Automatic pipetting device

Abstract

The invention relates to the technical field of pipetting guns for biological tests, and particularly discloses an automatic pipetting device which comprises a space mover and a pipetting assembly installed at the output end of the space mover, the space mover is used for driving the pipetting assembly to move in space, and the pipetting assembly comprises a pressing device, a rotating seat and a plurality of pipetting guns. The rotating base and the pressing device are both installed at the output end of the space mover, the multiple pipettes are distributed on the rotating base in the circumferential direction, the rotating base is used for rotating the pipettes to work stations, and the pressing device is used for pressing pressing heads of the pipettes located at the work stations so as to suck liquid or discharge the liquid. And the pressing device is used for pressing down the push head rod after the push head rod of the pipette head is replaced by aiming at the pipette. The scheme is used for solving the problems that the capacity of a pipette in an existing pipetting device is fixed and single, the wide measuring range required by scientific research experiments cannot be covered, and the replacement automation degree of a pipette head of the pipette is insufficient.

Description

Technical Field

[0001] The present invention relates to the technical field of pipettes for biological experiments, and particularly to an automatic pipetting device. Background Art

[0002] As a basic tool in modern biological laboratories, pipettes play an irreplaceable role in research fields such as cell culture, molecular biology, and immunology. Whether it is routine cell passage, medium replacement, or complex CO-IP (co-immunoprecipitation) experiments and ELISA detections, pipettes undertake the crucial task of precisely transferring various liquids. During the experiment, researchers need to frequently change pipettes with different ranges according to different liquid properties and transfer volume requirements (some requirements are in microliters while some are in milliliters). Taking a typical cell passage experiment as an example, the operator needs to first use a milliliter pipette to discard the old medium, then use a milliliter pipette to take PBS for washing, then use a milliliter pipette with a slightly smaller range or a microliter pipette with a slightly larger range to add digestive fluid (such as trypsin), then add the termination solution, use a milliliter pipette to add complete medium, use a milliliter pipette to remove the supernatant after centrifugation, then use a milliliter or microliter pipette to resuspend the cell solution, and after resuspension, use a microliter pipette with a small range such as 20 μL to inject the cell solution into a cell counting chamber, and finally use a microliter or milliliter pipette to aliquot the cell suspension. The whole process requires repeated replacement of pipettes with different ranges and the corresponding required pipette tips, and the operation is extremely cumbersome.

[0003] This pipetting mode that highly relies on manual operation has obvious limitations. First of all, biological experiments usually require a strict aseptic environment and precise operation timing. Manual pipetting is not only inefficient but also prone to errors due to operation fatigue. Secondly, the highly repetitive pipetting work takes up a large amount of time of scientific researchers. Statistics show that in a standard 96-well plate inoculation experiment, the time consumed by manual pipetting accounts for more than 60% of the total experiment time. More notably, biomedical experiments usually require researchers with a professional background to operate, and these highly educated talents spend a large amount of time on basic pipetting operations, resulting in serious waste of human resources. With the development of new technologies such as high-throughput screening and single-cell sequencing, the experimental throughput has increased exponentially, and the traditional manual pipetting mode has been difficult to meet the needs of modern scientific research.

[0004] To break through this bottleneck, automated pipetting equipment has emerged. The existing technologies are mainly divided into three categories: multi-channel parallel pipetting systems, dedicated pipetting robotic arms, and fully automated pipetting workstations. Taking the automatic pipetting system disclosed in CN111398613A as an example of multi-channel parallel pipetting, it uses a 96-channel pipette array and cooperates with an intelligent conveyor belt to achieve high-throughput sample addition to the microplate. This design is suitable for the standardized production in the pharmaceutical industry, but lacks flexibility and cannot adapt to the changing pipetting requirements in scientific research experiments. Taking the pipetting machine proposed in CN210752747U as an example of a dedicated pipetting robotic arm, it innovatively adopts a misaligned design of two pipettes and realizes the alternating use of two types of pipettes through gear transmission, performing well in specific biochemical detections. However, its dual-pipette structure limits the application scenarios and is difficult to meet the complex experiments that require more combinations of pipettes. For fully automated pipetting, taking the fully automated pipetting workstation in CN116139961A as an example, it realizes the automatic replacement function of the pipette and uses an electric guide rail to drive the plug-in mechanism to complete the loading and unloading of the pipette. Although this design solves some automation problems, obvious defects are exposed in practical applications: when the same pipette with the same range needs to be used multiple times in the same experiment, the system has to repeatedly disassemble and assemble the same pipette, reducing the usage efficiency; more importantly, the replacement of the pipette tip after each pipetting still requires manual intervention, greatly reducing the degree of automation. Summary of the Invention

[0005] The present invention aims to provide an automatic pipetting device to solve the problems that the pipette capacity in the current pipetting device is fixed and single, unable to cover the wide range required for scientific research experiments, and the degree of automation of pipette tip replacement is insufficient.

[0006] To achieve the above object, the present invention adopts the following technical solutions: An automatic pipetting device includes a spatial mover and a pipetting assembly installed at the output end of the spatial mover. The spatial mover is used to drive the pipetting assembly to move in space. The pipetting assembly includes a presser, a rotating seat, and multiple pipettes. The rotating seat and the presser are both installed at the output end of the spatial mover. The multiple pipettes are circumferentially distributed around the rotating seat. The rotating seat is used to rotate the pipette to the working position. The presser is used to press the pressing head of the pipette located at the working position to aspirate or discharge liquid, and the presser is used to press the push rod of the pipette after aligning with the push rod for replacing the pipette tip.

[0007] The principle and advantages of this solution are as follows: In this solution, multiple pipettes are arranged circumferentially around the rotating seat, and pipettes with different ranges can be installed according to the test requirements. Each pipette can be rotated to the working position under the rotating seat. After the pipette is in the working position, the presser can automatically press the pipette to aspirate or discharge liquid. At the same time, after the rotating seat rotates a certain angle, the presser can also press on the push rod of the pipette to automatically eject the pipette tip.

[0008] Compared with the prior art, a pipette with multiple ranges is installed at one time, which improves the usage range. When in use, only the rotating seat needs to be controlled to rotate the corresponding pipette to the working position, and there is no problem of low efficiency caused by multiple pick-ups and placements of the pipette in the prior art. Moreover, the presser is used not only for sucking / discharging liquid of the pipette in the working position, but also for automatically pushing out the used pipette tips on the pipette, which can meet the requirements of different range pipettes and frequent tip replacement in cell processing experiments, and the whole process can be realized through automated control.

[0009] Preferably, as an improvement, the pipetting assembly further includes a plurality of pushers. Each pipette is correspondingly installed at the output end of a pusher. The pusher is installed on the rotating seat. When the rotating seat rotates the pipette to the working position, the pusher is used to control the pipette to approach or move away from the aspirated object, so that when the space mover cannot accurately control the usage position of the pipette on the pipetting assembly, the pusher is used for more precise adjustment.

[0010] 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 to move away from or close to the pressing head of the pipette. The pressing block and the pressing head can be in concave-convex fit. The rotator is used to drive the pressing block to rotate, so that by acting on the pressing block through the rotator and then screwing the pressing head through the pressing block, the aspiration volume of the pipette can be adjusted.

[0011] Preferably, as an improvement, a plurality of aspiration volume data acquisition modules are provided on the rotating seat. Each aspiration volume data acquisition module is used to acquire the range of a corresponding pipette.

[0012] Beneficial effects: Through the setting of the aspiration volume data acquisition module in this solution, it is convenient to automatically adjust the range in different pipetting processes in different biological processing experiments. For example, the range of a pipette is 20-200 ul. When 100 ul needs to be taken, 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, and the displayed value is acquired by the aspiration volume data acquisition module. When the aspiration volume value is displayed as 100 ul, the control system controls the rotator to stop rotating the pressing block, so as to ensure the automatic adjustment of the aspiration volume under different usage requirements and further improve the degree of automation.

[0013] Preferably, as an improvement, a hollow cavity is provided in the middle of the rotating base. The pipette is installed on the peripheral side surface of the rotating base. Through holes are provided at both axial ends of the hollow cavity. The pipetting assembly further includes a connecting rod fixedly installed at the output end of the spatial mover. A end plate is fixed at the free end of the connecting rod. A vision module is installed on the end plate. The vision module is used to collect image data below the pipetting assembly.

[0014] Beneficial effects: The setting of the hollow cavity in this solution can, firstly, reduce the weight of the pipetting assembly, and secondly, provide a space for accommodating the wires of the electrical structures used on the pipetting assembly, avoiding the exposure of the wires on the outer periphery of the rotating base. In addition, the suction volume data acquisition module often uses a camera. The suction volume data acquisition module can only expose a very short section on the outer periphery of the rotating base or be directly installed in a hidden manner. The remaining section of the suction volume data acquisition module can be hidden in the hollow cavity, making the appearance of the pipetting assembly more concise and able to form a protection for the suction volume data acquisition module.

[0015] In addition, in this solution, by setting a connecting rod in the hollow cavity and then fixing the end plate through the connecting rod, the corresponding end position of the hollow cavity can be utilized to install the vision module, and the vision module is used to collect the image data below the pipetting assembly, which is equivalent to installing eyes on the pipetting assembly. Thus, after the vision module transmits the image data to the control system, it ensures that all the moving positions of the pipetting assembly can be recorded, and through the judgment of the image data transmitted by the vision module by the control system, it can accurately judge whether the pipetting assembly reaches the preset requirements, thereby further ensuring the accuracy of the actions of the pipetting assembly.

[0016] Preferably, as an improvement, the end plate blocks the through hole at the bottom end of the hollow cavity. The end plate can support the rotating structure part of the rotating base. There are rolling elements between the end plate and the bottom end surface of the hollow cavity. A plurality of rollers are installed on the end plate. The cross-section of the hollow cavity is circular. The plurality of rollers are evenly distributed along the circumferential direction of the hollow cavity and the side surfaces of the rollers roll and rub against the inner wall of the hollow cavity.

[0017] Beneficial effects: By setting the rolling elements and the rollers, both the rotational stability of the rotating structure part of the rotating base is ensured, and the end plate can also support the rotating base, improving the structural stability of the pipetting assembly.

[0018] Preferably, as an improvement, it further includes a material standby mechanism. The material standby mechanism includes a standby rack, a tube clamp, and a tube cap opener. The standby rack can rotate. A plurality of test tube placement holes are provided on the standby rack. The test tubes with tube caps can be placed on the placement holes of the standby rack and the test tubes are supported by the standby rack. The tube clamp is used to clamp the body of the test tube rotated to the cap-removing station. The tube cap opener is used to open the tube cap of the test tube at the cap-removing station. The spatial mover is used to drive the pipette of the pipetting assembly to extend into the test tube at the cap-removing station for liquid suction or injection.

[0019] Beneficial effects: By setting up a spare mechanism for materials, all the liquids required for biological treatment experiments can be filled in corresponding test tubes, and the test tubes are placed on a spare rack. Then, by rotating the spare rack, the test tubes to be opened each time are rotated to the corresponding cap-opening station. The clamping device at the cap-opening station clamps the body of the test tube, facilitating the opening of the test tube cap by a cap-opening device. After the test tube cap is opened, the liquid-transfer assembly moves to the area where the test tube is located driven by a spatial mover, and the working position of the pipette of the liquid-transfer assembly is aligned with the test tube, facilitating the aspiration or discharge of the liquid in the test tube. This further improves the degree of automation and facilitates the opening and closing of the required materials without the need for manual cooperation.

[0020] Preferably, as an improvement, it further includes a lid-opening mechanism for opening the lid of a petri dish. The lid-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 movements along the X-axis, Y-axis, and Z-axis. By setting up the lid-opening mechanism in this solution, the petri dish can be automatically opened, further improving the degree of automation.

[0021] Preferably, as an improvement, an elastic rod is provided between the suction cup and the output end of the multi-axis motion actuator. The deformation direction of the elastic rod is the Z-axis, so that there is elastic buffering when the multi-axis motion actuator drives the suction cup to press down on the lid of the petri dish, avoiding the problem that the multi-axis motion actuator presses down too far and damages or crushes the petri dish. Preferably, as an improvement, it further includes two parallel and equidistant support belts for supporting the petri dish. An inclination mechanism is provided between the two support belts. The inclination mechanism includes a pusher, a push rod fixed to the output end of the pusher, and a baffle. The push rod is used to push the petri dish. The distance between the push rod and the baffle is greater than the radius of the petri dish and less than the diameter of the petri dish. The baffle is used to make the petri dish tilt against the baffle when the push rod eccentrically pushes the petri dish, facilitating the pipette to aspirate the liquid in the petri dish.

[0022] Preferably, as an improvement, the push rod is an elastic push rod. The elastic push rod includes a push rod body and an elastic member. The push rod body is slidably connected to the output end of the pusher along the Z-axis, and the elastic member is arranged between the push rod body and the output end of the pusher. By setting up the elastic push rod with an elastic member, the elastic push rod slowly pushes the petri dish using its elasticity when pushing the petri dish, avoiding the problem of tipping over the petri dish due to too fast pushing. Description of the Drawings

[0023] Figure 1 It is a three-dimensional structure schematic diagram of Embodiment 1 of the present invention.

[0024] Figure 2 is Figure 1Three-dimensional structure diagram of the pipetting assembly when the reciprocating pressure rod in it moves downward until the pressing block and the pressing head of the pipette are in concave-convex fit (the space mover is not shown in the figure, only the pipetting assembly is shown, and the pressing block and the pressing head of the pipette are in concave-convex fit in the figure).

[0025] Figure 3 For Figure 2 Three-dimensional structure diagram after rotation angle (the connecting rod and the end plate are disassembled for convenient display of the hollow cavity of the rotating seat rotation structure part).

[0026] Figure 4 For Figure 2 Front view of

[0027] Figure 5 For Figure 3 Projection view towards the bottom end face of the rotating seat.

[0028] Figure 6 Three-dimensional structure diagram of the pipette when the push head rod of the pipette is facing the pressing block of the presser after the rotating seat rotates a certain angle in the first embodiment of the present invention.

[0029] Figure 7 For Figure 2 Three-dimensional schematic diagram of the pipetting assembly after rotation of the angle in, exploded state schematic diagram of the connecting rod and the end plate relative to the rotating seat, three-dimensional combined schematic diagram of the end plate after relative rotation of the angle (the figure shows a schematic diagram of the reciprocating movement of the reciprocating pressure rod constructed by driving the gear to rotate by a motor and then driving the rack by the gear, shows 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).

[0030] Figure 8 For Figure 7 I-I sectional view in

[0031] Figure 9 Three-dimensional structure diagram of setting the pipetting device in a laminar flow hood in the second embodiment of the present invention (the top of the laminar flow hood is disassembled for convenient display of the pipetting device structure in the figure).

[0032] Figure 10 For Figure 9 Top view of

[0033] Figure 11 For Figure 9 Three-dimensional structure diagram after disassembling the front side of the laminar flow hood in

[0034] Figure 12 For Figure 11 Three-dimensional structure diagram showing only the positional relationship of the open cover mechanism, the support belt, and the tilting mechanism in

[0035] Figure 13 For Figure 12Schematic diagram of the lid-opening mechanism therein.

[0036] Figure 14 is Figure 12 Only the top view showing the supporting belt and the tilting mechanism is presented.

[0037] Figure 15 Schematic three-dimensional structure diagram of the tilting mechanism.

[0038] Figure 16 Front view of the process of the tilting mechanism pushing the culture dish to tilt (in the figure, for the convenience of showing the action process of the tilting mechanism, only one supporting belt that does not block the front view of the tilting mechanism is presented).

[0039] Figure 17 is Figure 11 Schematic three-dimensional structure diagram of the material standby mechanism in

[0040] Figure 18 is Figure 17 Schematic three-dimensional structure diagram after the rotation angle (in the figure, the tube clamping of the test tube by the tube clamp is schematically shown, and the clamping fingers are in a state of moving away from each other). Specific implementation manners

[0041] The following is further detailed through specific implementation manners: The reference numerals in the accompanying drawings of the specification include: pipetting device 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, pipette 125, pressing head 1251, push head rod 1252, suction volume data acquisition module 126, connecting rod 127, end plate 128, vision module 129, rolling body 1281, roller 1282, supporting belt 2, lid-opening mechanism 3, multi-axis motion actuator 31, suction cup 32, elastic rod 33, tilting mechanism 4, pusher 41, ejector rod 42, ejector rod body 421, elastic member 422, baffle 43, laminar flow hood 10, waste liquid tank 101, tip collection cylinder 102, tip set 103, culture dish 100. Material standby mechanism 5, standby rack 51, placement hole 511, tube clamp 52, clamping finger 521, tube cap opener 53, test tube 54, cap-opening station A.

[0042] Example 1 Combined with Figures 1 to 8, an automatic pipetting device, which is set in the laminar flow hood 10 during use, 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 in 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 shown in the drawings of this embodiment. The spatial mover 11 drives the pipetting assembly 12 to perform spatial movement (such as spatial movement of the XYZ axes, such as horizontal movement of the XY axes). The spatial mover 11 only needs to meet the liquid suction and drainage requirements of the pipetting device 1.

[0043] The pipetting assembly 12 includes a mounting base 121, a presser 122, a rotating base 123, a plurality of pushers 124, and multiple pipettes 125. The mounting base 121 is fixed at the output end of the spatial mover 11. Both the rotating base 123 and the presser 122 are installed on the mounting base 121. The plurality of pushers 124 are circumferentially distributed around the rotating structure of the rotating base 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 125 is installed at the output end of each pusher 124. The rotating base 123 is used to rotate the pipette 125 to the working position. The pusher 124 is used to control the pipette 125 to approach or move away from the aspirated object when the rotating base 123 rotates the pipette 125 to the working position. The presser 122 is used to press the pipette 125 at the working position to aspirate or discharge liquid. The pipette 125 can be the pipette 125 disclosed in the patent publication number CN213193738U.

[0044] Among them, the pusher 124 is a linear module. The output slider of the linear module can reciprocate along the Z-axis. A connecting seat is fixedly installed on the output slider. The connecting seat is fitted with the structure of the pipette 125 and the connecting seat is provided with a strap to facilitate the disassembly and assembly of the pipette 125 on the connecting seat.

[0045] In addition, the multiple pipettes 125 carried by the pipetting assembly 12 can facilitate the installation of multiple pipettes 125 with different ranges, so as to meet different usage requirements. For example, when cell passage is required, it is necessary to aspirate the old culture medium in the culture dish, add PBS rinsing solution to the culture dish, add a termination solution, and add a new complete culture medium, etc.

[0046] In addition, since there is a push rod 1252 for replacing the tip of the pipette 125 on the pipette 125 in addition to the pressing head 1251 for aspirating liquid, when the tip of the pipette 125 needs to be replaced each time, only need to control the rotating base 123 to rotate so that the pressing head 1251 is aligned with the push rod 1252, then the used tip of the pipette 125 can be automatically ejected, which improves the automation degree of the pipetting device 1. The pipette 125 in this embodiment can be the pipette 125 disclosed in the patent publication number CN213193738U.

[0047] The presser 122 includes a pressing drive source 1221, a reciprocating pressing rod 1222, a rotator 1223 and a pressing block 1224. The pressing drive source 1221 is used to drive the reciprocating pressing rod 1222 to move along the Z-axis. The rotator 1223 is fixed to the downward output end of the reciprocating pressing rod 1222. The pressing block 1224 is fixedly installed at the output end of the rotator 1223. The rotator 1223 is used to drive the pressing block 1224 to rotate around its axis. The reciprocating pressing rod 1222 is used to drive the pressing block 1224 to move away from or close to the pressing head 1251 for aspirating control of the pipette 125. The pressing block 1224 and the pressing head 1251 of the pipette 125 can be in concave-convex fit. After the pressing block 1224 and the pressing head 1251 of the pipette 125 are in concave-convex fit, 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-convex fit. After the pressing head 1251 of the pipette 125 is screwed, the aspirating volume of the pipette 125 is adjusted. In order to facilitate automatic adjustment of the aspirating volume of the pipette 125 according to different liquid filling volume requirements through the rotator 1223, the automation degree is improved. And because the pipette 125 is installed on the rotating structure of the rotating base 123 along with the pusher 124, after the rotating base 123 rotates to align the pressing block 1224 with the push rod 1252 for replacing the tip of the pipette 125, the pressing of the pressing block 1224 on the push rod 1252 can realize the ejection of the tip of the pipette 125 on the pipette 125, which facilitates the automatic replacement of the tip of the pipette 125 on the pipette 125.

[0048] A suction volume data acquisition module 126 for image acquisition of the suction volume of the pipette 125 is further provided on the rotating structure of the rotating base 123. 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 pipettes 125, so as to facilitate each pipette 125 to have a corresponding camera for monitoring the suction volume and ensure the accuracy of the suction volume.

[0049] A hollow cavity 1231 is provided in the middle of the rotating base 123. The pipette 125 is installed on the peripheral side surface of the rotating base 123. The camera used by the aspiration 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 outside the periphery of the rotating base 123 or extends outside the periphery of the rotating base 123 (in the attached drawings of this embodiment, the camera extends a short distance outside the rotating base 123 as an example). The bottom of the camera is inserted into the rotating base 123, and the connected wires and data lines are placed into the hollow cavity 1231.

[0050] Both the fixed structure part 1230 and the rotating structure part of the rotating base 123 are 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 are provided with through holes. The top through hole of the hollow cavity 1231 communicates with the through hole of the fixed structure part 1230 of the rotating base 123, so that the connecting rod 127 provided on the pipetting assembly 12 can penetrate through the entire rotating base 123 and be fixed on the mounting base 121. A end plate 128 is fixed at the free end of the connecting rod 127 away from the mounting base 121. A vision module 129 is installed on the end plate 128. The vision module 129 is used to collect image data below the pipetting assembly 12. The vision module 129 is close to the working position of the pipetting assembly 12, so that the vision module 129 can record the working process of the pipetting assembly 12 as much as possible. For example, through the vision module 129, image data can be collected for the object to be acted on, such as the culture dish to be filled with liquid, or the position of the new pipette tip to be replaced. To ensure that the actions of the pipetting assembly 12 are more accurate. In a specific embodiment, the vision module 129 can be a camera.

[0051] In addition, the hollow cavity 1231 is a cylindrical cavity. A plurality of evenly distributed rolling elements 1281 are installed on the upper surface of the end plate 128 facing the bottom end surface of the rotating base 123. In this embodiment, the rolling elements 1281 are ball bearings. The ball bearings provide a certain supporting force for the rotating base 123 by the end plate 128, and at the same time, the rolling of the ball bearings enables the rotation of the rotating base 123 to be unaffected by the end plate 128. In addition, to further improve the rotation stability of the rotating structure part of the rotating base 123, a plurality of rollers 1282 are installed on the end plate 128. In this embodiment, the rollers 1282 are bearings. The plurality of rollers 1282 are evenly distributed along the circumferential direction 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.

[0052] The automatic pipetting device 1 of this embodiment installs pipettes 125 with multiple ranges at one time, which improves the scope of use and meets the usage requirements. When in use, only the rotating base 123 needs to be controlled to rotate the corresponding pipette 125 to the working position; moreover, the presser 122 is used both for sucking / discharging liquid of the pipette 125 in the working position (the discarded liquid is extruded into the waste liquid tank 101 provided in the clean bench 10), and for automatically pushing out the used pipette tips on the pipette 125. The pushed-out pipette tips are discarded in the pipette tip collection cylinder 102, where the pipette tip collection cylinder 102 is placed in the clean bench 10. A plurality of new pipette tips of different specifications are also uniformly placed in the boxed pipette tip set 103, which is convenient for taking pipette tips of different specifications according to requirements. In addition, in order to ensure the accuracy of pipette tip replacement, the vision module 129 on the pipetting assembly 12 can be used to photograph the position and quantity of the remaining pipette tips in the pipette tip set 103. The vision module 129 transmits the remaining pipette tip image data to the control system, and the control system controls the spatial mover 11 to move to the position where the required pipette tip can be accurately taken. Finally, the pusher 124 drives the pipette 125 in the working position to move downward, that is, the pipette tip is inserted onto the pipette 125.

[0053] The pipetting device 1 of the entire embodiment can automatically adjust the suction volume, automatically control the suction, automatically push out the used pipette tips, and automatically insert new pipette tips, which helps to realize the fully automated operation of pipetting.

[0054] Embodiment Two Combined with Figures 9 to 18 , Embodiment Two is improved as follows on the basis of Embodiment One: The automatic pipetting device 1 of Embodiment Two further includes a supporting belt 2, a lid opening mechanism 3, an inclination mechanism 4, and a material reserve mechanism. The number of the supporting belts 2 is two, and the two supporting belts 2 are parallel and at the same height. In this embodiment, the two supporting belts 2 are two synchronous first conveyor belts, and the two supporting belts 2 are used to jointly support and convey the culture dishes; the two supporting belts 2 are located on the tabletop of the clean bench 10, and the two supporting belts 2 are located below the pipetting device 1.

[0055] The lid opening mechanism 3 is used to open or cover the lids of the culture dishes on the supporting belt 2.

[0056] The inclination mechanism 4 is located between the two supporting belts 2 and is used to push the culture dish from the horizontal state to the inclined state to facilitate the pipette 125 to suck out the liquid in the culture dish.

[0057] The material standby mechanism is used to place the materials required for multi-tube cell processing. For example, when cell passage is needed, PBS washing solution, digestive solution, termination solution, complete culture medium, etc. are all loaded into test tube 54 and placed on the material standby mechanism. The material standby mechanism also has the function of opening the tube cap of test tube 54, so as to facilitate the opening of test tube 54 containing the required materials for the pipette 125 to aspirate or discharge the liquid.

[0058] The specific structure is as follows: I. The lid-opening mechanism 3: Combined with Figures 11 to 13 , the 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 used to drive the suction cup 32 to move in 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 negative pressure, so that after the suction cup 32 adsorbs the lid of the culture dish, the lid can be opened by the multi-axis motion actuator 31, facilitating the pipetting device 1 to add or aspirate liquid to / from the culture dish.

[0059] In this embodiment, in order to facilitate the passage of cells for which cell morphology observation has been completed, the number of suction cups 32 is set to multiple, and the negative pressure connections of each suction cup 32 do not affect each other, so that each suction cup 32 can adsorb the lid of the corresponding culture dish, facilitating the lid-opening mechanism 3 to open the lids of multiple culture dishes at one time.

[0060] In addition, because the lid-opening mechanism 3 can move in the X, Y, and Z axes, when the cell passage is completed and the cell liquid in the culture dish needs to be evenly spread, the suction cup 32 on the lid-opening mechanism 3 can be used to firmly adsorb the lid of the corresponding culture dish, and then the multi-axis motion actuator 31 can be controlled to drive the suction cup 32 to move in a cross shape on the horizontal plane to simulate manual cross movement of the culture dish, so as to achieve the even spreading of the cell liquid in the culture dish.

[0061] In addition, an elastic rod 33 is provided between the suction cup 32 and the output end of the multi-axis motion actuator 31 in 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 abuts against the output end of the actuator, and the other end abuts against the sliding rod. The free end of the sliding rod is fixed with the suction cup 32. This solution enables the elastic rod 33 to buffer when the multi-axis motion actuator 31 drives the suction cup 32 to press down on the lid of the culture dish, avoiding the problem that the multi-axis motion actuator 31 presses down too far and damages or crushes the culture dish.

[0062] II. The tilting mechanism 4 Combined with Figure 12 、 Figures 14 to 16, the tilting mechanism 4 includes a pusher 41, a push rod 42 and a baffle 43 fixed to the output end of the pusher 41. The pusher 41 drives the push rod 42 and the baffle 43 to lift and lower synchronously along the Z-axis. The push rod 42 is used to push the culture dish. The distance between the push rod 42 and the baffle 43 is greater than the radius of the culture dish and less than the diameter of the culture dish. The baffle 43 is used to make the culture dish tilt against the baffle 43 when the push rod 42 eccentrically pushes the culture dish, so as to facilitate the pipette 125 to aspirate the liquid in the culture dish. In this embodiment, the baffle 43 is an arc-shaped plate, and the arc-shaped plate cooperates with the arc structure of the culture dish to further ensure that after the push rod 42 pushes the culture dish to tilt, the culture dish will not tilt in other directions; the push rod 42 is an elastic push rod 42, and the elastic push rod 42 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. In this embodiment, the elastic member 422 is a spring, and the elastic member 422 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. By providing the elastic push rod 42, the push rod 42 slowly pushes the culture dish using its elasticity when pushing the culture dish, avoiding tipping over the culture dish due to too fast pushing.

[0063] The reason for designing the tilting mechanism 4 is that during the cell passage process, a series of operations need to be performed on the cells in the culture dish before observing the cell morphology. For example, first, all the old culture medium in the culture dish to be passaged needs to be pumped out of the culture dish. At this time, if the culture dish is placed flat on the supporting belt 2, it is very difficult to ensure that the old culture medium is pumped out as much as possible. The upward pushing operation of the tilting mechanism 4 can simulate manually tilting the round culture dish. Similarly, after the cell morphology observation is completed, when the cell liquid in the culture dish needs to be completely transferred into the centrifuge tube, the culture dish also needs to be tilted to ensure that the cell liquid can be basically completely pumped out.

[0064] III. Material standby mechanism Combined with Figure 11 , Figures 17 to 18 , the material standby mechanism includes a standby rack 51, a tube clamp 52 and a tube cap opener 53. The standby rack 51 can rotate, and the rotation of the standby rack 51 is controlled by a rotation driver. The standby rack 51 is in the shape of a frustum of a cone. A plurality of test tube 54 placement holes 511 are opened on the circumferential edge of the frustum of the standby rack 51. The test tubes 54 with tube caps can be placed on the placement holes 511 of the standby rack 51 and the standby rack 51 holds up the test tubes 54. Since the tube cap size of the test tube 54 is larger than the tube body of the test tube 54, the test tube 54 is equivalent to hanging on the placement hole 511 when the tube cap of the test tube 54 is not opened.

[0065] The tube gripper 52 is used to grip the tube body of the test tube 54 rotated to the uncapping station. The tube gripper 52 of this embodiment can adopt a finger cylinder or an electric clamp. The tube gripper 52 includes two clamping fingers 521 that can move closer to or away from each other. The two clamping fingers 521 move closer to each other to clamp the test tube 54. After the two clamping fingers 521 move away from each other, the test tube 54 can shuttle between the two clamping fingers 521 as the spare rack 51 rotates.

[0066] The tube cap opener 53 is used to open the tube cap of the test tube 54 at the cap opening station. The tube cap opener 53 includes a space manipulator and a tube cap opening structure installed at the output end of the space manipulator. The space 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 54. The specific structure can refer to the tube cap opener 53 composed of a multi-degree-of-freedom robot and a drive-control integrated opening device in the intelligent opening robot for the new coronavirus sampling tube disclosed in CN113003506A.

[0067] The spatial mover 11 is used to drive the pipette gun 125 of the pipetting assembly 12 to extend into the test tube 54 at the capping station to suck or inject the liquid.

[0068] In the second embodiment of the present invention, when pipetting during the cell processing process, the culture dish to be operated is placed on the supporting belt 2. The culture dish adopts a conventional round culture dish in the industry. The suction cup 32 of the cover opening mechanism 3 sucks the cover of the culture dish, and under the drive of the multi-axis motion actuator 31 of the cover opening mechanism 3, the cover of the culture dish is transferred to be staggered with the body of the culture dish, so that it is convenient for the pipette gun 125 to suck or add liquid into the culture dish, and the spare liquid added to the culture dish is all placed on the spare rack 51 of the material standby mechanism. When the spare liquid in the corresponding test tube 54 is needed, it is only necessary to control the corresponding test tube 54 to rotate to the cap opening station under the control of the spare rack 51, so that the tube clamp 52 can clamp the body of the test tube 54 while the tube cap opener 53 can be used to screw the tube cap to realize the opening of the test tube 54. After the test tube 54 is opened, it is convenient for the pipette gun 125 to suck or add liquid. After the test tube 54 is used up, the tube cap can be covered again.

[0069] After each transfer of the liquid transfer gun 125, the used liquid transfer gun 125 head can be replaced by controlling the liquid transfer assembly 12 to enable the pressing block 1224 to press the pusher rod 1252 of the liquid transfer gun 125.

[0070] During the pipetting process, if the liquid in the culture dish needs to be pumped out as much as possible, the pusher 41 of the tilting mechanism 4 is controlled to push upward so that the culture dish is tilted at a certain angle, which makes it convenient for the pipette gun 125 to pump out as much liquid as possible in the culture dish.

[0071] The pipetting device 1 of the entire present embodiment realizes automated operations including automatically opening the tube cap of the test tube 54, automatically opening the lid of the culture dish, automatically tilting the culture dish, automatically injecting / aspirating liquid, and automatically adjusting the aspiration volume of the pipette 125, greatly improving the degree of automation.

[0072] The above are only embodiments of the present invention, and specific technical solutions and / or common knowledge such as characteristics well known in the art are not described in detail herein. It should be noted that for those skilled in the art, without departing from the technical solution of the present invention, several deformations and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the implementation effect of the present invention and the practicality of the patent. The protection scope required by this application should be based on the content of its claims, and the specific implementation manners described in the specification can be used to interpret the content of the claims.

Claims

1. An automatic pipetting device, comprising a spatial mover and a pipetting assembly installed at the output end of the spatial mover, the spatial mover being used to drive the pipetting assembly to move in space, characterized in that: The pipetting assembly includes a presser, a rotating base, and multiple pipettes. Both the rotating base and the presser are installed at the output end of the spatial mover. The multiple pipettes are circumferentially distributed around the rotating base. The rotating base is used to rotate the pipette to the working position. The presser is used to press the pressing head of the pipette located at the working position to aspirate or discharge liquid. The presser is used to press the push rod after aligning it with the push rod for replacing the pipette tip.

2. The automatic pipetting device according to claim 1, wherein: The pipetting assembly further includes multiple pushers. Each pipette is correspondingly installed at the output end of a pusher. The pushers are installed on the rotating base. The pusher is used to control the pipette to approach or move away from the aspirated object when the rotating base rotates the pipette to the working position.

3. The automatic pipetting device according to claim 1, 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 to move away from or close to the pressing head of the pipette. The pressing block and the pressing head can be in concave-convex fit. The rotator is used to drive the pressing block to rotate.

4. The automatic pipetting device according to claim 3, wherein: A plurality of suction volume data acquisition modules are provided on the rotating base. Each suction volume data acquisition module is used to acquire the range on a corresponding pipette.

5. The automatic pipetting device according to claim 4, characterized in that: A hollow cavity is provided in the middle of the rotating base. The pipettes are installed on the peripheral sides of the rotating base. Through holes are provided at both axial ends of the hollow cavity. The pipetting assembly further includes a connecting rod fixedly installed at the output end of the spatial mover. A end plate is fixed at the free end of the connecting rod. A vision module is installed on the end plate. The vision module is used to acquire image data below the pipetting assembly.

6. The automatic pipetting device according to claim 5, characterized in that: The end plate blocks the bottom through hole of the hollow cavity. The end plate can support the rotating structure part of the rotating base. A rolling body is provided between the end plate and the bottom end face of the hollow cavity. A plurality of rollers are installed on the end plate. The cross section of the hollow cavity is circular. The plurality of rollers are evenly distributed along the circumference of the hollow cavity and the side surfaces of the rollers roll and rub against the inner wall of the hollow cavity.

7. The automatic pipetting device according to any one of claims 1-6, characterized in that: It further includes a material standby mechanism. The material standby mechanism includes a standby rack, a tube clamp, and a tube cap opener. The standby rack can rotate. A plurality of test tube placement holes are provided on the standby rack. The test tubes with tube caps can be placed on the placement holes of the standby rack and the test tubes are supported by the standby rack. The tube clamp is used to clamp the tube body of the test tube rotated to the cap-removing station. The tube cap opener is used to open the tube cap of the test tube at the cap-removing station. The spatial mover is used to drive the pipette of the pipetting assembly to extend into the test tube at the cap-removing station for liquid aspiration or injection.

8. The automatic pipetting device according to any one of claims 1-6, characterized in that: It further includes a lid-opening mechanism. The lid-opening mechanism is used to open the lid of the culture dish. The lid-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. The spatial movement includes movement in the X-axis, Y-axis, and Z-axis.

9. The automatic pipetting device according to claim 7, characterized in that: It further includes two parallel and equi-height support belts for supporting the culture dish. An inclination mechanism is provided between the two support belts. The inclination mechanism includes a pusher, a push rod, and a baffle fixed at the output end of the pusher. 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 less than the diameter of the culture dish.

10. The automatic pipetting device according to claim 9, wherein: The push rod is an elastic push rod. The elastic push rod includes a push rod body and an elastic member. The push rod body is slidably connected to the output end of the pusher along the Z-axis. The elastic member is provided between the push rod body and the output end of the pusher.

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