if there is only one test tube being centrifuged, the centrifuge frame can rotate stably during centrifugation, thereby ensuring the centrifugal effect.

[0028] Preferably, as an improvement, the cover opening mechanism includes a multi-axis motion actuator and a suction cup installed at the output end of the multi-axis motion actuator, the multi-axis motion actuator is used to drive the suction cup to move in space, and the spatial movement includes movement of the X-axis, Y-axis, and Z-axis to facilitate the opening of the culture dish cover / well plate cover by the cover opening mechanism. At the same time, after the culture dish / well plate is adsorbed by the cover opening mechanism, the cover opening mechanism is controlled to drive the adsorbed culture dish / well plate to draw a cross in the horizontal plane to simulate manual shaking of the cell fluid.

[0029] Preferably, as an improvement, an elastic rod is provided between the suction cup and the output end of the multi-axis motion actuator, and the deformation direction of the elastic rod is the Z axis, so that the suction cup will not make hard contact with the adsorbed object when moving downward.

[0030] Preferably, as an improvement, a second feeding and discharging device is further included, which includes a rotatable rotating disc and a fixedly installed enclosing ring. The rotating disc and the enclosing ring are both located in the clean bench. The enclosing ring is a circular structure. A plurality of placement holes are provided in the circumference of the rotating disc. The projection of the placement holes onto the horizontal plane is U-shaped. The U-shaped opening of the placement holes faces outward and faces the inner ring side of the enclosing ring. The placement holes are used to place test tubes, and the tube cap opener can open or close the test tubes on the rotating disc.

[0031] Beneficial effects: This solution enables multiple test tubes to be placed on the rotating disc through the design of the rotating disc, the enclosing ring and the inlet and outlet structures, thereby facilitating the placement and use of the test tubes, and facilitating pipetting, centrifugation and even subpackaging of the test tubes with the cooperation of the pipetting mechanism and the tube cap opener, further improving the applicability of this equipment.

[0032] Preferably, as an improvement, the enclosing ring is a circular ring structure with two notches, and the second feeding and discharging device also includes a hanging feeding structure and a hanging discharging structure, and the hanging feeding structure and the hanging discharging structure both include a left support and a right support, and the space between the left support and the right support is used for the test tube body to pass through, and the test tube cap is used to be suspended on the left support and the right support at the same time, and the hanging feeding structure and the hanging discharging structure are used to align with a notch position respectively, and the left support and the right support of the hanging feeding structure are inclined downward toward the notch, and the left support and the right support of the hanging discharging structure are inclined upward toward the notch.

[0033] Preferably, as an improvement, the second feeding and discharging device also includes a pushing block fixedly installed above the rotating disc, the pushing block is opposite to the hanging discharging structure, the side of the pushing block facing the hanging discharging structure is an arc surface, and an elastic block is pasted on the arc surface. The pushing block can enable the test tube aligned with the notch to be moved from the placement hole to the hanging discharging structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 Schematic diagram of the three-dimensional structure of an embodiment of the present invention.

[0035] Figure 2 for Figure 1 Schematic diagram of the three-dimensional structure after removing the side walls and top of the clean bench, detection room, storage room, well plate room and test tube room.

[0036] Figure 3 for Figure 2 Top view of .

[0037] Figure 4 Schematic diagram of the three-dimensional structure of the pipetting mechanism in an embodiment of the present invention.

[0038] Figure 5 for Figure 4 Schematic diagram of the three-dimensional structure of the pipette assembly when the reciprocating pressure rod moves downward to the concave-convex fit of the pressing block and the pressing head of the pipette (the spatial mover is not shown in the figure, only the pipette assembly is shown, and the pressing block and the pressing head of the pipette are matched concavely in the figure).

[0039] Figure 6 for Figure 5 Schematic diagram of the three-dimensional structure after rotation (the connecting rod and end plate are removed to facilitate the display of the hollow cavity of the rotating structure of the rotating seat).

[0040] Figure 7 for Figure 5 main view.

[0041] Figure 8 for Figure 6 Projected view toward the bottom end face of the rotating seat.

[0042] Figure 9 This is a schematic diagram of the three-dimensional structure when the push rod of the pipette is facing the pressing block of the presser after the rotating base rotates a certain angle in an embodiment of the present invention.

[0043] Figure 10 for Figure 5A three-dimensional schematic diagram of the pipetting component after rotation at an angle, a schematic diagram of the explosion state of the connecting rod and the end plate relative to the rotating seat, and a three-dimensional combined schematic diagram of the end plate after relative rotation at an angle (the figure shows a schematic diagram of the reciprocating pressure rod constructed by the pressing drive source to rotate the gear driven by the motor, and then the reciprocating movement of the rack driven by the gear, showing that the end plate at the end of the connecting rod blocks the end of the hollow cavity, the installation position of the vision module, and the circumferential uniform distribution of the rolling elements and rollers).

[0044] Figure 11 for Figure 10 Section II in the figure.

[0045] Figure 12 for Figure 2 After the rotation angle, only the three-dimensional structural diagram of the pipetting component and the first feeding and discharging device is displayed.

[0046] Figure 13 for Figure 12 Only the three-dimensional schematic diagram of the culture dish transfer mechanism is shown.

[0047] Figure 14 for Figure 12 Exploded view of the center feed and discharge carousel (also showing the mark recognition module and the first section of the receiving conveyor belt).

[0048] Figure 15 The top projection view of the output claw corresponding to the position of taking and placing culture dishes on the storage rack is shown for this embodiment.

[0049] Figure 16 for Figure 1 The figure in the middle is a three-dimensional structural diagram showing the cover opening mechanism, feed and discharge turntable, receiving conveyor belt, orifice plate transfer mechanism, second feed and discharge device, centrifugal mechanism and tube cap opener.

[0050] Figure 17 for Figure 16 The local figure in the figure shows the three-dimensional structure diagram of the integrated cell counting and morphology observation machine.

[0051] Figure 18 for Figure 17 main view.

[0052] Figure 19 for Figure 18 Only the top view of the structure of the conveyor belt, tilting mechanism and mark recognition module is shown.

[0053] Figure 20 Schematic diagram of the three-dimensional structure of the tilting mechanism of this embodiment.

[0054] Figure 21This is a front view of the process in which the tilting mechanism of the present invention pushes the culture dish to an inclined position (in order to conveniently show the action process of the tilting mechanism, only the second conveying section is shown which does not block the front view of the tilting mechanism).

[0055] Figure 22 This embodiment is a schematic diagram showing the three-dimensional structure between the second feeding and discharging device, the centrifugal mechanism, the tube cap opener, and the feeding and discharging turntable.

[0056] Figure 23 for Figure 22 Schematic diagram of the three-dimensional structure after rotation angle.

[0057] The reference numerals in the drawings of the specification include: pipetting mechanism 1, spatial mover 11, pipetting assembly 12, mounting seat 121, presser 122, pressing drive source 1221, reciprocating pressure rod 1222, rotator 1223, pressing block 1224, rotating seat 123, fixed structure part 1230, hollow cavity 1231, pusher 124, pipetting gun 125, pressing head 1251, pushing head rod 1252, suction volume data acquisition module 126, connecting rod 127, end plate 128, visual module 129, rolling body 1281, roller 1282, gun head assembly 13, waste container 14, first feeding and discharging device 2, feeding and discharging turntable 21, tray 211, air-avoiding slot 2111, observation hole 2112, turntable 212, air-avoiding hole 2121, mark identification module 213, receiving conveyor belt 22, culture dish transfer mechanism 23, multi-degree-of-freedom manipulator 231, rotating seat 2311, Z-axis linear module 2312, transverse module 2313, output claw 2314, support protrusion 23141, storage rack 232, layer plate 232 1. Support groove 23211, air-avoiding through hole 23212, storage chamber 230, orifice plate transfer mechanism 24, orifice plate conveyor belt 241, orifice plate pusher 242, orifice plate lifting platform 243, orifice plate storage conveyor belt 244, orifice plate pusher 245, orifice plate chamber 240, culture dish inkjet printer 25, orifice plate inkjet printer 26, lid opening mechanism 3, multi-axis motion actuator 31, suction cup 32, elastic rod 33, tilting mechanism 4, pusher 41, ejector 42, ejector body 421, elastic member 422, baffle 43, second inlet Discharging device 5, rotating assembly 51, rotating disc 511, enclosing ring 512, placement hole 510, tube clamp 52, hanging feeding structure 53, hanging discharging structure 54, pushing block 55, test tube chamber 50, tube cap opener 7, centrifugal mechanism 6, placement hole 61, counterweight 62, cell counting and morphology observation integrated machine 8, stage 81, detection chamber 80, pusher 82, push plate 821, returner 83, push back plate 831, transition support platform 84, culture dish 100, well plate 101, clean bench 1000. DETAILED DESCRIPTION

[0058] The following is further described in detail through specific implementation methods: The embodiment is basically as shown in the attached Figures 1 to 23 shown.

[0059] A multifunctional cell processing device includes an ultra-clean bench and a pipetting mechanism 1, a cover opening mechanism 3, a centrifugal mechanism 6, and a tube cap opener 7 located in the ultra-clean bench. It also includes a first feed and discharge device 2, a cell counting and morphology observation integrated machine 8, and a second feed and discharge device 5. The ultra-clean bench is provided with a fan system, which includes a filter. The fan system is used to provide air of a set cleanliness level to the ultra-clean bench so that the ultra-clean bench is in a positive pressure state when performing cell operations. The ultra-clean bench is also provided with an ultraviolet disinfection lamp and a lighting lamp; a plurality of feed and discharge channels are provided on the ultra-clean bench, which are respectively used for the first feed and discharge device 2 to deliver objects into / out of the ultra-clean bench, the second feed and discharge device 5 to deliver test tubes into or out of the ultra-clean bench, and to transfer culture dishes / counting plates between the cell counting and morphology observation integrated machine 8 and the ultra-clean bench.

[0060] The pipetting mechanism 1 is provided with a pipette gun 125 for performing pipetting operations during cell passage.

[0061] The cover opening mechanism 3 is used to open or close the culture dish cover / well plate cover of the cell processing operation area.

[0062] The centrifugal mechanism 6 is used to perform centrifugal operation on the cell fluid in the test tube.

[0063] The tube cap opener 7 is used to open / close the tube cap of the test tube.

[0064] The first inlet and outlet device 2 is used to deliver culture dishes / well plates / counting plates with the same outer contour as culture dishes into / out of the clean bench through corresponding inlet and outlet channels. The second device is used to deliver test tubes into / out of the clean bench through corresponding inlet and outlet channels.

[0065] The integrated cell counting and morphology observation machine 8 can not only count cells but also observe and record the cell morphology in the culture dish.

[0066] The specific structure is as follows: 1. Pipetting mechanism 1 Combine Figures 4 to 11The pipetting mechanism 1 includes a spatial mover 11 and a pipetting assembly 12 installed at the output end of the spatial mover 11. The spatial mover 11 is used to drive the pipetting assembly 12 to move in space. The spatial mover 11 of this embodiment can be a multi-degree-of-freedom robot or a truss manipulator that can move in the X-axis, Y-axis, and Z-axis, a three-dimensional linear module, or a spatial module that moves in the X-axis and Y-axis as shown in the accompanying drawings of this embodiment. The spatial mover 11 drives the pipetting assembly 12 to move in space (such as spatial movement of the XYZ axis, such as horizontal movement of the XY axis). The spatial mover 11 only needs to meet the liquid collection and discharge requirements of the pipetting mechanism 1.

[0067] The pipetting assembly 12 includes a mounting seat 121, a presser 122, a rotating seat 123, multiple pushers 124 and multiple pipette guns 125. The mounting seat 121 is fixed to the output end of the space mover 11. The rotating seat 123 and the presser 122 are both installed on the mounting seat 121. Multiple pushers 124 are circumferentially distributed around the rotating structure of the rotating seat 123. The pressing direction of the presser 122 and the pushing direction of the pusher 124 are both parallel to the Z axis. A pipette gun 125 is installed at the output end of each pusher 124. The rotating seat 123 is used to rotate the pipette gun 125 to the working position. The pusher 124 is used to control the pipette gun 125 to approach or move away from the object to be sucked when the rotating seat 123 rotates the pipette gun 125 to the working position. The presser 122 is used to press the pipette gun 125 located in the working position to absorb or discharge liquid.

[0068] The pusher 124 is a linear module, and the output slider of the linear module can move back and forth along the Z axis. A connecting seat is fixedly installed on the output slider. The connecting seat is engaged with the pipette gun 125 and the connecting seat is provided with a strap to facilitate the disassembly and assembly of the pipette gun 125 on the connecting seat.

[0069] In addition, the multiple pipettes 125 provided with the pipette assembly 12 can be easily installed with a variety of pipettes 125 of different ranges to meet different usage requirements, such as the need to suck out the old culture medium in the culture dish during cell processing, the need to add PBS rinse solution to the culture dish, the need to add stop solution, the need to add new complete culture medium, etc.

[0070] In addition, because the pipette 125 has a pushing rod 1252 for replacing the pipette head 125 in addition to the pressing head 1251 for aspirating liquid, every time the pipette 125 needs to replace the pipette head 125, it is only necessary to control the rotating seat 123 to rotate so that the pressing head 1251 is aligned with the pushing rod 1252, and the used pipette head 125 can be automatically pushed out, thereby improving the degree of automation of the pipette mechanism 1.

[0071] The presser 122 includes a pressing drive source 1221, a reciprocating rod 1222, a rotator 1223, and a pressing block 1224. The pressing drive source 1221 is used to drive the reciprocating rod 1222 to move along the Z axis. The rotator 1223 is fixed to the downward output end of the reciprocating rod 1222. The pressing block 1224 is fixedly mounted at the output end of the rotator 1223. The rotator 1223 is used to drive the pressing block 1224 to rotate about its axis. The reciprocating rod 1222 is used to drive the pressing block 1224 away from or toward the suction control pressing head 1251 of the pipette 125. The pressing block 1224 and the pressing head 1251 of the pipette 125 can be matched in a concave-convex manner. After the pressing block 1224 and the pressing head 1251 of the pipette 125 are matched in concave and convex manner, the rotator 1223 is started and the pressing block 1224 rotates. The pressing block 1224 realizes the screwing of the pressing head 1251 through the concave and convex matching. After the pressing head 1251 of the pipette 125 is screwed, the suction volume of the pipette 125 is adjusted, so as to facilitate the automatic adjustment of the suction volume of the pipette 125 through the rotator 1223 according to different liquid filling volume requirements, thereby improving the degree of automation. Because the pipette 125 is installed on the rotating structure of the rotating seat 123 along with the pusher 124, after the rotating seat 123 rotates to the point where the pressing block 1224 is aligned with the pushing rod 1252 for replacing the pipette tip of the pipette 125, the pressing of the pushing rod 1252 by the pressing block 1224 can push out the pipette 125 head on the pipette 125, thereby facilitating the automatic replacement of the pipette 125 head on the pipette 125.

[0072] The rotating structure of the rotating seat 123 is also provided with a suction volume data acquisition module 126 for capturing images of the suction volume of the pipette gun 125. The suction volume data acquisition module 126 uses a camera. The number of cameras in the suction volume data acquisition module 126 is the same as the number of the pipette guns 125, so that each pipette gun 125 has a corresponding camera to monitor the suction volume and ensure the accuracy of the suction volume.

[0073] A hollow cavity 1231 is provided in the middle of the rotating seat 123, and the pipette gun 125 is installed on the four sides of the rotating seat 123. The camera used by the suction volume data acquisition module 126 is installed on the side wall of the hollow cavity 1231, and the image acquisition end of the camera is hidden in the outer periphery of the rotating seat 123 or extends out of the outer periphery of the rotating seat 123 (the accompanying drawings of this embodiment take the camera extending a small section of the rotating seat 123 as an example), and the bottom of the camera is inserted into the rotating seat 123, and the connected wires and data cables are placed in the hollow cavity 1231.

[0074] The fixed structure part 1230 and the rotating structure part of the rotating seat 123 are both provided with through holes. The through hole of the rotating structure part is the above-mentioned hollow cavity 1231. Both ends of the hollow cavity 1231 have through holes. The top through hole of the hollow cavity 1231 is connected to the through hole of the fixed structure part 1230 of the rotating seat 123, so that the connecting rod 127 provided on the pipetting component 12 can pass through the entire rotating seat 123 and be fixed on the mounting seat 121. The free end of the connecting rod 127 away from the mounting seat 121 is fixed with an end plate 128, and a visual module 129 is installed on the end plate 128. The visual module 129 is used to collect image data below the pipetting component 12. The visual module 129 is close to the working position of the pipetting component 12, so that the visual module 129 can record the working process of the pipetting component 12 as much as possible. For example, the visual module 129 can collect image data of an object to be acted upon, such as a culture dish to be filled with liquid, or the position of a new gun tip that is about to be replaced, to ensure that the movement of the pipetting component 12 is more accurate. In a specific embodiment, the visual module 129 can be a camera.

[0075] In addition, the hollow cavity 1231 is a cylindrical cavity, and a plurality of evenly distributed rolling bodies 1281 are installed on the upper surface of the end plate 128 facing the bottom end surface of the rotating seat 123. The rolling bodies 1281 of this embodiment are ball bearings, and the end plate 128 provides a certain supporting force on the rotating seat 123 through the ball bearings. At the same time, the rolling of the ball bearings makes the rotation of the rotating seat 123 not affected by the end plate 128; in addition, in order to further improve the rotational stability of the rotating structure of the rotating seat 123, a plurality of rollers 1282 are installed on the end plate 128. The rollers 1282 are bearings in this embodiment. The plurality of rollers 1282 are evenly distributed along the circumference of the hollow cavity 1231 and the side surfaces of the rollers 1282 roll and rub against the inner wall of the hollow cavity 1231.

[0076] The pipetting mechanism 1 also includes a waste container 14 below the pipette 125 and a tip group 13 containing a plurality of tips of different specifications. The pipette 125 can be inserted into the tip of the tip group 13 to assemble a new tip. Tips or waste liquid pushed out of the pipette 125 can be received by the waste container 14. In order to store waste tips and waste liquid separately, the waste container 14 is divided into two cylinders, one for receiving waste tips and the other for receiving waste liquid. The pipette can be a pipette such as that disclosed in Patent Publication No. CN213193738U.

[0077] The automatic pipetting mechanism 1 of this embodiment is equipped with a variety of pipette guns 125 of different ranges at one time, which improves the scope of use and the demand for use. When in use, it is only necessary to control the rotating seat 123 to rotate the corresponding pipette gun 125 to the working position; and the presser 122 is used for both aspirating / discharging liquid from the pipette gun 125 in the working position and automatically pushing out the used gun tips on the pipette gun 125. A plurality of new gun tips of different specifications are also uniformly placed in the boxed gun tip group 13, which is convenient for taking gun tips of different specifications according to needs. In addition, in order to ensure the accuracy of gun tip replacement, the visual module 129 on the pipetting assembly 12 can be used to capture the position and number of the remaining gun tips in the gun tip group 13. The visual module 129 transmits the image data of the remaining gun tips to the control system, and the control system controls the spatial mover 11 to move to a position where the required gun tips can be accurately taken. Finally, the pusher 124 drives the working displacement liquid gun 125 to move downward, completing the insertion of the gun tip on the pipette gun 125.

[0078] The pipetting mechanism 1 of the entire embodiment can automatically adjust the suction volume, automatically control the suction, automatically push out the used gun tip, and automatically insert a new gun tip, which helps to achieve fully automated pipetting operations.

[0079] 2. The first feeding and discharging device 2 Combine Figures 12 to 15 The first feeding and discharging device 2 includes a feeding and discharging turntable 21, a receiving conveyor belt 22, a culture dish transfer mechanism 23, a hole plate transfer mechanism 24, a culture dish inkjet printer 25 and a hole plate inkjet printer 26. The feeding and discharging turntable 21 and the receiving conveyor belt 22 are located in the clean bench. The culture dish transfer mechanism 23 is used to send the culture dishes / counting plates outside the clean bench to the feeding and discharging turntable 21 through the feeding and discharging channels opened on the side wall of the clean bench. It is also used to transfer the culture dishes on the feeding and discharging turntable 21 out of the clean bench; the hole plate transfer mechanism 24 is used to transfer the culture dishes / counting plates outside the clean bench to the clean bench. The orifice plate outside the clean bench is sent to the inlet and outlet turntable 21 through another inlet and outlet channel opened on the side wall of the clean bench. It is also used to transfer the orifice plate on the inlet and outlet turntable 21 out of the clean bench. The inlet and outlet turntable 21 is used to send the culture dish / orifice plate to / from the receiving conveyor belt 22 in a rotating manner. The receiving conveyor belt 22 is used to send the culture dish / orifice plate to the area where the pipetting mechanism 1 on the automated cell processing equipment facilitates pipetting (the cell processing equipment can use the pipetting mechanism 1 for pipetting and can use the opening mechanism 3 for opening the cover).

[0080] The specific structures of the feed and discharge turntable 21, the receiving conveyor belt 22, the culture dish transfer mechanism 23 and the orifice plate transfer mechanism 24 are as follows: The feed / discharge turntable 21 comprises a fixed tray 211 and a rotating turntable 212. The turntable 212 is mounted above the tray 211 and includes a driver that controls the direction and angle of rotation. The tray 211 is coated with Teflon to prevent scratches on the bottoms of the culture dishes, well plates, or counting chambers as the turntable 212 propels them across the tray 211.

[0081] The loading and unloading turntable 21 of this embodiment is provided with four workstations, three of which are culture dish loading and unloading stations, orifice plate loading and unloading stations and transfer stations. The culture dish loading and unloading stations and orifice plate loading and unloading stations are symmetrically arranged with respect to the tray 211, one is close to the rear side wall of the clean bench, and the other is close to the front side wall of the clean bench. The transfer station is located between the culture dish loading and unloading stations and the orifice plate loading and unloading stations. The turntable 212 is provided with an air avoidance hole 2121 corresponding to each workstation. There are two types of air avoidance holes 2121. One air avoidance hole 2121 can accommodate culture dishes / counting plates, and the other air avoidance hole 2121 can place orifice plates.

[0082] The position of the tray 211 corresponding to the loading and unloading station of the culture dish is provided with an air-avoiding groove 2111 for facilitating the lowering of the culture dish / counting plate, and the part of the tray 211 corresponding to the transfer station is provided with a through hole for receiving the conveyor belt 22 in an air-avoiding manner.

[0083] After the culture dish / well plate / counting plate is pushed to the transfer station by the turntable 212, the culture dish / well plate / counting plate falls on the receiving conveyor belt 22. The receiving conveyor belt 22 is a conveyor belt in this embodiment. The receiving conveyor belt 22 includes a first conveying section and a second conveying section that are parallel, equal in height and arranged along the conveying direction. The first conveying section is a single conveyor belt located at the transfer station, and the second conveying section is immediately adjacent to the end of the first conveying section. The second conveying section includes two parallel, equal in height and synchronized conveyor belts. The receiving conveyor belt 22 is used to support and transport the culture dish / well plate / counting plate. The second conveying section is located below the pipetting mechanism 1 of the automated cell processing equipment to facilitate the pipetting gun 125 of the pipetting mechanism 1 to perform pipetting. A marking identification module can be set between the two conveyor belts with a spacing between them to record the containers (culture dishes / well plates / counting plates) passing through the marking identification module, so as to facilitate the tracking and recording of cell processing.

[0084] A tilting mechanism 4 is also provided between the two conveyor belts of the second conveyor section. Figures 16 to 21The tilting mechanism 4 includes a pusher 41 and a push rod 42 and a baffle 43 fixed at the output end of the pusher 41. The pusher 42 and the baffle 43 are located between the two conveyor belts of the first conveying section. The pusher 41 drives the pusher 42 and the baffle 43 to rise and fall synchronously along the Z axis. The pusher 42 is used to push the culture dish. The distance between the pusher 42 and the baffle 43 is greater than the radius of the culture dish and smaller than the diameter of the culture dish. The baffle 43 is used to tilt the culture dish against the baffle 43 when the pusher 42 eccentrically pushes the culture dish, so as to facilitate the pipette 125 to absorb the liquid in the culture dish. In this embodiment, the baffle 43 is an arc-shaped plate. Cooperating with the arc structure of the culture dish, it further ensures that after the push rod 42 pushes the culture dish to tilt, the culture dish will not fall in other directions. The push rod 42 is an elastic push rod 42, which includes a push rod body 421 and an elastic member 422. The push rod body 421 is slidably connected to the output end of the pusher 41 along the Z axis, and the elastic member 422 is arranged between the push rod body 421 and the output end of the pusher 41. The elastic member 422 of this embodiment is a spring, which is sleeved on the push rod body 421. One end of the elastic member 422 abuts against the push rod body 421, and the other end abuts against the output end of the pusher 41. The provision of the elastic push rod 42 allows the push rod 42 to slowly push the culture dish using its elasticity, avoiding overturning the culture dish due to excessive pushing.

[0085] Observation holes 2112 are provided on the trays 211 corresponding to the culture dish loading and unloading stations and the well plate loading and unloading stations. A mark recognition module 213 is installed under each observation hole 2112. The mark recognition module 213 is used to identify the labels on the culture dishes / well plates / counting plates placed at the corresponding loading and unloading stations. The mark recognition module 213 is connected to the control system to record the identity of the culture dishes / well plates / counting plates transferred from the inlet and outlet turntable 21, thereby improving the accuracy of control. At the same time, it is convenient to know the operation status of the corresponding culture dishes / well plates / counting plates in a marked manner after the cell passaging / plating is completed, so as to facilitate the tracking and tracing of the operations performed on the culture dishes / well plates / counting plates.

[0086] The tag recognition module 213 in this embodiment can be a camera or a radio frequency reader connected to the control system.

[0087] The culture dish transfer mechanism 23 includes a multi-degree-of-freedom manipulator 231 and a storage rack 232 located next to the multi-degree-of-freedom manipulator 231. In this embodiment, there are two storage racks 232, one for placing culture dishes that need to be sent to the clean bench, and the other for storing culture dishes taken out of the clean bench. The multi-degree-of-freedom manipulator 231 and all storage racks 232 are arranged in a storage chamber 230, and the storage chamber 230 is connected to the clean bench through an inlet and outlet channel. The clean bench and the storage chamber 230 are both equipped with a fan system, and the fan system includes a filter. The fan system is used to provide air with a set cleanliness level. During the cell processing process, the positive pressure in the clean bench is greater than the positive pressure in the storage chamber 230 to ensure that only the gas in the clean bench is blown into the storage chamber 230.

[0088] The output end of the multi-degree-of-freedom manipulator 231 is a U-shaped output claw 2314, and the output claw 2314 of the multi-degree-of-freedom manipulator 231 can be raised and lowered. The multi-degree-of-freedom manipulator 231 of this embodiment includes a rotating seat 2311, a Z-axis linear module 2312 installed at the output end of the rotating seat 2311, and a transverse module 2313 installed at the output end of the Z-axis linear module 2312. The output end of the transverse module 2313 is fixed with the output claw 2314, so that the output gripper can be raised and lowered in the Z direction, rotated around the Z axis and moved in the horizontal plane, so as to facilitate the removal and placement of culture dishes from the storage rack 232.

[0089] The output claw 2314 is provided with a sink for supporting and positioning the culture dish. The sink is integrally formed with multiple support protrusions 23141 for supporting the bottom edge area of ​​the culture dish. The multiple support protrusions 23141 correspond to the four sides of the culture dish, so that when the culture dish is lifted, the output claw 2314 can not only stably support the culture dish but also greatly reduce the contact area with the culture dish, especially not contacting the bottom middle area of ​​the culture dish, thereby ensuring that the middle area of ​​the culture dish used for cell morphology observation or microbial condition inspection is completely unaffected.

[0090] The culture dish loading and unloading station on tray 211 is equipped with a clearance slot 2111 for the output claw 2314 of the multi-degree-of-freedom robot 231 to move up and down. The clearance hole 2121 on the turntable 212 also clears the output claw 2314 of the multi-degree-of-freedom robot 231. After the clearance hole 2121 on the turntable 212 is aligned with the culture dish loading and unloading station, the output claw 2314 moves the supported culture dish / counting plate downward and places it on the tray 211.

[0091] A rotating platform 212 is installed at the bottom of the storage rack 232. The rotating platform 212 drives the entire storage rack 232 to rotate when needed. A plurality of layers 2321 are fixed on the storage rack 232 at equal intervals in the height direction. Weight-reducing holes are provided in the centers of the layers 2321 other than the top to reduce the pressure on the rotating platform 212, thereby reducing the energy consumption when the rotating platform 212 rotates.

[0092] Each shelf 2321 has multiple support grooves 23211 evenly distributed around the center of rotation. Each support groove 23211 can be used to support a culture dish. Each support groove 23211 also has a clearance hole 23212 for the output claw 2314. There is a gap between adjacent shelves 2321 for the output claw 2314 to enter and exit. The center of the support groove 23211 is a through groove, so that the culture dish / counting plate can be supported by the edge area of ​​the support groove 23211.

[0093] The multi-degree-of-freedom manipulator 231 transfers the culture dish / counting plate between the culture dish loading and unloading station and the storage rack 232 by lifting the culture dish / counting plate.

[0094] A culture dish inkjet printer 25 is installed in the storage room 230. The culture dish inkjet printer 25 is used to inkjet mark the culture dish / counting plate that is about to be sent to the clean bench from the bottom. The culture dish inkjet printer 25 makes the mark on the bottom edge of the culture dish to ensure that it does not affect the observation of cell morphology or the inspection of microbial conditions, but can accurately know the identity of the culture dish through the unique mark.

[0095] The plate transfer mechanism 24 includes a plate conveyor belt 241, a plate pusher 242, a plate lifting platform 243, a plate receiving conveyor belt 244, and a plate pusher 245. The plate conveyor belt 241 is used to transport the plate into or out of the clean bench. The plate conveyor belt 241 is used to pass through the clean bench used for cell processing experiments. The plate pusher 245, the plate pusher 242, and the plate receiving conveyor belt 244 are all located outside the clean bench.

[0096] The orifice plate conveyor belt 241 is opposite to the orifice plate loading and unloading station, the orifice plate lifting platform 243 and the inlet and outlet turntable 21 are located at both ends of the orifice plate conveyor belt 241, and the orifice plate pusher 242 is used to push the top orifice plate among the orifice plates stacked on the orifice plate lifting platform 243 onto the orifice plate conveyor belt 241.

[0097] The orifice plate conveyor 241 includes a first conveyor belt and a second conveyor belt. The first conveyor belt includes two synchronous belts of equal height with a spacing. The first conveyor belt is located outside the clean bench, and the second conveyor belt is a single belt. The second conveyor belt is located inside the clean bench. The orifice plate transfer mechanism 24 located outside the clean bench is partially provided with an orifice plate chamber 240. The orifice plate chamber 240 also has a fan system. The orifice plate chamber 240, the clean bench, and the storage chamber 230 are all provided with air outlet holes to facilitate the positive pressure gas blown out by the fan to be discharged to the outside. When cell processing is carried out in the clean bench, the wind pressure in the clean bench is greater than the wind pressure in the storage chamber 230, and also greater than the wind pressure in the orifice plate chamber 240. The storage chamber 230 and the orifice plate chamber 240 are both provided with door covers that can be opened to facilitate the placement of culture dishes / orifice plates in the corresponding chambers. The orifice plate conveyor belt 241 is set as the first conveyor belt and the second conveyor belt, so that when the loading and unloading device is maintained, the orifice plate transfer mechanism 24 except the second conveyor belt can be disassembled separately for maintenance, and the clean bench can still perform cell processing operations with manual cooperation. The specific method is that when the orifice plate is to be sent in and out, it is only necessary to manually cooperate to pass the orifice plate through the input and output channel opened on the clean bench and take the orifice plate on the second conveyor belt.

[0098] The orifice plate pusher 242 is used to push the topmost orifice plate among the orifice plates stacked on the orifice plate lifting platform 243 to the first conveyor belt of the orifice plate conveyor 241. An orifice plate inkjet printer 26 is arranged between the orifice plate lifting platform 243 and the first conveyor belt. The orifice plate inkjet printer 26 performs marking on the bottom of the orifice plate. The marking on the bottom of the orifice plate is between the two belts of the first conveyor belt to ensure that the marking will not come into contact with the belt immediately after the marking is completed.

[0099] The orifice plate storage conveyor 244 and the orifice plate pusher 245 are located on the left and right sides of the first conveyor belt. The orifice plate storage conveyor 244 is perpendicular to the first conveyor belt. The orifice plate pusher 245 is used to push the orifice plate on the first conveyor belt onto the orifice plate storage conveyor 244. The orifice plate storage conveyor 244 is a whole belt. The orifice plate pusher 242 and the orifice plate pusher 242 both use cylinders or electric cylinders in this embodiment, and the orifice plate lifting platform 243 uses electric cylinders, cylinders or linear modules to drive the platform to rise and fall.

[0100] When this solution is adopted, during cell processing, the culture dish / counting plate is removed from the storage rack 232, and after being coded and marked by the culture dish inkjet printer 25, it is sent to the tray 211 of the culture dish loading and unloading station. After the mark recognition module 213 under the tray 211 recognizes the identity of the culture dish, the control system controls the rotation of the turntable 212 of the loading and unloading turntable 21, thereby sending the culture dish / counting plate to the first conveying section of the receiving conveyor belt 22.

[0101] 3. Opening mechanism 3 Combine Figures 16 to 18The lid opening mechanism 3 includes a multi-axis motion actuator 31 and a suction cup 32 installed at the output end of the multi-axis motion actuator 31. The multi-axis motion actuator 31 is fixedly installed and is used to drive the suction cup 32 to move along the X-axis, Y-axis, and Z-axis. The multi-axis motion actuator 31 can specifically adopt a three-axis linear module. The suction cup 32 is connected to the negative pressure so that the suction cup 32 can open the lid of the culture dish / well plate through the multi-axis motion actuator 31 after being adsorbed to the lid of the culture dish / well plate, making it convenient for the pipetting mechanism 1 to add or absorb liquid to the culture dish / well plate.

[0102] In this embodiment, in order to facilitate opening multiple lids at the same time, the number of suction cups 32 is set to multiple, and the negative pressure of each suction cup 32 is connected without affecting each other, so that each suction cup 32 can absorb the lid of the culture dish at the corresponding position, making it convenient for the opening mechanism 3 to open the lids of multiple culture dishes at one time.

[0103] In addition, because the lid opening mechanism 3 can move in the XYZ axis, when the cell processing is completed and the culture dish / well plate needs to evenly spread the cell fluid in the container, the suction cup 32 on the lid opening mechanism 3 can be used to firmly suck the lid of the corresponding culture dish / well plate with the lid closed, and then the multi-axis motion actuator 31 can be controlled to drive the suction cup 32 to move in the horizontal plane to simulate the manual cross movement of the culture dish / well plate, thereby achieving uniform spreading of the cell fluid in the culture dish / well plate.

[0104] In addition, an elastic rod 33 is provided between the suction cup 32 and the output end of the multi-axis motion actuator 31 of this embodiment. The deformation direction of the elastic rod 33 is the Z axis. The elastic rod 33 includes a sliding rod slidably connected to the output end of the multi-axis motion actuator 31. A spring is sleeved on the sliding rod. One end of the spring is against the output end of the actuator, and the other end is against the sliding rod. The free end of the sliding rod is fixed to the suction cup 32. This solution allows the elastic rod 33 to buffer the process when the multi-axis motion actuator 31 drives the suction cup 32 to press down to the cover of the culture dish / well plate, thereby avoiding the problem that the multi-axis motion actuator 31 presses down a slightly larger distance and crushes or damages the culture dish / well plate.

[0105] 4. Second feeding and discharging device 5, centrifugal mechanism 6 and tube cap opener 7 Combine Figure 16 、 Figures 22 to 23 In this embodiment, the number of second inlet and outlet devices 5 is two, and the two second inlet and outlet devices 5 are respectively close to the front side and the rear side of the clean bench. Each second inlet and outlet device 5 is used to deliver / deliver test tubes into / out of the clean bench through the corresponding inlet and outlet channel, and the tube cap opener 7 can open the tube caps of the test tubes on the two second inlet and outlet devices 5.

[0106] Specifically, the second feeding and discharging device 5 includes a rotating component 51, a tube clamp 52, a hanging feeding structure 53 and a hanging discharging structure 54. The rotating component 51 can rotate, and the tube clamp 52 corresponds to the uncapping station of the rotating component 51. The rotating component 51 includes a rotatable rotating disc 511 and a fixedly installed enclosing ring 512. The rotation of the rotating disc 511 is controlled by a rotating driver. The rotating disc 511, the enclosing ring 512 and the tube clamp 52 are all located in the clean bench. The enclosing ring 512 is a circular ring structure with two notches, and the enclosing ring 512 encloses the rotating disc 511. The rotating disc 511 is provided with a plurality of placement holes 510 in a circumferential direction. The projection of the placement holes 510 onto the horizontal plane is U-shaped. The U-shaped opening of the placement holes 510 faces outward and is directly opposite to the inner ring side of the enclosing ring 512. The placement holes 510 are used to place test tubes. Test tubes with caps can be placed on the placement holes 510 of the rotating component 51 and the test tubes are held up by the rotating component 51. Because the size of the test tube caps is larger than the test tube bodies, when the test tube caps are not opened, the test tubes are equivalent to being hung on the placement holes 510. Since most of the placement holes 510 correspond to the enclosing ring 512, even if there is centrifugal force during the rotation of the rotating disc 511, the test tubes will be restricted by the enclosing ring 512.

[0107] The hanging feed structure 53 and the hanging discharge structure 54 installed outside the clean bench are used to send the test tubes into / out of the placement holes 510 corresponding to the gaps through the corresponding feed and discharge channels, and the tube cap opener 7 can open or close the test tubes on the rotating disk 511.

[0108] Specifically, the hanging feed structure 53 and the hanging discharge structure 54 each include a fixedly mounted left support and a right support. The space between the left and right supports is used for the test tube body to pass through. The test tube cap is used to be suspended on both the left and right supports. The hanging feed structure 53 and the hanging discharge structure 54 are used to align with the notch positions respectively. The left and right supports of the hanging feed structure 53 are tilted downward toward one of the notches, while the left and right supports of the hanging discharge structure 54 are tilted upward toward the other notch. The hanging feed structure 53 and the hanging discharge structure 54 are both located within the equipped test tube chamber 50. The test tube chamber 50 has an openable door and transparent sidewalls to facilitate intuitive viewing of the test tube chamber 50.

[0109] In one of the improved schemes, in order to ensure that the test tube actively moves toward the hanging discharge structure 54 when it needs to be sent out, the second feeding and discharging device 5 also includes a pushing block 55 fixedly installed above the rotating disc 511, and the pushing block 55 is opposite to the hanging discharge structure 54. The side of the pushing block 55 facing the hanging discharge structure 54 is an arc surface, and an elastic block is pasted on the arc surface, such as pearl cotton or sponge. The pushing block 55 can cover at least half of the placement hole 510, so that when the rotating disc 511 drives the test tube to rotate close to the hanging discharge structure 54, the test tube is gradually pushed outward by the elastic block on the arc surface of the pushing block 55 until the test tube falls from the placement hole 510 through the gap and along the hanging discharge structure 54. In this improved solution, the presence of the elastomer ensures that when the placement hole 510 has not yet aligned with the hanging discharge structure 54, the elastomer will not damage the test tube due to excessive squeezing force; this embodiment allows the rotating disc 511 to complete the operation of sending the test tube from the rotating disc 511 to the rotating disc 511 when it rotates one circle, making it convenient to send the test tube in and out in a timely manner. The test tubes required for cell processing can be placed on the hanging feeding mechanism in advance according to the required order, thereby facilitating the active use and delivery of the test tubes during the cell processing process.

[0110] In addition, in an improved solution, the end of the hanging discharge structure 54 aligned with the outer periphery of the rotating disk 511 is wrapped with an elastic band, and the elastic band adopts a sponge strip or foam strip with adhesive function to prevent the test tube from scratching the end of the hanging discharge structure 54 and damaging the test tube.

[0111] The tube gripper 52 is used to grip the test tube body rotated to the uncapping station. The tube gripper 52 of this embodiment can adopt a finger cylinder or an electric gripper. The tube gripper 52 includes two gripping fingers that can move closer to or away from each other. The two gripping fingers move closer to each other to clamp the test tube. After the two gripping fingers move away from each other, the test tube can be shuttled between the two gripping fingers as the rotating disk 511 rotates.

[0112] The tube cap opener 7 is used to open the tube cap of the test tube at the cap opening station with the cooperation of the tube clamp 52. The tube cap opener 7 includes a spatial manipulator and a tube cap opening structure installed at the output end of the spatial manipulator. The spatial manipulator is used to drive the tube cap opening structure to move in three-dimensional space. The tube cap opening structure is used to screw the tube cap of the test tube. The specific structure can refer to the tube cap opener 7 composed of a multi-degree-of-freedom robot and a drive-control integrated opening device in the virus sampling tube intelligent cap opening robot disclosed in CN113003506A.

[0113] The spatial mover 11 is used to drive the pipette gun 125 of the pipetting assembly 12 to extend into the test tube at the capping station to suck or inject liquid.

[0114] The centrifuge mechanism 6 includes a rotatable centrifuge frame with a receiving hole 61 and a counterweight 62 symmetrically arranged about the centrifuge frame's rotation axis. The counterweight 62 ensures stable rotation of the centrifuge frame during centrifugation, even when only a single test tube is being centrifuged, thereby ensuring the centrifugal effect. A tube cap opener 7 is used to place the test tube to be centrifuged from the rotating disc 511 into the receiving hole 61. After centrifugation is complete, the tube cap opener 7 is used to return the centrifuged test tube to the rotating disc 511. The tube cap of the centrifuged test tube is then removed by the cooperation of the tube gripper 52 and the tube cap opener 7.

[0115] 5. Cell counting and morphology observation machine8 Combine Figure 16 and Figure 17 The cell counting and morphology observation machine 8 is provided with a pushing mechanism, which is used to transfer the culture dish / counting plate between the second conveying section and the loading platform 81 of the cell counting and morphology observation machine 8. The cell counting and morphology observation machine 8 is installed in a detection chamber 80. The detection chamber 80, the well plate chamber 240, the storage chamber 230 and the clean bench are all provided with transparent side walls to facilitate observation of the situation in the chamber. The positive pressure of the fan system in the clean bench causes the air in the clean bench to be squeezed out of the clean bench during cell processing.

[0116] The pushing mechanism includes a pusher 82 and a returner 83. The pusher 82 and the first conveying section are located at both ends of the conveying direction of the second conveying section. The pusher 82 is used to send the culture dish / counting plate on the second conveying section to the stage 81, and the returner 83 is used to send the culture dish / counting plate on the stage 81 back to the second conveying section. The specific pusher 82 includes a pushing conveyor belt and a pushing plate 821 fixed on the pushing conveyor belt. The pushing conveyor belt is higher than the second conveying section. A transition support platform 84 is provided between the stage 81 and the receiving conveyor belt 22. The supporting surfaces of the transition support platform 84, the stage 81, and the receiving conveyor belt 22 are at the same height. After the pushing conveyor belt is started, the pushing plate 821 is used to push the culture dish / counting plate on the second conveying section to the stage 81 via the transition support platform 84. After the culture dish / counting plate is placed on the stage 81, the integrated cell counting and cell morphology observation equipment can facilitate cell morphology observation or cell counting.

[0117] The returner 83 is a pneumatic cylinder / electric cylinder capable of linear movement. A push-back plate 831 is fixed to the end of the output rod of the returner 83 . The returner 83 is used to drive the push-back plate 831 away from or close to the second conveying section.

[0118] The specific process of this embodiment is as follows: When using the embodiment, if cell passaging is performed, the culture dishes and counting plates used for cell passaging are sent to the inlet and outlet turntable 21 by the culture dish transfer mechanism 23 of the first inlet and outlet device 2. If a well plate (such as a 96-well plate) is used for plating, the well plate is sent to the inlet and outlet turntable 21 by the well plate transfer mechanism 24. The inlet and outlet turntable 21 then sends the objects to the receiving conveyor belt 22. The second conveying section of the receiving conveyor belt 22 serves as the operation area for cell processing. The culture dish / well plate can be opened by the lid opening mechanism 3. The opened lid is placed on an empty table on the clean bench / or is directly held in a sucker state by the suction cup 32 (this state is required not to affect the pipetting operation of the pipetting mechanism 1). The pipetting mechanism 1 uses the pipette gun 125 rotated to the working position to perform the pipetting operation. The pipette gun 125 can also perform the pipetting operation on the test tube on the second inlet and outlet device 5.

[0119] For culture dishes / counting plates that require cell morphology observation or cell counting, they are sent to the cell counting and morphology observation integrated machine 8 for cell morphology observation or cell counting. After use, they are returned to the culture dishes / counting plates through the corresponding inlet and outlet channels on the clean bench to facilitate subsequent pipetting operations or use the first inlet and outlet device 2 to send the culture dishes / counting plates out of the clean bench. The automated operation of cell counting and cell morphology observation is realized here.

[0120] For cell fluid that needs to be centrifuged, the second feeding and discharging device 5 cooperates with the tube cap opener 7 and the centrifugal mechanism 6 to realize the centrifugal operation and the timely delivery of the used test tubes.

[0121] The entire embodiment can satisfy the cell passage operation function as well as the operation functions such as plating and packaging, which helps to realize cell processing with different functions on the same device, and the device has a high degree of automation.

[0122] In addition, in this embodiment, the first material loading and unloading device 2 and the cell counting and morphology observation integrated machine 8, which occupy a large area, are both located outside the clean bench, so that the size of the entire clean bench can be greatly reduced, reducing the demand for the size of the clean bench, thereby reducing the purchase cost and maintenance cost of the clean bench.

[0123] In addition, the first material loading and unloading device 2 and the cell counting and morphology observation integrated machine 8 are independent of the clean bench, which also facilitates the maintenance and inspection of the first material loading and unloading device 2 and the cell counting and morphology observation integrated machine 8 themselves.

[0124] The above is only an embodiment of the present invention, and the common knowledge such as the specific technical solutions and / or characteristics in the solution are not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the description can be used to interpret the content of the claims.

Claims

1. A multifunctional cell processing device comprising an ultra-clean bench and a pipetting mechanism, a lid opening mechanism, a centrifuge mechanism, and a tube cap opener located within the ultra-clean bench. The pipetting mechanism is used to pipette liquid from opened culture dishes / well plates / test tubes. The centrifuge mechanism is used to centrifuge the contents of the test tubes. The tube cap opener is used to open and close the caps of test tubes and transfer test tubes between a test tube placement position and a centrifugal position of the centrifuge mechanism. The device is characterized by: It also includes a first feeding and discharging device and a cell counting and morphology observation integrated machine. The first feeding and discharging device includes a transfer mechanism and a receiving conveyor belt. The receiving conveyor belt is located below the pipetting mechanism and the receiving conveyor belt is located in the clean bench. The transfer mechanism and the cell counting and morphology observation integrated machine are both located outside the clean bench. The transfer mechanism takes and places culture dishes / well plates / counting plates on the receiving conveyor belt through a channel provided on the clean bench; the cell counting and morphology observation integrated machine is used to realize cell morphology observation and cell counting. The cell counting and morphology observation integrated machine is provided with a pushing mechanism, which is used to transfer culture dishes / counting plates between the receiving conveyor belt and the loading platform of the cell counting and morphology observation integrated machine.

2. The multifunctional cell processing device according to claim 1, characterized in that: The transfer mechanism includes a culture dish transfer mechanism and a well plate transfer mechanism. The culture dish transfer mechanism is located outside the clean bench and includes a storage rack and a transfer robot. The transfer robot is used to transfer the culture dish or a counting plate with the same outer contour as the culture dish between the receiving conveyor belt and the storage rack. The well plate transfer mechanism is used to send the well plate into or out of the receiving conveyor belt.

3. The multifunctional cell processing device according to claim 2, characterized in that: The transfer mechanism also includes an inlet and outlet turntable, which includes a fixedly installed tray and a rotatable turntable. The tray is provided with a through hole for avoiding air to receive the conveyor belt. The turntable is located above the tray. The turntable is provided with at least two kinds of air avoidance holes, one of which can cooperate with the culture dish, and the other can cooperate with the orifice plate. After the turntable rotates, the culture dish / counting plate / orifice plate can be transferred between the receiving conveyor belt and the tray.

4. The multifunctional cell processing device according to claim 3, characterized in that: The orifice plate transfer mechanism includes an orifice plate conveyor belt, an orifice plate pusher, an orifice plate lifting platform, an orifice plate storage conveyor belt and an orifice plate pusher. The orifice plate conveyor belt passes through a channel provided on the clean bench. The orifice plate pusher, orifice plate lifting platform, orifice plate pusher and orifice plate storage conveyor belt are all outside the clean bench; the orifice plate conveyor belt is perpendicular to the orifice plate storage conveyor belt, and the orifice plate conveyor belt has an orifice plate lifting platform and an in-and-out material turntable at both ends of the conveying direction. The orifice plate pusher is used to push the orifice plate at the top of the orifice plate lifting platform onto the orifice plate conveyor belt, the orifice plate conveyor belt is used to send the orifice plate into / out of the in-and-out material turntable, and the orifice plate pusher is used to push the orifice plate from the orifice plate conveyor belt to the orifice plate storage conveyor belt.

5. The multifunctional cell processing device according to any one of claims 1 to 4, characterized in that: The pipetting mechanism includes a space mover and a pipetting assembly installed at the output end of the space mover. The space mover is used to drive the pipetting assembly to move in space. The pipetting assembly includes a presser, a rotating seat and multiple pipette guns. The rotating seat and the presser are both installed at the output end of the space mover. The multiple pipette guns are distributed circumferentially on the rotating seat. The rotating seat is used to rotate the pipette gun to the working position. The presser is used to press the pressing head of the pipette gun located in the working position to absorb or discharge liquid. The presser is used to press the pushing head rod after aligning the pushing head rod of the pipette gun to replace the gun head.

6. The multifunctional cell processing device according to claim 5, characterized in that: The pipetting mechanism also includes a waste container placed on the clean bench and a gun tip group containing multiple gun tips of different specifications. The pipette can be inserted into the gun tip of the gun tip group to assemble a new gun tip, and the gun tip or waste liquid pushed out of the pipette can be received by the waste container.

7. The multifunctional cell processing device according to claim 6, characterized in that: The presser includes a reciprocating pressure rod, a rotator and a pressing block. The reciprocating pressure rod is used to drive the pressing block away from or close to the pressing head of the pipette, and the pressing block and the pressing head can fit together in a concave and convex manner. The rotator is used to drive the pressing block to rotate; a plurality of suction volume data acquisition modules are provided on the rotating seat, and each suction volume data acquisition module is used to collect the range on a corresponding pipette.

8. A multifunctional cell processing device according to any one of claims 1-4, 6-7, characterized in that: The centrifugal mechanism comprises a rotatable centrifugal frame, on which a counterweight symmetrical with respect to a rotating axis of the centrifugal frame and a placement hole are provided.

9. A multifunctional cell processing device according to any one of claims 1-4, 6-7, characterized in that: The cover opening mechanism includes a multi-axis motion actuator and a suction cup installed at the output end of the multi-axis motion actuator. The multi-axis motion actuator is used to drive the suction cup to move in space, and the spatial movement includes movement of the X-axis, Y-axis, and Z-axis.

10. A multifunctional cell processing device according to any one of claims 1-4, 6-7, characterized in that: It also includes a second feeding and discharging device, which includes a rotatable rotating disc and a fixedly installed enclosing ring. The rotating disc and the enclosing ring are both located in the clean bench. The enclosing ring is a circular structure. A plurality of placement holes are provided in the circumference of the rotating disc. The projection of the placement holes onto the horizontal plane is U-shaped. The U-shaped opening of the placement holes faces outward and faces the inner ring side of the enclosing ring. The placement holes are used to place test tubes, and the tube cap opener can open or close the test tubes on the rotating disc.

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