Intelligent biological control sample culture method and device

Abstract

The invention provides an intelligent biological control sample culture method and device, and solves the problem that systematic experimental errors are introduced in the processes of cytoskeleton, cell polarity, signal transduction and the like when a culture dish rotates along with a bracket body. The cabinet comprises a cabinet body, a drawer mounting box is arranged at the bottom of the cabinet body, and a plurality of drawers which can be pulled out forwards and are arranged at intervals are arranged in the drawer mounting box; a horizontally-arranged fourth partition plate is fixedly arranged in the drawer, a plurality of clamping bases arranged at intervals are fixedly arranged at the top of the fourth partition plate, detachable culture dishes are placed on the clamping bases, a temperature adjusting module is arranged on the fourth partition plate, the temperature adjusting module can heat and refrigerate to adjust the temperature of the culture dishes, and a microelectrode array is fixedly arranged at the groove bottom of each culture dish; an equipment grabbing translation mechanism is arranged in the cabinet body, detection equipment capable of being grabbed by the equipment grabbing translation mechanism is placed in the cabinet body, and the detection equipment comprises a camera, a fluorescence microscopic imaging head, an impedance detection head and a micro spectrometer.

Description

Technical Field

[0001] This invention relates to the field of biological sample culture technology, and in particular to an intelligent method and apparatus for culturing biological control samples. Background Technology

[0002] Traditional biological research, limited by experimental methods, typically only studies the static state of organisms at a specific time point, reflecting the cumulative effect of all biological dynamic processes prior to that point. However, biological growth and development is a combination of a series of time- and space-specific processes; only by observing dynamic changes can we gain a more comprehensive understanding of the spatiotemporal specificity of biological growth and development regulation.

[0003] In the prior art, patent application number 202011304188.0 discloses a petri dish rack fixing support, an incubator, and a biological sample morphology imaging device. The petri dish rack fixing support includes a rotating platform and a support body, wherein the support body is fixedly connected to the rotating platform. The support body includes a first support and a second support. The first support is radially distributed, and the second support is fixed to the end of the first support extending from the rotating platform. The space adjacent to the second support is used to fix the petri dish rack. However, the device still has the following problems when in use: (1) When in use, the continuous centripetal acceleration generated by the rotation of the support body will introduce systematic experimental errors in the process of cytoskeleton, cell polarity, signal transduction, etc.; (2) The rotation of the support body and the petri dish may disturb the gas-liquid interface and affect gas exchange and chemical reaction gradient. Summary of the Invention

[0004] To address the problem in the prior art that systematic experimental errors are introduced into the cytoskeleton, cell polarity, and signal transduction processes when the culture dish rotates with the scaffold body, this invention proposes an intelligent biological control sample culture method and device.

[0005] The technical solution of the present invention is: an intelligent biological control sample culture device, including a cabinet, a cabinet door that can be opened and closed is hinged to the front panel of the cabinet, and a touch panel is provided on the front panel of the cabinet; The bottom of the cabinet is equipped with a drawer mounting box, which contains multiple drawers that can be pulled forward at intervals. The drawer is fixed with a horizontally arranged fourth partition. The top of the fourth partition is fixed with multiple spaced card holders. A removable culture dish is placed on the card holders. The fourth partition is equipped with a temperature regulation module located directly below the culture dish. The temperature regulation module can heat and cool to regulate the temperature of the culture dish. A microelectrode array is fixed at the bottom of the culture dish. The drawer is equipped with a liftable cover. The top of the cover is fixedly connected to the lower end of the vertically arranged first push-pull device. The upper end of the first push-pull device is fixedly connected to the top plate or third partition of the adjacent drawer mounting box. The cover is used to close the upper port of the petri dish. The bottom of the cover is equipped with a light source and a temperature and humidity sensor corresponding to the upper and lower parts of the petri dish. The cabinet is equipped with an equipment gripping and translation mechanism. Inside the cabinet are detection devices that can be gripped by the equipment gripping and translation mechanism. The detection devices include a camera, a fluorescence microscopic imaging head, an impedance detection head, and a miniature spectrometer. The first push-pull device, temperature regulation module, microelectrode array, equipment gripping and translation mechanism, detection equipment, light source, and temperature and humidity sensor are all connected to the touch panel.

[0006] Preferably, the rear side of the drawer is connected to a second push-pull device for pushing it out. The drawer is equipped with an air supply system and an exhaust gas recovery system. Both the air supply system and the exhaust gas recovery system are located below the fourth partition. The upper ends of both the air supply system and the exhaust gas recovery system pass through the fourth partition and communicate with the interior of the petri dish and are detachably connected.

[0007] Preferably, the bottom of the petri dish is connected to a first gas supply pipe, the first gas supply pipe is equipped with a first liquid one-way valve, the upper part of the side wall of the petri dish is connected to a first exhaust pipe, and the first exhaust pipe is equipped with a second liquid one-way valve. The gas supply system includes a gas source buffer box, which is equipped with a first gas pressure sensor. The gas source buffer box is connected to one end of the gas supply pipe, which is equipped with a first solenoid valve. The other end of the gas supply pipe is connected to the inlet of a gas distributor. The gas distributor has multiple gas outlets, each of which is connected to one end of a gas supply branch pipe. The gas supply branch pipe is equipped with an electronically controlled regulating valve and a first gas check valve. The other end of the gas supply branch pipe passes through a fourth partition and is detachably connected to the lower end of the first gas supply pipe. The gas source buffer box is connected to one end of a first gas injection pipe, which is equipped with a second solenoid valve. The other end of the first gas injection pipe extends out of the front panel of the drawer and is equipped with a detachable first plug. The exhaust gas recovery system includes an exhaust gas storage box, which is connected to one end of a second exhaust pipe. The second exhaust pipe is equipped with a second pressure sensor and a second gas check valve. The other end of the second exhaust pipe passes through a fourth partition and is detachably connected to the lower end of the first exhaust pipe. The exhaust gas storage box is connected to one end of an exhaust gas emission pipe, and the other end of the exhaust gas emission pipe extends out of the front panel of the drawer. The other end of the exhaust gas emission pipe is equipped with a detachable second plug.

[0008] Preferably, the cabinet is fixedly provided with a vertically arranged first partition, which divides the interior of the cabinet into an independent sample culture space and an equipment installation space. The sample culture space is located in front of the equipment installation space, and the bottom of the sample culture space is provided with a drawer installation box. The equipment installation space is equipped with an air pump and an air purifier. An air intake is embedded in the rear panel of the cabinet. A filter screen is installed at the air intake. The air pump, the air inlet, the air purifier and the air intake are connected in sequence by pipes. The air outlet of the air pump is connected to one end of the first air supply pipe. A second air supply pipe is provided on the first air supply pipe and connected to it. A second gas injection pipe is connected to the gas source buffer box. A third solenoid valve is installed on the second gas injection pipe. The other end of the second gas injection pipe passes through the back of the drawer and is connected to the front end of the gas delivery hose. The rear end of the gas delivery hose passes through the first partition and is connected to the second gas delivery pipe.

[0009] Preferably, the top of the sample culture space is fixedly provided with a first support in the shape of an inverted U-shaped plate, and the top of the first support has four open placement slots. The camera, fluorescence microscopy imaging head, impedance detection head and micro spectrometer are all fixedly equipped with a first limiting plate on their tops. The camera, fluorescence microscopy imaging head, impedance detection head and micro spectrometer can all pass through the placement slot. The first limiting plate overlaps the top of the sample culture space. A power supply box is fixedly installed on the top of the first limiting plate. The power supply box contains a power bank and a wireless switch. A charging port is embedded on the power supply box. The charging port, power bank and wireless switch are connected in series. Each first limit plate is equipped with a distance sensor at its bottom. The camera, fluorescence microscopy imaging head, impedance detection head, miniature spectrometer and each distance sensor are electrically connected to the mobile power supply above them. The distance sensors and wireless switches are connected to the touch panel signal. The top of the power supply box is fixed with a plug for the three-jaw chuck to grip.

[0010] Preferably, a track extending in the left and right direction is fixedly provided inside the cabinet, a sliding sleeve is slidably fitted on the track, and a walking drive device is fixedly provided on the sliding sleeve. The walking drive device cooperates with the track to drive the sliding sleeve to move left and right along the track. One end of the equipment gripping and translation mechanism is fixedly connected to the sliding sleeve, and the walking drive device is controlled and connected to the touch panel.

[0011] Preferably, the device gripping and translation mechanism includes a robotic arm and a three-jaw chuck disposed at the end of the robotic arm. A first electromagnet is embedded at the end of the robotic arm, and a through hole is provided at the center of the three-jaw chuck, the first through hole corresponding to the first electromagnet. The top of the drawer mounting box is provided with a detachable second bracket. The second bracket includes a first base plate. A horizontally arranged support plate is provided above the first base plate. A vertically arranged third push-pull device is connected between the first base plate and the support plate. A plurality of spaced first insertion holes are provided on the support plate. A first syringe is movably inserted into the first insertion hole. The first syringe includes a first suction tube that is movably inserted into a first insertion hole, a first piston head that is slidably disposed inside the first suction tube, and a first magnet block that is fixedly disposed on the top of the first piston head; Multiple reagent kits with top openings are placed on the first base plate, and the lower end of the first pipette is inserted into the reagent kit; The bottom of the support plate is equipped with liquid level sensors corresponding to the top and bottom of each reagent kit. The first electromagnet is connected to the touch panel for control, and the liquid level sensors are connected to the touch panel for communication.

[0012] Preferably, the top of the drawer mounting box is provided with a third bracket, the third bracket includes a second base plate, the top of the second base plate is fixedly provided with a second support frame with an inverted U-shaped plate structure, the top of the second support frame is provided with a plurality of spaced second insertion holes, and a second syringe is movably inserted into the second insertion holes, the second syringe having the same structure as the first syringe.

[0013] Preferably, the left and right sides of the first base plate are respectively provided with mirror-supported first limiting strips. The vertical cross section of the first limiting strip is an L-shaped structure. The first limiting strip is fixedly installed on the top of the drawer mounting box, and the first base plate is slidably inserted between the two first limiting strips. The second base plate has mirror-supported second limiting strips on its left and right sides. The second limiting strips have the same structure as the first limiting strips. The second limiting strips are fixedly installed on the top of the drawer mounting box, and the second base plate is slidably inserted between the two second limiting strips.

[0014] An intelligent biological control sample culture method includes the following steps: Step 1, using a touch panel, each culture dish is labeled and grouped according to the crystal form of its drawer, and divided into blank control group, solvent control group and experimental group respectively; Step 2: Open the cabinet door and use the touch panel to push out the drawers corresponding to the blank control group, volume control group, and experimental group in sequence. Then, add biological samples and culture medium to the culture dish corresponding to the blank control group, add biological samples and culture medium containing the test drug solvent to the culture dish corresponding to the solvent control group, and add biological samples and test drugs of different concentrations to the culture dishes corresponding to the experimental group. Then, use the touch panel to put the drawers corresponding to the blank control group, volume control group, and experimental group back into the drawer installation box in sequence. Step 3: Control the first push-pull device via the touch panel to move the cover plate, so that the cover plate is pressed against the upper port of the petri dish; Based on the gas conditions required for the culture of the biological sample, the prepared gas source is directly injected into the gas source buffer box through the first gas injection tube, or the air purified by the air purifier is injected into the gas source buffer box through the air pump. Inject culture medium, culture medium containing the test drug solvent, different concentrations of the test drug, and fluorescent agent into each kit. After completion, close the cabinet door. Step 4: Use the touch panel to control the electronic regulating valve to adjust the gas supply speed of the gas supply system to each petri dish. The incubation time, culture medium, culture medium containing the test drug solvent, and time interval for adding different concentrations of the test drug can be set via the touch panel. The interval time for the robotic arm to grasp the camera, fluorescence microscopy imaging head, impedance detection head, and miniature spectrometer can be set via the touch panel; Step 5: Start the entire system via the touch panel. After running for a certain period of time, first, the robotic arm picks up the camera and pushes out one of the drawers using the second push-pull device. The camera quickly scans and locates the drawer. Then, the robotic arm picks up the first syringe and uses the attraction force of the first electromagnet on the first magnet to absorb the fluorescent agent. The repulsion force formed by the first electromagnet on the first magnet injects the fluorescent agent into the culture dish. Then, the robotic arm sequentially picks up the fluorescence microscopy imaging head, impedance detection head, and micro spectrometer. With the help of the fluorescent agent, the biological samples are detected sequentially. During the detection, the impedance detection head needs to be in contact with the microelectrode array to obtain the culture information of each biological sample in the drawer. Step six, referring to step five, sequentially complete the acquisition of culture information for each biological sample in all drawers; Step 7: After running for a certain period of time, refer to Step 5, use the robotic arm to sequentially grab each second syringe, draw up the supernatant from each culture dish in each drawer, and reset and store each second syringe after drawing up the supernatant for laboratory analysis. Step 8: Repeat steps 5 through 7 until the set incubation time is reached, then shut down the entire system via the touch panel.

[0015] Advantages of the present invention: (1) Each drawer can provide an independent temperature and gas source for its internal petri dish and can remain stable when the drawer moves, so that each petri dish can form an independent experimental control group, can be arbitrarily grouped for culture, and can achieve full automation during the culture process.

[0016] (2) When the biological sample is pushed out, it can quickly reach a static state and form a stable detection condition, which greatly reduces the waiting time for mechanical positioning.

[0017] (3) During the culture process, the biological samples are completely still, eliminating non-biological mechanical interference and making the culture data closer to the real biological state. Attached Figure Description

[0018] 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.

[0019] Figure 1 This is a structural schematic diagram from the main view angle of Example 1; Figure 2 for Figure 1 A schematic diagram of the internal structure after the front panel has been removed. Figure 3 for Figure 2 A partial structural diagram of the culture drawer and its connecting structure from the right-side view without the right side panel. Figure 4 for Figure 3 A partial structural diagram of the culture drawer in the image; Figure 5 for Figure 4 Enlarged view of the structure at point A in the image; Figure 6 for Figure 2 A schematic diagram of the internal structure at the end of the robotic arm; Figure 7 for Figure 2 A schematic diagram of the detection function head and the first bracket in the middle; Figure 8 for Figure 2 Enlarged view of the structure at point B in the image; Figure 9 for Figure 2 Enlarged view of the structure at point C in the image; In the diagram, 1. Cabinet, 2. Track, 3. Sliding sleeve, 4. Walking drive device, 5. Robotic arm, 6. Three-jaw chuck, 601. First through hole, 7. First electromagnet, 8. First partition, 9. Second partition, 901. Third partition, 10. Drawer, 11. Fourth partition, 12. Card holder, 13. Petri dish, 1301. Microelectrode array, 14. First liquid check valve, 15. First gas check valve, 16. Electrically controlled regulating valve, 17. Gas distributor, 18. First solenoid valve, 19. Gas source buffer tank, 20. First pressure sensor. 21. First air injection pipe; 22. Second solenoid valve; 23. First plug; 24. First exhaust pipe; 25. Second liquid check valve; 26. Second exhaust pipe; 27. Second gas check valve; 28. Second pressure sensor; 29. ​​Exhaust gas storage tank; 30. Exhaust gas discharge pipe; 31. Second plug; 32. Electric heating element; 33. Semiconductor cooling element; 34. Cover plate; 35. Light source; 36. Temperature and humidity sensor; 37. First push-pull device; 38. Second air injection pipe; 39. Third solenoid valve; 40. Gas delivery hose; 41. Second push-pull device. 42. Pull device, 43. Air pump, 44. First air supply pipe, 45. Second air supply pipe, 46. Air purifier, 47. Filter screen, 48. First bracket, 49. Power supply box, 50. Plug, 51. Charging port, 52. First limiting plate, 53. Camera, 54. First distance sensor, 55. Fluorescence microscopic imaging head, 56. Second distance sensor, 57. Impedance detection head, 58. Third distance sensor, 59. Miniature spectrometer, 60. Fourth distance sensor, 61. First limiting strip, 62. First base plate, 63. Third push-pull device Device, 63, support plate, 64, first suction tube, 65, first stop, 66, first support column, 67, first piston head, 68, first connecting rod, 69, first magnet, 70, reagent kit, 71, liquid level sensor, 72, second limiting strip, 73, second base plate, 74, second support frame, 75, second suction tube, 76, second stop, 77, second support column, 78, second piston head, 79, second connecting rod, 80, second magnet, 81, cabinet door, 82, observation window, 83, touch panel, 84, indicator light. Detailed Implementation

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

[0021] Example 1: An intelligent biological control sample culture device, such as Figure 1 and Figure 2As shown, the system includes a cabinet 1. A cabinet door 81 that can be opened and closed is hinged to the front panel of the cabinet 1. A transparent observation window 82 is provided on the cabinet door 81. A touch panel 83 and an indicator light 84 are provided on the front panel of the cabinet 1. The indicator light 84 is connected to the touch panel 83 for control. The indicator light 84 includes a green indicator light and a red indicator light. The green indicator light is used to indicate that the system is operating normally, and the red indicator light is used to indicate that there is a problem with the system operation.

[0022] The cabinet 1 is fixedly equipped with a vertically arranged first partition 8, which divides the interior of the cabinet 1 into an independent sample culture space and an equipment installation space. The sample culture space is located in front of the equipment installation space.

[0023] A second partition 9 is connected between the bottom plate of cabinet 1 and the front side of the first partition 8. The second partition 9 is an inverted L-shaped plate structure. The bottom plate of cabinet 1, the second partition 9 and the first partition 8 enclose each other to form a drawer mounting box. Multiple third partitions 901 are fixedly installed inside the drawer mounting box. Multiple drawers 10 are slidably installed on each third partition 901. The drawers 10 are box-shaped structures with an opening at the top. The rear side of the drawer 10 is fixedly connected to the front end of the second push-pull device 41. The rear end of the second push-pull device 41 is fixedly installed on the third partition 901. The front side of the second partition 9 has an entrance and exit for the drawers 10 to enter and exit. The second push-pull device 41 is used to push the drawers 10 to move back and forth.

[0024] A horizontally arranged fourth partition 11 is fixed inside the drawer 10. A plurality of spaced card holders 12 are fixed on the top of the fourth partition 11. A detachable culture dish 13 is placed on the card holder 12. The card holder 12 has a ring structure. A temperature regulation module is provided on the fourth partition 11 inside the card holder 12. The temperature regulation module can heat and cool to regulate the temperature of the culture dish 13. The temperature regulation module includes an electric heating element 32 and a semiconductor cooling element 33. The electric heating element 32 and the semiconductor cooling element 33 are located directly below the culture dish 13. A microelectrode array 1301 is fixed on the bottom of the culture dish 13.

[0025] A liftable cover 34 is provided above the drawer 10. The top of the cover 34 is fixedly connected to the lower end of the vertically arranged first push-pull device 37. The upper end of the first push-pull device 37 is fixedly connected to the top plate of the adjacent second partition 9 or the third partition 901. The cover 34 is used to close the upper port of the culture dish 13. The bottom of the cover 34 is provided with a light source 35 and a temperature and humidity sensor 36 corresponding to the upper and lower parts of the culture dish 13. In this embodiment, the light source 35 is an LED light strip.

[0026] Drawer 10 contains an air supply system and an exhaust gas recovery system, both located below the fourth partition 11. The upper ends of both systems pass through the fourth partition 11 and are detachably connected to the interior of the petri dish 13. Specifically, as... Figure 3 , Figure 4 and Figure 5 As shown, the bottom of the petri dish 13 is connected to a first gas supply pipe, and a first liquid check valve 14 is provided on the first gas supply pipe. The upper part of the side wall of the petri dish 13 is connected to a first exhaust pipe 24, and a second liquid check valve 25 is provided on the first exhaust pipe 24.

[0027] The gas supply system includes a gas source buffer box 19, on which a first pressure sensor 20 is provided. The gas source buffer box 19 is connected to one end of a gas supply pipe, on which a first solenoid valve 18 is provided. The other end of the gas supply pipe is connected to the inlet of a gas distributor 17. In this embodiment, the gas distributor 17 is a hollow circular box structure with multiple gas outlets. Each gas outlet is connected to one end of a gas supply branch pipe. The gas supply branch pipe is equipped with an electrically controlled regulating valve 16 and a first gas check valve 15. The other end of the gas supply branch pipe passes through a fourth partition 11 and is detachably connected to the lower end of the first gas supply pipe. The gas source buffer box 19 is connected to one end of a first gas injection pipe 21, on which a second solenoid valve 22 is provided. The other end of the first gas injection pipe 21 extends out of the front panel of the drawer 10, and the other end of the first gas injection pipe 21 is equipped with a detachable first plug 23.

[0028] The exhaust gas recovery system includes an exhaust gas storage tank 29, which is connected to one end of a second exhaust pipe 26. The second exhaust pipe 26 is equipped with a second pressure sensor 28 and a second gas check valve 27. The other end of the second exhaust pipe 26 passes through a fourth partition 11 and is detachably connected to the lower end of a first exhaust pipe 24. The exhaust gas storage tank 29 is connected to one end of an exhaust gas emission pipe 30. The other end of the exhaust gas emission pipe 30 extends out of the front panel of the drawer 10, and the other end of the exhaust gas emission pipe 30 is equipped with a detachable second plug 31.

[0029] The equipment installation space is equipped with an air pump 42 and an air purifier 45. An air intake is embedded in the rear panel of the cabinet 1. A filter screen 46 is installed at the air intake. The air pump 42, the air inlet, the air purifier 45 and the air intake are connected in sequence by pipes. The air outlet of the air pump 42 is connected to one end of the first air supply pipe 43. A second air supply pipe 44 is provided on the first air supply pipe 43 and connected to it. A second air injection pipe 38 is connected to the air source buffer box 19. A third solenoid valve 39 is provided on the second air injection pipe 38. The other end of the second air injection pipe 38 passes through the rear side of the drawer 10 and is connected to the front end of the air supply hose 40. The rear end of the air supply hose 40 passes through the first partition 8 and is connected to the second air supply pipe 44.

[0030] A track 2 extending in a left-right direction is fixedly installed inside the cabinet 1. A sliding sleeve 3 is slidably fitted on the track 2, and a travel drive device 4 is fixedly installed on the sliding sleeve 3. The travel drive device 4 cooperates with the track 2 to drive the sliding sleeve 3 to move left and right along the track 2. In this embodiment, the travel drive device 4 includes a servo motor and a fixed wheel fitted on the output shaft of the servo motor. A through groove is opened on the sliding sleeve 3 for the fixed wheel to pass through, and the bottom of the fixed wheel passes through the through groove and contacts the track 2. A device gripping and translation mechanism is provided at the bottom of the sliding sleeve 3. The device gripping and translation mechanism includes a robotic arm 5, and a three-jaw chuck 6 is provided at the end of the robotic arm 5. Figure 6 As shown, a first electromagnet 7 is embedded at the end of the robotic arm 5, and a first through hole 601 is provided at the center of the three-jaw chuck 6, which corresponds to the first electromagnet 7.

[0031] The cabinet 1 houses inspection equipment that can be gripped by a three-jaw chuck 6. This equipment includes a camera 52, a fluorescence microscopy imaging head 54, an impedance detection head 56, and a miniature spectrometer 58. To reduce the possibility of wire entanglement, in this embodiment, as... Figure 7 As shown, the top of the second partition 9 is fixedly provided with a first bracket 47 in the shape of an inverted U-shaped plate, and the top of the first bracket 47 is provided with four vertically open placement slots (not shown in the figure).

[0032] The camera 52, fluorescence microscopy imaging head 54, impedance detection head 56 and miniature spectrometer 58 are all fixedly provided with a first limiting plate 51. The camera 52, fluorescence microscopy imaging head 54, impedance detection head 56 and miniature spectrometer 58 can all pass through the placement slot. The first limiting plate 51 overlaps the top of the second partition 9. A power supply box 48 is fixedly installed on the top of the first limiting plate 51. The power supply box 48 contains a power bank and a wireless switch. A charging port 50 is embedded on the power supply box 48. The charging port 50, the power bank, and the wireless switch are connected in series. Each first limiting plate 51 has a distance sensor (including a first distance sensor 53, a second distance sensor 55, a third distance sensor 57, and a fourth distance sensor 59) at its bottom. The camera 52, the fluorescence microscopic imaging head 54, the impedance detection head 56, the miniature spectrometer 58, and each distance sensor are all electrically connected to the power banks above them. The distance sensors and the wireless switch are all connected to the touch panel 83 via signals. A plug 49 for the three-jaw chuck 6 to grip is fixedly installed on the top of the power supply box 48.

[0033] In order to enable the mid-process addition of culture medium, test reagents, fluorescent agents, and drug solvents during cultivation, such as... Figure 8As shown, the top of the second partition 9 is provided with a detachable second bracket. The second bracket includes a first base plate 61. A horizontally arranged support plate 63 is provided above the first base plate 61. A vertically arranged third push-pull device 63 is connected between the first base plate 61 and the support plate 63. A plurality of spaced first insertion holes are provided on the support plate 63. A first syringe is movably inserted into the first insertion hole.

[0034] The first syringe includes a first suction tube 64 that is movably inserted into a first insertion hole. A first piston head 67 is slidably disposed inside the first suction tube 64. A first magnet block 69 is fixedly connected to the top of the first piston head 67 through a first connecting rod 68. The first magnet block 69 can drive the first piston head 67 to move up and down under the action of the first electromagnet 7.

[0035] The top of the first suction tube 64 is surrounded by a first baffle 64, which can be inserted into the first through hole 601. The top of the support plate 63 is provided with a first support column 66, and the first baffle 64 is movably mounted on the top of the first support column 66.

[0036] Multiple reagent kits 70 with top openings are placed on the first base plate 61, and the lower end of the first pipette 64 is inserted into the reagent kit 70. The bottom of the support plate 63 is provided with liquid level sensors 71 corresponding to the upper and lower parts of each reagent kit 70. The first electromagnet 7 is connected to the touch panel 83 for control, and the liquid level sensors 71 are connected to the touch panel 83 for communication.

[0037] In order to extract the supernatant from culture dish 13 during the culturing process for subsequent laboratory testing, such as... Figure 9 As shown, the top of the second partition 9 is provided with a third support, which includes a second base plate 73. A second support frame 74 with an inverted U-shaped structure is fixedly mounted on the top of the second base plate 73. The top of the second support frame 74 has multiple spaced second insertion holes, into which a second syringe is movably inserted. The second syringe has the same structure as the first syringe. In this embodiment, the second syringe includes a second suction tube 75 inserted into the second insertion hole. A second piston head 78 is slidably mounted inside the second suction tube 75. A second magnet block 80 is fixedly connected to the top of the second piston head 78 via a second connecting rod 79. The second magnet block 80 can drive the second piston head 78 to move up and down under the action of the first electromagnet 7.

[0038] The top of the second suction tube 75 is provided with a second baffle 76, which can be inserted into the first through hole 601. The top of the second support frame 74 is provided with a second support column 77, and the second baffle 76 is movably mounted on the top of the second support column 77.

[0039] To prevent the second and third supports from being pulled up simultaneously when the robotic arm 5 grasps the first and second syringes, in this embodiment, the left and right sides of the first base plate 61 are respectively provided with mirror-image supporting first limiting strips 60, the vertical cross section of the first limiting strips 60 is L-shaped, and the first base plate 61 is slidably inserted between the two first limiting strips 60; the left and right sides of the second base plate 73 are respectively provided with mirror-image supporting second limiting strips 72, the second limiting strips 72 have the same structure as the first limiting strips 60, and the second base plate 73 is slidably inserted between the two second limiting strips 72, and the first limiting strips 60 and the second limiting strips 72 are both fixedly installed on the top of the second partition plate 9.

[0040] The second push-pull device 41, electric heating element 32, semiconductor cooling element 33, light source 35, air supply system, waste gas recovery system, robotic arm 5 and three-jaw chuck 6, camera 52, fluorescence microscopic imaging head 54, impedance detection head 56 and miniature spectrometer 58 are all connected to the touch panel 83 for control, and the touch panel 83 is connected to the temperature and humidity sensor 36 for communication.

[0041] In this embodiment, the fluorescence microscopy imaging head 54 can employ Thermo Fisher Scientific's Cellinsight CX7 Pro "dual-camera imaging module" technology. This technology integrates two independent scientific-grade CMOS cameras (one for wide field and one for confocal light slicing), a solid-state light source (LED), and a filter wheel, supporting rapid switching from bright field to up to 7 channels of fluorescence. The impedance detection head 56 can employ Cyagen Biosciences' Lucid RTCA module technology (real-time cell analysis module). The Lucid RTCA module technology is a standalone, portable detection module that integrates a complete impedance analysis electronic system.

[0042] In this embodiment, the push-pull device uses an electric push rod. In other embodiments, a cylinder or hydraulic cylinder can be used instead.

[0043] An intelligent biological control sample culture method includes the following steps: Step 1: Using the touch panel 83, each culture dish 13 is grouped into a single crystal form label based on its corresponding drawer 10, and then divided into a blank control group, a solvent control group, and an experimental group.

[0044] Step 2: Open cabinet door 81, and use touch panel 83 to push out the drawers 10 corresponding to the blank control group, volume control group, and experimental group in sequence. Then, add biological samples and culture medium to the culture dish 13 corresponding to the blank control group, add biological samples and culture medium containing the test drug solvent to the culture dish 13 corresponding to the solvent control group, and add biological samples and test drugs of different concentrations to the culture dishes 13 corresponding to the experimental group. Then, use touch panel 83 to put the drawers 10 corresponding to the blank control group, volume control group, and experimental group back into the drawer installation box in sequence.

[0045] Step 3: Control the first push-pull device 37 via the touch panel 83 to move the cover plate 34 so that the cover plate 34 is pressed against the upper port of the culture dish 13; According to the gas conditions required for the culture of the biological sample, the prepared gas source is directly injected into the gas source buffer box 19 through the first gas injection tube 21, or the air purified by the air purifier 45 is injected into the gas source buffer box 19 through the air pump 42. Inject culture medium, culture medium containing the test drug solvent, test drug of different concentrations, and fluorescent agent into each reagent kit 70. After completion, close the cabinet door 81.

[0046] Step 4: Control the electronically controlled regulating valve 16 via the touch panel 83 to adjust the gas supply speed of the gas supply system to each culture dish 13; The incubation time, culture medium, culture medium containing the test drug solvent, and time interval for adding different concentrations of the test drug can be set via the touch panel 83. The touch panel 83 sets the interval for the robotic arm 5 to grasp the camera 52, fluorescence microscopy imaging head 54, impedance detection head 56 and miniature spectrometer 58 to detect the biological samples in each of the pushed-out drawers 10.

[0047] Step 5: The entire system (lighting, gas source, detection, etc.) is started via the touch panel 83. After running for a certain period of time, the robotic arm 5 first picks up the camera 52, and pushes out one of the drawers 10 via the second push-pull device 41. The camera 52 quickly scans and locates the drawer 10. Then, the robotic arm 5 picks up the first syringe and uses the attraction force of the first electromagnet 7 on the first magnet 69 to absorb the fluorescent agent. The repulsion force formed by the first electromagnet 7 on the first magnet 69 is used to inject the fluorescent agent into the culture dish 13. Then, the robotic arm 5 sequentially picks up the fluorescence microscopic imaging head 54, the impedance detection head 56, and the miniature spectrometer 58. With the help of the fluorescent agent, the biological samples are detected sequentially. During the detection, the impedance detection head 56 needs to contact the microelectrode array 1301 to obtain the culture information of each biological sample in the drawer 10. Among them, the camera 52 can quickly locate biological samples and obtain information such as growth area, color quantification, colony count, and preliminary judgment of cell confluence. In combination with the fluorescence microscopy imaging head 54 and the fluorescent agent, information such as fluorescence reporter gene analysis, cell viability and apoptosis detection of biological samples can be obtained. In combination with the impedance detection head 56 and the microelectrode array 1301, information such as cell growth, morphological changes and barrier function can be continuously quantified. In addition, the miniature spectrometer 58 can non-invasively detect the molecular vibration spectrum of biological samples and monitor intracellular metabolic status (such as lipid accumulation and protein expression), drug distribution and cellular stress response.

[0048] Step six, referring to step five, sequentially complete the acquisition of culture information for each biological sample in all drawers 10.

[0049] Step 7: After running for a certain period of time, referring to Step 5, use the robotic arm 5 to sequentially grab each second syringe, draw up the supernatant from each culture dish 13 in each drawer 10, and reset and store each second syringe after drawing up the supernatant for laboratory analysis.

[0050] Step 8: Repeat steps 5 through 7 until the set incubation time is reached, then shut down the entire system via touch panel 83.

[0051] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims and not by the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

Claims

1. An intelligent biological control sample culture device, characterized in that: Includes a cabinet body, with hinged cabinet doors on the front panel that can be opened and closed, and a touch panel on the front panel of the cabinet body; The bottom of the cabinet is equipped with a drawer mounting box, which contains multiple drawers that can be pulled forward at intervals. The drawer is fixed with a horizontally arranged fourth partition. The top of the fourth partition is fixed with multiple spaced card holders. A removable culture dish is placed on the card holders. The fourth partition is equipped with a temperature regulation module located directly below the culture dish. The temperature regulation module can heat and cool to regulate the temperature of the culture dish. A microelectrode array is fixed at the bottom of the culture dish. The drawer is equipped with a liftable cover. The top of the cover is fixedly connected to the lower end of the vertically arranged first push-pull device. The upper end of the first push-pull device is fixedly connected to the top plate or third partition of the adjacent drawer mounting box. The cover is used to close the upper port of the petri dish. The bottom of the cover is equipped with a light source and a temperature and humidity sensor corresponding to the upper and lower parts of the petri dish. The cabinet is equipped with an equipment gripping and translation mechanism. Inside the cabinet are detection devices that can be gripped by the equipment gripping and translation mechanism. The detection devices include a camera, a fluorescence microscopic imaging head, an impedance detection head, and a miniature spectrometer. The first push-pull device, temperature regulation module, microelectrode array, equipment gripping and translation mechanism, detection equipment, light source, and temperature and humidity sensor are all connected to the touch panel.

2. The intelligent biological control sample culture device as described in claim 1, characterized in that: The drawer is connected to a second push-pull device at the rear to push it out. The drawer is equipped with an air supply system and an exhaust gas recovery system. Both the air supply system and the exhaust gas recovery system are located below the fourth partition. The upper ends of the air supply system and the exhaust gas recovery system pass through the fourth partition and are connected to the interior of the petri dish in a detachable manner.

3. The intelligent biological control sample culture device as described in claim 2, characterized in that: The bottom of the petri dish is connected to a first gas supply pipe, which is equipped with a first liquid check valve. The upper part of the side wall of the petri dish is connected to a first exhaust pipe, which is equipped with a second liquid check valve. The gas supply system includes a gas source buffer box, which is equipped with a first gas pressure sensor. The gas source buffer box is connected to one end of the gas supply pipe, which is equipped with a first solenoid valve. The other end of the gas supply pipe is connected to the inlet of a gas distributor. The gas distributor has multiple gas outlets, each of which is connected to one end of a gas supply branch pipe. The gas supply branch pipe is equipped with an electronically controlled regulating valve and a first gas check valve. The other end of the gas supply branch pipe passes through a fourth partition and is detachably connected to the lower end of the first gas supply pipe. The gas source buffer box is connected to one end of a first gas injection pipe, which is equipped with a second solenoid valve. The other end of the first gas injection pipe extends out of the front panel of the drawer and is equipped with a detachable first plug. The exhaust gas recovery system includes an exhaust gas storage box, which is connected to one end of a second exhaust pipe. The second exhaust pipe is equipped with a second pressure sensor and a second gas check valve. The other end of the second exhaust pipe passes through a fourth partition and is detachably connected to the lower end of the first exhaust pipe. The exhaust gas storage box is connected to one end of an exhaust gas emission pipe, and the other end of the exhaust gas emission pipe extends out of the front panel of the drawer. The other end of the exhaust gas emission pipe is equipped with a detachable second plug.

4. The intelligent biological control sample culture device as described in claim 3, characterized in that: The cabinet is fixedly equipped with a vertically arranged first partition, which divides the interior of the cabinet into an independent sample culture space and an equipment installation space. The sample culture space is located in front of the equipment installation space, and the bottom of the sample culture space is equipped with a drawer installation box. The equipment installation space is equipped with an air pump and an air purifier. An air intake is embedded in the rear panel of the cabinet. A filter screen is installed at the air intake. The air pump, the air inlet, the air purifier and the air intake are connected in sequence by pipes. The air outlet of the air pump is connected to one end of the first air supply pipe. A second air supply pipe is provided on the first air supply pipe and connected to it. A second gas injection pipe is connected to the gas source buffer box. A third solenoid valve is installed on the second gas injection pipe. The other end of the second gas injection pipe passes through the back of the drawer and is connected to the front end of the gas delivery hose. The rear end of the gas delivery hose passes through the first partition and is connected to the second gas delivery pipe.

5. The intelligent biological control sample culture device as described in claim 4, characterized in that: The top of the sample culture space is fixedly equipped with a first support with an inverted U-shaped plate structure, and the top of the first support has four open placement slots. The camera, fluorescence microscopy imaging head, impedance detection head and micro spectrometer are all fixedly equipped with a first limiting plate on their tops. The camera, fluorescence microscopy imaging head, impedance detection head and micro spectrometer can all pass through the placement slot. The first limiting plate overlaps the top of the sample culture space. A power supply box is fixedly installed on the top of the first limiting plate. The power supply box contains a power bank and a wireless switch. A charging port is embedded on the power supply box. The charging port, power bank and wireless switch are connected in series. Each first limit plate is equipped with a distance sensor at its bottom. The camera, fluorescence microscopy imaging head, impedance detection head, miniature spectrometer and each distance sensor are electrically connected to the mobile power supply above them. The distance sensors and wireless switches are connected to the touch panel signal. The top of the power supply box is fixed with a plug for the three-jaw chuck to grip.

6. The intelligent biological control sample culture device as described in claim 1, characterized in that: The cabinet is equipped with a track that extends in the left and right direction. A sliding sleeve is mounted on the track, and a travel drive device is fixed on the sliding sleeve. The travel drive device works with the track to drive the sliding sleeve to move left and right along the track. One end of the equipment's gripping and translation mechanism is fixedly connected to the sliding sleeve, and the travel drive device is connected to the touch panel for control.

7. The intelligent biological control sample culture device as described in claim 1 or 6, characterized in that: The equipment gripping and translation mechanism includes a robotic arm and a three-jaw chuck set at the end of the robotic arm. A first electromagnet is embedded at the end of the robotic arm, and a through hole is provided at the center of the three-jaw chuck, which corresponds to the first electromagnet. The top of the drawer mounting box is provided with a detachable second bracket. The second bracket includes a first base plate. A horizontally arranged support plate is provided above the first base plate. A vertically arranged third push-pull device is connected between the first base plate and the support plate. A plurality of spaced first insertion holes are provided on the support plate. A first syringe is movably inserted into the first insertion hole. The first syringe includes a first suction tube that is movably inserted into a first insertion hole, a first piston head that is slidably disposed inside the first suction tube, and a first magnet block that is fixedly disposed on the top of the first piston head; Multiple reagent kits with top openings are placed on the first base plate, and the lower end of the first pipette is inserted into the reagent kit; The bottom of the support plate is equipped with liquid level sensors corresponding to the top and bottom of each reagent kit. The first electromagnet is connected to the touch panel for control, and the liquid level sensors are connected to the touch panel for communication.

8. The intelligent biological control sample culture device as described in claim 7, characterized in that: The top of the drawer mounting box is provided with a third bracket, which includes a second base plate. A second support frame with an inverted U-shaped plate structure is fixed on the top of the second base plate. A number of spaced second insertion holes are opened on the top of the second support frame. A second syringe is movably inserted into the second insertion hole. The second syringe has the same structure as the first syringe.

9. The intelligent biological control sample culture device as described in claim 8, characterized in that: The first base plate has mirror-supported first limiting strips on its left and right sides. The vertical section of the first limiting strip is L-shaped. The first limiting strip is fixed to the top of the drawer mounting box. The first base plate is slidably inserted between the two first limiting strips. The second base plate has mirror-supported second limiting strips on its left and right sides. The second limiting strips have the same structure as the first limiting strips. The second limiting strips are fixedly installed on the top of the drawer mounting box, and the second base plate is slidably inserted between the two second limiting strips.

10. The intelligent biological control sample culture method according to claims 1-9, characterized in that, Includes the following steps: Step 1: Using the touch panel, label and group each culture dish according to the crystal form of its drawer, and divide them into blank control group, solvent control group and experimental group respectively; Step 2: Open the cabinet door and use the touch panel to push out the drawers corresponding to the blank control group, volume control group, and experimental group in sequence. Then, add biological samples and culture medium to the culture dish corresponding to the blank control group, add biological samples and culture medium containing the test drug solvent to the culture dish corresponding to the solvent control group, and add biological samples and test drugs of different concentrations to the culture dishes corresponding to the experimental group. Then, use the touch panel to put the drawers corresponding to the blank control group, volume control group, and experimental group back into the drawer installation box in sequence. Step 3: Control the first push-pull device via the touch panel to move the cover plate, so that the cover plate is pressed against the upper port of the petri dish; Based on the gas conditions required for the culture of the biological sample, the prepared gas source is directly injected into the gas source buffer box through the first gas injection tube, or the air purified by the air purifier is injected into the gas source buffer box through the air pump. Inject culture medium, culture medium containing the test drug solvent, different concentrations of the test drug, and fluorescent agent into each kit. After completion, close the cabinet door. Step 4: Use the touch panel to control the electronic regulating valve to adjust the gas supply speed of the gas supply system to each petri dish. The incubation time, culture medium, culture medium containing the test drug solvent, and time interval for adding different concentrations of the test drug can be set via the touch panel. The interval time for the robotic arm to grasp the camera, fluorescence microscopy imaging head, impedance detection head, and miniature spectrometer can be set via the touch panel; Step 5: Start the entire system via the touch panel. After running for a certain period of time, first, the robotic arm picks up the camera and pushes out one of the drawers using the second push-pull device. The camera quickly scans and locates the drawer. Then, the robotic arm picks up the first syringe and uses the attraction force of the first electromagnet on the first magnet to absorb the fluorescent agent. The repulsion force formed by the first electromagnet on the first magnet injects the fluorescent agent into the culture dish. Then, the robotic arm sequentially picks up the fluorescence microscopy imaging head, impedance detection head, and micro spectrometer. With the help of the fluorescent agent, the biological samples are detected sequentially. During the detection, the impedance detection head needs to be in contact with the microelectrode array to obtain the culture information of each biological sample in the drawer. Step six, referring to step five, sequentially complete the acquisition of culture information for each biological sample in all drawers; Step 7: After running for a certain period of time, refer to Step 5, use the robotic arm to sequentially grab each second syringe, draw up the supernatant from each culture dish in each drawer, and reset and store each second syringe after drawing up the supernatant for laboratory analysis. Step 8: Repeat steps 5 through 7 until the set incubation time is reached, then shut down the entire system via the touch panel.

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