WO2022102748A1 - 顕微鏡検査支援装置、顕微鏡検査支援方法、自動染色装置、自動染色物質推定システム、プログラム、及び記録媒体 - Google Patents

顕微鏡検査支援装置、顕微鏡検査支援方法、自動染色装置、自動染色物質推定システム、プログラム、及び記録媒体 Download PDF

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WO2022102748A1
WO2022102748A1 PCT/JP2021/041744 JP2021041744W WO2022102748A1 WO 2022102748 A1 WO2022102748 A1 WO 2022102748A1 JP 2021041744 W JP2021041744 W JP 2021041744W WO 2022102748 A1 WO2022102748 A1 WO 2022102748A1
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Prior art keywords
information
substance
image
unit
microscopic examination
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PCT/JP2021/041744
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English (en)
French (fr)
Japanese (ja)
Inventor
悠 平岡
達也 山田
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株式会社GramEye
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Priority to JP2022562205A priority Critical patent/JP7723425B2/ja
Publication of WO2022102748A1 publication Critical patent/WO2022102748A1/ja

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material

Definitions

  • the present invention relates to a microscopic inspection support device, a microscopic inspection support method, an automatic staining device, an automatic staining substance estimation system, a program, and a recording medium.
  • Patent Document 1 discloses a technique for classifying smear microscopic images and displaying similar images.
  • tests such as smear microscopic examination to detect stained substances (for example, pathogens, cells, etc.) involve a plurality of steps, require the procedure of a clinical laboratory technician, and have a problem that it takes time to obtain results. be. Therefore, in the actual medical field, there is also a problem that the test result is not transmitted to the doctor before prescribing the antibacterial drug and is rarely reflected in the prescription.
  • stained substances for example, pathogens, cells, etc.
  • an object of the present invention is to provide a microscopic inspection support device, a microscopic inspection support method, an automatic staining device, an automatic staining substance estimation system, a program, and a recording medium capable of estimating a staining substance.
  • the microscopic examination support device of the present invention includes image information acquisition unit, recognition estimation unit, count unit, and information output unit.
  • the image information acquisition unit acquires a microscopic image of a stained specimen of a specimen collected from an organism to be inspected, and obtains a microscope image.
  • the recognition estimation unit recognizes the stained substance image in the microscope image, estimates the type of the stained substance from the stained substance image, and generates the stained substance estimated type information.
  • the counting unit counts the image of the dyed substance and generates information on the estimated number of stained substances.
  • the information output unit outputs the dyeing substance estimated type information and the dyeing substance estimated number information. It is a device.
  • the microscopic examination support method of the present invention Including image information acquisition process, recognition estimation process, counting process, and information output process
  • image information acquisition step a microscope image of a stained specimen of a specimen collected from an organism to be inspected is acquired.
  • the recognition estimation step recognizes the stained substance image in the microscope image, estimates the type of the stained substance from the stained substance image, and generates the stained substance estimated type information.
  • the counting step the stained substance images are counted to generate the estimated number of stained substances, and the information is generated.
  • the information output step outputs the dyeing substance estimated type information and the dyeing substance estimated number information. , The way.
  • the automatic dyeing apparatus of the present invention Includes holding section, moving section, staining reagent supply section, and control section.
  • the holding portion can hold the slide glass and can hold the slide glass.
  • the slide glass is smeared with a sample collected from the organism to be inspected.
  • the moving portion can be connected to the holding portion to move the holding portion.
  • the staining reagent supply unit includes a plurality of reagent dropping units.
  • the plurality of reagent dropping portions are arranged side by side according to the dyeing step. Each of the reagent dropping parts of the plurality of reagent dropping parts can drop one kind of reagent according to the dyeing step.
  • the holding portion is arranged below the reagent dropping portion. By controlling the moving unit, the control unit moves the holding unit so as to be located below the reagent dropping unit capable of dropping the reagent that needs to be supplied to the slide glass according to the dyeing step. Let, It is a device.
  • the dyeing substance can be estimated. Therefore, for example, it is possible to support an inspection such as a smear inspection (also referred to as a smear inspection), and the result of the inspection can be obtained more quickly.
  • a smear inspection also referred to as a smear inspection
  • FIG. 1 is a block diagram showing an example of the configuration of the microscopic examination support device of the first embodiment.
  • FIG. 2 is a block diagram showing an example of the hardware configuration of the microscopic examination support device of the first embodiment.
  • FIG. 3 is a flowchart showing an example of processing in the microscopic examination support method of the first embodiment.
  • FIG. 4 is a schematic diagram showing an example of control by the microscope control unit.
  • FIG. 5 is a schematic diagram showing another example of control by the microscope control unit.
  • FIG. 6 is a block diagram showing an example of the configuration of the automatic dyeing apparatus of the second embodiment.
  • FIG. 7 is a schematic diagram showing an example of processing of the control unit during the dyeing process.
  • FIG. 1 is a block diagram showing an example of the configuration of the microscopic examination support device of the first embodiment.
  • FIG. 2 is a block diagram showing an example of the hardware configuration of the microscopic examination support device of the first embodiment.
  • FIG. 3 is a flowchart showing an example of
  • FIG. 8 is a block diagram showing an example of the configuration of the automatic staining substance estimation system of the third embodiment.
  • FIG. 9 is a schematic view showing an example in which the slide glass moves from the lower part of the reagent dropping portion of the automatic dyeing device to the lower part of the objective lens of the microscope device.
  • FIG. 10 is a schematic view showing an example in which the slide glass moves from the sample fixing device to the lower part of the objective lens of the microscope device through the lower part of the reagent dropping portion of the automatic staining device.
  • FIG. 11 is a block diagram showing an example of the configuration of the microscopic examination support device including the related information acquisition unit in the first embodiment.
  • FIG. 12 is a schematic diagram showing an example of information displayed on the display.
  • FIG. 13 is a block diagram showing an example of the configuration of an automatic dyeing substance estimation system including a shading recognition device in the third embodiment.
  • the image acquisition unit acquires a plurality of microscopic images of the stained specimen, and obtains a plurality of microscopic images.
  • the recognition estimation unit recognizes the stained substance image in the plurality of microscope images, estimates the type of the stained substance from the stained substance image, and generates the stained substance estimated type information. May be good.
  • the image acquisition unit acquires the microscope image obtained by capturing the stained specimen at a plurality of magnifications.
  • the recognition estimation unit recognizes the stain substance image in the microscope image of each magnification of the microscope image having a plurality of magnifications, estimates the type of the stain substance from the stain substance image, and obtains the stain substance estimation type information. It may be in the form of generating.
  • the recognition estimation unit calculates the probability of the estimated type of the dyeing substance and generates the estimated type probability information.
  • the information output unit may be in an embodiment in which the estimated type probability information is associated with the dyeing substance estimated type information and output.
  • the recognition estimation unit generates dyeing substance list information listing a plurality of estimated dyeing substances according to the magnitude of the probability.
  • the information output unit may be in the form of outputting the dyeing substance list information.
  • the staining substance may be at least one of a pathogen, a non-pathogen, and cells derived from the organism to be inspected.
  • the recognition estimation unit When the staining substance contains cells derived from the organism to be inspected, the recognition estimation unit generates Geckler classification information based on the staining substance estimation type information and the staining substance estimated number information.
  • the information output unit may be in the form of outputting the Geckler classification information.
  • the microscopic examination support device of the present invention is, for example, In addition, including the related information acquisition department,
  • the related information acquisition unit acquires related information regarding the stained specimen, and obtains the related information.
  • the recognition estimation unit may be in an embodiment of generating the staining substance estimation type information with reference to the related information.
  • the related information may be at least one of information about the sample target organism, information about the sample, and information about the environment.
  • the microscopic examination support device of the present invention is, for example, In addition, it includes a recommended information generator.
  • the recommended information unit generates recommended information based on the stained substance estimated type information.
  • the information output unit may be in the form of outputting the recommended information.
  • the recommended information may be in the form of at least one of the recommended test information and the recommended treatment information.
  • the microscopic examination support device of the present invention is, for example, In addition, including the medical record information acquisition department,
  • the medical record information acquisition unit acquires the medical record information of the organism to be inspected, and obtains the medical record information.
  • the recommended information generation unit may generate the recommended treatment information based on the medical record information.
  • the microscopic examination support device of the present invention is, for example, Including medical record information acquisition department
  • the medical record information acquisition unit acquires the medical record information of the organism to be inspected, and obtains the medical record information.
  • the recognition estimation unit calculates the probability of developing a disease using the medical record information and generates estimated onset probability information.
  • the information output unit may be in a mode of outputting the estimated onset probability information in association with the dyeing substance estimated type information.
  • the microscopic examination support device of the present invention is, for example, In addition, including the infected organ estimation department, the infected organ estimation unit estimates the organ from which the sample is collected as an infected organ and generates estimated infected organ information.
  • the information output unit may be in the form of outputting the estimated infected organ information.
  • the microscopic examination support device of the present invention is, for example, In addition, it includes an image switching judgment unit.
  • the image switching determination unit determines when the microscope image is acquired and when the microscope image is not acquired in the image acquisition unit.
  • the recognition estimation unit and the counting unit switch from the acquisition of the microscope image to the non-acquisition of the microscope image, and then generate the stained substance estimated type information and the stained substance estimated number information, respectively. It may be an embodiment.
  • the microscopic examination support device of the present invention is, for example, Further, it includes at least one of a staining device control unit, a microscope control unit, and a sample fixing device control unit.
  • the staining device control unit controls a staining device that automatically stains the sample and prepares the stained sample.
  • the microscope control unit controls a microscope that captures a microscope image of the stained specimen.
  • the sample fixing device control unit may be in an embodiment of controlling a sample fixing device that performs a fixing process on a sample smeared on a slide glass.
  • the microscope control unit determines whether or not the image is appropriate for each microscope image, and if it is determined that the image is not appropriate, the holding unit is moved in the longitudinal direction of the slide glass, and if it is determined that the image is appropriate, the holding unit is moved.
  • the movement of the holding portion may be controlled so as to move the holding portion in the lateral direction of the slide glass.
  • the microscope control unit acquires the shading data of the entire slide glass, analyzes the shading data to identify a position having a density within a preset range, and starts the visual field search from the position. It may be an aspect of controlling the microscope.
  • the dyeing device control unit can specify the decolorization time in the decolorization step, which is one step of the dyeing step, for each sample, and controls the dyeing device so that the decolorization step is performed at the designated decolorization time. It may be an embodiment.
  • the microscopic examination support device of the present invention is, for example, In addition, it includes a priority setting section.
  • the priority setting unit can set an arbitrary priority for each sample.
  • At least one of the staining device control unit, the microscope control unit, and the sample fixing device control unit is such that the staining device, the microscope, and the sample fixing device are processed in descending order of priority. It may be an aspect of controlling.
  • the image acquisition step a plurality of microscopic images of the stained specimen are acquired, and the image acquisition step is performed.
  • the recognition estimation step is an embodiment in which the stain substance image is recognized in the plurality of microscope images, and the type of the stain substance is estimated from the stain substance image to generate the stain substance estimation type information. May be good.
  • the image acquisition step the microscope image obtained by capturing the stained specimen at a plurality of magnifications is acquired.
  • the recognition estimation step the stain substance image is recognized in the microscope image of each magnification of the microscope image having a plurality of magnifications, and the type of the stain substance is estimated from the stain substance image to obtain the stain substance estimation type information. It may be in the form of generating.
  • the recognition estimation step calculates the estimated probability of the type of dyeing substance and generates the estimated type probability information.
  • the information output step may be in an embodiment in which the estimated type probability information is associated with the dyeing substance estimated type information and output.
  • the staining substance may be at least one of a pathogen, a non-pathogen, and cells derived from the organism to be inspected.
  • the recognition estimation step When the staining substance contains cells derived from the organism to be inspected, the recognition estimation step generates Geckler classification information based on the stained substance estimated type information and the stained substance estimated number information.
  • the information output step may be in the form of outputting the Geckler classification information.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes a related information acquisition process.
  • the related information acquisition step acquires related information regarding the stained specimen, and obtains the related information.
  • the recognition estimation step may be in an embodiment of generating the staining substance estimation type information with reference to the related information.
  • the related information may be at least one of information about the sample target organism, information about the sample, and information about the environment.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes a recommended information generation process.
  • the recommended information generation step generates recommended information based on the stained substance estimated type information.
  • the information output step may be in the form of outputting the recommended information.
  • the recommended information may be in the form of at least one of the recommended test information and the recommended treatment information.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes a medical record information acquisition process.
  • the medical record information acquisition step the medical record information of the organism to be inspected is acquired, and the medical record information is acquired.
  • the medical record information includes the cell estimation type information and the cell estimation number information.
  • the recommended information generation step may be in the form of generating the recommended information based on the medical record information.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes a medical record information acquisition process.
  • the medical record information acquisition step the medical record information of the organism to be inspected is acquired, and the medical record information is acquired.
  • the medical record information includes the cell estimation type information and the cell estimation number information.
  • the recognition estimation step uses the medical record information to calculate the probability of developing a disease and generate estimated onset probability information.
  • the information output step may be in an embodiment in which the estimated onset probability information is associated with the dyeing substance estimated type information and output.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes an infected organ estimation process.
  • the infected organ estimation step using the stained substance image recognized by the recognition estimation step, the organ from which the sample is collected is estimated as an infected organ to generate estimated infected organ information.
  • the information output step may be in the form of outputting the estimated infected organ information.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes an image switching judgment process.
  • image switching determination step in the image acquisition step, it is determined when the microscope image is acquired and when the microscope image is not acquired.
  • the recognition estimation step and the counting step are switched from the acquisition of the microscope image to the non-acquisition of the microscope image, and then the generation of the staining substance estimation type information and the staining substance estimation number information is performed, respectively. May be.
  • the microscopic examination support method of the present invention is, for example, Further, it comprises at least one of a staining device control step, a microscope control step, and a sample fixation device control step.
  • the staining device control step controls a staining device that automatically stains the sample to prepare a stained sample.
  • the microscope control step controls a microscope that captures a microscopic image of the stained specimen.
  • the sample fixing device control step may be an embodiment in which the sample fixing device that performs the fixing process on the sample smeared on the slide glass is controlled.
  • the microscope control step determines whether or not the image is appropriate for each microscope image, and if it is determined that the image is not appropriate, the holding portion is moved in the longitudinal direction of the slide glass, and if it is determined that the image is appropriate.
  • the movement of the holding portion may be controlled so as to move the holding portion in the lateral direction of the slide glass.
  • the shading data of the entire slide glass is acquired, the shading data is analyzed to identify a position having a density within a preset range, and the visual field search is started from the position. It may be an aspect of controlling the microscope.
  • the decolorization time in the decolorization step which is one step of the dyeing step, can be specified for each sample, and the dyeing device is controlled so that the decolorization step is performed at the designated decolorization time. It may be an embodiment.
  • the microscopic examination support method of the present invention is, for example, In addition, it includes a priority setting process.
  • the priority setting step any priority can be set for each sample.
  • At least one of the staining device control step, the microscope control step, and the sample fixing device control step is such that the staining device, the microscope, and the sample fixing device are processed in descending order of priority. It may be an aspect of controlling.
  • the program of the present invention is a program for causing a computer to execute each step of the method of the present invention as a procedure.
  • the recording medium of the present invention is a computer-readable recording medium on which the program of the present invention is recorded.
  • the control unit controls the moving unit after the decolorizing liquid is dropped onto the slide glass by the reagent dropping unit, so that the slide is centered on at least one of the longitudinal direction and the lateral direction of the slide glass.
  • the holding portion may be driven so that the glass is tilted.
  • the control unit has at least one of the longitudinal direction and the lateral direction of the slide glass as an axis, and the lateral direction and the longitudinal direction other than the axis.
  • the holding portion may be driven in at least one of clockwise and counterclockwise so that the inclination of each end portion of the slide glass in the direction becomes a degree predetermined from the reference.
  • the automatic staining substance estimation system of the present invention includes an automatic dyeing device, a microscopic device, and a microscopic inspection support device, and the microscopic inspection support device is the microscopic inspection support device of the present invention.
  • the automatic dyeing apparatus may be an embodiment of the automatic dyeing apparatus of the present invention.
  • the microscopic examination support device includes a display unit and includes a display unit.
  • the display unit may be in an embodiment in which the information output by the information output unit can be displayed.
  • the display unit may be capable of displaying microscope images captured at different focal points for the same field of view.
  • the automated stain estimation system of the present invention is, for example, In addition, including user terminals,
  • the user terminal can display the information output by the information output unit.
  • Arbitrary information may be added to the information output by the information output unit in a situation where it can be shared with other user terminals.
  • the automated stain estimation system of the present invention is, for example, Further, the embodiment may include a sample fixing device.
  • the automated stain estimation system of the present invention is, for example, In the microscopic examination support device
  • the information output unit may also output report information according to the information to be output.
  • the "dyeing substance” is a substance dyed by a dyeing treatment.
  • Specific examples thereof include pathogens, non-pathogens (for example, indigenous bacteria, etc.), cells derived from the organism to be inspected, substances derived from the organism to be inspected (for example, fibrin, crystals, etc.), and the like. It is not limited to these.
  • the pathogen is a substance exhibiting pathogenicity, and includes, for example, organisms such as protozoa, bacteria, viruses, and fungi.
  • the non-pathogenic substance is a substance that does not show pathogenicity, and for example, an example of the pathogen can be incorporated.
  • the dyeing process is not particularly limited. Examples of the dyeing treatment include known dyeing treatments such as Gram stain, Thirneilzen stain, ink stain, Giemsa stain, and Grocott stain. By the staining treatment, a stained specimen described later is prepared.
  • FIG. 1 is a block diagram showing an example of the configuration of the microscopic examination support device 100 of the present embodiment.
  • the present apparatus 100 includes an image information acquisition unit 101, a recognition estimation unit 102, a counting unit 103, and an information output unit 104. Further, the apparatus 100 has an arbitrary configuration, further, a related information acquisition unit 105, a recommended information generation unit 106, a chart information acquisition unit 107, an infected organ estimation unit 108, an image switching determination unit 109, a staining device control unit 110, and the like.
  • the microscope control unit 111, the priority setting unit 112, the sample fixing device control unit 113, the display unit 114, and the like may be included.
  • Reference numeral 109 can be said to be, for example, the inspection support processing unit 100A.
  • the respective parts are connected to each other by, for example, an internal bus.
  • the device 100 may be, for example, one device including the above-mentioned parts, or may be a device in which the above-mentioned parts can be connected via a communication network. Further, the present device 100 can be connected to an external device described later via the communication network.
  • the communication network is not particularly limited, and a known network can be used, and may be wired or wireless, for example.
  • the communication line network includes, for example, an internet line, WWW (World Wide Web), a telephone line, a LAN (Local Area Network), a SAN (Storage Area Network), a DTN (Delay Orient Network), and an LPWA (L). L5G (local 5G), etc. can be mentioned.
  • wireless communication examples include Wi-Fi (registered trademark), Bluetooth (registered trademark), local 5G, LPWA and the like.
  • the wireless communication may be a form in which each device directly communicates (Ad Hoc communication), an infrastructure (infrastructure communication), an indirect communication via an access point, or the like.
  • the apparatus 100 may be incorporated in the server as a system, for example. Further, the apparatus 100 may be, for example, a personal computer (PC, for example, a desktop type, a notebook type), a smartphone, a tablet terminal, a wearable terminal, or the like in which the program of the present invention is installed. Further, all or a part of each part of the apparatus 100 may be realized on the cloud.
  • the present device 100 is in the form of cloud computing, edge computing, or the like, for example, such that at least one of the above parts is on a server (cloud) and the other parts are on a terminal. You may.
  • FIG. 2 illustrates a block diagram of the hardware configuration of the present device 100.
  • the apparatus 100 may include, for example, a central processing unit (CPU, GPU, etc.) 1, a memory 2, a bus 3, a storage device 4, an input device 5, an output device 6, a communication device 7, and the like. It should be noted that these are examples, and the hardware configuration of the present device 100 is not limited to this as long as the processing of each part can be executed. Further, the number of the central processing unit 1 and the like included in the present apparatus 100 is not limited to the example of FIG. 2, and for example, a plurality of central processing units 1 may be included in the present apparatus 100. Each part of the hardware configuration of the present apparatus 100 is connected to each other via the bus 3 by each interface (I / F).
  • I / F interface
  • the central processing unit 1 is responsible for overall control of the device 100.
  • the program of the present invention and other programs are executed by the central processing unit 1, and various information is read and written. Then, the central processing unit 1 can execute the processing of each part of the apparatus 100.
  • Bus 3 can also be connected to, for example, an external device.
  • the external device include an external storage device (external database, etc.), an external input device, an external output device, and the like.
  • the device 100 can be connected to an external network (the communication network) by, for example, a communication device 7 connected to the bus 3, and can also be connected to another device via the external network.
  • the memory 2 may be, for example, a main memory (main storage device).
  • main memory main storage device
  • the memory 2 reads various operation programs such as the program of the present invention stored in the storage device 4 described later, and the central processing unit 1 reads the various operation programs from the memory 2. Receive the data and run the program.
  • the main memory is, for example, a RAM (random access memory).
  • the memory 2 may be, for example, a ROM (read-only memory).
  • the storage device 4 is also referred to as a so-called auxiliary storage device with respect to the main memory (main storage device), for example.
  • the storage device 4 stores an operation program including the program of the present invention.
  • the storage device 4 may be, for example, a combination of a recording medium and a drive for reading and writing to the recording medium.
  • the recording medium is not particularly limited, and may be an internal type or an external type, and examples thereof include HD (hard disk), CD-ROM, CD-R, CD-RW, MO, DVD, flash memory, and memory card. Be done.
  • the storage device 104 may be, for example, a hard disk drive (HDD) in which a recording medium and a drive are integrated, and a solid state drive (SSD).
  • HDD hard disk drive
  • SSD solid state drive
  • the memory 2 and the storage device 4 perform log information, information acquired from an external database (not shown) or an external device, information generated by each process of the device 100, and each process of the device 100. It is also possible to store various information such as information used at the time of execution. It should be noted that at least a part of the information may be stored in an external server other than the memory 2 and the storage device 4, or may be distributed and stored in a plurality of terminals by using blockchain technology or the like. ..
  • the device 100 may further include, for example, an input device 5 and an output device 6.
  • the input device 5 is, for example, a device for inputting characters, numbers, the position of an object displayed on the screen, an image, a sound, and the like, and specifically, a digitizer (touch panel, etc.), a keyboard, a mouse, a scanner, and an image pickup. Devices, microphones, sensors and the like can be mentioned.
  • Examples of the output device 6 include a display device (LED display, liquid crystal display), a printer, a speaker, and the like.
  • the display unit 114 may display various information using, for example, the display device of the output device 6.
  • the present device 100 can be applied to, for example, an inspection using a microscope image taken by a microscope.
  • the examination is not particularly limited, and is, for example, a smear inspection (inspection relating to staining such as Gram stain, Thirneilzen staining, fungal staining, Giemsa staining, etc.), pathological specimen inspection, and the like.
  • the microscopic examination support method of the present embodiment is carried out as follows, for example, by using the microscopic examination support device 100 of FIG.
  • the microscopic examination support method of the present embodiment is not limited to the use of the microscopic examination support device 100 of FIG.
  • the image information acquisition step can be executed by, for example, the image information acquisition unit 101
  • the recognition estimation step can be executed by, for example, the recognition estimation unit 102
  • the counting process can be executed by, for example, the counting unit 103.
  • the information output step can be executed by, for example, the information output unit 104
  • the related information acquisition step can be executed by, for example, the related information acquisition unit 105
  • the recommended information generation step can be executed by, for example, the recommended information generation unit 106.
  • the chart information acquisition step can be executed, for example, by the chart information acquisition unit 107
  • the infected organ estimation step can be executed by, for example, the infected organ estimation unit 108
  • the image switching determination step can be executed, for example, by image switching.
  • the staining device control step can be executed by, for example, the staining device control unit 110
  • the microscope control step can be executed by, for example, the microscope control unit 111
  • the priority setting step can be executed, for example, by the microscope control unit 111.
  • the sample fixing device control step can be executed by, for example, the sample fixing device control unit 113.
  • the image information acquisition unit 101 acquires a microscopic image of a stained specimen of a specimen collected from an organism to be inspected (S101).
  • the organism to be inspected is not particularly limited, and may be, for example, a human or a non-human organism.
  • the microscope image refers to an image captured by a microscope.
  • the recognition estimation unit 102 recognizes the stained substance image in the microscope image, estimates the type of the stained substance from the stained substance image, and generates the stained substance estimated type information (S102A).
  • the dyed substance image means an image to which the dyed substance is transferred. That is, it can be said that the recognition estimation unit 102 recognizes the staining substance in the microscope image.
  • the recognition estimation unit 102 may be able to estimate the types of the plurality of dyeing substances, for example.
  • the dyeing substance estimation type information may indicate, for example, a plurality of types of the dyeing substance.
  • the recognition estimation unit 102 may estimate morphological characteristics such as gram-positive streptococcus, gram-negative streptococcus, and yeast-like fungus, or organisms such as Enterobacteriaceae , Pseudomonas , and Streptococcus . It may be estimated by the family name and genus name in the classification, or by the species name in the biological classification such as Streptococcus agalactiae , Escherichia coli , Pseudomonas aeruginosa and the like.
  • the counting unit 103 counts the stained substance images and generates information on the estimated number of stained substances (S103). More specifically, the number of the dyed substances recognized by the recognition estimation unit 102 in the stained substance image is counted.
  • the information on the estimated number of dyed substances is information indicating the number of the dyed substances. The counting may be performed for each type of the dyeing substance estimated by the recognition estimation unit 102.
  • the information output unit 104 outputs the stain substance estimated type information and the stain substance estimated number information (S104), and ends (END).
  • the method of output by the information output unit 104 is not particularly limited, and for example, the output device 6 may be used for output, or the communication device 7 may be used for output to an external device.
  • the type of the dyeing substance can be automatically estimated, and the count can also be automated. Therefore, according to the present embodiment, it is possible to support an inspection such as a smear microscopic examination. Specifically, the automation can reduce the time required for inspection and the human cost. In addition, the burden on the inspection engineer can be reduced. Further, according to the present embodiment, it is possible to present the information to the medical staff by outputting the information on the estimated type of the dyeing substance and the information on the estimated number of the dyeing substances.
  • the image information acquisition unit 101 may acquire a plurality of microscope images of the stained specimen in the step S101, for example.
  • the recognition estimation unit 102 recognizes the stain image in the plurality of microscope images, estimates the type of the stain substance from the stain image, and estimates the stain substance type. Information may be generated.
  • the recognition estimation unit 102 may generate the stain substance estimation type information for each of the microscope images, or the stain substance estimation type information (the said for a plurality of microscope images) for one stain sample. Staining substance estimation type information) summarizing the estimation results may be generated.
  • the plurality of microscope images may be images captured in different fields of view, or may be images captured at different focal points for one field of view. By acquiring a plurality of microscope images in this way, it is possible to improve the accuracy of the processing of the recognition estimation unit 102 and, by extension, the inspection.
  • the image information acquisition unit 101 may acquire, for example, the microscope image obtained by capturing the stained specimen at a plurality of magnifications in the step S101.
  • the recognition estimation unit 102 recognizes the stain substance image in the microscope image of each magnification of the microscope image having a plurality of magnifications, and the type of the stain substance from the stain substance image. May generate the estimated type information of the staining substance.
  • the recognition estimation unit 102 may generate the stain substance estimation type information for each microscope image of each magnification, or one stain substance estimation type information (of each magnification) for one stain sample. (Staining substance estimation type information) that summarizes the estimation results for the microscope image may be generated.
  • the accuracy of the processing of the recognition estimation unit 102 and, by extension, the inspection can be improved by taking the microscope image taken at a plurality of magnifications.
  • the recognition estimation unit 102 may calculate the estimated probability of the type of the dyeing substance and generate the estimated type probability information.
  • the probability of the type of the dyeing substance means "the certainty that the dyeing substance is the type".
  • the recognition estimation unit 102 may calculate the estimated probability of the type of dyeing substance by machine learning, for example.
  • the estimated type probability information may be, for example, "Pseudomonas 90%” or the like, and may be associated with the type of the dyeing substance to express the probability numerically (percentage or the like), or may be a character (for example,).
  • the information output unit 104 may output the estimated type probability information in association with the stained substance estimated type information in the step S104, for example.
  • the estimated type probability information linked to the estimated type information of the stained substance a format in which the name of the stained substance and the probability are combined, such as "Streptococcus pneumoniae 95%” and "Mycoplasma 80%".
  • this is an example and is not limited to this. In this way, by generating the estimated type probability information, it is possible to further support the inspection, and a person (for example, a medical worker) who has acquired the estimated type probability information can easily determine the type of the dyeing substance and its probability. It is possible to grasp.
  • the test information includes, for example, information on various tests such as CRP (C-reactive protein) indicating the degree of inflammation, white blood cell count, body temperature, respiratory function, urine volume, and ⁇ -D glucan.
  • the text information includes, for example, information on the presence / absence of cough, the presence / absence of dyspnea, the presence / absence of lower back pain, X-ray findings, severity, infected organs, drug processing function, and the like.
  • the inspection information and the text information may be acquired by, for example, the medical record information acquisition unit 107 described later.
  • the recognition estimation unit 102 calculates the weight of the parameter for each type of the dyeing substance using the inspection information and each information included in the text information as parameters, and uses the weight of the parameter to calculate the weight according to a specific calculation formula. Calculate the probability.
  • the specific calculation formula is not particularly limited and can be set arbitrarily.
  • the recognition estimation unit 102 calculates the probability by using each information generated by the present apparatus 100 such as the stain substance estimation type information and the stain substance estimated number information, in addition to the inspection information and the text information, for example. You may.
  • the recognition estimation unit 102 may generate a dyeing substance list information listing a plurality of estimated dyeing substances according to the magnitude of the probability of the estimated type of the dyeing substance. ..
  • the stain substance list information may also serve as, for example, the estimated type probability information associated with the stain substance estimated type information.
  • the dyeing substance list information may be those in which the types of the dyeing substances are arranged in descending order of the probability, or may be those in which the types of the dyeing substances are arranged in the order of the smaller probability.
  • the information output unit 104 may output the dyeing substance list information in the step S104, for example.
  • the dyeing substance list information by generating the dyeing substance list information, it is possible to further support the inspection, and a person (for example, a medical worker) who has acquired the dyeing substance list information can easily determine the type of the dyeing substance and its probability. It is possible to grasp.
  • the staining substance is, for example, at least one of a pathogen, a non-pathogen, and cells derived from the organism to be inspected.
  • the cells derived from the test target organism are, for example, epithelial cells and leukocyte cells in a sputum sample, phagocytic leukocyte cells and the like.
  • the recognition estimation unit 102 When the staining substance includes cells derived from the organism to be inspected, the recognition estimation unit 102, for example, after the step S103, has Geckler classification information based on the staining substance estimation type information and the staining substance estimated number information. May be generated. The generation of the Geckler classification information may be performed, for example, before the step S104 or after the step S104. Then, the information output unit 104 may output, for example, the Geckler classification information.
  • the Geckler classification information is information indicating to which group of the Geckler classification the sample of the organism to be inspected belongs.
  • the recognition estimation unit 102 estimates at least leukocytes and squamous epithelial cells from the stained substance image, and the counting unit 13 at least determines the number of the leukocytes and the number of the squamous epithelial cells. Count. By generating the Geckler classification information in this way, the sample can be evaluated.
  • the apparatus 100 may further include, for example, the related information acquisition unit 105.
  • FIG. 11 shows an example of the configuration of the present apparatus 100 including the related information acquisition unit 105.
  • the related information acquisition unit 105 acquires, for example, related information regarding the stained specimen before the step S102A (S105).
  • the step S105 is an arbitrary step and may not be executed.
  • the related information is, for example, at least one of information about the sample target organism, information about the sample, and information about the environment. More specifically, for example, the age of the sample target organism (human or the like), the disease name, the biological state of the sample target organism, the medication history, the location of the medical institution, the antibiogram in the medical institution, and the like.
  • the apparatus 100 may further include, for example, the recommended information generation unit 106.
  • the recommended information generation unit 106 may generate recommended information based on the dyeing substance estimation type information, for example, after the step S102A (S106).
  • the step S106 is an arbitrary step and may not be executed.
  • the recommended information is, for example, at least one of recommended test information and recommended treatment information.
  • the recommended test information is, for example, information on additional tests for identifying bacterial species such as culture. More specifically, for example, when a fungal-like object is confirmed by Gram stain of sputum, recommended test information is generated that recommends culturing in a selective medium that selectively grows fungi.
  • the recommended treatment information is, for example, information on the type of antibiotic to be prescribed, the treatment policy, and the like.
  • the recommended information generation unit 106 may generate the recommended information by referring to the related information, for example. Then, the information output unit 104 may output the recommended information, for example (S104). For example, when the recommended test information is generated, the information output unit 104 may notify a medical worker such as a test technician that the recommended test information has been generated. By generating the recommended information in this way, it is possible to support medical professionals such as laboratory technicians.
  • the recommended treatment information since the staining substance can be estimated in more detail and accurately, the recommended treatment information also has more detailed and accurate contents, and the selection of the therapeutic agent by the medical staff And can more support the decision of treatment policy.
  • the present device 100 may further include, for example, a medical record information acquisition unit 107.
  • the medical record information acquisition unit 107 acquires, for example, the medical record information of the organism to be inspected before the step S102B or the step S106 described later (S107).
  • the step S107 is an arbitrary step and may not be executed.
  • the chart information may include, for example, the above-mentioned test information and the text information, and more specifically, as a result of the test, body temperature, leukocyte count, C-reactive protein value, X-ray finding, severity, and the like.
  • There is information about the living body of the sample target organism such as an infected organ and a drug processing function.
  • the result of the inspection may be, for example, the dyeing substance estimated type information and the dyeing substance estimated number information.
  • the medical record information acquisition unit 107 may acquire the medical record information from an external device via the communication network, or may acquire the medical record information input via the input device 5.
  • the recommended information generation unit 106 may generate the recommended treatment information based on the medical record information, for example, in the step S106.
  • a narrow-range antibacterial drug is selected, it becomes possible to suppress the outbreak of drug-resistant bacteria and the drug price.
  • the present invention by generating the recommended treatment information using the medical record information, it is possible to support the selection of a narrow-range antibacterial drug and the like, and more appropriate and effective treatment becomes possible.
  • the recognition estimation unit 102 may generate the estimated onset probability information by calculating the probability of developing a disease by using at least the medical record information, for example (S102B). In addition to the chart information, the recognition estimation unit 102 may calculate the probability by using each information generated by the present apparatus 100 such as the dyeing substance estimation type information and the dyeing substance estimated number information. As the method for calculating the probability, for example, a known method may be used, or a method described later may be used. The recognition estimation unit 102 may calculate the probability of developing a disease by machine learning, for example.
  • the estimated onset probability information may be, for example, expressing the probability numerically (percentage or the like) in association with the type of the disease, characters (for example, "high probability", “low probability”, etc.). ), Symbols, and other numbers may be used to express the probability.
  • the information output unit 104 may output the estimated onset probability information in association with the stained substance estimated type information in, for example, in the step S104.
  • the estimated type probability information linked to the estimated type information of the stained substance the name and probability of the stained substance such as "bacterial pneumonia 95%” and "atypical pneumonia 80%" are used. There are combined formats, but this is an example and is not limited to this.
  • the estimated onset probability information is output in association with the estimated onset probability information, for example, it is possible to support a medical worker.
  • the recognition estimation unit 102 calculates the weight of the parameter for each type of disease by using, for example, each information included in the test information and the text information as a parameter, and uses the weight of the parameter to calculate the probability by a specific calculation formula. Is calculated.
  • the specific calculation formula is not particularly limited and can be set arbitrarily.
  • the apparatus 100 may further include, for example, an infected organ estimation unit 108.
  • the infected organ estimation unit 108 estimates that the organ from which the sample is collected is an infected organ by analysis using the staining substance image recognized by the recognition estimation unit 102, and estimates the infected organ. Information may be generated (S108). Further, the infected organ estimation unit 108 may estimate the organ from which the sample was collected, for example, by analyzing the image of the stained substance.
  • the infected organ means an organ infected with the staining substance (particularly, at least one of a pathogen and a non-pathogen).
  • the information output unit 104 outputs, for example, the estimated infected organ information in the step S104.
  • the information output unit 104 outputs, for example, the estimated infected organ information in the step S104.
  • the infected organ estimation unit 108 uses the organ from which the sample was collected as an infected organ. May be estimated.
  • (1) At least one of the pathogen and the non-pathogen, and both leukocytes
  • the cause of the disease is not limited to the pathogen, and for example, indigenous bacteria may be the cause of the disease.
  • the present device 100 may further include, for example, an image switching determination unit 109.
  • the image switching determination unit 109 determines when the microscope image is acquired and when the microscope image is not acquired (S109). Then, the recognition estimation unit 102 and the counting unit 103 switch from the acquisition of the microscope image to the non-acquisition of the microscope image, and then generate the stained substance estimated type information and the stained substance estimated number information, respectively. You may.
  • the apparatus 100 may further include, for example, at least one of the staining apparatus control unit 110, the microscope control unit 111, and the sample fixing device control unit 113.
  • the staining device control unit 110 controls a staining device that automatically stains the sample and prepares the stained sample.
  • the timing of control by the dyeing apparatus control unit 110 is not particularly limited, but is executed, for example, before the step S101.
  • the dyeing device may be, for example, the automatic dyeing device of the present invention.
  • the microscope control unit 111 controls a microscope that captures a microscope image of the stained specimen.
  • the timing of control by the microscope control unit 111 is not particularly limited, but is executed, for example, before the step S101.
  • the image acquisition unit 101 acquires, for example, the microscope image captured by the microscope.
  • the "slide glass” in the present invention may be laminated with a cover glass, if necessary. That is, the “slide glass” in the present invention can be read as "preparation” as needed. For example, if the method of staining the sample is Gram stain, imaging with the microscope may be performed without a cover glass.
  • FIG. 4 An example of control by the microscope control unit 111 will be described with reference to FIG.
  • the sample is often spread on the slide glass 10 in the direction of the arrow from A. Therefore, when observing with a microscope in the longitudinal direction of the slide glass 10, as shown on the right side of FIG. 4, darkly smeared portions of the sample appear at regular intervals.
  • the right side of FIG. 4 is a partially enlarged view of the slide glass 10.
  • the shading means the density of the smear of the sample, and the darker the shading in the figure, the darker the sample is the smeared region.
  • the portion surrounded by the thick frame means the visual field region by the microscope (that is, the microscope image), and the arrow indicates the movement of the visual field region (that is, the slide glass 10). It means the movement of the holding part that holds the.
  • the microscope control unit 111 determines whether or not the microscope image in the visual field region (1) is an appropriate image.
  • the proper image is, for example, an image in which a dyeing substance with good dyeing is reflected or an image in which the dyeing substance is clearly visible.
  • the smear of the sample is too thin, so that the dyeing substance cannot be clearly seen, and it is determined that the image is not appropriate.
  • the microscope control unit 111 determines whether or not the image is appropriate for each of the microscope images, and if it is determined that the image is not appropriate, the microscope control unit 111 moves in the longitudinal direction of the slide glass 10 and determines that the image is appropriate. In this case, the movement of the holding portion is controlled so as to move in the lateral direction of the slide glass 10.
  • the smear of the sample on the slide glass 10 is often spread as shown on the left side of FIG. 4, so when observed with a microscope in the longitudinal direction of the slide glass 10, the right side of FIG. 4 is observed.
  • areas where the sample is heavily smeared appear at regular intervals. Therefore, when an image with an appropriate darkness that is useful for clinical judgment is found, there is a high possibility that an image with an appropriate darkness will also be found on the side in the lateral direction.
  • more efficient visual field search becomes possible.
  • the microscope control unit 111 acquires the shading data of the entire slide glass 10.
  • the shading data is, for example, as shown on the left side of FIG. 5, information indicating the shading of the smear of the sample generated by reading the entire slide glass 10 with the shading recognition device 20.
  • the shade recognition device 20 for example, a known device such as a camera or a sensor can be used.
  • the shade recognition device 20 may be, for example, an input device 5 or an external device.
  • the microscope control unit 111 analyzes the shading data and identifies a position having a density within a preset range. The density can be set arbitrarily.
  • the microscope control unit 111 controls the movement of the holding unit so as to start the visual field search from the position.
  • the sample is smeared on the slide glass by an inspection engineer, but there is a problem that it takes time to search for an appropriate field of view and detect pathogens and the like because shading is formed in the slide glass.
  • the pathogens or cells are often invisible even when the spot where the sample is thinly smeared is observed with a microscope.
  • this aspect since it is possible to grasp the shading of the smear, more efficient visual search can be performed.
  • the dyeing apparatus control unit 110 may be able to specify, for example, the decolorization time in the decolorization step, which is one step of the dyeing step, for each sample.
  • the decolorization time can be specified by inputting the decolorization time by a user (medical personnel or the like).
  • the dyeing step is not particularly limited, and may be a step of a conventionally known dyeing method.
  • a staining method there are Gram stain, which mainly examines the presence or absence and characteristics of bacteria, and Thirneilsen staining, which mainly examines the presence and characteristics of acid-fast bacilli.
  • the dyeing device control unit 110 controls the dyeing device so as to carry out the decolorization step at the designated decolorization time, for example.
  • the dyeing apparatus control unit 110 may be able to specify the time required for steps other than the decolorization step for each sample. Then, the dyeing device control unit 110 may control the dyeing device so as to carry out the step at a designated time, for example. This makes it possible to improve the accuracy of dyeing.
  • pathogens that should be stained with Gram-positive (purple) due to excessive decolorization are stained with Gram-negative (red), and pathogens that should be stained with Gram-negative (red) are stained with Gram-positive (purple).
  • this problem is not limited to Gram stain and can occur. Therefore, incorrect test results may be obtained.
  • factors that determine the degree of decolorization include the decolorization time and the contact between the sample and the decolorizing liquid.
  • the decolorization time is about 5 to 7 seconds for a sample whose smear is watery and thin (for example, blood culture sample or urine), but it takes 10 seconds or more for a sample such as highly viscous sputum. Sometimes.
  • the staining device control unit 110 can specify the decolorization time input by the user for each sample, any sample can be appropriately decolorized.
  • the present device 100 may further include, for example, a priority setting unit 112.
  • the priority setting unit 112 can set an arbitrary priority for each sample. Specifically, the present device 10 sets the priority input by the medical staff to the sample via, for example, the input device 5.
  • the priority is represented by, for example, numbers, letters, symbols, and the like.
  • at least one of the staining device control unit 110, the microscope control unit 111, and the sample fixing device control unit 113 is subjected to processing of the staining device, the microscope, and the sample fixing device in descending order of priority. To control.
  • the processing for the sample is not in the order of setting in various devices but in the order of priority, so that one sample is processed before the other sample set before the one sample.
  • So-called interrupts can occur.
  • the time priority for returning test results differs depending on the type of sample and the clinical department. For example, when a blood culture sample becomes positive for culture, sepsis is suspected, but since sepsis is a very urgent disease, immediate bacterial species (staining substance) estimation and antibacterial drug administration are required. It is also desirable to return the test results as soon as possible for the samples submitted by the emergency department.
  • the priority setting unit 112 since the priority can be set, it is possible to give priority to the sample having the highest priority for processing by the apparatus 100 or the like.
  • FIG. 6 is a schematic view showing an example of the configuration of the automatic dyeing apparatus 200 of the present embodiment.
  • the apparatus 200 includes a holding unit 201, a moving unit 202, a staining reagent supply unit 203, and a control unit 204.
  • the apparatus 200 may further include, as an arbitrary configuration, a waste liquid tank 205, a staining reagent bottle 206, and the like, and conventionally known configurations.
  • the control unit 204 is executed by, for example, a central processing unit 1 which is one of the hardware included in the automatic dyeing device 200.
  • the configuration of other hardware of the automatic dyeing apparatus 200 is not particularly limited, and for example, the hardware configuration described in the first embodiment can be incorporated.
  • the holding portion 201 can hold the slide glass 10. As described above, also in the present embodiment, "slide glass” can be read as "preparation” as needed. On the slide glass 10, for example, after the dyeing step is completed, a cover glass is placed on the slide glass 10 to prepare the slide glass 10.
  • the form of the holding portion 201 is not particularly limited as long as it can hold the slide glass 10.
  • the holding portion 201 is, for example, as shown in FIG. 6, a stage-shaped holding portion 201, which may be capable of mounting and holding the slide glass 10, or a clip-shaped holding portion as described later.
  • the number is 201, and the slide glass 10 may be sandwiched and held. It is assumed that the slide glass 10 is smeared with a sample collected from the organism to be inspected.
  • the holding portion 201 is arranged below the reagent dropping portion 2031 and holds the surface of the slide glass 10 on which the sample is smeared toward the reagent dropping portion 2031.
  • the moving unit 202 is connected to the holding unit 201 and can move the holding unit 201.
  • the form of the moving unit 202 is not particularly limited as long as the holding unit 201 can be moved.
  • the movement may be horizontal movement, vertical movement, or rotational movement.
  • the dyeing reagent supply unit 203 includes a plurality of reagent dropping units 2031. As shown in FIG. 6, the plurality of reagent dropping portions 2031 are arranged side by side according to the dyeing step.
  • the dyeing step is not particularly limited and is, for example, the same as described above.
  • Each reagent dropping section 2031 of the plurality of reagent dropping sections 2031 can drop one type of reagent according to the dyeing step.
  • the reagent is housed in, for example, a stain reagent bottle 206.
  • the staining reagent supply unit 203 supplies the reagent from the staining reagent bottle 206 to the reagent dropping unit 2031, for example.
  • the reagent dropping unit 2031 may, for example, drop the reagent only on or around the sample, or may drop the reagent so as to fill the stage-shaped holding portion 201 with the reagent.
  • control unit 204 may control each unit so that the reagent is dropped after the lapse of time instructed by the dyeing apparatus control unit 110, for example. Further, the control unit 204 may control the time from the dropping of the reagent to the waste liquid tank 205 by controlling the dyeing reagent supply unit 203, for example. Specifically, the control unit 204 drains the reagent dropped on the surface of the slide glass 10 on which the sample is smeared after the lapse of time instructed by the dyeing device control unit 110 into the waste liquid tank 205. Each part may be moved to.
  • FIG. 7 shows an example of the slide glass 10 held by the clip-shaped holding portion 201.
  • the surface of the slide glass 10 facing the reagent dropping portion 2031 is smeared with a sample collected from the organism to be inspected.
  • the control unit 204 controls the moving unit 202 after the decolorizing liquid is dropped on the slide glass 10 by the reagent dropping unit 2031 to axis the longitudinal direction of the slide glass 10.
  • the holding portion 201 is driven so that the slide glass 10 is tilted in the lateral direction. Not limited to the example shown in FIG.
  • control unit 204 may drive the holding unit 201 so that the slide glass 10 is tilted in the longitudinal direction with respect to the lateral direction of the slide glass 10, for example. Further, the control unit 204 may drive the holding unit 201 so that the slide glass 10 is tilted alternately in the longitudinal direction and the lateral direction, for example, with the longitudinal direction and the lateral direction of the slide glass 10 as axes alternately. ..
  • the control unit 204 may use at least one of the longitudinal direction and the lateral direction of the slide glass 10 as an axis. Even if the holding portion 201 is driven to at least one of clockwise and counterclockwise so that the inclination of each end of at least one of the slide glass 10 in the lateral direction and the longitudinal direction becomes a degree predetermined from the above reference. good.
  • the degree is not particularly limited and can be set arbitrarily.
  • the degree is, for example, -10 degrees or more and +10 degrees or less, -5 degrees or more and +5 degrees or less, -3 degrees or more and +3 degrees or less, etc., when the inclination of one end in the reference state is 0 degrees. It is the state of any value in the range of.
  • the driving of the holding unit 201 is executed by the control unit 204 controlling the moving unit 202.
  • the control unit 204 drives the holding unit 201 in specific seconds (for example, 1 to 5 seconds, 1 to 3 seconds, 1 second, etc.) and at specific time intervals (for example, 1 to 5 seconds, 1 second, etc.). It may be repeated a plurality of times in ⁇ 3 seconds, 1 second, etc.). By performing such control, each reagent can be uniformly applied to the sample, and the accuracy of staining can be improved.
  • the decolorization process is a process in which it is difficult to properly decolorize as described above.
  • factors that determine the degree of bleaching include the bleaching time and the contact between the sample and the bleaching solution. Since the control unit 204 can efficiently touch these by the above control, the accuracy of decolorization can be improved.
  • the sample staining process can be performed automatically, it is possible to support inspections such as smear inspection.
  • the sample fixing device 500 is not particularly limited as long as it is a device that performs a fixing process on the sample smeared on the slide glass.
  • the fixing process is not particularly limited, and a conventionally known fixing process can be applied.
  • the fixing treatment includes, for example, a treatment using heat, a treatment using alcohol, and the like.
  • the sample subjected to the fixing treatment is stained by the automatic staining apparatus 200.
  • the sample in a tube or the like is smeared on a slide glass to kill bacteria and viruses, and immobilization is performed. After that, the processes of dyeing, drying, microscopic observation, and medical record entry are continued.
  • alcohol also referred to as alcohol fixation
  • the fixing process can be automated and the burden on the site can be further reduced. Further, by using the sample fixing device 500, the method used for the fixing process can be unified, so that the accuracy of the inspection can be improved.
  • the automatic staining apparatus 200 is not particularly limited as long as it is an apparatus that automatically stains the specimen to prepare a stained specimen, and is, for example, the automatic staining apparatus 200 according to the second embodiment.
  • the stained specimen prepared by the automatic staining device 200 is set in the microscope device 300, and a microscope image is taken. The set may be performed manually, for example.
  • the slide glass 10 may be manually moved from the lower part of the reagent dropping part 2031 of the automatic dyeing device 200 to the lower part of the objective lens 301 of the microscope device 300, but the moving part 202 is moved as shown in FIG. You may go by. If necessary, the cover glass may or may not be laminated on the slide glass 10 before the slide glass 10 is moved to the lower part of the objective lens 301 of the microscope device 300.
  • the laminating may be performed manually, for example.
  • FIG. 9 is a schematic view showing an example in which the slide glass 10 moves from the lower part of the reagent dropping portion 2031 of the automatic dyeing device 200 to the lower part of the objective lens 301 of the microscope device 300. As shown in FIG.
  • the sample is smeared on the slide glass 10 by the inspection engineer, and the slide glass 10 is set on the holding unit 201, whereby the staining process, the imaging with a microscope, and the imaging are performed.
  • the estimation of the dyeing substance can be performed fully automatically. As a result, it is possible to significantly reduce the labor required for Gram stain, Ziehl-Neelsen stain, and the like.
  • the slide glass 10 may be manually moved from the sample fixing device 500 to the lower part of the reagent dropping section 2031 of the automatic staining device 200, but it may also be moved by moving the moving section 202 as shown in FIG. good.
  • FIG. 10 is a schematic view showing an example in which the slide glass 10 moves from the sample fixing device 500 to the lower part of the objective lens 301 of the microscope device 300 through the lower part of the reagent dropping portion 2031 of the automatic staining device 200.
  • the moving unit 202 may be movable to, for example, the lower part of the sample fixing device 500.
  • the moving unit 202 may move in this way under the control of, for example, the control unit 204.
  • the moving unit 202 may be movable from the sample fixing device 500 to the lower part of the objective lens 301 of the microscope device 300, passing through the lower part of the reagent dropping part 2031 of the automatic staining device 200, for example.
  • a series of steps from fixing process, staining process, imaging with a microscope, and estimation of the stained substance can be performed fully automatically, and the labor can be further reduced.
  • the microscope device 300 (also simply referred to as a microscope 300) is not particularly limited as long as it can capture a microscope image of the stained specimen, and may be, for example, a known device.
  • the microscope image taken by the microscope device 300 is acquired by the microscope inspection support device 100.
  • the microscopic examination support device 100 may include, for example, a display unit 114 that displays information output by the information output unit 104.
  • the display unit 114 may be able to display microscope images captured at different focal points for the same field of view, for example, by a user's operation.
  • the microscopic images taken at the different focal points are included, for example, in the stained substance estimation type information.
  • the user's operation is not particularly limited, and is, for example, an operation such as moving a mouse wheel. This enables three-dimensional observation.
  • This aspect is particularly useful for confirming, for example, a capsule formation image of Streptococcus pneumoniae.
  • the capsule formation image of Streptococcus pneumoniae is difficult to confirm on a flat surface, and can be confirmed by intentionally shifting the focus.
  • the various processes performed by the display unit 114 can be said to be, for example, a display process.
  • the display unit 114 may attach identification information to each slide glass 10 and display the identification information.
  • the identification information is not particularly limited, and may be, for example, numbers, letters, symbols, and combinations thereof.
  • FIG. 12 shows an example of the identification information and the like displayed on the display by the processing of the display unit 114.
  • the display unit 114 has, for example, the identification information of the slide glass 10 (indicated as a unique number for each slide glass 10) and the inserted state of the slide glass 10 (whether or not it is held by the holding unit 201). Or) may be displayed in association with each other.
  • the inserted state is displayed as "inserted”, and if the slide glass 10 is removed from the holding portion 201, for example, the inserted state is "removed”. Is displayed.
  • the terms "inserted” and “removed” are examples, and the present invention is not limited thereto.
  • the display unit 114 displays, for example, the time taken for each step of the dyeing process set by the dyeing device control unit 110 based on the input to the user in association with the identification information. You may. Further, the display unit 114 may display the priority set by the priority setting unit 112 based on the input to the user in association with the identification information, for example, as shown in FIG. In FIG. 12, the priorities are displayed as “ ⁇ ”, “ ⁇ ”, and “ ⁇ ” in descending order of priority.
  • the display unit 114 may display, for example, each information generated by the microscopic examination support device 100 in a table format as shown in FIG. 12, but this is an example and is not limited thereto.
  • the user terminal 400 is a terminal of a user such as a medical worker. Specifically, there are personal computers (PCs, for example, desktop type, notebook type), smartphones, tablet terminals, wearable terminals and the like.
  • the user terminal 400 is not particularly limited as long as it can display the information output by the information output unit 104 and can add arbitrary information to the information output by the information output unit.
  • the information output by the information output unit 104 may be, for example, in a situation where it can be shared by a plurality of user terminals 400.
  • the situation that can be shared by a plurality of user terminals 400 is, for example, a situation in which the automatic staining substance estimation system 1000 is stored in a server, a database, or the like inside or outside the system 1000.
  • the Gram stain and the chart input place, and the work called culture determination, which is a post-staining step in the microbial identification test, are carried out at different places. Even if each work is performed in different places in this way, by performing the addition to the information under the situation, the information and the information can be added to the plurality of user terminals 400. It is possible to share the contents that have been made.
  • the information output unit 104 may output the report information in association with the information according to the information to be output, for example.
  • the notification information is information that means, for example, that an infectious disease is suspected or that a specific response is required. For example, when the stained substance estimated type information is generated and an infectious disease is suspected, when the recommended test information is generated and the need for the additional test (test other than routine test) is high, the stained substance estimated type information is generated.
  • the notification information is output when it is determined that an urgent response is necessary based on the content of the information on the estimated number of stained substances.
  • the stained substance estimation type information indicating that a gram-positive staphylococcus was estimated is generated, it is suspected that a resistant bacterium called MRSA is ineffective, and a strong antibacterial drug different from the routine is administered. You will need it.
  • the stained substance estimation type information indicating that leukocytes or phagocytic leukocytes were estimated is generated, it means that an inflammatory reaction is occurring at the place where the sample was collected, and many of these objects are present. If found, it will need to be treated as an infectious disease. When such a sample can be confirmed, the medical worker can promptly respond by outputting the notification information in association with information such as information on the estimated type of dyeing substance.
  • a specific process associated with the notification information is executed in the output destination device and device. For example, if the output destination is a speaker, an alarm sounds, if the output destination is a monitor, notification information is displayed on the monitor, or if the output destination is a lamp, the lamp blinks. ..
  • the automatic dyeing substance estimation system 1000 may further include, for example, a shade recognition device 20.
  • the microscopic examination support device 100 can communicate with the light and shade recognition device 20.
  • the shading recognition device 20 is a device capable of recognizing the shading of an object, and the above description can be incorporated.
  • the automatic staining substance estimation system 1000 may use the shading recognition device 20 and the sample fixing device 500 in combination.
  • the stained specimen prepared by the staining device 200 is subjected to the shade recognition device 20.
  • the microscope control unit 111 acquires the shade data generated by the shade recognition device 20, and then the stained specimen is set in the microscope device 300.
  • the moving unit 202 may be movable to, for example, a position where the light and shade can be recognized by the light and shade recognition device 20.
  • the program of the present embodiment is a program for causing a computer to execute each step of the method of the present invention as a procedure.
  • "procedure” may be read as "processing”.
  • the program of the present embodiment may be recorded on a computer-readable recording medium, for example.
  • the recording medium is, for example, a non-transitory computer-readable storage medium.
  • the recording medium is not particularly limited, and examples thereof include a read-only memory (ROM), a hard disk (HD), and an optical disk.
  • the present invention it is possible to support inspections such as smear inspection.
  • the present invention is useful in estimating dyeing substances.

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