WO2022262717A1 - 一种确定细胞的迁移能力的方法和系统 - Google Patents

一种确定细胞的迁移能力的方法和系统 Download PDF

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Publication number
WO2022262717A1
WO2022262717A1 PCT/CN2022/098641 CN2022098641W WO2022262717A1 WO 2022262717 A1 WO2022262717 A1 WO 2022262717A1 CN 2022098641 W CN2022098641 W CN 2022098641W WO 2022262717 A1 WO2022262717 A1 WO 2022262717A1
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Prior art keywords
scratch
scratching
cell
cells
image analysis
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PCT/CN2022/098641
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English (en)
French (fr)
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陈燕芳
夏浩涵
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上海睿钰生物科技有限公司
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Publication of WO2022262717A1 publication Critical patent/WO2022262717A1/zh
Priority to US18/540,799 priority Critical patent/US20240124828A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control

Definitions

  • This description relates to the field of biotechnology, in particular to a method and system for determining cell migration ability.
  • Cell migration is closely related to the occurrence and development of cancer, and cell migration ability is one of the main indicators to measure the metastasis ability of cancer cells.
  • the study of cell migration ability on the one hand, can deepen the understanding of cell migration behavior, and on the other hand, it is of great value for the treatment and exploration of cancer and other diseases closely related to cell migration.
  • the cell scratch experiment is one of the common methods to study the ability of cell migration. The manufacture of "scratches", the acquisition of images during cell migration, and the processing and analysis of image data in the later stage are the key steps in the scratch experiment. Therefore, it is desired to provide a method and system for determining cell migration ability, which can ensure the uniform stability of scratches and the reproducibility of scratch experiments, so that the migration ability of cells can be detected efficiently, comprehensively and accurately.
  • a method of determining the migratory capacity of a cell includes: scratching the cells with a cell scratching device to form at least one scratch; and photographing and analyzing the at least one scratch with a cell image analysis device to determine the migration ability of the cells.
  • the photographing and analysis of the at least one scratch by the cell image analysis device to determine the migration ability of the cells includes: performing a photographic analysis of the at least one scratch by the cell image analysis device Positioning and photographing to obtain at least one image of the at least one scratch; and determining the migration ability of the cells based on the at least one image of the at least one scratch.
  • the cell scratching device includes a culture part and a scratch part
  • the culture part is used for culturing the cells
  • the scratch part includes a scratch cover and a scratch piece
  • the cover plate includes a bottom plate, a connecting piece and a limiting structure connected in sequence, the bottom plate and the limiting structure are respectively located at two ends of the connecting piece, and the bottom plate is provided with at least one scratch gap.
  • the scratching operation on the cells by using the cell scratching device to form at least one scratch includes: fixing the scratch cover on the culture part through the limiting structure; and The scratching operation is performed on the cells by inserting the scratching member into the at least one scratching gap and moving from one end to the other end of the at least one scratching gap, the at least one scratching The location is determined by the location of the at least one scratch gap.
  • the photographing and analysis of the at least one scratch by the cell image analysis device to determine the migration ability of the cells includes: using the cell image analysis device, based on the photographing parameters and the obtained The position of the at least one scratch, and the at least one scratch is automatically photographed to obtain a plurality of images of the at least one scratch, wherein each image in the plurality of images corresponds to a preset time point; And based on the plurality of images of the at least one scratch and the plurality of preset time points corresponding to the plurality of images, the migration ability of the cells is determined.
  • a plurality of scratches are formed after performing the scratching operation on the cells, the plurality of scratches include a first scratch and a second scratch, and the cell image analysis device , automatically photographing the at least one scratch based on the photographing parameters and the position of the at least one scratch, comprising: controlling the cell image analysis based on the photographing parameters and the position of the first scratch The device automatically photographs the first scratch; based on the positional relationship between the first scratch gap corresponding to the first scratch and the second scratch gap corresponding to the second scratch, determine the the positional relationship between the first scratch and the second scratch; and based on the positional relationship between the first scratch and the second scratch and the shooting parameters, control the cell image analysis device to The second scratch is taken automatically.
  • the cell image analysis device includes a sample stage and a photographing module
  • the at least one scratch is performed by the cell image analysis device based on the photographing parameters and the position of the at least one scratch Automatically photographing to obtain multiple images of the at least one scratch, comprising: at each preset time point among multiple preset time points, positioning the culture part of the cell scratching device on the At the target position of the sample stage; based on the shooting parameters and the position of the at least one scratch, control the shooting module to automatically shoot the at least one scratch, so as to obtain the at least one scratch in the preset Set at least one image at a time point.
  • the shooting module is controlled to automatically shoot the at least one scratch, so as to obtain the at least one scratch on the At least one image at a preset time point, comprising: controlling the sample stage or the photographing module to move along a direction parallel to the extension of the at least one scratch, so as to obtain the image of the at least one scratch along the extension Multiple images for multiple fields of view in one direction.
  • a plurality of scratches are formed after the scratching operation is performed on the cells, the extension directions of the plurality of scratches are parallel to each other, and the based on the shooting parameters and the at least one scratch Controlling the photographing module to automatically photograph the at least one scratch to obtain at least one image of the at least one scratch at the preset time point, including: controlling the sample stage or the photographing The module moves along the extension direction perpendicular to the plurality of scratches to acquire a plurality of images of the plurality of scratches.
  • the determining the migration ability of the cells based on the multiple images of the at least one scratch and the multiple preset time points corresponding to the multiple images includes: based on the multiple determine the migration distance or migration area of the cells; and determine the migration ability of the cells based on the migration distance or the migration area and the plurality of preset time points.
  • a system for determining the ability of cells to migrate includes: a cell scratching device, used for scratching the cells to form at least one scratch; and a cell image analysis device, used for positioning, shooting and analyzing the at least one scratch to determine the cell migration ability.
  • the cell image analysis device includes: a photographing module, configured to positionally photograph the at least one scratch, so as to acquire at least one image of the at least one scratch.
  • the cell image analysis device includes: an analysis module, configured to determine the migration ability of the cells based on the at least one image.
  • the cell image analysis device includes: a sample stage for positioning the culture part of the cell scratching device.
  • the cell image analysis device includes: a control module, configured to control the sample stage and/or the photographing module.
  • the cell scratching device includes: a scratching part for scratching the cells, the scratching part includes a scratching cover; the scratching cover includes sequentially connected The bottom plate, the connecting piece and the limiting structure, the bottom plate and the limiting structure are respectively located at the two ends of the connecting piece, the bottom plate is provided with a plurality of scratch gaps, and the plurality of scratch gaps are parallel to each other and Evenly spaced distribution; when the scratches are scratched, the scratch cover is installed and fixed by the limiting structure.
  • a control system for determining the migration ability of cells comprising: at least one storage device for storing a set of instructions; and at least one processor and the at least one storage device In communication, the at least one processor, when executing the stored instructions, causes the system to perform the method of determining the migration capacity of cells according to the first aspect of the present specification.
  • Fig. 1 is a schematic diagram of an application scenario of a system for determining cell migration ability according to some embodiments of this specification
  • Figure 2A is an exemplary flowchart for determining cell migration ability according to some embodiments of the present specification
  • Figure 2B is an exemplary flowchart for determining cell migration ability according to some embodiments of the present specification
  • Fig. 3 is an exemplary flow chart of acquiring a scratch image according to some embodiments of the present specification
  • Fig. 4A is a schematic diagram of shooting along the extending direction parallel to the scratch according to some embodiments of the present specification
  • Fig. 4B is a schematic diagram of shooting along the extending direction perpendicular to the scratch according to some embodiments of the present specification
  • Figure 5 is an exemplary flowchart for determining cell migration ability according to some embodiments of the present specification
  • FIG. 6 is a schematic diagram of an exemplary scratch image according to some embodiments of the present specification.
  • Fig. 7 is a block diagram of an exemplary cell image analysis device according to some embodiments of the present specification.
  • Fig. 8 is a schematic cross-sectional structure diagram of an exemplary cell scratching device according to some embodiments of the present specification.
  • Fig. 9 is a schematic top view of an exemplary scratch cover 120 according to some embodiments of the present specification.
  • Fig. 10 is a schematic top view of an exemplary culture unit 110 according to some embodiments of the present specification.
  • Fig. 11 is a schematic structural view of an exemplary scratch cover 120 according to some embodiments of the present specification.
  • Fig. 12 is a first schematic diagram of the cooperative structure of the exemplary scratching member 130 and the scratching gap 1213-1 according to some embodiments of the present specification;
  • Fig. 13 is a second schematic diagram of the cooperation structure of the exemplary scratching member 130 and the scratching gap 1213-1 according to some embodiments of the present specification;
  • Fig. 14 is a schematic structural diagram of an exemplary bottom plate 1213 according to some embodiments of the present specification.
  • Fig. 15 is a schematic structural diagram of an exemplary scratching member 130 according to some embodiments of the present specification.
  • Fig. 16A and Fig. 16B are schematic diagrams of the connection structure between the driving member 140 and the scratching member 130 according to some embodiments of the present specification.
  • system used in this specification are used to distinguish different components, elements, parts, parts or method of the component. However, these terms may also be replaced by other expressions if the same purpose can be achieved.
  • the flowchart used in this specification shows the operations performed by the system according to some embodiments disclosed in this specification. It should be understood that the operations in the flowcharts may be performed out of order. Instead, various steps may be processed in reverse order or concurrently. Also, one or more other operations can be added to these flowcharts. It is also possible to delete one or more operations from the flowchart.
  • Cell migration is one of the basic functions of normal cells, a physiological process of normal growth and development of the body, and a common form of movement in living cells. Cell migration is involved in processes such as embryonic development, angiogenesis, wound healing, immune response, inflammatory response, atherosclerosis, and cancer metastasis.
  • the cell scratch test is the most commonly used and simplest method for laboratory analysis of cell migration ability. The principle is that when cells grow and fuse into a monolayer state, artificially create a blank area on the fused monolayer cells, called "scratch". Cells at the edge of the scratch will gradually move into the blank area to heal the "scratch".
  • the method includes scratching the cell using a cell scratching device to form at least one scratch.
  • the method includes using a cell image analysis device to automatically photograph the at least one scratch based on preset shooting parameters and the position of the at least one scratch, so as to obtain multiple images of the at least one scratch, wherein Each image corresponds to a preset time point.
  • the preset shooting parameters include: at least one of sample injection coordinates, a total shooting length of the at least one scratch, or a number of fields of view of the at least one scratch.
  • the method includes determining the migration ability of the cells based on the plurality of images of the at least one scratch and a plurality of preset time points corresponding to the plurality of images.
  • the system includes a cell scratching device and a cell image analysis device.
  • the cell scratching device includes a culture part for culturing cells, and a scratch part for performing a scratch operation on the cells to form at least one scratch.
  • the cell image analysis device is used for automatically photographing and analyzing the at least one scratch based on preset photographing parameters and the position of the at least one scratch, so as to determine the migration ability of the cells.
  • the uniformity and stability of the scratching and the reproducibility of the scratching experiment can be guaranteed.
  • the scratches can be precisely located, and continuous photography, imaging and analysis can be done at fixed points without marking with a marker pen, and the migration distance and cell migration distance can be obtained. Migration area, and can realize the cumulative observation analysis of a single scratch and the comparative observation analysis of multiple scratches. Therefore, the method for determining cell migration ability provided in this manual does not require marking with a marker pen, overcomes errors such as uneven scratches and manual operations in the traditional scratch method, and can detect cell migration ability more efficiently, comprehensively and accurately .
  • Fig. 1 is a schematic diagram of an application scenario of a system for determining cell migration ability according to some embodiments of the present specification.
  • the system 100 for determining cell migration ability (or the control system 100 for determining cell migration ability) (may be referred to as the system 100 for short) may include a cell scratching device 101 , a cell image analysis device 102 , a network 105 , a storage device 104 and a processing device 103 .
  • the components in the system for determining cell migration capacity 100 can be connected in various ways.
  • the cell scarification device 101 and/or the cell image analysis device 102 may be connected to the processing device 103 or the storage device 104 directly or via the network 105 .
  • the cell scratching device 101 and the cell image analysis device 102 may be connected directly or through the network 105 .
  • the cell scratching device 101 can be used for scratching on cultured cells.
  • the cell scarification device 101 may include a culture part 101-1 and a scratch part 101-2.
  • the culture part 101-1 also called a cell culture device
  • the scratch part 101-2 can be used for scratching cells.
  • the culture section 101-1 may include a culture dish or a culture plate.
  • the culture dish can be made of glass or plastic.
  • the culture section 101-1 may include a D90 culture dish, a six-well culture plate, and the like.
  • the scratch part 101-2 may include a scratch cover and a scratch piece.
  • the scratch cover may include a bottom plate, a connecting piece, and a limiting structure connected in sequence, and the bottom plate and the limiting structure are respectively located at two ends of the connecting piece.
  • the cell scarring device 101 please refer to other parts of this specification (eg, FIGS. 8-16B and related descriptions).
  • the cell image analysis device 102 can be used to analyze cell physiological activities by capturing images.
  • the cell image analysis device 102 can be used to locate the scratches, control the shooting trajectory, acquire images of the scratches, analyze the images of the scratches to determine the migration ability of cells, and so on.
  • the cell image analysis device 102 may include a sample stage, a photographing module, an analysis module, a control module, etc. or any combination thereof.
  • FIGS. 2A-7 and their related descriptions please refer to other parts of this specification (eg, FIGS. 2A-7 and their related descriptions).
  • Processing device 103 may process data and/or information obtained from other devices or components of system 100 .
  • the processing device 103 may execute program instructions based on these data, information and/or processing results to perform one or more functions described in this specification.
  • the processing device 103 can obtain the position of the scratch gap from the cell scratching device 101 .
  • the processing device 103 may acquire images of scratches from the cell image analysis device 102 .
  • the processing device 103 may determine the migration ability of cells based on the image of the scratch.
  • the processing device 103 may directly acquire image analysis results (eg, cell migration ability) from the cell image analysis device 102 .
  • processing device 103 may be a single server or a group of servers. Server groups can be centralized or distributed.
  • processing device 103 may be a local or remote component relative to one or more other components of system 100 .
  • the processing device 103 can access information and/or data stored in the cell scarification device 101 , the cell image analysis device 102 and/or the storage device 104 via the network 105 .
  • the processing device 103 may be directly connected to the cell scarification device 101 , the cell image analysis device 102 and/or the storage device 104 to access stored information and/or data.
  • the processing device 103 can be implemented on a cloud platform.
  • a cloud platform may include a private cloud, a public cloud, a hybrid cloud, a community cloud, a distributed cloud, an internal cloud, a multi-tier cloud, etc., or any combination thereof.
  • the processor 103 may include a central processing unit (CPU), an application specific integrated circuit (ASIC), an application specific instruction processor (ASIP), a graphics processing unit (GPU), a physical processing unit (PPU), a digital signal processing Device (DSP), Field Programmable Gate Array (FPGA), Programmable Logic Circuit (PLD), Controller, Microcontroller Unit, Reduced Instruction Set Computer (RISC), Microprocessor, etc. or any combination of the above.
  • CPU central processing unit
  • ASIC application specific integrated circuit
  • ASIP application specific instruction processor
  • GPU graphics processing unit
  • PPU physical processing unit
  • DSP digital signal processing Device
  • FPGA Field Programmable Gate Array
  • PLD Programmable Logic Circuit
  • Controller Microcontroller Unit, Reduced Instruction Set Computer (RISC), Microprocessor, etc. or any combination of the above.
  • Network 105 may connect various components of system 100 and/or connect parts of the system with external resources.
  • the network 105 enables communication among various components and with other components outside the system, facilitating the exchange of data and/or information.
  • the network 105 may be any one or more of a wired network or a wireless network.
  • the network 105 may include a cable network, a fiber optic network, a telecommunications network, the Internet, a local area network (LAN), a wide area network (WAN), a wireless local area network (WLAN), a metropolitan area network (MAN), a public switched telephone network (PSTN) , Bluetooth network, ZigBee network (ZigBee), near field communication (NFC), internal bus, internal line, cable connection, etc.
  • the network connection among the various parts may adopt one of the above-mentioned methods, or may adopt multiple methods.
  • the network may be in various topologies such as point-to-point, shared, and central, or a combination of multiple topologies.
  • Storage device 104 may be used to store data and/or instructions.
  • the storage device 104 may include one or more storage components, and each storage component may be an independent device or a part of other devices.
  • the storage device 104 may include random access memory (RAM), read only memory (ROM), mass storage, removable memory, volatile read-write memory, etc., or any combination thereof.
  • mass storage may include magnetic disks, optical disks, solid-state disks, and the like.
  • the storage device 104 may be implemented on a cloud platform.
  • the cloud platform may include a private cloud, a public cloud, a hybrid cloud, a community cloud, a distributed cloud, an internal cloud, a multi-layer cloud, etc., or any combination thereof.
  • the cell scratching device 101 and the cell image analysis device 102 can be integrated into a scratch analysis device.
  • a scratching member for example, a scratch needle
  • the processing equipment 103 When scratching cells, a scratching member (for example, a scratch needle) is installed at a fixed position on the sample stage of the scratch analysis device, and after the installation and positioning of the culture part are completed on the sample stage, the processing equipment 103 The position coordinates of the culture part on the sample stage and the installation position coordinates of the scratched parts can be obtained, and the processing device 103 can calculate the initial scratch position and the end scratch position of each scratch according to the scratch plan, and control the sample stage The upper culture part moves according to the initial scratching position and the ending scratching position, and scratches by the scratching piece in turn.
  • a shooting device for example, a camera
  • the storage device 104 and/or the processing device 103 can be integrated into the cell scarring device 101 and/or the cell image analysis device 102 .
  • the cell scarring device 101 and the cell image analysis device 102 each have corresponding processing equipment.
  • one or more components in system 100 may be omitted.
  • network 105, storage device 104, and/or processing device 103 may be omitted.
  • the user can use the cell scratching device 101 to perform a scratch operation, and input the position of the scratch to the cell image analysis device 102, and the cell image analysis device 102 can take pictures and analyze the scratch based on the position of the scratch.
  • system 100 may include one or more other components.
  • system 100 may include a terminal device (not shown in FIG. 1 ).
  • Terminal devices may include mobile devices, tablet computers, laptop computers, etc. or any combination thereof.
  • the user can use the terminal device to control one or more components in the system 100 (for example, the cell scarring device 101 , the cell image analysis device 102 ).
  • the user may input an instruction to control the cell scarring device 101 to perform scratching operations and/or an instruction to control the cell image analysis device 102 to perform photographing and analysis through the terminal device.
  • the cell scratching device 101 can perform scratching operations based on instructions input by the user.
  • the cell image analysis device 102 can photograph and analyze the scratches based on instructions input by the user.
  • the terminal device can display the data of the system 100 .
  • the terminal device can display information such as the location, shape, and outline of scratches.
  • the terminal device may display an image of a scratch.
  • the terminal device can display information such as cell migration distance, migration area, and migration ability.
  • FIG. 2A is an exemplary flowchart for determining cell migration ability according to some embodiments of the present description.
  • the process 200 may be performed by the cell scarification device 101 , the cell image analysis device 102 , or the processing device 103 .
  • the process 200 may be stored in a storage device (for example, the storage device 104) in the form of an instruction (for example, an application program), and called and/or implement.
  • the operation of the procedure shown below is for illustration purposes only. In some embodiments, process 200 may be accomplished with one or more additional operations not described and/or without one or more operations discussed. Additionally, the order of operations of process 200 shown in FIG. 2A and described below is not intended to be limiting.
  • step 210 cells are cultured in a cell culture device (eg, culture section 101-1).
  • a cell culture device eg, culture section 101-1
  • cells that grow well in the logarithmic phase can be inoculated into the culture part, and the culture medium is used to culture the cells.
  • the amount of inoculum is based on the fusion rate reaching 100% after 24 hours of culture.
  • the confluency rate can refer to the percentage of adherent growing cells in the monolayer culture to the area of the growing area.
  • a confluence rate of 100% may mean that the cells cover the bottom of the culture section.
  • the medium in the culture section is removed after the cells reach 100% confluency.
  • a user eg, an experimenter
  • step 220 a scratching operation is performed on the cells by a cell scratching device (for example, the scratching unit 101-2) to form at least one scratch.
  • a cell scratching device for example, the scratching unit 101-2
  • the cell scarification device can be a manual scarification device, a semi-automatic scarification device, or a fully automatic scarification device.
  • the scratching part of the cell scratching device may include a scratch cover plate and a scratch piece, the scratch cover plate includes a bottom plate connected in sequence, a connecting piece and a limiting structure, and the bottom plate and the limiting structure are respectively located at two ends of the connecting piece , the bottom plate is provided with at least one scratch gap.
  • the user can fix the culture part after removing the culture medium on the operation table; then, fix the scratch cover on the culture part through the limiting structure and finally, scratching the cells by inserting the scratching member into at least one scratching gap and moving along one end of the at least one scratching gap to the other end.
  • the scratch piece can be moved to the end of the scratch gap, and inserted into the scratch gap, the scratch piece can be slid to the other end along the scratch gap, and then the scratch piece can be taken out (especially, the scratch piece can be Swipe repeatedly to remove as much cells as possible along the scratch path).
  • the location of at least one scratch is determined by the location of at least one scratch gap.
  • step 230 the cells are washed, and the cells are continued to be cultured in the cell culture device (for example, culture section 101-1).
  • the user can use buffer (for example, sterile phosphate-buffered saline (PBS)) to wash the cell surface several times to wash away the non-adherent cells produced during the scratch, so that the boundary between the scratch and the cells is clear clean.
  • buffer for example, sterile phosphate-buffered saline (PBS)
  • PBS sterile phosphate-buffered saline
  • the at least one scratch is automatically photographed by the cell image analysis device (for example, the cell image analysis device 102 ), so as to acquire multiple images of the at least one scratch.
  • the at least one scratch can be automatically photographed by the cell image analysis device based on the preset photographing parameters and the position of the at least one scratch, so as to obtain multiple images of the at least one scratch. image.
  • each of the plurality of images corresponds to a preset time point.
  • the preset time point may be a preset shooting time point.
  • the preset time points may be 0 hour, 6 hours, 12 hours, 24 hours, etc. after the scratch operation on the cells.
  • the preset shooting parameters may refer to relevant parameters for shooting images.
  • the preset shooting parameters can be parameters preset by the user according to the model of the cell culture device, the model of the cell image analysis device, the type of cells, the position of the scratch, the area of the scratch, and the accuracy requirements of the experiment.
  • the preset shooting parameters may include sampling coordinates, the total shooting length of at least one scratch, the number of fields of view of at least one scratch, etc., or any combination thereof.
  • sample injection coordinates may refer to the relative position between the zero position of the sample stage and the first shooting field of view.
  • sample stage zero can refer to the initial position of the sample stage.
  • the sample stage may be at the zero position of the sample stage.
  • the sample stage can return to zero position.
  • the shooting field of view may refer to a location on the scratch to be shot.
  • the first photographing field of view may refer to the first position on the scratch to be photographed.
  • the coordinates of the position of the first shooting field of view of the scratch can be input into the cell image analysis device, and the cell image analysis device can , to determine the injection coordinates of the sample stage.
  • the cell image analysis device can control the moving direction and moving distance of the sample stage based on the sample injection coordinates of the sample stage, so that the photographing module (for example, the photographing module 720) of the cell image analysis device can scan the area drawn in the culture section on the sample stage.
  • the first shooting field of view of the trace is used for shooting.
  • the total length of the scratch can refer to the length of the scratch that needs to be photographed.
  • the number of fields of view of scratches may refer to the number of shots of the scratches. For example, assuming that the length of a scratch is 5 cm, the total length of the scratch is set to 3 cm, and the number of fields of view is 10, then it can be determined that starting from the starting position of a certain end of the scratch, every 0.3 cm is a Capture the field of view.
  • the total shooting length and the number of fields of view may be determined according to the shooting situation or the accuracy requirements of the experiment. For example, in order to improve the accuracy of the experiment, more experimental data can be obtained by increasing the total shooting length and the number of fields of view. For another example, if the gap of a certain scratch is too small or too large due to uneven cell tiling, the scratch may not be photographed.
  • the user can set the total length of the captured first scratch and the number of fields of view, and the cell image analysis device can automatically generate images of other scratches based on the positional relationship between other scratches and the first scratch.
  • Overall length and number of fields of view For example, assuming that the length of the first scratch is 5 cm, the total length of the first scratch is 3 cm, the number of fields of view is 10, and the length of the second scratch is equal to that of the first scratch, then the cell image analysis device can automatically Set the total length of the shot for the second scratch to also be 3 cm and the number of fields to be 10. Assuming that the length of the second scratch is 2.5 cm, the cell image analysis device can automatically set the total length of the second scratch to be 1.5 cm, and the number of fields of view to be 5.
  • the shooting parameters may also include exposure, shooting focal length, and the like.
  • the user can pre-set the exposure and shooting focal length based on experience.
  • the shooting focus value can be dynamically adjusted based on images captured in real time.
  • the focal length value for optimal imaging can be determined according to the clarity of scratches in multiple images captured in real time. Specifically, the focal length value corresponding to the image with the best definition is determined as the focal length value for the best imaging. And the focal length value of the best imaging is used for the shooting of other fields of view.
  • focal length values of corresponding shooting fields of view at other preset time points may be determined based on the focal length values of multiple shooting fields of view determined at the first preset time point.
  • the scratches are photographed with multiple fields of view, the focus of each field of view is adjusted and the focal length value of the best imaging is recorded, and at other preset time points (such as 6 hours, 12 hours and 24 hours, etc.) when shooting, you can obtain the recorded focal length value and adjust the focus based on this value.
  • the same shooting parameters can be used to acquire images of all scratches.
  • the preset shooting parameters or the shooting parameters when shooting the first scratch can be stored in the storage device, and images of other scratches can be shot by calling the shooting parameters when shooting other scratches subsequently.
  • the current shooting parameters can be recorded by setting a barcode or two-dimensional code on the culture device, and then the shooting parameters can be obtained directly by scanning the code in the next shooting.
  • the distance that the sample stage moves each time can be determined according to the total length of the scratch and the number of fields of view, so as to realize the automatic shooting of the scratch. For example, assuming that the total length of shots of scratches is 3 cm and the number of fields of view is 10, the movement distance per shot is 0.3 cm. That is, the sample stage was moved 0.3 cm along the extending direction of the scratch each time, and the field of view was photographed once.
  • multiple scratches may be formed after scratching the cells, and the cell image analysis device may sequentially photograph the multiple scratches based on preset shooting parameters corresponding to the multiple scratches.
  • the first scratch and the second scratch can be formed after scratching the cell, and the cell image analysis device can control the first scratch based on the preset shooting parameters corresponding to the first scratch and the position of the first scratch.
  • the cell image analysis device automatically photographs the first scratch.
  • the cell image analysis device may determine the first scratch and the second scratch gap based on the positional relationship between the first scratch gap corresponding to the first scratch and the second scratch gap corresponding to the second scratch. Describe the positional relationship of the second scratch.
  • the cell image analysis device may control the cell image analysis device to automatically photograph the second scratch based on the positional relationship between the first scratch and the second scratch and the preset shooting parameters. For example, after the shooting of the first scratch is completed, the moving direction and moving distance of the sample stage can be controlled according to the shooting end position coordinates of the first scratch and the shooting starting position coordinates of the second scratch, so as to capture the second scratch. marks. Wherein, the shooting end position coordinates of the first scratch and the shooting starting position coordinates of the second scratch can be determined according to the positions of the first scratch gap and the second scratch gap on the scratch part.
  • a moving sequence with higher moving efficiency may be determined according to the positions of the multiple scratches. For example, according to the coordinates of each shooting field of view of each scratch in multiple scratches, the algorithm can automatically calculate the most efficient moving sequence of the shooting module or sample stage, and control the shooting module or sample stage according to the moving sequence Make a move. Specifically, when shooting multiple scratches parallel to each other, a "bow" shape can be selected for shooting. More descriptions about shooting positions can be found in FIGS. 4A and 4B and their related descriptions.
  • the cell image analysis device 102 may determine the migration ability of the cell based on multiple images of at least one scratch and multiple preset time points corresponding to the multiple images.
  • the migratory ability of a cell can refer to the ability of a cell to move from an initial location to another location.
  • Cell migration ability can be evaluated by cell migration rate.
  • the cell migration rate may refer to the ratio of the cell migration area (or migration distance) to the detection time.
  • the processing device 103 may extract the contour of the at least one scratch from each of the plurality of images.
  • the processing device 103 can determine the migration distance or migration area of the cells based on the contour.
  • the processing device 103 may determine the migration ability of the cells based on the migration distance or the migration area, and the multiple preset time points. Further description of determining cell migration capacity can be found elsewhere in this specification (eg, Figures 5-6 and their associated descriptions).
  • step 210 and/or step 230 may be omitted.
  • steps 220 and 230 may be combined into one step.
  • step 240 the cell image analysis device may automatically photograph the scratch based only on the position of the scratch. Specifically, the position coordinates of multiple fields of view of the scratch can be input into the cell image analysis device, and the cell analysis device can automatically photograph and analyze the multiple fields of view based on the position coordinates of the multiple fields of view of the scratch.
  • the medium in the culture part needs to be aspirated and then the scratches are photographed and analyzed, and new medium is added after the photographing is completed.
  • the cells may be scratched by a cell scratching device to form at least one scratch.
  • the scoring operation can be performed using a manual scoring device, a semi-automatic scoring device, or a fully automatic scoring device.
  • scratching can be performed using the cell scratching device illustrated in Figure 2A.
  • the scratching operation can be performed using the cell scratching device illustrated in FIGS. 8-16B .
  • other methods can also be used to perform the cell scratching operation.
  • the at least one scratch can be photographed and analyzed by a cell image analysis device to determine the migration ability of the cells.
  • the cell image analysis device illustrated in FIGS. 2A-7 can be used to photograph and analyze the scratches.
  • other methods may be used to perform photographic analysis on scratches. For example, scratches can be photographed and analyzed using a microscope.
  • FIG. 2B is an exemplary flowchart for determining cell migration ability according to some embodiments of the present description.
  • the process 205 may be performed by the cell scratching device 101 , the cell image analysis device 102 , or the processing device 103 .
  • the process 205 may be stored in a storage device (for example, the storage device 104) in the form of instructions (for example, an application program), and invoked and/or implement.
  • a storage device for example, the storage device 104
  • instructions for example, an application program
  • step 260 a scratching operation is performed on the cells by a cell scratching device (for example, the scratching unit 101-2) to form at least one scratch.
  • a cell scratching device for example, the scratching unit 101-2
  • step 220 in FIG. 2A For more descriptions of the cell scratching device and the scratching operation using the cell scratching device, please refer to step 220 in FIG. 2A , FIGS. 8-16B and related descriptions.
  • step 270 the at least one scratch is photographed and analyzed by the cell image analysis device 102 (or the processing device 103), so as to determine the migration ability of the cells.
  • At least one scratch can be positioned and photographed by the cell image analysis device 102 to obtain at least one image of the at least one scratch.
  • the cell image analysis device 102 can determine the migration ability of cells based on at least one image of at least one scratch. Please refer to the relevant descriptions of steps 240 and 250 in FIG. 2A for more descriptions about performing image analysis on at least one scratch to determine the migration ability of cells.
  • Fig. 3 is an exemplary flow chart of acquiring scratch images according to some embodiments of the present specification.
  • process 300 may be performed by cell image analysis apparatus 102 or processing device 103 .
  • the process 300 may be stored in a storage device (eg, the storage device 104 ) in the form of instructions (eg, an application program), and invoked and/or executed by the cell image analysis device 102 or the processing device 103 .
  • the operation of the procedure shown below is for illustration purposes only. In some embodiments, process 300 may be accomplished with one or more additional operations not described and/or without one or more operations discussed. Additionally, the order of operations of process 300 shown in FIG. 3 and described below is not intended to be limiting.
  • Step 310 at each preset time point among multiple preset time points, position the culture part at the target position of the sample stage (for example, sample stage 710 ) of the cell image analysis device.
  • the target position may refer to a position on the sample stage for placing the culture section.
  • the target position may be the center position of the sample stage.
  • manual positioning can be performed by designing base points or baselines on the culture part and the sample stage.
  • a number mark of a cross orientation can be set on both the culture part and the sample stage, and the positioning of the culture part on the sample stage can be realized by aligning the corresponding numbers of the cross orientation on the culture part and the sample stage.
  • a culture part adapter can be provided on the sample stage to realize the positioning of the culture part on the sample stage.
  • the bottom of the culture part is provided with a groove adapter, and the surface of the sample stage is provided with a corresponding raised adapter, and the culture part can be positioned by matching the two.
  • a direction mark can be set at a non-central position of the culture part, and different culture parts have their own labels.
  • the position and orientation of each culture section placed on the sample stage can be automatically recorded based on the number and orientation mark of the culture section.
  • the culture part can be positioned again according to the position and direction of the culture part placed on the sample stage at the first preset time point, so as to ensure that the culture part is placed on the sample at different preset time points.
  • the position and direction of the stage are the same.
  • a culture part moving mechanism may be provided on the sample stage, and the moving mechanism may move the culture part to a target position.
  • the cell image analysis device can take pictures of the culture part (for example, the culture part can be photographed with a low magnification) to obtain images of the culture part.
  • the center of the circle of the culture part can be determined. Based on the positional relationship between the center of the culture part and the zero position of the sample stage, the moving direction and moving distance of the culture part are determined, and the culture part moving mechanism is controlled to move the culture part.
  • corresponding baselines can be set on the culture part and the sample stage (for example, a straight line passing through the center of the petri dish is used as the baseline).
  • the baseline of the culture part can be extracted from the image of the culture part, and the moving direction and moving distance of the culture part can be determined according to the positional relationship between the culture part baseline and the sample stage baseline, and the movement of the culture part can be controlled
  • the institution moves to the training department.
  • the position of the culture part on the sample stage needs to be corrected, In order to ensure that the culture part is at the same target position of the sample stage during each shooting.
  • a base point (or baseline) corresponding to each other can be set on the culture part and the sample stage, and whether the movement of the base point (or baseline) on the culture part and the sample stage occurs to determine whether it is necessary to correct the position of the culture part on the sample.
  • the position on the stage, and the method of correction (for example, the direction and distance that the culture part needs to be moved).
  • Step 320 the cell image analysis device 102 (for example, the control module 740) (or the processing device 103) can control the photographing module (for example, the photographing module 720) to automatically detect the scratch based on the preset photographing parameters and the position of the scratch. shooting to acquire at least one image of the scratch at the preset time point.
  • the photographing module for example, the photographing module 720
  • the positions of the formed scratches correspond to the positions of the scratch gaps in the cell scratching device.
  • the scratch information is determined based on the position information of the scratch gap, and multiple scratches are photographed sequentially based on the scratch information.
  • the scratch information includes various scratch-related information, for example, scratch intervals, scratch locations, scratch endpoints, and positional relationships between scratches.
  • the cell image analysis device can acquire the position of the scratch gap corresponding to the scratch from the cell scratch device, determine the position of the scratch based on the position of the scratch gap, and take pictures of the scratch.
  • the user can input the position information of the scratch gap corresponding to the scratch into the cell image analysis device, and the cell image analysis device can determine the position of the scratch based on the position of the scratch gap, and take pictures of the scratch.
  • the scratching gaps of the cell scratching device can be numbered, and the information (for example, length, width, position coordinates) of the corresponding scratching gaps can be stored based on the numbering.
  • the information of the gap between the scratches can be directly obtained as the scratch information.
  • the scratch information can be determined by marking the endpoint of the scratch, acquiring an image of the culture part, and based on the degree of light transmission of the cells.
  • the endpoints of scratches can be fluorescently labeled and determined by fluorescence tracking.
  • the light transmittance of the scratched area is different from that of the non-scratched area (the non-scratched area is covered by cells, so the light transmittance is lower than the scratched area)
  • appropriate intensity of light can be placed on the bottom of the culture section (for example, without White light that will affect cell growth)
  • the area with better light transmittance is the scratch area
  • the area with poor light transmittance is the non-scratch area
  • the length of scratches and the gap between different scratches are recorded.
  • the cultured part may be photographed at a low magnification, an image of the cultured part may be obtained, and the scratches in the image of the cultured part may be recognized to determine the scratch information.
  • the photographing module of the cell image analysis device may include at least one local camera and a global camera, the global camera can capture a global image of the scratch, and determine the information of the scratch based on the global image, and the local camera can further photograph the scratch Images from multiple fields of view.
  • the scratches may be located by mechanical means.
  • the bottom of the culture part is provided with a groove adapter for scratch positioning at the position corresponding to the scratch
  • the bottom of the sample stage is provided with a corresponding protrusion adapter, and the scratch positioning is realized by matching the two.
  • Fig. 4A is a schematic diagram showing shooting along a direction parallel to the extension of scratches according to some embodiments of the present specification.
  • Fig. 4B is a schematic diagram showing shooting along a direction perpendicular to the extending direction of scratches according to some embodiments of the present specification.
  • the black dots in the figure represent the shooting field of view.
  • scratch A includes 10 shooting fields of view, respectively A1, A2... and A10; scratch B includes 13 shooting fields of view, respectively B1, B2... and B13; scratch C includes 10 shooting fields of view , respectively C1, C2... and C10.
  • the extending directions of scratch A, scratch B, and scratch C are parallel to each other.
  • the cell image analysis device can control the sample stage (or the photographing module) to move along the extension direction parallel to the scratch, so as to acquire multiple images of multiple fields of view of the scratch along the extension direction.
  • the cell image analysis device can control the shooting module (for example, camera) to move to the starting shooting position of scratch A (for example, shooting field of view A1), and control the shooting module to move along the extension direction parallel to scratch A, Sequentially shoot A1, A2... to A10 until the shooting of scratch A is completed, so as to realize the observation and analysis of different fields of view of a single scratch.
  • the shooting module for example, camera
  • the shooting module to move to the starting shooting position of scratch A (for example, shooting field of view A1)
  • the shooting module to move along the extension direction parallel to scratch A, Sequentially shoot A1, A2... to A10 until the shooting of scratch A is completed, so as to realize the observation and analysis of different fields of view of a single scratch.
  • the cell image analysis device can control the shooting module to move to the initial shooting position of the scratch B (for example, the shooting field of view B1), and control the shooting module to move along the direction parallel to the extension of the scratch B, and shoot B1 and B2 sequentially. ...to B10 until the scratch B is shot.
  • the cell image analysis device can control the shooting module to move to the initial shooting position of the scratch C (for example, the shooting field of view C1), and control the shooting module to move along the direction parallel to the extension of the scratch C, and shoot C1 and C2 sequentially. ...to C10 until the scratch C is shot.
  • the shooting module can move to the shooting field of view B13 of the scratch B, and shoot B13, B12... to B1 in sequence until the shooting of the scratch B is completed . Then, the photographing module moves to the photographing field of view C1 of the scratch C, and successively photographs C1, C2... to C10 until the photographing of the scratch C is completed.
  • scratch D, scratch E, and scratch F each have two shooting fields of view.
  • the extending directions of the scratch D, the scratch E, and the scratch F are parallel to each other.
  • the cell image analysis device may control the sample stage (or the photographing module) to move along a direction perpendicular to the extension of the scratches, so as to acquire multiple images of the multiple scratches.
  • the cell image analysis device may control the photographing module (for example, a camera) to move to the initial photographing position of the scratch D (for example, the photographing field of view D1), and control the photographing module to move along a direction perpendicular to the extension of the scratch D, Sequentially photograph the field of view D1 of the scratch D, the field of view E1 of the scratch E, and the field of view F1 of the scratch F, so as to realize the comparative observation and analysis of multiple scratches.
  • the photographing module for example, a camera
  • the photographing module for example, a camera
  • the photographing module for example, a camera
  • the cell image analysis device can control the photographing module to move to the photographing field of view D2 of the scratch D, and control the photographing module to move along the extension direction perpendicular to the scratch D, and successively photograph the photographing field of view D2 of the scratch D, the scratch E
  • the shooting field of view E2 of the scratch F and the shooting field of view F2 of the scratch F can move to the shooting field of view F2 of the scratch F, and take pictures of the shooting field of view F2 of the scratch F and the shooting of the scratch E in sequence.
  • the field of view E2 and the field of view D2 of the scratch D are photographed.
  • Fig. 5 is an exemplary flow chart for determining cell migration ability according to some embodiments of the present specification.
  • process 500 may be performed by cell image analysis apparatus 102 or processing device 103 .
  • the process 500 may be stored in a storage device (eg, the storage device 104 ) in the form of instructions (eg, an application program), and invoked and/or executed by the cell image analysis device 102 or the processing device 103 .
  • the operation of the procedure shown below is for illustration purposes only. In some embodiments, process 500 may be accomplished with one or more additional operations not described and/or without one or more operations discussed. Additionally, the order of operations of process 500 shown in FIG. 5 and described below is not intended to be limiting.
  • the cell image analysis apparatus 102 may extract a contour of the scratch from each of the plurality of images of the scratch.
  • the multiple images of the scratches are captured at multiple preset time points.
  • the multiple images of scratches may be obtained by shooting at preset time points of 0 hour, 2 hours, and 4 hours, respectively.
  • the processing device 103 or cell image analysis device
  • Exemplary image segmentation algorithms may include region-based algorithms (eg, threshold segmentation, region-growing segmentation), edge-detection segmentation algorithms, compression-based algorithms, histogram-based algorithms, dual clustering algorithms, and the like.
  • the cell image analysis device 102 (for example, the analysis module 730) (or the processing device 103 ) can determine the migration distance or the migration area of the cells based on the multiple contours in the multiple images.
  • the migration distance of cells may refer to the difference between the distances between the cells on both sides of the scratch at different preset time points.
  • the distance difference between the lines connecting the cells on both sides of the scratch outline in the images acquired at different preset time points can be determined as the cell migration distance within the time range. Specifically, assuming that in the image acquired at the preset time point of 0 hours, the distance between the cells in the middle of the two sides of the outline of the scratch is 1.50mm, and in the image acquired at the preset time point of 2 hours, the outline of the scratch The distance between the cells connecting the corresponding positions in the middle of the two sides of the cell becomes 1.20mm, then it can be determined that the migration distance of the cells is 0.3mm within two hours.
  • multiple migration distances for multiple locations of the scratch may be determined based on the scratch profile.
  • the migration distance may include a maximum migration distance, a minimum migration distance, an average migration distance, and the like.
  • the migration area of cells can refer to the difference in the area of scratches at different time points.
  • the difference of the area of the scratch outline in the images acquired at different preset time points may be determined as the migration area within the time range. Specifically, assuming that in the image acquired at the preset time point of 2 hours, the area of the scratch outline is 20mm 2 , and in the image acquired at the preset time point of 4 hours, the area of the scratch outline becomes 15mm 2 , then it can be determined that The migration area of the cells was 5 mm 2 within two hours.
  • FIG. 6 is a schematic diagram of an exemplary scratch image according to some embodiments of the present specification.
  • the white lines on both sides of the scratch area in Figure 6 indicate the scratch width.
  • the maximum scratch width AB i.e. the maximum distance between the cells on both sides of the outline
  • the minimum scratch width CD i.e. the minimum distance between the cells on both sides of the outline
  • the average scratch width That is, the average distance between the cells on both sides of the contour
  • the scratch area is 1641960 pixels
  • the shooting time that is, the time difference between the time when the scratch operation is completed and the time when the scratch image is taken
  • the cell image analysis device 102 may determine the migration ability of the cells based on the migration distance or the migration area.
  • the migration ability of cells can be determined based on migration distance or migration area, and multiple preset time points corresponding to multiple images. For example, the ratio of the migration distance (or migration area) to the time taken to generate the migration distance (or migration area) (ie, migration rate) can be determined as the migration ability of the cells. Specifically, assuming that the cell migration area is 5 mm 2 within two hours, it can be determined that the cell migration capacity is 2.5 mm 2 /h.
  • multiple shooting fields of view of multiple scratches of a certain cell can be analyzed at different preset time points, and multiple cell migrations corresponding to different preset time points, different scratches, and different shooting fields of view can be determined.
  • rate, the average value of the plurality of cell migration rates can be used as the cell migration ability.
  • Fig. 7 is a block diagram of an exemplary cell image analysis device according to some embodiments of the present specification.
  • the cell image analysis device 102 may include a sample stage 710 , a photographing module 720 , an analysis module 730 and a control module 740 .
  • the sample stage 710 can be used to place a cell culture device (for example, the culture section 101-1).
  • the sample stage 710 can be provided with base points (or baselines), adapters and/or movement mechanisms for positioning the cell culture device. See Figure 3 and its description for more description of the positioning of the cell culture device on the sample stage.
  • the photographing module 720 can be used to photograph images.
  • the camera module 720 may be and/or include any suitable device capable of acquiring image data.
  • the photographing module 720 may include a spherical camera, a hemispherical camera, and the like.
  • the photographing module 720 may include a black and white camera, a color camera, an infrared camera, and the like.
  • the photographing module 720 may include a digital camera, an analog camera, and the like.
  • the photographing module 720 may include a monocular camera, a binocular camera, a multi-camera, and the like.
  • the photographing module 720 may photograph the scratches to obtain images of the scratches.
  • the photographing module 720 may photograph the cultivation part to obtain images of the cultivation part.
  • Analysis module 730 may be used to analyze data.
  • the analysis module 730 can determine the ability of cells to migrate based on the images of the scratches. For example, the analysis module 730 can extract the outline of a scratch in the image. The analysis module 730 can determine the migration distance or the migration area of the cells based on the contour of the scratch. The analysis module 730 can determine the migration ability of the cells based on the migration distance or the migration area. See Figures 2A, 5-6 and their descriptions for more on determining the migratory capacity of cells.
  • the control module 740 is used to control other components in the cell image analysis device 102 .
  • the control module 740 can control the movement of the sample stage.
  • the control module 840 may control the photographing module to photograph the scratches.
  • the analysis module 730 and/or the control module 740 can be integrated into one module.
  • the analysis module 730 and/or the control module 740 may be omitted.
  • the processing device 103 can be used to analyze data and control other components in the cell image analysis device 102 .
  • Fig. 8 is a schematic cross-sectional structure diagram of an exemplary cell scarring device according to some embodiments of the present specification.
  • the cell scratching device 101 may include a culture part 110 and a scratching part 120 .
  • the culture part 110 can be used for cell culture
  • the scratch part 120 can be used for scratching the cells.
  • culture section 110 may include a culture dish or plate.
  • the culture dish can be made of glass or plastic.
  • the culture part 110 may include a D90 culture dish, a six-well culture plate (as shown in FIG. 10 ), and the like.
  • the scratch part 120 may include a scratch cover 1210 and a scratch member 130 .
  • the scratch cover 1210 may include a bottom plate 1213 , a connecting piece 1212 and a limiting structure 1211 sequentially connected, and the bottom plate 1213 and the limiting structure 1211 are respectively located at two ends of the connecting piece 1212 .
  • the scratch cover 1210 when scratching, can be installed and fixed on the culture part 110 through the stop structure 1211 to prevent loosening between the culture part 110 and the scratch part 120 and affect the scratches.
  • the distance between the bottom plate 1213 of the scratch cover 1210 and the bottom of the culture part 110 may be 0.5-1.5 mm.
  • the limiting structure 1211 may include at least one of an inverted U-shaped groove, a flange protrusion, a flange groove, a rubber block, a threaded structure, and a mortise and tenon structure, and the limiting structure 1211 matches the side wall of the cultivation part 110 .
  • the limiting structure 1211 is a flanged groove structure
  • the width of the groove matches the thickness of the side wall of the culture part 110 .
  • the bottom plate 1213 may be provided with a plurality of scratch gaps 1213 - 1 , and the plurality of scratch gaps are parallel to each other and distributed evenly at intervals. As shown in FIG. 8, in some embodiments, when scratching, the tip of the scratching member 130 can be inserted into one of the scratching gaps 1213-1, by moving from one end to the other end of the scratching gap 1213-1, realizing Cell scratches.
  • the bottom plate 1213 may be provided with 6-15 scratch gaps 1213-1, and the distance between any two adjacent scratch gaps may be 0.5-1 cm.
  • the bottom plate 1213 may be provided with seven scratch gaps, and the distance between two adjacent scratch gaps may be 1 cm. For another example, as shown in FIG.
  • the bottom plate 1213 may be provided with 14 scratch gaps, and the distance between two adjacent scratch gaps may be 0.5 cm.
  • different numbers and shapes of scratching gaps and/or scratching gaps of different widths can be set on the bottom plate 1213 .
  • the corresponding scratch cover can have 3 or 5 scratch gaps, and the distance between two adjacent scratch gaps can be 0.5 cm or 1 cm.
  • each scratching gap 1231-1 can be a trapezoid with a wide top and a narrow bottom, and the trapezoid can match the shape of the tip of the scratching member 130, so that the tip of the scratching member 130 can be inserted into the scratch.
  • the scratch cover 1210 is detachably connected to the scratch member 130 .
  • the length of the connecting member 1212 may be a preset length.
  • the user can design the length of the corresponding connecting piece 1212 according to the actual size of the culture part 110 and other related requirements (such as the distance between the bottom plate 1213 and the bottom of the culture part 110 after the scratch cover 1210 is installed). Therefore, after the scratch cover 1210 is installed and fixed on the culture part 110 through the limiting structure 1211 , the distance between the bottom plate 1213 and the bottom of the culture part 110 may be 0.5-1.5 mm. Preferably, the distance between the bottom plate 1213 and the bottom of the culture part 110 may be 1 mm.
  • FIG. 11 is a schematic structural diagram of a scratch cover 1210 in some embodiments.
  • the limiting structure 1211 may be an inverted U-shaped groove. As shown in FIG. 11 , the limiting structure 1211 may include two fixing pieces 1211-1, one of which is connected to the connecting piece 1212, and a limiting groove 1211-2 is formed between the two fixing pieces 1211-1. In addition, the width of the limiting groove 1211 - 2 matches the thickness of the side wall of the culture part 110 .
  • the limiting structure 1211 may also include only one fixing piece 1211 - 1 , and a limiting groove 1211 - 2 is formed between the fixing piece 1211 - 1 and the connecting piece 1212 .
  • the fixing part 1211 - 1 may be a flange of the connecting part 1212 .
  • the fixing member 1211-1 may be a rubber block.
  • the friction between the rubber block and the side wall of the culture part 110 is greater, and relative displacement is less likely to occur, so the installation of the scratch cover 1210 is more stable and less likely to loosen.
  • the surface of the rubber block close to the connecting piece 1212 may be provided with textures such as bumps to improve the stability of the position limit.
  • an internal thread can also be provided in the limiting groove 1211-2, and a corresponding external thread (not shown in the figure) is provided on the outer wall of the cultivation part 110, and the scratch cover 1210 and the cultivation part 110 are threaded. connect.
  • the arrangement of the screw connection not only makes the installation of the scratch cover 1210 more stable, but also makes the scratch cover 1210 move in the thread length direction while rotating. Therefore, the screw connection can make the distance between the base plate 1213 and the bottom of the culture part 110 adjustable, which is convenient for the experimenter to operate, and can adjust the distance between the base plate 1213 and the bottom of the culture part 110 according to different models of the culture part 110 and the scratching part 130. spacing to enhance the scratch effect.
  • the limiting structure 1211 may also be connected with the cultivating part 110 using a mortise and tenon structure, that is, snap-fit.
  • the inner wall of the limiting groove 1211-2 is provided with a groove
  • the outer wall of the cultivation part 110 is provided with a corresponding protrusion (not shown in the figure)
  • the scratch cover 1210 is fixed by the cooperation of the groove and the protrusion.
  • the outer wall of the culture part 110 can be provided with a plurality of corresponding protrusions along the height direction, and the grooves can be engaged with the protrusions at different height positions to change the distance between the bottom plate 1213 and the bottom of the culture part 110. spacing. Therefore, experimenters can adjust the distance between the bottom plate 1213 and the bottom of the culture part 110 according to different models of the culture part 110 and the scratching part 130 to improve the scratching effect.
  • the scoring member 130 may include a scoring needle 1310 .
  • a first limiting member 1214 and a second limiting member 1215 that match each other are provided on both sides of the scratch gap 1213 - 1 .
  • the first limiting member 1214 and the second limiting member 1215 may both be located on a side of the bottom plate 1213 close to the bottom of the culture part 110 . And along the direction from the bottom plate 1213 to the bottom of the culture part 110 , the distance between the first limiting member 1214 and the second limiting member 1215 gradually decreases.
  • an inverted tapered shape with a large upper opening and a smaller lower opening can be used to clamp the scoring needle 1310 when the scoring needle 1310 is inserted into the gap, so as to facilitate the marking of the scoring needle. 1310 to limit the position to ensure that the length of the scratch needle 1310 protruding from the bottom plate 1213 remains unchanged, thereby improving the stability of the scratch.
  • the width of the lower opening between the first limiting member 1214 and the second limiting member 1215 is smaller than the width of the scratch gap 1213-1, that is, the first limiting member 1214 and the second limiting member
  • the distance between the ends of 1215 near the bottom of the culture part 110 is smaller than the width of the scratch gap 1213-1.
  • the scoring member 130 may further include a slider 1320 , and the scoring needle 1310 may be mounted on the slider 1320 .
  • the slider 1320 can slide with the scratching gap 1213-1 as a guide rail to drive the scratching needle 1310 to move from one end of one of the scratching gaps to the other end to realize cell scratching. Since the slider 1320 fits closely with the scratching gap 1213-1 as a guide rail, deflection is not easy to occur, so the scratching needle 1310 can be better perpendicular to the bottom of the culture part 110 and has a high degree of stability, thereby ensuring a uniform scratching effect. , Stability guarantee.
  • FIG. 12 is a first schematic diagram of the cooperative structure of the scratching member 130 and the scratching gap 1213 - 1 in some embodiments.
  • the slider 1320 can be provided with a threaded hole, and the threaded hole can be arranged perpendicular to the bottom plate 1213, and the outer wall of the scratch needle 1310 can be provided with an external thread (not shown) corresponding to the threaded hole, so that The scoring needle 1310 is threadedly connected to the slide block 1320 .
  • the setting of the screw connection enhances the installation stability of the scoring needle 1310, and on the other hand, allows the scoring needle 1310 to adjust the length extending out of the slider 1320 during the rotation.
  • the length of the scratch needle 1310 extending out of the slider 1320 can be adjusted to ensure that the tip of the scratch needle 1310 can touch the bottom of the culture part 110.
  • a handle (not shown in the figure) may also be provided on the top of the slider 1320 to facilitate operation by experimenters.
  • FIG. 13 is a second schematic diagram of the cooperation structure of the scratching member 130 and the scratching gap 1213 - 1 in some embodiments.
  • the slider 1320 can be a spherical slider, and the inside of the scratch gap 1213 - 1 can be shaped to match the spherical slider.
  • the setting of the spherical slider can reduce the probability that the slider 1320 gets stuck in a corner to a certain extent.
  • other limiting structures can be added, for example, a limiting structure 1320-1 is provided at the position where the bottom of the ball slider is exposed from the scratch gap 1213-1 , so as to prevent the ball slider from rolling itself.
  • the limiting structure 1320-1 can also be arranged on the top of the spherical slider, and it can also be used as a handle while performing a limiting function.
  • FIG. 14 is a schematic structural diagram of the bottom plate 1213 in some embodiments.
  • the ends of the multiple scratch gaps 1213 - 1 on the same side can be connected through a connecting path 1216 . Therefore, the same slider 1320 can enter multiple scratching gaps 1213-1, thereby reducing the number of scratching pieces 130, avoiding the influence of the difference between different scratching pieces 130 on the scratching effect, thereby improving the Stability and uniformity of scratches.
  • the scratch gap 1213 - 1 may also be provided with an access hole 1217 .
  • the size of the access hole 1217 is not smaller than the slider 1320, so the slider 1320 can enter the scratch gap 1213-1 from the access hole 1217, thereby realizing the detachable connection between the scratch member 130 and the bottom plate 1213, which facilitates experiments Personnel use the scratch piece 130 of the corresponding specification to scratch.
  • the setting of the entry hole 1217 is equivalent to that one end of the guide rail (ie, the scratch gap 1213-1) is not closed, so the slider 1320 can easily enter and exit the guide rail (ie, the scratch gap 1213-1).
  • the scratching member 130 may further include a mounting body 1330, multiple groups of scratching needles 1310 may be fixed to the mounting body 1330, each group of scratching needles 1310 may include one or more scratching needles 1310, each group Each of the scratch pins 1310 corresponds to a scratch gap 1213-1.
  • FIG. 15 is a schematic structural diagram of a scratching member 130 in some embodiments.
  • the position distribution of multiple sets of scoring needles 1310 can form two curves, and the two curves are respectively corresponding to the shape of the line connecting the two ends of the multiple scoring gaps 1213-1 (such as the connecting path 1216). match.
  • one of the two curves (which can be regarded as the starting curve) can be coincident with the end lines of the multiple scratch gaps 1213-1.
  • the scratches on the starting curve The needles 1310 are all located at the first end of the scratch gap 1213-1, and the scratch needles 1310 on the other curve (which can be regarded as the end curve) are located at the middle of the scratch gap 1213-1.
  • the scratching needles 1310 on the ending curve are located at the second end of the scratching gap 1213-1, and the scratching needles 1310 on the starting curve are located at the middle of the scratching gap 1213-1.
  • the scratching needles 1310 on the starting curve are located at the middle of the scratching gap 1213-1.
  • only one scribe needle 1310 may be included.
  • the scoring part 120 may further include a first magnet, and the scoring part 130 is provided with a second magnet matching the first magnet.
  • the first magnet may be disposed on the bottom plate 1213 .
  • the second magnet can be the slider 1320 , or other structures connected with the scoring needle 1310 .
  • the first magnet can be moved to attract or repel the second magnet to move, thereby achieving the purpose of driving the scratch needle 1310 to move the scratch.
  • the first magnet and the second magnet repel each other, and the experimenter can manually move the first magnet along the scratch gap 1213 - 1 to drive the second magnet and then drive the scratch needle 1310 to scratch.
  • the repulsion force of the first magnet to the second magnet can be maintained at a stable level in the length direction of the scratching needle 1310, so that the pressure of the scratching needle 1310 on the bottom of the culture part 110 remains stable , thus better improving the uniformity and stability of scratches.
  • the marking part 120 may further include a driver 140 and one or more sensors 150 .
  • the driving member 140 can be used to drive the scratching member 130 to scratch along the scratching gap 1213 - 1
  • the sensor can be used to identify the pressure and/or the sliding distance of the scratching member 130 when scratching. Please refer to FIG. 16A and FIG. 16B .
  • FIG. 16A and FIG. 16B are schematic diagrams showing the connection structure of the driving member 140 and the scratching member 130 .
  • the driver 140 may include a motor.
  • the sensor 150 may include a pressure sensor, a displacement sensor, etc., or any combination thereof.
  • the pressure sensor may include a piezoresistive pressure sensor, a ceramic pressure sensor, a diffused silicon pressure sensor, a sapphire pressure sensor, a piezoelectric pressure sensor, and the like.
  • the displacement sensor may include a strain sensor, an inductive sensor, a differential transformer sensor, an eddy current sensor, and a Hall sensor.
  • the sensor 150 when the sensor 150 is a pressure sensor, ensuring that the reading of the sensor 150 is stable during scratching can ensure that the scratching member 130 is subjected to a stable push/pull force, thereby ensuring uniform scratching.
  • the sensor 150 when the sensor 150 is a displacement sensor, it can identify whether the scratching member 130 has moved a specified distance, or reached the end of the scratch (ie, the end of the scratch gap 1213 - 1 ).
  • the scratching member 130 can be connected to the driving member 140 through a spring 160 , and the spring 160 can be arranged along the direction of the scratching gap 1213 - 1 (ie, the direction AB in FIG. 16A ).
  • the scratching member 130 before starting to scratch, if the scratching member 130 is located at the position shown in FIG. 16B (1), the horizontal position of the tip of the scratching member 130 can be set in the culture part 110 without contacting cells.
  • the driver 140 may be directly connected to the scoring member 130 , ie without the spring 160 .
  • the senor 150 may be arranged along the length direction of the scratching member 130 . Therefore, the sensor 150 can recognize the pressure received by the scratching member 130 when it is scratched. Keeping the reading of the sensor 150 stable during scratching ensures that the scratching piece 130 is subjected to a stable pressure, thereby ensuring uniform scratching.
  • the cell scratching device 101 may include a culture unit 110 , a scratching member 130 , a processor, a scratching table, and a motor.
  • the culture section 110 may include a culture dish.
  • the motor can be used to drive the scratching member 130 to work, and the processor can be used to control the work of the motor.
  • the scratching workbench may include a sample stage, a Petri dish fixing device, and a Petri dish identifying device.
  • the sample table can be used to provide an operation support platform for cell scratching
  • the culture dish fixing device and the culture dish identification device are both installed on the sample table.
  • the culture dish fixing device can be used to fix the cell culture dish, and the culture dish identification device can be used to identify information such as the position and/or model of the culture dish.
  • the culture dish fixing device may include a groove matching the culture dish, or a supporting and fixing frame.
  • the petri dish recognition device may include a sensor (for example, a pressure sensor, etc.) located on the sample stage, and/or a camera device (that is, identify the position of the petri dish by image).
  • the culture dish can be fixed to the designated position of the sample stage through the culture dish fixing device.
  • the petri dish can be manually placed in the designated position.
  • the scratching workbench may further include a culture dish moving mechanism, and the culture dish fixing device is installed on the culture dish moving mechanism.
  • the processor can identify the position of the culture dish through the culture dish identification device, so as to control the culture dish moving mechanism to move the culture dish to a designated position on the sample stage.
  • the culture dish moving mechanism can be a grid-shaped guide rail, and the culture dish fixing device is slidingly connected with the guide rail, and can move in the plane of the sample stage by switching between different guide rails (the sliding structure can refer to the above-mentioned spherical slider and its matching rail).
  • the culture dish moving mechanism can also be set with two-stage guide rails, the first-stage guide rail is fixed on the sample stage along the X-axis direction, the second-stage guide rail is slidingly connected with the first-stage guide rail, the second-stage guide rail is arranged along the Y-axis direction, and the culture dish fixing device is connected with the second-stage guide rail. Rail slide connection. The position in the X-axis direction is adjusted through the primary guide rail, and the position in the Y-axis direction is adjusted through the secondary guide rail, so that any position in the XY plane can be adjusted.
  • the petri dish identification device may send the recognized model of the petri dish to the processor, and the processor selects a preset scratch scheme according to the model of the petri dish.
  • the scratch scheme may include the distance corresponding to the gap between scratches, the number of scratches, and the like.
  • the scratching scheme may be determined according to experimental requirements input by a user (eg, an experimenter).
  • the processor can calculate the initial scratch position and the end scratch position of each scratch according to the corresponding scratch scheme, and control the motor to drive the scratch member 130 to calculate the initial scratch position and the end scratch position Make moves, scratches in turn.
  • it is possible to identify whether the current scratching ends by setting a lateral pressure sensor on the scratching device. For example, when the scratching member 130 scratches the edge of the petri dish, the pressure sensor senses an increase in lateral pressure, which means that the marking is over, and the processor can control the marking member 130 to move to the initial scratching position of the next scratch. Proceed to the next scratch.
  • the sample stage can also be driven by another motor, and can move back and forth along the XY axis in the plane.
  • the bottom of the sample stage can also be provided with two-stage guide rails (see above).
  • the processor can control the motor to drive the sample stage to move in the XY plane, so as to achieve scratching.
  • the processor may also control the culture dish moving mechanism to move the culture dish in the XY plane, so as to achieve scratching.
  • the cell scratching device 101 can be made of glass, metal, plastic, resin and other materials. Since the cell scratching device 101 in this specification is mainly used in cell scratching experiments, the transparent material is convenient for observing the scratching effect, and at the same time, the utensils for the cell scratching experiment need to be frequently sterilized by autoclaving, and the materials need to be resistant to high temperature and high pressure, so the scratching
  • the cover plate is preferably glass.
  • the possible beneficial effects of the cell scratching device disclosed in this specification include but are not limited to: (1) The scratch cover and the culture part are installed through a limit structure, which can reduce the lateral swing of the scratch part during scratching, and make the scratch The shape of the scratches is more regular; (2) The scratched parts move along the scratch gap, and the scratches are straight, and the distance between different scratches is uniform, which is convenient for follow-up observation; (3) The scratched parts and the scratched cover are limited, The movement of the scratching piece in the vertical direction is limited, so that the force of the scratching piece acting on the cells is just moderate, neither too little force will cause incomplete scratches, nor too much force will scratch the culture part, ensuring the integrity of the scratches Stable; (4) The scratched part is driven by the motor, and the sensor detects the pressure and displacement of the scratched part to realize automatic scratching, reduce manpower, improve efficiency, and ensure uniform and stable scratching.
  • the possible beneficial effects of the system for determining cell migration ability disclosed in this specification include but are not limited to: (1)
  • the cell image analysis device is used to automatically photograph and analyze scratches, which is simple and convenient to operate, reduces manpower, and improves the efficiency of photographing and analysis; 2) By combining the cell scratching device and the cell image analysis device, when analyzing the migration of scratched cells, the scratches can be precisely located, and fixed-point continuous photo imaging and analysis can be realized, ensuring the scientificity and reliability of the experimental results. Reliability; (3) By controlling the moving direction of the sample stage or the shooting module, the cumulative observation and analysis of a single scratch and the comparative observation and analysis of multiple scratches can be realized. It should be noted that different embodiments may have different beneficial effects. In different embodiments, the possible beneficial effects may be any one or a combination of the above, or any other possible beneficial effects.
  • numbers describing the quantity of components and attributes are used. It should be understood that such numbers used in the description of the embodiments use the modifiers "about”, “approximately” or “substantially” in some examples. grooming. Unless otherwise stated, “about”, “approximately” or “substantially” indicates that the stated figure allows for a variation of ⁇ 20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximations that can vary depending upon the desired characteristics of individual embodiments. In some embodiments, numerical parameters should take into account the specified significant digits and adopt the general digit reservation method. Although the numerical ranges and parameters used in some embodiments of this specification to confirm the breadth of the range are approximations, in specific embodiments, such numerical values are set as precisely as practicable.

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Abstract

一种确定细胞的迁移能力的方法和系统。所述方法包括：通过细胞划痕装置对细胞进行划痕操作，形成至少一个划痕；以及通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力。

Description

一种确定细胞的迁移能力的方法和系统
交叉引用
本申请基于并要求2021年6月17日提交的申请号为202110671398.1的中国申请的优先权。此申请的全部内容以引用方式被包含于此。
技术领域
本说明书涉及生物技术领域，具体涉及一种确定细胞迁移能力的方法和系统。
背景技术
细胞迁移与癌症的发生和发展关系密切，细胞迁移能力是衡量癌细胞转移能力的主要指标之一。对于细胞迁移能力的研究，一方面能够加深对细胞迁移行为的认识，另一方面对癌症等和细胞迁移密切相关的疾病的治疗探索具有重要价值。细胞划痕实验是研究细胞迁移能力的常用方法之一，“划痕”的制造、细胞迁移期间图像的获取以及后期图像数据的处理分析是划痕实验的关键步骤。因此，希望提供一种确定细胞迁移能力的方法和系统，可以保证划痕的均一稳定性和划痕实验的重现性，从而可以高效、全面、准确地检测细胞的迁移能力。
发明内容
在本说明书的第一方面，提供了一种确定细胞的迁移能力的方法。所述方法包括：通过细胞划痕装置对细胞进行划痕操作，形成至少一个划痕；以及通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力。
在一些实施例中，所述通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力，包括：通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像；以及基于所述至少一个划痕的所述至少一个图像，确定所述细胞的迁移能力。
在一些实施例中，所述细胞划痕装置包括培养部和划痕部，所述培养部用于培养所述细胞，所述划痕部包括划痕盖板和划痕件，所述划痕盖板包括依次连接的底板、连接件与限位结构，所述底板与所述限位结构分别位于所述连接件的两端，所述底板设有至少一个划痕间隙。
在一些实施例中，所述通过细胞划痕装置对细胞进行划痕操作，形成至少一个划痕，包括：通过所述限位结构将所述划痕盖板固定在所述培养部上；以及通过将所述划痕件插入所述至少一个划痕间隙且沿所述至少一个划痕间隙的一端移动到另一端，以对所述细胞进行所述划痕操作，所述至少一个划痕的位置由所述至少一个划痕间隙的位置决定。
在一些实施例中，所述通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力，包括：通过所述细胞图像分析装置，基于所述拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像，其中所述多个图像中的每个图像对应一个预设时间点；以及基于所述至少一个划痕的所述多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力。
在一些实施例中，在对所述细胞进行所述划痕操作后形成多个划痕，所述多个划痕包括第一划痕和第二划痕，所述通过所述细胞图像分析装置，基于所述拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，包括：基于所述拍摄参数和所述第一划痕的位置，控制所述细胞图像分析装置对所述第一划痕进行自动拍摄；基于对应于所述第一划痕的第一划痕间隙和对应于所述第二划痕的第二划痕间隙之间的位置关系，确定所述第一划痕和所述第二划痕的位置关系；以及基于所述第一划痕和所述第二划痕之间的位置关系和所述拍摄参数，控制所述细胞图像分析装置对所述第二划痕进行自动拍摄。
在一些实施例中，所述细胞图像分析装置包括样品台和拍摄模块，所述通过细胞图像分析装置，基于所述拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像，包括：在多个预设时间点中的每个预设时间点，将所述细胞划痕装置的所述培养部定位于所述样品台的目标位置处；基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕在所述预设时间点 的至少一个图像。
在一些实施例中，所述基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕在所述预设时间点的至少一个图像，包括：控制所述样品台或所述拍摄模块沿着平行于所述至少一个划痕的延伸方向进行移动，以获取所述至少一个划痕沿着所述延伸方向的多个视野的多个图像。
在一些实施例中，在对所述细胞进行所述划痕操作后形成多个划痕，所述多个划痕的延伸方向相互平行，所述基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕在所述预设时间点的至少一个图像，包括：控制所述样品台或所述拍摄模块沿着垂直于所述多个划痕的所述延伸方向进行移动，以获取所述多个划痕的多个图像。
在一些实施例中，所述基于所述至少一个划痕的所述多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力，包括：基于所述多个图像，确定所述细胞的迁移距离或迁移面积；以及基于所述迁移距离或所述迁移面积，和所述多个预设时间点，确定所述细胞的迁移能力。
在本说明书的第二方面，提供了一种确定细胞迁移能力的系统。所述系统包括：细胞划痕装置，用于对细胞进行划痕操作，形成至少一个划痕；以及细胞图像分析装置，用于对所述至少一个划痕进行定位拍摄及分析，以确定所述细胞的迁移能力。
在一些实施例中，所述细胞图像分析装置包括：拍摄模块，用于对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像。
在一些实施例中，所述细胞图像分析装置包括：分析模块，用于基于所述至少一个图像确定所述细胞的迁移能力。
在一些实施例中，所述细胞图像分析装置包括：样品台，用于定位所述细胞划痕装置的培养部。
在一些实施例中，所述细胞图像分析装置包括：控制模块，用于控制所述样品台和/或所述拍摄模块。
在一些实施例中，所述细胞划痕装置，包括：用于对所述细胞进行划痕操作的划痕部，所述划痕部包括划痕盖板；所述划痕盖板包括依次连接的底板、连接件与限位结构，所述底板与所述限位结构分别位于所述连接件的两端，所述底板设有多个划痕间隙，所述多个划痕间隙相互平行且均匀间隔分布；划痕时所述划痕盖板通过所述限位结构安装固定。
在本说明书的第三方面，提供了一种确定细胞的迁移能力的控制系统，所述系统包括：至少一个存储设备，用于存储一组指令；以及至少一个处理器与所述至少一个存储设备通信，当执行所述存储的指令时，所述至少一个处理器使所述系统执行本说明书的第一方面所述的确定细胞的迁移能力的方法。
在本说明书的第四方面，提供了一种根据本说明书的第一方面所述的方法、本说明书的第二方面所述的系统和本说明书的第三方面所述的控制系统在细胞迁移能力的确定中的应用。
本说明书的一部分附加特性可以在以下描述中进行说明。通过对以下描述和相应附图的研究或者对实施例的生产或操作的了解，本说明书的一部分附加特性对于本领域技术人员是明显的。本说明书的特征可以通过对以下描述的具体实施例的各个方面的方法、手段和组合的实践或使用得以实现和达到。
附图说明
本说明书将通过示例性实施例进行进一步描述。这些示例性实施例将通过附图进行详细描述。这些实施例是非限制性的示例性实施例，在这些实施例中，各图中相同的编号表示相似的结构，其中：
图1是根据本说明书一些实施例所示的确定细胞迁移能力系统的应用场景示意图；
图2A是根据本说明书一些实施例所示的确定细胞迁移能力的示例性流程图；
图2B是根据本说明书一些实施例所示的确定细胞迁移能力的示例性流程图；
图3是根据本说明书一些实施例所示的获取划痕图像的示例性流程图；
图4A是根据本说明书一些实施例所示的沿平行于划痕的延伸方向进行拍摄的示意图；
图4B是根据本说明书一些实施例所示的沿垂直于划痕的延伸方向进行拍摄的示意图；
图5是根据本说明书一些实施例所示的确定细胞迁移能力的示例性流程图；
图6是根据本说明书一些实施例所示的示例性划痕图像的示意图；
图7是根据本说明书一些实施例所示的示例性细胞图像分析装置的模块图；
图8是根据本说明书一些实施例所示的示例性细胞划痕装置的剖面结构示意图；
图9是根据本说明书一些实施例所示的示例性划痕盖板120的俯视结构示意图；
图10是根据本说明书一些实施例所示的示例性培养部110的俯视结构示意图；
图11是根据本说明书一些实施例所示的示例性划痕盖板120的结构示意图；
图12是根据本说明书一些实施例所示的示例性划痕件130与划痕间隙1213-1的配合结构示意图一；
图13是根据本说明书一些实施例所示的示例性划痕件130与划痕间隙1213-1的配合结构示意图二；
图14是根据本说明书一些实施例所示的示例性底板1213的结构示意图；
图15是根据本说明书一些实施例所示的示例性划痕件130的结构示意图；
图16A和图16B是根据本说明书一些实施例所示的示例性驱动件140与划痕件130的连接结构示意图。
具体实施方式
为了更清楚地说明本说明书实施例的技术方案，下面将对实施例描述中所需要使用的附图作简单的介绍。然而，本领域技术人员应该明白，可以在没有这些细节的情况下实施本说明书。在其它情况下，为了避免不必要地使本说明书的各方面变得晦涩难懂，已经在较高的层次上描述了众所周知的方法、过程、系统、组件和/或电路。对于本领域的普通技术人员来讲，显然可以对所披露的实施例做出各种改变，并且在不偏离本说明书的原则和范围的情况下，本说明书中所定义的普遍原则可以适用于其他实施例和应用场景。因此，本说明书不限于所示的实施例，而是符合与申请专利范围一致的最广泛范围。
本说明书中所使用的术语仅出于描述特定示例实施例的目的，而非限制性的。如本说明书使用的单数形式“一”、“一个”及“该”同样可以包括复数形式，除非上下文明确提示例外情形。还应当理解，如在本申请说明书中使用的术语“包括”、“包含”仅提示存在所述特征、整数、步骤、操作、组件和/或部件，但并不排除存在或添加以上其它特征、整数、步骤、操作、组件、部件和/或其组合的情况。
可以理解的是，本说明书使用的术语“系统”、“引擎”、“单元”、“模块”和/或“区块”是用于按升序区分不同级别的不同构件、元件、部件、部分或组件的方法。然而，如果可以达到相同的目的，这些术语也可以被其他表达替换。
根据以下对附图的描述，本说明书的这些和其它的特征、特点以及相关结构元件的功能和操作方法，以及部件组合和制造经济性，可以变得更加显而易见，这些附图都构成本申请说明书的一部分。然而，应当理解的是，附图仅仅是为了说明和描述的目的，并不旨在限制本说明书的范围。应当理解的是，附图并不是按比例绘制的。
本说明书使用的流程图示出了根据本说明书公开的一些实施例所示的系统所执行的操作。应当理解的是，流程图中的操作可以不按顺序执行。相反，可以按照倒序或同时处理各种步骤。同时，也可以将一个或以上其他操作添加到这些流程图中。也可以从流程图中删除一个或以上操作。
细胞迁移是正常细胞的基本功能之一，是机体正常生长发育的生理过程，也是活细胞普遍存在的一种运动形式。胚胎发育、血管生成、伤口愈合、免疫反应、炎症反应、动脉粥样硬化、癌症转移等过程中都涉及细胞迁移。
细胞划痕实验是实验室分析细胞迁移能力最常用最简单的方法，原理是当细胞生长融合成单层状态时，在融合的单层细胞上人为制造一个空白区域，称为“划痕”。划痕边缘的细胞会逐渐进入空白区域使“划痕”愈合。
传统的细胞划痕实验一般需要通过记号笔先在培养皿的平板背面(即不与细胞接触的一面)画出一道或多道均匀的横线，然后培养细胞，待得到细胞层后，按照平板背面横线的方向，通过枪头或牙签在细胞层上划出一道或多道划痕。然后，在适当的时间点，如0、6、12、24小时取出培养皿，通过平板背面的标记，在显微镜下找到划痕，观察并测量划痕的宽度并拍照。最后，使用图像分析软件(Image J软件)打开图片后，随机划选取6至8条水平线，计算细胞间距离的均值，从而得到细胞的迁移能力(例如，细胞迁移率)。
但是，传统的细胞划痕方法常常会因为用力不匀，导致划痕不均。另外，在拍摄和分析划 痕时，仅通过记号笔的标记难以实现定点的连续观测且主观因素影响大。显微镜下拍照耗时且操作繁琐，Image J软件图像分析效率较低。
本说明书的一方面提供了一种确定细胞的迁移能力的方法。所述方法包括使用细胞划痕装置对所述细胞进行划痕操作，形成至少一个划痕。所述方法包括通过细胞图像分析装置，基于预设拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像，其中每个图像对应一个预设时间点。所述预设拍摄参数包括：进样坐标、所述至少一个划痕的拍摄总长度、或所述至少一个划痕的视野数量中的至少一个。所述方法包括基于所述至少一个划痕的所述多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力。
本说明书的另一方面提供了一种确定细胞迁移能力的系统。所述系统包括细胞划痕装置和细胞图像分析装置。细胞划痕装置包括用于培养细胞的培养部，和用于对所述细胞进行划痕操作以形成至少一个划痕的划痕部。细胞图像分析装置用于基于预设拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄分析，以确定所述细胞的迁移能力。
通过使用本说明书提供的细胞划痕装置对细胞进行划痕操作，可以保证划痕的均一稳定和划痕实验的重现性。通过结合使用细胞划痕装置和细胞图像分析装置，在分析划痕的细胞的迁移情况时，可以精确定位划痕，无需记号笔标记，即可定点连续拍照成像和分析，得到细胞的迁移距离和迁移面积，并且可以实现单条划痕的累计观测分析和多条划痕的对比观测分析。因此，本说明书提供的确定细胞迁移能力的方法无需记号笔标记，克服了传统划痕方法上的划痕不均、人工操作等误差，可以更高效、更全面、更准确地检测细胞的迁移能力。
图1是根据本说明书一些实施例所示的确定细胞迁移能力系统的应用场景示意图。确定细胞迁移能力系统100(或称为确定细胞迁移能力控制系统100)(可以简称为系统100)可以包括细胞划痕装置101、细胞图像分析装置102、网络105、存储设备104和处理设备103。确定细胞迁移能力系统100中的组件可以以各种方式连接。仅作为示例，细胞划痕装置101和/或细胞图像分析装置102可以直接或通过网络105连接到处理设备103或存储设备104。作为又一个示例，细胞划痕装置101和细胞图像分析装置102之间可以直接或通过网络105连接。
细胞划痕装置101可以用于在培养好的细胞上进行划痕操作。在一些实施例中，细胞划痕装置101可以包括培养部101-1和划痕部101-2。其中，培养部101-1(也可以称为细胞培养装置)可以用于细胞培养，划痕部101-2可以用于实现细胞划痕。在一些实施例中，培养部101-1可以包括培养皿或培养板。所述培养皿可以为玻璃或塑料材质。在一些实施例中，培养部101-1可以包括D90培养皿、六孔培养板等。在一些实施例中，划痕部101-2可以包括划痕盖板与划痕件。在一些实施例中，划痕盖板可以包括依次连接的底板、连接件与限位结构，底板与限位结构分别位于连接件的两端。关于细胞划痕装置101的更多描述请见本说明书的其它部分(例如，图8-图16B及其相关描述)。
细胞图像分析装置102可以用于通过拍摄图像对细胞生理活动进行分析。例如，细胞图像分析装置102可以用于定位划痕、控制拍摄轨迹、获取划痕的图像、分析划痕的图像以确定细胞的迁移能力等。在一些实施例中，细胞图像分析装置102可以包括样品台、拍摄模块、分析模块、控制模块等或其任意组合。关于细胞图像分析装置102的更多描述请见本说明书的其它部分(例如，图2A-7及其相关描述)。
处理设备103可以处理从其他设备或系统100组成部分中获得的数据和/或信息。处理设备103可以基于这些数据、信息和/或处理结果执行程序指令，以执行一个或多个本说明书中描述的功能。例如，处理设备103可以从细胞划痕装置101获取划痕间隙的位置。又例如，处理设备103可以从细胞图像分析装置102获取划痕的图像。又例如，处理设备103可以基于划痕的图像确定细胞的迁移能力。又例如，处理设备103可以从细胞图像分析装置102直接获取图像分析结果(例如，细胞的迁移能力)。在一些实施例中，处理设备103可以是单个服务器或服务器组。服务器组可以是集中式或分布式的。在一些实施例中，处理设备103可以是相对于系统100的一个或多个其他组件的本地组件或远程组件。例如，处理设备103可以经由网络105访问存储在细胞划痕装置101、细胞图像分析装置102和/或存储设备104中的信息和/或数据。作为另一示例，处理设备103可以直接连接至细胞划痕装置101、细胞图像分析装置102和/或存储设备104以访问所存储的信息和/或数据。在一些实施例中，处理设备103可以在云平台上实现。仅作为示例，云平台可以包括私有云、公共云、混合云、社区云、分布云、内部云、多层云等或其任意组合。在一些实施例中，处理器103可以包括中央处理器(CPU)、专用集成电路(ASIC)、专用指令处理器(ASIP)、图形处理器(GPU)、物理处理器(PPU)、数字信号处理器(DSP)、现场可编程门阵列(FPGA)、可编辑逻辑电路(PLD)、 控制器、微控制器单元、精简指令集电脑(RISC)、微处理器等或以上任意组合。
网络105可以连接系统100的各组成部分和/或连接系统与外部资源部分。网络105使得各组成部分之间，以及与系统之外其他部分之间可以进行通讯，促进数据和/或信息的交换。在一些实施例中，网络105可以是有线网络或无线网络中的任意一种或多种。例如，网络105可以包括电缆网络、光纤网络、电信网络、互联网、局域网络(LAN)、广域网络(WAN)、无线局域网络(WLAN)、城域网(MAN)、公共交换电话网络(PSTN)、蓝牙网络、紫蜂网络(ZigBee)、近场通信(NFC)、设备内总线、设备内线路、线缆连接等或其任意组合。各部分之间的网络连接可以是采用上述一种方式，也可以是采取多种方式。在一些实施例中，网络可以是点对点的、共享的、中心式的等各种拓扑结构或者多种拓扑结构的组合。
存储设备104可以用于存储数据和/或指令。存储设备104可以包括一个或多个存储组件，每个存储组件可以是一个独立的设备，也可以是其他设备的一部分。在一些实施例中，存储设备104可包括随机存取存储器(RAM)、只读存储器(ROM)、大容量存储器、可移动存储器、易失性读写存储器等或其任意组合。示例性的，大容量储存器可以包括磁盘、光盘、固态磁盘等。在一些实施例中，所述存储设备104可在云平台上实现。仅作为示例，所述云平台可以包括私有云、公共云、混合云、社区云、分布云、内部云、多层云等或其任意组合。
应该注意的是，上述描述仅出于说明性目的而提供，并不旨在限制本说明书的范围。对于本领域普通技术人员而言，在本说明书内容的指导下，可做出多种变化和修改。可以以各种方式组合本说明书描述的示例性实施例的特征、结构、方法和其他特征，以获得另外的和/或替代的示例性实施例。然而，这些变化与修改不会背离本说明书的范围。在一些实施例中，细胞划痕装置101和细胞图像分析装置102可以集成为一个划痕分析装置。在对细胞进行划痕操作时，在划痕分析装置的样品台上某一固定位置安装划痕件(例如，划痕针)，在样品台上完成培养部的安装及定位后，处理设备103可以获取培养部在样品台上的位置坐标和划痕件的安装位置坐标，处理设备103可以根据划痕方案，计算每条划痕的初始划痕位置和结束划痕位置，并通过控制样品台上的培养部根据初始划痕位置和结束划痕位置进行移动，依次通过划痕件进行划痕。拍照时，仅需将划痕件替换为拍摄装置(例如，摄像头)，采取同样的方式实现各条划痕的定点拍摄。
在一些实施例中，存储设备104和/或处理设备103可以集成至细胞划痕装置101和/或细胞图像分析装置102中。例如，细胞划痕装置101和细胞图像分析装置102中各自有相应的处理设备。
在一些实施例中，系统100中的一个或多个组件可以省略。例如，可以省略网络105、存储设备104和/或处理设备103。用户可以使用细胞划痕装置101进行划痕操作，并将划痕的位置输入至细胞图像分析装置102，细胞图像分析装置102可以基于划痕的位置对划痕进行拍摄分析。
在一些实施例中，系统100可以包括一个或多个其它组件。例如，系统100可以包括终端设备(未在图1中示出)。终端设备可以包括移动设备、平板计算机、膝上型计算机等或其任何组合。在一些实施例中，用户可以使用终端设备控制系统100中的一个或多个组件(例如，细胞划痕装置101、细胞图像分析装置102)。例如，用户可以通过终端设备输入控制细胞划痕装置101进行划痕操作的指令和/或控制细胞图像分析装置102进行拍摄分析的指令。细胞划痕装置101可以基于用户输入的指令进行划痕操作。细胞图像分析装置102可以基于用户输入的指令对划痕进行拍摄分析。在一些实施例中，终端设备可以显示系统100的数据。例如，终端设备可以显示划痕的位置、形状、轮廓等信息。又例如，终端设备可以显示划痕的图像。又例如，终端设备可以显示细胞的迁移距离、迁移面积、迁移能力等信息。
图2A是根据本说明书的一些实施例所示的确定细胞迁移能力的示例性流程图。在一些实施例中，过程200的至少一部分可以由细胞划痕装置101、细胞图像分析装置102、或处理设备103执行。例如，过程200可以以指令(例如，应用程序)的形式存储在存储设备(例如，存储设备104)中，并由细胞划痕装置101、细胞图像分析装置102、或处理设备103调用和/或执行。以下所示过程的操作仅出于说明的目的。在一些实施例中，过程200可以利用一个或以上未描述的附加操作和/或没有所讨论的一个或以上操作来完成。另外，图2A中示出的和下面描述的过程200的操作的顺序不旨在是限制性的。
在步骤210中，在细胞培养装置(例如，培养部101-1)中培养细胞。
在一些实施例中，可以取对数期生长良好的细胞接种到培养部中，使用培养基培养细胞。接种量以培养24小时以后融合率达到100％为准。融合率可以指单层培养的贴壁生长细胞占所生长区域面积的百分比。融合率达到100％可以指细胞长满培养部底部。
在一些实施例中，在细胞达到100％融合后，去除培养部中的培养基。例如，用户(例如，实验人员)可以使用移液器吸弃培养部中的培养基，使用划痕部(例如，划痕部101-2)对细胞进行划痕操作。
在步骤220中，通过细胞划痕装置(例如，划痕部101-2)对所述细胞进行划痕操作，形成至少一个划痕。
在一些实施例中，细胞划痕装置可以是手动划痕装置、半自动划痕装置或全自动划痕装置。例如，细胞划痕装置的划痕部可以包括划痕盖板和划痕件，划痕盖板包括依次连接的底板、连接件与限位结构，底板与限位结构分别位于连接件的两端，底板设有至少一个划痕间隙。在用户使用细胞划痕装置进行划痕操作时，首先，用户可以将去除培养基后的培养部固定在操作台上；然后，通过限位结构将所述划痕盖板固定在所述培养部上；最后，通过将划痕件插入至少一个划痕间隙且沿至少一个划痕间隙的一端移动到另一端，以对细胞进行划痕操作。具体地，可以将划痕件移动至划痕间隙的端部，并插入划痕间隙，将划痕件沿划痕间隙滑动至另一端，再将划痕件取出(特殊地，划痕件可以反复滑动，以尽可能地使划痕路径上的细胞被刮除干净)。至少一个划痕的位置由至少一个划痕间隙的位置决定。关于细胞划痕装置和使用细胞划痕装置进行划痕操作的更多描述请见图8-图16B及其相关描述。
在步骤230中，清洗所述细胞，并在所述细胞培养装置(例如，培养部101-1)中继续培养所述细胞。
划痕操作完成后，用户可以使用缓冲液(例如，无菌磷酸缓冲盐溶液(PBS))多次冲洗细胞表面，洗去划痕时产生的不贴壁细胞，使划痕与细胞的界限清晰干净。清洗完成后加入新的培养基，继续培养。例如，可以将细胞放入37℃的5％CO 2培养箱内继续培养。
在步骤240中，通过细胞图像分析装置(例如，细胞图像分析装置102)，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像。在一些实施例中，可以通过细胞图像分析装置，基于预设拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像。
在一些实施例中，多个图像中的每个图像对应一个预设时间点。预设时间点可以是预先设置的拍摄时间点。例如，预设时间点可以为在对细胞进行划痕操作后的0小时、6小时、12小时和24小时等。
预设拍摄参数可以指用于拍摄图像的相关参数。预设拍摄参数可以是用户根据细胞培养装置的型号、细胞图像分析装置的型号、细胞的种类、划痕的位置、划痕的面积、实验的精度要求等预先设定的参数。在一些实施例中，预设拍摄参数可以包括进样坐标、至少一个划痕的拍摄总长度、至少一个划痕的视野数量等或其任何组合。
进样坐标可以指样品台零位与第一个拍摄视野的相对位置。在一些实施例中，样品台零位可以指样品台的初始位置。例如，当细胞图像分析装置处于未使用的初始状态时，样品台可以处于样品台零位。当细胞图像分析装置结束拍摄时，样品台可以回归至零位。拍摄视野可以指划痕上的待拍摄位点。第一拍摄视野可以指划痕上的第一个待拍摄的位点。
在一些实施例中，可以将划痕的第一个拍摄视野的位置的坐标输入至细胞图像分析装置中，细胞图像分析装置可以根据样品台零位的坐标和第一个拍摄视野的位置的坐标，确定样品台的进样坐标。细胞图像分析装置可以基于样品台的进样坐标，控制样品台的移动方向和移动距离，以使细胞图像分析装置的拍摄模块(例如，拍摄模块720)可以对样品台上的培养部中的划痕的第一拍摄视野进行拍摄。
划痕的拍摄总长度可以指所述划痕需要拍摄的长度。划痕的视野数量可以指所述划痕的拍摄次数。例如，假设一条划痕的长度为5厘米，设置划痕的拍摄总长度为3厘米，视野数量为10，那么可以确定从所述划痕的某一端起始位置开始，每隔0.3厘米为一个拍摄视野。
在一些实施例中，可以根据拍摄情况或实验的精度要求确定拍摄总长度和视野数量。例如，为提高实验的精度，可以通过增加拍摄总长度和视野数量获取更多实验数据。又例如，由于细胞平铺不均造成某个划痕的间隙过小或过大，可以不对该划痕进行拍摄。
在一些实施例中，用户可以设置拍摄的第一划痕的拍摄总长度和视野数量，细胞图像分析装置可以自动基于其他划痕与第一划痕之间的位置关系，生成其他划痕的拍摄总长度和视野数量。例如，假设第一划痕的长度为5厘米，第一划痕的拍摄总长度为3厘米，视野数量为10，第二划痕与第一划痕的长度相等，那么细胞图像分析装置可以自动设置第二划痕的拍摄总长度同样为3厘米，视野数量为10。假设第二划痕的长度为2.5厘米，那么细胞图像分析装置可以自动设置第二划痕的 拍摄总长度为1.5厘米，视野数量为5。
在一些实施例中，拍摄参数还可以包括曝光度和拍摄焦距等。在一些实施例中，用户可以根据经验预先设定曝光度和拍摄焦距。在一些实施例中，可以基于实时拍摄的图像，动态调整拍摄焦距值。例如，可以根据实时拍摄的多张图像中划痕的清晰度确定最佳成像的焦距值。具体地，将清晰度最佳的图像对应的焦距值确定为最佳成像的焦距值。并将最佳成像的焦距值用于其他视野的拍摄。又例如，由于培养部的制作工艺的问题，无法保证培养部的底部的不同部位与摄像头之间的距离相同，因此可以在对每个拍摄视野进行拍摄前，进行自动调焦，从而保证每次拍摄都可以获得较好的图像质量。在一些实施例中，可以基于第一预设时间点确定的多个拍摄视野的焦距值确定其他预设时间点相应拍摄视野的焦距值。例如，在预设时间点0小时对划痕进行多个视野的拍摄，对每个视野进行调焦并记录下最佳成像的焦距值，在其他预设时间点(如6小时、12小时和24小时等)进行拍摄时，可获取记录下的焦距值并基于该值调焦。
在一些实施例中，为了确保图像分辨率的一致性，可以使用同样的拍摄参数获取所有划痕的图像。例如，可以将预先设置好的拍摄参数或拍摄第一条划痕时的拍摄参数存储在存储设备中，在后续拍摄其它划痕时通过调用该拍摄参数拍摄其他划痕的图像。在一些实施例中，可以通过在培养装置上设置条形码或二维码等来记录当前的拍摄参数，则下次拍摄时直接通过扫码即可完成拍摄参数的获取。
在一些实施例中，可以根据划痕的拍摄总长度和视野数量确定样品台每次移动的距离，实现划痕的自动拍摄。例如，假设划痕的拍摄总长度为3厘米，视野数量为10，则每次拍摄的移动距离为0.3厘米。即，样品台每次沿划痕的延伸方向移动0.3厘米，进行一次视野的拍摄。
在一些实施例中，在对所述细胞进行划痕操作后可以形成多个划痕，细胞图像分析装置可以基于多个划痕对应的预设拍摄参数，对多个划痕依次进行拍摄。例如，在对所述细胞进行划痕操作后可以形成第一划痕和第二划痕，细胞图像分析装置可以基于对应第一划痕的预设拍摄参数和第一划痕的位置，控制所述细胞图像分析装置对所述第一划痕进行自动拍摄。细胞图像分析装置可以基于对应于所述第一划痕的第一划痕间隙和对应于所述第二划痕的第二划痕间隙之间的位置关系，确定所述第一划痕和所述第二划痕的位置关系。细胞图像分析装置可以基于所述第一划痕和所述第二划痕之间的位置关系和所述预设拍摄参数，控制所述细胞图像分析装置对所述第二划痕进行自动拍摄。例如，在对第一划痕拍摄完成后，可以根据第一划痕的拍摄终点位置坐标和第二划痕的拍摄起始位置坐标，控制样品台的移动方向和移动距离，以对第二划痕进行拍摄。其中，第一划痕的拍摄终点位置坐标和第二划痕的拍摄起始位置坐标可以根据划痕部上的第一划痕间隙和第二划痕间隙的位置确定。
在一些实施例中，为了提高对多个划痕的拍摄效率，可以根据多个划痕的位置，确定走位效率更高的走位顺序。例如，可以根据多个划痕中的每个划痕的每个拍摄视野的坐标，通过算法自动计算拍摄模块或样品台最高效率的走位顺序，并控制拍摄模块或样品台按该走位顺序进行走位。具体的，对多条互相平行的划痕进行拍摄时，可以选择“弓”字形进行拍摄。关于拍摄走位的更多描述可以见图4A和4B及其相关描述。
在步骤250中，细胞图像分析装置102(或处理设备103)可以基于至少一个划痕的多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力。
细胞的迁移能力可以指细胞从初始位置移动到另一个位置的能力。细胞的迁移能力可以通过细胞的迁移率来评价。细胞的迁移率可以指细胞迁移面积(或迁移距离)与检测时长的比值。
在一些实施例中，处理设备103(或细胞图像分析装置)可以从多个图像中的每个图像提取所述至少一个划痕的轮廓。处理设备103(或细胞图像分析装置)可以基于所述轮廓确定所述细胞的迁移距离或迁移面积。处理设备103(或细胞图像分析装置)可以基于所述迁移距离或所述迁移面积，和所述多个预设时间点，确定所述细胞的迁移能力。关于确定细胞迁移能力的更多描述可以在本说明书的其它地方找到(例如，图5-6及其相关描述)。
应当注意，本说明书的以上描述仅出于说明的目的而提供的，而无意于限制本说明书的范围。对于本领域的普通技术人员来说，可以根据本说明书的描述，做出各种各样的变化和修改。然而，这些变化和修改不脱离本说明书的范围。例如，步骤210和/或步骤230可以省略。又例如，步骤220和230可以合并为一个步骤。又例如，在步骤240中，细胞图像分析装置可以仅基于划痕的位置对划痕进行自动拍摄。具体地，可以将划痕的多个视野的位置坐标输入细胞图像分析装置中，细胞分析装置可以基于划痕的多个视野的位置坐标对多个视野进行自动拍摄分析。在一些实施例中，在步骤240之前，需要吸弃培养部中的培养基再对划痕进行拍摄分析，拍摄完成后再加入新的培养 基。在一些实施例中，可以不需要吸弃培养部中的培养基，而是在有培养基的情况下对划痕进行拍摄分析。在这种情况下，在将培养部放置在样品台上后，需要等培养基的液面平静后再进行拍照，以防液面波动影响划痕拍摄的准确性。
在一些实施例中，可以通过细胞划痕装置对细胞进行划痕操作，形成至少一个划痕。在一些实施例中，可以使用手动划痕装置、半自动划痕装置或全自动划痕装置进行划痕操作。例如，可以使用图2A所说明的细胞划痕装置进行划痕操作。又例如，可以使用图8-图16B所说明的细胞划痕装置进行划痕操作。再例如，也可以使用其他方式进行细胞划痕操作。然后，可以通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力。在一些实施例中，可以使用图2A-7所说明的细胞图像分析装置对划痕进行拍摄分析。在一些实施例中，可以使用其他方式对划痕进行拍摄分析。例如，可以使用显微镜对划痕进行拍摄分析。
图2B是根据本说明书的一些实施例所示的确定细胞迁移能力的示例性流程图。在一些实施例中，过程205的至少一部分可以由细胞划痕装置101、细胞图像分析装置102、或处理设备103执行。例如，过程205可以以指令(例如，应用程序)的形式存储在存储设备(例如，存储设备104)中，并由细胞划痕装置101、细胞图像分析装置102、或处理设备103调用和/或执行。以下所示过程的操作仅出于说明的目的。在一些实施例中，过程205可以利用一个或以上未描述的附加操作和/或没有所讨论的一个或以上操作来完成。
在步骤260中，通过细胞划痕装置(例如，划痕部101-2)对细胞进行划痕操作，形成至少一个划痕。
关于细胞划痕装置和使用细胞划痕装置进行划痕操作的更多描述请见图2A中的步骤220、图8-图16B及其相关描述。
在步骤270中，通过细胞图像分析装置102(或处理设备103)对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力。
在一些实施例中，可以通过细胞图像分析装置102对至少一个划痕进行定位拍摄，以获取至少一个划痕的至少一个图像。细胞图像分析装置102可以基于至少一个划痕的至少一个图像，确定细胞的迁移能力。关于对至少一个划痕进行拍摄分析，以确定细胞的迁移能力的更多描述请见图2A中的步骤240和250的相关描述。
应当注意，本说明书的以上描述仅出于说明的目的而提供的，而无意于限制本说明书的范围。对于本领域的普通技术人员来说，可以根据本说明书的描述，做出各种各样的变化和修改。然而，这些变化和修改不脱离本说明书的范围。
图3是根据本说明书的一些实施例所示的获取划痕图像的示例性流程图。在一些实施例中，过程300的至少一部分可以由细胞图像分析装置102或处理设备103执行。例如，过程300可以以指令(例如，应用程序)的形式存储在存储设备(例如，存储设备104)中，并由细胞图像分析装置102或处理设备103调用和/或执行。以下所示过程的操作仅出于说明的目的。在一些实施例中，过程300可以利用一个或以上未描述的附加操作和/或没有所讨论的一个或以上操作来完成。另外，图3中示出的和下面描述的过程300的操作的顺序不旨在是限制性的。
步骤310，在多个预设时间点中的每个预设时间点，将培养部定位于细胞图像分析装置的样品台(例如，样品台710)的目标位置处。
目标位置可以指样品台上用于放置培养部的位置。例如，目标位置可以是样品台的中心位置。
在一些实施例中，可以通过在培养部和样品台上设计基点或基线，进行人工定位。例如，可以在培养部和样品台上均设置十字方位的数字标记，通过将培养部和样品台上的相应的十字方位的数字进行对准，可以实现培养部在样品台上的定位。在一些实施例中，可以在样品台上设置培养部适配器，以实现培养部在样品台上的定位。例如，培养部的底部设置有凹槽适配器，样品台表面设置有与之对应的凸起适配器，通过两者匹配实现培养部的定位。
在一些实施例中，由于培养部是对称结构(例如，圆形的培养皿)，可以在培养部非中心位置设置方向标记，且不同的培养部均有各自的标号。可以基于培养部的标号和方向标记自动记录每个培养部放置在样品台的位置和方向。在不同的预设时间点，可以根据培养部在第一个预设时间点放置在样品台上的位置和方向再次对培养部进行定位，以确保培养部在不同的预设时间点放置在样品台的位置和方向都是一致的。
在一些实施例中，样品台上可以设置有培养部移动机构，移动机构可以移动培养部到目标位置。例如，当把培养部放置在样品台上后，细胞图像分析装置可以对培养部进行拍摄(如可以通 过低放大倍数拍摄培养部)，以获取培养部的图像。通过分析培养部的图像，可以确定培养部的圆心。基于培养部的圆心与样品台零位之间的位置关系，确定培养部的移动方向和移动距离，并控制培养部移动机构对培养部进行移动。
在一些实施例中，为了更加准确的定位，可以在培养部和样品台上设置相互对应的基线(例如，以过培养皿圆心的一条直线为基线)。在获取培养部的图像后，可以从培养部的图像中提取培养部的基线，根据培养部基线和样品台基线之间的位置关系，确定培养部的移动方向和移动距离，并控制培养部移动机构对培养部进行移动。
在一些实施例中，在每个预设时间点对划痕进行拍摄之前，或者在一个预设时间点对多条划痕进行拍摄之前，都需要对培养部在样品台上的位置进行校正，以保证每次拍摄时，培养部都处于样品台的同一个目标位置处。例如，可以在培养部和样品台上均设定一个相互对应的基点(或基线)，通过确定培养部和样品台上基点(或基线)之间是否发生移动，确定是否需要校正培养部在样品台上的位置，以及校正的方式(例如，培养部需要移动的方向和距离)。
步骤320，细胞图像分析装置102(例如，控制模块740)(或处理设备103)可以基于预设拍摄参数和划痕的位置，控制拍摄模块(例如，拍摄模块720)对所述划痕进行自动拍摄，以获取所述划痕在所述预设时间点的至少一个图像。
在一些实施例中，由于本说明书使用细胞划痕装置代替人工划线，形成的划痕的位置与细胞划痕装置中的划痕间隙的位置相对应，因此可以通过获取细胞划痕装置的划痕间隙的位置信息确定划痕信息，并基于该划痕信息依次对多个划痕进行拍摄。划痕信息包括各种与划痕相关的信息，例如，划痕间隔、划痕位置、划痕端点和划痕之间的位置关系等。例如，细胞图像分析装置可以从细胞划痕装置处获取与划痕对应的划痕间隙的位置，并基于划痕间隙的位置确定划痕的位置，并对划痕进行拍摄。又例如，用户可以将与划痕对应的划痕间隙的位置信息输入至细胞图像分析装置中，细胞图像分析装置可以基于划痕间隙的位置确定划痕的位置，并对划痕进行拍摄。
在一些实施例中，可以对细胞划痕装置的划痕间隙进行编号，并基于编号存储相应的划痕间隙的信息(例如，长度、宽度、位置坐标)，当需要对某一个划痕间隙产生的划痕进行拍摄时，可以直接获取所述划痕间隙的信息作为划痕信息。
在一些实施例中，可以通过对划痕的端点进行标记、获取培养部图像、基于细胞透光程度等方法确定划痕信息。例如，可以对划痕端点进行荧光标记，通过荧光追踪确定划痕端点。又例如，由于划痕区域与非划痕区域的透光程度不同(非划痕区域有细胞覆盖因此透光度低于划痕区域)，可以在培养部底部进行适当强度的光照(例如，不会影响细胞生长的白光)，透光度较好的区域为划痕区域，透光度较差的区域为非划痕区域，并记录划痕的长度和不同划痕之间的间隙。又例如，可以通过低放大倍数拍摄培养部，获取培养部的图像，通过识别培养部的图像中的划痕，以确定划痕的信息。具体地，细胞图像分析装置的拍摄模块可以包括至少一个局部相机和一个全局相机，全局相机可以拍摄的划痕的全局图像，并基于全局图像确定划痕的信息，局部相机可以进一步拍摄划痕的多个视野的图像。
在一些实施例中，可以通过机械装置定位划痕。例如，培养部的底部与划痕对应的位置设置有用于划痕定位的凹槽适配器，样品台底部设置有与之对应的突起适配器，通过两者匹配实现划痕定位。
应当注意，本说明书的以上描述仅出于说明的目的而提供的，而无意于限制本说明书的范围。对于本领域的普通技术人员来说，可以根据本说明书的描述，做出各种各样的变化和修改。然而，这些变化和修改不脱离本说明书的范围。
图4A是根据本说明书的一些实施例所示的沿平行于划痕的延伸方向进行拍摄的示意图。图4B是根据本说明书的一些实施例所示的沿垂直于划痕的延伸方向进行拍摄的示意图。图中黑点表示拍摄视野。
如图4A所示，划痕A包括10个拍摄视野，分别为A1、A2…和A10；划痕B包括13个拍摄视野，分别为B1、B2…和B13；划痕C包括10个拍摄视野，分别为C1、C2…和C10。划痕A、划痕B和划痕C的延伸方向相互平行。在一些实施例中，细胞图像分析装置可以控制样品台(或拍摄模块)沿着平行于划痕的延伸方向进行移动，以获取划痕沿着所述延伸方向的多个视野的多个图像。例如，细胞图像分析装置可以控制拍摄模块(例如，摄像头)移动至划痕A的起始拍摄位置(例如，拍摄视野A1)，并控制拍摄模块沿着平行于划痕A的延伸方向进行移动，依次拍摄A1、A2…至A10，直至完成划痕A的拍摄，以实现单条划痕的不同视野的观测分析。
然后，细胞图像分析装置可以控制拍摄模块移动至划痕B的起始拍摄位置(例如，拍摄视 野B1)，并控制拍摄模块沿着平行于划痕B的延伸方向进行移动，依次拍摄B1、B2…至B10，直至完成划痕B的拍摄。最后，细胞图像分析装置可以控制拍摄模块移动至划痕C的起始拍摄位置(例如，拍摄视野C1)，并控制拍摄模块沿着平行于划痕C的延伸方向进行移动，依次拍摄C1、C2…至C10，直至完成划痕C的拍摄。
在一些实施例中，为了提高拍摄效率，在完成划痕A的拍摄后，拍摄模块可以移动至划痕B的拍摄视野B13处，依次拍摄B13、B12…至B1，直至完成划痕B的拍摄。而后，拍摄模块移动至划痕C的拍摄视野C1处，依次拍摄C1、C2…至C10，直至完成划痕C的拍摄。
如图4B所示，划痕D、划痕E和划痕F分别有两个拍摄视野。划痕D、划痕E和划痕F的延伸方向相互平行。在一些实施例中，细胞图像分析装置可以控制样品台(或拍摄模块)沿着垂直于划痕的延伸方向进行移动，以获取所述多个划痕的多个图像。例如，细胞图像分析装置可以控制拍摄模块(例如，摄像头)移动至划痕D的起始拍摄位置(例如，拍摄视野D1)，并控制拍摄模块沿着垂直于划痕D的延伸方向进行移动，依次拍摄划痕D的拍摄视野D1、划痕E的拍摄视野E1和划痕F的拍摄视野F1，以实现多条划痕的对比观测分析。
然后，细胞图像分析装置可以控制拍摄模块移动至划痕D的拍摄视野D2，并控制拍摄模块沿着垂直于划痕D的延伸方向进行移动，依次拍摄划痕D的拍摄视野D2、划痕E的拍摄视野E2和划痕F的拍摄视野F2。在一些实施例中，为了提高拍摄效率，在完成划痕F的拍摄视野F1，拍摄模块可以移动至划痕F的拍摄视野F2处，依次拍摄划痕F的拍摄视野F2、划痕E的拍摄视野E2和划痕D的拍摄视野D2。
图5是根据本说明书的一些实施例所示的确定细胞迁移能力的示例性流程图。在一些实施例中，过程500的至少一部分可以由细胞图像分析装置102或处理设备103执行。例如，过程500可以以指令(例如，应用程序)的形式存储在存储设备(例如，存储设备104)中，并由细胞图像分析装置102或处理设备103调用和/或执行。以下所示过程的操作仅出于说明的目的。在一些实施例中，过程500可以利用一个或以上未描述的附加操作和/或没有所讨论的一个或以上操作来完成。另外，图5中示出的和下面描述的过程500的操作的顺序不旨在是限制性的。
在步骤510中，细胞图像分析装置102(例如，分析模块730)(或处理设备103)可以从划痕的多个图像中的每个图像中提取划痕的轮廓。
在一些实施例中，划痕的多个图像是在多个预设时间点下拍摄得到的。例如，划痕的多个图像可以分别是在0小时、2小时、4小时的预设时间点下拍摄得到的。在一些实施例中，处理设备103(或细胞图像分析装置)可以根据图像分割算法从图像中提取划痕的轮廓。示例性图像分割算法可以包括基于区域的算法(例如，阈值分割、区域增长分割)、边缘检测分割算法、基于压缩的算法、基于直方图的算法、双重聚类算法等。
步骤520，细胞图像分析装置102(例如，分析模块730)(或处理设备103)可以基于所述多个图像中的多个轮廓确定细胞的迁移距离或迁移面积。
细胞的迁移距离可以指不同预设时间点的划痕两侧细胞连线的距离的差值。例如，可以将不同预设时间点获取的图像中的划痕轮廓两侧细胞连线的距离差确定为该时间范围内的细胞迁移距离。具体地，假设在预设时间点0小时获取的图像中，划痕的轮廓的两侧中间位置的细胞连线距离为1.50mm，在预设时间点2小时获取图像中，该划痕的轮廓的两侧中间对应位置的细胞连线距离变为1.20mm，那么可以确定在两个小时内细胞的迁移距离为0.3mm。
在一些实施例中，可以基于划痕轮廓确定对应划痕的多个位置的多个迁移距离。迁移距离可以包括最大迁移距离、最小迁移距离、平均迁移距离等。
细胞的迁移面积可以指不同时间点的划痕的面积的差值。例如，可以将不同预设时间点获取的图像中的划痕轮廓的面积的差确定为该时间范围内的迁移面积。具体地，假设在预设时间点2小时获取的图像中，划痕轮廓的面积为20mm 2，在预设时间点4小时获取的图像中，划痕轮廓的面积变为15mm 2，那么可以确定在两个小时内细胞的迁移面积为5mm 2。
图6是根据本说明书的一些实施例所示的示例性划痕图像的示意图。图6中划痕区域两侧的白线表示划痕宽度。如图6所示，最大划痕宽度AB(即轮廓两侧细胞连线最大距离)为1128像素，最小划痕宽度CD(即轮廓两侧细胞连线最小距离)为856像素，平均划痕宽度(即轮廓两侧细胞连线平均距离)为708像素，划痕面积为1641960像素，拍摄耗时(即划痕操作完成时的时间与拍摄划痕图像的时间的时间差)为2216ms。
步骤530，细胞图像分析装置102(例如，分析模块730)(或处理设备103)可以基于所述迁移距离或所述迁移面积，确定所述细胞的迁移能力。
在一些实施例中，可以基于迁移距离或迁移面积，和多个图像对应的多个预设时间点，确定细胞的迁移能力。例如，可以将迁移距离(或迁移面积)与产生迁移距离(或迁移面积)所用的时间的比值(即迁移率)，确定为细胞的迁移能力。具体地，假设在两个小时内细胞的迁移面积为5mm 2，那么可以确定细胞迁移能力为2.5mm 2/h。
在一些实施例中，可以在不同预设时间点对某种细胞的多条划痕的多个拍摄视野进行分析，确定对应不同预设时间点、不同划痕和不同拍摄视野的多个细胞迁移率，可以将所述多个细胞迁移率的平均值作为细胞迁移能力。
应当注意，本说明书的以上描述仅出于说明的目的而提供的，而无意于限制本说明书的范围。对于本领域的普通技术人员来说，可以根据本说明书的描述，做出各种各样的变化和修改。然而，这些变化和修改不脱离本说明书的范围。
图7是根据本说明书的一些实施例所示的示例性细胞图像分析装置的模块图。如图7所示，细胞图像分析装置102可以包括样品台710、拍摄模块720、分析模块730和控制模块740。
样品台710可以用于放置细胞培养装置(例如，培养部101-1)。在一些实施例中，样品台710可以设置有基点(或基线)、适配器和/或移动机构，用于定位细胞培养装置。关于细胞培养装置在样品台上的定位的更多描述请见图3及其描述。
拍摄模块720可以用于拍摄图像。在一些实施例中，拍摄模块720可以是和/或包括能够获取图像数据的任何合适的设备。例如，拍摄模块720可以包括球面摄像头、半球摄像头等。在一些实施例中，拍摄模块720可以包括黑白摄像头、彩色摄像头、红外摄像头等。在一些实施例中，拍摄模块720可以包括数码相机、模拟相机等。在一些实施例中，拍摄模块720可以包括单目相机、双目相机、多目相机等。在一些实施例中，拍摄模块720可以对划痕进行拍摄，以获取划痕的图像。在一些实施例中，拍摄模块720可以对培养部进行拍摄，以获取培养部的图像。
分析模块730可以用于分析数据。在一些实施例中，分析模块730可以基于划痕的图像确定细胞的迁移能力。例如，分析模块730可以提取图像中的划痕的轮廓。分析模块730可以基于划痕的轮廓确定细胞的迁移距离或迁移面积。分析模块730可以基于迁移距离或所述迁移面积，确定细胞的迁移能力。关于确定细胞的迁移能力的更多描述请见图2A、5-6及其描述。
控制模块740用于控制细胞图像分析装置102中的其它组件。例如，控制模块740可以控制样品台的移动。又例如，控制模块840可以控制拍摄模块对划痕进行拍摄。
应当注意，本说明书的以上描述仅出于说明的目的而提供的，而无意于限制本说明书的范围。对于本领域的普通技术人员来说，可以根据本说明书的描述，做出各种各样的变化和修改。然而，这些变化和修改不脱离本说明书的范围。例如，分析模块730和/或控制模块740可以集成为一个模块。又例如，分析模块730和/或控制模块740可以省略。处理设备103可以用于分析数据和控制细胞图像分析装置102中的其它组件。
以下将结合图8-图16B对本说明书实施例所涉及的细胞划痕装置101进行详细说明。值得注意的是，以下实施例仅仅用以解释本说明书，并不构成对本说明书的限定。
图8是根据本说明书一些实施例所示的示例性细胞划痕装置的剖面结构示意图。如图8所示，在一些实施例中，细胞划痕装置101可以包括培养部110和划痕部120。其中，培养部110可以用于细胞培养，划痕部120可以用于实现细胞划痕。
在一些实施例中，培养部110可以包括培养皿或培养板。所述培养皿可以为玻璃或塑料材质。在一些实施例中，培养部110可以包括D90培养皿、六孔培养板(如图10所示)等。
在一些实施例中，划痕部120可以包括划痕盖板1210与划痕件130。在一些实施例中，划痕盖板1210可以包括依次连接的底板1213、连接件1212与限位结构1211，底板1213与限位结构1211分别位于连接件1212的两端。
如图8所示，在一些实施例中，划痕时，划痕盖板1210可以通过限位结构1211安装固定于培养部110，以防止培养部110和划痕部120之间发生松动，影响划痕。在一些实施例中，划痕部120通过限位结构1211安装固定于培养部110时，划痕盖板1210的底板1213与培养部110的底部之间的间距可以为0.5-1.5mm。通过在划痕盖板的底板与培养部底部之间预留一定距离，可以避免划痕盖板压到培养部中的细胞。在一些实施例中，限位结构1211可以包括倒U型槽、翻边凸起、翻边凹槽、橡胶卡块、螺纹结构以及卯榫结构等中的至少一种，且所述限位结构1211与培养部110的侧壁相匹配。例如，图8中所示，限位结构1211为翻边凹槽结构时，凹槽的宽度与培养部110的侧壁厚度相匹配。通过限位结构1211与培养部110的侧壁相匹配，可以使得划痕盖板与培养部配合后不存在间隙，划痕时划痕盖板不会偏移，从而能够保证划痕是直线的、均一的。
在一些实施例中，底板1213可以设有多个划痕间隙1213-1，所述多个划痕间隙相互平行且均匀间隔分布。如图8所示，在一些实施例中，划痕时，划痕件130的尖端可以插入其中一个划痕间隙1213-1中，通过沿划痕间隙1213-1的一端移动到另一端，实现细胞划痕。在一些实施例中，底板1213可以设有6-15条划痕间隙1213-1，任意相邻的两个划痕间隙之间的间距可以为0.5-1cm。例如，底板1213可以设有7条划痕间隙，且相邻两个划痕间隙之间的间距可以为1cm。又例如，图9中所示，底板1213可以设有14条划痕间隙，且相邻两个划痕间隙之间的间距可以为0.5cm。在一些实施例中，根据培养部110结构的不同和/或细胞划痕实验需求的不同，可以在底板1213设置不同数量、不同形状的划痕间隙和/或不同宽度的划痕间隙。例如，针对六孔培养皿，其对应的划痕盖板的划痕间隙可以为3条或5条，相邻两个划痕间隙之间的间距可以为0.5cm或1cm。
在一些实施例中，每个划痕间隙1231-1的横截面可以为上宽下窄的梯形，所述梯形可以与划痕件130的尖端形状匹配，以使划痕件130的尖端插入划痕间隙至最底部时，刚好与培养部110中的细胞接触。在一些实施例中，划痕盖板1210与划痕件130可拆卸连接。
在一些实施例中，连接件1212的长度可以为预设长度。一般情况下，用户可以根据实际培养部110的尺寸以及其他相关要求(例如划痕盖板1210安装好之后，底板1213与培养部110底部之间的间距等)设计对应的连接件1212的长度。因此在划痕盖板1210通过限位结构1211安装固定于培养部110之后，底板1213与培养部110底部之间的间距可以为0.5-1.5mm。优选地，底板1213与培养部110底部之间的间距可以为1mm。
请参照图11，图11所示为一些实施例中划痕盖板1210的结构示意图。
在一些实施例中，限位结构1211可以是倒U型槽设置。如图11所示，限位结构1211可以包括两个固定件1211-1，其中一个固定件1211-1与连接件1212相连，两个固定件1211-1之间形成限位槽1211-2，且限位槽1211-2的宽度与培养部110的侧壁厚度相匹配。
在另一些实施例中，限位结构1211也可以只包括一个固定件1211-1，此固定件1211-1与连接件1212之间形成限位槽1211-2。
在一些实施例中，固定件1211-1可以是连接件1212的翻边。
在另一些实施例中，固定件1211-1可以是橡胶卡块。橡胶卡块与培养部110的侧壁摩擦更大，更不容易发生相对位移，因此划痕盖板1210的安装更加稳定不易松动。在一些实施例中，橡胶卡块靠近连接件1212一侧的表面可以设置凸点等纹路，以提高限位的稳定性等。
在另一些实施例中，限位槽1211-2内也可以设置内螺纹，培养部110的外侧壁对应位置设置对应外螺纹(图中未示出)，划痕盖板1210与培养部110螺纹连接。螺纹连接的设置不仅使得划痕盖板1210的安装更加稳固，而且使得划痕盖板1210在旋转的同时也会在螺纹长度方向上移动。因此采用螺纹连接可以使得底板1213与培养部110底部之间的间隔可调，方便实验人员操作，可以根据不同型号的培养部110与划痕件130，自行调整底板1213与培养部110底部之间的间距，以提升划痕效果。
在另一些实施例中，限位结构1211也可以与培养部110采用榫卯结构连接，即卡接。限位槽1211-2的内壁设置凹槽，培养部110外侧壁设置有对应凸起(图中未示出)，通过凹槽与凸起的配合实现划痕盖板1210的固定。在另一些实施例中，培养部110外侧壁可以沿高度方向设置有多个对应凸起，通过凹槽与不同高度位置的凸起的卡接，以改变底板1213与培养部110底部之间的间距。因此实验人员可以根据不同型号的培养部110与划痕件130，自行调整底板1213与培养部110底部之间的间距，以提升划痕效果。
在一些实施例中，划痕件130可以包括划痕针1310。划痕间隙1213-1两侧分别设有相互匹配的第一限位件1214与第二限位件1215。在一些实施例中，第一限位件1214与第二限位件1215可以均位于底板1213靠近培养部110底部的一侧。且沿底板1213至培养部110底部的方向上，第一限位件1214与第二限位件1215之间的距离逐渐减小。因此第一限位件1214与第二限位件1215之间呈现上口大下口小的倒锥形，能够在划痕针1310插入间隙时卡住划痕针1310，以便于对划痕针1310进行限位，保证划痕针1310伸出底板1213的长度不变，从而提升划痕的稳定性。在一些实施例中，第一限位件1214与第二限位件1215之间的下口宽度的值小于划痕间隙1213-1的宽度，即第一限位件1214与第二限位件1215靠近培养部110底部的一端之间的距离小于划痕间隙1213-1的宽度。
在一些实施例中，划痕件130还可以包括滑块1320，划痕针1310可以安装于滑块1320。划痕时，滑块1320能够以划痕间隙1213-1作为导轨进行滑动带动划痕针1310从其中一个划痕间隙的一端移动到另一端以实现细胞划痕。由于滑块1320与作为导轨的划痕间隙1213-1配合紧密，不 易产生偏转，因此划痕针1310能够较好地与培养部110的底部垂直且稳定度较高，从而为划痕效果的均匀、稳定性提供保障。
请参照图12，图12所示为一些实施例中划痕件130与划痕间隙1213-1的配合结构示意图一。
在一些实施例中，滑块1320可以设置有螺纹孔，螺纹孔可以垂直于底板1213设置，划痕针1310外壁可以设有于所述螺纹孔对应的外螺纹(图中未示出)，从而使得划痕针1310与滑块1320螺纹连接。螺纹连接的设置，一方面加强了划痕针1310安装稳定性，另一方面使得划痕针1310可以在旋转过程中调节伸出滑块1320的长度。因此，在底板1213与培养部110底部之间的间距过大或过小时，可以通过调节划痕针1310伸出滑块1320的长度，保证划痕针1310的针尖能够接触培养部110的底部，方便展开划痕工作。进一步地，滑块1320的顶部还可以设置把手(图中未示出)，以方便实验人员进行操作。
请参照图13，图13所示为一些实施例中划痕件130与划痕间隙1213-1的配合结构示意图二。
在一些实施例中，如图13所示，滑块1320可以采用球形滑块，划痕间隙1213-1内部可以采用于所述球形滑块相匹配的形状。球形滑块的设置可以一定程度上降低滑块1320卡在拐角的概率。进一步地，为了避免球形滑块自身发生滚动导致划痕针1310不稳，可以额外添加其他限制结构，例如，在球形滑块底部从划痕间隙1213-1露出的位置设置一个限制结构1320-1，从而避免球形滑块自身发生滚动。在另一些实施例中，限制结构1320-1也可以设置在球形滑块顶部，在起到限位功能的同时，还能作为把手使用。
请参照图14，图14所示为一些实施例中底板1213的结构示意图。
如图14所示，在另一些实施例中，多个划痕间隙1213-1同一侧的端部可以通过连接路径1216连通。因此，同一个滑块1320可以进入多个划痕间隙1213-1，从而减少了划痕件130的数量，避免了因不同划痕件130之间的差异对划痕效果的影响，从而提高了划痕的稳定性与均匀度。
更进一步的，如图14所示，在一些实施例中，划痕间隙1213-1还可以设置有进入孔1217。在一些实施例中，进入孔1217的尺寸不小于滑块1320，因此滑块1320可以从进入孔1217进入划痕间隙1213-1，从而实现划痕件130与底板1213的可拆卸连接，方便实验人员采用对应规格的划痕件130进行划痕。进入孔1217的设置，相当于导轨(即划痕间隙1213-1)的一端未封闭，因此滑块1320可以很轻易地进出导轨(即划痕间隙1213-1)。
在另一些实施例中，划痕件130还可以包括安装主体1330，多组划痕针1310可以固定于安装主体1330，每组划痕针1310可以包括一个或多个划痕针1310，每组划痕针1310均对应一个划痕间隙1213-1。
请参照图15，图15所示为一些实施例中划痕件130的结构示意图。
在一些实施例中，多组划痕针1310的位置分布可以形成两条曲线，两条曲线分别与多个划痕间隙1213-1的两个端部连线(例如连接路径1216)的形状相匹配。在进行划痕时，可以先将两条曲线中的其中一条曲线(可以视为起始曲线)与多个划痕间隙1213-1的端部连线重合，此时起始曲线上的划痕针1310均位于划痕间隙1213-1的第一端部，另一条曲线(可以视为终止曲线)上的划痕针1310位于划痕间隙1213-1的中部。当划痕至终点后，终止曲线上的划痕针1310均位于划痕间隙1213-1的第二端部，起始曲线上的划痕针1310位于划痕间隙1213-1的中部。特殊的，对于最短的划痕间隙1213-1对应的那组划痕针1310，可以只包括一个划痕针1310。
在一些实施例中，划痕部120还可以包括第一磁体，划痕件130设有与所述第一磁体相匹配的第二磁体。在一些实施例中，第一磁体可以设置在底板1213上。在一些实施例中，第二磁体可以是滑块1320，也可以是其他与划痕针1310相连的结构。划痕时，可以通过移动第一磁体，从而吸引或排斥第二磁体进行移动，进而达到驱动划痕针1310移动划痕的目的。例如，第一磁体与第二磁体相斥，实验人员可以手动沿划痕间隙1213-1移动第一磁体，从而驱动第二磁体进而驱动划痕针1310进行划痕。由于第一磁体始终紧贴底板1213，因此在划痕针1310长度方向上，第一磁体对第二磁体的斥力能够维持在稳定水平，从而使得划痕针1310对培养部110底部的压力维持稳定，进而较好的提升了划痕的均匀度与稳定性。
在一些实施例中，划痕部120还可以包括驱动件140、一个或多个传感器150。其中，驱动件140可以用于驱动划痕件130沿划痕间隙1213-1进行划痕，传感器可以用于识别划痕件130划痕时受到的压力和/或划痕件130的滑动距离。请参照图16A和图16B，图16A和图16B所示为驱动件140与划痕件130的连接结构示意图。
在一些实施例中，驱动件140可以包括电机。在一些实施例中，传感器150可以包括压力传感器、位移传感器等，或其任意组合。例如，压力传感器可以包括压阻式压力传感器、陶瓷压力传感器、扩散硅压力传感器、蓝宝石压力传感器、压电式压力传感器等。又例如，位移传感器可以包括应变式传感器、电感式传感器、差动变压器式传感器、涡流式传感以及霍尔传感器等。
在一些实施例中，当传感器150为压力传感器时，划痕时保证传感器150的读数稳定，即可保证划痕件130受到稳定的推/拉力，从而保证划痕均匀。当传感器150为位移传感器时，可以识别划痕件130是否移动了指定距离、或到达了划痕终点(即划痕间隙1213-1的端部)。
另一方面，可以通过传感器150判断是否开始划痕。如图16A所示，在一些实施例中，划痕件130可以通过弹簧160与驱动件140相连，弹簧160可以沿划痕间隙1213-1方向(即图16A中AB方向)设置。如图图16B所致，在开始划痕前，若划痕件130位于图16B(1)中所示的位置，可以将划痕件130尖端的水平位置设定在培养部110中未接触细胞的位置，然后将划痕件130往培养部110的一端移动(如箭头指向B的方向)，若弹簧160的拉力(或压力)开始增大，代表划痕件130到达了划痕间隙1213-1的其中一端的端部(如图16B(2)中所示的位置)，此时可以将划痕件130尖端的水平位置下移到最佳划痕高度，开始对培养部110中细胞进行划痕，直到弹簧160的压力(或拉力)开始增大(如图16B(3)中所示)，代表本次划痕结束。特别地，若是同时驱动多个划痕件130分别划痕，那么需要当全部弹簧160的拉力或压力均开始增大时，才下移划痕件130开始划痕或是结束划痕。在一些实施例中，驱动机140可以划痕件130直接连接，即没有弹簧160。
在另一些实施例中，传感器150可以沿划痕件130长度方向设置。因此，传感器150可以识别划痕件130划痕时受到的压力。划痕时保证传感器150的读数稳定，即可保证划痕件130受到稳定的压力，从而保证划痕均匀。
在一些实施例中，细胞划痕装置101可以包括培养部110、划痕件130、处理器、划痕工作台及电机。培养部110可以包括培养皿。电机可以用于驱动划痕件130工作，处理器可以用于控制电机工作。在一些实施例中，划痕工作台可以包括样品台、培养皿固定装置与培养皿识别装置。其中，样品台可以用于提供细胞划痕的操作支撑平台，培养皿固定装置与培养皿识别装置均安装于所述样品台。培养皿固定装置可以用于固定细胞培养皿，培养皿识别装置可以用于识别培养皿的位置和/或型号等信息。
在一些实施例中，培养皿固定装置可以包括与培养皿相匹配的凹槽，或支撑固定框架。在一些实施例中，培养皿识别装置可以包括位于所述样品台上的感应器(例如，压力感应器等)，和/或摄像头装置(即通过图像识别培养皿位置)。
在进行划痕操作时，可以将培养皿通过培养皿固定装置固定至样品台的指定位置。固定时，可以人工将培养皿放置在指定位置。在另一些实施例中，划痕工作台还可以包括培养皿移动机构，培养皿固定装置安装于培养皿移动机构。处理器可以通过培养皿识别装置识别培养皿的位置，以控制培养皿移动机构将培养皿移动至样品台的指定位置。例如，培养皿移动机构可以是网格状的导轨，培养皿固定装置与导轨滑动连接，通过在不同导轨之间的切换，从而在样品台平面内移动(滑动结构可以参照上述的球形滑块及其匹配的导轨)。培养皿移动机构也可以是两级导轨设置，一级导轨沿X轴方向固定于样品台，二级导轨与一级导轨滑动连接，二级导轨沿Y轴方向布置，培养皿固定装置与二级导轨滑动连接。通过一级导轨调整X轴方向上的位置，通过二级导轨调节Y轴方向的位置，从而实现XY平面内任意位置可调。
在一些实施例中，培养皿识别装置可以将识别出的培养皿的型号发送给处理器，处理器根据培养皿的型号选取预先设置的划痕方案。在一些实施例中，划痕方案可以包括划痕间隙对应的间距、划痕条数等。在一些实施例中，所述划痕方案可以根据用户(例如，实验人员)输入的实验需求确定。
在一些实施例中，处理器可以根据相应的划痕方案，计算每条划痕的初始划痕位置和结束划痕位置，并控制电机驱动划痕件130根据初始划痕位置和结束划痕位置进行移动，依次进行划痕。在一些实施例中，可以通过在划痕装置上设置横向压力传感器识别当前划痕是否结束。例如，当划痕件130划到培养皿边缘时，压力传感器感应到横向压力增大，则代表本次划线结束，处理器可以控制划痕件130移动到下一个划痕的初始划痕位置进行下一个划痕。
在另一些实施例中，样品台也可以由另一电机驱动，可以在平面内沿XY轴来回移动。例如，样品台底部也可以为两级导轨设置(参照上述)。处理器可以控制电机驱动样品台在XY平面内移动，从而实现划痕。
在另一些实施例中，处理器也可以控制培养皿移动机构使培养皿在XY平面内移动，从而实现划痕。
在一些实施例中，所述细胞划痕装置101可以为玻璃、金属、塑料、树脂等材质。由于本说明书的细胞划痕装置101主要应用于细胞划痕实验，透明材料方便观察划痕效果，同时细胞划痕实验的用具需要经常进行高压灭菌，材料需要耐高温高压，因此所述划痕盖板优选为玻璃制品。
本说明书所披露的细胞划痕装置可能带来的有益效果包括但不限于：(1)划痕盖板与培养部通过限位结构安装，可以减少划痕时划痕部的横向摆动，使划痕形状更加规则；(2)划痕件沿划痕间隙移动，划出的划痕笔直，不同划痕间距离均匀，方便后续观察；(3)划痕件与划痕盖板限位配合，限制了划痕件垂直方向的移动，使划痕件作用在细胞上的力刚好适中，既不会用力过小导致划痕不彻底，也不会用力过大划伤培养部，保证划痕的稳定；(4)通过电机驱动划痕件，传感器检测划痕件压力与位移，实现自动划痕，减少人力，提高效率，同时能够保证划痕的均一稳定。
本说明书所披露的确定细胞迁移能力系统可能带来的有益效果包括但不限于：(1)应用细胞图像分析装置对划痕进行自动拍摄分析，操作简单方便，减少人力，提高拍摄分析效率；(2)通过结合使用细胞划痕装置和细胞图像分析装置，在分析划痕的细胞的迁移情况时，可以精确定位划痕，可以实现定点连续拍照成像和分析，保证了实验结果的科学性和可信度；(3)通过控制样品台或拍摄模块的移动方向，可以实现单条划痕的累计观测分析和多条划痕的对比观测分析。需要说明的是，不同实施例可能产生的有益效果不同，在不同的实施例里，可能产生的有益效果可以是以上任意一种或几种的组合，也可以是其他任何可能获得的有益效果。
上文已对基本概念做了描述，显然，对于本领域技术人员来说，上述详细披露仅仅作为示例，而并不构成对本说明书的限定。虽然此处并没有明确说明，本领域技术人员可能会对本说明书进行各种修改、改进和修正。该类修改、改进和修正在本说明书中被建议，所以该类修改、改进、修正仍属于本说明书示范实施例的精神和范围。
同时，本说明书使用了特定词语来描述本说明书的实施例。如“一个实施例”、“一实施例”、和/或“一些实施例”意指与本说明书至少一个实施例相关的某一特征、结构或特点。因此，应强调并注意的是，本说明书中在不同位置两次或多次提及的“一实施例”或“一个实施例”或“一个替代性实施例”并不一定是指同一实施例。此外，本说明书的一个或多个实施例中的某些特征、结构或特点可以进行适当的组合。
此外，除非权利要求中明确说明，本说明书所述处理元素和序列的顺序、数字字母的使用、或其他名称的使用，并非用于限定本说明书流程和方法的顺序。尽管上述披露中通过各种示例讨论了一些目前认为有用的发明实施例，但应当理解的是，该类细节仅起到说明的目的，附加的权利要求并不仅限于披露的实施例，相反，权利要求旨在覆盖所有符合本说明书实施例实质和范围的修正和等价组合。例如，虽然以上所描述的系统组件可以通过硬件设备实现，但是也可以只通过软件的解决方案得以实现，如在现有的服务器或移动设备上安装所描述的系统。
同理，应当注意的是，为了简化本说明书披露的表述，从而帮助对一个或多个发明实施例的理解，前文对本说明书实施例的描述中，有时会将多种特征归并至一个实施例、附图或对其的描述中。但是，这种披露方法并不意味着本说明书对象所需要的特征比权利要求中提及的特征多。实际上，实施例的特征要少于上述披露的单个实施例的全部特征。
一些实施例中使用了描述成分、属性数量的数字，应当理解的是，此类用于实施例描述的数字，在一些示例中使用了修饰词“大约”、“近似”或“大体上”来修饰。除非另外说明，“大约”、“近似”或“大体上”表明所述数字允许有±20％的变化。相应地，在一些实施例中，说明书和权利要求中使用的数值参数均为近似值，该近似值根据个别实施例所需特点可以发生改变。在一些实施例中，数值参数应考虑规定的有效数位并采用一般位数保留的方法。尽管本说明书一些实施例中用于确认其范围广度的数值域和参数为近似值，在具体实施例中，此类数值的设定在可行范围内尽可能精确。
针对本说明书引用的每个专利、专利申请、专利申请公开物和其他材料，如文章、书籍、说明书、出版物、文档等，特此将其全部内容并入本说明书作为参考。与本说明书内容不一致或产生冲突的申请历史文件除外，对本说明书权利要求最广范围有限制的文件(当前或之后附加于本说明书中的)也除外。需要说明的是，如果本说明书附属材料中的描述、定义、和/或术语的使用与本说明书所述内容有不一致或冲突的地方，以本说明书的描述、定义和/或术语的使用为准。
最后，应当理解的是，本说明书中所述实施例仅用以说明本说明书实施例的原则。其他的变形也可能属于本说明书的范围。因此，作为示例而非限制，本说明书实施例的替代配置可视为与本说明书的教导一致。相应地，本说明书的实施例不仅限于本说明书明确介绍和描述的实施例。

Claims (56)

  1. 一种确定细胞的迁移能力的方法，其特征在于，所述方法包括：
    通过细胞划痕装置对细胞进行划痕操作，形成至少一个划痕；以及
    通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力。
  2. 根据权利要求1所述的方法，其特征在于，所述通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力，包括：
    通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像；以及
    基于所述至少一个划痕的所述至少一个图像，确定所述细胞的迁移能力。
  3. 根据权利要求2所述的方法，其特征在于，所述至少一个划痕的划痕端点设有荧光标记，所述通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，包括：
    所述细胞图像分析装置通过追踪所述荧光标记确定所述至少一个划痕的划痕端点，以实现对所述至少一个划痕的定位拍摄。
  4. 根据权利要求2所述的方法，其特征在于，所述至少一个划痕的底部设有照射光，所述通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，包括：
    所述细胞图像分析装置基于所述至少一个划痕的透光表现对所述至少一个划痕进行定位，以实现对所述至少一个划痕的定位拍摄。
  5. 根据权利要求2所述的方法，其特征在于，所述细胞图像分析装置包括至少一个局部相机和一个全局相机，所述通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，包括：
    通过所述全局相机拍摄所述至少一个划痕的全局图像；
    基于所述全局图像确定所述至少一个划痕的划痕信息；以及
    通过所述局部相机基于所述划痕信息拍摄所述至少一个划痕的多个视野的图像，以实现对所述至少一个划痕的定位拍摄。
  6. 根据权利要求2至5中任一所述的方法，其特征在于，所述细胞图像分析装置基于相同的拍摄参数对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的所述至少一个图像。
  7. 根据权利要求6所述的方法，其特征在于，所述细胞图像分析装置包括用于存储所述拍摄参数的存储设备，所述细胞图像分析装置通过调取所述存储设备中的所述拍摄参数以对所述至少一个划痕进行定位拍摄。
  8. 根据权利要求6所述的方法，其特征在于，所述至少一个划痕的所述至少一个图像对应一个所述拍摄参数，所述拍摄参数记录于可扫描读取的信息载体中，所述细胞图像分析装置通过扫描所述信息载体获取所述拍摄参数。
  9. 根据权利要求8所述的方法，其特征在于，所述可扫描读取的信息载体包括设置在所述细胞划痕装置上的条形码或二维码。
  10. 根据权利要求6至9中任一所述的方法，其特征在于，所述拍摄参数包括：进样坐标、所述至少一个划痕的拍摄总长度、所述至少一个划痕的视野数量、曝光度或拍摄焦距中的至少一个。
  11. 根据权利要求1至10中任一所述的方法，其特征在于，所述细胞划痕装置包括培养部和划痕部，所述培养部用于培养所述细胞，所述划痕部包括划痕盖板和划痕件，所述划痕盖板包括依次连接的底板、连接件与限位结构，所述底板与所述限位结构分别位于所述连接件的两端，所述底板设有至少一个划痕间隙。
  12. 根据权利要求11所述的方法，所述通过细胞划痕装置对细胞进行划痕操作，形成至少一个划痕，包括：
    通过所述限位结构将所述划痕盖板固定在所述培养部上；以及
    通过将所述划痕件插入所述至少一个划痕间隙且沿所述至少一个划痕间隙的一端移动到另一端，以对所述细胞进行所述划痕操作，所述至少一个划痕的位置由所述至少一个划痕间隙的位置决定。
  13. 根据权利要求12所述的方法，其特征在于，所述通过细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力，包括：
    通过所述细胞图像分析装置，基于所述拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像，其中所述多个图像中的每个图像对应一个预设时间点；以及
    基于所述至少一个划痕的所述多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力。
  14. 根据权利要求13所述的方法，其特征在于，在对所述细胞进行所述划痕操作后形成多个划痕，所述多个划痕包括第一划痕和第二划痕，所述通过所述细胞图像分析装置，基于所述拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，包括：
    基于所述拍摄参数和所述第一划痕的位置，控制所述细胞图像分析装置对所述第一划痕进行自动拍摄；
    基于对应于所述第一划痕的第一划痕间隙和对应于所述第二划痕的第二划痕间隙之间的位置关系，确定所述第一划痕和所述第二划痕的位置关系；以及
    基于所述第一划痕和所述第二划痕之间的位置关系和所述拍摄参数，控制所述细胞图像分析装置对所述第二划痕进行自动拍摄。
  15. 根据权利要求13所述的方法，其特征在于，所述细胞图像分析装置包括样品台和拍摄模块，所述通过细胞图像分析装置，基于所述拍摄参数和所述至少一个划痕的位置，对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕的多个图像，包括：
    在多个预设时间点中的每个预设时间点，
    将所述细胞划痕装置的所述培养部定位于所述样品台的目标位置处；
    基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕在所述预设时间点的至少一个图像。
  16. 根据权利要求15所述的方法，其特征在于，所述将所述细胞划痕装置的所述培养部定位于所述样品台的目标位置处，包括：
    通过在所述培养部和所述样品台上设计基点或基线，以将所述培养部定位于所述样品台的所述目标位置处。
  17. 根据权利要求15所述的方法，其特征在于，所述样品台上设置有培养部适配器，所述将所述细胞划痕装置的所述培养部定位于所述样品台的目标位置处，包括：
    通过将所述培养部放置在所述培养部适配器上，以将所述培养部定位于所述样品台的所述目标位置处。
  18. 根据权利要求15所述的方法，其特征在于，所述培养部具有标号，在所述培养部上设置有方向标记，所述将所述细胞划痕装置的所述培养部定位于所述样品台的目标位置处，包括：
    基于所述培养部的标号和所述培养部上设置的方向标记，将所述培养部定位于所述样品台的目标位置处。
  19. 根据权利要求15所述的方法，其特征在于，所述样品台上设置有移动机构，所述将所述细胞划痕装置的所述培养部定位于所述样品台的目标位置处，包括：
    通过所述细胞图像分析装置对所述培养部进行拍摄，获取所述培养部的图像；
    通过分析所述培养部的所述图像，确定所述培养部的中心点；
    基于所述培养部的中心点与所述样品台零位之间的位置关系，确定所述培养部的移动方向和移动距离；以及
    通过所述移动机构，基于所述培养部的所述移动方向和所述移动距离，以将所述培养部定位于所述样品台的目标位置处。
  20. 根据权利要求15所述的方法，其特征在于，所述培养部的底部设置有用于划痕定位的第一适配器，所述样品台的底部设置有对应的第二适配器，所述基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，包括：
    通过将第一适配器与第二适配器进行匹配，以实现对所述至少一个划痕的自动定位拍摄。
  21. 根据权利要求15所述的方法，其特征在于，所述基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕在所述预设时间点的至少一个图像，包括：
    控制所述样品台或所述拍摄模块沿着平行于所述至少一个划痕的延伸方向进行移动，以获取所述至少一个划痕沿着所述延伸方向的多个视野的多个图像。
  22. 根据权利要求15所述的方法，其特征在于，在对所述细胞进行所述划痕操作后形成多个划痕，所述多个划痕的延伸方向相互平行，所述基于所述拍摄参数和所述至少一个划痕的位置，控制所述拍摄模块对所述至少一个划痕进行自动拍摄，以获取所述至少一个划痕在所述预设时间点的至少一个图像，包括：
    控制所述样品台或所述拍摄模块沿着垂直于所述多个划痕的所述延伸方向进行移动，以获取所述多个划痕的多个图像。
  23. 根据权利要求13至22中任一所述的方法，其特征在于，所述基于所述至少一个划痕的所述多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力，包括：
    基于所述多个图像，确定所述细胞的迁移距离或迁移面积；以及
    基于所述迁移距离或所述迁移面积，和所述多个预设时间点，确定所述细胞的迁移能力。
  24. 根据权利要求23所述的方法，其特征在于，所述基于所述多个图像，确定所述细胞的迁移距离或迁移面积，包括：
    从所述多个图像中的每个图像中提取所述至少一个划痕的轮廓；以及
    基于所述多个图像中的多个轮廓确定所述细胞的迁移距离或迁移面积。
  25. 根据权利要求24所述的方法，其特征在于，所述基于所述多个图像中的多个轮廓确定所述细胞的迁移距离或迁移面积，包括：
    基于所述多个轮廓的面积确定所述迁移面积；或
    基于所述多个轮廓的轮廓两侧细胞连线的距离确定所述迁移距离。
  26. 根据权利要求13至22中任一所述的方法，其特征在于，所述至少一个划痕包括多个划痕，所述基于所述至少一个划痕的所述多个图像和所述多个图像对应的多个预设时间点，确定所述细胞的迁移能力，包括：
    确定对应所述多个划痕的多个所述细胞的候选迁移能力；以及
    基于所述多个候选细胞的迁移能力的平均值，确定所述细胞的迁移能力。
  27. 根据权利要求2所述的方法，其特征在于，所述通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像，包括：
    将所述至少一个划痕的第一个拍摄视野的位置的坐标输入至所述细胞图像分析装置；
    所述细胞图像分析装置基于样品台零位的坐标和所述第一个拍摄视野的位置的坐标，确定所述样品台的进样坐标；以及
    所述细胞图像分析装置基于所述样品台的进样坐标，控制所述样品台的移动方向和/或移动距离，以使所述细胞图像分析装置对所述样品台上的所述至少一个划痕的所述第一拍摄视野进行拍摄。
  28. 根据权利要求2所述的方法，其特征在于，所述通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像，包括：
    获取所述至少一个划痕中的第一个待拍摄划痕的拍摄总长度和视野数量；
    基于所述至少一个划痕中的其他划痕与所述第一个待拍摄划痕之间的位置关系，确定所述其他划痕的拍摄总长度和视野数量；以及
    基于所述至少一个划痕的拍摄总长度和视野数量，对所述至少一个划痕依次进行定位拍摄。
  29. 根据权利要求2所述的方法，其特征在于，所述通过所述细胞图像分析装置对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像，包括：
    将所述至少一个划痕的多个视野的位置坐标输入至所述细胞图像分析装置；以及
    所述细胞分析装置基于所述至少一个划痕的所述多个视野的位置坐标对所述多个视野进行自动拍摄。
  30. 根据权利要求1至29中任一所述的方法，其特征在于，所述细胞划痕装置包括培养部，所述方法进一步包括：
    在所述通过细胞划痕装置对细胞进行划痕操作之前，通过所述培养部培养所述细胞。
  31. 根据权利要求1至30中任一所述的方法，其特征在于，所述细胞划痕装置包括培养部，所述方法进一步包括：
    在所述通过细胞图像分析装置对所述至少一个划痕进行拍摄分析之前，
    清洗所述细胞；以及
    通过所述培养部培养所述清洗后的细胞。
  32. 一种确定细胞迁移能力的系统，其特征在于，所述系统包括：
    细胞划痕装置，用于对细胞进行划痕操作，形成至少一个划痕；以及
    细胞图像分析装置，用于对所述至少一个划痕进行定位拍摄及分析，以确定所述细胞的迁移能力。
  33. 根据权利要求32所述的系统，其特征在于，所述细胞图像分析装置包括：
    拍摄模块，用于对所述至少一个划痕进行定位拍摄，以获取所述至少一个划痕的至少一个图像。
  34. 根据权利要求33所述的系统，其特征在于，所述细胞图像分析装置包括：
    分析模块，用于基于所述至少一个图像确定所述细胞的迁移能力。
  35. 根据权利要求32至34中任一所述的系统，其特征在于，所述细胞图像分析装置包括：
    样品台，用于定位所述细胞划痕装置的培养部。
  36. 根据权利要求32至35中任一所述的系统，其特征在于，所述细胞图像分析装置包括：
    控制模块，用于控制所述样品台和/或所述拍摄模块。
  37. 根据权利要求32至36中任一所述的系统，其特征在于，所述细胞划痕装置，包括：
    用于对所述细胞进行划痕操作的划痕部，所述划痕部包括划痕盖板；所述划痕盖板包括依次连接的底板、连接件与限位结构，所述底板与所述限位结构分别位于所述连接件的两端，所述底板设有多个划痕间隙，所述多个划痕间隙相互平行且均匀间隔分布；划痕时所述划痕盖板通过所述限位结构安装固定。
  38. 根据权利要求37所述的系统，其特征在于，所述划痕装置还包括培养部，划痕时所述划痕盖板通过所述限位结构安装固定于所述培养部。
  39. 根据权利要求38所述的系统，其特征在于，所述限位结构包括倒U型槽、翻边凸起、橡胶卡块、螺纹结构以及卯榫结构中的至少一种，且所述限位结构与所述培养部的侧壁相匹配。
  40. 根据权利要求38所述的系统，其特征在于，所述限位结构包括第一固定件和第二固定件，第一固定件与所述连接件相连，所述第一固定件和所述第二固定件之间形成限位槽。
  41. 根据权利要求38所述的系统，其特征在于，所述划痕部通过所述限位结构安装固定于所述培养部时，所述划痕盖板的底板与所述培养部的底部之间的间距为0.5-1.5mm。
  42. 根据权利要求38所述的系统，其特征在于，所述划痕间隙两侧分别设有相互匹配的第一限位件与第二限位件，所述第一限位件与所述第二限位件均位于所述底板靠近所述培养部底部的一侧，所述第一限位件与所述第二限位件的间隙的其中一侧的距离小于所述划痕间隙的宽度，所述其中一侧靠近所述培养部的底部。
  43. 根据权利要求37所述的系统，其特征在于，所述划痕盖板的所述底板设有3-15条划痕间隙，任意相邻的两个所述划痕间隙之间的间距为0.5-1cm。
  44. 根据权利要求37所述的系统，其特征在于，所述划痕部还包括划痕件，划痕时所述划痕件的尖端插入所述划痕间隙且沿所述划痕间隙的一端移动到另一端。
  45. 根据权利要求44所述的系统，其特征在于，所述划痕件包括划痕针与滑块，所述滑块滑动安装于所述划痕间隙，所述划痕针与所述滑块螺纹连接。
  46. 根据权利要求45所述的系统，其特征在于，所述滑块为球形，所述划痕间隙内部形状与所述滑块相匹配，所述滑块还设有限制结构，所述限制结构与所述划痕间隙左右两侧的底部均接触。
  47. 根据权利要求45所述的系统，其特征在于，所述多个划痕间隙同一侧的端部联通。
  48. 根据权利要求44所述的系统，其特征在于，所述划痕件包括安装主体与多组划痕针，所述多组划痕针均固定于所述安装主体，每组划痕针均对应一个所述划痕间隙。
  49. 根据权利要求48所述的系统，其特征在于，所述多组划痕针的位置分布与所述多个划痕间隙的端部连线形状相匹配。
  50. 根据权利要求44-49中任一所述的系统，其特征在于，所述划痕部还包括驱动件，所述驱动件用于驱动所述划痕件沿所述划痕间隙移动。
  51. 根据权利要求50所述的系统，其特征在于，所述划痕部还包括至少一个传感器，所述传感器用于确定划痕操作的进度、识别所述划痕件划痕时受到的压力和/或所述划痕件的滑动距离。
  52. 根据权利要求51所述的系统，其特征在于，所述划痕部还包括弹簧，所述划痕件通过所述弹簧与所述驱动件相连，所述弹簧沿所述划痕间隙方向设置。
  53. 根据权利要求44所述的系统，其特征在于，所述划痕部还包括第一磁体，所述划痕件设有与所述第一磁体相匹配的第二磁体，所述第一磁体用于配合所述第二磁体驱动所述划痕件划痕。
  54. 根据权利要求32所述的系统，其特征在于，所述细胞划痕装置包括手动划痕装置、半自动划痕装置或全自动划痕装置中的至少一个。
  55. 一种确定细胞的迁移能力的控制系统，其特征在于，所述系统包括：
    至少一个存储设备，用于存储一组指令；以及
    至少一个处理器与所述至少一个存储设备通信，当执行所述存储的指令时，所述至少一个处理器使所述系统执行以下操作：
    控制细胞划痕装置对细胞进行划痕操作，形成至少一个划痕；以及
    控制细胞图像分析装置对所述至少一个划痕进行拍摄分析，以确定所述细胞的迁移能力。
  56. 一种根据权1-31中任一所述的方法、权32-54中任一所述的系统以及权55所述的控制系统在细胞迁移能力的确定中的应用。
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