A high throughput bioreactor system

Abstract

This invention discloses a high-throughput biological culture system, comprising a housing with an inlet and outlet, characterized by further including a monitoring-support integrated device and a culture device disposed within the housing; the culture device includes a rotating platform mechanism disposed within the housing for placing culture plates; the monitoring-support integrated device includes: a central cantilever coaxially connected to the rotating platform mechanism; a support mechanism disposed at one end of the central cantilever for supporting the culture plates to move along the Z-axis; and a monitoring mechanism disposed at the other end of the central cantilever for illuminating and observing the cell state of the culture plates. This invention offers advantages over existing cell or organoid biological culture devices, including higher integration, faster observation and analysis speed, maintenance of strict environmental conditions during culture and analysis, lower disturbance to other culture plates when retrieving them, and lower cost, thus meeting the high-throughput and low-disturbance requirements of high-throughput biological culture systems in an industrial and automated context.

Description

Technical Field

[0001] This invention relates to a high-throughput biological culture system, belonging to the field of automation equipment technology. Background Technology

[0002] Automated equipment can precisely complete various fixed mechanical actions, freeing up manpower, and is therefore gradually being applied to various industries. The current mainstream scheme for cell or organoid culture and analysis is: using a biological incubator for batch array culture of cells or organoids in well plates (8) (see instruction manual). Figure 20 When it is necessary to observe and analyze the well plates, the incubator needs to be opened, the layer containing the well plate is removed, the robotic arm takes out the well plate, the layer containing the well plate is moved in, the incubator is closed, the robotic arm places the well plate on the live cell analyzer for analysis, after which the well plate is taken out, the incubator is opened, the robotic arm puts the well plate back in its original position, and then another well plate is taken for observation and analysis. The operation is repeated until all well plates have been observed and analyzed.

[0003] The aforementioned mainstream solutions can meet researchers' needs for high-content, low-throughput cell culture. However, existing live-cell analyzers contain multiple optical analysis devices, resulting in complex optical paths and limited lens movement, thus restricting the number of cells analyzed per session and failing to meet industrial-scale high-throughput requirements. Furthermore, this approach requires separate steps for culture and analysis, leading to low integration and high cost. Removing a single well plate disturbs other wells in the same layer; some biological observation analyzers even disturb well plates during operation, and the existing technology causes significant disturbance to other wells. Additionally, the static layout of the well plate array in existing biological incubators results in varying cell or organoid survival environments within different wells, greatly reducing experimental precision and accuracy. Moreover, analyzing well plates requires multiple opening and closing of the incubator, and since cell or organoid culture requires extremely stringent environmental control, this can easily contaminate other wells. Therefore, existing technologies have shortcomings and require improvement. Summary of the Invention

[0004] The technical objective of this invention is to propose a high-throughput biological culture system. This invention analyzes the limitations of existing mainstream cell or organoid culture and analysis schemes in the context of industrial high-throughput requirements. By integrating culture and analysis functions into a single device and optimizing the existing array fixed culture layout into a rotating and moving culture layout, this invention achieves the goal of maintaining a consistent culture environment for all well plates during the culture process, ensuring no disturbance to other well plates when removing them, maintaining strict environmental conditions during culture and observation, and achieving faster observation and analysis speed.

[0005] The technical solution adopted in this invention is:

[0006] A high-throughput biological culture system includes a box with an inlet and outlet, and a monitoring-lifting integrated device and a culture device disposed within the box; the culture device includes a rotating platform mechanism disposed within the box for placing culture well plates; the monitoring-lifting integrated device includes a central cantilever, a lifting mechanism and a monitoring mechanism.

[0007] Specifically, the monitoring-lifting integrated device includes:

[0008] The central cantilever is coaxially connected to the rotating platform mechanism;

[0009] A lifting mechanism is installed at one end of the central cantilever to lift the perforated plate to move along the Z-axis.

[0010] A monitoring mechanism is installed at the other end of the central cantilever for illumination and observation of the cell status in the well plate.

[0011] The monitoring, lifting, and culture devices are all housed within a box, with a sliding door mechanism located on top. A lifting mechanism is connected to side A of the central cantilever; a monitoring mechanism is located on side B of the central cantilever. The lifting mechanism, in conjunction with an external robotic arm, enables automatic plate replacement and pipetting operations. The monitoring mechanism and rotating platform mechanism allow for automatic in-situ online monitoring and recording of any orifice. Preferably, the box features a sliding door mechanism, which includes a baffle that engages with the inlet / outlet, and a baffle motor that drives the baffle to close and open the inlet. Furthermore, the output end of the baffle motor is fixed to a baffle screw slide, and the baffle is fixed to the baffle screw slide, moving synchronously with it to achieve closing and opening operations.

[0012] Furthermore, the enclosure includes an upper enclosure and a lower enclosure. In actual use, the lower enclosure is placed on a work platform, and the upper enclosure is fastened to the lower enclosure to form a sealed space. Alternatively, the monitoring, lifting, and culture devices are all placed inside the lower enclosure; plate changing or liquid transfer is achieved through the inlet / outlet. Furthermore, the upper enclosure is provided with the inlet / outlet; simultaneously, the sliding door mechanism is located on the upper enclosure.

[0013] Preferably, the culture device includes:

[0014] A C-shaped support mechanism is installed inside the box;

[0015] The rotating platform mechanism is located within the C-shaped support mechanism.

[0016] The rotating platform mechanism is used for cell or organoid culture.

[0017] Furthermore, the C-shaped support mechanism is equipped with a heating unit, a humidification unit, an oxygen vent, and a carbon dioxide vent; the box is also equipped with a temperature sensor, a humidity sensor, an oxygen sensor, and a carbon dioxide sensor.

[0018] The C-shaped support mechanism is equipped with a rotating platform mechanism at its center.

[0019] Preferably, the rotating platform mechanism includes:

[0020] Shafts fixed within the C-shaped support mechanism;

[0021] A tray is attached to this shaft.

[0022] The central cantilever is simultaneously mounted on this shaft.

[0023] The tray and the central cantilever can rotate independently around the aforementioned shafts under the drive of their respective drive mechanisms.

[0024] The tray is evenly provided with multiple perforated plate placement openings around its circumference, and the length and width of the perforated plate placement openings are both greater than the length and width of the largest perforated plate used.

[0025] Preferably, the rotating platform mechanism further includes a bidirectional clamping mechanism disposed on the tray, the bidirectional clamping mechanism including a radial clamping component for radial clamping of the orifice plate and a circumferential clamping component for circumferential clamping of the orifice plate.

[0026] As a further preferred embodiment, the radial clamping assembly and the circumferential clamping assembly are driven by the same drive mechanism. More specifically, the drive mechanism is a servo motor. The orifice plate placement opening is simultaneously provided with radial and circumferential limiting edge structures, which, in conjunction with the radial and circumferential clamping assemblies, achieve radial and circumferential fixation of the orifice plate.

[0027] The radial clamping assembly includes a radial gripper guide rail, radial grippers slidably mounted on the radial gripper guide rail, a drive mechanism for driving the radial grippers to release the orifice plate, and a radial elastic element for clamping the radial grippers. Driven by the drive mechanism, the radial grippers slide along the radial gripper guide rail, unfolding and releasing the orifice plate. When clamping is required, the drive mechanism releases the radial grippers, and under the tension of the radial elastic element, the inner side of the orifice plate abuts against the radial limiting edge, thus clamping the orifice plate.

[0028] Furthermore, a pulley is provided on the side of the radial gripper where it clamps. The radial gripper has a positioning protrusion (or a pin). A transmission component is provided between the drive mechanism and the radial gripper, and the positioning protrusion is used to fix the transmission component. For example, the transmission component can be a long rope and several cooperating guide wheels, with the long rope wrapped around the guide wheels and secured to the positioning protrusion and the drive mechanism (such as a servo motor) respectively. The radial elastic element is a spring, with both ends of the spring secured to the tray and the radial gripper respectively.

[0029] The tray has a fan-shaped opening; the circumferential clamping assembly includes a tangential jaw, a drive mechanism for driving the tangential jaw to release the orifice plate, a tangential rotating arm connected between the output end of the drive mechanism and the tangential jaw, and a tangential elastic element that causes the tangential jaw to clamp. The tangential rotating arm is rotatably disposed within the fan-shaped opening around a central hole, and the fan-shaped opening guides and limits the rotation direction of the tangential rotating arm. Simultaneously, the other end of the tangential rotating arm is connected to the tangential elastic element. The drive mechanism drives the tangential jaw to open circumferentially; the tangential elastic element retracts the tangential jaw circumferentially, and the inner side of the orifice plate abuts against the circumferential limiting edge, thus achieving clamping of the orifice plate by the tangential jaw.

[0030] Furthermore, the tangential elastic element can be a spiral spring. One end of the tangential rotating arm revolves around the center of the spiral spring, and the other end is fixed to the tangential gripper through a fan-shaped opening. Driven by the spiral spring or the drive mechanism, the tangential rotating arm can rotate along the fan-shaped opening. The transmission component between the drive mechanism and the tangential gripper can be a short rope, with both ends of the short rope fastened to the servo motor and the tangential rotating arm, respectively. The tangential gripper rotates around the center of the other end of the tangential rotating arm.

[0031] The C-shaped support mechanism is used to integrate various sensors and environmental control devices. Further, the C-shaped support mechanism includes a lower base plate, an upper base plate, and a heat dissipation plate that fixes the lower base plate and the upper base plate together. Even further, the rotating platform mechanism is installed between the upper base plate and the lower base plate in the C-shaped support mechanism.

[0032] Specifically, the lower base plate is used to fix the lower central half-shaft. The lower base plate has fixing holes for the lower central half-shaft and a line collection groove α. A humidifier is provided around the lower base plate. A heat dissipation plate is provided behind the lower base plate. An oxygen vent and a carbon dioxide vent are provided in the center of the heat dissipation plate. A heating rod is provided on one side of the heat dissipation plate and a sensor fixing plate is provided on the other side. A humidity sensor, a carbon dioxide sensor and an oxygen sensor are provided on the sensor fixing plate. An upper base plate is provided above the heat dissipation plate. The upper base plate has fixing holes for the upper central half-shaft and a line collection groove β.

[0033] Furthermore, the shaft component includes an upper central half-shaft and a lower central half-shaft. The upper central half-shaft and the lower central half-shaft are concentrically and fastened together. The lower central half-shaft and the upper central half-shaft fastened to it are respectively fixed between the lower base plate and the upper base plate of the C-shaped support mechanism in the culture device. The central cantilever is rotated on the lower central half-shaft, and the central cantilever rotates around the lower central half-shaft of the rotating platform mechanism in the culture device.

[0034] Furthermore, the top of the upper central half-shaft is provided with a hole for connecting to the upper base plate of the C-shaped support mechanism, and the middle of the upper central half-shaft is fastened to the DD motor that drives the tray to rotate. The upper central half-shaft and the lower central half-shaft are concentrically fastened, and the lower central half-shaft is provided with a hole for connecting to the lower base plate of the C-shaped support mechanism.

[0035] Preferably, the tray is provided with a ring array of multiple perforated plate mounting positions and electronic tags for recording perforated plate information (perforated plate encoding information and temperature, etc.), and the box is also equipped with a wireless scanner for reading and writing information in the electronic tags.

[0036] Through the above structural design, the rotating platform mechanism can achieve precise control of the pallet and effectively record and read the perforated plate information.

[0037] Preferably, the lifting mechanism includes:

[0038] Z-axis lifting platform with perforated plate mounting position;

[0039] An axial drive mechanism and an axial transmission mechanism that drive the Z-axis lifting platform to move vertically.

[0040] The monitoring agency includes:

[0041] Microscopic monitoring components and illumination components;

[0042] A radial drive mechanism and a radial transmission mechanism that drive the microscopic monitoring component and the illumination component to move synchronously in the horizontal direction (i.e., radially of the rotating platform mechanism).

[0043] Furthermore, 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 or synchronous sliders; the drive mechanism is a servo motor.

[0044] The belt drive mechanism can be a simple belt mechanism that achieves transmission in one direction, or a belt mechanism that can be arranged in a circuitous manner to achieve transmission in multiple directions. Preferably, in the radial transmission mechanism, the belt drive mechanism is a synchronous belt drive mechanism, which includes several transmission gears and a synchronous belt. The synchronous belt is arranged in a circuitous manner, with at least two horizontal segments having the same transmission direction. The microscopic monitoring component and the illumination component are respectively fixed to the two horizontal segments by their corresponding synchronous sliders.

[0045] Furthermore, as a preferred embodiment, in the monitoring mechanism, the output end of the drive mechanism is connected to its corresponding synchronous belt drive mechanism via a coupling to a linear lead screw slide; the synchronous belt drive mechanism is further fixed to the microscopic monitoring component and the illumination component respectively via two synchronous sliders.

[0046] Preferably, the lifting mechanism or the monitoring mechanism further includes a guide member for guiding the movement direction of the slider or synchronous slider. The guide member can be a smooth rod slide or a linear guide rail. For example, in the lifting mechanism, the slider fixed to the Z-axis lifting platform is guided by a smooth rod slide; in the monitoring mechanism, the synchronous sliders fixed to the microscopic monitoring component and the illumination component are respectively guided by corresponding linear guide rails.

[0047] Furthermore, the monitoring and lifting integrated device includes a central cantilever, with a central axis platform at its center to enable the central cantilever to rotate around the axis; one side (e.g., the top) of the central axis platform is provided with holes and grooves for connecting the perforated plate tray in the rotating platform mechanism, and the other side (e.g., the bottom) of the central axis platform is provided with holes and grooves for connecting the DD motor to drive the perforated plate to rotate; the two holes are coaxial and interconnected, allowing the shafts in the rotating platform mechanism to pass through.

[0048] Furthermore, the central cantilever is located below the tray, with a C-shaped structure for fixing the monitoring mechanism at one end (side B of the central axis platform) and a fork arm structure for fixing the lifting mechanism at the other end (side A of the central axis platform), and a hole in the middle for connecting with the shaft.

[0049] Furthermore, a lifting mechanism is provided on one side of the central cantilever. The lifting mechanism includes a servo motor α fixed to the fork arm structure on side A of the central cantilever. The output end of the servo motor α is provided with a belt drive mechanism. One side of the belt drive mechanism is fastened (fixed) to the Z-axis slider that moves along the linear guide slide, so as 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.

[0050] Furthermore, a monitoring mechanism is provided on the other side of the central cantilever. This monitoring mechanism includes a servo motor β fixed to the F side of the C-shaped structure on the B side of the central cantilever. The servo motor β drives a linear screw slide to move along the X-axis direction via a coupling. Above the linear screw slide is an X-axis slider α for transporting a synchronous slider α. The X-axis slider α is fixedly connected to the D end of the synchronous slider α. The central area of ​​the synchronous slider α is fixed to the J area of ​​the synchronous belt drive mechanism. The E end of the synchronous slider α is fixed to the X-axis slider β and the microscopic monitoring component. The X-axis slider β moves along a linear guide rail α fixed to the G side of the C-shaped structure. The synchronous belt drive mechanism is fixed to the F side of the C-shaped structure. The K area of ​​the synchronous belt drive mechanism is fixed to the H end of the synchronous slider β. The upper part of the I end of the synchronous slider β is fixed to the lighting component, and the lower part of the I end of the synchronous slider β is fixed to the X-axis slider γ. The X-axis slider γ moves along the linear guide rail β fixed above the C-shaped structure.

[0051] Preferably, 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 inlet and outlet. The culture device automatically completes the control of culture conditions and the writing and reading of well plate information.

[0052] In actual use, the operating steps are as follows: Upon powering on, the humidifier, heating rod, oxygen vent, and carbon dioxide vent begin operation. The humidity sensor, the electronic tag with temperature sensing and recording capabilities, the oxygen sensor, and the carbon dioxide sensor provide real-time feedback of various information to the host computer. After a period of time, the internal conditions of the incubator meet the requirements for cell or organoid culture. Further, the host computer controls the DD motor fixed to the upper central half-axis to drive the tray to rotate. Simultaneously, it controls the servo motor fixed to the rotating platform to drive the bidirectional clamping mechanism to open. The robotic arm places the well plates sequentially onto the tray. Subsequently, the servo motor rotates in the opposite direction, releasing the elastic potential energy of the tension spring and the spiral spring. The bidirectional clamping mechanism then secures the well plates. The servo motor is powered off, and the wireless scanner fixed to the upper base plate writes the corresponding well plate information (such as incubation time, culture duration, number of medium changes, survival status, etc.) into the corresponding electronic tag, initiating cell or organoid culture. When plate replacement or lifting is required, the host computer controls the DD motor to drive the central cantilever to rotate, positioning the lifting mechanism directly beneath the well plate requiring lifting or medium replacement. A servo motor α, fixed to the C-shaped structure on side A of the central cantilever, drives a belt-driven mechanism to move. This causes a Z-axis slider, fastened to one side of the belt-driven mechanism, to move along a linear guide slide. A Z-axis lifting platform, also fastened to the Z-axis slider, raises the orifice plate to a certain height. The host computer controls a DD motor to rotate the central cantilever, positioning the raised orifice plate directly below the plate changing or pipetting inlet / outlet. A servo motor then drives a bidirectional clamping mechanism to open, further raising the Z-axis lifting platform and lifting the orifice plate out of the incubator. After the robotic arm completes the plate changing or pipetting operation, the Z-axis lifting platform lowers the orifice plate, reversing the process to return it to its original position. Repeating this operation enables the lifting and liquid changing of all orifice plates. Taking the monitoring of cell viability in a 2×3 well plate as an example, the operation steps are as follows: The host computer controls the DD motor to drive the central cantilever to rotate, so that the illumination component in the monitoring mechanism is positioned directly above the row of culture wells closest to the monitoring mechanism in the desired observation plate, and the microscopic monitoring component in the monitoring mechanism is positioned directly below the row of culture wells closest to the monitoring mechanism in the desired observation plate. The servo motor β drives the linear screw slide to move along the X-axis direction via a coupling. The X-axis slider α, through a synchronous slider α, drives the microscopic monitoring component to move along the linear guide α to directly below the desired observation culture well. Simultaneously, the synchronous belt drive mechanism J, which is fastened to the central area of ​​the synchronous slider α, moves the same distance in the same direction as the microscopic monitoring component. The synchronous belt drive mechanism K rotates around a wheel to achieve two changes of direction relative to the synchronous belt drive mechanism J, ensuring that the movement direction and distance of the synchronous belt drive mechanism K and the synchronous belt drive mechanism J are always consistent. The synchronous slider β, fastened to the synchronous belt drive mechanism K, drives the illumination component to move along the linear guide β to directly above the desired observation culture well, thus achieving the effect of synchronous operation of the illumination component and the microscopic monitoring component.Once in-situ online monitoring of a single culture well is complete, the monitoring mechanism repeats the above positioning operation in the X-axis direction according to the host computer signal. In the angular direction, the DD motor drives it to rotate relative to the well plate by a certain angle, enabling monitoring of the remaining culture wells. Once all six culture wells in a single well plate have been monitored, the above operation is repeated according to the host computer signal, enabling monitoring of all wells in the plate.

[0053] Compared with existing structures, the beneficial effects of this invention are: This invention has a higher degree of integration, faster observation and analysis speed, maintains strict environmental conditions during culture and analysis, provides better consistency of the culture environment for all wells during culture, causes less disturbance to other wells when handling wells, does not disturb the observed wells during observation and analysis, maintains strict environmental conditions during culture and observation, and has lower costs. It can meet the high-throughput, low-disturbance requirements of high-throughput biological culture systems in the context of industrialization and automation, providing technical and theoretical possibilities for the successful development of intelligent automated production lines for cell or organoid culture and observation. To make the above-mentioned objectives, features, and advantages of this invention more apparent and understandable, the specific embodiments of this invention will be described in detail below with reference to the accompanying drawings. Attached Figure Description

[0054] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0055] Figure 1 This is a three-dimensional structural diagram of the high-throughput biological culture system in the embodiment, with the box portion shown transparently.

[0056] Figure 2 This is a schematic diagram of the three-dimensional structure of the high-throughput biological culture system in the embodiment, omitting the box portion.

[0057] Figure 3 yes Figure 2 Top view.

[0058] Figure 4 This is a schematic diagram of the integrated monitoring and support device.

[0059] Figure 5 This is a structural schematic diagram of the monitoring and lifting integrated device from another angle.

[0060] Figure 6 This is a schematic diagram of the central cantilever structure.

[0061] Figure 7This is a structural diagram of the central cantilever from another angle.

[0062] Figure 8 This is a schematic diagram of the lifting mechanism.

[0063] Figure 9 This is a schematic diagram of the monitoring mechanism.

[0064] Figure 10 This is the left view of the monitoring agency.

[0065] Figure 11 This is a schematic diagram of the culture device.

[0066] Figure 12 This is a schematic diagram of the culture device after the top plate has been removed.

[0067] Figure 13 This is a top view of the rotating platform mechanism.

[0068] Figure 14 This is a front view of the rotating platform mechanism.

[0069] Figure 15 This is a schematic diagram of a C-shaped support mechanism.

[0070] Figure 16 This is another schematic diagram of the C-shaped support mechanism.

[0071] Figure 17 This is a partial structural diagram of the bidirectional clamping mechanism.

[0072] Figure 18 This is a partial top view of the bidirectional clamping mechanism.

[0073] Figure 19 This is a structural schematic diagram of the bidirectional clamping mechanism viewed from below.

[0074] Figure 20 This is a schematic diagram of an existing biological culture device.

[0075] Figure 21 This is a structural diagram of the disassembled box section.

[0076] In the picture

[0077] 1. Central cantilever; 1-1. Fork arm structure; 1-2. Hole plate tray holes; 1-3. DD motor holes; 1-4. C-shaped structure; 2. Lifting mechanism; 2-1. Servo motor α; 2-2. Belt drive mechanism; 2-3. Z-axis slider; 2-4. Z-axis lifting platform; 2-5. Linear guide rail 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 rail α; 3 -8. Microscopic monitoring component; 3-9. Synchronous belt drive mechanism; 3-10. Linear guide rail β; 3-11. X-axis slider γ; 3-12. Illumination component; 3-13. Synchronous slider β; 4. Rotary platform mechanism; 4-1. Wireless scanner; 4-2. Electronic tag; 4-3. Upper central half-shaft; 4-4. DD motor; 4-5. Tray; 4-6. Lower central half-shaft; 5. C-shaped support mechanism; 5-1. Humidifier; 5-2. Lower base plate; 5-2-1. Lower central half-shaft fixing hole; 5-2-2. Line collection groove 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 half-shaft fixing hole; 5-5-2. Line collection groove β; 5-6. Humidity sensor; 5-7. Sensor fixing plate; 5-8. Carbon dioxide sensor; 5-9. Oxygen sensor; 6. Cabinet; 6-1. Upper cabinet; 6-2. Lower cabinet; 7. Sliding door assembly; 7-1. Baffle; 7-2. Screw slide; 7-3. Motor; 8. Perforated plate; 9. Entrance / exit ; 10. Bidirectional clamping mechanism; 10-1. Radial gripper; 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 motor; 10-8. Short rope; 10-9. Spiral spring; 10-10. Tangential rotating arm; 10-11. Fan-shaped opening; 10-12. Tangential gripper; 10-12-1. Pulley β; 10-13. Tension spring; 10-14. Radial gripper guide rail. Detailed Implementation

[0078] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0079] like Figures 1-3 , Figure 19 As shown in this embodiment, a high-throughput biological culture system includes a box 6, a sliding door assembly 7 disposed on the top of the box, and a monitoring and lifting integrated device, a culture device, etc. disposed inside the box 6. The top of the box 6 is provided with an entrance and exit 9.

[0080] The integrated monitoring and support device mainly consists of a central cantilever 1, a support mechanism 2, and a monitoring mechanism 3. The culture device mainly consists of a rotating platform mechanism 4, a C-shaped support mechanism 5, and a bidirectional clamping mechanism 10. Generally, the C-shaped support mechanism 5 is fixed inside the housing 6, providing installation space for other mechanisms. The central cantilever 1 is connected to the C-shaped support mechanism 5 and can rotate according to a set direction and speed under the drive of its corresponding drive mechanism. The support mechanism 2 and the monitoring mechanism 3 are installed at both ends of the central cantilever 1 and can rotate synchronously with it. The rotating platform mechanism 4 is coaxially connected to the central cantilever 1 within the C-shaped support mechanism 5, and similarly, can rotate according to a set direction and speed under the drive of its corresponding drive mechanism. The rotating platform mechanism 4 and the central cantilever 1 rotate independently according to their respective set speeds and directions under the drive of their corresponding drive mechanisms. The rotating platform mechanism 4 provides positioning space for the well plates 8 used for cell culture. The bidirectional clamping mechanism 10 is used to position the well plates 8 on the rotating platform mechanism 4.

[0081] The present invention will be further described below with reference to the accompanying drawings:

[0082] like Figures 4-10 As shown, in this embodiment, the integrated monitoring and lifting device includes a central cantilever 1, a lifting mechanism 2, and a monitoring mechanism 3.

[0083] See Figure 6 and Figure 7 The central cantilever 1 has a central axis platform in the middle, with a fork arm structure 1-1 and a C-shaped structure 1-4 on both sides. Specifically, the central axis platform has holes 1-2 and grooves for connecting the perforated plate tray above it, and holes 1-3 and grooves for mounting the DD motor below it. The fork arm structure 1-1 is located on side A of the central axis platform, and the C-shaped structure 1-4 is located on side B. The fork arm structure 1-1 has holes α1-5 for fixing the servo motor α2-1, holes β1-6 for fixing the belt drive mechanism 2-2, and holes γ1-7 for fixing the linear guide slide 2-5. The C-shaped structure 1-4 is equipped with a mounting plate α1-8 for fixing the servo motor β3-1 and the linear lead screw slide 3-3, a hole δ1-9 for fixing the synchronous belt drive mechanism 3-9 (on the F side of the C-shaped structure 1-4), a mounting plate β1-10 for mounting the linear guide rail β3-10, and a mounting plate γ1-11 for mounting the linear guide rail α3-7. The components in the lifting mechanism 2 and the monitoring mechanism 3 are fixed to the central cantilever 1 through the aforementioned holes and mounting plates.

[0084] See also Figure 8The lifting mechanism 2 includes a servo motor α2-1, whose output end is equipped with a belt drive mechanism 2-2. A Z-axis slider 2-3, fastened to one side of the belt drive mechanism 2-2, can move along a linear guide slide 2-5. The inner side of the Z-axis slider 2-3 is fastened to a Z-axis lifting platform 2-4, which is used to lift the perforated plate 8. The belt drive mechanism 2-2 consists of several transmission gears (…). Figure 8 The system comprises a drive wheel fixed to the output end of the servo motor α2-1, two vertically arranged transmission wheels, an adjusting wheel for adjusting belt tension, and a belt. The Z-axis slider 2-3 is fixed to the belt portion that moves in the Z-axis direction. The Z-axis lifting platform 2-4 is equipped with a lifting structure that mates with the perforated plate.

[0085] See also Figure 9 and Figure 10 The monitoring mechanism 3 includes a servo motor β3-1, which drives the X-axis slider α3-4 on the linear lead screw slide 3-3 to move via a coupling 3-2. The X-axis slider α3-4 can reciprocate under the drive of the linear lead screw slide 3-3. The X-axis slider α3-4 is fastened to a synchronous slider α3-5, allowing the synchronous slider α3-5 to 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 drive 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 synchronous belt drive mechanism 3-9 consists of several transmission gears (two sets of horizontally arranged gears and one set of vertically arranged gears are shown in the figure; the vertically arranged gears 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, with at least two horizontal sections having the same transmission direction. Synchronous slider α3-5 is fixed to the synchronous belt of its horizontal section (J part), and X-axis slider β3-6 moves along linear guide rail α3-7 to guide synchronous slider α3-5. The other horizontal section (K part) of synchronous belt drive mechanism 3-9 is simultaneously fastened to one end (H end) of synchronous slider β3-13, and the other end (I end) of synchronous slider β3-13 is fixed to X-axis slider γ3-11 and lighting assembly 3-12. X-axis slider γ3-11 moves along linear guide rail β3-10.

[0086] like Figures 11-16 As shown, in this embodiment, the cultivation device includes a rotating platform mechanism 4 and a C-shaped support mechanism 5. See details... Figure 12The rotating platform mechanism 4 includes an upper central half-shaft 4-3, the middle of which is fastened to a DD motor 4-4 and simultaneously connected to a tray 4-5. The DD motor 4-4 drives the rotation of the tray 4-5. The tray 4-5 has multiple perforated plate placement openings 4-7 evenly distributed around its circumference, the shape of which corresponds to the shape of the perforated plates. Electronic tags 4-2, corresponding to the respective perforated plates, are located around the perimeter of the tray 4-5. A wireless scanner 4-1 for scanning and reading information from the electronic tags 4-2 is located above the tray 4-5. The upper central half-shaft 4-3 is fastened to the lower central half-shaft 4-6.

[0087] See details Figure 14 and Figure 15 The C-shaped support mechanism 5 includes an upper base plate 5-5, a lower base plate 5-2, and a heat dissipation plate 5-4 that fixes one side of the upper base plate 5-5 and the lower base plate 5-2 to each other. The lower base plate 5-2 has a lower central half-shaft fixing hole 5-2-1 and a line collection groove α5-2-2 inside, and a humidifier 5-1 around its periphery. A heat dissipation plate 5-3 is located behind the lower base plate 5-2. An oxygen vent 5-3-1 and a carbon dioxide vent 5-3-2 are located at the center of the heat dissipation plate 5-3. A heating rod 5-4 is located on the left side of the heat dissipation plate 5-3, and a sensor fixing plate 5-7 is located on the right side. A humidity sensor 5-6, a carbon dioxide sensor 5-8, and an oxygen sensor 5-9 are located on the right side of the sensor fixing plate. An upper base plate 5-5 is located above the heat dissipation plate, and the upper base plate has an upper central half-shaft fixing hole 5-5-1 and a line collection groove β5-5-2 inside. Meanwhile, the electronic tag has a temperature detection function. Through the combination of the electronic tag's temperature detection function and the heating rod 5-4, precise control of the temperature inside the chamber can be achieved. The humidifier 5-1 and humidity sensor 5-6 work together to achieve precise control of the humidity inside the chamber. The carbon dioxide sensor 5-8 and oxygen sensor 5-9 can detect and control the carbon dioxide and oxygen levels inside the chamber.

[0088] In this invention, the trays 4-5 and the central cantilever 1 can be driven by independent DD motors.

[0089] like Figures 17-18As shown, in this embodiment, the bidirectional clamping mechanism 10 is positioned at the location corresponding to the perforated plate placement opening 4-7 on the tray 4-5. The bidirectional clamping mechanism 10 includes a radial gripper guide rail 10-14 arranged radially along the tray 4-5, and a radial gripper 10-1 arranged on the radial gripper guide rail 10-14 and capable of sliding along the radial gripper guide rail 10-14. The radial gripper 10-1 is elongated and arranged along the vertical radial direction, mainly used for radial positioning of the perforated plate. A pulley α10-1-1 is provided on the inner side of the radial gripper 10-1, and a pin α10-1-2 is provided on the top. The tray 4-5 is equipped with pins β10-2 and γ10-5 and a servo motor 10-7. The servo motor 10-7 is the drive mechanism, and the transmission component is a long rope 10-4. Pins β10-2 and γ10-5 are respectively equipped with guide wheels α10-3 and β10-6. One end of the long rope 10-4 is fixed to the output end of the servo motor 10-7, and the other end passes around the guide wheels α10-3 and β10-6 and is fastened to pin α10-1-2. A radially arranged tension spring 10-13 is fastened to the tray 4-5 and the radial gripper 10-1 at both ends, and is stretched towards the central axis of the tray 4-5. The tray 4-5 is also equipped with a tangential gripper 10-12 for circumferential positioning of the orifice plate; a pulley β10-12-1 is provided on the inner side of the tangential gripper 10-12; the tray 4-5 is also equipped with a circumferentially arranged fan-shaped opening 10-11 and a tangential rotating arm 10-10. One end of the tangential rotating 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 on the tray and is connected to the tangential gripper 10-12, driving the tangential gripper 10-12 to rotate synchronously; the end of the tangential rotating arm 10-10 connected to the spiral spring 10-9 is fastened to the output end of the servo motor 10-7 through a short rope 10-8, and the tangential gripper 10-12 rotates around the center of the other end of the tangential rotating arm 10-10.

[0090] In the bidirectional clamping mechanism 10, the radial jaw 10-1, the radial jaw guide rail 10-14, and the tension spring 10-13 form a radial positioning assembly, while the tangential jaw 10-12 and the spiral spring 10-9, together with the fan-shaped opening 10-11, form a circumferential positioning assembly. The servo motor 10-7 simultaneously provides driving force to both the radial jaw 10-1 and the tangential jaw 10-12, respectively, to open the radial jaw 10-1 radially outward and the tangential jaw 10-12 circumferentially outward. The radial jaw 10-1 also uses the tension spring 10-13 to clamp the orifice plate radially inward. Under the torsion of the spiral spring 10-9, the tangential jaw 10-12 clamps the orifice plate circumferentially.

[0091] The orifice plate placement opening is equipped with both radial and circumferential limiting edges, which, together with the radial and circumferential clamping components, achieve radial and circumferential fixation of the orifice plate. When clamping is required, the drive mechanism releases the radial jaws, and under the tension of the radial elastic element, the inner side of the orifice plate abuts against the radial limiting edge, thus clamping the orifice plate. Simultaneously, the drive mechanism releases the tangential jaws, and the tangential elastic element retracts the tangential jaws circumferentially, causing the inner side of the orifice plate to abut against the circumferential limiting edge, thereby clamping the orifice plate with the tangential jaws.

[0092] Meanwhile, a clearance is provided between the radial gripper 10-1 and the tangential gripper 10-12 to allow the Z-axis lifting platform 2-4 to pass.

[0093] like Figure 21 As shown, in this embodiment, the box 6 includes an upper box 6-1 and a lower box 6-2. The monitoring, lifting integrated device and the culture device are all placed in the lower box 6-2. The upper box 6-1 is fastened to the lower box 6-2 to form a sealed space. The upper left side of the upper box 6-2 is provided with a sliding door mechanism 7 for controlling the opening and closing of the box plate changing or lifting port. At the same time, the top of the upper box is provided with a plate changing or liquid changing inlet / outlet 9.

[0094] The sliding door mechanism 7 mainly consists 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 housing 6-2. The baffle 7-1 corresponds to the door structure and is used to close and open the housing 6. The other end of the baffle 7-1 is fixed to the baffle screw slide 7-2, allowing them to move synchronously. The baffle screw slide 7-2 is connected to the output end of the baffle motor 7-3.

[0095] In this embodiment, the operation process is as follows: First, the power is turned on, and then the humidifier 5-1, heating rod 5-4, and oxygen vent 5-3-1 and carbon dioxide vent 5-3-2 are activated to begin adjusting the environment inside the incubator. Simultaneously, 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 feed real-time monitoring data back to the host computer. After an appropriate period, the environment inside the incubator will meet the culture conditions for cells or organoids. Then, the host computer commands the DD motor 4-4 on the upper central half-shaft 4-3 to drive its tray 4-5 to rotate. The robotic arm sequentially places the well plates 8 onto the rotating tray 4-5, and the bidirectional clamping mechanism 10 clamps the well plates 8. At this time, the wireless scanner 4-1 on the upper base plate 5-5 writes the well plate information (including the time of entry into the incubator, culture duration, number of medium 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. During plate medium changes or plate replacements, the robotic arm precisely removes the required plate without disturbing other plates. After the operation, the plate is reset, and tray 4-5 continues to rotate. When electronic tag 4-2 is aligned with the underside of wireless scanner 4-1, wireless scanner 4-1 updates its information. After the update, the cell or organoid culture process continues.

[0096] Specifically, when plate replacement or liquid transfer is required, the host computer controls the DD motor corresponding to the central cantilever to drive the central cantilever 1 to rotate, positioning the lifting mechanism 2 directly below the orifice plate to be lifted or having its liquid transferred. The servo motor 10-7 drives the bidirectional clamping mechanism 10 to release the orifice plate. The servo motor α2-1, located on the C-shaped structure 1-4 on the side of the central cantilever 1A, drives the Z-axis slider 2-3 to move along the linear guide slide 2-5 via the belt drive mechanism 2-2, thus lifting the orifice plate. Subsequently, the DD motor again drives the central cantilever 1 to rotate, rotating the orifice plate directly below the plate replacement or liquid transfer inlet / outlet 9. The Z-axis lifting platform 2-4 rises, completing the lifting of the orifice plate out of the incubator. After the robotic arm performs the plate replacement or liquid transfer, the orifice plate descends and the above steps are reversed to return it to its original position. Repeating this process allows for the lifting and liquid transfer of all orifice plates.

[0097] The monitoring operation is as follows: The host computer controls the DD motor to drive the central cantilever 1, positioning the lighting component 3-12 of the monitoring mechanism 3 directly above the nearest culture well (or target culture well) to the monitoring mechanism 3. Simultaneously, the microscopic monitoring component 3-8 is positioned directly below it. The servo motor β3-1 drives the linear screw slide 3-3 along the X-axis via coupling 3-2. The X-axis slider α3-4 moves the microscopic monitoring component 3-8 along the linear guide α3-7 directly below the desired culture well. The synchronous belt drive mechanism 3-9J moves synchronously with the microscopic monitoring component 3-8, and the synchronous belt drive mechanism 3-9K performs two direction changes relative to the J area, ensuring that the movement direction and distance are consistent. The synchronous slider β3-13 moves the lighting component 3-12 along the linear guide β3-10 directly above the desired culture well, completing the synchronous operation of the lighting and monitoring components. After in-situ online monitoring of a single culture well, the monitoring mechanism 3 repositions itself along the X-axis based on signals from the host computer and rotates a certain angle in the angular direction to monitor the remaining culture wells. Once all culture wells in a single well plate have been monitored, the above operation is repeated to monitor all well plates.

[0098] Unless otherwise stated, if any of the technical solutions disclosed in this invention specify a numerical range, then the disclosed numerical range is a preferred numerical range. Anyone skilled in the art should understand that the preferred numerical range is merely one among many feasible numerical values ​​that has a more obvious or representative technical effect. Because there are many numerical values, it is impossible to list them all. Therefore, this invention discloses only some numerical values ​​to illustrate the technical solutions of this invention. Furthermore, the numerical values ​​listed above should not constitute a limitation on the scope of protection of this invention.

[0099] Furthermore, if the present invention discloses or relates to components or structural parts that are "fixed", "fixed to", "fastened", or "fixedly connected" to each other, then, unless otherwise stated, a fixed connection can be understood as: a detachable fixed connection (e.g., a connection using bolts or screws), or a non-detachable fixed connection (e.g., riveting, welding). Of course, mutual fixed connections can also be replaced by an integral structure (e.g., manufactured using a casting process) (except where it is obviously impossible to use an integral molding process).

[0100] If the terms "first" or "second" are used in this document to specify components, those skilled in the art should know that the use of "first" or "second" is merely for the purpose of distinguishing components in description, and unless otherwise stated, the above terms have no special meaning.

[0101] When “α”, “β”, “γ”, and “δ” are used as suffixes in the part names defined in this article, it is only for the purpose of distinguishing the parts in the description; unless otherwise stated, the above words have no special meaning and no other limiting function.

[0102] In addition, unless otherwise stated, the terms used in any of the technical solutions disclosed in this invention to indicate positional relationships or shapes include states or shapes that are similar to, close to, or approximate with those states or shapes.

[0103] Any component provided by this invention can be assembled from multiple individual components or can be a single component manufactured by a one-piece molding process.

[0104] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of the present invention or equivalent substitutions can be made to some technical features without departing from the spirit of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the technical solutions claimed in the present invention.

Claims

1. A high-throughput biological culture system, comprising a housing with an inlet and outlet, characterized in that, It also includes a monitoring-supporting integrated device and a culture device installed inside the box; the culture device includes a rotating platform mechanism installed inside the box for placing culture well plates; The monitoring-lifting integrated device includes: The central cantilever is coaxially connected to the rotating platform mechanism; A lifting mechanism is installed at one end of the central cantilever to lift the perforated plate to move along the Z-axis. A monitoring mechanism is installed at the other end of the central cantilever for illumination and observation of the cell status in the well plate; The culture apparatus includes: A C-shaped support mechanism is installed inside the box; The rotating platform mechanism is disposed within the C-shaped support mechanism; The rotating platform mechanism includes: Shafts fixed within the C-shaped support mechanism; A tray is attached to this shaft. The central cantilever is simultaneously mounted on this shaft. The tray and the central cantilever can each rotate independently around the aforementioned shafts under the drive of their respective drive mechanisms. The central cantilever is located below the tray, with a C-shaped structure for fixing the monitoring mechanism at one end and a fork-arm structure for fixing the lifting mechanism at the other end, and a hole in the middle for connecting with the shaft.

2. The high-throughput biological culture system according to claim 1, characterized in that, The C-shaped support structure is equipped with a heating unit, a humidification unit, an oxygen vent, and a carbon dioxide vent; the chamber is equipped with a temperature sensor, a humidity sensor, an oxygen sensor, and a carbon dioxide sensor.

3. The high-throughput biological culture system according to claim 1, characterized in that, The rotating platform mechanism also includes a bidirectional clamping mechanism disposed on the tray, which includes a radial clamping component for radial clamping of the orifice plate and a circumferential clamping component for circumferential clamping of the orifice plate.

4. The high-throughput biological culture system according to claim 1, characterized in that, The tray has a circular array of multiple perforated plate mounting positions and electronic tags for recording perforated plate information. The box also contains a wireless scanner for reading and writing information from the electronic tags.

5. The high-throughput biological culture system according to claim 1, characterized in that, The lifting mechanism includes: Z-axis lifting platform with perforated plate mounting position; An axial drive mechanism and an axial transmission mechanism that drive the Z-axis lifting platform to move vertically. The monitoring agency includes: The microscopic monitoring components and lighting components are positioned accordingly; A radial drive mechanism and a radial transmission mechanism that drive the microscopic monitoring components and the illumination components to move synchronously along the radial direction of the rotating platform mechanism.

6. The high-throughput biological culture system according to claim 5, characterized in that, The radial transmission mechanism or the axial transmission mechanism is a belt drive mechanism, and the microscopic monitoring component and the lighting component or the Z-axis lifting platform are respectively fixed to the belt drive mechanism through corresponding synchronous sliders; the drive mechanism is a servo motor.

7. The high-throughput biological culture system according to claim 1, characterized in that, Controlled by the host computer, the monitoring-lifting integrated device automatically completes the plate changing operation and monitoring of any culture well through the inlet and outlet. The culture device automatically controls the culture conditions and writes and reads the plate information. The housing is equipped with a sliding door mechanism, which includes a baffle that cooperates with the inlet and outlet, and a baffle motor that drives the baffle to close and open the inlet and outlet.

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