JP6176471B2 - Cell picking support device and display device - Google Patents

Description

  The present invention relates to a cell picking support apparatus and a display apparatus.

  In recent years, in the field of regenerative medicine, culturing pluripotent cells such as ES cells and iPS cells, and culturing them while maintaining their pluripotent properties, or certain cells Cultures that induce differentiation are performed.

  These culturing steps include a step of selecting necessary cells and cell groups and extracting them.

  As an apparatus for supporting this type of cell extraction process, a picking work support apparatus that guides the extraction position by lighting the position of the target cell in the culture vessel fixed on the display unit is disclosed. (For example, refer to Patent Document 1). Hereinafter, the operation of extracting cells in the culture container and transferring them to another culture container is referred to as picking work.

International Publication No. 2011/004854

  By the way, if the cells extracted by the picking work are not suitable as the cells to be extracted, the picking work must be performed again, resulting in poor work efficiency. Therefore, there has been a demand for performing the picking operation after confirming whether the target cell is suitable as a cell to be extracted.

  The present invention has been made in view of such a situation, and when performing a cell picking operation, it is possible to confirm whether the target cell is suitable as a cell to be extracted, thereby improving work efficiency. It is to be able to be made.

The cell picking support apparatus according to the first aspect of the present invention includes an acquisition means for acquiring observation information for each cell cultured in a predetermined culture environment, and the cells to be picked based on the acquired observation information Cell identification means for identifying candidate cells that are candidates for picking from among the cells stored in the culture container containing the cell, and a display provided on the mounting surface side of the culture container based on the obtained observation information A first display area for displaying position information indicating the position of the candidate cell among the cells accommodated in the culture container, and a second display area for displaying detailed information regarding the candidate cell Display control means for displaying the first display area, wherein the first display area is an area corresponding to a placement area on the bottom surface of the culture vessel in the display area of the display means, and the second display area Is a region different from the previous described depositing area, wherein the display control unit, a manipulation that is accepted by the operation acceptance means, the target from the picking among said candidate cells displayed in the second display area The cell picking support apparatus displays information indicating a position of a selected cell to be picked in the first display area in accordance with an operation of an operator who selects a cell.
The display device according to the first aspect of the present invention includes display means provided on a placement surface side of a culture vessel that contains cells cultured in a predetermined culture environment, and is observation information for each cell. Based on the acquired observation information, based on the acquired observation information, cell specifying means for specifying candidate cells that are candidates for picking from the cells accommodated in the culture container, and based on the acquired observation information The display means displays a first display area for displaying position information indicating the position of the candidate cell among the cells accommodated in the culture container, and a first display area for displaying detailed information regarding the candidate cell. Display control means for displaying two display areas, wherein the first display area is an area corresponding to the placement area on the bottom surface of the culture vessel among the display areas of the display means, Table of Region is a region different from the previous described depositing area, wherein the display control unit, a operation accepted by the operation accepting means, said picking from among the candidate cells displayed in the second display area The display device displays information indicating the position of a selected cell to be picked in the first display area in accordance with an operation of an operator who selects a target cell .

The cell picking support apparatus according to the second aspect of the present invention includes an acquisition means for acquiring observation information for each cell cultured in a predetermined culture environment, and the cells to be picked based on the acquired observation information A first display region for displaying position information indicating a position of a specific cell among the cells stored in the culture container on the display means provided on the mounting surface side of the culture container storing Display control means for displaying a second display area for displaying detailed information regarding the cells of the display means, wherein the first display area is placed on the bottom surface of the culture vessel in the display area of the display means The second display area is an area different from the placement area, and the display control means assigns cells contained in the culture container to the second display area. Vs picking Is displayed in a predetermined display form in accordance with the operator's operation for selecting operations, a operation accepted by the operation acceptance means, subject to picking out a cell displayed on the second display area cells The cell picking support apparatus is characterized in that information indicating a position of a selected cell to be picked is displayed in the first display area in response to an operation of an operator who selects
The display device according to the second aspect of the present invention includes display means provided on a placement surface side of a culture container that contains cells cultured in a predetermined culture environment, and is observation information for each cell. And a first display area for displaying position information indicating the position of a specific cell among the cells accommodated in the culture vessel on the basis of the acquired observation information. And a display control means for displaying a second display area for displaying detailed information related to the specific cell, wherein the first display area is the display area of the culture vessel of the display means. The second display area is an area corresponding to the placement area on the bottom surface, and the display control means is accommodated in the culture container in the second display area. Picked cells It is displayed in a predetermined display form in accordance with the operator's operation to perform target selection task, an operation that is accepted by the operation accepting means, subject to picking from among the displayed on the second display area cells The display device displays information indicating a position of a selected cell to be picked in the first display area in accordance with an operation of an operator who selects a cell .

  According to the first aspect and the second aspect of the present invention, work efficiency can be improved.

It is a figure explaining the outline | summary of the cell picking work assistance of this invention. It is a figure which shows the structure of one Embodiment of the tablet terminal device to which this invention is applied. It is a figure which shows the structural example of a control program. It is a flowchart explaining the 1st cell picking work assistance process in auto mode. It is a figure which shows the example of a display of the screen for picking assistance of an auto mode. It is a flowchart explaining the 2nd cell picking work assistance process in auto mode. It is a flowchart explaining the cell picking work support process in a manual mode. It is a figure which shows the example of a display of the screen for picking assistance of a manual mode. It is a figure which shows the example of a display of the screen for picking assistance of a manual mode. It is a flowchart explaining a setting process. It is a figure explaining an operation pattern. It is a figure which shows the example of a display of the screen for other picking assistance. It is a figure which shows the structural example of a computer.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  FIG. 1 is a diagram for explaining the outline of cell picking work support according to the present invention.

  As shown in FIG. 1, in the cell culture observation apparatus 10, a sample such as a cell accommodated in a well plate 111 is cultured. By seeding these cells, for example, optimization of cell colony formation is performed. In order to achieve the above, a picking operation is performed in which a portion of the well formed in the well plate 111 is picked up by a pipette (so-called picking), and the picked colony (cell lump) is transferred to another culture container.

  This picking operation is usually performed by transporting the well plate 111 to the clean bench 40 or the aseptic room (not shown) of FIG. By performing the picking operation in the clean bench 40, it is possible to perform the operation in an aseptic and dust-free environment. Then, the culture container to which the colonies have been transferred by the picking operation is transported again to the cell culture observation apparatus 10, and cell culture is resumed. The well plate 111 is a transparent member in which a plurality of concave culture wells (wells) are arranged for culturing cells. Samples such as cells are accommodated in the wells for culturing. It will be.

  The basic work process of the picking work has been described above. Next, detailed configurations of the cell culture observation apparatus 10, the tablet terminal apparatus 20, and the data analysis server 30 of FIG. 1 will be described.

  In the cell culture observation apparatus 10 of FIG. 1, the solid line indicates the structure of the part that appears on the appearance, and the broken line indicates the structure of the internal part that does not appear on the appearance. A temperature-controlled room 101 covered with a heat insulating material is formed inside the upper casing of the cell culture observation apparatus 10. The temperature-controlled room 101 is hermetically sealed in order to maintain a cell culture environment during cell culture, and maintains a room environment such as a temperature control device, a spray device, or a gas introduction unit provided therein. To maintain a constant temperature, humidity, or carbon dioxide concentration.

  In the temperature-controlled room 101, a stocker 102 and an observation unit 103 are accommodated. The stocker 102 is partitioned vertically by a plurality of shelves and can store the well plate 111 horizontally.

  The observation unit 103 is an apparatus for observing cells contained in the well plate 111 conveyed by a container conveyance mechanism (not shown), and observes the cells based on the phase difference of light transmitted through the cells. The cells are observed by two observation methods: observation and fluorescence observation in which the cells are observed by light excited by a fluorescent substance contained in the cells. In the observation unit 103, an image of light obtained at the time of observation is picked up by an image pickup device, and the image signal is subjected to predetermined signal processing to be cultured in each well of the well plate 111. An observation image of a sample such as a cell is obtained.

  The control unit 104 controls the operation of each part of the cell culture observation apparatus 10. The control unit 104 includes a recording unit 121 and a communication unit 122. The recording unit 121 accumulates observation images obtained by phase difference observation and fluorescence observation by the observation unit 103. The communication unit 122 is compatible with wireless communication, and transmits observation images accumulated in the recording unit 121 and information necessary when supporting the picking work in the tablet terminal device 20 to the data analysis server 30. To do.

  The data analysis server 30 is a server for providing the tablet terminal device 20 with information related to the cells cultured and observed by the cell culture observation device 10 (hereinafter referred to as culture observation information). Although not shown, the data analysis server 30 includes a communication unit corresponding to wireless communication in addition to the recording unit and the analysis unit, and an observation image transmitted from the cell culture observation apparatus 10 is transmitted by the communication unit. Received and recorded in the recording unit.

  For example, the analysis unit extracts a specific cell such as a colony by performing a predetermined image analysis process on the observation image obtained by the phase difference observation, and determines the position of the extracted specific cell. Coordinate information for determination is calculated. That is, in phase difference observation, transparent cells can be visualized and observed, and thus specific cells such as colonies can be extracted by detecting the visualized cells from the observed image. For example, two-dimensional coordinates (x, y) for determining the position of the extracted colony are calculated using one of the four corners of the well plate 111 having a rectangular shape as a base point coordinate (reference position). It is associated with identification information for identification (hereinafter referred to as a colony ID).

  Thus, the so-called time-lapse observation is performed by the cell culture observation apparatus 10, so that the data analysis server 30 has coordinates for each colony (colony ID) accommodated in each well of the well plate 111 observed by the observation unit 103. Information is sequentially accumulated in time series. The communication unit transmits culture observation information including observation images and analysis results to the tablet terminal device 20 in response to a request from the tablet terminal device 20.

  The tablet terminal device 20 is a portable personal computer having a display unit composed of a touch panel, and has a flat outer shape. In addition, the tablet terminal device 20 is configured to be able to store a battery such as a lithium ion secondary battery, and has no wiring and can be easily carried.

  The tablet terminal device 20 fixes and mounts the well plate 111 at a predetermined position on the screen of the display unit with an adapter (not shown). Although not shown, an insulating sheet is provided between the mounting surface of the well plate 111 and the screen of the display unit.

  In addition, the tablet terminal device 20 receives and records culture observation information transmitted from the data analysis server 30. And the tablet terminal device 20 displays the positional information which shows the position of a specific cell, such as a colony, or the detailed information regarding a specific cell based on culture observation information, By the operator, in the clean bench 40 Support picking work to be done. Hereinafter, a specific configuration of the tablet terminal device 20 will be described.

  FIG. 2 is a diagram showing a configuration of an embodiment of a tablet terminal device to which the present invention is applied.

  In the tablet terminal device 20 of FIG. 2, the solid line indicates the structure of the part that appears on the appearance, and the broken line indicates the structure of the internal part that does not appear on the appearance. That is, the tablet terminal device 20 is provided with a control unit 201, a communication unit 202, a display unit 203, and a recording unit 204 therein. As shown in FIG. 2, a well plate 111 is placed at a predetermined position on the screen of the display unit 203.

  The control unit 201 controls the operation of each unit of the tablet terminal device 20. The communication unit 202 performs wireless communication with the data analysis server 30 according to control from the control unit 201 and receives culture observation information.

  Based on the culture observation information received by the communication unit 202, the control unit 201 causes the display unit 203 to display various screens for supporting picking work (hereinafter referred to as “picking support screens”). The display unit 203 includes a touch panel, receives operator instructions for various GUI (Graphical User Interface) images, and supplies an operation signal corresponding to the instructions to the control unit 201. The control unit 201 controls the operation of each unit of the tablet terminal device 20 based on the operation signal from the display unit 203.

  As shown in FIG. 2, the picking support screen displayed on the display unit 203 includes a pick area 301 and a navigation area 302.

  The pick area 301 is a display area for displaying position information indicating a position where a specific cell exists. That is, as shown in FIG. 2, since the well plate 111 is placed on the pick area 301, the display unit 203 arranged on the placement surface side has specific cells in the pick area 301. When the position is displayed, the operator can confirm the display position transmitted through the well plate 111 which is a transparent member. Then, using the display position as a mark, the worker performs a picking operation for cells existing at the position.

  The navigation area 302 is a display area for displaying detailed information regarding a specific cell. In the navigation area 302, a plate selection button 311, a sample selection button 312, a cell display area 313, a tab 314, a setting button 315, and a cross button 316 are displayed.

  The plate selection button 311 is a button for setting the well plate 111 placed on the pick area 301. For example, when the operator taps the plate selection button 311, the thumbnail image of the well plate to be selected, the name of the sample, and the like are displayed in the navigation area 302, so that the operator can select the pick area 301. The well plate 111 placed on the top is selected. However, the “tap operation” means an operation of tapping a desired area on the touch panel with a finger or the like.

  The sample selection button 312 is a button for designating which of the wells of the well plate 111 selected by the plate selection button 311 is to be used as a picking target.

  The cell display area 313 is an area for displaying specific cells to be picked. In the cell display area 313, specific cells are displayed in various forms according to the touch panel operation by the operator.

  The tab 314 is a tab for switching the display form of the cells displayed in the cell display area 313. As shown in FIG. 2, the tab 314 includes a mask tab, a Ph tab, a Ch1 tab, a Ch2 tab, and a Ch3 tab.

  When the mask tab is tapped, a predetermined color (for example, red) is superimposed on a specific cell in the cell display area 313. When the Ph tab is tapped, an observation image obtained by phase difference observation of a specific cell is displayed in the cell display area 313.

  When the Ch1 to Ch3 tabs are tapped, an observation image obtained by fluorescence observation corresponding to the channel is displayed in the cell display area 313. However, each channel corresponds to the type of fluorescence observation performed by the cell culture observation apparatus 10.

  The setting button 315 is tapped when performing various settings. For example, since there are an auto mode and a manual mode as operation modes when supporting picking work, when the setting button 315 is tapped, a setting screen for setting the operation mode is displayed and the operation is performed. The mode is set. Here, the auto mode is a mode in which candidate cells that are candidates for picking are automatically presented and the operator determines whether the candidate cells are to be picked. The manual mode is a mode in which the operator manually selects a cell to be picked.

  Here, the setting screen for the operation mode has been described. However, when the setting button 315 is tapped, a setting screen for setting other setting items necessary for supporting picking work. Can be displayed.

  The cross button 316 is a button for adjusting the offset when the attachment position of the well plate 111 placed on the pick area 301 and fixed by an adapter (not shown) has an offset.

  The recording unit 204 records various data according to the control from the control unit 201.

  The tablet terminal device 20 is configured as described above.

  FIG. 3 is a diagram illustrating a configuration of the control program 251 executed by the control unit 201.

  The control program 251 includes a culture observation information acquisition unit 261, a recording control unit 262, an operation reception unit 263, a cell specification unit 264, a display control unit 265, and a setting unit 266.

  The culture observation information acquisition unit 261 controls the communication unit 202 to acquire culture observation information transmitted from the data analysis server 30. The recording control unit 262 causes the recording unit 204 to record the culture observation information acquired by the culture observation information acquisition unit 261.

  The operation accepting unit 263 accepts an operation by an operator in response to an operation signal from the display unit 203 configured as a touch panel. The recording control unit 262 causes the recording unit 204 to record various data according to the operation content received by the operation receiving unit 263.

  When the operation mode is the auto mode, the cell specifying unit 264 is based on the cell observation information recorded in the recording unit 204, and according to a predetermined condition determined in advance, from among the cells stored in the well plate 111, Identify candidate cells that are candidates for picking.

  The display control unit 265 causes the display unit 203 to display a picking support screen based on the cell observation information recorded in the recording unit 204. Specifically, the display control unit 265 displays position information of a specific cell in the pick area 301 and displays detailed information about the specific cell in the navigation area 302. Further, when the operation mode is the auto mode, the display control unit 265 displays an enlarged image of the candidate cell in the cell display region 313 based on the result of specifying the candidate cell by the cell specifying unit 264.

  The setting unit 266 sets various setting items according to the operation content of the operator on the setting screen received by the operation receiving unit 263.

  The control program 251 is configured as described above.

  By the way, as described above, the tablet terminal device 20 operates in either the auto mode or the manual mode when supporting the picking work. Therefore, next, a case where the tablet terminal device 20 operates in the auto mode and a case where the tablet terminal device 20 operates in the manual mode will be described.

  First, the first cell picking work support process in the auto mode will be described with reference to the flowchart of FIG. Note that the processing shown in the flowchart of FIG. 4 is executed when the auto mode is set as the operation mode.

  In step S <b> 10, the culture observation information acquisition unit 261 acquires the culture observation information transmitted from the data analysis server 30. As a result, the culture observation information of the cells stored in the well plate 111 is recorded in the recording unit 204.

  In step S <b> 11, the operation accepting unit 263 accepts selection of a plate to be picked in response to an operator tap operation on the plate selection button 311. As a result, the well plate 111 placed at a predetermined position on the screen of the display unit 203 is specified.

  In step S <b> 12, the cell specifying unit 264 specifies a cell candidate to be picked based on a predetermined condition for specifying a candidate cell based on the culture observation information recorded in the recording unit 204.

  This candidate cell is identified by, for example, the following method. That is, a specific cell such as a colony is extracted by the data analysis server 30 performing a predetermined image analysis process on the observation image obtained by the fluorescence observation in the cell culture observation apparatus 10. In addition, the data analysis server 30 further extracts expressed cells such as iPS cells from the extracted colonies, and acquires cell information related to the classification of the expressed cells. That is, in the fluorescence observation, the expressed cell emits fluorescence of a predetermined color. Therefore, it is possible to extract the expressed cell by detecting the fluorescence from the observation image. And since this cell information is matched with above-mentioned colony ID, the position and the presence or absence of expression will be calculated | required for every extracted colony. It is possible to determine whether or not a colony is present by the culture observation information including these pieces of information, and if a colony is present, whether or not it is expressed. For example, H.264 can identify iPS cells (expressed cells) or non-iPS cells (non-expressed cells) as candidate cells.

  In step S13, the display control unit 265 enlarges and displays the image corresponding to the candidate cell specified by the cell specifying unit 264 in the cell display area 313 of the navigation area 302 based on the culture observation information.

  At this time, a predetermined color (for example, red) is superimposed and displayed on the enlarged image of the candidate cell. However, since this state is a state in which the mask tab is selected from the tabs 314, when the Ph tab is tapped by the operator, an enlarged image of the candidate image obtained by phase difference observation is displayed. When any of the Ch1 tab to Ch3 tab is tapped, an enlarged image of the candidate image obtained by fluorescence observation is displayed.

  In step S14, the display control unit 265 displays a position corresponding to the candidate cell in the pick area 301 in a predetermined color (for example, red) based on the culture observation information.

Thereby, for example, as shown in FIG. 5, an image I _C1 corresponding to the enlarged candidate cell C1 is displayed in the cell display region 313 of the navigation area 302, and the position P corresponding to the candidate cell C1 of the pick area 301 is displayed. _C1 is displayed in red. At this time, in the pick area 301, the position P _C1 corresponding to the candidate cell C1 is displayed in red, the position of the other cells yellow, for example, because the position P _C1 of the candidate cell C1 is displayed in a different color, work The person can immediately determine the position of the candidate cell C1.

  Returning to the description of the flowchart of FIG. 4, in step S <b> 15, the operation reception unit 263 determines whether or not a picking operation has been performed on the candidate cell.

For example, in FIG. 5, when the operator confirms the image I _C1 corresponding to the candidate cell C1 enlarged and displayed in the cell display region 313 and decides to perform the picking operation of the cell C1, Using the position _PC1 as a mark, the picking operation of the candidate cell C1 existing at that position is performed. When the picking work is actually performed, it is determined that the picking work is performed on the candidate cell C1 by the operator tapping the pick button 317 on the touch panel ("S15" YES ").

  Returning to the description of the flowchart of FIG. 4, if it is determined in step S15 that the picking operation for the candidate cell has been performed, the process proceeds to step S16. In step S <b> 16, the recording control unit 262 records the picking history of candidate cells in the recording unit 204.

  Here, the picking history is recorded in association with the colony ID of the picked cell, for example. That is, it is managed for each colony ID whether or not it is a picking target. In addition, by analyzing the picking history accumulated sequentially, it can be determined whether or not the cells that have been selected as candidate cells have been targeted for picking. Would be wrong. In that case, when specifying the candidate cell next time, the cell specifying unit 264 feeds back the analysis result, and sets conditions for specifying the candidate so that a more appropriate candidate cell is specified. Change it.

  Thereby, whenever the tablet terminal device 20 repeats the cell picking work support process, the accuracy of specifying candidate cells by the cell specifying unit 264 can be improved. In addition, from the image of the target cell before and during the picking work and the experimental result of the target cell after the picking work, whether the cell specifying result by the cell specifying unit 264 and the judgment by the operator were appropriate, It will be possible to verify at a later date.

  In step S17, it is determined whether or not the picking work is to be ended. If it is determined that the work is to be continued, the process proceeds to step S18.

In step S18, the cell identification unit 264 identifies a candidate cell to be picked next. When step S18 ends, the process returns to step S13, and the subsequent processing is repeated. For example, in FIG. 5, when the operator taps the next button 318, the image I _C2 corresponding to the next candidate cell C2 is enlarged and displayed in the cell display area 313, and corresponds to the candidate cell C2 in the pick area 301. The position _PC2 is displayed in red. The operator confirms the image I _C2 of candidate cells C2 which is enlarged, if determines to picking the candidate cell C2, and the mark position P _C2 of the pick area 301, present at that position candidate The cell C2 is picked and the pick button 317 is tapped. On the other hand, if it is determined that the candidate cell C2 should not be picked, the next button 318 is operated without performing the picking operation.

  The above operation is repeated until it is determined that the picking work is finished (“YES” in S17), and the picking work is performed on the candidate cells C1 to Cn (n = 1, 2,..., N). become. For example, when a candidate cell that has already been displayed in the navigation area 302 is to be picked, such as when a desired cell is missed or when a certain cell has not been picked but has been reconsidered, By tapping the next button 318 or the previous button 319, a displayed desired candidate cell can be displayed again.

  The first cell picking work support process in the auto mode has been described above. In the first cell picking work support process in the auto mode, the enlarged images of the candidate cells are automatically and sequentially displayed in the navigation area 302. Therefore, the operator selects the candidate cells as the picking target while checking the enlarged images. Can be determined. When the candidate cell is selected as the picking target, the position of the candidate cell is displayed in the pick area 301. Therefore, the operator picks the candidate cell existing at the position using the display position as a mark. Work can be done.

  As a result, in addition to iPS cells (expressed cells) or non-iPS cells (non-expressed cells), for example, cardiomyocytes (pulsating cells) or non-myocardial cells (non-pulsating cells) When performing the cell picking work, work efficiency can be improved. Moreover, since it can be judged whether it is made the picking object, confirming the enlarged image of those cells, the precision of picking work can be improved.

  By the way, in the first cell picking work support process, the picking target selection work for selecting the cells to be picked from the candidate cells and the picking work were performed in units of cells, but in the auto mode, Such picking target selection work and picking work can also be regarded as independent work. Next, the second cell picking work support process in which the picking target selecting work and the picking work are performed independently and performed in units of work will be described with reference to the flowchart of FIG.

  In the second cell picking work support process, the picking target selection work is first performed, and the picking work is performed after the picking target selection work is completed. That is, in steps S110 to S113, as in steps S10 to S13 of FIG. 4, candidate cells on the target plate are specified, and the candidate cells are enlarged and displayed in the cell display area 313.

  In step S <b> 114, the operation reception unit 263 determines whether a candidate cell has been selected for picking according to the tap operation performed on the pick button 317 or the next button 318 by the operator. In step S114, when the pick button 317 is tapped and it is determined that the candidate cell is selected as a picking target, the process proceeds to step S115.

  In step S115, the recording control unit 262 records information on the selected picking target cell (hereinafter referred to as selected cell information) in the recording unit 204. For example, as the selected cell information, a colony ID of a cell to be picked is recorded. When step S115 ends, the process proceeds to step S116. If it is determined in step S114 that the next button 318 is tapped without the pick button 317 being tapped and the candidate cell is not selected for picking, the process in step S115 is skipped, The process proceeds to step S116.

  In step S116, the operation reception unit 263 determines whether or not to finish the picking target selection work according to the operation of the worker. If it is determined in step S116 that the picking target selection operation is not to be ended, the process proceeds to step S117.

  In step S117, the cell identification unit 264 identifies a candidate cell to be picked next. When step S117 ends, the process returns to step S113, and the subsequent processes are repeated. For example, when the next button 318 is tapped by the operator, the next candidate cell is enlarged and displayed in the cell display area 313, and a determination process is performed to determine whether or not the next candidate cell that has been enlarged is selected as a picking target. If selected as a picking target, selected cell information is recorded.

  The above processing for the picking target selection work is repeated until it is determined that the picking target selection work is to be finished (“YES” in S116), and the enlarged candidate cells C1 to Cn (n = 1, 2,... , N), for example, a candidate cell in which the pick button 317 is tapped is selected as a picking target, while a candidate cell in which the next button 318 is tapped without the pick button 317 being operated is excluded from the picking target. Will be.

  When the picking target selection work is completed, in step S118, the operation reception unit 263 determines whether to start the picking work according to the operation of the worker. If it is determined in step S118 that the picking operation is not started, the determination process in step S118 is repeated. Then, after the picking operation is started, the process proceeds to step S119.

  In step S119, the recording control unit 262 reads the selected cell information recorded in the recording unit 204.

  In step S120, the cell specifying unit 264 specifies a cell to be picked from the cells selected by the picking target selection operation based on the selected cell information. In steps S121 to S125, as in steps S14 to S18 of FIG. 4, the position corresponding to the cell to be picked is displayed in a predetermined color (for example, red) (S121), and the picking operation for the cell is performed. If it is detected (“YES” in S122), the picking history is recorded (S123).

  The above-described processing for the picking operation is repeated until it is determined that the picking operation is finished, and the picking target cell in which the pick button 317 is tapped among the picking target cells selected in the picking target selecting operation is picked. History is recorded. On the other hand, the picking history is not recorded since the picking target cell in which the pick button 317 is not operated and the next button 318 is tapped is not picked.

  At the time of the picking work, an image corresponding to the cell to be picked may be enlarged and displayed in the navigation area 302 so that the worker can perform the picking work while confirming the cell to be picked. Thereby, for example, even if the selection of a cell to be picked is mistaken in the picking target selection operation, it is possible to reliably pick only desired cells by stopping the picking operation of the cell.

  The second cell picking work support process in the auto mode has been described above. In the second cell picking work support process in the auto mode, the picking target cell is selected from the candidate cells by the picking target selecting work, and then the picking of the cell selected in the picking target selecting work is performed by the picking work. Done.

  Thereby, for example, when performing the picking work of specific cells such as iPS cells and cardiomyocytes, the working efficiency can be improved. In addition, for example, some workers may prefer a work form in which one work is repeatedly performed. However, since the picking target selection work and the picking work can be made independent, a flexible work form is provided. It becomes possible to do.

  Next, the cell picking work support process in the manual mode will be described with reference to the flowchart of FIG. The process shown in the flowchart of FIG. 7 is executed when the manual mode is selected as the operation mode.

  In steps S210 and S211, culture observation information is acquired as in steps S10 and S11 of FIG. 4, and a plate to be picked is selected according to the operator's operation.

  In step S212, the display control unit 265 displays an image corresponding to the entire area of the selected well of the selected well plate 111 on the cell display area 313 of the navigation area 302 based on the culture observation information. .

  In step S213, the operation reception unit 263 determines whether enlargement or reduction of a predetermined area of the image displayed in the cell display area 313 is instructed according to the operation of the operator.

  If it is determined in step S213 that enlargement or reduction of the predetermined area has been instructed, the process proceeds to step S214. In step S214, when the enlargement of the predetermined region is instructed, the display control unit 265 displays an image in which the predetermined region of the target well is enlarged on the cell display region 313 based on the culture observation information. . Further, when the reduction of the predetermined area is instructed, the display control unit 265 displays an image in which the predetermined area of the target well is reduced on the cell display area 313 based on the culture observation information.

  That is, as shown in FIG. 8, in the manual mode, first, an image corresponding to the entire area of the target well is displayed in the cell display area 313. At this time, a predetermined color (for example, yellow) is superimposed and displayed on each cell included in the entire image. In the pick area 301, the position corresponding to each cell is displayed in a predetermined color (for example, yellow).

  For example, when the operator performs a pinch-out operation on the image displayed in the cell display region 313, the display control unit 265 scales the image being displayed at an enlargement rate corresponding to the operation amount. Display. However, the “pinch-out operation” refers to an operation in which two fingers are placed on a desired area on the touch panel to widen the distance between the fingers.

  When the operator performs a pinch-in operation on the image displayed in the cell display area 313, the display control unit 265 scales and displays the displayed image at a reduction ratio corresponding to the operation amount. Let However, the “pinch-in operation” refers to an operation in which two fingers are placed on a desired area on the touch panel to narrow the distance between the fingers.

  That is, when a pinch-out operation or a pinch-in operation is performed, a predetermined area of the image displayed in the cell display area 313 is enlarged or reduced, so that the operator can move to a desired cell as shown in FIG. A corresponding enlarged image is displayed in the cell display area 313, and it can be determined whether or not to be picked.

  Returning to the description of the flowchart of FIG. 7, in step S <b> 215, the operation reception unit 263 determines whether a cell to be picked is selected. If it is determined in step S215 that the cell to be picked is not selected, the process returns to step S213, and the subsequent processes are repeated.

  For example, when an enlarged image of a desired cell is displayed in the cell display area 313 according to the operator's pinch-out operation, when the enlarged image is long-tapped, the cell is selected for picking. Can be determined. However, the “long tap operation” refers to an operation in which a desired area on the touch panel is touched for a certain time and then released. In other words, the above-described “tap operation” is an operation corresponding to a so-called long press. Further, the selection of the picking target is not limited to the long tap operation. For example, a predetermined operation screen having a determination button or a cancel button is displayed, and the picking target is selected when the determination button is operated by the operator. You may do it.

  If it is determined in step S215 that the cell to be picked has been selected, the process proceeds to step S216. In step S216, the display control unit 265 displays the position corresponding to the cell to be picked in the pick area 301 in a predetermined color (for example, red) according to the selection result of the cell to be picked.

Thereby, as in the case of the auto mode shown in FIG. 5 above, for example, in the cell display area 313 of the navigation area 302, the image I _C1 corresponding to the enlarged cell C1 to be picked is displayed, and the pick area A position _PC1 corresponding to 301 picking target cell C1 is displayed in red. Then, the operator performs the picking operation of the cell C1 existing at the position with the position _PC1 as a mark.

  Returning to the description of the flowchart of FIG. 7, in step S <b> 217, the operation reception unit 263 determines whether or not a picking operation has been performed on a cell to be picked. In step S217, when it is determined that the pick button 317 is tapped by the operator and the picking operation is performed on the cell to be picked, the process proceeds to step S218.

  In step S218, the recording control unit 262 records the picking history of the cell to be picked in the recording unit 204. When the picking history is recorded, the process proceeds to step S219.

  If it is determined in step S217 that the pick button 317 is not operated by the operator and the picking operation for the cell to be picked is not performed, step S218 is skipped, and the process proceeds to step S219.

  In step S219, it is determined whether or not to end the picking work. For example, if it is determined that the next button 318 is tapped and the work is to be continued, the process returns to step S212. And the process after step S212 is repeated. If it is determined in step S219 that the picking operation is to be continued, the processing may be returned to step S213 and the subsequent processing may be executed. As a result, the whole cell of the well is not displayed, but the next cell (for example, an adjacent colony) is displayed with the recognizable enlargement ratio instructed by the operator and can be confirmed. Can be saved.

  If it is determined in step S219 that the picking work is to be finished, the cell picking work support process in the manual mode is finished.

  The cell picking work support process in the manual mode has been described above. In the cell picking work support process in the manual mode, an enlarged image of the cell according to the operator's operation is displayed in the navigation area 302, so that the worker can pick up the cell while checking the enlarged image. You can judge whether or not. If the cell is a desired cell, the position of the cell is displayed in the pick area 301, and the operator picks the desired cell existing at the position with the display position as a mark. Work can be done.

  Thereby, for example, when performing a picking operation of a specific cell such as an iPS cell or a cardiomyocyte, the working efficiency can be improved. In addition, since it is possible to determine whether or not to pick a cell while confirming an enlarged image of the cell according to the operation of the operator, it is possible to improve the accuracy of the picking operation.

  Next, the setting process will be described with reference to the flowchart of FIG. Note that the process shown in the flowchart of FIG. 10 is executed at an arbitrary timing separately from the above-described cell picking work support process.

  In step S311, the operation reception unit 263 determines whether or not the cross button 316 has been tapped or long tapped by the operator. If it is determined in step S311 that the cross button 316 has been operated, the process proceeds to step S312.

  In step S312, the setting unit 266 performs offset adjustment according to the operator's tap operation or long tap operation on the cross button 316. Thereby, when there is an offset in the attachment position of the well plate 111 placed on the pick area 301, the offset is adjusted.

  If it is determined in step S311 that the cross button 316 has not been tapped, the process in step S312 is skipped, and the process proceeds to step S313.

  In step S313, the operation reception unit 263 determines whether or not the setting button 315 has been tapped by the operator. If it is determined in step S313 that the setting button 315 has been tapped, the process proceeds to step S314.

  In step S314, the setting unit 266 sets the auto mode or the manual mode to the operation mode according to the operator's tap operation on the setting screen for setting the operation mode. Thereby, the operator can switch the operation mode at an arbitrary timing.

  If it is determined in step S313 that the setting button 315 has not been tapped, the process in step S314 is skipped, and the process proceeds to step S315. In step S315, it is determined whether or not the setting is to be ended. If it is determined that the setting is not to be ended, the process returns to step S311 and the subsequent processes are repeated. If it is determined that the setting is to be ended, the setting process is ended.

  The setting process has been described above. In the above setting process, offset adjustment and operation mode setting have been described as examples. However, the present invention is not limited to this, and other setting items necessary for performing the cell picking work support process are set. Can do. For example, when the display form of the picking support screen is changed according to the handedness of the operator, right-handed and left-handed screen display may be selected on the setting screen.

  In the above description, the cell picking work support process has been described as proceeding mainly in response to a button operation displayed as a GUI image by the worker. However, in response to other touch panel operations or voice instructions from the worker. You may make it progress.

  Specifically, as shown in FIG. 11, a voice instruction such as a right flick operation or “next” may be performed instead of a tap operation on the next button 318. Further, instead of the tap operation on the front button 319, a left flick operation or a voice instruction such as “front” may be performed. However, “right flick operation” refers to an operation of placing a finger on a desired area on the touch panel and sliding the finger in the right direction. The “left flick operation” is an operation that slides a finger on the touch panel to the left, contrary to the “right flick operation”. Further, instead of a tap operation on the pick button 317, a voice instruction such as a long tap operation or “decision” may be performed.

  Then, when changing such an operation pattern, a predetermined setting screen may be displayed so that one of the above operation patterns is selected.

Note that the above-described display form of the picking support screen is merely an example, and other display forms may be employed. For example, as shown in FIG. 12, when the operator selects the picking target, the navigation area 302, together with the enlarged image I _C1 of the cell C1, it is possible to display the reference image I _R for reference. Thus, the operator while viewing the reference image I _R, switches the display of a cell of the enlarged image, it is possible to locate reliably desired cells.

  In the above description, the image analysis result (mask) by the data analysis server 30 is displayed for the picking target cell (colony). However, the image analysis result may not be displayed. The procedure of the picking operation in this case is performed according to the following flow, for example. That is, the operator selects the manual mode as the operation mode, confirms the enlarged image displayed in the navigation area 302 in a state where the picking target is not displayed, and determines the cell (colony) determined to be the picking target. ) Is selected (recorded) and picking is performed. Also in this case, in the same manner as the above-described cell picking work support process, the picking target selection work and the picking work are performed in units of cells as a series of work, and the picking target selection work and the picking work are performed independently in the work unit. You may make it perform.

  In the above description, the example in which the culture observation information is transmitted / received by wireless communication has been described. 20 may be acquired. In addition, when exchanging culture observation information via a recording medium such as a memory card, the tablet terminal device 20 is provided with an interface corresponding to the recording medium. Furthermore, the cell culture observation apparatus 10 performs analysis processing executed by the data analysis server 30, so that the culture observation information is directly transferred from the cell culture observation apparatus 10 to the tablet terminal device 20 without using the data analysis server 30. It may be sent.

  In the above description, the well plate 111 is described as an example of the culture container. However, the present invention is not limited to this, and various culture containers can be used. In addition, it has been described that an operation using the plate selection button 311 or the like is performed to identify a culture vessel placed on the pick area 301. For example, this corresponds to a vessel ID for uniquely identifying a culture vessel. An IC chip with a built-in RF (Radio Frequency) tag that records the barcode or the container ID may be attached to the culture container, and the tablet terminal device 20 may read the container ID to identify the culture container.

  Furthermore, in the above description, the observation unit 103 has been described as performing both the phase difference observation and the fluorescence observation when acquiring the culture observation information, but it is not necessary to perform both observations. If information on cells is not required and only information on the presence / absence of colonies is to be obtained, only phase difference observation may be performed without performing fluorescence observation.

  Moreover, when the tip of the pipette used for the picking work is made of a material that can be detected by, for example, a projected capacitive touch panel, when picking is performed by the operator, Since it can be detected, for example, it is possible to perform processing such as recording a picking history even if a predetermined operation by the operator is not performed.

  The series of processes described above can be executed by hardware or can be executed by software. When a series of processing is executed by software, a control program 251 (FIG. 3) constituting the software is installed in the computer. Here, the computer includes, for example, a general-purpose personal computer capable of executing various functions by installing a computer incorporated in dedicated hardware and various programs.

  FIG. 13 is a block diagram illustrating an example of a hardware configuration of a computer that executes the series of processes described above according to a program.

  In the computer 400, a CPU (Central Processing Unit) 401, a ROM (Read Only Memory) 402, and a RAM (Random Access Memory) 403 are connected to each other by a bus 404.

  An input / output interface 405 is further connected to the bus 404. An input unit 406, an output unit 407, a recording unit 408, a communication unit 409, and a drive 410 are connected to the input / output interface 405.

  The input unit 406 includes a keyboard, a mouse, a microphone, and the like. The output unit 407 includes a display, a speaker, and the like. The recording unit 408 includes a hard disk, a nonvolatile memory, and the like. The communication unit 409 includes a network interface. The drive 410 drives a removable medium 411 such as a magnetic disk, an optical disk, a magneto-optical disk, or a semiconductor memory.

  In the computer 400 configured as described above, for example, the CPU 401 loads the program stored in the recording unit 408 to the RAM 403 via the input / output interface 405 and the bus 404 and executes the program, as described above. A series of processing is performed.

  The program executed by the computer 400 (CPU 401) can be provided by being recorded on a removable medium 411 as a package medium, for example. The program can be provided via a wired or wireless transmission medium such as a local area network, the Internet, or digital satellite broadcasting.

  In the computer 400, the program can be installed in the recording unit 408 via the input / output interface 405 by attaching the removable medium 411 to the drive 410. Further, the program can be received by the communication unit 409 via a wired or wireless transmission medium and installed in the recording unit 408. In addition, the program can be installed in the ROM 402 or the recording unit 408 in advance.

  Note that the program executed by the computer 400 may be a program that is processed in time series in the order described in this specification, or a necessary timing such as in parallel or when a call is made. It may be a program in which processing is performed.

  The embodiments of the present invention are not limited to the above-described embodiments, and various modifications can be made without departing from the scope of the present invention.

  10 cell culture observation device, 20 tablet terminal device, 30 data analysis server, 40 clean bench, 111 well plate, 201 control unit, 202 communication unit, 203 display unit, 204 recording unit, 251 control program, 261 culture observation information acquisition unit , 262 Recording control unit, 263 operation accepting unit, 264 cell specifying unit, 265 display control unit, 266 setting unit, 301 pick area, 302 navigation area, 313 cell display region, 317 pick button, 318 next button, 319 previous button, 400 computers, 401 CPU

Claims (10)

An acquisition means for acquiring observation information for each cell cultured in a predetermined culture environment;
Based on the obtained observation information, cell identifying means for identifying candidate cells that are candidates for picking from among the cells accommodated in the culture container that accommodates the cells to be picked;
Based on the acquired observation information, the display means provided on the placement surface side of the culture container displays first position information indicating the position of the candidate cell among the cells stored in the culture container. And display control means for displaying a second display area for displaying detailed information on the candidate cell,
The first display area is an area corresponding to the placement area on the bottom surface of the culture vessel among the display areas of the display means,
The second display area is an area different from the placement area ,
The display control means is an operation received by an operation receiving means, and according to an operation of an operator who selects a cell to be picked from the candidate cells displayed in the second display area, A cell picking support apparatus for displaying information indicating a position of a selected cell to be picked on the first display area . The cell picking support apparatus according to claim 1, further comprising: a recording control unit that records a history of the picking work of the candidate cell when the picking work is performed on the candidate cell. When the picking operation is performed on the candidate cell, or when the candidate cell is not a target for picking, the cell specifying unit specifies a candidate cell that is a candidate for the next picking. Item 2. The cell picking support apparatus according to Item 2. Detailed information on the candidate cell is an enlarged image of the candidate cell,
The display control means includes
In the second display area, the enlarged images of the candidate cells are sequentially displayed, and the operator performs a picking target selection operation for selecting a cell to be picked from the candidate cells.
When the picking target selection work is completed, information indicating the position of the cell to be picked is sequentially displayed in the first display area to cause the operator to perform the picking work. The cell picking support apparatus according to claim 2. The cell picking support apparatus according to claim 3 or 4, wherein the cell specifying unit specifies the candidate cell according to a recorded history of picking work. The display control means displays, in the second display area, an image expressing the candidate cell so as to be distinguishable from other cells, or an image according to an observation method of the candidate cell in the culture environment. The cell picking support apparatus according to claim 1, wherein: The cell picking support apparatus according to claim 4, wherein the display control means displays a reference image for reference together with the enlarged image of the candidate cell in the second display area. Display means provided on the placement surface side of a culture container that contains cells cultured in a predetermined culture environment, which is a target of picking;
Obtaining means for obtaining observation information for each cell;
Based on the acquired observation information, cell identifying means for identifying candidate cells that are candidates for picking from the cells accommodated in the culture container;
Based on the obtained observation information, a first display area for displaying position information indicating the position of the candidate cell among the cells accommodated in the culture container on the display means, and details regarding the candidate cell Display control means for displaying a second display area for displaying information, and
The first display area is an area corresponding to the placement area on the bottom surface of the culture vessel among the display areas of the display means,
The second display area is an area different from the placement area ,
The display control means is an operation received by an operation receiving means, and according to an operation of an operator who selects a cell to be picked from the candidate cells displayed in the second display area, A display device that displays information indicating a position of a selected cell to be picked on the first display area . An acquisition means for acquiring observation information for each cell cultured in a predetermined culture environment;
Based on the obtained observation information, the display means provided on the placement surface side of the culture container that contains the cells to be picked indicates the position of a specific cell among the cells contained in the culture container. A display control means for displaying a first display area for displaying position information and a second display area for displaying detailed information on the specific cell;
The first display area is an area corresponding to the placement area on the bottom surface of the culture vessel among the display areas of the display means,
The second display area is an area different from the placement area,
The display control means includes
In the second display area, cells stored in the culture container are displayed in a predetermined display form according to an operation of an operator who performs a picking target selection operation,
An operation received by the operation receiving means , in response to an operation of an operator who selects a cell to be picked from cells displayed in the second display area, in the first display area, cells picking assisting apparatus characterized by displaying the information indicating the subject to the location of cells of the selected picking. Display means provided on the placement surface side of a culture container that contains cells cultured in a predetermined culture environment, which is a target of picking;
Obtaining means for obtaining observation information for each cell;
Based on the acquired observation information, a first display region for displaying position information indicating a position of a specific cell among the cells stored in the culture container on the display means, and the specific cell Display control means for displaying a second display area for displaying detailed information,
The first display area is an area corresponding to the placement area on the bottom surface of the culture vessel among the display areas of the display means,
The second display area is an area different from the placement area,
The display control means includes
In the second display area, cells stored in the culture container are displayed in a predetermined display form according to an operation of an operator who performs a picking target selection operation,
An operation received by the operation receiving means , in response to an operation of an operator who selects a cell to be picked from cells displayed in the second display area, in the first display area, A display device that displays information indicating a position of a selected cell to be picked .

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