Support system, support method, information processing apparatus, and program

Abstract

To acquire a sample in an amount sufficient for analysis.SOLUTION: A support system 1 for supporting an operation of aspirating a specific cell or cell component from a cell group in a cell culture vessel 60 acquires a captured image of the cell group captured by an imaging unit, analyzes the acquired captured image to detect a cell or cell component satisfying a predetermined condition among the cells or cell components included in the cell group, and receives designation of whether or not to store the detected cell or cell component in the same storing unit 351. And a control unit 11 that causes the tip 33 to suck the detected cell or cell component, and causes the same or a different preservation unit 351 to preserve the cell or cell component sucked by the tip 33 on the basis of the received designation.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to a support system, a support method, an information processing device, and a program. [Background technology]

[0002] There is known an automatic cell suction device that takes an image of cells seeded in a container such as a well plate (microplate) and automatically aspirates any one or more cells, cell clumps, cell parts, or tissue slices. Patent Document 1 describes a support system that assists in the aspirating of specific cells or cell components from a group of cells in a cell culture container. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2016-7 A Summary of the Invention [Problem to be solved by the invention]

[0004] In conventional support systems, cells or cell-containing samples aspirated from different wells are stored in separate locations each time they are aspirated. Depending on the resolution and detection limit of the analytical device used to analyze samples such as cells, the amount of sample obtained by a single aspirate using a tip may not be sufficient for analysis after aspirating. Therefore, conventional support systems for analysis based on cell aspirate may not be able to obtain a sufficient amount of sample for analysis.

[0005] An object of the present disclosure is to provide an assistance system, an assistance method, an information processing device, and a program that are capable of obtaining a sufficient amount of sample for analysis. [Means for solving the problem]

[0006] In some embodiments, an assistance system assists in the task of aspirating specific cells or cellular components from a cell population in a cell culture vessel, and includes a control unit that acquires an image of the cell population captured by an imaging unit, analyzes the acquired image, detects cells or cellular components contained in the cell population that satisfy predetermined conditions, accepts a designation as to whether the detected cells or cellular components should be stored in the same storage unit, aspirates the detected cells or cellular components using a tip, and stores the cells or cellular components aspirated by the tip in the same or a different storage unit based on the designation. In this way, the assistance system accepts a designation as to whether the detected cells or cellular components should be stored in the same storage unit, and stores the aspirated cells or cellular components in the same or a different storage unit based on the designation. Therefore, by storing the aspirated cells or cellular components in the same storage unit, the assistance system is able to obtain a sufficient amount of sample for analysis.

[0007] In one embodiment, the control unit receives, for each of the detected cells or cellular components, a designation of a storage unit to store the cell or cellular component, and stores the cell or cellular component aspirated by the tip in the designated storage unit. In this way, the support system receives a designation of a storage unit for each of the detected cells or cellular components, allowing the user to obtain an appropriate amount of sample depending on the application.

[0008] In one embodiment, the control unit analyzes the captured image to identify the position of the detected cell or cellular component, and causes the tip to aspirate the detected cell or cellular component based on the identified position. In this way, the support system analyzes the captured image to identify the position of the detected cell or cellular component, and is therefore able to appropriately aspirate the detected cell or cellular component.

[0009] In one embodiment, the control unit acquires a photographed image of the detected cell or cellular component when the cell or cellular component is being aspirated, corrects the identified position based on the photographed image of the cell or cellular component when the cell or cellular component is being aspirated, and causes the tip to aspirate the detected cell or cellular component based on the corrected position. In this manner, the assistance system acquires a photographed image of the cell or cellular component immediately before aspirating, corrects the position of the cell or cellular component based on the photographed image, and aspirates the cell or cellular component. Therefore, even if the cell moves or divides between the time of photographing to detect the aspirated cell or cellular component and the time of aspirating, the assistance system can accurately aspirate and store the desired cell or cellular component.

[0010] In one embodiment, the control unit acquires photographed images of the cell group containing the detected cell or cellular component before and after the cell or cellular component is aspirated by the tip, analyzes the photographed images before and after the cell or cellular component is aspirated by the tip, determines whether or not to preserve the aspirated cell or cellular component, and if it is determined that the aspirated cell or cellular component should be preserved, stores the cell or cellular component in the storage unit. In this way, the support system analyzes the photographed images before and after aspiration to determine whether or not to preserve the aspirated cell or cellular component, so it is possible to preserve only cells or cellular components that have been appropriately aspirated.

[0011] In one embodiment, if the controller determines that the aspirated cell or cellular component is not to be preserved, the controller discards the cell or cellular component. In this way, the support system discards cells or cellular components that are not determined to be preserved, and therefore, it is possible to preserve cells or cellular components that were not properly aspirated, thereby preventing sample contamination.

[0012] In some embodiments, an assistance method is provided for an assistance system that assists in the task of aspirating specific cells or cellular components from a cell population in a cell culture vessel, the assistance method comprising the steps of: acquiring a photographed image of the cell population from an imaging unit; analyzing the acquired photographed image to detect cells or cellular components contained in the cell population that satisfy predetermined conditions; receiving a designation as to whether the detected cells or cellular components should be stored in the same storage unit; aspirating the detected cells or cellular components using a tip; and storing the cells or cellular components aspirated by the tip in the same or a different storage unit based on the designation. Thus, the assistance method receives a designation as to whether the detected cells or cellular components should be stored in the same storage unit, and stores the aspirated cells or cellular components in the same or a different storage unit based on the designation. Therefore, by storing the aspirated cells or cellular components in the same storage unit, the assistance method can obtain a sufficient amount of sample for analysis.

[0013] According to some embodiments, an information processing device is an information processing device for a support system that assists in the aspirating of specific cells or cellular components from a cell population in a cell culture vessel, and includes a control unit that acquires a photographed image of the cell population from an imaging unit, analyzes the acquired photographed image, detects cells or cellular components contained in the cell population that satisfy predetermined conditions, accepts a designation as to whether the detected cells or cellular components should be stored in the same storage unit, aspirates the detected cells or cellular components using a tip, and stores the cells or cellular components aspirated by the tip in the same or a different storage unit based on the designation. In this way, the information processing device accepts a designation as to whether the detected cells or cellular components should be stored in the same storage unit, and stores the aspirated cells or cellular components in the same or a different storage unit based on the designation. Therefore, by storing the aspirated cells or cellular components in the same storage unit, the information processing device can obtain a sufficient amount of sample for analysis.

[0014] In one embodiment, a program causes a computer to operate as the information processing device. The program receives a specification from the information processing device as to whether the detected cells or cellular components are to be stored in the same storage unit, and causes the information processing device to store the aspirated cells or cellular components in the same or a different storage unit based on the specification. Therefore, by storing the aspirated cells or cellular components in the same storage unit, it is possible to obtain a sufficient amount of sample for analysis. [Effects of the Invention]

[0015] According to one embodiment of the present disclosure, it is possible to obtain a sufficient amount of sample for analysis. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a schematic diagram illustrating a configuration of a support system according to an embodiment. [Figure 2A] FIG. 2 is a diagram showing an example of the sample rack in FIG. 1. [Figure 2B] FIG. 2 is a diagram showing an example of the sample rack in FIG. 1. [Figure 3] FIG. 2 is a schematic diagram illustrating the operation of the support system according to an embodiment. [Figure 4] FIG. 2 is a schematic diagram illustrating the operation of the support system according to an embodiment. [Figure 5] FIG. 2 is a schematic diagram illustrating the operation of the support system according to an embodiment. [Figure 6] 10 is a flowchart illustrating an operation procedure of the support system according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0017] <Comparative Example> The assistance system according to the comparative example assists in the task of aspirating specific cells or cell components from a cell group in a cell culture vessel. The assistance system according to the comparative example detects cells that meet predetermined conditions based on a microscopic image of the cell group, and upon receiving the designation of a specific cell, aspirates the cell using an aspirating tip and stores the tip in a sample rack such as a well plate. The tip stored in the sample rack is used for analysis. The assistance system according to the comparative example stores cells or cell-containing samples aspirated from different wells in a different location on the sample rack each time they are aspirated.

[0018] However, depending on the resolution and detection limit of the analytical device that analyzes samples such as cells, the amount of sample obtained by a single suction using the tip may not be sufficient for analysis after suction. For example, when performing PCR (Polymerase Chain Reaction) and cloning, a single cell may not be sufficient for analysis with sufficient accuracy. Therefore, in the comparative example, the analysis support system based on cell suction may not be able to obtain a sufficient amount of sample for analysis.

[0019] <Embodiment> Hereinafter, an embodiment of the present disclosure will be described with reference to the drawings. In each drawing, parts having the same configuration or function are denoted by the same reference numerals. In the description of this embodiment, duplicated descriptions of the same parts may be omitted or simplified as appropriate.

[0020] 1 is a schematic diagram showing the configuration of an assistance system 1 according to one embodiment. The assistance system 1 is a device that assists in the suction process of cellular components such as cells, intracellular organelles, or cell slices (hereinafter collectively referred to as "cells, etc."). The assistance system 1 includes an information processing unit 10, an optical system unit 20, and a suction operation unit 30.

[0021] The optical system unit 20 includes an XY stage 201, a microscope 21, a bright field illumination 213, a dichroic mirror (hereinafter referred to as "DM") 220, a variable magnification lens 221, a camera 222 as an imaging unit, and a confocal scanner unit 23. A cell culture vessel is placed on the XY stage 201. In this embodiment, the cell culture vessel placed on the XY stage 201 is, for example, a well plate 60 having a plurality of wells (holes) 61 formed therein, but may instead be a cell culture dish, a cover glass chamber, a petri dish, or the like. A specimen (sample) 62 such as a cell is placed in the well 61 of the well plate 60. The microscope 21 includes an objective lens 211.

[0022] The bright-field illuminator 213, DM 220, variable magnification lens 221, and camera 222 constitute a bright-field optical system for performing bright-field observation. In bright-field observation, bright-field signal light 71 is irradiated from the bright-field illuminator 213 toward the well plate 60. The DM 220 is designed to reflect the bright-field signal light 71 and transmit the excitation light beam 72 and fluorescence signal 73 (described later). The bright-field signal light 71 passes through the microscope 21, is reflected by the DM 220, and is imaged by the variable magnification lens 221 on a camera 222 for bright-field observation. Based on an exposure signal from the information processing unit 10, the camera 222 exposes the image projected on the light-receiving surface of its two-dimensional sensor for a specified time and converts it into digital image data. The image acquisition unit 16 of the information processing unit 10 acquires the digital image data from the camera 222. The bright-field illuminator 213 has a space formed in the center and has, for example, a torus (doughnut) shape.

[0023] The confocal scanner unit 23 includes dichroic mirrors (hereinafter referred to as "DM") 231, 235, a pinhole array disk (hereinafter referred to as "Nipkow disk") 232, a microlens array disk (hereinafter referred to as "ML disk") 233, a relay lens 234, bandpass filters 236 (236a, 236b), lenses 237 (237a, 237b), cameras 238 (238a, 238b) as an imaging unit, and a light source 239. In fluorescence observation, the excitation light source 239 emits an excitation light beam 72 having a specific wavelength toward the well plate 60. A fluorescent reagent is added to the sample 62, and when the excitation light beam 72 is irradiated, a fluorescent signal 73 having a wavelength longer than that of the excitation light beam 72 is emitted from the excited sample 62.

[0024] The DM 231 is designed to transmit the excitation light beam 72 and reflect the desired fluorescence signal 73. The ML disk 233 has a plurality of focusing optical elements (microlenses) arranged, for example, in a spiral shape. The Nipkow disk 232 has a plurality of pinholes arranged at positions where the excitation light beam 72 is focused by the plurality of focusing optical elements of the ML disk 233. The confocal scanner unit 23 can rotate the Nipkow disk 232 and the ML disk 233, which are mechanically connected to each other by a member 241, at high speed around the central axis of rotation using a motor or the like based on a control signal transmitted from the information processing unit 10. Here, the individual microlenses and pinholes formed on the Nipkow disk 232 are arranged so that the individual pinholes sweep the surface of the sample 62. Therefore, the Nipkow disk 232 functions as a scanner that scans the illumination light (excitation light beam 72) over the sample 62. The Nipkow disk 232 rotates the multiple pinholes in a plane that is approximately perpendicular to the optical axis of the excitation light beam 72. During imaging, the ML disk 233 and the Nipkow disk 232 are constantly rotating.

[0025] Most of the excitation light beam 72 that passes through the ML disk 233 passes through the Nipkow disk 232. Therefore, compared to when the Nipkow disk 232 is used alone, the confocal scanner unit 23 uses the ML disk 233 and the Nipkow disk 232 in combination, thereby increasing the irradiation intensity of the excitation light beam 72 on the sample 62. Furthermore, reflection of the excitation light beam 72 at parts of the Nipkow disk 232 other than the pinhole is suppressed. Therefore, the signal-to-noise ratio (SN ratio) of the image of the sample 62 increases.

[0026] The excitation light beam 72 is focused into individual light beams by the ML disk 233, passes through the DM 231, and then passes through individual pinholes in the Nipkow disk 232. The excitation light beam 72 passes through the DM 220 and is focused on the samples 62 placed in the wells 61 of the well plate 60 by the objective lens 211 of the microscope 21. As described above, a fluorescent reagent is added to each of the samples 62 in the well plate 60. Fluorescence signals 73 emitted by the fluorescent reagent in each of the samples 62 pass through the objective lens 211 and DM 220 again and are focused on individual pinholes in the Nipkow disk 232.

[0027] A fluorescent signal 73 that passes through the pinhole of the Nipkow disk 232 forms a confocal image. The fluorescent signal 73 is reflected by the DM 231 and passes through a relay lens 234 and lenses 237 (237a, 237b) to form an image on a camera 238 (238a, 238b) for fluorescence observation.

[0028] 1, in order to accommodate the simultaneous use of excitation light sources 239 of multiple wavelengths, the confocal scanner unit 23 is equipped with a DM 235 that has the property of spectrally dispersing the fluorescence signal 73. Furthermore, the confocal scanner unit 23 is equipped with bandpass filters 236 (236a, 236b) to improve the S / N ratio of the image and to pass only the necessary wavelength band of the fluorescence signal 73. The fluorescence signal 73 emitted by the sample 62 has various wavelengths, and it is desirable to prepare multiple bandpass filters 236 corresponding to the necessary wavelengths using, for example, filter foil or the like.

[0029] The plane on which the pinholes of the Nipkow disk 232 are arranged, the surface of the sample 62, and the light-receiving surface of the two-dimensional sensor of the camera 238 (238a, 238b) are arranged in an optically conjugate relationship with one another. Therefore, an optical cross-sectional image of the sample 62, i.e., a confocal image, is formed on the two-dimensional sensor of the camera 238. Based on an exposure signal from the information processing unit 10, the camera 238 exposes the image projected on the light-receiving surface of the two-dimensional sensor for a specified time and converts it into digital image data. The image acquisition unit 16 of the information processing unit 10 acquires the image data from the camera 238.

[0030] In this embodiment, the optical system unit 20 is configured to perform confocal two-color fluorescence observation and bright-field observation, as an example, but the configuration of the optical system unit 200 is not limited to this. For example, the optical system unit 200 may be configured to perform epi-fluorescence one-color without the confocal scanner unit 23 and bright-field observation system, or may be configured to perform confocal one-color only, or may be configured to perform confocal one-color and bright-field observation. Furthermore, the optical system unit 20 may be configured to acquire an image of the sample 62 using an observation method other than fluorescence observation, bright-field observation, and epi-fluorescence observation.

[0031] The suction operation section 30 includes an XYZ stage 31, a suction unit 32, a tip rack 34, a sample rack 35, and a discard box 39. A plurality of tips 33 for aspirating cells and the like are arranged on the tip rack 34. The sample rack 35 has a storage section 351 that stores tips 33 that have aspirated cells and the like, or cells and the like aspirated using the tips 33. The discard box 39 is a box in which tips 33 to be discarded are discarded.

[0032] The suction unit 32 moves in the X-axis, Y-axis, and Z-axis directions using the XYZ stage 31. The X-axis and Y-axis directions are two mutually orthogonal directions in a plane perpendicular to the optical axis of the excitation light beam 72. The Z-axis direction is a direction parallel to the optical axis of the excitation light beam 72. When performing the suction operation of cells or the like, the suction unit 32 retrieves and mounts a tip 33 from the tip rack 34. The suction unit 32 then moves toward the well plate 60 and suctions a sample 62, such as a cell, from a well 61 at a predetermined suction location. The suction location can be, for example, on the optical axis of the microscope 21.

[0033] At this time, the XY stage 201 moves the well plate 60 so that the sample 62 to be aspirated is positioned at the aspirating location. As a result, the tip 33 and the sample 62 to be aspirated are stacked vertically. The bright field illumination 213 is in the form of a ring so as not to interfere with the aspirating unit 32 during the aspirating operation. After aspirating the cells, etc., the aspirating unit 32 moves toward the sample rack 35 and stores the cells, etc. aspirated into the tip 33, or the tip 33 from which the cells, etc. have been aspirated, in the storage section 351 of the sample rack 35.

[0034] 2A and 2B are diagrams showing an example of the sample rack 35 of FIG. 1. FIG. 2A shows a sample rack 35a for storing cells and the like aspirated into the tip 33. The sample rack 35a includes a storage section 351a for storing cells and the like. The sample rack 35a of FIG. 2A is configured as a well plate having a plurality of wells (holes) formed as the storage section 351a, but is not limited thereto. For example, the sample rack 35a for storing cells and the like may be a cell culture dish, a cover glass chamber, a petri dish, or the like.

[0035] 2B shows a sample rack 35b for storing tips 33 after cells etc. have been aspirated. The sample rack 35b has holes for supporting the tips 33 as storage sections 351b for storing the tips 33.

[0036] When the operation mode of the assistance system 1 supports the pooling function, the assistance system 1 uses a sample rack 35a as shown in FIG. 2A for storing cells and the like aspirated into a tip 33. When the operation mode does not support the pooling function, the assistance system 1 uses a sample rack 35b as shown in FIG. 2B for storing the tip 33 itself after aspirating cells and the like. The user may switch between the sample rack 35a and the sample rack 35b as appropriate depending on the operation mode of the assistance system 1. Alternatively, the assistance system 1 may use a sample rack 35 that includes both the sample rack 35a for storing cells and the like as shown in FIG. 2A and the sample rack 35b for storing the tip 33 after aspirating cells and the like as shown in FIG. 2B.

[0037] Returning to the explanation of Fig. 1, the information processing unit 10 controls the overall operation of the support system 1. The information processing unit 10 can be configured using an information processing device such as a PC (Personal Computer). The information processing unit 10 includes a control unit 11, a storage unit 12, an operation reception unit 13, a display unit 14, an image processing unit 15, and an image acquisition unit 16.

[0038] The control unit 11 includes one or more processors. In one embodiment, the "processor" may be, but is not limited to, a general-purpose processor or a dedicated processor specialized for a particular process. The control unit 11 is communicatively connected to each component of the information processing unit 10 and controls the overall operation of the information processing unit 10. Furthermore, the control unit 11 controls the overall operation of the assistance system 1 by controlling each component of the information processing unit 10. For example, the control unit 11 controls the operation of the microscope 21, the bright field illumination 213, the camera 222, the confocal scanner unit 23, the XY stage 201, the XYZ stage 31, etc.

[0039] The storage unit 12 includes any storage module including a hard disk drive (HDD), a solid state drive (SSD), a read-only memory (ROM), and a random access memory (RAM). The storage unit 12 may function as, for example, a main storage device, an auxiliary storage device, or a cache memory. The storage unit 12 stores any information used in the operation of the information processing unit 10 or obtained as a result of the operation of the information processing unit 10. The storage unit 12 records, for example, image data acquired by the image acquisition unit 16 and analysis results of the image processing unit 15.

[0040] The operation reception unit 13 receives various operations from the user. The operation reception unit 13 is realized by, for example, a physical key, a capacitance key, a pointing device, a touch screen provided integrally with the display of the display unit 14, or a microphone that receives voice input.

[0041] The display unit 14 performs display processing of the images acquired by the image acquisition unit 16 and the analysis results of the image processing unit 15. The display unit 14 is realized by, for example, a liquid crystal display, an organic EL (Electro-Luminescence) display, or the like.

[0042] The image processing unit 15 performs various analyses after image processing on the image data acquired by the image acquisition unit 16. Specifically, the image processing unit 15 recognizes cells and organelles by template matching or the like, and calculates feature quantities such as size, brightness, protein amount, and ion amount for each identified cell. Furthermore, the image processing unit 15 uses the calculated feature quantities to perform processes such as listing and graphing information about the cells, etc.

[0043] The image acquisition unit 16 acquires image data from the cameras 222 and 238 (238a and 238b).

[0044] The functions of the information processing unit 10 can be realized by executing a program (computer program) that can be used to make the support system 1 according to this embodiment function, on a processor included in the control unit 11. That is, the functions of the information processing unit 10 can be realized by software. The program makes the computer execute the processing of steps included in the operation of the information processing unit 10, thereby making the computer realize the functions corresponding to the processing of each step. That is, the program is a program that makes the computer function as the information processing unit 10 according to this embodiment.

[0045] The program can be recorded on a computer-readable recording medium. Examples of the computer-readable recording medium include a magnetic recording device, an optical disc, a magneto-optical recording medium, and a semiconductor memory. The program can be distributed by, for example, selling, transferring, or lending a portable recording medium such as a DVD (Digital Versatile Disc) or a CD-ROM (Compact Disc ROM) on which the program is recorded. The program can also be distributed by storing the program in a server's storage and transferring the program from the server to another computer via a network. The program can also be provided as a program product.

[0046] A computer temporarily stores a program recorded on a portable recording medium or transferred from a server in its main storage device. The computer then reads the program stored in the main storage device with a processor and executes processing in accordance with the read program. The computer may also read the program directly from a portable recording medium and execute processing in accordance with the program. The computer may also execute processing in accordance with the received program each time a program is transferred from a server to the computer. Such processing may be executed by a so-called ASP (Application Service Provider) type service that realizes its functions simply by issuing execution instructions and obtaining results, without transferring a program from a server to the computer. Programs include information used for processing by a computer that is equivalent to a program. For example, data that does not directly instruct a computer but has properties that define computer processing falls under the category of "equivalent to a program."

[0047] Some or all of the functions of the information processing unit 10 may be realized by a dedicated circuit included in the control unit 11. That is, some or all of the functions of the information processing unit 10 may be realized by hardware. Furthermore, the information processing unit 10 may be realized by a single information processing device, or may be realized by cooperation of multiple information processing devices.

[0048] Next, an outline of the operation of the assistance system 1 will be described with reference to FIGS. 3 to 5. FIGS. 3 to 5 are schematic diagrams illustrating the operation of the assistance system 1 according to one embodiment. The assistance system 1 first accepts the setting of a well plate 60 on which a sample 62 is placed. At least one cell is placed in each well 61 of the well plate 60. The assistance system 1 performs an operation of identifying cells or the like having specific attributes from among these cells, aspirating them, and discharging them into the sample rack 35. Specifically, the assistance system 1 photographs each well 61 on the well plate 60 and analyzes the photographed image to detect cells or the like that are candidates for aspirating. The assistance system 1 displays images of the detected cells or the like on the display unit 14 and accepts the selection of target cells or the like to be aspirated from the user. At this time, the assistance system 1 also accepts a selection of whether to turn on a pooling function that stores the aspirated cells or the like in the same storage unit 351a of the sample rack 35a. When aspirating cells or the like, the support system 1 also accepts a selection as to whether or not to take another image of the cells or the like to be aspirated and correct the aspirating position based on the taken image.

[0049] The assistance system 1 starts an operation of aspirating cells or the like in response to a user's operation on the operation reception unit 13 of the information processing unit 10. The assistance system 1 moves the suction unit 32 to above the tip rack 34 using the XYZ stage 31 and attaches the tip 33 to the suction unit 32 (FIG. 3). Next, the assistance system 1 moves the suction unit 32 to above the well plate 60 using the XY stage 201. The assistance system 1 moves the well plate 60 using the XY stage 201 so that the target cells or the like are positioned below the tip 33, and aspirates the cells or the like (FIG. 4). After aspirating the cells or the like, the assistance system 1 moves the suction unit 32 to above the sample rack 35 using the XYZ stage 31. If the pooling function is set to ON, the assistance system 1 can discharge the aspirated cells or the like into a specific storage unit 351a into which multiple cells or the like are discharged (FIG. 5). After discharging the cells, etc., the assistance system 1 moves the suction unit 32 to above the disposal box 39 using the XYZ stage 31, releases the tip 33, and discards the tip 33. The assistance system 1 executes this series of operations of mounting the tip 33, suctioning the cells, etc., discharging the cells, etc., and discarding the tip 33 for each of the cells, etc. to be suctioned.

[0050] In this manner, the support system 1 according to the present disclosure operates as an automatic cell suction device capable of switching a pooling function ON / OFF. The pooling function is a function that allows multiple cells, etc., with the same attribute to be dispensed into the same storage unit 351a of the sample rack 35a. The support system 1 may, for example, display a checkbox on the display unit 14 of the information processing unit 10, and enable the pooling function to be switched ON / OFF in response to a user's selection of the checkbox via the operation reception unit 13. Alternatively, the support system 1 may be configured to set a storage unit 351a on the sample rack 35a for each well 61 of the well plate 60 on which the cells, etc., to be suctioned are placed. If the same storage unit 351a is set for multiple cells, etc., the support system 1 may control storage according to the setting. This allows multiple cells, etc., with the same attribute to be stored in the same storage unit 351a, etc.

[0051] The pooling function may be used in applications such as PCR and cloning. When performing such analyses, the assistance system 1 dispenses and stores the number of cells required for the analysis in the same storage unit 351a of a sample rack 35, such as a well plate. The user removes the stored cells from the assistance system 1 and analyzes or stores them in an incubator. The assistance system 1 may allow the user to set the number of cells pooled in the same storage unit 351a to an arbitrary value to ensure a sufficient number of cells for such applications and enable sufficiently accurate analysis. For example, when accepting the selection of target cells to be aspirated, the assistance system 1 may also accept the selection of a storage destination and generate a list including information on the target cells and the storage destination. For example, if the sample rack 35a is a well plate with 8 × 12 (= 96) wells arranged in a grid, the wells serving as the storage unit 351a of the sample rack 35a can be identified by two-dimensional coordinates (X, Y). Here, X may take any value from A to H, and Y may take any value from 1 to 12. Information on the storage destination of cells, etc. may be recorded in the list as information such as (A, 1). For example, if two targets are registered in the list and the storage destination for each is set to (A, 1), the two cells, etc. will be pooled in the well (A, 1).

[0052] In addition to the operating mode corresponding to the pooling function as described above, the assistance system 1 may also switch to an operating mode not corresponding to the pooling function, depending on the user's selection. In the operating mode corresponding to the pooling function, the assistance system 1 stores cells, etc., aspirated by the tip 33 in the sample rack 35a, whereas in the operating mode not corresponding to the pooling function, the assistance system 1 stores the tip 33 itself, which has aspirated the cells, etc., in the sample rack 35b. That is, the operating mode corresponding to the pooling function stores aspirated cells, etc., whereas the operating mode not corresponding to the pooling function stores the tip 33, which has aspirated the cells, etc. In the operating mode not corresponding to the pooling function, the assistance system 1 places the tip 33, which has aspirated the cells, etc., in the storage section 351b of the sample rack 35b without discharging the cells, etc., from the tip 33. For example, in applications such as direct MS (Mass Spectrometry), the operating mode not corresponding to the pooling function is selected, and the tip 33, which has aspirated the cells, etc., is used for analysis as is. Even in an operation mode compatible with the pooling function, the support system 1 may not use the pooling function and may store the aspirated cells and the like in different storage units 351a.

[0053] The assistance system 1 may perform position correction when aspirating a sample 62 such as cells from the well plate 60. This allows for accurate sampling by dealing with cell movement and division that occurs over time between the time when an image is taken to select a target and the time when the cells are aspirated. The assistance system 1 performs position correction based on image analysis by the image processing unit 15, but instead, the assistance system 1 may perform position correction by aspirating cells at a position specified by the user via the operation reception unit 13. The assistance system 1 may be able to specify position correction on the order of 0.1 μm to several hundred μm.

[0054] After aspirating cells, the assistance system 1 may select whether to store the cells in the sample rack 35 based on image analysis or a user instruction. The user can avoid contamination of stored samples by discarding samples that the user determines not to store based on the aspirated state of the cells. For example, if whole cells are sampled while sampling and pooling intracellular substances, pooling the cells as they are would result in excess material being mixed with the cells pooled just before. Therefore, the user can determine whether to store such aspirated material by viewing an image immediately after sampling or by image processing. The assistance system 1 may make such a determination for each aspirated cell or for only specific cells. For example, the assistance system 1 may display a checkbox on the display unit 14 to confirm the decision to store the cells, and determine whether to store the aspirated cells depending on whether the checkbox is selected by the user. When the user selects to store the cells, the assistance system 1 stores the cells in the storage unit 351a at a pre-designated position in the sample rack 35.

[0055] The assistance system 1 may count the number of cells or the like (number of samples) stored in each storage unit 351a of the sample rack 35. For example, the assistance system 1 may manage the number of samples of cells or the like stored in each storage unit 351a, and may increment the number of samples in that storage unit 351a by one each time one cell or the like is stored in that storage unit 351a. The assistance system 1 may display such number of samples in each storage unit 351a on the display unit 14 in response to a user instruction. This allows the user to easily check the number of samples stored in each storage unit 351a.

[0056] Fig. 6 is a flowchart showing the operation procedure of the support system 1 according to one embodiment. The operation of the support system 1 described with reference to Fig. 6 corresponds to one support method according to this embodiment. The operation of each step in Fig. 6 is executed under the control of the control unit 11 of the information processing unit 10. A program for causing a computer to execute the support method according to this embodiment may include each step shown in Fig. 6.

[0057] In step S1, the control unit 11 receives a set of samples and other items required for analysis from the user. The user places the well plate 60 in which cells have been cultured in a predetermined position on the support system 1. At this time, the user may fluorescently stain the sample as needed. The user also places a tip 33 in the tip rack 34 that corresponds to the purpose of suction. For example, when suctioning cellular components, the user may place a nanospray tip in the tip rack 34. For example, when suctioning a single cell, the user may place a regular suction tip in the tip rack 34.

[0058] In step S2, the control unit 11 receives imaging conditions and the like from the user via the operation reception unit 13. When receiving imaging conditions, for example, the optical system such as confocal, epifluorescence, or phase contrast is specified, and settings such as wavelength setting, imaging interval, and total imaging time are made. Taking images using a confocal optical system makes it easy to select three-dimensional components when aspirating cells.

[0059] In step S3, the control unit 11 receives the analysis content, etc. When receiving the analysis content, the target for feature calculation and the detection conditions for the cells of interest are set. The feature may be brightness, size, etc. When setting the detection conditions, thresholds for the feature are set. These feature are used when automatically detecting cells that satisfy the detection conditions in step S6.

[0060] In step S4, the control unit 11 receives from the user a setting of the imaging range of the wells 61 in the well plate 60. For example, if the wells 61 are arranged in a grid pattern in the well plate 60, the position of each well 61 can be specified by two-dimensional coordinates (X, Y). Therefore, the control unit 11 may receive a setting of the imaging range using, for example, a range of two-dimensional coordinates (X, Y).

[0061] In step S5, control unit 11 performs photography using camera 222, camera 238a, and camera 238b as photography units in the photography range set in step S4. Control unit 11 may also photograph using some of these cameras.

[0062] In step S6, the control unit 11 controls the image acquisition unit 16 to acquire images from the cameras 222, 238a, and 238b, and the image processing unit 15 to perform analysis by image processing. The control unit 11 performs image analysis based on the analysis content etc. received in step S3. The control unit 11 detects cells that satisfy the extraction conditions through the analysis by image processing.

[0063] In step S7, the control unit 11 displays the analysis results of step S6 on the display unit 14. The control unit 11 may display the analysis results so as to clarify cells, etc. that satisfy the detection conditions. Specifically, for example, the control unit 11 may display a microscope image on the display unit 14 and highlight cells, etc. that satisfy the detection conditions in the microscope image. Alternatively, for example, the control unit 11 may display a list of recognized cells, etc., and highlight cells, etc. that satisfy the detection conditions. Alternatively, for example, the control unit 11 may display a scatter plot based on the feature quantities (e.g., size, brightness, etc.) of the recognized cells, etc., and highlight cells, etc. that satisfy the detection conditions in the scatter plot. The display of the analysis results is not limited to these examples and can be in various forms.

[0064] In step S8, the control unit 11 determines whether the operation mode of the assistance system 1 is compatible with the pooling function. As described above, the assistance system 1 provides multiple operation modes according to conditions such as cell aspiration and imaging, and some operation modes are compatible with the pooling function and some are not. In operation modes compatible with the pooling function, cells, etc., aspirated by the tip 33 are stored in the sample rack 35a, while in operation modes not compatible with the pooling function, the tip 33 itself that aspirated the cells, etc., is stored in the sample rack 35b. In step S8, the control unit 11 determines whether the currently executed operation mode is compatible with the pooling function based on the type of operation mode. If the control unit 11 determines that the pooling function is compatible (YES in step S8), the control unit 11 proceeds to step S9; if not (NO in step S8), the control unit 11 proceeds to step S10.

[0065] In step S9, the control unit 11 accepts a selection of ON / OFF of the pooling function from the user. The control unit 11 may, for example, display a check box on the display unit 14 and accept the selection of ON / OFF in response to an operation on the check box via the operation accepting unit 13. When the pooling function is ON, the support system 1 can store one or more cells, etc. in the same storage unit 351a of the sample rack 35a. When the pooling function is OFF, the support system 1 can store only one cell, etc. in the same storage unit 351a of the sample rack 35a.

[0066] In step S10, the control unit 11 accepts registration of cells, etc. to be sucked (targets). For example, the control unit 11 may accept a user's selection of desired cells, etc., from among the cells, etc. that satisfy the detection conditions displayed in step S7. Specifically, for example, the control unit 11 may allow the user to select cells to be sucked from the microscope image using the operation receiving unit 13. Since the image processing unit 15 identifies individual cells, when a specific cell is designated in the displayed image, the control unit 11 can identify that cell in the well plate 60. Alternatively, the control unit 11 may register targets by automatically selecting the cells, etc., detected in step S6 in sequence.

[0067] In step S11, the control unit 11 accepts the setting of a storage location for storing the aspirated cells, etc. The control unit 11 may, for example, accept the setting of the storage unit 351a in the sample rack 35a for each of the cells, etc. to be aspirated selected in step S10. Alternatively, the control unit 11 may accept the setting of a storage unit 351a common to all of the aspirated cells, etc. If the pooling function is set to ON, the same storage unit 351a may be set for multiple cells, etc., or a different storage unit 351a may be set for each cell, etc. If the pooling function is set to OFF, a different storage unit 351a is set for each cell, etc. Note that the storage location may not be specified by the user, but may be automatically selected by the control unit 11 depending on whether the pooling function is ON or OFF.

[0068] In step S12, the control unit 11 accepts a setting as to whether or not to perform position correction when aspirating cells, etc. Depending on the measurement target, cells, etc. may move or divide between the time of imaging in step S5 and the time of actual aspirating of cells, etc. If there is such a possibility, the user sets to perform position correction. The control unit 11 may, for example, display a check box on the display unit 14 and accept the selection of position correction in response to an operation on the check box via the operation acceptance unit 13.

[0069] After the above preparation work, the control unit 11 starts the suction operation of the cells etc. in response to an instruction from the user. In step S13, the control unit 11 controls the XY stage 201 to move the cells etc. to be sucked to the suction position. The suction position may be, for example, on the optical axis of the microscope 21.

[0070] In step S14, the control unit 11 controls the XYZ stage 31 to move the suction unit 32 in the direction of the tip rack 34, as shown in FIG.

[0071] In step S15, the control unit 11 controls the XYZ stage 31 to move the suction unit 32 so that the tip 33 coincides with the suction position based on the result of the image analysis in step S6, as shown in Fig. 4. Here, the bright field illumination 213 has a space in the center, so that it does not interfere with the suction unit 32.

[0072] In step S16, the control unit 11 determines whether or not to perform position correction based on the setting in step S12. If position correction is to be performed (YES in step S16), the process proceeds to step S17, and if not (NO in step S16), the process proceeds to step S18.

[0073] In step S17, the control unit 11 again captures an image of the well 61 containing the sample 62, such as cells to be sucked, and controls the XY stage 201 so that the cells to be sucked coincide with the position of the tip 33. As a result of the processing in steps S14 and S15, the cells to be sucked and the tip 33 are generally vertically overlapped at the suction position. This facilitates the suction of the target cells. However, the cells may have moved or divided since the image was acquired in step S5. Furthermore, a specific organ to be sucked may have moved within the cells. Even in such cases, the assistance system 1 can accurately suck the cells by performing position correction in step S17. The control unit 11 may also correct the suction unit 32 in the Z-axis direction.

[0074] The control unit 11 may also display a captured image of the well 61 immediately before suction on the display unit 14 and perform position correction in response to a user instruction. To facilitate position correction by the user, for example, the control unit 11 may display a microscope image on the display unit 14 in real time and receive a movement instruction from the user via the operation reception unit 13. At this time, a fluorescent substance may be applied to the tip of the tip 33 so that the position of the tip 33 can be identified in the fluorescence observation image. Alternatively, an LED (Light Emitting Diode) light source may be provided near the attachment portion of the suction unit 32 to the tip 33, and the tip 33 may be visualized by irradiating it with light of a predetermined wavelength in the direction of the tip 33. After completing the process of step S17, the control unit 11 proceeds to step S18.

[0075] In step S18, the control unit 11 performs suction (sampling) of the cells. At this time, the control unit 11 may take images of the cells before and after suction. This allows the control unit 11 to confirm the reliability of the suction operation after the fact. For example, if a cell different from the one to be suctioned is sucked, or if the entire cell is sucked even though only a specific organelle within the cell is the one to be suctioned, the control unit 11 or the user can determine that the suction was not performed appropriately based on the images before and after suction.

[0076] In step S19, the control unit 11 determines whether or not to preserve the aspirated sample of cells or the like. The control unit 11 may, for example, determine whether or not the aspirated sample was properly performed based on images of the cells or the like taken before and after the aspirated sample, and if the aspirated sample was properly performed, may determine to preserve the sample. Alternatively, for example, the control unit 11 may display images of the cells or the like taken before and after the aspirated sample on the display unit 14, receive an instruction from the user as to whether or not to preserve the sample, and determine whether or not to preserve the aspirated cells or the like according to the instruction. If the control unit 11 determines that the sample of cells or the like will be preserved (YES in step S19), the process proceeds to step S20; if not (NO in step S19), the process proceeds to step S23.

[0077] In step S20, the control unit 11 determines whether or not the tip 33 into which cells, etc. have been aspirated will be used for analysis. As described above, in an operation mode that does not support the pooling function, the tip 33 into which cells, etc. have been aspirated is used for analysis as is, and in an operation mode that supports the pooling function, the cells, etc. discharged from the tip 33 are used for analysis. If the control unit 11 determines that the tip 33 into which cells, etc. have been aspirated will be used for analysis (YES in step S20), the process proceeds to step S21; otherwise (NO in step S20), the process proceeds to step S22.

[0078] In step S21, the control unit 11 stores the tip 33 into which cells or the like have been aspirated in the storage unit 351b designated or set in step S11. Specifically, the control unit 11 controls the XYZ stage 31 to move the tip 33 into which cells or the like have been aspirated toward the sample rack 35b, and releases and stores the tip 33 in the designated or set storage unit 351b. Then, the control unit 11 proceeds to step S24.

[0079] In step S22, the control unit 11 stores the cells, etc., aspirated into the tip 33 in the storage unit 351a specified in step S11. Specifically, as shown in Fig. 5, the control unit 11 controls the XYZ stage 31 to move the tip 33, which has aspirated the cells, etc., toward the sample rack 35a, and discharges and stores the cells, etc., in the specified or set storage unit 351a. Then, the control unit 11 proceeds to step S23.

[0080] In step S23, the control unit 11 releases and discards the tip 33 in the discard box 39. Then, the control unit 11 proceeds to step S24. Note that, during the work of step S21 or S23, the control unit 11 may store in the memory unit 12 an image taken during the suction work of cells, etc., in association with the tip 33 or cells, etc., from which cells have been suctioned.

[0081] If there is a suction instruction for another cell in the image captured in the process (step S105) (YES in step S115), the process of moving the cell to the suction position (step S109) and subsequent processes are repeated.

[0082] In step S24, the control unit 11 determines whether or not the processes of steps S13 to S23 have been performed for all targets registered in step S10. If the processes have been performed for all targets (YES in step S24), the control unit 11 ends the processing of the flowchart. If the processes have not been performed for all targets (NO in step S24), the control unit 11 returns to step S13 and performs the processes of steps S13 to S23 for targets that have not yet been processed.

[0083] The order of the above steps is an example, and the control unit 11 may execute the steps in a different order. For example, the control unit 11 may appropriately modify and execute the processes of steps S1 to S4 and S8 to S12.

[0084] As described above, the assistance system 1 assists in the task of aspirating specific cells or cellular components from a cell group in a cell culture vessel. The control unit 11 of the information processing unit 10 acquires images of the cell group captured by at least one of the cameras 222 and 238, analyzes the acquired images, and detects cells or cellular components contained in the cell group that meet predetermined conditions. The control unit 11 receives a designation as to whether to store the detected cells or cellular components in the same storage unit 351, and causes the chip 33 to aspirate the detected cells or cellular components. The control unit 11 stores the cells or cellular components aspirated by the chip 33 in the same or a different storage unit 351 based on the designation. In this way, the assistance system 1 receives a designation as to whether to store the detected cells or cellular components in the same storage unit 351, and stores the aspirated cells or cellular components in the same or a different storage unit 351 based on the designation. Therefore, by storing the aspirated cells or cellular components in the same storage unit 351, the assistance system 1 can obtain a sufficient amount of sample for analysis.

[0085] Furthermore, the control unit 11 receives a designation of a storage unit 351 for storing the cells or cellular components for each detected cell or cellular component, and stores the cells or cellular components aspirated by the tip 33 in the designated storage unit 351. In this way, the support system 1 receives a designation of a storage unit 351 for each detected cell or cellular component, allowing the user to obtain an appropriate amount of sample depending on the application.

[0086] Furthermore, the control unit 11 analyzes the captured image to identify the position of the detected cell or cellular component, and based on the identified position, causes the detected cell or cellular component to be aspirated by the tip 33. In this way, the support system 1 analyzes the captured image to identify the position of the detected cell or cellular component, and is therefore able to appropriately aspirate the detected cell or cellular component.

[0087] Furthermore, the control unit 11 acquires a photographed image of the cell or cellular component when the detected cell or cellular component is aspirated. Based on the photographed image of the cell or cellular component when aspirated, the control unit 11 corrects the identified position and causes the tip 33 to aspirate the detected cell or cellular component based on the corrected position. In this way, the assistance system 1 acquires a photographed image of the cell or cellular component immediately before aspirating, corrects the position of the cell or cellular component based on the photographed image, and aspirates the cell or cellular component. Therefore, even if the cell moves or divides between the time of photographing to detect the aspirated cell or cellular component and the time of aspirating, the assistance system 1 can accurately aspirate and store the desired cell or cellular component.

[0088] The control unit 11 also acquires captured images of a cell group containing the cells or cellular components before and after the detected cells or cellular components are aspirated by the tip 33. The control unit 11 analyzes the captured images before and after aspirating by the tip 33 to determine whether or not to preserve the aspirated cells or cellular components. If the control unit 11 determines that the aspirated cells or cellular components should be preserved, it stores the cells or cellular components in the storage unit 351. In this way, the support system 1 analyzes the captured images before and after aspirating to determine whether or not to preserve the aspirated cells or cellular components, and is therefore able to preserve only cells or cellular components that have been appropriately aspirated.

[0089] Furthermore, if it is determined that the aspirated cells or cellular components are not to be preserved, the control unit 11 discards the cells or cellular components. In this way, the support system 1 discards cells or cellular components that are not determined to be preserved, and therefore it is possible to preserve cells or cellular components that were not properly aspirated, thereby preventing contamination of the sample.

[0090] As described above, the assistance system 1 enables pools to be set according to the content of the post-sampling analysis process. The assistance system 1 discards samples that are not to be preserved, thereby preventing contamination of preserved samples with inappropriate cells, etc. The assistance system 1 also flexibly accommodates sample movement over time, enabling accurate sampling. The assistance system 1 also counts the number of cells, etc. preserved in each storage unit 351 and displays that number on the display unit 14, allowing the user to easily grasp the number of cells, etc. preserved in each storage unit 351.

[0091] 6, the support system 1 may perform machine learning based on a large amount of data in advance and execute the processing based on the results of the machine learning. This enables the support system 1 to automatically and accurately perform processing such as identifying the suction target, correcting its position, and determining whether to save the material.

[0092] The present disclosure is not limited to the above-described embodiments. For example, multiple blocks shown in the block diagrams may be integrated, or one block may be divided. Multiple steps shown in the flowcharts may be executed in parallel or in a different order depending on the processing capabilities of the device executing each step, or as needed, instead of being executed in chronological order as described. Other modifications are possible without departing from the spirit of the present disclosure. [Explanation of symbols]

[0093] 1. Support System 10 Information Processing Section 11 Control section 12 Storage section 13 Operation reception section 14 Display section 15 Image processing section 16 Image acquisition unit 20 Optical system section 201 XY Stage 21 Microscope 211 Objective Lens 213 Brightfield illumination 220 Dichroic Mirror 221 Variable Magnification Lens 222 Camera 23 Confocal scanner unit 231 Dichroic Mirror 232 Pinhole Array Disk 233 Microlens Array Disk 234 Relay Lens 235 Dichroic Mirror 236 Bandpass Filter 237 Lens 238 Camera 239 Light source 30 Suction operation part 31 XYZ Stage 32 Suction unit 33 chips 34 Tip Rack 35 sample racks 351 Preservation Department 39 Disposal Box 60-well plate 61 wells 62 samples 71 Brightfield signal light 72 Excitation beam 73 Fluorescence Signal

Claims

1. A support system for supporting an operation of aspirating a specific cell or cell component from a group of cells in a cell culture vessel, comprising: Acquiring a photographed image of the cell group photographed by an imaging unit; Analyzing the acquired photographed image to detect cells or cell components that satisfy predetermined conditions among the cells or cell components contained in the cell group; Accepting a designation as to whether or not the detected cells or cellular components are to be stored in the same storage unit; The detected cells or cell components are aspirated by a tip; storing the cells or cell components aspirated by the tip in the same or a different storage unit based on the received designation; An assistance system comprising a control unit.

2. the control unit receives, for each of the detected cells or cellular components, a designation of the storage unit that stores the detected cells or cellular components; storing the cells or cell components aspirated by the tip in the designated storage unit; The assistance system according to claim 1 .

3. The control unit Analyzing the captured image to identify the location of the detected cells or cellular components; aspirating the detected cell or cellular component by the tip based on the identified location; The assistance system according to claim 1 or 2.

4. The control unit acquiring a photographed image of the detected cell or cellular component when the cell or cellular component is being aspirated; correcting the identified position based on the captured image of the cell or cellular component during the aspirating process, and aspirating the detected cell or cellular component using the tip based on the corrected position; The assistance system according to claim 3 .

5. The control unit Acquire photographic images of the cell group including the detected cell or cell component before and after the cell or cell component is aspirated by the tip; Analyzing the captured images before and after the aspirated cells or cell components by the tip to determine whether or not to preserve the aspirated cells or cell components; If it is determined that the aspirated cells or cellular components should be preserved, the cells or cellular components are preserved in the preservation unit. Assistance system according to any one of claims 1 to 4.

6. The assistance system according to claim 5 , wherein the control unit discards the aspirated cells or cellular components when it is determined that the aspirated cells or cellular components should not be preserved.

7. 1. A method for assisting a system for assisting a task of aspirating a specific cell or cell component from a group of cells in a cell culture vessel, comprising: A control unit of the assistance system acquiring an image of the cell group from an imaging unit; analyzing the acquired photographed image to detect cells or cell components that satisfy predetermined conditions among the cells or cell components contained in the cell group; Accepting a designation as to whether or not the detected cells or cellular components are to be stored in the same storage unit; aspirating the detected cells or cell components with a tip; storing the cells or cell components aspirated by the tip in the same or a different storage unit based on the received designation; and how to help.

8. An information processing device of a support system that supports an operation of aspirating a specific cell or cell component from a group of cells in a cell culture vessel, Acquire a photographed image of the cell group from an imaging unit; Analyzing the acquired photographed image to detect cells or cell components that satisfy predetermined conditions among the cells or cell components contained in the cell group; Accepting a designation as to whether or not the detected cells or cellular components are to be stored in the same storage unit; The detected cells or cell components are aspirated by a tip; storing the cells or cell components aspirated by the tip in the same or a different storage unit based on the received designation; An information processing device including a control unit.

9. A program that causes a computer to operate as the information processing device according to claim 8.

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