Organ-like culture pipetting module

Abstract

The utility model discloses an organoid culture pipetting module which comprises an operation platform, and a gun head reagent storage area and an organoid sample operation area are arranged on the operation platform. A spear head box placing area for placing spear head boxes and a cooling module for storing reagents are arranged in the spear head reagent storage area; a temporary storage hole position for placing a hole plate is arranged in the organ-like sample operation area; a pipetting three-axis mechanical arm and a carrying three-axis mechanical arm are arranged above the operation platform, a pipetting gun matched with a gun head is installed on the pipetting three-axis mechanical arm, and a carrying clamping jaw used for clamping a pore plate and opening or covering a pore plate cover is installed on the carrying three-axis mechanical arm. According to the organoid culture pipetting module, automatic treatment of organoids can be achieved, organoid culture failures caused by manual operation are reduced, and the organoid culture efficiency is improved.

Description

Technical Field

[0001] The utility model belongs to the technical field of organoid culture, and specifically relates to a pipetting module for organoid culture. Background Art

[0002] Tumor organoids refer to models established by culturing a patient's tumor tissue in vitro to be similar to the patient's tumor tissue type. Compared with other tumor models, they largely retain the histological and genetic information of the original tumor tissue, and are closer to the original tumor in terms of tissue structure, being a good in vitro "substitute" for the patient's tumor. In addition, the amount of sample tissue required for constructing tumor organoids is small, the model establishment time is short, it is easy to observe in vitro, and the genome is stable. Therefore, it has great potential in the fields of constructing disease models, clinical cancer research, and drug sensitivity testing.

[0003] However, currently, the culture and drug sensitivity detection of organoids mainly rely on manual operation, lacking automated equipment. For conventional organoid culture, the whole process is completed manually, including a series of processes such as seeding the hydrogel, changing the liquid, recovering the organoids, and organoid drug sensitivity. The operation is cumbersome and time-consuming. The time for a single operation ranges from 10 minutes to several hours, and it has relatively high requirements for the personnel quality and operation experience. In addition, when performing organoid drug sensitivity detection, errors will occur due to different personal operation methods during manual drug preparation and liquid aspiration. Especially when the dosage is small, the error of manual operation has a greater impact on the results. Moreover, due to differences in the experimental methods of different operators, the reference significance between the drug sensitivity results obtained by different operators is low. Summary of the Invention

[0004] In view of this, the purpose of the utility model is to provide a pipetting module for organoid culture, which can realize the automated processing of organoids, reduce the failure of organoid culture caused by manual operation, and improve the efficiency of organoid culture.

[0005] To achieve the above purpose, the utility model provides the following technical solutions:

[0006] A pipetting module for organoid culture includes an operation platform, on which there are a pipette tip reagent storage area and an organoid sample operation area; in the pipette tip reagent storage area, there are a pipette tip box placement area for placing a pipette tip box and a cooling module for storing reagents; in the organoid sample operation area, there is a temporary placement position for placing a well plate; above the operation platform, there are a pipetting three-axis robotic arm and a handling three-axis robotic arm. A pipetting gun cooperating with a pipette tip is installed on the pipetting three-axis robotic arm, and a handling gripper for clamping the well plate and opening or covering the well plate lid is installed on the handling three-axis robotic arm.

[0007] Further, a waste storage area is provided on or at one side of the operation platform.

[0008] Further, a liquid waste component for storing liquid waste and a solid waste component for storing solid waste are provided in the waste storage area.

[0009] Further, a safety transfer passage is provided on the operation platform, and the safety transfer passage is used to connect the waste storage area with the pipette tip reagent storage area and the organoid sample operation area.

[0010] Further, the waste storage area is arranged in the safety transfer passage or at the end of the safety transfer passage.

[0011] Further, the pipette tip reagent storage area and the organoid sample operation area are arranged side by side, the safety transfer passage is arranged between one side of the pipette tip reagent storage area and the organoid sample operation area, and the waste storage area is arranged in the safety transfer passage or at one end of the safety transfer passage.

[0012] Further, an inclination module for inclining the well plate is provided in the organoid sample operation area; and / or, a constant temperature oscillation module for incubating organoids is provided in the organoid sample operation area.

[0013] The beneficial effects of the present utility model are as follows:

[0014] For the organoid culture pipetting module of the present utility model, by providing an operation platform, and arranging a pipette tip reagent storage area and an organoid sample operation area in the operation platform, a pipette tip box placement area and a cooling module are arranged in the pipette tip reagent storage area to place the pipette tip box and store reagents, and a pipette can be used to wear a pipette tip from the pipette tip box at the end of the pipetting three-axis robotic arm to achieve the pipetting purpose; by arranging a temporary placement position in the organoid sample operation area for placing the well plate to be operated, a handling gripper arranged at the end of the handling three-axis robotic arm can open or cover the well plate lid, and can also grab the well plate to achieve the transfer of the well plate; in summary, the organoid culture pipetting module of the present utility model can realize the automatic processing of organoids, safely, efficiently and accurately complete the organoid processing and drug sensitivity screening work; reduce the failure of organoid culture caused by manual operation and improve the efficiency of organoid culture. Description of the Drawings

[0015] In order to make the objectives, technical solutions and beneficial effects of the present utility model clearer, the following drawings are provided for illustration of the present utility model:

[0016] Figure 1 It is a schematic structural diagram of an embodiment of an automated organoid culture workstation;

[0017] Figure 2 It is a schematic structural diagram of a clean hood;

[0018] Figure 3 Schematic diagram of the structure of the clean hood after the maintenance door is opened;

[0019] Figure 4 Explosion diagram of the clean hood;

[0020] Figure 5 Principle block diagram of the wire monitoring control system;

[0021] Figure 6 Schematic diagram of the structure of the control panel;

[0022] Figure 7 First-direction isometric view of the organoid culture and drug sensitivity detection system;

[0023] Figure 8 Second-direction isometric view of the organoid culture and drug sensitivity detection system;

[0024] Figure 9 Schematic diagram of the structure of the end gripper;

[0025] Figure 10 Schematic diagram of the structure of the organoid culture pipetting module according to the embodiment of the present utility model;

[0026] Figure 11 Layout diagram of the operation platform;

[0027] Figure 12 Schematic diagram of the structure of the handling three-axis robotic arm;

[0028] Figure 13 Schematic diagram of the structure of the Z-direction support arm;

[0029] Figure 14 Schematic diagram of the structure of the automatic incubator;

[0030] Figure 15 Schematic diagram of the structure of the image acquisition and analyzer;

[0031] Figure 16 Schematic diagram of the structure of the tilting module;

[0032] Figure 17 Schematic diagram of the structure of the microplate reader.

[0033] Explanation of reference numerals:

[0034] 100 - Clean hood; 110 - Clean room; 1101 - Frame; 1102 - Tempered glass; 1101 - Inlet; 1102 - Outlet; 1103 - Fan filter unit; 11031 - Fan; 11032 - Second filter; 1104 - First filter; 1105 - Protective cover; 1106 - Maintenance opening; 1107 - Maintenance door; 120 - Controller; 1201 - Cleanliness sensor; 1202 - Differential pressure sensor; 1203 - Alarm; 1204 - Control panel; 1205 - Display screen; 1206 - Switch button.

[0035] 200 - Organoid culture and drug sensitivity detection system; 210 - Base; 211 - Four-axis robotic arm; 212 - End gripper; 2121 - Chuck; 2122 - Gripper arm; 2123 - Slide rail; 213 - Pipetting support; 214 - Reagent bottle; 215 - Pipette pump;

[0036] 220 - Pipetting module; 221 - Operating platform; 222 - Tip reagent storage area; 2221 - Tip box placement area; 2222 - Cooling module; 223 - Organoid sample operation area; 2231 - Tilt module; 2231a - Power base; 2231b - Well plate tray; 2231c - Rotating shaft; 2231d - Rotation drive mechanism; 2232 - Constant temperature shaking module; 2233 - Temporary storage well; 224 - Pipetting three-axis robotic arm; 2241 - First Y-direction support arm; 2242 - Pipette; 225 - Handling three-axis robotic arm; 2251 - Second Y-direction support arm; 2252 - Second Y-direction track; 2253 - Second Y-direction slider; 2254 - Lead screw; 2255 - Guide rod; 2256 - Z-direction support arm; 2257 - Motor; 2258 - Handling gripper; 226 - Baffle; 2271 - X-direction track; 2272 - Walking track; 228 - Waste storage area; 2281 - Liquid waste component; 2282 - Second solid waste component; 229 - Safe transfer channel;

[0037] 230 - Well plate rack; 231 - Liquid storage plate rack; 240 - Tip box rack; 250 - Automatic incubator; 251 - Well plate inlet and outlet; 252 - First well plate support; 260 - Image acquisition and analyzer; 261 - Second well plate support; 270 - Centrifuge; 271 - Fifth well plate support; 280 - Microplate reader; 281 - Sixth well plate support; 290 - First solid waste component. Detailed implementation manners

[0038] The following further illustrates the present utility model in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present utility model and be able to implement it, but the specific embodiments cited do not limit the present utility model.

[0039] As Figure 1As shown in the figure, the automated organoid culture workstation of this embodiment includes a clean hood 100 and an organoid culture and drug sensitivity detection system 200 disposed within the clean hood.

[0040] As Figures 2 - 5 shown, the clean hood of this embodiment includes a clean room 110 and a clean component. An air inlet 111 and an air outlet 112 are provided on the side wall of the clean room 110. A fan filter unit 113 is installed in the air inlet 111, and a first filter 114 is installed in the air outlet 112. Specifically, the air inlet 111 and the air outlet 112 are oppositely disposed at both ends of the clean room 110. For example, the air inlet 111 and the air outlet 112 can be respectively disposed at the upper and lower ends of the clean room 110, or can be respectively disposed at the left and right ends of the clean room 110. In this embodiment, the air inlet 111 is disposed on the top surface of the clean room 110, and the air outlet 112 is disposed at the bottom of the two side walls of the clean room 110, that is, the air inlet 111 and the air outlet 112 of this embodiment can be respectively disposed at the upper and lower ends of the clean room 110. In order to make the incoming air flow distribution more uniform, the air inlet 111 is uniformly arranged on the top surface of the clean room 110. At this time, the air inlet 111 can be set to at least two, and the fan filter units 113 at this time are arranged in one-to-one correspondence with the air inlets 111. In this embodiment, 3 air inlets 111 are uniformly arranged on the top surface of the clean room 110, and fan filter units 113 are respectively installed in the 3 air inlets 111. Of course, in some other embodiments, the number of air inlets 111 can also be set to 4 or more, that is, the number of air inlets 111 and fan filter units 113 can be set according to the actual application scenario, which will not be elaborated here.

[0041] Preferably, in this embodiment, the fan filter unit 113 includes a fan 1131 and a second filter 1132. The second filter 1132 is disposed on the side of the fan 1131 facing the inside of the clean room 110. In this way, the air flow injected by the fan 1131 is filtered by the second filter 1132 and then enters the clean room 110 to ensure the cleanliness of the gas entering the clean room 110.

[0042] Preferably, in this embodiment, a protective cover 115 is provided outside the first filter 114, and ventilation holes are arranged in an array on the protective cover 115. The first filter 114 is protected by providing the protective cover 115.

[0043] Preferably, in this embodiment, an ultraviolet disinfection device (not shown in the figure) for performing ultraviolet sterilization and disinfection is provided in the clean room 110.

[0044] Specifically, in this embodiment, the first filter 114 is an H14 high-efficiency filter; the second filter 1132 is a HEPA high-efficiency filter. The fan filter unit 113 sucks external air into the clean room 110 through the fan. The clean air obtained by filtering the passing air by the second filter 1132 arranged at the rear end of the fan 1131 is input into the clean room 110. The internally contaminated air is filtered into clean air by the first filter 114 and discharged to the outside. In this way, a Class 100 clean environment can be created inside and the leakage of internally contaminated substances can be ensured.

[0045] In this embodiment, the clean room 110 includes a frame 1101 built by profiles. A toughened glass 1102 is installed on the frame 1101. Pressing blocks for pressing and fixing the toughened glass 1102 to the frame 1101 are provided around the toughened glass 1102, which can ensure the overall rigidity and airtight performance of the clean room 110, and at the same time, the inside of the clean room 110 can be observed through the toughened glass to observe the organoid culture and experimental process in real time. In the preferred implementation manner of this embodiment, a maintenance port 116 is provided on the side wall of the clean room 110, and a maintenance door 117 is installed on the maintenance port 116 to facilitate the maintenance and repair of the equipment in the clean room 110. Specifically, the maintenance port 116 and the maintenance door 117 can be set to multiple according to needs to facilitate the maintenance and repair of the equipment in different areas of the clean room 110.

[0046] The organoid culture clean hood of this embodiment further includes an on-line monitoring and control system. Specifically, as Figure 4 shown, the on-line monitoring and control system includes a controller 120 and a cleanliness sensor 121. The cleanliness sensor 121 is electrically connected to the controller 120. The cleanliness sensor 121 is arranged in the clean room 110 and is used to collect the air cleanliness data in the clean room in real time. The controller 120 controls the opening or closing of the fan filter unit 113 according to the cleanliness data collected by the cleanliness sensor 121. For example, when the cleanliness data collected by the cleanliness sensor 121 is lower than the set first threshold, the controller 120 controls the fan filter unit 113 to open; when the cleanliness data collected by the cleanliness sensor 121 is higher than the set second threshold, the controller 120 controls the fan filter unit 113 to close; in this way, the cleanliness in the clean room 110 can always be maintained between the set first threshold and the second threshold. Specifically, the first threshold is lower than the second threshold.

[0047] In a preferred embodiment of the present embodiment, the on-line monitoring and control system further includes a differential pressure sensor 122 for detecting the differential pressure inside and outside the clean room 110. The differential pressure sensor 122 is electrically connected to the controller 120, and the controller 120 adjusts the power of the fan filter unit 113 according to the differential pressure data inside and outside the clean room 110 collected by the differential pressure sensor 122. Specifically, under the normal operating condition of the fan filter unit 113, if the differential pressure data inside and outside the clean room 110 collected by the differential pressure sensor 122 is lower than the set first differential pressure threshold value, it indicates that there may be a leak in the clean room 110. At this time, a control instruction should be issued through the controller 120 to increase the power of the fan filter unit 113 and increase the air intake volume to keep the differential pressure inside and outside the clean room 110 within the set range; if the differential pressure data inside and outside the clean room 110 collected by the differential pressure sensor 122 is greater than the set second differential pressure threshold value, it indicates that the first filter 114 is blocked. At this time, a control instruction should be issued through the controller 120 to decrease the power of the fan filter unit 113 and reduce the air intake volume to keep the differential pressure inside and outside the clean room 110 within the set range; in this way, the differential pressure inside and outside the clean room 110 can always be maintained between the first differential pressure threshold value and the second differential pressure threshold value. Specifically, the first differential pressure threshold value is less than the second differential pressure threshold value.

[0048] In a preferred embodiment of the present embodiment, the on-line monitoring and control system further includes an alarm 123 for fault alarm. The alarm 123 is electrically connected to the controller 120. When the differential pressure data inside and outside the clean room 110 collected by the differential pressure sensor 122 is abnormal, such as when the differential pressure data is lower than the first differential pressure threshold value or higher than the second differential pressure threshold value, the controller 120 issues a control instruction to the alarm 123, and the alarm 123 then issues a fault alarm. In particular, under the normal operating condition of the fan filter unit 113, when the differential pressure data is greater than the set second differential pressure threshold value, relevant information reminding the user to update the filter cotton can also be displayed on the display screen 125.

[0049] In this embodiment, a control panel 124 is installed outside the side wall of the clean room 110. As Figure 6 shown, the control panel 124 of this embodiment is provided with a display screen 125. The controller 120 and the alarm 123 are arranged inside the control panel 124. The display screen 125 is electrically connected to the controller 120 and is used to display in real time the cleanliness data collected by the cleanliness sensor 121 and the differential pressure data collected by the differential pressure sensor 122. Of course, a switch button 126 can also be set on the control panel 124 to realize the manual control of the opening and closing of the ultraviolet disinfection device and the fan filter unit 113.

[0050] The organoid culture clean hood of this embodiment is provided with an air inlet and an air outlet on the side wall of the clean room, a fan filter unit is installed on the air inlet, and a first filter is installed on the air outlet. In this way, the fan filter unit can supply fresh air to the clean room, and the gas in the clean room is discharged through the air outlet and the first filter, keeping the clean room clean. In this way, a clean space can be provided for organoid culture and experiments, ensuring that the organoid culture and experimental processes are not contaminated.

[0051] As Figures 7 - 8 shown, in this embodiment, the organoid culture and drug sensitivity detection system 200 includes a base 210, and a four-axis robotic arm 211 and a centrifuge 270 are installed on the base 210. Specifically, the base 210 can be an integral structure or composed of multiple brackets spliced together. The base 210 of this embodiment is composed of multiple brackets spliced together. The four-axis robotic arm 211 is provided with an end gripper 212 for clamping the well plate and the tip box, and the centrifuge 270 is used for centrifuging the organoids. As Figure 9 shown, the end gripper 212 of this embodiment includes a chuck 2121 and two clamping arms 2122. The chuck 2121 is provided with a slide rail 2123, and the clamping arms 2122 are slidably matched with the slide rail 2123. A gripper driving mechanism for driving the two clamping arms 2122 to move towards each other or away from each other is arranged in the chuck 2121. Specifically, the gripper driving mechanism can be realized by various existing methods, such as a screw thread lead screw mechanism, etc., which will not be elaborated here. Specifically, when the gripper driving mechanism drives the two clamping arms 2122 to move towards each other, the well plate, the tip box or the liquid storage plate can be clamped; when the gripper driving mechanism drives the two clamping arms 2122 to move away from each other, the well plate, the tip box or the liquid storage plate is released and put down. In this embodiment, a feedback for grasping and dropping objects is also arranged in the end gripper 212, which can monitor whether the well plate cover is normally opened.

[0052] As Figures 7 - 8As shown, in this embodiment, a pipetting module 220, a well plate rack 230, a liquid storage plate rack 231, a gun tip box rack 240, an automatic incubator 250, an image acquisition analyzer 260 and an ELISA reader 280 are provided within the working space of the four-axis robot arm. Specifically, the well plate rack 230 is used to store well plates. The liquid storage plate rack 231 is used to store liquid storage plates. The gun tip box rack 240 is used to store gun tip boxes, and gun tips are stored in the gun tip boxes. The automatic incubator 250 is used for organoid culture. The image acquisition analyzer 260 is used to perform quality inspection on the organoid culture status. The ELISA reader 280 is used to perform drug sensitivity testing. In this embodiment, a first solid waste assembly 290 for storing discarded well plates is also provided within the working space of the four-axis robot arm 211. In this embodiment, the base 210 includes a pipetting bracket 213, the pipetting module 220 is installed on the pipetting bracket 213, and the tip box rack 240 and the image acquisition analyzer 260 are both arranged below the pipetting bracket 213, which can make the spatial layout more compact.

[0053] Specifically, in this embodiment, an operating platform 221 is provided in the liquid transfer module 220. Figures 10 - 11 As shown, a gun tip reagent storage area 222 and an organoid sample operation area 223 are provided on the operation platform 221. Specifically, a gun tip box placement area 2221 for placing a gun tip box and a cooling module 2222 for storing reagents are provided in the gun tip reagent storage area 222. Specifically, in this embodiment, a plurality of gun tip box stations for placing gun tip boxes are provided in the gun tip box placement area 2221, and gun tip boxes can be placed in each gun tip box station. After the four-axis robot arm clamps the gun tip box from the gun tip box rack 240, it places the gun tip box in the corresponding gun tip box station. The cooling module 2222 can store the liquid storage plate at a low temperature, and a variety of reagents are stored in the liquid storage plate. A temporary storage hole position 2233 for placing a well plate and a liquid storage plate is provided in the organoid sample operation area 223, and the temporary storage hole position 2233 is set to at least one. In this embodiment, the temporary storage hole position 2233 is set to two. In a preferred implementation of this embodiment, a tilting module 2231 for tilting the well plate and / or a constant temperature oscillation module 2232 for incubating organoids is provided in the organoid sample operation area 223. The constant temperature oscillation module 2232 uses a semiconductor patch in conjunction with a pid temperature controller to achieve temperature control. The constant temperature oscillation module 2232 is provided with a cam structure driven by a motor to achieve the technical purpose of oscillating at a set frequency.

[0054] like Figure 10As shown in the figure, above the operation platform 221 of this embodiment, there are a pipetting three-axis robotic arm 224 and a handling three-axis robotic arm 225. A pipetting gun 2242 that cooperates with the pipette tip is installed on the pipetting three-axis robotic arm 224. A pipetting pump 215 is connected to the pipetting gun 2242. The pipetting pump 215 is used to control the pipetting gun 2242 to suck or discharge liquid. A handling gripper 2258 for gripping the well plate and opening or covering the well plate lid is installed on the handling three-axis robotic arm 225. Specifically, in the pipetting module 220 of this embodiment, a baffle 226 is provided on one side of the operation platform 221 facing the four-axis robotic arm 211, and an X-direction track 2271 is provided on the side of the operation platform 221 facing away from the four-axis robotic arm 211. A first Y-direction support arm 2241 is provided on the pipetting three-axis robotic arm 224, and a second Y-direction support arm 2251 is provided on the handling three-axis robotic arm 225. One end of the first Y-direction support arm 2241 and the second Y-direction support arm 2251 are slidably matched with the X-direction track 2271 through X-direction sliders. The other ends of the first Y-direction support arm 2241 and the second Y-direction support arm 2251 are provided with rollers, and a walking track 2272 that cooperates with the rollers is provided on the baffle 226.

[0055] In this embodiment, a first Y-direction track and a first Y-direction slider slidably matched with the first Y-direction track are provided inside the first Y-direction support arm 2241. The pipetting gun 2242 moves synchronously with the first Y-direction slider along the Y direction, and the first Y-direction slider is provided with a Z-direction moving mechanism for driving the pipetting gun 2242 to move along the Z direction. In this way, the pipetting gun 2242 can be driven to move along the X direction, Y direction, and Z direction to adjust the position of the pipetting gun 2242 in the space above the operation platform 221. In this embodiment, both the X direction and the Y direction are in the horizontal direction, the Z direction is in the vertical direction, and the pipetting gun 2242 is in the vertical direction. In this embodiment, the pipetting gun 2242 includes 4 pipetting tubes arranged in parallel, and the lower end of each pipetting tube can be respectively loaded with a pipette tip.

[0056] As Figures 12 - 13As shown, in this embodiment, a second Y-direction track 2252 and a second Y-direction slider 2253 slidably engaged with the second Y-direction track 2252 are provided on the second Y-direction support arm 2251. The handling three-axis robotic arm 225 of this embodiment includes a lead screw 2254 in the Z direction and a guide rod 2255 parallel to the lead screw 2254. The lower ends of the lead screw 2254 and the guide rod 2255 are connected to a Z-direction support arm 2256, and the lower end of the Z-direction support arm 2256 is connected to a handling gripper 2258. A nut threadedly engaged with the lead screw 2254 and a guide hole engaged with the guide rod 2255 are provided inside the second Y-direction slider 2253, and a motor 2257 for driving the nut to rotate to adjust the position of the handling gripper 2258 in the Z direction is provided inside the second Y-direction slider 2253. The handling gripper 2258 of this embodiment has four clamping arms, and a clamping drive mechanism for controlling the movement of the four clamping arms is provided inside the Z-direction support arm 2256, which can meet the operation requirements of orifice plate transfer and opening or closing the orifice plate cover.

[0057] As Figure 11As shown, in this embodiment, a waste storage area 228 is provided on the operation platform 221 or on one side of the operation platform 211. Inside the waste storage area 228, there is a liquid waste component 2281 for storing liquid waste and a second solid waste component 2282 for storing discarded pipette tips. In a preferred implementation manner of this embodiment, a safety transfer passage 229 is provided on the operation platform 211. The safety transfer passage 229 is used to connect the waste storage area 228 with the pipette tip reagent storage area 222 and the organoid sample operation area 223. Specifically, in this embodiment, the pipette tip reagent storage area 222 and the organoid sample operation area 223 are arranged side by side along the X direction. The safety transfer passage 229 is provided between one side of the pipette tip reagent storage area 222 and the organoid sample operation area 223. The waste storage area 228 is arranged inside the safety transfer passage 229 or at one end of the safety transfer passage 229. Specifically, the safety transfer passage 229 of this embodiment is located on the side of the pipette tip reagent storage area 222 and the organoid sample operation area 223 that is opposite to the four-axis robotic arm 211, and the safety transfer passage 229 is located in the X direction. The safety transfer passage 229 mainly reserves a position for the liquid transfer three-axis robotic arm 224 and the handling three-axis robotic arm 225 when transferring waste liquid and waste. Specifically, when the liquid transfer three-axis robotic arm 224 controls the pipette 2242 to discharge waste liquid, it first drives the pipette 2242 to move along the Y direction to the safety transfer passage 229, and then moves along the X direction to the liquid waste component 2281 to discharge the waste liquid into the liquid waste component 2281. Particularly, when the pipette 2242 transfers waste liquid at the tilting module 2231, it should be ensured that the temporary hole position 2233 in the Y direction of the tilting module 2231 does not place a well plate or the well plate cover of the well plate should be in a closed state to prevent the waste liquid in the pipette 2242 from dripping into the well plate. When the liquid transfer three-axis robotic arm 224 controls the pipette 2242 to discard the pipette tip, it first drives the pipette 2242 to move along the Y direction to the safety transfer passage 229, and then moves along the X direction to the liquid waste component 2281 to discard the pipette tip into the second solid waste component 2282. When discarding the well plate outside the operation platform 221, the four-axis robotic arm 211 is used to clamp the corresponding well plate and discard the well plate into the first solid waste component 290.

[0058] In this embodiment, the centrifuge 270 is arranged on the side of the liquid transfer module 220 close to the organoid sample operation area 223 and within the working space range of the handling three-axis robotic arm 225. Thus, when centrifugation operation is required, the handling three-axis robotic arm 225 can be used to directly transfer the corresponding well plate in the organoid sample operation area 223 to the centrifuge 270.

[0059] Specifically, in this embodiment, at least two liquid storage bottles 214 are further installed on the base 210. At least one liquid storage bottle 214 stores sterile water for use by the liquid transfer module and the automatic incubator, and at least one liquid storage bottle 214 is used to store waste liquid.

[0060] To achieve the purpose of automatically culturing organoids, sensors are provided in multiple components in this embodiment to achieve closed-loop detection. Specifically, as Figure 14 shown, in this embodiment, on one side of the automatic incubator 250 facing the four-axis robotic arm 211, there are a orifice plate inlet / outlet 251 and a first orifice plate holder 252 for carrying the orifice plate. A first sensor for detecting whether an orifice plate is placed is provided on the first orifice plate holder 252, and inside the automatic incubator 250, there is a first plate holder driving mechanism for controlling the first orifice plate holder 252 to extend outside the orifice plate inlet / outlet 251 or retract back into the orifice plate inlet / outlet 251. Specifically, when an orifice plate is placed into the automatic incubator 250, the initial state of the first orifice plate holder 252 is located outside the orifice plate inlet / outlet 251; when the first sensor detects that an orifice plate is placed on the first orifice plate holder 252, the first plate holder driving mechanism drives the first orifice plate holder 252 to retract back into the orifice plate inlet / outlet 251; after the first orifice plate holder 252 is placed into the automatic incubator 250, the first sensor detects that no orifice plate is placed on the first orifice plate holder 252. At this time, the first plate holder driving mechanism is used to drive the first orifice plate holder 252 to extend outside the orifice plate inlet / outlet 251 to wait for receiving the next orifice plate; or, the first orifice plate holder 252 remains in the automatic incubator 250 to wait for receiving the orifice plate that has completed organoid culture in the automatic incubator 250. When an orifice plate is taken out of the automatic incubator 250, the initial state of the first orifice plate holder 252 is located inside the orifice plate inlet / outlet 251; when the first sensor detects that an orifice plate is placed on the first orifice plate holder 252, the first plate holder driving mechanism drives the first orifice plate holder 252 to extend outside the orifice plate inlet / outlet 251; after the four-axis robotic arm 211 takes away the orifice plate on the first orifice plate holder 252, the first sensor detects that no orifice plate is placed on the first orifice plate holder 252. At this time, the first plate holder driving mechanism is used to drive the first orifice plate holder 252 to retract back into the orifice plate inlet / outlet 251 to wait for receiving the next orifice plate; or, the first orifice plate holder 252 remains outside the orifice plate inlet / outlet 251 to receive the orifice plate to be subjected to organoid culture.

[0061] As Figure 15As shown in the figure, the image acquisition and analysis instrument 260 of this embodiment is provided with a second orifice plate holder 261 for the entry and exit of the orifice plate, and a second sensor for detecting whether there is an orifice plate is provided on the second orifice plate holder 261. Similarly, a second plate holder driving mechanism is provided inside the image acquisition and analysis instrument 260, and the second plate holder driving mechanism is used to drive the second orifice plate holder 261 to extend out of the image acquisition and analysis instrument 260 or retract into the image acquisition and analysis instrument 260. Specifically, in the initial state, the second orifice plate holder 261 is located outside the image acquisition and analysis instrument 260. When the second sensor detects that there is an orifice plate placed on the second orifice plate holder 261, the second plate holder driving mechanism drives the second orifice plate holder 261 to retract into the image acquisition and analysis instrument 260 for quality inspection of the orifice plate. After the orifice plate completes the quality inspection, the second plate holder driving mechanism drives the second orifice plate holder 261 to extend out of the image acquisition and analysis instrument 260, and it is taken away by the four-axis robotic arm 211 to restore the initial state.

[0062] As Figure 16 shown, the tilting module 2231 of this embodiment includes a power base 2231a and an orifice plate tray 2231b. One end of the orifice plate tray 2231b is rotatably engaged with the power base 2231a through a rotating shaft 2231c, and a rotating driving mechanism 2231d for driving the orifice plate tray 2231b to rotate around the rotating shaft 2231c is provided inside the power base 2231a. Specifically, in this embodiment, a third sensor for detecting whether there is an orifice plate is provided on the orifice plate tray 2231b. When the third sensor detects that there is an orifice plate placed on the orifice plate tray 2231b, the rotating driving mechanism 2231d drives the orifice plate tray 2231b to rotate by a set angle around the rotating shaft 2231c relative to the power base 2231a, so as to facilitate the pipette 2242 to aspirate the culture medium from the orifice plate. The tilting angle of the orifice plate tray 2231b of this embodiment relative to the horizontal plane is 30°.

[0063] A fourth sensor for detecting whether there is an orifice plate is provided inside the constant temperature shaking module 2232 of this embodiment. When the fourth sensor detects that there is an orifice plate stored in the constant temperature shaking module 2232, the constant temperature shaking module 2232 incubates the organoids at a set temperature and vibration frequency according to a set program.

[0064] The centrifuge 270 of this embodiment is provided with a fifth orifice plate holder 271, and a fifth sensor for detecting whether there is an orifice plate is provided on the fifth orifice plate holder 271. When the fifth sensor detects that there is an orifice plate placed in the fifth orifice plate holder 271, the centrifuge 270 performs centrifugation on the orifice plate according to a set program.

[0065] As Figure 17As shown in the figure, the microplate reader 280 of this embodiment is provided with a sixth microplate holder 281 for the entry and exit of the microplate, and a sixth sensor for detecting whether there is a microplate is provided on the sixth microplate holder 281. A sixth holder driving mechanism for driving the sixth microplate holder 281 to extend outside the microplate reader 280 or retract into the microplate reader 280 is provided inside the microplate reader 280. Specifically, the sixth microplate holder 281 is initially located outside the microplate reader 280. When the sixth sensor detects that a microplate is placed on the sixth microplate holder 281, the sixth holder driving mechanism drives the sixth microplate holder 281 to retract into the microplate reader 280 to perform drug sensitivity detection on the microplate. Specifically, the microplate reader 280 reads the cell activity according to the program settings, and statistically analyzes the activity detection readings according to the preset program, and outputs the drug sensitivity detection results. After the detection is completed, the sixth holder driving mechanism drives the sixth microplate holder 281 to extend outside the microplate reader 280, and the four-axis robotic arm 211 takes away the detected microplate and restores to the initial state.

[0066] Specifically, in this embodiment, the first sensor, the second sensor, the third sensor, the fourth sensor, the fifth sensor, and the sixth sensor all adopt photoelectric sensors. Of course, in some other embodiments, the first sensor, the second sensor, the third sensor, the fourth sensor, the fifth sensor, and the sixth sensor may also adopt other types of sensors, such as proximity switches, contact sensors, infrared sensors, etc., which can all meet the corresponding functional requirements and will not be elaborated here.

[0067] The above-described embodiments are only preferred embodiments given to fully illustrate the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present invention are all within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. An organoid culture pipetting module, characterized in that: It comprises an operating platform, on which are provided a gun tip reagent storage area and an organoid sample operating area; the gun tip reagent storage area is provided with a gun tip box placement area for placing gun tip boxes and a cooling module for storing reagents; the organoid sample operating area is provided with a temporary storage hole for placing a well plate; a three-axis pipetting robot arm and a three-axis transport robot arm are provided above the operating platform, the three-axis pipetting robot arm is provided with a pipette gun that matches the gun tip, and the three-axis transport robot arm is provided with a transport clamp for clamping the well plate and opening or covering the well plate cover.

2. The organoid culture pipetting module according to claim 1, characterized in that: A waste storage area is provided on the operating platform or on one side of the operating platform.

3. The organoid culture pipetting module according to claim 2, characterized in that: The waste storage area is provided with a liquid waste assembly for storing liquid waste and a solid waste assembly for storing solid waste.

4. The organoid culture pipetting module according to claim 2, characterized in that: The operating platform is provided with a safety transfer channel, and the safety transfer channel is used to connect the waste storage area with the gun tip reagent storage area and the organoid sample operation area.

5. The organoid culture pipetting module according to claim 4, characterized in that: The waste storage area is arranged in the safe transfer passage or at the end of the safe transfer passage.

6. The organoid culture pipetting module according to claim 4, characterized in that: The gun tip reagent storage area and the organoid sample operation area are arranged side by side, the safe transfer channel is arranged between the gun tip reagent storage area and one side of the organoid sample operation area, and the waste storage area is arranged in the safe transfer channel or at one end of the safe transfer channel.

7. The organoid culture pipetting module according to any one of claims 1 to 6, characterized in that: The organoid sample operation area is provided with a tilting module for tilting the well plate; and / or, the organoid sample operation area is provided with a constant temperature oscillation module for incubating organoids.

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