A spatial multi-omics experiment system

Abstract

This application discloses a space multi-omics experimental system, including a space multi-omics experimental device, a robot, and at least two marking devices, one of which is used for marking along a first direction and the other for marking along a second direction; the space multi-omics experimental device is used to install the marking devices and sample glass slides to mark the sample glass slides in the first direction or the second direction; the robot is used to transport the marking devices or sample glass slides to the space multi-omics experimental device, or to remove the marking devices or sample glass slides from the space multi-omics experimental device.

Description

Technical Field

[0001] This application relates to the field of space multi-omics experimental technology, and in particular to a space multi-omics experimental system. Background Technology

[0002] Spatial multi-omics technology based on microfluidics uses a microfluidic chip with multiple channels to add markers to molecules within tissue slide cells, thereby encoding the spatial coordinates of intracellular molecules. Typically, the labeling process involves placing the tissue to be labeled on a glass slide, attaching the slide to a microfluidic chip with channels, adding different markers to each channel, and allowing the markers to bind to the tissue to be labeled, thus adding coordinate information to the tissue.

[0003] In related technologies, adding labels to each channel of a microfluidic chip is usually done manually. Furthermore, to meet the labeling accuracy requirements, the tissue to be labeled needs to be sliced ​​into thin slices, such as 10 μm thick. Taking a tissue slice with a volume of 1 cm x 1 cm x 1 cm as an example, each tissue slice needs to be made into 1000 slices. Each tissue slice to be labeled is combined with the microfluidic chip, and the microfluidic chip has at least 50 sample wells. Therefore, the labeling operation needs to be performed on the sample wells at least 100,000 times. Clearly, given such a large workload, manual operation by researchers is insufficient to meet the efficiency requirements of the experiments. Utility Model Content

[0004] To solve at least one of the above-mentioned technical problems, this application provides a space multi-omics experimental system, and the technical solution adopted is as follows.

[0005] This application also provides a space-based multi-omics experimental system, including: At least two marking devices, one of which is used for marking along a first direction and the other of which is used for marking along a second direction; A space-based multi-omics experimental apparatus is used to mount the marking device and sample glass slides to mark the sample glass slides in a first direction or a second direction. A robot is used to transport the labeling device or the sample glass slide to or from the space multi-omics experimental device.

[0006] In some embodiments of this application, the spatial multi-omics experimental system includes at least two spatial multi-omics experimental devices, and each spatial multi-omics experimental device is equipped with one of the marking devices.

[0007] In some embodiments of the third aspect of this application, the spatial multi-omics experimental system further includes a transfer box for holding the labeling device or sample glass slide.

[0008] In some embodiments of this application, multiple transfer boxes are provided, and the multiple transfer boxes can be stacked.

[0009] In some embodiments of this application, the spatial multi-omics experimental system further includes a spare station and a finished product station. The finished product station has at least one empty transfer box, which is used to hold a sample glass slide with completed markings. The spare station is used to hold the remaining empty transfer boxes.

[0010] In some embodiments of this application, the spatial multi-omics experimental system further includes a first cleaning fluid storage station, which is used to store the first cleaning fluid.

[0011] In some embodiments of this application, the spatial multi-omics experimental system further includes a cleaning station equipped with a nozzle for providing a second cleaning fluid to clean the sample glass slide.

[0012] In some embodiments of this application, the spatial multi-omics experimental system further includes a drying station, which is located in the cleaning station and is equipped with a blowing device for drying the cleaned sample glass slide.

[0013] In some embodiments of this application, the cleaning station includes a cleaning tank, a pair of nozzles spaced apart on one side of the cleaning tank, the spraying directions of the two nozzles being opposite to each other, a sample glass slide being placed between the two nozzles, the two surfaces of the glass slide facing the two nozzles respectively, a pair of air blowing devices spaced apart on the other side of the cleaning tank, the air outlet directions of the two air blowing devices being opposite to each other, a sample glass slide being placed between the two air blowing devices, the two surfaces of the glass slide facing the two air blowing devices respectively, and the air blowing devices being positioned above the nozzles along the direction of gravity.

[0014] In some embodiments of this application, the spatial multi-omics experimental system further includes adjacent marker storage stations and gun head storage stations.

[0015] In some embodiments of this application, the marker storage station is provided with a cooling module, a temperature sensor, and a marker storage tank. The marker storage tank is disposed on the cooling module, and the temperature sensor is disposed in the cooling module or between the marker storage tank and the cooling module. The temperature sensor is used to detect the temperature of the marker storage tank, and the cooling module can adjust the cooling power according to the temperature detected by the temperature sensor.

[0016] In some embodiments of this application, the gun head storage station is provided with a gun head storage box. The gun head storage box has two layers of gun head fixing holes along the axial direction of the gun head. The two layers of gun head fixing holes are arranged in a one-to-one correspondence. The gun head is inserted into the upper gun head fixing hole, and the lower gun head fixing hole is used to collect the liquid dripping from the gun head.

[0017] In some embodiments of this application, the gun head storage box includes a body and a base. The gun head fixing hole is provided in the body. The base is provided with a first positioning structure. The body is provided with a second positioning structure corresponding to the first positioning structure. The first positioning structure and the second positioning structure are plugged into each other. The body and the base are detachably connected. The bottom of the body is provided with at least two working holes along the horizontal direction. The two working holes are used for inserting the fork arm of the work vehicle.

[0018] In some embodiments of this application, the robot includes a first mobile arm with a liquid injection structure, the first mobile arm being used to drive the liquid injection structure to move and add markers.

[0019] In some embodiments of this application, the robot further includes a second mobile arm, which is provided with grippers.

[0020] In some embodiments of this application, the second mobile arm is provided with at least one of a visual alignment module and a laser ranging module, the identification direction of the visual alignment module and / or the laser ranging module is set toward the gripper, and the visual alignment module and / or the laser ranging module is used to locate the movement of the second mobile arm.

[0021] In some embodiments of this application, the robot further includes a third mobile arm on which a microscope module is mounted.

[0022] In some embodiments of this application, the robot further includes a fourth mobile arm equipped with an electric suction cup.

[0023] In some embodiments of this application, the spatial multi-omics system further includes an experimental platform, and the labeling device, the spatial multi-omics experimental equipment, and the robot are all mounted on the experimental platform.

[0024] In some embodiments of this application, the spatial multi-omics experimental system further includes a motion component disposed on the upper surface of the experimental platform and spaced apart from the experimental platform to form an operating space. The robot is movably disposed on the motion component and is movable within the operating space.

[0025] In some embodiments of this application, the motion component includes a support, a guide rail, a transmission component, and a drive component. The support is disposed on the upper surface of the experimental platform, the guide rail is disposed in the support, the transmission component is disposed along the extension direction of the guide rail, the transmission component connects the drive component and the robot, and the drive component is used to drive the transmission component to move the robot along the guide rail.

[0026] In some embodiments of this application, the spatial multi-omics experimental system further includes a recycling station located at the edge of the experimental platform, the recycling station being used to recycle the marking device after use.

[0027] In some embodiments of this application, the recycling station is provided with a recycling container, which is located below the experimental platform, and the opening of the recycling container protrudes from the edge of the experimental platform.

[0028] In some embodiments of this application, the spatial multi-omics experimental system further includes a guide groove, which is disposed at the edge of the experimental platform corresponding to the recovery container, and the guide groove is inclined toward the opening of the recovery container.

[0029] The embodiments of this application have at least the following beneficial effects: Using two marking devices enables marking of sample glass slides in two directions, thereby encoding the spatial coordinates of the tissue sections and meeting the needs of experimental research. The spatial multi-omics experimental equipment, in conjunction with a robot, can automatically complete the above-mentioned marking operation, improving the degree of automation in the experiment, helping to reduce the workload of manual operations, and improving operational efficiency. Attached Figure Description

[0030] The aspects and advantages described and / or added to the embodiments of this application will become apparent and readily understood in conjunction with the following drawings. It should be noted that the embodiments illustrated in the following drawings are exemplary and are used only to explain this application, and should not be construed as limiting this application.

[0031] Figure 1 A flowchart of a spatial multi-omics experimental method provided in the embodiments of this application; Figure 2 A schematic diagram of the structure of the spatial multi-omics experimental device provided in the embodiments of this application; Figure 3A schematic diagram of the structure of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 4 A top view of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 5 This is a schematic diagram of the first example of the cleaning station of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 6 A schematic diagram of a second example of the cleaning station of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 7 for Figure 6 CC section view; Figure 8 A schematic diagram of the marker storage station of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 9 An exploded view of the marker storage station for the spatial multi-omics experimental system provided in this application embodiment; Figure 10 A schematic diagram of the structure of the gun head storage station of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 11 An exploded view of the gun head storage station of the spatial multi-omics experimental system provided in the embodiments of this application; Figure 12 for Figure 3 A magnified view of part A; Figure 13 for Figure 3 A magnified view of section B; Figure 14 A schematic diagram of the structure of the motion components of the spatial multi-omics experimental system provided in the embodiments of this application.

[0032] Reference numerals: 1000, Space multi-omics experimental system; 100, Space multi-omics experimental equipment; 200, Labeling device; 210, First labeling device; 220, Second labeling device; 300, Sample glass slide; 400, Robot; 410, First moving arm; 411, Liquid injection structure; 420, Second moving arm; 421, Gripper; 422, Vision alignment module; 423, Laser ranging module; 430, Third moving arm; 431, Microscope; 440, Fourth moving arm; 441, Electric suction cup; 500, Transfer box; 10. Experimental platform; 11. First marking station; 12. Second marking station; 21. Backup station; 22. Finished product station; 31. First cleaning fluid storage station; 32. Cleaning station; 321. Nozzle; 322. Cleaning tank; 323. Blowing device; 41. Marker storage station; 4101. Cooling module; 4102. Marker liquid storage tank; 4103. Temperature equalization metal plate; 4104. Insulation panel; 42. Gun head storage station; 4201. Gun head storage box; 42011. Gun head fixing hole; 4202. Main body; 42021. Second positioning structure; 42022. Working hole; 4203. Base; 42031. First positioning structure; 50. Motion component; 51. Operating space; 52. Support; 53. Guide rail; 60. Recycling station; 61. Recycling container; 70. Guide groove. Detailed Implementation

[0033] The embodiments of this application are described in detail below with reference to the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain this application, and should not be construed as limiting this application.

[0034] In the description of this application, it should be understood that the terms "center", "middle", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0035] In the description of this application, "several" means one or more, "multiple" means two or more, "greater than," "less than," and "exceeding" are understood to exclude the stated number, while "above," "below," and "within" are understood to include the stated number. The use of "first" and "second" in the description is merely for distinguishing technical features and should not be construed as indicating or implying relative importance, or implicitly indicating the number of indicated technical features, or implicitly indicating the order of the indicated technical features.

[0036] In the description of this application, unless otherwise expressly specified and limited, the terms "set up," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0037] In the description of this application, the use of terms such as "as one implementation," "an embodiment," "some examples," "some embodiments," "illustrative embodiment," "example," "specific example," "some examples," etc., indicates that the specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0038] Firstly, please refer to Figure 1 This application provides a spatial multi-omics experimental method, including S100. Provide a first marking device 210 and combine the sample glass slide 300 with the first marking device 210; S200. The first marking device 210 is marked in the first direction in the first round; S300. Provides a second marking device 220; S400. Transfer the sample glass slide 300 to the second marking device 220; S500. The second marking device 220 performs a second round of marking along a second direction, which is perpendicular to the first direction; S600. Remove the sample glass slide 300.

[0039] By setting a first marking device 210, which has multiple channels, a marker is added to the tissue slice along a first direction, allowing the tissue slice on the sample glass slide 300 to bind with the marker, thereby marking the tissue slice on the sample glass slide 300 along the first direction and achieving coordinate encoding in the first direction. Similarly, a second marking device 220, which has multiple channels, adds a marker to the tissue slice along a second direction, allowing the tissue slice to bind with the marker again and achieve coordinate encoding in the second direction. Since the second direction is perpendicular to the first direction, the two intersecting directions can achieve spatial coordinate encoding of the tissue slice, meeting the needs of experimental research. This application separates the two marking operations by sequentially marking the sample glass slide 300 in two rounds, using different marking devices for each round, thus satisfying the requirement of adding markers in both directions. Therefore, during the first round of labeling, there is an opportunity to prepare the second labeling device 220 simultaneously, or during the second round of labeling, there is an opportunity to retrieve the first labeling device 210 simultaneously and prepare a new first labeling device 210 for the next sample glass slide 300. This means that separating the two labeling operations facilitates the parallel operation design of space multi-omics experiments, allowing one round of labeling in one labeling device to proceed without affecting another round of labeling in the other labeling device, thereby helping to shorten the operation time of space multi-omics experiments and improve experimental efficiency.

[0040] In some embodiments, after performing step S200, marking the first marking device 210 along a first direction, and before performing step S400, transferring the sample glass slide 300 to the second marking device 220, the spatial multi-omics experimental method further includes: S700. Add a first cleaning solution to the first marking device 210 to clean the sample glass slide 300.

[0041] By setting a cleaning step to flush the flow channel of the first marking device 210, the markings in the flow channel can be cleaned before the first marking device 210 is separated from the sample glass slide 300. This prevents the markings from flowing between the channels and onto the surface of the sample glass slide 300 after the seals are broken, thus ensuring that the markings in each channel do not mix, thereby improving the accuracy and reliability of the marking.

[0042] In some embodiments, after implementing step S700, adding a first cleaning solution to the first labeling device 210 to clean the sample glass slide 300, the space multi-omics experimental method further includes: S710. Remove the sample glass slide 300; S720. Dry the sample glass slide 300.

[0043] After separating the sample glass slide 300 from the first marking device 210, the sample glass slide 300 is dried by blowing it dry, which can prevent residual cleaning solution from affecting the subsequent second marking or subsequent observation operations.

[0044] In some embodiments, please refer to Figure 4 After implementing step S700, which involves adding a first cleaning solution to the first labeling device 210 to clean the sample glass slide 300, the space multi-omics experimental method further includes: S730. Remove the sample glass slide 300 and transfer it to the cleaning station 32; S740. Clean the sample glass slide 300 using the second cleaning solution.

[0045] After cleaning the first marking device 210 and separating the sample glass slide 300, the sample glass slide 300 can be cleaned separately to remove any residual markings on the sample glass slide 300 and avoid affecting subsequent observation.

[0046] In some embodiments, after performing step S740, cleaning the sample glass slide 300 with the second cleaning solution, the space multi-omics experimental method further includes: S741. Dry the sample glass slide 300°C.

[0047] Drying the sample glass slide by blowing it dry 300 can prevent residual cleaning solution from affecting subsequent second labeling or observation operations.

[0048] In some embodiments, step S720. Drying the sample glass slide 300 or step S741. Drying the sample glass slide 300 includes: S721. While drying the sample glass slide 300, move the sample glass slide 300 back and forth.

[0049] Drying by reciprocating the movement of the sample glass slide 300 helps to increase the airflow rate on the surface of the sample glass slide 300, thereby improving drying efficiency. This method avoids high-temperature drying methods, preventing damage to the microstructure of the sample glass slide 300 surface from excessive heat.

[0050] Optionally, the removal, cleaning, drying, and reciprocating movement of the sample glass slide 300 can be performed manually by an experimenter or by a robot.

[0051] In some embodiments, after performing step S500, marking the second marking device 220 in a second direction for the second round, the space multi-omics experimental method further includes: S800. Add a third cleaning solution to the second marking device 220 to clean the sample glass slide 300.

[0052] Similar to cleaning the first marking device 210, by setting a cleaning step to rinse the flow channel of the second marking device 220, the markings in the flow channel can be cleaned before the second marking device 220 is separated from the sample glass slide 300. This prevents the markings from flowing between the channels and onto the surface of the sample glass slide 300 after the seals are broken, thus ensuring that the markings in each channel do not mix, thereby improving the accuracy and reliability of the marking.

[0053] In some embodiments, please refer to Figure 4 After implementing step S800, which involves adding a third cleaning solution to the second labeling device 220 to clean the sample glass slide 300, the space multi-omics experimental method further includes: S810. Remove the sample glass slide 300 and transfer it to the cleaning station 32; S820. Clean the sample glass slide 300 using the fourth cleaning solution.

[0054] In some embodiments, after implementing step S800, adding a third cleaning solution to the second labeling device 220 to clean the sample glass slide 300, or after implementing step S820, cleaning the sample glass slide 300 with a fourth cleaning solution, the spatial multi-omics experimental method further includes: S821. Dry the sample glass slide by 300°C.

[0055] The implementation methods and beneficial effects of cleaning the sample glass slide 300 with the third and fourth cleaning solutions and drying the sample glass slide 300 are the same as those when operating the first marking device 210, and will not be repeated here.

[0056] Optionally, the first cleaning solution, the second cleaning solution, the third cleaning solution, and the fourth cleaning solution can be the same type or different types of cleaning solutions. Alternatively, the first cleaning solution and the third cleaning solution can be the same type of cleaning solution, the second cleaning solution and the fourth cleaning solution can be the same type of cleaning solution, and the first cleaning solution and the second cleaning solution can be the same type or different types of cleaning solutions.

[0057] In some embodiments, please refer to Figure 4The first marking device 210 is disposed at the first marking station 11. Step S300, providing the second marking device 220, includes: simultaneously performing any of the following steps while disposing of the second marking device 220 at the second marking station 12: S200. The first marking device 210 performs a first round of marking along a first direction; or S700. Add a first cleaning solution to the first marking device 210; or S710. Remove the sample glass slide 300; S720. Dry the sample glass slide 300; or S741. Dry the sample glass slide at 300°C; or S740. Clean the sample glass slide 300 using the second cleaning solution.

[0058] By setting the first marking device 210 and the second marking device 220 at the first marking station 11 and the second marking station 12 respectively, the first and second rounds of marking can be carried out without affecting each other. This means that while the first round of marking or the cleaning after marking is being carried out, the second marking device 220 can be prepared and installed at, for example, the second marking station 12. Therefore, these two actions can be carried out simultaneously, thereby saving waiting time and improving experimental efficiency.

[0059] In some embodiments, a first marking device 210 is disposed at a first marking station 11, and a second marking device 220 is disposed at a second marking station 12. The spatial multi-omics experimental method includes: simultaneously marking a first sample glass slide 300 using the first marking device 210, and marking a second sample glass slide 300 using the second marking device 220. This allows for the simultaneous marking of different sample glass slides 300 using the first marking device 210 and the second marking device 220 at two marking stations, thus enabling multiple marking operations to be performed concurrently and improving experimental efficiency.

[0060] In some embodiments, the first labeling device 210, the second labeling device 220, and the sample glass slide 300 are all placed in the transfer box 500, and the spatial multi-omics experimental method includes: S10. Take out the first marking device 210 from the transfer box 500 and load the first marking device 210 into the spatial multi-omics experimental device 100 of the first marking station 11; S20. Take out the sample glass slide 300 from the transfer box 500, load the sample glass slide 300 into the spatial multi-omics experimental device 100 of the first marking station 11, and cover the sample glass slide 300 with the first marking device 210. S30. Transfer any of the vacated transfer boxes 500 from any of the above steps to the finished product station 22; S40. After removing the sample glass slide 300, transfer the sample glass slide 300 to the transfer box 500 at the finished product station 22.

[0061] By setting up a transfer box 500 to hold the first marking device 210, the second marking device 220, and the sample glass slide 300, the dimensions of these experimental instruments can be standardized. This facilitates the gripping and releasing of these instruments by the robot 400's moving arm, allowing it to adapt to different instrument sizes, simplifying its operation, and improving the uniformity of its actions. Furthermore, the transfer box 500 enables the vertical stacking of multiple marking devices 200 or sample glass slides 300, reducing space occupancy during experiments. When empty, the transfer box 500 can also hold marked sample glass slides 300, further reducing the variety of instruments in the experimental system and facilitating instrument management.

[0062] In some embodiments, step S300, providing the second marking device 220, includes: S310. Take out the second marking device 220 from the transfer box 500 and load the second marking device 220 into the spatial multi-omics experimental device 100 of the second marking station 12; S320. Take out the sample glass slide 300 from the spatial multi-omics experimental device 100 at the first labeling station 11, load the sample glass slide 300 into the spatial multi-omics experimental device 100 at the second labeling station 12, and cover the sample glass slide 300 with the second labeling device 220. S330. Transfer any of the vacated transfer boxes 500 from any of the above steps to the finished product station 22; S340. After removing the sample glass slide 300, transfer the sample glass slide 300 to the transfer box 500 at the finished product station 22.

[0063] After the transfer box 500 is emptied, it can still be used to hold the labeled sample glass slide 300. This helps reduce the types of equipment in the experimental system and facilitates equipment management. The emptied transfer box 500 can come from the transfer box 500 that holds the second marking device 220, the transfer box 500 that holds the first marking device 210, or the transfer box 500 that holds the sample glass slide 300. That is, the source of the emptied transfer box 500 can be diverse. Reusing the emptied transfer box 500 allows for the timely recovery of empty transfer boxes 500, reducing the occupation of experimental space, and also reduces the number of transfer boxes 500 used, facilitating equipment management.

[0064] In some embodiments, after implementing step S30. or step S330., which involves transferring any of the vacated transfer boxes 500 from any of the above steps to the finished product station 22, the spatial multi-omics experimental method further includes: S50. Transfer the remaining vacated transfer boxes 500 to the standby workstation 21.

[0065] Recycling the remaining unused empty transfer boxes 500 in a timely manner can reduce the occupation of experimental space and improve the convenience of experimental operations.

[0066] In some embodiments, after performing step S200, marking the first marking device 210 along the first direction in a first round, the space multi-omics experimental method further includes: S201. Transfer the first marking device 210 to the recycling station 60.

[0067] In some embodiments, after step S500, in which the second marking device 220 performs a second round of marking along the second direction, the space multi-omics experimental method further includes: S501. Transfer the second marking device 220 to the recycling station 60.

[0068] After the first marking device 210 and the second marking device 220 have completed marking, there will be marker residue on the flow channel of the marking device. Therefore, it is necessary to recycle the residue to avoid affecting subsequent experiments.

[0069] In some embodiments, step S200. Performing a first round of marking on the first marking device 210 along a first direction includes sequentially adding different markers to a plurality of addition holes of the first marking device 210, and replacing the nozzle of the injection structure 411 before each addition of a marker. Step S500. Performing a second round of marking on the second marking device 220 along the second direction includes sequentially adding different markers to the multiple addition holes of the second marking device 220, and replacing the nozzle of the injection structure 411 before each addition of a marker.

[0070] Because the added markers are different each time, they can be combined with the tissue sections on different channels of different marking devices 200 to achieve the effect of marking and encoding. Therefore, in order to avoid confusion between markers on each channel, the nozzle of the injection structure 411 is replaced before each addition of a new marker to ensure that the addition of markers is not affected each time, thus ensuring the accuracy of marking.

[0071] A second aspect of this application also provides a space-based multi-omics experimental device 100, please refer to [link / reference needed]. Figures 2 to 4The space multi-omics experimental device 100 is used to implement the space multi-omics experimental method provided in the first aspect above. The space multi-omics experimental device 100 is used to perform a first round of marking on the first marking device 210 along a first direction, and is also used to perform a second round of marking on the second marking device 220 along a second direction.

[0072] In some embodiments, at least two spatial multi-omics experimental devices 100 are provided at the first labeling station 11 and the second labeling station 12. The spatial multi-omics experimental device 100 at the first labeling station 11 is used for the first round of labeling, and the spatial multi-omics device at the second labeling station 12 is used for the second round of labeling. By providing two spatial multi-omics experimental devices 100, two different labeling devices 200 can be labeled simultaneously at two stations, improving experimental efficiency. Alternatively, sample glass slides 300 carrying the same tissue section can complete the first and second rounds of labeling sequentially at the first labeling station 11 and the second labeling station 12. Preparation for the second labeling station 12 can be carried out during the first round of labeling, and cleaning of the first labeling station 11 can be carried out during the second round of labeling, or the first round of labeling of another sample glass slide 300 can be performed, thereby reducing waiting time and improving experimental efficiency.

[0073] Of course, in other embodiments, the same marking station can also perform the first round of marking and the second round of marking on the same marking device in sequence. For example, the first round of marking is performed at the first marking station 11, and then the sample glass slide 300 is separated from the first marking device 210. Then the sample glass slide 300 is combined with the second marking device 220, and the second round of marking is completed in the first marking station 11.

[0074] Thirdly, please refer to Figures 3 to 4This application also provides a spatial multi-omics experimental system 1000 (hereinafter referred to as the experimental system 1000), which can be used to implement the spatial multi-omics experimental method provided in the first aspect above. The spatial multi-omics experimental system includes a spatial multi-omics experimental device 100, a robot 400, and at least two marking devices 200, one marking device for marking along a first direction and the other marking device for marking along a second direction. The spatial multi-omics experimental device 100 is used to mount the marking devices and sample glass slides 300 to mark the sample glass slides 300 in the first direction or the second direction. The robot 400 is used to transport the marking devices or sample glass slides 300 to or from the spatial multi-omics experimental device 100. Using the two marking devices 200, marking of the sample glass slides 300 in two directions can be achieved, thereby encoding the spatial coordinates of the tissue sections and meeting the needs of experimental research. The space multi-omics experimental device 100, in conjunction with the robot 400, can automatically complete the above-mentioned labeling operations, improve the degree of automation of the experiment, help reduce the workload of manual operation, and improve operational efficiency.

[0075] In some embodiments, the space multi-omics experimental system 1000 includes at least two space multi-omics experimental devices 100, each equipped with a marking device. By using at least two space multi-omics experimental devices 100, two different marking devices 200 can be marked simultaneously at two workstations, improving experimental efficiency. Alternatively, sample glass slides 300 carrying the same tissue section can undergo the first and second rounds of marking sequentially at different workstations. While the first round of marking is being performed, preparations can be made for another workstation, and while the second round of marking is being performed, the remaining workstations can be cleaned, or the first round of marking for another sample glass slide 300 can be performed, thereby reducing waiting time and improving experimental efficiency.

[0076] In some embodiments, the space multi-omics experimental system 1000 further includes a transfer box 500 for holding the marking device 200 or the sample glass slide 300. By setting the transfer box 500 to hold the marking device 200 and the sample glass slide 300, the size of these experimental instruments can be standardized, making it easier for the robot 400's mobile arm to grip and release them. This also allows the robot 400's mobile arm to adapt to the size of different experimental instruments, simplifies the operation of the robot 400's mobile arm, and improves the uniformity of the operation.

[0077] In some embodiments, multiple transfer boxes 500 are provided, and the multiple transfer boxes 500 can be stacked. The transfer boxes 500 facilitate the vertical stacking of multiple marking devices 200 or sample glass slides 300, reducing space occupation during the experiment.

[0078] In some embodiments, the space multi-omics experimental system 1000 further includes a spare station 21 and a finished product station 22. The finished product station 22 holds at least one empty transfer box 500, which is used to hold labeled sample glass slides 300. The spare station 21 is used to hold the remaining empty transfer boxes 500. After the transfer boxes 500 are emptied, they can still be used to hold labeled sample glass slides 300, which helps to reduce the types of equipment in the experimental system and facilitates equipment management.

[0079] In some embodiments, please combine Figure 3 and Figure 4 The space multi-omics experimental system 1000 also includes a first cleaning solution storage station 31, which is used to store the first cleaning solution.

[0080] In some embodiments, please refer to Figure 5 The space multi-omics experimental system 1000 also includes a cleaning station 32, which is equipped with a nozzle 321 for providing a second cleaning solution to clean the sample glass slide 300. Exemplarily, the cleaning station 32 may be equipped with a cleaning tank 322, in which the nozzle 321 is disposed. The sample glass slide 300 can be placed into the cleaning tank 322, and the nozzle 321 can rinse the sample glass slide 300 when activated.

[0081] In some embodiments, the space multi-omics experimental system 1000 further includes a drying station, which is located in the cleaning station 32. The drying station is equipped with a blower 323, which is used to dry the cleaned sample glass slides 300.

[0082] In some embodiments, the nozzle 321 and the blowing device 323 are respectively disposed at both ends of the cleaning tank 322. On the one hand, different sample glass slides 300 can be cleaned and dried simultaneously in the cleaning tank 322. On the other hand, mutual interference between the two sample glass slides 300 can be avoided.

[0083] In some embodiments, please refer to Figure 6 and Figure 7A pair of nozzles 321 are spaced apart on one side of the cleaning tank 322, with their spray directions facing each other. A sample glass slide 300 can be placed between the two nozzles 321, with its two surfaces facing each nozzle 321. A pair of air blowers 323 are spaced apart on the other side of the cleaning tank 322, with their air outlet directions facing each other. The sample glass slide 300 can also be placed between the two air blowers 323, with its two surfaces facing each air blower 323. The air blowers 323 are positioned above the nozzles 321 along the direction of gravity. The paired nozzles 321 allow for simultaneous spraying of both surfaces of the sample glass slide 300, improving rinsing efficiency. Similarly, the paired air blowers 323 also allow for simultaneous drying of both surfaces of the sample glass slide 300, shortening the time spent on cleaning and drying. To prevent the cleaning solution from contaminating the blower 323, the blower 323 is positioned above the nozzle 321 along the direction of gravity; that is, the two are offset in the direction of gravity. This ensures that the cleaning solution avoids passing over the blower 323 as it falls, thus preventing contamination of the blower 323. Similarly, when two sample glass slides 300 are simultaneously cleaned and dried in the cleaning tank 322, the sample glass slide 300 being dried is also prevented from being contaminated by the cleaning solution.

[0084] In some embodiments, the spatial multi-omics experimental system 1000 further includes a marker storage station 41 and a gun head storage station 42 arranged adjacent to each other.

[0085] By setting up a first cleaning solution storage station 31, a cleaning station 32, a drying station, a marker storage station 41, and a pipette tip storage station 42, the functions of cleaning the marking device 200, cleaning and drying the sample glass slide 300, and adding and replacing marker tips can be realized respectively. The pipette tip storage station 42 and the marker storage station 41 are arranged adjacent to each other, which can shorten the movement distance of the robot 400 between these two stations and improve the operating efficiency of the robot 400.

[0086] Since the markers need to maintain good activity at around 4°C, please refer to [the relevant documentation / reference]. Figure 8 and Figure 9In some embodiments, the marker storage station 41 is equipped with a cooling module 4101, a temperature sensor, and a marker storage tank 4102. The marker storage tank 4102 is mounted on the cooling module 4101, and the temperature sensor is located within the cooling module 4101 or between the marker storage tank 4102 and the cooling module 4101. The temperature sensor is used to detect the temperature of the marker storage tank 4102, and the cooling module 4101 can adjust its cooling power according to the temperature detected by the temperature sensor. The cooling module 4101 provides a low-temperature environment for the marker storage tank 4102, thereby ensuring that the markers stored in the marker storage tank 4102 are maintained at a suitable temperature, ensuring good activity of the markers during the labeling experiment. The temperature sensor can detect the temperature in the marker storage tank in real time, and the cooling power of the cooling module 4101 can be adjusted according to the detected temperature to ensure that the marker storage tank 4102 is maintained at a suitable temperature.

[0087] For example, the cooling module 4101 can be a semiconductor cooling chip. Semiconductor cooling chips have a stable cooling effect and are small in size. Therefore, using a semiconductor cooling chip can reduce the space occupied in the experimental system 1000 and save space in the experimental system 1000.

[0088] Optionally, the marker storage station 41 is also equipped with a bracket for fixing the cooling module 4101 onto the experimental platform 10. To facilitate the placement of the marker storage tank 4102, the marker storage station 41 can also be equipped with a temperature-regulating metal plate 4103. Utilizing the excellent thermal conductivity of metal, and with the temperature-regulating metal plate 4103 in direct contact with the cooling module 4101, the cooling effect of the cooling module 4101 can be quickly transferred to the marker storage tank 4102, improving the cooling effect of the marker storage tank 4102. The top surface of the temperature-regulating metal plate 4103 can also be provided with a groove for placing the marker storage tank 4102. The marker storage station 41 can also be equipped with a heat preservation panel 4104. The heat preservation panel 4104 is set on the surface of the uniform temperature metal plate 4103. The heat preservation panel 4104 can be made of a material with low thermal conductivity, such as plastic, so as to prevent the temperature of the marker storage tank 4102 from rising too quickly and ensure that the marker storage tank 4102 has better cooling and heat preservation effects.

[0089] In some embodiments, please refer to Figure 10 and Figure 11The nozzle storage station 42 is equipped with a nozzle storage box 4201. The nozzle storage box 4201 has two layers of nozzle fixing holes 42011 along the axial direction of the nozzle. The two layers of nozzle fixing holes 42011 are arranged one-to-one. The nozzle is inserted into the upper nozzle fixing hole 42011, while the lower nozzle fixing hole 42011 is used to collect liquid dripping from the nozzle. The lower nozzle fixing hole 42011 helps to catch residual liquid dripping from the nozzle, and its shallower depth facilitates subsequent cleaning.

[0090] In some embodiments, the gun head storage box 4201 includes a body 4202 and a base 4203. A gun head fixing hole 42011 is provided in the body 4202. The base 4203 is provided with a first positioning structure. The body 4202 is provided with a second positioning structure 42021 corresponding to the first positioning structure 42031. The first positioning structure 42031 and the second positioning structure 42021 are plugged into each other. The body 4202 and the base 4203 are detachably connected. The bottom of the body 4202 is provided with at least two working holes 42022 along the horizontal direction for inserting the fork arm of the work vehicle. Through the cooperation of the first positioning structure 42031 and the second positioning structure 42021, the connection strength and stability between the body 4202 and the base 4203 can be improved, and the body 4202 can be prevented from shaking during use.

[0091] For example, the first positioning structure 42031 and the second positioning structure 42021 can adopt a combination of a socket and a positioning pin. The positioning pin can be inserted into the socket to achieve a detachable connection between the body part 4202 and the base 4203. When the gun head needs to be replaced, the entire body part 4202 can be removed for replacement. Specifically, the working hole 42022 provided in the body part 4202 allows the fork arm of the work vehicle to be inserted. By raising the fork arm, the body part 4202 is separated from the base 4203. Moreover, the fork arm can be inserted into two working holes 42022 at a time, which can improve the connection stability between the fork arm and the body part 4202. Optionally, two fork arms can be provided, and correspondingly, two pairs of working holes 42022 can be provided, that is, four, thereby further improving the stability when the fork arm is inserted into the body part 4202.

[0092] In some embodiments, please combine Figure 3 , Figure 4 and Figure 13 The robot 400 includes a first movable arm 410, which is equipped with a liquid injection structure 411. The first movable arm 410 is used to drive the liquid injection structure 411 to move and add markers. The first movable arm 410 enables automatic addition of additives, improving the convenience and efficiency of experiments. The first movable arm 410 can be used in conjunction with structures such as the liquid injection structure 411 to meet the needs of pipetting operations.

[0093] For example, the injection structure 411 can be a pipette.

[0094] In some embodiments, please combine Figure 3 , Figure 4 and Figure 12 The robot 400 also includes a second mobile arm 420, which is equipped with a gripper 421. By using the gripper 421, different actions such as grasping, releasing, and clamping can be performed to meet experimental needs. For example, the gripper 421 can be used to grasp the transfer box 500 or experimental equipment placed in the transfer box 500, further reducing manual operation and improving the automation level of the experimental process.

[0095] In some embodiments, the second moving arm 420 is provided with at least one of a vision alignment module 422 and a laser ranging module 423. The recognition direction of the vision alignment module 422 and the laser ranging module 423 is set towards the gripper 421. The vision alignment module 422 and the laser ranging module 423 are used to locate the movement of the second moving arm 420. The vision alignment module 422 can detect and determine the movement position of the second moving arm 420 and the gripper 421. The laser ranging module 423 can detect the relative distance between the gripper 421 and the second moving arm 420, or the distance between the gripper 421 and the target object, thereby accurately controlling the movement position of the gripper 421 and improving the working accuracy of the gripper 421.

[0096] Optionally, the second moving arm 420 may be equipped with both a visual alignment module 422 and a laser ranging module 423 to improve the accuracy of motion positioning. Of course, in other examples, either the visual alignment module 422 or the laser ranging module 423 may be provided separately; no specific limitation is made here.

[0097] In some embodiments, the robot 400 further includes a third movable arm 430, on which a microscope 431 module is mounted. The microscope 431 module allows observation of the sample glass slide 300 during the labeling process, facilitating control and adjustment of the reaction progress. The microscope 431 module, along with the aforementioned gripper 421, liquid injection structure 411, and other structures, is connected to different movable arms, allowing each movable arm to operate independently, avoiding mutual interference and improving the reliability of the robot 400. In some embodiments, please reassemble... Figure 3 , Figure 4 and Figure 13The robot 400 also includes a fourth movable arm 440, which is equipped with an electric suction cup 441. The electric suction cup 441 provides negative pressure to the spatial multi-omics experimental device 100, specifically by applying negative pressure to the liquid outlet side of the labeling device 200. This guides the labeled material from the liquid inlet side to the liquid outlet side, allowing it to flow through the tissue section and bind to the tissue, achieving the labeling effect. Similarly, the fourth movable arm 440 can operate independently of the first movable arm 410, the second movable arm 420, and the third movable arm 430, without interfering with each other during use.

[0098] In some embodiments, please combine Figure 4 and Figure 14 The space multi-omics experimental system 1000 also includes an experimental platform 10, on which the labeling device 200, the space multi-omics experimental equipment 100, and the robot 400 are all mounted. The experimental platform 10 can be used to carry the experimental equipment required for the experiment, such as the labeling device 200, the space multi-omics experimental equipment 100, and the robot 400, facilitating experimental operations.

[0099] In some embodiments, please combine Figure 3 , Figure 4 and Figure 14 The spatial multi-omics experimental system 1000 also includes a motion component 50, which is disposed on the upper surface of the experimental platform 10 and spaced apart from the experimental platform 10 to form an operating space 51. A robot 400 is movably disposed on the motion component 50 and can move within the operating space 51. By setting up the motion component 50, space can be provided for the installation and movement of the robot 400, and power and guidance can be provided during the movement of the mobile arm, ensuring smooth movement of the mobile arm.

[0100] In some embodiments, the motion component 50 includes a support 52, a guide rail 53, a transmission component, and a drive component. The support 52 is disposed on the upper surface of the experimental platform 10, the guide rail 53 is disposed in the support 52, the transmission component is disposed along the extension direction of the guide rail 53, the transmission component connects the drive component and the robot 400, and the drive component drives the transmission component to move the robot 400 along the guide rail 53. The guide rail 53 provides a guiding function, on the one hand providing a track for the robot 400's mobile arm to be installed, and on the other hand guiding the movement of the mobile arm, improving the stability and accuracy of the mobile arm during the movement process.

[0101] Optionally, the first movable arm 410, the second movable arm 420, the third movable arm 430, and the fourth movable arm 440 can be set independently, that is, each movable arm has three degrees of freedom in the x, y, and z directions. In some examples, to simplify the drive structure of these movable arms, the second movable arm 420 and the third movable arm 430 are grouped together and can share the same guide rail 53, and the first movable arm 410 and the fourth movable arm 440 are grouped together and share the same guide rail 53. In this way, the second movable arm 420 and the third movable arm 430 are simultaneously fixed on the same y-axis, and the first movable arm 410 and the fourth movable arm 440 are simultaneously fixed on the same y-axis. The movable arms in the same group always move simultaneously on the x-axis or y-axis. Two movable arms in the same group, such as the first movable arm 410 and the fourth movable arm 440, can be set with independently operating linear modules, so that the first movable arm 410 and the fourth movable arm 440 can rise and fall independently along the z-axis without interfering with each other. Similarly, the second moving arm 420 and the third moving arm 430 can be equipped with independently operating linear modules so that the second moving arm 420 and the third moving arm 430 can lift and lower independently along the z-axis.

[0102] Optionally, the first movable arm 410 and the second movable arm 420 may be connected to the same guide rail 53, or two guide rails 53 may be provided respectively, with the first movable arm 410 and the fourth movable arm 440 on one guide rail 53 and the second movable arm 420 and the third movable arm 430 on the other guide rail 53.

[0103] In some embodiments, please refer to Figure 3 The space multi-omics experimental system 1000 also includes a recycling station 60, which is located at the edge of the experimental platform 10. The recycling station 60 is used to recycle the used marking devices 200. By setting up and utilizing the recycling station 60, the used marking devices 200 can be uniformly recycled, avoiding the accumulation of marking devices 200 on the surface of the experimental platform 10, which would occupy space, improve the cleanliness and orderliness of the surface of the experimental platform 10, and improve the convenience of experimental operation.

[0104] In some embodiments, the recycling station 60 is provided with a recycling container 61, which is disposed below the experimental platform 10, with the opening of the recycling container 61 protruding from the edge of the experimental platform 10. The recycling container 61 is capable of catching and accommodating the marking device 200 for collection and further cleaning.

[0105] In some embodiments, the spatial multi-omics experimental system 1000 further includes a guide groove 70, which is disposed at the edge of the experimental platform 10 corresponding to the recovery container 61, and is inclined toward the opening of the recovery container 61. The inclined guide groove 70 facilitates the sliding of the used marking device 200 into the recovery container 61, improving the accuracy of placing the marking device 200 into the recovery container and reducing the operational difficulty of recovering the marking device 200.

[0106] The embodiments of this application have been described in detail above with reference to the accompanying drawings. However, this application is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of this application. Furthermore, unless otherwise specified, the embodiments and features described in the embodiments of this application can be combined with each other.

Claims

1. A space-based multi-omics experimental system, characterized in that: include At least two marking devices, one of which is used for marking along a first direction and the other of which is used for marking along a second direction; A space-based multi-omics experimental apparatus is used to mount the marking device and sample glass slides to mark the sample glass slides in a first direction or a second direction. A robot is used to transport the labeling device or the sample glass slide to or from the space multi-omics experimental device.

2. The space multi-omics experimental system according to claim 1, characterized in that: The space multi-omics experimental system includes at least two space multi-omics experimental devices, and each space multi-omics experimental device is equipped with one of the labeling devices.

3. The space multi-omics experimental system according to claim 1, characterized in that: The space multi-omics experimental system also includes a transfer box for holding the labeling device or sample glass slide.

4. The space multi-omics experimental system according to claim 3, characterized in that: Multiple transfer boxes are configured, and these transfer boxes can be stacked.

5. The space multi-omics experimental system according to claim 4, characterized in that: The spatial multi-omics experimental system also includes a spare station and a finished product station. The finished product station has at least one empty transfer box. The transfer box located at the finished product station is used to hold the marked sample glass slide. The spare station is used to hold the remaining empty transfer boxes.

6. The space multi-omics experimental system according to claim 1, characterized in that: The space multi-omics experimental system also includes a first cleaning fluid storage station, which is used to store the first cleaning fluid.

7. The space multi-omics experimental system according to claim 1, characterized in that: The space multi-omics experimental system also includes a cleaning station equipped with a nozzle for providing a second cleaning solution to clean the sample glass slide.

8. The space multi-omics experimental system according to claim 7, characterized in that: The space multi-omics experimental system also includes a drying station, which is located in the cleaning station. The drying station is equipped with a blowing device, which is used to dry the sample glass slides after cleaning.

9. The space multi-omics experimental system according to claim 8, characterized in that: The cleaning station includes a cleaning tank. A pair of nozzles are spaced apart on one side of the cleaning tank, with the spraying directions of the two nozzles facing each other. A sample glass slide is placed between the two nozzles, with its two surfaces facing the two nozzles respectively. A pair of air blowing devices are spaced apart on the other side of the cleaning tank, with the air outlet directions of the two air blowing devices facing each other. A sample glass slide is placed between the two air blowing devices, with its two surfaces facing the two air blowing devices respectively. The air blowing devices are positioned above the nozzles along the direction of gravity.

10. The space multi-omics experimental system according to claim 1, characterized in that: The spatial multi-omics experimental system also includes adjacent marker storage stations and gun head storage stations.

11. The space multi-omics experimental system according to claim 10, characterized in that: The marker storage station is equipped with a cooling module, a temperature sensor, and a marker storage tank. The marker storage tank is located on the cooling module, and the temperature sensor is located in the cooling module or between the marker storage tank and the cooling module. The temperature sensor is used to detect the temperature of the marker storage tank, and the cooling module can adjust its cooling power according to the temperature detected by the temperature sensor.

12. The space multi-omics experimental system according to claim 10, characterized in that: The gun head storage station is equipped with a gun head storage box. The gun head storage box has two layers of gun head fixing holes along the axial direction of the gun head. The two layers of gun head fixing holes are arranged one-to-one. The gun head is inserted into the upper gun head fixing hole, and the lower gun head fixing hole is used to collect the liquid dripping from the gun head.

13. The space multi-omics experimental system according to claim 12, characterized in that: The gun head storage box includes a main body and a base. The gun head fixing hole is provided in the main body. The base is provided with a first positioning structure. The main body is provided with a second positioning structure corresponding to the first positioning structure. The first positioning structure and the second positioning structure are plugged into each other. The main body and the base are detachably connected. The bottom of the main body is provided with at least two working holes along the horizontal direction. The two working holes are used for the insertion of the fork arm of the work vehicle.

14. The space multi-omics experimental system according to claim 1, characterized in that: The robot includes a first mobile arm, which has a liquid injection structure. The first mobile arm is used to drive the liquid injection structure to move and add markers.

15. The space multi-omics experimental system according to claim 1, characterized in that: The robot also includes a second mobile arm, which is equipped with grippers.

16. The space multi-omics experimental system according to claim 15, characterized in that: The second mobile arm is provided with at least one of a visual alignment module and a laser ranging module. The visual alignment module and / or the laser ranging module are positioned toward the gripper. The visual alignment module and / or the laser ranging module are used to locate the movement of the second mobile arm.

17. The space multi-omics experimental system according to claim 1, characterized in that: The robot also includes a third mobile arm, on which a microscope module is mounted.

18. The space multi-omics experimental system according to claim 1, characterized in that: The robot also includes a fourth mobile arm, which is equipped with an electric suction cup.

19. The space multi-omics experimental system according to claim 1, characterized in that: The space multi-omics system also includes an experimental platform, on which the labeling device, the space multi-omics experimental equipment, and the robot are all mounted.

20. The space multi-omics experimental system according to claim 19, characterized in that: The spatial multi-omics experimental system also includes a motion component, which is disposed on the upper surface of the experimental platform and spaced apart from the experimental platform to form an operating space. The robot is movably disposed on the motion component and can move within the operating space.

21. The space multi-omics experimental system according to claim 20, characterized in that: The motion component includes a support, a guide rail, a transmission component, and a drive component. The support is disposed on the upper surface of the experimental platform, the guide rail is disposed in the support, the transmission component is disposed along the extension direction of the guide rail, the transmission component connects the drive component and the robot, and the drive component is used to drive the transmission component to move the robot along the guide rail.

22. The space multi-omics experimental system according to claim 19, characterized in that: The space multi-omics experimental system also includes a recycling station located at the edge of the experimental platform, which is used to recycle the marking device after use.

23. The space multi-omics experimental system according to claim 22, characterized in that: The recycling station is equipped with a recycling container, which is located below the experimental platform, with the opening of the recycling container protruding from the edge of the experimental platform.

24. The space multi-omics experimental system according to claim 23, characterized in that: The spatial multi-omics experimental system also includes a guide groove, which is disposed on the edge of the experimental platform corresponding to the recovery container, and the guide groove is inclined toward the opening of the recovery container.

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