Monitoring and lifting integrated device for high-throughput biological culture system

Abstract

The invention discloses a monitoring and lifting integrated device for a high-throughput biological culture system. The monitoring and lifting integrated device comprises a central cantilever, a rotating platform mechanism and a lifting mechanism, wherein the central cantilever is coaxially connected with the rotating platform mechanism in a rotating manner; the lifting mechanism is arranged at one end of the central cantilever and used for lifting the pore plate to move in the Z-axis direction; the monitoring mechanism is arranged at the other end of the central cantilever and is used for illuminating and observing the cell state of the pore plate. Compared with an existing cell or organoid culture and analysis mainstream scheme, the system has the advantages that the integration degree is higher, the observation and analysis speed is higher, strict environmental conditions can be kept in the culture and analysis process and the like, the brand-new requirements of a high-flux biological culture system under the industrial and automatic background can be met, and the application prospect is wide. Technical and theoretical possibilities are provided for successful cell or organoid culture and observation of an intelligent automatic production line.

Description

Technical Field

[0001] The invention relates to a monitoring and lifting integrated device for a high-throughput biological culture system, belonging to the technical field of automation equipment. Background Art

[0002] Automated equipment can accurately complete various fixed mechanical actions and free up manpower, and is therefore gradually being applied to all walks of life. The current mainstream solution for cell or organoid culture and analysis is: the biological culture system cultures cells or organoids in batch arrays. When the well plate needs to be observed and analyzed, the incubator needs to be opened, the well plate is taken out by a robotic arm, the incubator is closed, and the robotic arm places the well plate on a living cell analyzer for analysis. After the analysis is completed, the well plate is taken out, the incubator is opened, the robotic arm puts the well plate back in place, and another well plate is taken for observation and analysis. The operation is repeated until all well plates are observed and analyzed.

[0003] The above mainstream solutions can meet the high-content, low-throughput needs of laboratory researchers for cell culture. The existing live cell analyzers contain a variety of optical analysis devices, with complex optical paths and the camera lens cannot move over a large range, resulting in a limited number of single observations and analyses, which cannot meet the requirements of industrial high-throughput. This solution requires step-by-step cultivation and analysis, with low integration and high cost. The incubator needs to be opened and closed many times when analyzing the well plate, and the cultivation of cells or organoids requires extremely strict environmental control, which can easily cause contamination to the remaining well plates. Therefore, the existing technical solutions have defects and need to be improved.

[0004] Patent document No. 104862226A discloses a microorganism incubator, including a box and a control system arranged on the box, and also including multiple independent culture units, a video microscope and an XYZ mobile platform, wherein the culture unit is arranged at the upper inner part of the box; the video microscope is arranged on the XYZ mobile platform, and the XYZ mobile platform is arranged at the lower inner part of the box; the outer wall of the culture unit is made of transparent material. The device requires manual replacement of the well plate, which is inefficient and easy to cause environmental pollution during replacement. Summary of the invention

[0005] The technical purpose of the present invention is to propose a monitoring and integration device for high-throughput biological culture systems. The present invention analyzes the limitations of existing mainstream cell or organoid culture and analysis solutions under the background of industrial high-throughput requirements, and achieves the goal of maintaining strict environmental conditions and faster observation speed during the culture and analysis process by integrating the culture and analysis functions into a single device.

[0006] The technical solution adopted by the present invention is: a monitoring and liquid transfer integrated device for a high-throughput biological culture system, comprising a central cantilever, a lifting mechanism and a monitoring mechanism. The lifting mechanism is used to lift the well plate to move along the Z-axis direction; the monitoring mechanism is used to illuminate and observe the state of cells in the well plate.

[0007] The central cantilever for fixing the lifting mechanism and the monitoring mechanism includes a central axis platform for realizing rotation around the axis; the central cantilever A side is provided with a fork arm structure for fixing the lifting mechanism, and the axis platform B side is provided with a C-shaped structure for fixing the monitoring mechanism.

[0008] Furthermore, the monitoring-lifting integrated device comprises:

[0009] A central cantilever coaxially connected to the rotating platform mechanism;

[0010] A lifting mechanism provided at one end of the central cantilever for lifting the orifice plate to move along the Z-axis direction;

[0011] A monitoring mechanism is provided at the other end of the central cantilever for illuminating and observing the status of cells in the well plate.

[0012] In actual use, the monitoring and lifting integrated device and the culture device can be placed in a box, and a sliding door mechanism is provided above the box. A lifting mechanism is connected to the A side of the central cantilever; a monitoring mechanism is provided on the B side of the central cantilever. The lifting mechanism cooperates with an external robotic arm to realize automatic replacement of the well plate and pipetting operation. Through the monitoring mechanism, in-situ online monitoring of any arbitrary position can be automatically realized.

[0013] Preferably, the lifting mechanism comprises:

[0014] Z-axis lifting platform with orifice plate placement;

[0015] An axial drive mechanism and an axial transmission mechanism that drive the Z-axis lifting platform to move in the vertical direction.

[0016] Preferably, the monitoring mechanism comprises:

[0017] Microscopic monitoring components and lighting components;

[0018] A radial driving mechanism and a radial transmission mechanism are used to drive the microscopic monitoring component and the lighting component to move horizontally.

[0019] Furthermore, the radial transmission mechanism or the axial transmission mechanism is a belt transmission mechanism, and the microscopic monitoring assembly and the lighting assembly or the Z-axis lifting platform are respectively fixed to the belt transmission mechanism through corresponding sliders; and the driving mechanism is a servo motor.

[0020] The belt transmission mechanism can be a simple belt mechanism for realizing single-direction transmission, or a belt mechanism for realizing multiple-direction circuitous transmission. Preferably, in the radial transmission mechanism, the belt transmission mechanism is a synchronous belt transmission mechanism, which includes a plurality of transmission gears and a synchronous belt, and the synchronous belt is arranged circuitously, and there are at least two horizontal sections with the same transmission direction, and the microscopic monitoring assembly and the lighting assembly are respectively fixed to the above two horizontal sections through their corresponding synchronous sliders.

[0021] Furthermore, in the monitoring mechanism, the output end of the driving mechanism is connected to its corresponding synchronous belt transmission mechanism through a coupling and a linear screw slide; the synchronous belt transmission mechanism is further fixed to the microscopic monitoring component and the lighting component respectively through two synchronous sliders.

[0022] Preferably, the lifting mechanism or the monitoring mechanism further includes a guide member for guiding the moving direction of the slider or the synchronous slider. The guide member may be a bare slide or a linear guide rail. The slider or the synchronous slider is provided with a guide hole or a guide groove that cooperates with the bare slide or the linear guide rail. For example, in the lifting mechanism, the slider fixed to the Z-axis lifting platform is guided by the bare slide; in the monitoring mechanism, the synchronous sliders fixed to the microscopic monitoring assembly and the lighting assembly are respectively guided by the corresponding linear guide rails.

[0023] Furthermore, the monitoring and lifting integrated device includes a central cantilever, and a central axis platform is provided at the center of the central cantilever to realize the rotation of the central cantilever around the axis; in actual use, a rotating platform mechanism for placing the orifice plate can be installed on the central cantilever; one side of the central axis platform (such as the top end) is provided with a hole position and a groove structure for connecting the orifice plate tray in the rotating platform mechanism, and the other side of the central axis platform (such as the bottom end) is provided with a hole position and a groove structure for connecting the DD motor; the two holes are coaxial and interpenetrating for the shaft of the peripheral device to pass through. By providing the central axis platform, the connection between the monitoring and lifting integrated device of the present invention and the shaft of the peripheral device can be realized, and in particular, more efficient monitoring and lifting operations can be realized in cooperation with the rotating shaft.

[0024] Furthermore, one end of the central cantilever (for example, the side of the central axis platform B) is provided with a C-shaped structure for fixing the monitoring mechanism, and the other end (for example, the side of the central axis platform A) is provided with a fork arm structure for fixing the lifting mechanism, and a hole for connecting with the shaft is provided in the middle. The lifting mechanism is fastened to the fork arm structure on the side of the central cantilever A, which can realize functions such as replacing the orifice plate or adding nutrients to the orifice plate; the monitoring mechanism is fastened to the C-shaped structure on the side of the central axis platform B, which can realize rapid lighting and monitoring functions.

[0025] Furthermore, a lifting mechanism is provided on one side of the central cantilever, and the lifting mechanism includes a servo motor α fixed on the fork arm structure on the A side of the central cantilever, and a belt transmission mechanism is provided at the output end of the servo motor α. One side of the belt transmission mechanism is fastened (fixed) to the Z-axis slider that moves along the linear light rod slide to realize the linear displacement of the Z-axis slider along the Z-axis direction; the inner side of the Z-axis slider is fastened to the Z-axis lifting platform to ensure the synchronous movement of the Z-axis slider and the Z-axis lifting platform.

[0026] Furthermore, the monitoring mechanism includes a servo motor β, which is fixed to the F side of the C-shaped structure on the B side of the central cantilever; the servo motor β drives the linear screw slide to move along the X-axis direction through a coupling. An X-axis slider α is provided above the linear screw slide, which is used to transport the synchronous slider α and is fixedly connected to the D end of the synchronous slider α. The central area of ​​the synchronous slider α is fixedly connected to the synchronous belt drive mechanism J, and its E end is fixedly connected to the X-axis slider β and the microscopic monitoring assembly. The X-axis slider β moves along the linear guide α on the G side of the C-shaped structure. The synchronous belt drive mechanism is fixed to the F side of the C-shaped structure, and its K area is fixedly connected to the H end of the synchronous slider β. The I end of the synchronous slider β is fixedly connected to the lighting assembly above, and the bottom is fixedly connected to the X-axis slider γ, and the X-axis slider γ moves along the linear guide β above the C-shaped structure.

[0027] Under the control of the host computer, the monitoring-lifting integrated device automatically completes the plate changing operation and the in-situ online monitoring function of any culture well through the entrance and exit, and the culture device automatically completes the control of culture conditions and the writing and reading of well plate information.

[0028] The monitoring and lifting integrated device of the present invention can be fixed to a rotating shaft driven by a DD motor as a part of a high-throughput biological culture system, and can be installed as a whole in a closed culture box with an inlet and outlet, and the central cantilever can be driven to rotate by a DD motor.

[0029] In actual use, taking the pipetting operation as an example, the steps are as follows: turn on the power, control the DD motor to drive the central cantilever to rotate through the upper computer, so that the lifting mechanism reaches the bottom of the orifice plate that needs to be lifted and replaced. The servo motor α fixed on the C-shaped structure on the A side of the central cantilever drives the belt transmission mechanism to move, so that the Z-axis slider fastened to one side of the belt transmission mechanism moves along the linear light rod slide, and the Z-axis lifting platform fastened to the Z-axis slider lifts the orifice plate that needs to be lifted and replaced to a certain height. The upper computer controls the DD motor to drive the central cantilever to rotate, so that the lifted orifice plate rotates to the bottom of the inlet and outlet for plate replacement or liquid replacement, and the Z-axis lifting platform is further raised to lift the orifice plate out of the incubator. After the mechanical arm completes the plate replacement or liquid replacement operation, the Z-axis lifting platform drives the orifice plate to descend, and the above operation is performed in reverse to put the orifice plate back to its original position. Repeat the above operation to realize the lifting and liquid replacement functions of all orifice plates. Taking monitoring the survival status of cells in a 2×3-size plate as an example, the operation steps are as follows: the upper computer controls the DD motor to drive the central cantilever to rotate, so that the lighting component in the monitoring mechanism reaches the top of the row of culture holes in the desired observation plate that is closest to the monitoring mechanism, and the microscopic monitoring component in the monitoring mechanism reaches the bottom of the row of culture holes in the desired observation plate that is closest to the monitoring mechanism. The servo motor β drives the linear screw slide to move along the X-axis direction through the coupling, and the X-axis slider α drives the microscopic monitoring component to move along the linear guide rail α to the bottom of the desired observation culture hole through the synchronous slider α; at the same time, the synchronous belt transmission mechanism J area fastened to the central area of ​​the synchronous slider α moves the same distance as the microscopic monitoring component in the same direction, and the synchronous belt transmission mechanism K area rotates around the wheel to achieve two changes of direction relative to the synchronous belt transmission mechanism J area, so that the movement direction and movement distance of the synchronous belt transmission mechanism K area and the synchronous belt transmission mechanism J area are always consistent; the synchronous slider β fastened to the synchronous belt transmission mechanism K area drives the lighting component to move along the linear guide rail β to the top of the desired observation culture hole, so as to achieve the effect of synchronous operation of the lighting component and the microscopic monitoring component. When monitoring of a single culture well is completed, the monitoring mechanism repeats the above positioning operation in the X-axis direction according to the host computer signal, and is driven by the DD motor to rotate a certain angle relative to the well plate in the angular direction, so as to realize the monitoring function of the remaining culture wells. When monitoring of all six culture wells in a single well plate is completed, the above operation is repeated according to the host computer signal to realize the monitoring function of all well plates.

[0030] Compared with the existing structure, the beneficial effects of the present invention are: the present invention has the advantages of higher degree of integration than the existing mainstream solutions for cell or organoid culture and analysis, faster observation and analysis speed, and the ability to maintain strict environmental conditions during culture and analysis. It can meet the new requirements of high-throughput biological culture systems in the context of industrialization and automation, and provides technical and theoretical possibilities for the success of intelligent automated production lines for cell or organoid culture and observation. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] in

[0033] Figure 1 It is a structural diagram of the device of the present invention.

[0034] Figure 2 It is another structural diagram of the device of the present invention.

[0035] Figure 3 This is the structural diagram of the central cantilever.

[0036] Figure 4 This is another structural diagram of the central cantilever.

[0037] Figure 5 It is a structural diagram of the lifting mechanism.

[0038] Figure 6 It is a diagram of the structure of the monitoring organization.

[0039] Figure 7 It is the left view of the monitoring mechanism.

[0040] Figure 8 3D is a three-dimensional structural diagram of a high-throughput biological culture system in an embodiment, in which the box body is partially transparent.

[0041] Fig. 9 It is a schematic structural diagram of the three-dimensional structure of the high-throughput biological culture system in the embodiment, omitting the box part.

[0042] Fig.10 yes Figure 2 Top view of the .

[0043] Fig.11 It is a schematic diagram of the structure of the culture device.

[0044] Fig.12 It is a schematic diagram of the structure of the culture device after removing the upper bottom plate.

[0045] Fig.13 It is a top view of the rotating platform mechanism.

[0046] Fig.14 It is the front view of the rotating platform mechanism.

[0047] Fig.15 It is a schematic diagram of the C-shaped support mechanism structure.

[0048] Fig.16It is another structural schematic diagram of the C-shaped support mechanism.

[0049] Fig.17 It is a schematic diagram of the local structure of the bidirectional clamping mechanism.

[0050] Fig.18 It is a partial top view of the bidirectional clamping mechanism.

[0051] Fig.19 It is a schematic diagram of the structure of the bidirectional clamping mechanism from an upward angle.

[0052] Fig. 20 This is a schematic diagram of the structure after the box is partially disassembled.

[0053] In the figure:

[0054] 1. Central cantilever; 1-1. Fork arm structure; 1-2. Hole position of orifice plate tray; 1-3. Hole position of DD motor; 1-4. C-shaped structure; 2. Lifting mechanism; 2-1. Servo motor α; 2-2. Belt transmission mechanism; 2-3. Z-axis slider; 2-4. Z-axis lifting platform; 2-5. Linear light rod slide; 3. Monitoring mechanism; 3-1. Servo motor β; 3-2. Coupling; 3-3. Linear lead screw slide; 3-4. X-axis slider α; 3-5. Synchronous slider α; 3-6. X-axis slider β; 3-7. Linear guide α; 3 -8, microscopic monitoring assembly; 3-9, synchronous belt transmission mechanism; 3-10, linear guide β; 3-11, X-axis slider γ; 3-12, lighting assembly; 3-13, synchronous slider β; 4, rotating platform mechanism; 4-1, wireless scanner; 4-2, electronic tag; 4-3, upper center semi-axis; 4-4, DD motor; 4-5, tray; 4-6, lower center semi-axis; 5, C-shaped support mechanism; 5-1, humidifier; 5-2, lower base plate; 5-2-1, lower center semi-axis fixing hole; 5-2-2, line collection slot α; 5-3, heat sink; 5-3-1, oxygen vent; 5-3-2, carbon dioxide vent; 5-4 heating rod; 5-5, upper base plate; 5-5-1, upper center semi-axis fixing hole; 5-5-2, line collection slot β; 5-6, humidity sensor; 5-7, sensor fixing plate; 5-8, carbon dioxide sensor; 5-9, oxygen sensor; 6, box; 6-1, upper box; 6-2, lower box; 7, sliding door assembly; 7-1, baffle; 7-2, screw slide; 7-3, motor; 8, orifice plate; 9, entrance and exit ; 10. Bidirectional clamping mechanism; 10-1. Radial clamp; 10-1-1. Pulley α; 10-1-2. Pin α; 10-2. Pin β; 10-3. Guide wheel α; 10-4. Long rope; 10-5. Pin γ; 10-6. Guide wheel β; 10-7. Servo; 10-8. Short rope; 10-9. Volute spring; 10-10. Tangential swing arm; 10-11. Fan-shaped opening; 10-12. Tangential clamp; 10-12-1. Pulley β; 10-13. Tension spring; 10-14. Radial clamp guide. DETAILED DESCRIPTION

[0055] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0056] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0057] like Figures 1-2As shown, in this embodiment, a monitoring and lifting integrated device for a high-throughput biological culture system includes a central cantilever 1, a lifting mechanism 2 and a monitoring mechanism 3.

[0058] like Figures 3-4 As shown, in this embodiment, the middle of the central cantilever 1 is a central axis platform, and the two sides are respectively a fork arm structure 1-1 and a C-shaped structure 1-4. The top of the central central axis platform is used to connect the hole position 1-2 of the orifice plate tray, and the bottom of the central axis platform has a DD motor hole position 1-3. The fork arm structure 1-1 is provided on the A side of the central axis platform, and the C-shaped structure 1-4 is provided on the B side of the central axis platform. The fork arm structure 1-1 is provided with a hole position α1-5 for fixing the servo motor α2-1, a hole position β1-6 for fixing the belt transmission mechanism 2-2, and a hole position γ1-7 for fixing the linear light rod slide 2-5. The C-shaped structure 1-4 is provided with a mounting plate α1-8 for fixing the servo motor β3-1 and the linear lead screw slide 3-3, a hole position δ1-9 (F side of the C-shaped structure 1-4) for fixing the synchronous belt transmission mechanism 3-9, a mounting plate β1-10 for installing the linear guide rail β3-10, and a mounting plate γ1-11 for installing the linear guide rail α3-7. The components of the lifting mechanism 2 and the monitoring mechanism 3 are fixed on the central cantilever 1 through the above-mentioned holes and the mounting plate.

[0059] like Figure 5 As shown, in this embodiment, the lifting mechanism 2 includes a servo motor α2-1, whose output end is provided with a belt transmission mechanism 2-2, and a Z-axis slider 2-3 fastened to one side of the belt transmission mechanism 2-2 can move along a linear light rod slide 2-5, and the inner side of the Z-axis slider 2-3 is fastened to a Z-axis lifting platform 2-4, and the Z-axis lifting platform 2-4 is used to lift the orifice plate. The belt transmission mechanism 2-2 is composed of a plurality of transmission gears (including a driving wheel fixed to the output end of the servo motor α2-1, two transmission wheels arranged in the vertical direction, and an adjustment wheel for adjusting the tightness of the belt) and a belt, and the Z-axis slider 2-3 is fixed to the belt portion moving in the z-axis direction. The Z-axis lifting platform 2-4 is provided with a lifting structure that cooperates with the orifice plate.

[0060] like Figures 6-7As shown, in this embodiment, the monitoring mechanism 3 includes a servo motor β3-1, which drives the X-axis slider α3-4 above the linear screw slide 3-3 to move through the coupling 3-2. The X-axis slider α3-4 can move back and forth under the drive of the linear screw slide 3-3. The X-axis slider α3-4 is fastened to the synchronous slider α3-5, so that the synchronous slider α3-5 can move synchronously with the X-axis slider α3-4. One end (end D) of the synchronous slider α3-5 is fixed to the X-axis slider α3-4, the middle part is fixed to the synchronous belt transmission mechanism 3-9, and the other end (end E) is fixed to the X-axis slider β3-6 and the microscopic monitoring component 3-8. The X-axis slider β3-6 moves along the linear guide rail α3-7 to guide the synchronous slider α3-5. The synchronous belt transmission mechanism 3-9 is composed of a number of transmission gears (in the figure, there are two groups of horizontally arranged gear groups and one group of vertically arranged gear groups, and the vertically arranged gear groups are mainly used to adjust the horizontal direction and position of the belt) and a synchronous belt. The synchronous belt is arranged in a circuitous manner, and there are at least two horizontal sections with the same horizontal transmission direction. The synchronous slider α3-5 is fixed to the synchronous belt in the horizontal section (J section). The X-axis slider β3-6 moves along the linear guide α3-7. The other horizontal section (K section) of the synchronous belt transmission mechanism 3-9 is also fastened to one end (H end) of the synchronous slider β3-13. The synchronous slider β3-13 is fastened to the lighting assembly 3-12 and the X-axis slider γ3-11. The X-axis slider γ3-11 moves along the linear guide β3-10 to guide the synchronous slider β3-13.

[0061] In this embodiment, when in use, the pipetting operation is as follows: first, turn on the power supply, use the upper computer to control the DD motor to drive the central cantilever 1 to rotate, and position the lifting mechanism 2 to be directly below the orifice plate that needs to be lifted or replaced. The servo motor α2-1 is located on the C-shaped structure 1-4 on the side of the central cantilever 1A, and drives the Z-axis slider 2-3 to move along the linear light rod slide 2-5 through the belt transmission mechanism 2-2 to achieve the lifting of the orifice plate. Subsequently, the DD motor drives the central cantilever 1 to rotate again, and rotates the orifice plate to be directly below the inlet and outlet for plate replacement or liquid replacement, and the Z-axis lifting platform 2-4 is raised to complete the operation of lifting the orifice plate out of the incubator. After the robotic arm performs the plate replacement or liquid replacement, the orifice plate descends and performs the above steps in reverse and puts it back in place. Repeating this process can achieve the lifting and liquid replacement of all orifice plates. The monitoring operation is as follows: the DD motor is controlled by the host computer to drive the central cantilever 1, and the lighting component 3-12 of the monitoring mechanism 3 is positioned just above the culture hole closest to the monitoring mechanism 3, and the microscopic monitoring component 3-8 is positioned just below. The servo motor β3-1 drives the linear screw slide 3-3 to move along the X-axis direction through the coupling 3-2, and the X-axis slider α3-4 drives the microscopic monitoring component 3-8 to move along the linear guide α3-7 to just below the desired observation culture hole. The synchronous belt transmission mechanism 3-9J area moves synchronously with the microscopic monitoring component 3-8, and the synchronous belt transmission mechanism 3-9K area realizes two changes of direction relative to the J area to ensure that the movement direction and distance of the two are consistent. The synchronous slider β3-13 drives the lighting component 3-12 to move along the linear guide β3-10 to just above the desired observation culture hole, completing the synchronous operation of the lighting and monitoring components. After monitoring a single culture hole, the monitoring mechanism 3 repeats the positioning in the X-axis direction according to the host computer signal, and rotates a certain angle in the angular direction to monitor the remaining culture holes. When all the culture wells in a single well plate have been monitored, repeat the above operation to complete the monitoring of all the well plates.

[0062] Figures 8 to 20 This is a structural diagram of a high-throughput biological culture system suitable for the above-mentioned monitoring and integration device of the present invention.

[0063] like Figures 8 to 10 , Fig.19 As shown, in this embodiment, a high-throughput biological culture system includes a box body 6, a sliding door assembly 7 arranged on the top of the box body, and a monitoring and lifting integrated device, a culture device, etc. arranged in the box body 6. An entrance and exit 9 is provided on the top of the box body 6.

[0064] The monitoring and lifting integrated device is mainly composed of a central cantilever 1, a lifting mechanism 2, a monitoring mechanism 3, etc., and the culture device is mainly composed of a rotating platform mechanism 4, a C-shaped support mechanism 5, a bidirectional clamping mechanism 10, etc. Generally speaking, the C-shaped support mechanism 5 is fixed in the box 6 to provide installation space for other mechanisms. The central cantilever 1 is transferred to the C-shaped support mechanism 5 and can rotate in a set direction and speed under the drive of the corresponding driving mechanism. The lifting mechanism 2 and the monitoring mechanism 3 are installed at both ends of the central cantilever 1 and can rotate synchronously with the central cantilever 1. The rotating platform mechanism 4 is coaxially transferred with the central cantilever 1 in the C-shaped support mechanism 5, and similarly, can rotate in a set direction and speed under the drive of the corresponding driving mechanism. The rotating platform mechanism 4 and the central cantilever 1 are driven by their corresponding driving mechanisms and rotate independently at a set speed and direction. The rotating platform mechanism 4 provides a positioning and placement space for the well plate 8 for cell culture. The bidirectional clamping mechanism 10 is used to realize the positioning of the well plate 8 on the rotating platform mechanism 4.

[0065] For the detailed structure of the monitoring and lifting integrated device, please refer to the above content.

[0066] like Figures 11 to 16 As shown, in this embodiment, the culture device includes a rotating platform mechanism 4 and a C-shaped support mechanism 5. Fig.12 The rotating platform mechanism 4 includes an upper center semi-axis 4-3, and the middle part of the upper center semi-axis is fastened to the DD motor 4-4. The rotation of the tray 4-5 is driven by the DD motor 4-4. The tray 4-5 is evenly provided with a plurality of orifice plate placement openings 4-7 in the circumferential direction, and the shape of the orifice plate placement openings 4-7 corresponds to the shape of the orifice plate; the tray 4-5 is provided with electronic tags 4-2 corresponding to the corresponding orifice plates around it. A wireless scanner 4-1 for scanning and reading the information of the electronic tag 4-2 is provided above the tray 4-5. The upper center semi-axis 4-3 is fastened to the lower center semi-axis 4-6. For details, see Fig.14 and Fig.15The C-shaped support mechanism 5 includes an upper base plate 5-5, a lower base plate 5-2, and a heat sink 5-4 that fixes the upper base plate 5-5 and the lower base plate 5-2 to each other. Among them, the lower base plate 5-2 is provided with a lower center semi-axis fixing hole 5-2-1 and a line collection groove α5-2-2, and a humidifier 5-1 is provided on the periphery of the lower base plate 5-2. A heat sink 5-3 is provided behind the lower base plate 5-2. An oxygen vent 5-3-1 and a carbon dioxide vent 5-3-2 are provided in the center of the heat sink 5-3; a heating rod 5-4 is provided on the left side of the heat sink 5-3, and a sensor fixing plate 5-7 is provided on the right side. A humidity sensor 5-6, a carbon dioxide sensor 5-8, and an oxygen sensor 5-9 are provided on the right side of the sensor fixing plate. An upper base plate 5-5 is provided above the heat sink, and an upper center semi-axis fixing hole 5-5-1 and a line collection groove β5-5-2 are provided in the upper base plate. At the same time, the electronic tag has a temperature detection function. Through the cooperation of the temperature detection function of the electronic tag and the heating rod 5-4, the temperature in the box can be accurately controlled. The humidifier 5-1 and the humidity sensor 5-6 can be used to accurately control the humidity in the box. The carbon dioxide sensor 5-8 and the oxygen sensor 5-9 can detect and control carbon dioxide and oxygen in the box.

[0067] In the present invention, the trays 4-5 and the central cantilever 1 can be driven separately by independent DD motors.

[0068] like Figures 17-18As shown, in this embodiment, the bidirectional clamping mechanism 10 is arranged at a position corresponding to the orifice plate placement opening 4-7 on the tray 4-5. The bidirectional clamping mechanism 10 includes a radial clamping claw guide 10-14 arranged along the radial direction of the tray 4-5, and a radial clamping claw 10-1 arranged on the radial clamping claw guide 10-14 and capable of sliding along the radial clamping claw guide 10-14. The radial clamping claw 10-1 is in the shape of a long strip and arranged along a vertical radial direction, and is mainly used for positioning the orifice plate in the radial direction; a pulley α10-1-1 is provided inside the radial clamping claw 10-1, and a pin α10-1-2 is provided above. The tray 4-5 is provided with a pin β10-2, a pin γ10-5 and a steering gear 10-7. The steering gear 10-7 is a driving mechanism, and the transmission member is a long rope 10-4. The pin β10-2 and the pin γ10-5 are provided with a guide wheel α10-3 and a guide wheel β10-6 respectively. The long rope 10-4 is fixed to the output end of the steering gear 10-7 at one end, and the guide wheel α10-3 and the guide wheel β10-6 are fastened to the pin α10-1-2 at the other end. The two ends of a radially arranged tension spring 10-13 are fastened to the tray 4-5 and the radial clamp 10-1 respectively, and are stretched toward the center axis direction of the tray 4-5. A tangential clamp 10-12 is also provided on the tray 4-5 for realizing circumferential positioning of the orifice plate; a pulley β10-12-1 is provided on the inner side of the tangential clamp 10-12; a fan-shaped opening 10-11 and a tangential swing arm 10-10 arranged along the circumference are also provided on the tray 4-5, one end of the tangential swing arm 10-10 is connected to the center of the spiral spring 10-9, and the other end passes through the fan-shaped opening 10-11 arranged on the tray and is connected to the tangential clamp 10-12, driving the tangential clamp 10-12 to rotate synchronously; one end of the tangential swing arm 10-10 connected to the spiral spring 10-9 is fastened to the output end of the steering gear 10-7 through a short rope 10-8, and the tangential clamp 10-12 rotates around the center of the other end of the tangential swing arm 10-10.

[0069] In the bidirectional clamping mechanism 10, the radial jaws 10-1, the radial jaw guide rails 10-14 and the tension springs 10-13 constitute a radial positioning assembly, and the tangential jaws 10-12 and the spiral springs 10-9 cooperate with the fan-shaped opening 10-11 to form a circumferential positioning assembly; the servo 10-7 provides driving force for the radial jaws 10-1 and the tangential jaws 10-12 at the same time, which are respectively used to realize the radial outward opening of the radial jaws 10-1 and the circumferential outward opening of the tangential jaws 10-12; the radial jaws 10-1 simultaneously use the tension springs 10-13 to realize the radial inward clamping of the orifice plate; the tangential jaws 10-12 realize the circumferential clamping of the orifice plate under the torsion of the spiral springs 10-9.

[0070] The orifice plate placement opening is provided with radial limiting edge and circumferential limiting edge structures, which cooperate with the radial clamping assembly and the circumferential clamping assembly to achieve radial and circumferential fixation of the orifice plate. When clamping is required, the driving mechanism releases the radial clamping claw, and under the tension of the radial elastic member, the inner side of the orifice plate abuts against the radial limiting edge, and the radial clamping claw achieves the clamping operation on the orifice plate. At the same time, the driving mechanism releases the tangential clamping claw, and the tangential elastic member retracts the tangential clamping claw circumferentially, and the inner side of the orifice plate abuts against the circumferential limiting edge, so that the tangential clamping claw clamps the orifice plate.

[0071] At the same time, an avoidance gap is left between the radial clamping jaw 10-1 and the tangential clamping jaw 10-12 to avoid the Z-axis lifting platform 2-4.

[0072] like Fig. 20 As shown, in this embodiment, the box 6 includes an upper box 6-1 and a lower box 6-2, and the monitoring, lifting integrated device and the culture device are placed in the lower box 6-2. The upper box 6-1 is fastened to the lower box 6-2 to form a closed space. The upper left side of the upper box 6-2 is provided with a sliding door mechanism 7 device for controlling the box plate changing or lifting port switch, and the top of the upper box is provided with a plate changing or liquid changing inlet and outlet 9.

[0073] The sliding door mechanism 7 is mainly composed of a baffle 7-1, a baffle screw slide 7-2 and a baffle motor 7-3. A door structure is provided on the upper box body 6-2. The baffle 7-1 corresponds to the above-mentioned door structure and is used to close and open the box body 6. The other end of the baffle 7-1 is fixed to the baffle screw slide 7-2 and can move synchronously. The baffle screw slide 7-2 is connected to the output end of the baffle motor 7-3.

[0074] In this embodiment, when used, the operation process is as follows: first, turn on the power, then activate the humidifier 5-1, the heating rod 5-4, and open the oxygen vent 5-3-1 and the carbon dioxide vent 5-3-2 to start adjusting the environment inside the incubator. At the same time, the humidity sensor 5-6, the electronic tag 4-2 with temperature sensing and recording functions, the oxygen sensor 5-3-1 and the carbon dioxide sensor 5-3-2 will feed back the real-time monitoring data to the host computer. After an appropriate time, the internal environment of the incubator will meet the culture conditions of cells or organoids. Subsequently, the host computer commands the DD motor 4-4 on the upper center semi-axis 4-3 to drive its tray 4-5 to rotate. The robotic arm places the well plate 8 on the rotating tray 4-5 in turn, and the bidirectional clamping mechanism 10 clamps the well plate 8. At this time, the wireless scanner 4-1 on the upper bottom plate 5-5 writes the well plate information (including the time of entry, culture time, number of liquid changes, cell or organoid survival status, etc.) into the electronic tag 4-2 of each well plate, and then starts the cell or organoid culture program. When changing the plate fluid or replacing the plate, the robot arm will accurately move the required plate without disturbing other plates. After the operation is completed, the plate is reset and the tray 4-5 continues to rotate. When the electronic tag 4-2 is aligned with the bottom of the wireless scanner 4-1, the wireless scanner 4-1 will complete the update of the information. After the update, the culture process of cells or organoids will continue.

[0075] Specifically, when it is necessary to change plates or transfer liquids, the upper computer controls the DD motor corresponding to the central cantilever to drive the central cantilever 1 to rotate, and positions the lifting mechanism 2 to be directly below the orifice plate that needs to be lifted or the liquid needs to be changed. The servo 10-7 drives the bidirectional clamping mechanism 10 to loosen the orifice plate. The servo motor α2-1 is located on the C-shaped structure 1-4 on the side of the central cantilever 1A, and drives the Z-axis slider 2-3 to move along the linear light rod slide 2-5 through the belt transmission mechanism 2-2 to lift the orifice plate. Subsequently, the DD motor drives the central cantilever 1 to rotate again, rotating the orifice plate to be directly below the inlet and outlet 9 for changing plates or changing liquids, and the Z-axis lifting platform 2-4 rises to complete the operation of lifting the orifice plate out of the incubator. After the robot arm performs the plate change or liquid change, the orifice plate descends and performs the above steps in reverse, and is put back in place. Repeating this process can achieve the lifting and liquid change of all orifice plates.

[0076] The monitoring operation is as follows: the DD motor is controlled by the upper computer to drive the central cantilever 1, and the lighting component 3-12 of the monitoring mechanism 3 is positioned directly above the culture hole (or target culture hole) closest to the monitoring mechanism 3, and the microscopic monitoring component 3-8 is positioned directly below. The servo motor β3-1 drives the linear screw slide 3-3 to move along the X-axis direction through the coupling 3-2, and the X-axis slider α3-4 drives the microscopic monitoring component 3-8 to move along the linear guide α3-7 to the desired observation culture hole. The synchronous belt drive mechanism 3-9J area moves synchronously with the microscopic monitoring component 3-8, and the synchronous belt drive mechanism 3-9K area realizes two changes of direction relative to the J area to ensure that the movement direction and distance of the two are consistent. The synchronous slider β3-13 drives the lighting component 3-12 to move along the linear guide β3-10 to the desired observation culture hole, completing the synchronous operation of the lighting and monitoring components. After the single culture well is monitored in situ online, the monitoring mechanism 3 repeatedly locates in the X-axis direction according to the host computer signal and rotates a certain angle in the angular direction to monitor the remaining culture wells. When all the culture wells in a single well plate are monitored, the above operation is repeated to achieve monitoring of all well plates.

[0077] Unless otherwise stated, any technical solution disclosed in the present invention disclosed above, if it discloses a numerical range, then the disclosed numerical range is a preferred numerical range, and any technician in the field should understand that the preferred numerical range is only a numerical value with a more obvious technical effect or representative value among many implementable numerical values. Since there are too many numerical values ​​to be exhaustive, the present invention discloses some numerical values ​​to illustrate the technical solution of the present invention, and the numerical values ​​listed above should not constitute a limitation on the scope of protection of the present invention.

[0078] At the same time, if the above-mentioned invention discloses or involves components or structural parts that are "fixed", "fixed to", "fastened" or "fixedly connected" to each other, then, unless otherwise stated, the fixed connection can be understood as: a detachable fixed connection (for example, connected by bolts or screws), and can also be understood as: a non-detachable fixed connection (for example, riveting, welding). Of course, the mutual fixed connection can also be replaced by an integrated structure (for example, manufactured by one-piece molding using a casting process) (except where it is obviously impossible to use an one-piece molding process).

[0079] If the words "first", "second", etc. are used in this article to limit components, those skilled in the art should know that the use of "first" and "second" is only to distinguish the components for the convenience of description. Unless otherwise stated, the above words have no special meaning.

[0080] When "α", "β", "γ" and "δ" are used as suffixes to define component names in this article, it is only for the convenience of distinguishing the components for the purpose of description; unless otherwise stated, the above words have no special meaning and have no other limiting effect.

[0081] In addition, unless otherwise stated, the terms used to indicate positional relationships or shapes in any of the technical solutions disclosed in the present invention include states or shapes that are approximate, similar, or close to them.

[0082] Any component provided by the present invention can be assembled from multiple separate components, or can be a separate component manufactured by an integral forming process.

Claims

1. A monitoring and lifting integrated device for a high-throughput biological culture system, characterized in that: include: A central cantilever coaxially connected to the rotating platform mechanism; A lifting mechanism provided at one end of the central cantilever for lifting the orifice plate to move along the Z-axis direction; A monitoring mechanism is provided at the other end of the central cantilever for illuminating and observing the status of cells in the well plate.

2. The integrated monitoring and lifting device for a high-throughput biological culture system according to claim 1, characterized in that: The lifting mechanism comprises: Z-axis lifting platform with orifice plate placement; An axial drive mechanism and an axial transmission mechanism drive the Z-axis lifting platform to move in the vertical direction.

3. The integrated monitoring and lifting device for a high-throughput biological culture system according to claim 1, characterized in that: The monitoring agencies include: Microscopic monitoring components and lighting components are arranged correspondingly in the positions; A radial driving mechanism and a radial transmission mechanism are used to drive the microscopic monitoring component and the lighting component to move horizontally.

4. The integrated monitoring and lifting device for a high-throughput biological culture system according to claim 2 or 3, characterized in that: The radial transmission mechanism or the axial transmission mechanism is a belt transmission mechanism, and the microscopic monitoring component and the lighting component or the Z-axis lifting platform are respectively fixed to the belt transmission mechanism through corresponding sliders; the driving mechanism is a servo motor.

5. The integrated monitoring and lifting device for a high-throughput biological culture system according to claim 4, characterized in that: In the radial transmission mechanism, its belt transmission mechanism is a synchronous belt transmission mechanism, which includes a plurality of transmission gears and a synchronous belt. The synchronous belt is arranged in a circuitous manner and has at least two horizontal sections with the same transmission direction. The microscopic monitoring assembly and the lighting assembly are respectively fixed to the above two horizontal sections through their corresponding synchronous sliders.

6. The integrated monitoring and lifting device for a high-throughput biological culture system according to claim 4, characterized in that: The lifting mechanism or the monitoring mechanism also includes a guide member for guiding the moving direction of the synchronous slider.

7. The integrated monitoring and lifting device for a high-throughput biological culture system according to claim 1, characterized in that: One end of the central cantilever is provided with a C-shaped structure for fixing the monitoring mechanism, the other end is provided with a fork arm structure for fixing the lifting mechanism, and the middle part is provided with a hole for switching with the shaft member.

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