WO2024087105A1 - 自动化片材操作设备及其使用方法、和空间组学分析系统 - Google Patents
自动化片材操作设备及其使用方法、和空间组学分析系统 Download PDFInfo
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- WO2024087105A1 WO2024087105A1 PCT/CN2022/127984 CN2022127984W WO2024087105A1 WO 2024087105 A1 WO2024087105 A1 WO 2024087105A1 CN 2022127984 W CN2022127984 W CN 2022127984W WO 2024087105 A1 WO2024087105 A1 WO 2024087105A1
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- sheet
- suction cup
- cover sheet
- carrier
- cover
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- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000004458 analytical method Methods 0.000 title claims abstract description 10
- 238000012546 transfer Methods 0.000 claims abstract description 44
- 239000012636 effector Substances 0.000 claims abstract description 24
- 239000000463 material Substances 0.000 claims description 41
- 238000001179 sorption measurement Methods 0.000 claims description 20
- 230000033001 locomotion Effects 0.000 claims description 7
- 238000007789 sealing Methods 0.000 claims description 6
- 230000000717 retained effect Effects 0.000 claims description 3
- 238000005842 biochemical reaction Methods 0.000 description 18
- 239000012472 biological sample Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000000018 DNA microarray Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 101000827703 Homo sapiens Polyphosphoinositide phosphatase Proteins 0.000 description 1
- 102100023591 Polyphosphoinositide phosphatase Human genes 0.000 description 1
- 101100233916 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR5 gene Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
- C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
Definitions
- Embodiments of the present disclosure generally relate to the field of biochemical technology, and more specifically, to an automated sheet handling device that is at least capable of automatically covering and taking sheets, and to a method for using the automated sheet handling device and a spatial omics analysis system including the automated sheet handling device.
- coverslip machines on the market mainly perform unilateral coverslip operations on tissues, without considering the automated application of slides of different sizes and subsequent biochemical processes. They cannot adapt to the development of subsequent automated full-processes for different biochemical reactions, resulting in increased usage costs and risks, and a complicated process.
- the present disclosure is proposed to overcome at least one of the above and other problems and drawbacks of the prior art.
- an embodiment provides an automated sheet handling device, comprising: a first drive device; and a terminal actuator, which is installed to be moved by the first drive device to transfer sheets between a sheet handling station and a non-operating station, the sheets comprising at least one of a carrier and a cover sheet, wherein at the sheet handling station, the terminal actuator can be driven to automatically perform the following operations: sealing a cover sheet on the carrier; and detaching a cover sheet from the carrier.
- the automated sheet material handling device further comprises: a second driving device connected to the terminal actuator to drive the terminal actuator to perform the operation.
- the automated sheet material handling device further comprises: a mounting assembly detachably connected to the first drive device, and the second drive device is fixedly mounted to the mounting assembly.
- the mounting assembly includes: a vertical mounting shaft, which is detachably connected to the mounting end of the first drive device; an adapter plate, which is horizontally connected to the mounting shaft; and a first mounting plate, which is vertically connected to the adapter plate, the second drive device is mounted to the first mounting plate on one side of the first mounting plate, and the terminal actuator is connected to the second drive device on the other side opposite to the first mounting plate.
- the second driving device includes a motor
- the terminal effector includes a suction cup assembly rotatably connected to the motor in a cantilever form.
- the suction cup assembly is configured to: be driven by the motor to rotate in a first rotational direction to seal the cover sheet on the carrier; and be driven by the motor to rotate in an opposite second rotational direction to detach the cover sheet from the carrier.
- the suction cup assembly is rotatably connected to the motor via a shaft.
- the suction cup assembly includes at least one suction cup capable of vacuum-adsorbing a slide and a cover slip.
- the at least one suction cup is configured to perform at least one of the following operations: adsorbing the carrier and being moved by the first driving device to transfer and place the adsorbed carrier to the sheet operating station; adsorbing the cover sheet and being moved by the first driving device to transfer the adsorbed cover sheet to the sheet operating station so that the adsorbed cover sheet is located directly above the carrier; being moved downward by the first driving device and driven by the motor to seal the adsorbed cover sheet on the carrier located at the second sheet operating station; adsorbing the sealed carrier and cover sheet and being moved by the first driving device to transfer the sealed carrier and cover sheet to another operating station for photographing; being moved by the first driving device to transfer the sealed carrier and cover sheet from the other operating station to the sheet operating station; and adsorbing the cover sheet and being driven by the motor at the sheet operating station to detach the cover sheet from the carrier.
- the at least one suction cup includes: a first suction cup; a second suction cup; and a mounting bracket connected to the motor, and the first suction cup and the second suction cup are fixed to the mounting bracket at intervals in a first horizontal direction to adsorb different positions of the cover sheet or the carrier sheet.
- the first suction cup and/or the second suction cup can be replaced by suction cups having different sizes.
- the first suction cup and the second suction cup are installed so that at least their suction surfaces are lower than the lowermost end of the mounting bracket.
- the first suction cup and the second suction cup are further installed so that: in an initial state, the first adsorption surface of the first suction cup is positioned lower than the second adsorption surface of the second suction cup, and there is a height difference in the vertical direction between the first adsorption surface and the second adsorption surface; and in the operation of covering the cover sheet, after the first adsorption surface contacts and adsorbs the cover sheet, the second adsorption surface contacts the cover sheet by rotating the suction cup assembly along the first rotation direction by the motor.
- the suction cup assembly is configured to: in an operation of "sealing a cover sheet on a carrier", the motor is rotated along the first rotation direction to cause the cover sheet to be sealed on the carrier in a manner of pressing from one side of the carrier to the other side in the first direction, while at least partially squeezing out the air between the carrier and the cover sheet; and in an operation of "detaching the cover sheet from the carrier", the first driving device is rotated while the first suction cup and the second suction cup are adsorbing the cover sheet to cause the cover sheet to be partially separated from the carrier, and then the motor is rotated along the second rotation direction to detach the cover sheet from the carrier.
- the mounting bracket includes a vertically positioned second mounting plate, the first suction cup and the second suction cup are mounted to the second mounting plate, and the second mounting plate has: a lower surface, which extends obliquely from a first side edge close to the first suction cup to a second side edge close to the second suction cup, and is positioned to be higher than the first adsorption surface and the second adsorption surface so as not to contact the sheet during the operation of the first suction cup and the second suction cup adsorbing the sheet.
- the lower surface comprises an inclined surface or a curved surface.
- the mounting bracket includes a pair of second mounting plates spaced apart in a second horizontal direction perpendicular to the first direction, and the first suction cup and the second suction cup are mounted between the pair of second mounting plates.
- the first drive device is configured to perform at least one of the following operations: move the terminal actuator holding the carrier to transfer and place the held carrier to the sheet operation station; move the terminal actuator holding the cover sheet to transfer the held cover sheet to the sheet operation station so that the held cover sheet is located directly above the carrier; move the terminal actuator downward to cover the held cover sheet on the carrier located at the sheet operation station; move the terminal actuator holding the carrier and cover sheet sealed together to transfer the sealed carrier and cover sheet to another operation station for photographing; move the terminal actuator holding the carrier and cover sheet sealed together to transfer the sealed carrier and cover sheet from the other operation station to the sheet operation station; and at the sheet operation station, move the terminal actuator holding the cover sheet to detach the cover sheet from the carrier.
- the first driving device includes a manipulator, a multi-degree-of-freedom motion module, or a motor.
- an embodiment further provides a spatial omics analysis system, which includes the automated sheet material manipulation device described in any embodiment of the present disclosure.
- an embodiment also provides a method for operating a sheet using the automated sheet handling device described in any embodiment of the present disclosure, comprising driving the terminal actuator to perform at least one of the following operations: sealing a cover sheet on a carrier; and detaching a cover sheet from the carrier.
- the operation of "sealing a cover sheet on a carrier” includes the following steps: holding the carrier by the terminal actuator, and moving the terminal actuator by the first driving device to transfer and place the held carrier to the sheet operation station; holding the cover sheet by the terminal actuator, and moving the terminal actuator by the first driving device to transfer the held cover sheet to the sheet operation station so that the held cover sheet is located directly above the carrier; and moving the terminal actuator by the first driving device or rotating the terminal actuator along the first rotation direction by the second driving device.
- a terminal actuator is used to seal the retained cover sheet on the carrier located at the sheet operation station; the operation of "detaching the cover sheet from the carrier" includes: at the sheet operation station, while the cover sheet is held by the terminal actuator, the first drive device rotates the terminal actuator to cause the cover sheet to be partially separated from the carrier; and the first drive device moves the terminal actuator horizontally or vertically, or the second drive device rotates the terminal actuator in an opposite second rotation direction, or moves the terminal actuator horizontally or vertically, to detach the cover sheet from the carrier.
- the method further includes: the terminal actuator holds the carrier and cover sheet sealed together and moves the terminal actuator by the first drive device to transfer the carrier and cover sheet sealed together to another operating station for photographing; and after photographing, the terminal actuator holds the carrier and cover sheet sealed together and moves the terminal actuator by the first drive device to transfer the carrier and cover sheet sealed together from the other operating station to the sheet operating station.
- FIG. 1 is a perspective view schematically showing the structure of an automated sheet handling apparatus according to an exemplary embodiment of the present disclosure
- FIG. 2 is a side perspective view schematically showing the structure of a portion of an automated sheet handling device according to an exemplary embodiment of the present disclosure
- FIG3 is another side perspective view schematically showing the structure of a portion of the automated sheet handling device according to an exemplary embodiment of the present disclosure
- FIG4 is a side perspective view schematically showing the structure of a suction cup assembly according to an exemplary embodiment of the present disclosure
- FIG. 5 is a side view schematically showing the structure of a suction cup assembly according to an exemplary embodiment of the present disclosure, wherein a suction cup mounting plate on one side is removed;
- FIG6 is another side perspective view schematically showing the structure of a suction cup assembly according to an exemplary embodiment of the present disclosure
- FIG. 7A is a flow chart schematically illustrating a method of operating a sheet using an automated sheet operating device according to an exemplary embodiment of the present disclosure.
- FIG. 7B is a flow chart schematically illustrating a method of operating a sheet using an automated sheet operating device according to another exemplary embodiment of the present disclosure.
- an automated sheet material handling device which can replace manual labor to automatically perform the operation of covering and removing sheets, so as to adapt to the whole process of biochemical reaction automation with different needs or different sizes.
- the automated sheet material handling device 100 mainly includes a first drive device 110 and a terminal actuator 120, and the first drive device 110 can drive the terminal actuator 120 to move or move, so as to automatically or controllably transfer sheets between sheet material operation stations and non-operation stations.
- the sheet material described may include a slide 10 and a cover sheet 11, and the chip 1 carrying the biological sample can be positioned (e.g., fitted or fixed) on the slide.
- the sheet material includes, but is not limited to, a glass slide (e.g., a glass plate), a plastic sheet, or other suitable carrier forms.
- a glass slide e.g., a glass plate
- plastic sheet or other suitable carrier forms.
- cover sheet 11 In the field of biochemical technology, it is usually necessary to cover the cover sheet 11 on the slide 10 carrying the chip 1, so that the chip and the biological sample thereon can be protected, and used for subsequent various operations, such as taking pictures or performing biochemical reactions of biological samples.
- the cover sheet and the slide may be different in shape, size/dimension, material, etc.
- the cover sheet may be larger than the slide, or the cover sheet may be smaller than the slide, which can be selected according to the specific operation application.
- the terminal actuator 120 can be operated or driven to at least automatically perform the operations of covering the cover sheet 11 on the carrier 10 (which can be simply referred to as “covering the sheet”), and detaching or removing the cover sheet 11 from the carrier 10 (which can be simply referred to as “taking the sheet”).
- covering the sheet 11 on the carrier 10 which can be simply referred to as "covering the sheet”
- taking the sheet detaching or removing the cover sheet 11 from the carrier 10
- This can ensure the continuity of the biochemical reaction and achieve the purpose of low cost and high efficiency. Combined with the function of transporting the sheet, it can adapt to different biochemical reaction automation processes.
- the automated sheet handling device 100 can be used as a component of a system for performing spatial omics sequencing or analysis, such as performing the function of a coverslip machine, such as performing a coverslip operation on a slide after the biological sample on the chip is stained, and can also perform an operation of removing or removing the coverslip after subsequent operations such as taking pictures are completed.
- the sheet handling station can include a stage or a workbench.
- a spatial omics sequencing or analysis system may include equipment such as a space-time integrated machine, an automated sheet handling equipment, and an imaging device such as a microscope; illustratively, incubation, permeabilization, reverse transcription, tissue removal, product recovery and other biochemical reactions may be performed in equipment such as a space-time integrated machine, and a slide carrying a biochip may flow out from its unloading station, and then the automated sheet handling equipment may transfer the slide to its sheet handling station, seal a cover slip on the slide, and then the automated sheet handling equipment may transfer the sealed slides and cover slips to a photographing station of an imaging device; after the photographing is completed, the automated sheet handling equipment may transfer the sealed slides and cover slips back to its sheet handling station, remove the cover slip, and then transfer the slide carrying the biochip back to the unloading station of the space-time integrated machine for subsequent biochemical reactions.
- equipment such as a space-time integrated machine
- an automated sheet handling equipment may transfer the slide to its sheet handling station, seal a cover slip on the slide
- the first drive device 110 for driving the terminal actuator 120 to transfer sheets between different workstations may include a (such as a multi-axis) manipulator, a multi-degree-of-freedom (XYZ) motion module or a motor.
- a multi-axis such as a multi-axis
- XYZ multi-degree-of-freedom
- the multi-degree-of-freedom motion module or linear motor can be installed between the workstations or automation equipment used in the previous and next processes, which can optimize its floor space and usage.
- the automated sheet handling device may also include a second driving device 130, which is connected to the terminal actuator 120 and is used to drive the terminal actuator 120 to perform the operations of "covering sheets" and "taking sheets".
- the second driving device 130 drives the terminal actuator 120 to cover the cover sheet 11 on the carrier 10 carrying the chip 1 thereon.
- Relevant biochemical reagents such as glycerol may be added to the carrier to achieve a seal between the cover sheet and the carrier.
- the first driving device 110 drives the terminal actuator 120 to move the sealed carrier 10 and cover sheet 11 to the sheet operation station, and then the second driving device 130 drives the terminal actuator 120 to remove or detach the cover sheet 11 from the carrier 10.
- the second driving device 130 can be controlled to drive the terminal actuator 120 by the controller 140.
- the controller 140 can be a component of the spatial omics analysis system or a separate device.
- the movement of the first driving device 110 itself and/or the driving of the terminal actuator 120 can also be controlled by the controller 140 or other control devices.
- the automated sheet material handling device 100 further includes or is provided with a mounting assembly 150, which can be detachably or fixedly connected to the first drive device 110, and the second drive device 130 can also be detachably or fixedly mounted to the mounting assembly 150, so as to be fixed relative to the mounting assembly 150 and thus relative to the first drive device 110, the terminal actuator 120 is connected to the second drive device 130 to be driven thereby, and the first drive device 110 moves the mounting assembly 150 and thus moves the terminal actuator 120 to transfer between different stations.
- the terminal actuator can be connected to the first drive device and the second drive device through different mounting structures.
- the mounting assembly 150 mainly includes a mounting shaft 151, an adapter plate 152, and a first mounting plate 153.
- the mounting shaft 151 may extend vertically and, for example, be detachably connected to the mounting end 111 of the first drive device 110.
- the adapter plate 152 may extend horizontally and be connected to the mounting shaft 151, and the first mounting plate 153 is vertically connected to the adapter plate 152.
- the second drive device 130 is mounted or fixed to the first mounting plate 153 on one side, and the end effector 120 is connected to the second drive device 130 in a cantilevered manner on the other side opposite to the first mounting plate 153.
- the form and connection method of the mounting assembly shown in the figure are merely examples, but the present disclosure is not limited thereto.
- the mounting assembly may be formed in the form of other mounting components other than a shaft or a plate, or the first mounting plate may be directly connected to the mounting shaft, or the end effector and the second drive device may be located on the same side of the first mounting plate.
- the second drive device 130 may include a motor, such as a servo motor or a stepper motor, and the terminal actuator 120 may include a suction cup assembly for sucking or removing the sheet according to the operation requirements; as described below, the suction cup assembly may be rotatably connected to the motor or may be rotated by the motor to perform the above-mentioned operations such as covering the sheet, taking the sheet or transferring the sheet.
- a motor such as a servo motor or a stepper motor
- the terminal actuator 120 may include a suction cup assembly for sucking or removing the sheet according to the operation requirements; as described below, the suction cup assembly may be rotatably connected to the motor or may be rotated by the motor to perform the above-mentioned operations such as covering the sheet, taking the sheet or transferring the sheet.
- the automated sheet handling equipment may also include, for example, other standard movable parts or drive devices mounted to the terminal actuator, such as a pneumatic slide, an electric slide, a pneumatic clamp, an electric clamp, etc.; the slide may realize movement along one or more axes to cope with interference with the movement of the first drive device or working conditions that require precise control; a pneumatic or electric slide may be selected according to the application; the use of the clamp may complete the action of grabbing and releasing the target component (for example, when the suction cup cannot meet the corresponding action).
- other standard movable parts or drive devices mounted to the terminal actuator such as a pneumatic slide, an electric slide, a pneumatic clamp, an electric clamp, etc.
- the slide may realize movement along one or more axes to cope with interference with the movement of the first drive device or working conditions that require precise control
- a pneumatic or electric slide may be selected according to the application
- the use of the clamp may complete the action of grabbing and releasing the target component (for example, when the suction cup cannot meet the
- the suction cup assembly can be driven by a motor to rotate in a first rotational direction (such as clockwise or counterclockwise) to press or seal the cover sheet on the carrier, and can be driven by a motor to rotate in an opposite second rotational direction (such as counterclockwise or clockwise) to remove or detach the cover sheet from the carrier.
- a motor to rotate in a first rotational direction (such as clockwise or counterclockwise) to press or seal the cover sheet on the carrier
- an opposite second rotational direction such as counterclockwise or clockwise
- the end effector 120 or the suction cup assembly may be rotatably connected to the second driving device 130 or the motor via a shaft 154.
- the shaft 154 and the output shaft of the motor may be connected by means of a coupling 155.
- the suction cup assembly includes at least one suction cup capable of vacuum adsorbing the carrier and the cover sheet.
- the automated sheet handling device or the spatial omics analysis system may include or be provided with a vacuum generator, which is connected to the suction cup through a suction tube to provide vacuum adsorption force as needed.
- the terminal effector 120 or the suction cup of the suction cup assembly can be used to perform one or more operations on the sheet, including but not limited to:
- the second driving device 130 or its motor is driven (e.g., rotated around a horizontal axis) to press or seal the held or adsorbed cover sheet 11 on the slide 10 located at the sheet operation station; alternatively, in other examples, the first driving device 110 can continuously move the terminal actuator 120 or suction cup downward to seal the held or adsorbed cover sheet 11 on the slide 10 located at the sheet operation station; thus, automatically covering the sheet for sheet transportation and subsequent microscope photography can further reduce the time that the biological sample on the chip is in contact with the air, thereby reducing the risk of deterioration of related biochemical reactions;
- the first driving device 110 moves to transfer the carrier sheet 10 and the cover sheet 11 sealed together from other operating stations to the sheet material operating station;
- the cover sheet 11 is held or adsorbed and driven by the second drive device 130 or its motor (such as moving sideways or rotating) to separate the cover sheet 11 from the carrier 10; alternatively, in other examples, the terminal actuator 120 or suction cup that holds or adsorbs the cover sheet 11 can be driven by the first drive device 110, such as being rotated around a vertical axis and/or being moved sideways or upward to separate the cover sheet 11 from the carrier 10; or alternatively, the first drive device 110 can first move the terminal actuator 120 or suction cup that holds or adsorbs the cover sheet 11 by a certain distance or rotate it around the vertical axis by a certain angle, so that the cover sheet 11 is at least partially separated from the carrier 10, and then the second drive device 130 or its motor moves the cover sheet 11 sideways or rotates it around the horizontal axis, so that the cover sheet 11 is completely separated from the carrier 10, and finally the first drive device 110 moves the terminal actuator 120 or suction cup and the cover sheet 11 held or adsorbed upward or side
- the provided automated sheet handling equipment can realize automatic "covering the sheet” and “taking the sheet” operations, thereby ensuring the continuity of the reaction, reducing the complexity of the experimental operation, and being adaptable to different biochemical reaction automation processes.
- the terminal actuator 120 or the suction cup assembly includes a first suction cup 121, a second suction cup 122 and a mounting bracket, and the mounting bracket is connected to the second drive device 130 or the motor, for example, through a rotating shaft 154, and the first suction cup 121 and the second suction cup 122 are spaced apart in a horizontal first direction Y and are detachably fixed to the mounting bracket, so that different positions of the cover sheet or the carrier can be adsorbed.
- the mounting bracket may include a second mounting plate 123, the second mounting plate 123 may be vertically positioned and fixed to the rotating shaft 154, the first suction cup 121 and the second suction cup 122 are mounted to the second mounting plate 123, so that the second driving device 130 or the motor can drive the mounting bracket and the first suction cup 121 and the second suction cup 122 mounted thereon to move or rotate accordingly by driving or rotating the rotating shaft 154.
- the mounting bracket may include a pair of second mounting plates 123 spaced apart in a horizontal second direction X perpendicular to the first direction Y, and the first suction cup 121 and the second suction cup 122 are mounted between the pair of second mounting plates 123 via a partition 124.
- the form and connection method of the mounting bracket shown in the figure are merely examples, but the present disclosure is not limited thereto.
- the mounting bracket may be formed in the form of other mounting components other than the plate.
- first suction cup 121 and/or the second suction cup 122 can be replaced by suction cups or sheet holding devices of different sizes to meet the operational requirements for sheets of different sizes and can take into account the processing of samples of different sizes and multiple specifications.
- the first suction cup 121 and/or the second suction cup 122 may be installed so that at least their suction surfaces or suction heads are exposed from the mounting bracket in the vertical direction below the lowest end or the lowest part of the mounting bracket or the second mounting plate 123, so as to avoid any part of the mounting bracket from contacting or interfering with the sheet material during operation.
- the second mounting plate 123 has a lowest surface or lower surface 1231, and the lower surface 1231 is positioned higher than the first suction surface 1211 of the first suction cup 121 and the second suction surface 1221 of the second suction cup 122, so as not to contact the sheet material during the operation of the first suction cup 121 and the second suction cup 122 sucking the sheet material.
- the first suction cup 121 and the second suction cup 122 can be appropriately installed so that in the initial state (such as the state not being rotated), the first suction surface 1211 of the first suction cup 121 is positioned lower than the second suction surface 1221 of the second suction cup 122, and there is a height difference ⁇ h in the vertical direction Z between the first suction surface 1211 and the second suction surface 1221, as shown in FIG5.
- the first suction cup 121 and the second suction cup 122 can be driven to contact the sheet material in sequence by driving the suction cup assembly to rotate around the horizontal axis.
- the second suction surface 1221 of the second suction cup 122 can be driven to contact the cover sheet 11 by the second driving device 130 or the motor driving the suction cup assembly to rotate around the horizontal axis along the first rotation direction.
- the first suction cup 121 and the second suction cup 122 can be connected to a vacuum generator (not shown) through different suction pipes 125 and 126, respectively. Activating the vacuum generator can make the first suction cup 121 and the second suction cup 122 contacting the sheet material suck the sheet material simultaneously or at different times.
- the lower surface 1231 of the second mounting plate 123 extends obliquely from the first side 1232 close to the first suction cup 121 to the second side 1233 close to the second suction cup 122, such as bending upward, so that the first adsorption surface 1211 of the first suction cup 121 and the second adsorption surface 1221 of the second suction cup 122 are both lower than the lower surface 1231 in the vertical direction or exposed from the lower surface 1231, so as to contact and adsorb the sheet.
- the lower surface 1231 may include an inclined surface or a curved surface (such as an arc surface).
- the second driving device 130 or the motor drives the terminal actuator 120 or the suction cup assembly to rotate around the horizontal axis along the first rotation direction, for example, the first suction cup 121 and the second suction cup 122 successively contact and adsorb the cover sheet 11, and appropriately press the cover sheet 11, so that the held or adsorbed cover sheet can be pressed or capped on the carrier 10 in a manner of pressing from one side of the carrier 10 to the other side in the first direction Y, and at least partially squeeze out excess air between the carrier and the cover sheet; and in the operation of detaching the cover sheet 11 from the carrier 10, the first driving device 110 drives the suction cup assembly to rotate a certain angle while the first suction cup 121 and the second suction cup 122 adsorb the cover sheet 11, so as to cause the cover sheet 11 to be partially separated from the carrier 10, and then the second driving device 130 or the motor rotates in the opposite second rotation direction to detach the cover sheet 11 from the carrier 10,
- the spatial omics analysis system itself or a separately arranged imaging device (not shown) can take a photo or image the biological samples (including but not limited to pathological samples, tissue samples, cell samples, etc., for example, tissue sections, pathological sections, etc.) on the chip carried by the slide. After the chip is photographed or imaged, the automated sheet handling device can move the coverslips and slides covered in some places back to the aforementioned sheet handling station for sheet removal operation, or transfer them to other stations for subsequent biochemical reactions.
- the biological samples including but not limited to pathological samples, tissue samples, cell samples, etc., for example, tissue sections, pathological sections, etc.
- a method for automatically operating a sheet using the described automated sheet operating device wherein a driving terminal actuator automatically performs the operations of capping a cover sheet on a slide and detaching the cover sheet from the slide.
- FIG7A shows a schematic flow of a "covering sheet” operation
- FIG7B shows a schematic flow of a "taking sheet” operation.
- the operation of “sealing a coverslip on a slide” may include the following steps:
- the carrier sheet 10 is held by the terminal actuator 120, and the first driving device 110 moves the terminal actuator 120 to transfer and place the held carrier sheet 10 to the sheet material operation station;
- the cover sheet 11 is held by the terminal actuator 120, and the first driving device 110 moves the terminal actuator 120 to transfer the held cover sheet 11 to the sheet operation station, so that the held cover sheet 11 is located directly above the carrier sheet 10; and
- the first driving device 110 moves the terminal actuator 120 or the second driving device 130 rotates the terminal actuator 120 along the first rotation direction to cover the retained cover sheet 11 on the carrier sheet 10 located at the sheet operation station;
- the sealed carrier 10 and cover sheet 11 can be maintained by the terminal actuator 120, and the first driving device 110 can move the terminal actuator 120 to transfer the sealed carrier 10 and cover sheet 11 to a subsequent workstation for chip photography or other subsequent biochemical reactions.
- the sealed slide 10 and cover sheet 11 can be held by the terminal actuator 120 in step S20, and in step S21, the first driving device 110 moves the terminal actuator 120 to move the sealed slide 10 and cover sheet 11 from other workstations back to the sheet material operation station, and then perform the operation of "detaching the cover sheet from the slide".
- the operation of "detaching the cover sheet from the slide” may include:
- the first driving device 110 or the second driving device 130 drives the end effector 120 to rotate or move a certain angle around the vertical axis, so as to partially separate the cover sheet 11 from the carrier sheet 10;
- the first driving device 110 moves the terminal actuator 120 horizontally or vertically, or the second driving device 130 drives the terminal actuator 120 to rotate around the horizontal axis in the opposite second rotation direction, or to move horizontally or vertically, so as to detach the cover sheet 11 from the carrier sheet 10.
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- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
一种自动化片材操作设备及其使用方法和空间组学分析系统。自动化片材操作设备（100）包括:第一驱动装置（110）和终端执行器（120），其被安装成由第一驱动装置（110）移动，以在片材操作工位和非操作工位之间转移片材，片材包括载片（10）和盖片（11）中的至少一个，其中在片材操作工位处，终端执行器能够被驱动以自动地执行在载片（10）上封盖盖片（11）和从载片（10）上脱离盖片（11）的操作。
Description
本公开的实施例一般地涉及生化技术领域，并且更具体地，涉及自动化片材操作设备，其至少能够自动地盖片材和取片材，并涉及自动化片材操作设备的使用方法和包括该自动化片材操作设备的空间组学分析系统。
在生化技术领域中，通常在特定生化反应技术环境下需要对载玻片上带组织的芯片进行盖玻片的操作，以便随后进行显微镜拍照流程。在常规技术中，对拥有生物组织样本的玻片的处理中，通常通过人工来盖玻片，且不能自动地移除玻片。
目前市场上的封片机主要是针对组织进行单方面的封片操作，没有考虑不同尺寸的载玻片及后续生化流程的自动化应用，不能适配后续不同生化反应的自动化全流程的开发，导致使用成本和风险增加，且过程复杂。
发明内容
为了克服现有技术存在的上述和其它问题和缺陷中的至少一种，提出了本公开。
在本公开的一个方面中，实施例提供了一种自动化片材操作设备，包括：第一驱动装置；和终端执行器，其被安装成由所述第一驱动装置移动，以在片材操作工位和非操作工位之间转移片材，所述片材包括载片和盖片中的至少一个，其中在所述片材操作工位处，所述终端执行器能够被驱动以自动地执行下述操作：在载片上封盖盖片；和从载片上脱离盖片。
在一些实施例中，自动化片材操作设备还包括：第二驱动装置，其连接至所述终端执行器，以驱动所述终端执行器执行所述操作。
在一些实施例中，自动化片材操作设备还包括：安装组件，其可拆卸地连接至所述第一驱动装置，所述第二驱动装置固定地安装至所述安装组件。
在一些实施例中，所述安装组件包括：竖直的安装轴，其可拆卸地连接至所述第一驱动装置的安装端；转接板，其水平地连接至所述安装轴；和第一安 装板，其竖直地连接至所述转接板，所述第二驱动装置在所述第一安装板的一侧安装至所述第一安装板，并且所述终端执行器在所述第一安装板的相反的另一侧连接至所述第二驱动装置。
在一些实施例中，所述第二驱动装置包括电机，所述终端执行器包括以悬臂形式可转动地连接至所述电机的吸盘组件。
在一些实施例中，所述吸盘组件被配置成：由所述电机驱动以沿第一旋转方向转动，以将盖片封盖在载片上；以及由所述电机驱动以沿相反的第二旋转方向转动，以从载片上脱离盖片。
在一些实施例中，所述吸盘组件通过转轴可转动地连接至所述电机。
在一些实施例中，吸盘组件包括能够真空吸附载片和盖片的至少一个吸盘。
在一些实施例中，所述至少一个吸盘被配置成执行下述操作中的至少一种：吸附载片并被所述第一驱动装置移动，以将所吸附的载片转移并放置到所述片材操作工位；吸附盖片并被所述第一驱动装置移动，以将所吸附的盖片转移到所述片材操作工位处，使得所吸附的盖片位于所述载片的正上方；被所述第一驱动装置向下移动，并被所述电机驱动以将所吸附的盖片封盖在位于所述片材操作二工位处的载片上；吸附封盖在一起的载片和盖片并被所述第一驱动装置移动，以将封盖在一起的载片和盖片转移至另一操作工位以用于拍照；由所述第一驱动装置移动，以将封盖在一起的载片和盖片从所述另一操作工位转移至所述片材操作工位；以及在所述片材操作工位处，吸附所述盖片并被所述电机驱动，以使所述盖片从所述载片上脱离。
在一些实施例中，所述至少一个吸盘包括：第一吸盘；第二吸盘；和连接至所述电机的安装支架，所述第一吸盘和第二吸盘在水平的第一方向上间隔开地固定至所述安装支架，以吸附所述盖片或所述载片的不同位置。
在一些实施例中，第一吸盘和/或第二吸盘能够由具有不同尺寸的吸盘替换。
在一些实施例中，所述第一吸盘和第二吸盘被安装成使得至少它们的吸附面低于所述安装支架的最下端。
在一些实施例中，所述第一吸盘和第二吸盘进一步被安装成使得：在初始状态中，所述第一吸盘的第一吸附面定位成低于所述第二吸盘的第二吸附面，在所述第一吸附面和第二吸附面之间在竖直方向上存在高度差；并且在封盖盖片的操作中，在所述第一吸附面接触并吸附所述盖片之后，通过由所 述电机沿所述第一旋转方向转动所述吸盘组件，使第二吸附面接触所述盖片。
在一些实施例中，所述吸盘组件被配置以：在“在载片上封盖盖片”的操作中，由所述电机沿所述第一旋转方向转动，以促使所述盖片以在所述第一方向上从所述载片的一侧压向另一侧的方式封盖在所述载片上，同时至少部分地挤出所述载片和所述盖片之间的空气；以及在“从载片上脱离盖片”的操作中，在所述第一吸盘和第二吸盘吸附所述盖片的状态下由所述第一驱动装置转动，以促使所述盖片与所述载片部分地分离，随后由所述电机沿所述第二旋转方向转动，以将所述盖片从所述载片上脱离。
在一些实施例中，所述安装支架包括竖直地定位的第二安装板，所述第一吸盘和第二吸盘安装至所述第二安装板，并且所述第二安装板具有：下表面，其从靠近所述第一吸盘的第一侧边向靠近所述第二吸盘的第二侧边倾斜地延伸，并定位成高于所述第一吸附面和第二吸附面，以在所述第一吸盘和第二吸盘吸附片材的操作中不接触片材。
在一些实施例中，所述下表面包括斜面或曲面。
在一些实施例中，所述安装支架包括在垂直于所述第一方向的水平的第二方向上间隔开的一对第二安装板，所述第一吸盘和第二吸盘安装在所述一对第二安装板之间。
在一些实施例中，所述第一驱动装置被配置成执行以下操作中的至少一种：移动保持载片的所述终端执行器，以将所保持的载片转移并放置到所述片材操作工位；移动保持盖片的所述终端执行器，以将所保持的盖片转移到所述片材操作工位处，使得所保持的盖片位于所述载片的正上方；向下移动所述终端执行器，以将所保持的盖片盖在位于所述片材操作工位处的载片上；移动保持封盖在一起的载片和盖片的所述终端执行器，以将封盖在一起的载片和盖片转移至另一操作工位以用于拍照；移动保持封盖在一起的载片和盖片的所述终端执行器，以将封盖在一起的载片和盖片从所述另一操作工位转移至所述片材操作工位；以及在所述片材操作工位处，移动保持盖片的所述终端执行器，以使所述盖片从所述载片上脱离。
在一些实施例中，第一驱动装置包括机械手、多自由度运动模块或电机。
在本公开的另一方面中，实施例还提供了空间组学分析系统，其包括在本公开的任一实施例中描述的自动化片材操作设备。
在本公开的又一方面中，实施例还提供了使用在本公开的任一实施例中 描述的自动化片材操作设备操作片材的方法，包括驱动所述终端执行器以执行下述操作中的至少一种：在载片上封盖盖片；和从载片上脱离盖片。
在一些实施例中，“在载片上封盖盖片”的操作包括下述步骤：由所述终端执行器保持载片，并由所述第一驱动装置移动所述终端执行器，以将所保持的载片转移并放置到所述片材操作工位；由所述终端执行器保持盖片，并由所述第一驱动装置移动所述终端执行器，以将所保持的盖片转移到所述片材操作工位处，使得所保持的盖片位于所述载片的正上方；以及由所述第一驱动装置移动所述终端执行器或由第二驱动装置沿第一旋转方向转动所述终端执行器，以将所保持的盖片封盖在位于所述片材操作工位处的载片上；“从载片上脱离盖片”的操作包括：在所述片材操作工位处，在由所述终端执行器保持所述盖片的同时由所述第一驱动装置转动所述终端执行器，以促使所述盖片与所述载片部分地分离；以及由所述第一驱动装置水平地或竖直地移动所述终端执行器，或由第二驱动装置沿相反的第二旋转方向转动、或水平地或竖直地移动所述终端执行器，以将所述盖片从所述载片上脱离。
在一些实施例中，所述方法还包括：由所述终端执行器保持封盖在一起的载片和盖片并由所述第一驱动装置移动所述终端执行器，以将封盖在一起的载片和盖片转移至另一操作工位以用于拍照；以及在拍照之后由所述终端执行器保持封盖在一起的载片和盖片并由所述第一驱动装置移动所述终端执行器，以将封盖在一起的载片和盖片从所述另一操作工位转移至所述片材操作工位。
通过下文中参照附图对本公开所作的详细描述，本公开的其它目的和优点将显而易见，并可帮助对本公开有全面的理解。
通过参考附图能够更加清楚地理解本公开的特征和优点，附图是示意性的而不应理解为对本公开进行任何限制，在附图中：
图1为示意性地示出根据本公开的示例性实施例的自动化片材操作设备的结构的透视图；
图2为示意性地示出根据本公开的示例性实施例的自动化片材操作设备的一部分的结构的侧视透视图；
图3为示意性地示出根据本公开的示例性实施例的自动化片材操作设备的 一部分的结构的另一侧视透视图；
图4为示意性地示出根据本公开的示例性实施例的吸盘组件的结构的侧视透视图；
图5为示意性地示出根据本公开的示例性实施例的吸盘组件的结构的侧视图，其中移除了一侧的吸盘安装板；
图6为示意性地示出根据本公开的示例性实施例的吸盘组件的结构的另一侧视透视图；
图7A为示意性地示出根据本公开的示例性实施例的、使用自动化片材操作设备操作片材的方法的流程图；以及
图7B为示意性地示出根据本公开的另一示例性实施例的、使用自动化片材操作设备操作片材的方法的流程图。
下面将结合本公开实施例中的附图，对本公开实施例中的技术方案进行清楚、完整的描述，显然，所描述的实施例仅仅是本公开一部分实施例，而不是全部的实施例。基于本公开中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本公开保护的范围。
另外，在下面的详细描述中，为便于解释，阐述了许多具体的细节以提供对本公开内容的实施例的全面理解。然而明显地，一个或多个实施例在没有这些具体细节的情况下也可以被实施。在其他情况下，公知的结构和装置以图示的方式体现以简化附图。
根据本公开的示例性实施例提供了自动化的片材操作设备，其可以替代人工来自动地执行盖片材和移除片材的操作，以适配不同需求或不同尺寸的生化反应自动化全流程。如图1-6所示，自动化片材操作设备100主要包括第一驱动装置110和终端执行器120，第一驱动装置110可以驱动终端执行器120移动或运动，以在片材操作工位和非操作工位之间自动地或受控制地转移片材。
在本文中，所描述的片材可以包括载片10和盖片11，携载生物样本的芯片1可以定位(如，贴合或固定)在载片上。片材包括但不限于玻片(如玻璃板)、塑料片或其他合适的载体形式。在生化技术领域，通常需要在承载有芯片1的载片10上封盖盖片11，可以对芯片及其上的生物样本进行保护，并且用于进行后续的多种操作，如拍照或进行生物样本的生化反应。需要说明的是，虽然在图示的 实施例中，盖片与载片具有大致相同的尺寸和形状，但本公开不限于此，在其他实施例中，盖片与载片在形状、大小/尺寸、材质等方面可以不一样，例如盖片可以比载片大，或者盖片可以比载片小，这可以根据具体操作应用来选择。
根据本公开的实施例，在片材操作工位处，终端执行器120能够被操作或驱动，以至少自动地执行在载片10上封盖盖片11(可以简称为“盖片材”)、和从载片10上脱离或取下盖片11(可以简称为“取片材”)的操作，这能够保证生化反应的连贯性，可以实现低成本高效率的目的，结合转运片材的功能，能够适配不同的生化反应自动化全流程。
在一些实施例中，自动化片材操作设备100可以作为用于进行空间组学测序或分析系统的组成部分，如执行封片机的功能，如在芯片上的生物样本被染色之后进行在载片上盖上盖片的封片操作，并且可以在诸如拍照之类的后续操作完成之后还可以执行取下或移除盖片的操作。片材操作工位可以包括载物台或工作台。作为示例，空间组学测序或分析系统可以包括诸如时空一体机之类的设备、自动化片材操作设备、以及诸如显微镜之类的成像设备；说明性地，在诸如时空一体机之类的设备中可以进行孵育、透化、反转录、组织去除、产物回收等生化反应，从其下料二工位流出携载生物芯片的载片，随后自动化片材操作设备可以将载片转移至其片材操作工位，在载片上封盖盖片，之后自动化片材操作设备将封盖在一些的载片和盖片转移至成像设备的拍照工位；在拍照完成之后，由自动化片材操作设备将封盖在一些的载片和盖片转移回到至其片材操作工位，取下盖片，随后将携载生物芯片的载片转移返回至时空一体机的下料工位，以进行后续生化反应。
作为示例，根据不同生化反应自动化流程的场景应用设计，用于驱动终端执行器120在不同工位之间转移片材的第一驱动装置110可以包括(如多轴)机械手、多自由度(XYZ)运动模块或电机，例如可以将多自由度运动模块或直线电机架设于前后两个工序所使用的工位或自动化设备之间，这可以优化其占地面积及使用。
在如图所示的示例性实施例中，除了可以通过第一驱动装置110驱动终端执行器120在不同工位之间转运片材之外，自动化片材操作设备还可以包括第二驱动装置130，第二驱动装置130连接至终端执行器120，用于驱动终端执行器120执行“盖片材”和“取片材”的操作。例如，可以在通过第一驱动装置110驱动终端执行器120将盖片11移动到位于片材操作工位处的载片10上方之后，由第二 驱动装置130驱动终端执行器120以将盖片11封盖在其上承载有芯片1的载片10上。在载片上可以添加由甘油等相关生化试剂，以在盖片与载片之间实现密封。在拍照或其他生化反应之后，通过第一驱动装置110驱动终端执行器120将封盖在一起的载片10和盖片11移动到片材操作工位处，随后由第二驱动装置130驱动终端执行器120以从载片10上取下或脱离盖片11。
如图1-3所示，可以通过控制器140来控制第二驱动装置130对终端执行器120的驱动。控制器140可以是空间组学分析系统的组成部分或是单独设置的。类似地，也可以由控制器140或其他的控制装置来控制第一驱动装置110自身的运动和/或对终端执行器120的驱动。
如图1-4所示，自动化片材操作设备100还包括或设置有安装组件150，安装组件150可以可拆卸地或固定地连接至第一驱动装置110，而第二驱动装置130也可以可拆卸地或固定地安装至安装组件150，以相对于安装组件150并且因此相对于第一驱动装置110是固定的，终端执行器120连接至第二驱动装置130以由其驱动，而第一驱动装置110移动安装组件150并且因此移动终端执行器120在不同工位之间转移。在其他实施例中，终端执行器可以通过不同的安装结构与第一驱动装置和第二驱动装置相连接。
在图示的实施例中，安装组件150主要包括安装轴151、转接板152和第一安装板153。安装轴151可以竖直地延伸并且例如可拆卸地连接至第一驱动装置110的安装端111。转接板152可以水平地延伸并连接至安装轴151，而第一安装板153竖直地连接至转接板152。作为示例，第二驱动装置130在一侧安装或固定至第一安装板153，而终端执行器120在第一安装板153的相反的另一侧以悬臂形式连接至第二驱动装置130。但将会理解，图示的安装组件的形式和连接方式仅仅是示例，但本公开不限于此，在其他示例中，可以由不同于轴或板的其他安装部件的形式来形成安装组件，或者第一安装板可以直接连接至安装轴，或者终端执行器和第二驱动装置可以位于第一安装板的同一侧。
示例性地，第二驱动装置130可以包括电机，如伺服电机或步进电机，而终端执行器120可以包括用于根据操作需要吸附或卸下片材的吸盘组件；如下所述，吸盘组件例如可以可转动地连接至电机或可以由电机转动，以执行上述盖片材、取片材或转移片材等操作。替换地或附加地，自动化片材操作设备还可以包括例如安装至终端执行器的其他标准活动件或驱动装置，如气动滑台、电动滑台、气动夹爪、电动夹爪等；滑台可以实现完成沿一个或更多个轴线的运动，以应 对第一驱动装置的运动存在干扰的情况或需要精密控制的工况；可以根据使用应用情况来选择气动或电动滑台；夹爪的使用可以完成对目标部件的抓取及释放的动作(例如在吸盘无法满足相应动作的情况下)。
在一些实施例中，吸盘组件可以由电机驱动以沿第一旋转方向(如顺时针或逆时针方向)转动，以将盖片压在或封盖在载片上，并且可以由电机驱动以沿相反的第二旋转方向(如逆时针或顺时针方向)转动，以从载片上取下或脱离盖片。
如图1-3所示，终端执行器120或吸盘组件可以通过转轴154可转动地连接至第二驱动装置130或电机。作为示例，可以借助于联轴器155来连接转轴154和电机的输出轴。
示例性地，吸盘组件包括能够真空吸附载片和盖片的至少一个吸盘。虽然未图示，但自动化片材操作设备或空间组学分析系统可以包括或设置有真空发生器，其通过吸管连接至吸盘，以根据需要提供真空吸附力。
在根据本公开的示例性实施例中，终端执行器120或吸盘组件的吸盘可以用于对片材执行一种或更多种操作，包括但不限于：
(1)保持或吸附例如承载有芯片1的载片10，随后由第一驱动装置110驱动或移动，以将所保持或吸附的载片转移并放置到片材操作工位；
(2)保持或吸附盖片11，随后由第一驱动装置110驱动或移动，以将所保持或吸附的盖片11转移到片材操作工位处，使得所保持或吸附的盖片11位于载片10的正上方；
(3)在被第一驱动装置110向下移动到合适的位置后，由第二驱动装置130或其电机驱动(如围绕水平轴线转动)，以将所保持或吸附的盖片11压在或封盖在位于片材操作工位处的载片10上；可替换地，在其他示例中，可以由第一驱动装置110持续向下移动终端执行器120或吸盘，以将其保持或吸附的盖片11封盖在位于片材操作工位处的载片10上；因此自动地盖上片材以用于片材转运及后续显微镜拍照可以进一步地减少芯片上的生物样本与空气接触的时间，降低相关生化反应恶化的风险；
(4)保持或吸附封盖在一起的载片10和盖片11，并被第一驱动装置110移动，以将封盖在一起的载片和盖片转移至其他操作工位，以例如用于芯片的拍照等；
(5)例如在拍照等操作完成之后，由第一驱动装置110移动，以将封盖在 一起的载片10和盖片11从其他操作工位转移至片材操作工位；以及
(6)在片材操作工位处，保持或吸附盖片11并被第二驱动装置130或其电机驱动(如侧向移动或转动)，以使盖片11从载片10上脱离；可替换地，在其他示例中，保持或吸附盖片11的终端执行器120或吸盘可以由第一驱动装置110驱动，如被围绕竖直轴线转动和/或被侧向或向上移动，以使盖片11从载片10上脱离；或者可替换地，可以先由第一驱动装置110将保持或吸附盖片11的终端执行器120或吸盘移动一定距离或围绕竖直轴线转动一定角度，使得盖片11至少部分地与载片10分离，随后由第二驱动装置130或其电机侧向移动或围绕水平轴线转动盖片11，使盖片11完全从载片10上分离，最后由第一驱动装置110向上或侧向地移动终端执行器120或吸盘及其保持或吸附的盖片11，完成取下盖片的动作。
因此，根据本公开的实施例，利用所提供的自动化片材操作设备能够实现自动“盖片材”和“取片材”的操作，保证了反应的连贯性，降低了实验操作复杂性，可以适配不同的生化反应自动化流程。
在示例性实施例中，如图1-6所示，终端执行器120或吸盘组件包括第一吸盘121、第二吸盘122和安装支架，安装支架例如通过转轴154连接至第二驱动装置130或电机，而第一吸盘121和第二吸盘122在水平的第一方向Y上间隔开并可拆卸地固定至安装支架，从而可以吸附盖片或载片的不同位置。
作为示例，安装支架可以包括第二安装板123，第二安装板123可以竖直地定位并固定至转轴154，第一吸盘121和第二吸盘122安装至第二安装板123，因此，第二驱动装置130或电机通过驱动或转动转轴154，可以带动安装支架以及安装在其上的第一吸盘121和第二吸盘122相应地移动或转动。例如，安装支架可以包括在垂直于第一方向Y的水平的第二方向X上间隔开的一对第二安装板123，第一吸盘121和第二吸盘122经由隔板124安装在一对第二安装板123之间。但将会理解，图示的安装支架的形式和连接方式仅仅是示例，但本公开不限于此，在其他示例中，可以由不同于板的其他安装部件的形式来形成安装支架。
在一些实施例中，第一吸盘121和/或第二吸盘122可以由具有不同尺寸的吸盘或片材保持装置替换，以满足对不同尺寸的片材的操作需求，能兼顾不同尺寸、多种规格的样品处理。
如图1和图3-6所示，第一吸盘121和/或第二吸盘122可以被安装成使得至少它们的吸附面或吸头低于安装支架或第二安装板123的最下端或最低部分在竖直方向上从安装支架露出，以避免安装支架的任何部分在操作中接 触或干扰片材。作为示例，第二安装板123具有最低表面或下表面1231，下表面1231定位成高于第一吸盘121的第一吸附面1211和第二吸盘122的第二吸附面1221，从而在第一吸盘121和第二吸盘122吸附片材的操作中不接触片材。
在一些实施例中，可以合适地安装第一吸盘121和第二吸盘122，使得在初始状态(如未被转动的状态)中，第一吸盘121的第一吸附面1211定位成低于第二吸盘122的第二吸附面1221，在第一吸附面1211和第二吸附面1221之间在竖直方向Z上存在高度差Δh，如图5所示。在这种情况下，通过驱动吸盘组件围绕水平轴线转动可以促使第一吸盘121和第二吸盘122依次接触片材。因此，在封盖盖片11的操作中，在第一吸盘121的第一吸附面1211接触或吸附盖片11之后，通过由第二驱动装置130或电机驱动吸盘组件沿第一旋转方向围绕水平轴线转动，可以使第二吸盘122的第二吸附面1221接触盖片11。
第一吸盘121和第二吸盘122可以通过不同的吸管125、126分别地连通至真空发生器(未示出)，启动真空发生器可以使接触片材的第一吸盘121和第二吸盘122同时地或不同时地吸附片材。
如图1-6所示，第二安装板123的下表面1231从靠近第一吸盘121的第一侧边1232向靠近第二吸盘122的第二侧边1233倾斜地延伸，如向上弯曲，使得第一吸盘121的第一吸附面1211和第二吸盘122的第二吸附面1221在竖直方向上都低于下表面1231或从下表面1231露出，以便于接触和吸附片材。作为示例，下表面1231可以包括斜面或曲面(如弧形面)。
在一些示例性实施例中，在在载片10上封盖盖片11的操作中，通过由第二驱动装置130或电机驱动终端执行器120或吸盘组件沿第一旋转方向围绕水平轴线转动，例如由第一吸盘121和第二吸盘122先后接触并吸附盖片11，适当地下压盖片11，可以促使所保持或吸附的盖片以在第一方向Y上从载片10的一侧压向另一侧的方式压在或封盖在载片10上，同时至少部分地挤出载片和盖片之间的多余空气；而在从载片10上脱离盖片11的操作中，在第一吸盘121和第二吸盘122吸附盖片11的状态下由第一驱动装置110驱动吸盘组件转动一定角度，以促使盖片11与载片10部分地分离，随后由第二驱动装置130或电机沿相反的第二旋转方向转动，以将盖片11从载片10上脱离，最后通过第一驱动装置130向上或侧向地移动终端执行器120或吸 盘组件，以最终取下盖片。
在自动化片材操作设备完成“盖片”操作并将封盖在一些的盖片和载片转移至拍照工位或工作台时，例如可以由空间组学分析系统自身的或单独设置的成像装置(未示出)对载片承载的芯片上的生物样本(包括但不限于病理样本、组织样本、细胞样本等，例如，可以是组织切片、病理切片等)进行拍照或成像。在芯片拍照或成像完成之后，自动化片材操作设备可以将封盖在一些的盖片和载片移回到前述片材操作工位进行取片材操作，或转移至其他工位，以进行后续生化反应。
在本公开的实施例中，还提供了采用所描述的自动化片材操作设备自动地操作片材的方法，其中驱动终端执行器自动地执行在载片上封盖盖片和从载片上脱离盖片的操作。图7A示出了“盖片材”操作的示意性流程，图7B示出了“取片材”操作的示意性流程。
在一些实施例中，如图7A所示并参照图1-6，“在载片上封盖盖片”的操作可以包括下述步骤：
S10：由终端执行器120保持载片10，并由第一驱动装置110移动终端执行器120，以将所保持的载片10转移并放置到片材操作工位；
S11：由终端执行器120保持盖片11，并由第一驱动装置110移动终端执行器120，以将所保持的盖片11转移到片材操作工位处，使得所保持的盖片11位于载片10的正上方；以及
S12：由第一驱动装置110移动终端执行器120或由第二驱动装置130沿第一旋转方向转动终端执行器120，以将所保持的盖片11封盖在位于片材操作工位处的载片10上；
可选地，在步骤S13中，可以由终端执行器120保持封盖在一起的载片10和盖片11，并由第一驱动装置110移动终端执行器120，以将封盖在一起的载片10和盖片11转移至后续工位，以用于芯片拍照或其他后续生化反应。
在拍照或其他后续生化反应完成之后，可以在步骤S20中由终端执行器120保持封盖在一起的载片10和盖片11，并在步骤S21中，由第一驱动装置110移动终端执行器120，以封盖在一起的载片10和盖片11从其他工位移回到上述片材操作工位，随后进行“从载片上脱离盖片”的操作。在一些实施例中，如图7B所示并参照图1-6，“从载片上脱离盖片”的操作可以包括：
S22：在片材操作工位处，在由终端执行器120保持盖片11的同时由第 一驱动装置110或第二驱动装置130驱动终端执行器120围绕竖直轴线转动或移动一定角度，以促使盖片11与载片10部分地分离；
S23：由第一驱动装置110水平地或竖直地移动终端执行器120，或由第二驱动装置130驱动终端执行器120沿相反的第二旋转方向围绕水平轴线转动、或水平地或竖直地移动，以将盖片11从载片10上脱离。
根据本公开的示例性实施例，可以实现对生化反应流程中不同尺寸的载片的自动盖片材及取片材，保证了生化反应的连贯性，同时，采用了诸如机械手、电机之类的驱动装置与诸如吸盘组件之类的终端执行器的组合来替代人工，可以实现低成本高效率的目的，并且可以适配不同需求或不同尺寸的生化反应自动化全流程。
尽管已经示出和描述了本公开的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本公开的原理和精神的情况下可以对这些实施例进行变化，本公开的范围由所附权利要求及其等同物限定。
Claims (23)
- 一种自动化片材操作设备，包括：第一驱动装置；和终端执行器，其被安装成由所述第一驱动装置移动，以在片材操作工位和非操作工位之间转移片材，所述片材包括载片和盖片中的至少一个，其中，在所述片材操作工位处，所述终端执行器能够被驱动以自动地执行下述操作：在载片上封盖盖片；和从载片上脱离盖片。
- 根据权利要求1所述的自动化片材操作设备，还包括：第二驱动装置，其连接至所述终端执行器，以驱动所述终端执行器执行所述操作。
- 根据权利要求2所述的自动化片材操作设备，还包括：安装组件，其可拆卸地连接至所述第一驱动装置，其中，所述第二驱动装置固定地安装至所述安装组件。
- 根据权利要求3所述的自动化片材操作设备，其中，所述安装组件包括：竖直的安装轴，其可拆卸地连接至所述第一驱动装置的安装端；转接板，其水平地连接至所述安装轴；和第一安装板，其竖直地连接至所述转接板，所述第二驱动装置在所述第一安装板的一侧安装至所述第一安装板，并且所述终端执行器在所述第一安装板的相反的另一侧连接至所述第二驱动装置。
- 根据权利要求2-4中的任一项所述的自动化片材操作设备，其中，所述第二驱动装置包括电机，所述终端执行器包括以悬臂形式可转动地连接至所述电机的吸盘组件。
- 根据权利要求5所述的自动化片材操作设备，其中，所述吸盘组件被配置成：由所述电机驱动以沿第一旋转方向转动，以将盖片封盖在载片上； 以及由所述电机驱动以沿相反的第二旋转方向转动，以从载片上脱离盖片。
- 根据权利要求6所述的自动化片材操作设备，其中，所述吸盘组件通过转轴可转动地连接至所述电机。
- 根据权利要求6所述的自动化片材操作设备，其中，所述吸盘组件包括能够真空吸附载片和盖片的至少一个吸盘。
- 根据权利要求8所述的自动化片材操作设备，其中，所述至少一个吸盘被配置成执行下述操作中的至少一种：吸附载片并被所述第一驱动装置移动，以将所吸附的载片转移并放置到所述片材操作工位；吸附盖片并被所述第一驱动装置移动，以将所吸附的盖片转移到所述片材操作工位处，使得所吸附的盖片位于所述载片的正上方；被所述第一驱动装置向下移动，并被所述电机驱动以将所吸附的盖片封盖在位于所述片材操作工位处的载片上；吸附封盖在一起的载片和盖片并被所述第一驱动装置移动，以将封盖在一起的载片和盖片转移至另一操作工位以用于拍照；由所述第一驱动装置移动，以将封盖在一起的载片和盖片从所述另一操作工位转移至所述片材操作工位；以及在所述片材操作工位处，吸附所述盖片并被所述电机驱动，以使所述盖片从所述载片上脱离。
- 根据权利要求9所述的自动化片材操作设备，其中，所述至少一个吸盘包括：第一吸盘；第二吸盘；和连接至所述电机的安装支架，所述第一吸盘和第二吸盘在水平的第一方向上间隔开地固定至所述安装支架，以吸附所述盖片或所述载片的不同位置。
- 根据权利要求10所述的自动化片材操作设备，其中，所述第一吸盘和/或第二吸盘能够由具有不同尺寸的吸盘替换。
- 根据权利要求10所述的自动化片材操作设备，其中，所述第一吸盘和第二吸盘被安装成使得至少它们的吸附面低于所述安装支架的最下端。
- 根据权利要求12所述的自动化片材操作设备，其中，所述第一吸盘和第二吸盘进一步被安装成使得：在初始状态中，所述第一吸盘的第一吸附面定位成低于所述第二吸盘的第二吸附面，在所述第一吸附面和第二吸附面之间在竖直方向上存在高度差；并且在封盖盖片的操作中，在所述第一吸附面接触并吸附所述盖片之后，通过由所述电机沿所述第一旋转方向转动所述吸盘组件，使所述第二吸附面接触所述盖片。
- 根据权利要求13所述的自动化片材操作设备，其中，所述吸盘组件被配置以：在“在载片上封盖盖片”的操作中，由所述电机沿所述第一旋转方向转动，以促使所述盖片以在所述第一方向上从所述载片的一侧压向另一侧的方式封盖在所述载片上，同时至少部分地挤出所述载片和所述盖片之间的空气；以及在“从载片上脱离盖片”的操作中，在所述第一吸盘和第二吸盘吸附所述盖片的状态下由所述第一驱动装置转动，以促使所述盖片与所述载片部分地分离，随后由所述电机沿所述第二旋转方向转动，以将所述盖片从所述载片上脱离。
- 根据权利要求13所述的自动化片材操作设备，其中，所述安装支架包括竖直地定位的第二安装板，所述第一吸盘和第二吸盘安装至所述第二安装板，并且所述第二安装板具有：下表面，其从靠近所述第一吸盘的第一侧边向靠近所述第二吸盘的第二侧边倾斜地延伸，并定位成高于所述第一吸附面和第二吸附面，以在所述第一吸盘和第二吸盘吸附片材的操作中不接触片材。
- 根据权利要求15所述的自动化片材操作设备，其中，所述 下表面包括斜面或曲面。
- 根据权利要求15所述的自动化片材操作设备，其中，所述安装支架包括在垂直于所述第一方向的水平的第二方向上间隔开的一对第二安装板，所述第一吸盘和第二吸盘安装在所述一对第二安装板之间。
- 根据权利要求1所述的自动化片材操作设备，其中，所述第一驱动装置被配置成执行以下操作中的至少一种：移动保持载片的所述终端执行器，以将所保持的载片转移并放置到所述片材操作工位；移动保持盖片的所述终端执行器，以将所保持的盖片转移到所述片材操作工位处，使得所保持的盖片位于所述载片的正上方；向下移动所述终端执行器，以将所保持的盖片盖在位于所述片材操作工位处的载片上；移动保持封盖在一起的载片和盖片的所述终端执行器，以将封盖在一起的载片和盖片转移至另一操作工位以用于拍照；移动保持封盖在一起的载片和盖片的所述终端执行器，以将封盖在一起的载片和盖片从所述另一操作工位转移至所述片材操作工位；以及在所述片材操作工位处，移动保持盖片的所述终端执行器，以使所述盖片从所述载片上脱离。
- 根据权利要求1-18中的任一项所述的自动化片材操作设备，其中，所述第一驱动装置包括机械手、多自由度运动模块或电机。
- 一种空间组学分析系统，包括权利要求1-19中的任一项所述的自动化片材操作设备。
- 一种使用权利要求1-19中的任一项所述的自动化片材操作设备操作片材的方法，包括：驱动所述终端执行器以执行下述操作中的至少一种：在载片上封盖盖片；和从载片上脱离盖片。
- 根据权利要求21所述的方法，其中，“在载片上封盖盖片”的操作包括下述步骤：由所述终端执行器保持载片，并由所述第一驱动装置移动所述终端执行器，以将所保持的载片转移并放置到所述片材操作工位；由所述终端执行器保持盖片，并由所述第一驱动装置移动所述终端执行器，以将所保持的盖片转移到所述片材操作工位处，使得所保持的盖片位于所述载片的正上方；以及由所述第一驱动装置移动所述终端执行器或由第二驱动装置沿第一旋转方向转动所述终端执行器，以将所保持的盖片封盖在位于所述片材操作工位处的载片上；并且“从载片上脱离盖片”的操作包括：在所述片材操作工位处，在由所述终端执行器保持所述盖片的同时由所述第一驱动装置转动所述终端执行器，以促使所述盖片与所述载片部分地分离；以及由所述第一驱动装置水平地或竖直地移动所述终端执行器，或由第二驱动装置沿相反的第二旋转方向转动、或水平地或竖直地移动所述终端执行器，以将所述盖片从所述载片上脱离。
- 根据权利要求21或22所述的方法，还包括：由所述终端执行器保持封盖在一起的载片和盖片并由所述第一驱动装置移动所述终端执行器，以将封盖在一起的载片和盖片转移至另一操作工位以用于拍照；以及在拍照之后由所述终端执行器保持封盖在一起的载片和盖片并由所述第一驱动装置移动所述终端执行器，以将封盖在一起的载片和盖片从所述另一操作工位转移至所述片材操作工位。
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009033128A2 (en) * | 2007-09-07 | 2009-03-12 | Biogenex Laboraties Inc | Sample processing system |
| US20190375619A1 (en) * | 2017-02-03 | 2019-12-12 | Brooks Automation, Inc. | A Capping And De-Capping Apparatus And A Method Of Operating Such An Apparatus |
| CN110857181A (zh) * | 2018-08-23 | 2020-03-03 | 达科为（深圳）医疗设备有限公司 | 一种新型智能封片机 |
| CN211784707U (zh) * | 2019-05-24 | 2020-10-27 | 浙江艾明德生物科技有限公司 | 一种全自动封片仪 |
| CN212302063U (zh) * | 2020-07-24 | 2021-01-05 | 杜波 | 一种临床医学检验用载玻片装置 |
| CN214408287U (zh) * | 2020-12-21 | 2021-10-15 | 广东金泉医疗科技有限公司 | 盖玻片装载运输装置及自动封片设备 |
| CN114104737A (zh) * | 2021-12-24 | 2022-03-01 | 达科为（深圳）医疗设备有限公司 | 一种盖玻片吸片装置及其控制方法 |
| CN216880925U (zh) * | 2022-03-24 | 2022-07-05 | 山东第一医科大学(山东省医学科学院) | 一种载玻片清洗装置 |
-
2022
- 2022-10-27 WO PCT/CN2022/127984 patent/WO2024087105A1/zh unknown
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009033128A2 (en) * | 2007-09-07 | 2009-03-12 | Biogenex Laboraties Inc | Sample processing system |
| US20190375619A1 (en) * | 2017-02-03 | 2019-12-12 | Brooks Automation, Inc. | A Capping And De-Capping Apparatus And A Method Of Operating Such An Apparatus |
| CN110857181A (zh) * | 2018-08-23 | 2020-03-03 | 达科为（深圳）医疗设备有限公司 | 一种新型智能封片机 |
| CN211784707U (zh) * | 2019-05-24 | 2020-10-27 | 浙江艾明德生物科技有限公司 | 一种全自动封片仪 |
| CN212302063U (zh) * | 2020-07-24 | 2021-01-05 | 杜波 | 一种临床医学检验用载玻片装置 |
| CN214408287U (zh) * | 2020-12-21 | 2021-10-15 | 广东金泉医疗科技有限公司 | 盖玻片装载运输装置及自动封片设备 |
| CN114104737A (zh) * | 2021-12-24 | 2022-03-01 | 达科为（深圳）医疗设备有限公司 | 一种盖玻片吸片装置及其控制方法 |
| CN216880925U (zh) * | 2022-03-24 | 2022-07-05 | 山东第一医科大学(山东省医学科学院) | 一种载玻片清洗装置 |
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