WO2023238564A1 - Système de traitement d'informations, procédé de traitement d'informations, dispositif de traitement d'informations et programme - Google Patents

Système de traitement d'informations, procédé de traitement d'informations, dispositif de traitement d'informations et programme Download PDF

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Publication number
WO2023238564A1
WO2023238564A1 PCT/JP2023/017247 JP2023017247W WO2023238564A1 WO 2023238564 A1 WO2023238564 A1 WO 2023238564A1 JP 2023017247 W JP2023017247 W JP 2023017247W WO 2023238564 A1 WO2023238564 A1 WO 2023238564A1
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Prior art keywords
data
information processing
information
biological particle
processing system
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PCT/JP2023/017247
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English (en)
Japanese (ja)
Inventor
弘人 河西
道治 佐藤
宏行 山田
功輔 三田
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ソニーグループ株式会社
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Publication of WO2023238564A1 publication Critical patent/WO2023238564A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry

Definitions

  • the present technology relates to an information processing system, an information processing method, an information processing device, and a program. More specifically, the present technology provides an information processing system including an information processing device that generates image data using data acquired from a biological particle analyzer, an information processing method executed by the information processing system, and the information processing device. and a program for causing an information processing device to execute processing.
  • a technology called flow cytometry is used to analyze microparticles (biological particles) related to living organisms such as cells and microorganisms.
  • Flow cytometry involves irradiating light onto microparticles that flow in a sheath flow that is fed into a flow channel formed in a flow cell or microchip, and detects the fluorescence and light emitted from individual microparticles. This is an analysis method that analyzes or separates microparticles by detecting scattered light.
  • a device that performs flow cytometry is called a flow cytometer.
  • devices that can perform particle sorting for example, biological particle sorting devices that can sort biological particles
  • cell sorters are also called cell sorters.
  • a vibration element may be provided in a part of the flow path through which microparticles flow.
  • the vibration element applies vibration to a part of the flow path, and the fluid discharged from the discharge port of the flow path is continuously turned into droplets. Then, a predetermined electric charge is charged to the droplets containing these microparticles, and based on this charge, the traveling direction of the droplets is changed by a deflection plate, etc., and only the desired microparticles are collected into a predetermined container. It can be done.
  • Patent Document 1 listed below discloses an analyzer capable of analyzing a biological sample such as blood, and a management device connected to the analyzer via a network. When an error occurs during measurement, the analysis device transmits the error information to the management device. The management device notifies error information to a preset notification destination.
  • the performance of droplet formation and bioparticle separation in a biological particle sorting device may deteriorate under the influence of environmental changes. Furthermore, these performances of the biological particle sorting device can also be influenced by the operational control of the components, such as whether or not the vibrating elements that form droplets are appropriately controlled. As described above, there are various factors that can affect the performance of a biological particle sorting device.
  • Detecting factors that may affect the above performance is considered useful for stabilizing or improving the performance of the biological particle sorting device.
  • the management device described in Patent Document 1 does not have a configuration suitable for grasping the state of the analyzer except when a trouble occurs.
  • bioparticle sorting device when detecting a plurality of the above-mentioned factors in parallel, it is desirable to be able to present information regarding the plurality of factors in an easy-to-understand manner to the user (for example, the user or supervisor of the bioparticle sorting device).
  • these multiple factors that can affect device performance are not limited to bioparticle separation devices, but also apply to bioparticle analyzers (devices that analyze bioparticles without separating them). It is desirable to be able to present information in an easy-to-understand manner.
  • the present technology aims to provide an information processing system that can present information on factors that may affect the performance of a bioparticle analyzer in an easy-to-understand manner.
  • this technology including a biological particle analyzer and an information processing device
  • the biological particle analyzer includes a control unit that controls a vibration element to form droplets containing biological particles
  • the information processing device includes a processing unit that generates image data using device information data acquired from the biological particle analysis device
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer.
  • Parameters relating to the adjustment of the vibrating element may include parameters obtained from a fluid stream image and a frequency and/or amplitude of a drive voltage supplied to the vibrating element.
  • the parameters obtained from the fluid stream image include parameters relating to the break-off point where the flux separates into droplets, parameters relating to the position of satellite droplets, and relating to the width and position of waists in the flux. It may include at least one selected from parameters.
  • the parameters related to factors that can affect the droplet state may include at least one selected from temperature, pressure for fluid control, and power of light irradiated to the biological particles.
  • the data regarding the operating status of the bioparticle analyzer includes data indicating that the bioparticle analyzer is in the process of automatic adjustment before starting bioparticle collection, and data indicating that the bioparticle analyzer is in the process of bioparticle collection. and data indicating that the biological particle analyzer is being cleaned.
  • the image data may be image data in which two or more pieces of the device information data are displayed on the same time axis.
  • the device information data is a parameter obtained from a fluid stream image and a frequency and/or amplitude of a drive voltage supplied to the vibration element, and the image data is a parameter obtained from a fluid stream image, and the image data is a parameter obtained from a fluid stream image, and the image data is a parameter obtained from a fluid stream image.
  • the image data may be image data displayed on the screen.
  • the device information data includes parameters related to factors that may affect the droplet state and data related to the operating status of the biological particle analyzer, and the image data includes the device information data on the same time axis. It may be displayed image data.
  • the information processing system further includes a client terminal, and the processing unit generates notification information based on log information and/or error information acquired from the bioparticle analyzer, and notifies the client terminal of the notification information. You may do so.
  • the notification information may include at least one of information regarding auto-calibration completion, analysis completion, separation completion, warning, and error.
  • the processing unit may predict errors based on the device information data or the image data.
  • the information processing device may further include a storage unit that stores the device information data and error information acquired from the biological particle analyzer.
  • the processing unit generates a learned model by performing machine learning using teacher data in which the device information data and the error information are associated with each other, and the device information data is input using the learned model.
  • the information processing device may further include a storage unit that stores the image data and error information acquired from the biological particle analyzer.
  • the processing unit When the processing unit generates a trained model by performing machine learning using teacher data that associates the image data and the error information, and image data is input using the trained model. It is possible to predict errors.
  • this technology a step in which the biological particle analyzer controls a vibrating element to form droplets containing biological particles; an information processing device generating image data using device information data acquired from the biological particle analyzer, The device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer. Information processing methods are also provided.
  • this technology A processing unit that generates image data using device information data acquired from a biological particle analyzer,
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer. It also provides information processing equipment.
  • this technology A step of generating image data using device information data obtained from a biological particle analyzer,
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer.
  • a program for causing an information processing device to execute the information processing method is also provided.
  • FIG. 1 is a diagram illustrating an example of an information processing system according to a first embodiment.
  • 1 is a diagram showing an example of a hardware configuration of a computer.
  • FIG. 1 is a diagram schematically showing an example of the configuration of a biological particle sorting device. It is a figure which shows the state of the fluid and satellite droplet discharged from the orifice. It is a figure which shows the state of the fluid and satellite droplet discharged from the orifice.
  • It is a flowchart which shows an example of the process of generating image data. This is an example of image data in which two pieces of device information data are displayed on the same time axis. This is an example of image data in which two pieces of device information data are displayed on the same time axis.
  • First embodiment (information processing system) 1-1.
  • Modification example 2 Second embodiment (information processing method) 3.
  • Fourth embodiment (program) Second embodiment (information processing method)
  • FIG. 1 is a diagram showing an example of an information processing system 1 according to the first embodiment.
  • the information processing system 1 includes a biological particle sorting device 200, a control device 300, a management device 400, and a user terminal 500, which are installed in a user facility 110.
  • the user facility 110 is, for example, a base of users who use the biological particle sorting device 200.
  • the user facility 110 is an example of a facility in the present technology, and may be expressed as a first facility, for example.
  • the biological particle sorting device 200 is an example of a biological particle analysis device in the present technology.
  • a bioparticle analyzer irradiates light onto bioparticles flowing within a sheath flow fed into a channel formed in a microchip, etc., and detects the fluorescence and scattered light emitted by individual bioparticles. This device analyzes bioparticles by detecting them.
  • a bioparticle sorting device is a device that can perform bioparticle fractionation in addition to bioparticle analysis.
  • the biological particle sorting device 200 shown in FIG. 1 separates and collects droplets containing specific particles based on the results of analysis using, for example, an optical method.
  • the biological particle sorting device 200 may be a cell sorter.
  • the control device 300 is connected to the biological particle sorting device 200, and controls the operation of the biological particle sorting device 200, as well as acquiring, processing, and displaying data from the biological particle sorting device 200.
  • the management device 400 is connected to the control device 300, and acquires, processes, and displays data from the control device 300, and sends notifications to other devices or terminals.
  • the management device 400 is an example of an information processing device in the present technology, and may be expressed as a first information processing device, for example.
  • the user terminal 500 is connected to the management device 400, and receives and displays notifications.
  • the user terminal 500 is an example of a client terminal in the present technology, and may be expressed as, for example, a first client terminal.
  • the information processing system 1 includes a customer support server 600 installed in a customer support center 120.
  • the customer support center 120 provides, for example, a service that remotely monitors the biological particle sorting device 200 installed in the user facility 110 and sends notifications regarding the biological particle sorting device 200 to devices or terminals in other facilities as necessary. It is a base that provides The customer support center 120 is another example of a facility in the present technology, and may be expressed as a second facility, for example.
  • the customer support server 600 is communicably connected to the management device 400 installed in the user facility 110 via the network NW.
  • the customer support server 600 acquires, processes, and displays data from the management device 400, and sends notifications to other devices or terminals.
  • the customer support server 600 is also communicably connected to a supporter terminal 700 (described later) installed at the service center 130 via the network NW.
  • the customer support server 600 is another example of the information processing device according to the present technology, and may be expressed as a second information processing device, for example.
  • the information processing system 1 includes a supporter terminal 700 installed at the service center 130.
  • the service center 130 is, for example, a base of a service provider that remotely checks the status of the biological particle sorting device 200 installed in the user facility 110 when a trouble occurs in the biological particle sorting device 200.
  • the service center 130 is another example of a facility in the present technology, and may be expressed as a third facility, for example.
  • the supporter terminal 700 is communicably connected to a customer support server 600 installed in the customer support center 120 via the network NW.
  • the supporter terminal 700 receives, for example, a notification regarding the biological particle sorting device 200 from the customer support server 600.
  • the supporter terminal 700 is also communicably connected to a management device 400 installed in the user facility 110 via the network NW.
  • the supporter terminal 700 remotely accesses the management device 400 and acquires, processes, and displays information regarding the biological particle sorting device 200.
  • Supporter terminal 700 is another example of a client terminal in the present technology, and may be expressed as, for example, a second client terminal.
  • the control device 300, the management device 400, the user terminal 500, the customer support server 600, and the supporter terminal 700 are configured by, for example, a computer.
  • the network NW is constituted by a communication network through which data is transmitted and received.
  • the communication network may be, for example, the Internet, a telephone line network, a mobile communication network, a satellite communication network, a leased line network, a LAN (Local Area Network), or a combination thereof.
  • the network NW may be a wired communication network, a wireless communication network including Wi-Fi (registered trademark) and Bluetooth (registered trademark), or a combination thereof.
  • the biological particle sorting device 200 and the information processing device are essential. It is a component of Devices and terminals other than the essential components may be arbitrary components.
  • the number of devices and terminals shown in FIG. 1 is one each, the number of devices and terminals is not limited to this, and may be multiple. Further, although there is one user facility 110, one customer support center 120, and one service center 130 each shown in FIG. 1, the number of facilities is not limited to this and may be plural.
  • the control device 300, management device 400, user terminal 500, customer support server 600, and supporter terminal 700 are configured by, for example, the computer 1000 shown in FIG. 2.
  • FIG. 2 is a diagram showing an example of the hardware configuration of the computer 1000.
  • the computer 1000 includes a processor 1100, a memory 1200, a storage 1300, a network interface (network I/F) 1400, and an input/output interface (input/output I/F) 1500.
  • the processor 1100 controls the operation of the computer 1000.
  • An example of the processor 1100 is a CPU (Central Processing Unit).
  • Memory 1200 stores instructions that, when executed by processor 1100, cause computer 1000 to perform operations.
  • Examples of the memory 1200 include computer memories such as ROM (Read Only Memory) and RAM (Random Access Memory).
  • the storage 1300 stores information and programs related to the operation and use of the computer 1000. Examples of the storage 13 include an HDD (Hard Disk Drive) and an SSD (Solid State Drive).
  • Examples of the storage 13 include an HDD (Hard Disk Drive) and an SSD (Solid State Drive).
  • the network I/F 1400 is an interface for connecting to a predetermined communication network.
  • Network I/F 1400 allows computer 1000 to send and receive various data to and from other computers.
  • the input/output I/F 1500 is an interface for connecting to an input/output device.
  • An input device and an output device are connected to the input/output I/F 1500.
  • the input device may be any one of all devices that can accept input of various data to the computer 1000, or a combination thereof. Examples of the input device include a keyboard, mouse, touch panel, and button interface.
  • the output device may be any one of all devices capable of outputting various data or a combination thereof. Examples of output devices include displays, printers, and speakers.
  • the processor 1100, memory 1200, storage 1300, network I/F 1400, and input/output I/F 1500 are interconnected by, for example, a bus 1600.
  • a bus 1600 Although each piece of hardware is shown as a single piece in FIG. 2, this is merely an example and there may be more than one piece of any piece of hardware. Further, in FIG. 2, all the hardware is provided in a single computer 1000, but this is merely an example, and these hardware may be provided in a distributed manner in a plurality of computers.
  • FIG. 3 is a diagram schematically showing an example of the configuration of the biological particle sorting device 200.
  • the biological particle sorting device 200 includes a microchip 2 (a chip having a flow path on the order of micrometers), a vibration element 3, a charging electrode 4, deflection plates 5a and 5b, collection containers 6a to 6c, and a voltage supply section 31. We are prepared. These are arranged inside the biological particle sorting device 200. Furthermore, the biological particle sorting device 200 includes a droplet detection section 7 that detects droplets containing biological particles, and a control section 8 that controls the vibration element 3 to form droplets containing biological particles. There is.
  • Examples of biological particles separated by the biological particle sorting device 200 include cells, microorganisms, and biologically related microparticles.
  • Examples of cells include plant cells, animal cells, and blood cell cells.
  • Examples of microorganisms include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, and fungi such as yeast.
  • Examples of biologically relevant microparticles include chromosomes, ribosomes, mitochondria, organelles (cellular organelles), nucleic acids, proteins, and complexes of nucleic acids and proteins that constitute various cells.
  • the biological particles may be labeled with one or more labeling substances (for example, a dye (particularly a fluorescent dye), a fluorescent dye-labeled antibody, etc.).
  • the bioparticle sorting device 200 may analyze particles other than bioparticles, and beads or the like may be analyzed for calibration or the like.
  • the microchip 2 includes a sample inlet 22 into which a liquid (sample liquid) containing biological particles to be separated is introduced, a sheath inlet 23 into which a sheath liquid is introduced, and a suction outlet for eliminating clogging or air bubbles. 24 is formed.
  • the sample liquid is introduced into the sample inlet 22, merges with the sheath liquid introduced into the sheath inlet 23, is sent to the sample flow path, and is passed through the orifice 21 provided at the end of the sample flow path. It is discharged.
  • the fluid containing biological particles discharged from the orifice 21 is ejected as a jet flow.
  • the vibration element 3 by applying vibration to the whole or part of the sample flow path by the vibration element 3, the horizontal section of the jet flow is modulated along the vertical direction in synchronization with the frequency of the vibration element 3, and the break-off point is Droplets are separated and generated at The vibration element 3 and the break-off point will be described later.
  • the sample flow path is configured so that the sample liquid flows.
  • the sample flow path may be configured such that a flow of biological particles contained in the sample liquid is aligned by hydrodynamic focusing.
  • the channel structure including the sample channel may be designed to create laminar flow.
  • the channel structure is designed such that a laminar flow is formed in which the sample liquid is surrounded by the flow of the sheath liquid.
  • the design of the channel structure may be appropriately selected by those skilled in the art, and a known design may be adopted.
  • the sample flow path may be formed in a flow channel structure such as a flow cell.
  • the width of the sample channel may be formed, for example, between 10 ⁇ m and 10 mm, particularly between 10 ⁇ m and 1 mm.
  • a suction flow path that communicates with the suction outlet 24 is connected to the sample flow path.
  • This suction channel is used to eliminate the blockage or bubbles by creating negative pressure in the sample channel and temporarily reverse the flow when a blockage or bubbles occur in the sample channel.
  • 24 is connected to a negative pressure source such as a vacuum pump.
  • the microchip 2 may be made of glass or various plastics (PP, PC, COP, PDMS, etc.).
  • the material of the microchip 2 is desirably a material that is transparent to the measurement light, has low autofluorescence, and has low wavelength dispersion, so that optical errors are small. .
  • the microchip 2 may be formed by wet etching or dry etching of a glass substrate, or by nanoimprinting, injection molding, or machining of a plastic substrate.
  • the microchip 2 may be formed, for example, by sealing a substrate on which a sample channel is formed with a substrate made of the same material or a different material.
  • the vibration element 3 is placed in contact with a part of the microchip 2 or is provided as an internal structure of the microchip 2.
  • the vibration element 3 applies minute vibrations to the sheath liquid by vibrating the microchip 2 at a predetermined frequency, converts the fluid (sample liquid and sheath liquid) discharged from the orifice 21 into droplets, and generates a fluid stream S.
  • This vibration element 3 may be, for example, a piezo element.
  • the voltage supply section 31 supplies a driving voltage to the vibration element 3.
  • the driving voltage is supplied according to a sinusoidal wave to form a stable droplet.
  • the drive voltage may be controlled by parameters such as frequency (clock value) and/or amplitude (drive value). That is, the parameters related to the adjustment of the vibration element 3 may include the frequency and/or amplitude of the drive voltage supplied to the vibration element 3.
  • the charging unit applies a positive or negative charge to the droplet discharged from the orifice 21.
  • the charging section includes a charging electrode 4 that applies a charge to the sheath liquid and/or the sample liquid, a voltage source (not shown) that applies a predetermined voltage to the charging electrode 4, and the like.
  • the charging electrode 4 is arranged so as to be in contact with the sheath liquid and/or the sample liquid flowing through the channel.
  • the charging electrode 4 may be inserted into a charging electrode inlet of the microchip 2, for example.
  • the charging electrode 4 is arranged so as to be in contact with the sample liquid, but the arrangement of the charging electrode 4 is not limited to this.
  • the charging electrode 4 may be placed in contact with the sheath liquid, or may be placed in contact with both the sample liquid and the sheath liquid.
  • the charging electrode 4 is preferably arranged so as to contact only the sheath liquid.
  • the deflection plates 5a and 5b are a pair of deflection plates disposed opposite to each other with the fluid stream S interposed therebetween.
  • the deflection plates 5a and 5b change the traveling direction of each droplet in the fluid stream S by the electric force applied to the droplet and direct the droplet containing biological particles to a predetermined collection container. Induce.
  • the deflection plates 5a and 5b may be, for example, electrodes commonly used in general biological particle sorting devices.
  • Different positive or negative voltages are applied to the deflection plates 5a and 5b, respectively.
  • an electric force (Coulomb force) is generated, and each droplet is attracted to either deflection plate 5a or 5b.
  • the direction of the flow (side stream) of droplets drawn by an electric field can be controlled by changing the positive/negative charge on the droplets and the amount of charge. Thereby, different types of biological particles can be sorted at the same time.
  • the collection containers 6a to 6c are containers for collecting droplets that have passed between the deflection plates 5a and 5b.
  • the collection containers 6a to 6c may be, for example, general-purpose plastic tubes or glass tubes.
  • the collection containers 6a to 6c are preferably arranged in the biological particle sorting device 200 so as to be replaceable. Furthermore, a drainage path for collected droplets may be connected to one of the collection containers 6a to 6c that receives particles that are not to be separated.
  • the number of collection containers arranged in the biological particle sorting device 200 is not limited to the three illustrated. For example, when more than three collection containers are arranged, each droplet is guided to one of the collection containers depending on the presence or absence of electrical force between the deflection plates 5a and 5b and its magnitude. , can be recovered.
  • the droplet detection unit 7 detects the state of the droplets discharged from the orifice 21 of the microchip 2 and the satellite droplets present between the droplets.
  • the droplet detection unit 7 includes an image sensor 71 that images the fluid stream S to obtain an image with the fluid stream as a subject (i.e., a fluid stream image), a position adjustment mechanism 72 that changes the position of the image sensor 71, and a position adjustment mechanism 72 that changes the position of the image sensor 71. It may be configured by an image data processing section 73 that processes images.
  • the image sensor 7 may be an image sensor such as a CCD or a CMOS camera, or may be any type of image sensor such as a photoelectric conversion element.
  • the biological particle sorting device 200 may be provided with a light source (not shown) that illuminates the imaging area in addition to the imaging device 7.
  • the fluid stream image acquired by the image sensor 71 is input to the image data processing section 73.
  • the image data processing unit 73 may process, for example, a fluid stream image and acquire various parameters from the fluid stream image.
  • Parameters obtained from the fluid stream image may include parameters related to the break off point (BOP), which is the location where the flux separates into droplets, and parameters related to the location of satellite droplets.
  • Parameters obtained from the fluid stream image may also include parameters related to the width and position of the waist in the flux. Note that the "constriction" means a constricted portion in the flux immediately before being turned into droplets.
  • the control unit 8 controls the voltage supply unit 31 based on the parameters acquired from the fluid stream image by the image data processing unit 73, thereby controlling the vibration element 3. For example, the control unit 8 automatically adjusts the drive voltage and frequency supplied to the vibration element 3 based on the parameters acquired from the fluid stream image. That is, the parameters related to the adjustment of the vibration element 3 may include parameters obtained from the fluid stream image. The parameters are selected from parameters related to the break-off point where the flux separates into droplets, parameters related to the position of the satellite droplet, and parameters related to the width and position of the waist in the flux, as described above. may include at least one.
  • the biological particle sorting device 200 separates biological particles using an optical method, for example, light (measurement light) is irradiated to a predetermined part of the sample flow path to collect particles generated from particles flowing through the sample flow path.
  • a light detection section (not shown) that detects light (measurement target light) is provided.
  • the light detection unit includes, for example, a laser light source, an irradiation system including a condensing lens and a dichroic mirror that collect and irradiate laser light onto particles, a bandpass filter, and the like, and an irradiation system that collects and irradiates particles with laser light.
  • the detection system may also include a detection system that detects the light to be measured.
  • the detection system is composed of, for example, a PMT (Photo Multiplier Tube) and an area imaging device such as a CCD or a CMOS device.
  • the irradiation system and the detection system may be formed by the same optical path or may be formed by separate optical paths.
  • the measurement target light detected by the detection system of the photodetector is light generated from particles by irradiation with the measurement light.
  • the light to be measured may be, for example, scattered light such as forward scattered light, side scattered light, Rayleigh scattered light, and Mie scattered light, or fluorescence. These measurement target lights are converted into electrical signals, and the optical properties of the particles are detected based on these electrical signals.
  • the biological particle sorting device 200 that is, the biological particle sorting method executed in the biological particle sorting device 200 will be described.
  • the biological particle separation method includes, for example, a step of detecting the state of a droplet discharged from the orifice 21 and a satellite droplet existing between the droplets, and a step of detecting the presence of a break-off point or a satellite droplet.
  • a step of controlling the drive voltage and frequency supplied to the vibration element 3 based on the position of the vibration element 3 may be performed.
  • the above biological particle separation method may include, for example, the following steps. First, a sample liquid containing particles to be separated is introduced into the sample inlet 22, and a sheath liquid is introduced into the sheath inlet 23, respectively. Then, for example, the optical detection unit detects the optical characteristics of the particles, and at the same time detects the flow velocity (flow velocity) of the particles, the interval between the particles, and the like. The optical characteristics, flow velocity, spacing, etc. of the detected particles are converted into electrical signals and output to an overall control unit (not shown) of the apparatus.
  • the laminar flow of the sample liquid and sheath liquid that has passed through the light irradiation part of the sample channel is discharged from the orifice 21 to the space outside the microchip 2.
  • the orifice 21 is vibrated by the vibration element 3 to turn the discharged fluid into droplets.
  • each charged droplet in the sample flow path has its traveling direction changed by the deflection plates 5a and 5b based on the detection result in the photodetector, is guided to a predetermined collection container 6a to 6c, and is collected. be done.
  • the droplet detection unit 7 detects the state of the droplets discharged from the orifice 21 and the satellite droplets present between the droplets, and obtains parameters regarding the break-off point or the position where the satellite droplets exist. Then, based on the parameters, the control section 8 controls the voltage supply section 31 to control the drive voltage and frequency supplied to the vibration element 3.
  • the vibration frequency optimal for droplet formation is automatically adjusted.
  • the following is known in droplet formation.
  • (2) A state in which the satellite droplet is absorbed by the previous droplet (Fast) or a state in which the satellite droplet is absorbed by the subsequent droplet (Slow) is suitable for sorting.
  • a fluid stream image (droplet image) is acquired by the image sensor 71 of the droplet detection unit 7.
  • the position adjustment mechanism 72 adjusts the position of the image element so that the break-off point BOP matches the preset marker position (bold line shown in FIG. 5).
  • 71 is moved, and the position of the image sensor 71 at that time is acquired from the sensor.
  • the image sensor 71 is lowered by a certain amount by the position adjustment mechanism 72, so that the state of the droplet below can be acquired as a droplet image.
  • the image data processing unit 73 determines whether the satellite droplet SD is absorbed by the droplet D or not.
  • the target to be automatically adjusted may be, for example, the amplitude of the drive voltage.
  • the management device 400 and the customer support server 600 are examples of information processing devices in the present technology, as described above.
  • the information processing device will be described below using the management device 400 as an example.
  • the configuration and operation of the management device 400 described below may be realized in the customer support server 600.
  • similar configurations and operations may be realized in both the management device 400 and the customer support server 600.
  • FIG. 6 is a flowchart illustrating an example of the process of generating image data.
  • the control unit 8 of the biological particle sorting device 200 controls the vibration element 3 to form droplets containing biological particles (step S101).
  • the processing unit 410 of the management device 400 acquires device information data from the biological particle sorting device 200 (step S102), and generates image data using the acquired device information data (step S103).
  • the management device 400 includes the processing unit 410 that generates image data using the device information data acquired from the biological particle sorting device 200.
  • the device information data may be data acquired from the biological particle sorting device 200 via the control device 300.
  • the device information data is not limited to data acquired via the control device 300, and may be data directly acquired from the bioparticle sorting device 200, or data obtained by using a device other than the control device 300. It may also be data acquired via.
  • the image data generated by the processing unit 410 of the management device 400 may be displayed on the display unit 420 of the management device 400, for example. Furthermore, the management device 400 may transmit the image data to another device or terminal using the communication unit 430. Thereby, the image data may be configured to be displayed on the display section of another device or terminal.
  • the communication unit 520 may receive image data from the management device 400, and the image data may be displayed on the display unit 510.
  • the communication unit 630 may receive image data from the management device 400, and the image data may be displayed on the display unit 620.
  • the communication unit 720 may receive image data from the management device 400, and the image data may be displayed on the display unit 710.
  • the device information data used in the processing unit 410 of the management device 400 includes parameters related to the adjustment of the vibration element (see FIG. 3), parameters related to factors that may affect droplets, and biological particle sorting device 200. This is at least one piece of data selected from data related to the operating status of.
  • the device information data is data related to factors that may affect the performance of the biological particle sorting device 200.
  • the processing unit 410 of the management device 400 displays data that is easy to visually understand based on the device information data. Generate image data.
  • the parameters related to the adjustment of the vibrating element may include, for example, parameters obtained from the fluid stream image and the frequency and/or amplitude of the drive voltage supplied to the vibrating element.
  • the parameters obtained from the fluid stream image may include at least one selected from parameters related to the break-off point, parameters related to the position of the satellite droplet, and parameters related to the width and position of the waist in the flux. .
  • Parameters related to factors that may affect the droplet state may include, for example, temperature, pressure for fluid control, and power of light irradiated to biological particles.
  • the pressure for fluid control is the pressure for controlling the delivery of each of the sheath liquid and sample liquid.
  • These parameters may be acquired from various sensors (eg, temperature sensors) installed in the biological particle sorting device 200, or from log information of the biological particle sorting device 200, for example.
  • the data regarding the operating status of the biological particle sorting device 200 includes data indicating that the biological particle sorting device 200 is in the process of automatic adjustment before starting bioparticle sorting, data indicating that the biological particle sorting device 200 is in the process of separating biological particles. and data indicating that the biological particle sorting device 200 is being cleaned. These data may be obtained from log information of the biological particle sorting device 200, for example.
  • the processing unit 410 of the management device 400 may generate image data using one piece of device information data, or may generate image data using two or more pieces of device information data.
  • An example of a case where the processing unit 410 generates image data using two or more pieces of device information data is a case where a plurality of factors that can affect the performance of the biological particle sorting device 200 are simultaneously detected.
  • the processing unit 410 preferably performs a process of displaying two or more pieces of device information data on the same time axis. That is, the image data generated by the processing unit 410 may be image data in which two or more pieces of device information data are displayed on the same time axis. As a result, image data can be provided that allows at a glance changes over time in a plurality of factors that may affect the performance of the biological particle sorting device 200.
  • FIG. 7 is an example of image data in which parameters related to the break-off point and the amplitude (drive value) of the drive voltage supplied to the vibration element are displayed on the same time axis.
  • the horizontal axis is time.
  • the vertical axis on the left side is the value of the parameter regarding the break-off point, and as an example, the value of the coordinate of the height of the break-off point in the fluid stream image.
  • the vertical axis on the right side is the amplitude (drive value) of the drive voltage.
  • the break-off point changes suddenly around 13:30.
  • the amplitude (drive value) of the drive voltage is automatically adjusted in accordance with the variation in the break-off point, and it can therefore be seen that the position control of the break-off point has been executed.
  • the device information data displayed in the image data is not limited to the data shown in FIG.
  • the image data of FIG. 7 may be further combined with other device information data and displayed.
  • Such image data is used, for example, to analyze the correlation between the break-off point variation factor, the parameter variation indicating the variation factor, and the tracking status of the automatic adjustment of the drive voltage of the vibrating element. can be used. Therefore, the above image data can contribute to more efficient analysis of the true variation factors of the break-off point. In this way, the image data generated using the device information data can be utilized to analyze factors that may affect the performance of the biological particle sorting device 200.
  • FIG. 8 is an example of image data in which parameters related to factors that may affect the state of droplets and data related to the operating status of the biological particle sorting device 200 are displayed on the same time axis.
  • the parameter related to the factor that can affect the droplets shown in FIG. 8 is the temperature inside the biological particle sorting device 200.
  • the horizontal axis is time
  • the vertical axis is the temperature.
  • the three shaded areas in FIG. 8 indicate the operating status of the biological particle sorting device 200. Specifically, the three shaded areas indicate, from the left, that automatic adjustment is in progress before starting bioparticle collection, that bioparticle collection is in progress, and that cleaning is in progress. There is. Referring to FIG.
  • Image data such as that shown in FIG. 8, which displays the operating status of the biological particle sorting device 200 along with parameters related to factors that may affect droplets on the same time axis, is, for example, the operating status of the biological particle sorting device 200. It can be used to analyze the correlation between and parameters. Therefore, the above-mentioned image data can contribute to more efficiently determining which parameter is associated with a change in the operating status of the biological particle sorting device 200. For example, when an error occurs in the biological particle sorting device 200, by checking image data that displays the operating status of the biological particle sorting device 200 at the time of the error occurrence and various parameters on the same time axis, The cause of an error occurrence can be determined more efficiently. In this way, image data generated using device information data can be utilized to more efficiently investigate the cause when an error occurs.
  • the operation of the information processing device generating notification information and notifying the client terminal will be mainly explained.
  • the user terminal 500 and the supporter terminal 700 are examples of client terminals in the present technology, as described above.
  • FIG. 9 is a flowchart illustrating an example of the process of notifying notification information to a client terminal.
  • the processing unit 410 of the management device 400 or the processing unit 610 of the customer support server 600 obtains log information and/or error information obtained from the biological particle sorting device 200 (step S201).
  • notification information is generated based on the log information and/or error information (step S202), and the notification information is notified to the user terminal 500 and the supporter terminal 700 (step S203).
  • the notification information may include, for example, at least one of information regarding auto-calibration completion, analysis completion, fractionation completion, warning, and error.
  • the information regarding the completion of auto-calibration may be, for example, information indicating that the automatic adjustment of the vibration element executed by the control unit 8 of the biological particle sorting device 200 has been completed.
  • the information regarding the warning may be, for example, information regarding an event other than an error that requires notification.
  • the information regarding the warning may be information that prompts to replenish the sheath liquid in the sheath tank because the sheath tank is empty.
  • the notification information to be notified to the user terminal 500 may be generated in the processing unit 410 of the management device 400, as an example.
  • the storage unit 440 of the management device 400 may store a template used to generate notification information and email address information when the notification information is sent by email. Thereby, the user (the user of the bioparticle sorting device 200) can grasp the state of the bioparticle sorting device 200 even if he is not near the bioparticle sorting device 200. Note that whether or not to receive the notification information may be settable in the user terminal 500.
  • the notification information to be notified to the supporter terminal 700 may be generated in the processing unit 610 of the customer support server 600, as an example.
  • the storage unit 640 of the customer support server 600 may store a template used to generate notification information and, if the notification information is sent by email, email address information.
  • the supporter terminal 700 is installed at the base of a service provider that remotely checks the status of the biological particle sorting device 200 when a trouble occurs in the biological particle sorting device 200. By receiving the notification information, the service provider can quickly grasp the status of the biological particle sorting device 200, and can therefore respond quickly when trouble occurs. Note that whether or not to receive the notification information may be settable in the supporter terminal 700.
  • a modification of the information processing system 1 will be described.
  • the information processing apparatus will be described below using the customer support server 600 as an example.
  • the configuration and operation of the customer support server 600 described below may be realized in the management device 400. Further, the same configuration and operation may be realized in both the customer support server 600 and the management device 400.
  • the processing unit 610 of the customer support server 600 may be configured to predict errors based on the device information data or the image data.
  • the processing unit 610 may analyze device information data or image data based on a specific threshold value or based on statistical processing to predict errors. Thereby, before an error occurs in the bioparticle sorting device 200, information regarding error prediction can be notified to the user, and the device can be controlled based on the error prediction.
  • FIG. 10 is a flowchart showing another example of processing in the customer support server 600.
  • the storage unit 640 of the customer support server 600 may store device information data and error information acquired from the biological particle sorting device 200 (step S301).
  • the processing unit 610 of the customer support server 600 generates a trained model by performing machine learning using teacher data that associates device information data and error information (steps S302 and S303), and The system may be configured to predict errors when device information data is input using a completed model (step S304).
  • FIG. 11 is a flowchart showing another example of processing in the customer support server 600.
  • the storage unit 640 of the customer support server 600 may store image data and error information acquired from the biological particle sorting device 200 (step S401).
  • the processing unit 610 of the customer support server 600 generates a trained model by performing machine learning using teacher data that associates image data and error information (steps S402 and S403), and The model may be configured to predict errors when image data is input (step S404).
  • the biological particle sorting device 200 may perform sorting abort processing. Alternatively, a process may be executed to notify the user terminal 500 and the supporter terminal 700 of a warning that an error is predicted to occur.
  • the storage unit 640 of the customer port server 600 links the information acquired from the biological particle sorting device 200 as time series data with information that uniquely identifies the biological particle sorting device 200 (for example, device ID). You may memorize it.
  • the processing unit 610 of the customer support server 600 is configured to determine the state of the biological particle sorting device 200 based on past information stored in the storage unit 640 and to present preferred settings for the device to the user. It's okay.
  • the information processing method includes a step in which a biological particle analyzer (for example, a biological particle sorting device) controls a vibrating element to form droplets containing biological particles, and a step in which the information processing device controls a vibrating element to form droplets containing biological particles. generating image data using the obtained device information data.
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of droplets, and data related to the operating status of the biological particle analyzer.
  • the information processing method according to the present technology includes, for example, the above-mentioned 1. (In particular, it may be performed as described in 1-4. above). In addition, the information processing method described in 1. (In particular, it may be executed by the information processing system described in 1-1. to 1-3. above). In this way, above 1.
  • the matters explained in 2 also apply to the information processing method according to the present technology.
  • the information processing device includes a processing unit that generates image data using device information data acquired from a bioparticle analyzer (for example, a bioparticle sorting device).
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of droplets, and data related to the operating status of the biological particle analyzer.
  • the information processing device is, for example, the above-mentioned 1. (In particular, it may operate as described in 1-4. above). Further, the information processing device described in 1. (In particular, it may have the configuration described in 1-1. to 1-2. above). In this way, above 1.
  • the matters described in 2 also apply to the information processing device according to the present technology.
  • the present technology also provides a program for causing an information processing device to execute an information processing method.
  • the information processing method includes a step of generating image data using device information data acquired from a biological particle analyzer.
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of droplets, and data related to the operating status of the biological particle analyzer.
  • a program according to the present technology is, for example, 1. above. (In particular, it may be a program for operating the information processing device as described in 1-4.). Further, the information processing device described in 1. (In particular, it may have the configuration described in 1-1. to 1-2. above). In this way, above 1.
  • the matters explained in 2 also apply to programs according to the present technology.
  • Non-transitory computer-readable media include various types of tangible storage media.
  • Examples of non-transitory computer-readable media are magnetic recording media (e.g., flexible disks, magnetic tape, and hard disk drives), magneto-optical recording media (e.g., magneto-optical disks), CD-ROMs, CD-Rs, CD-Rs. /W, including semiconductor memory (e.g., mask ROM, programmable ROM (PROM), erasable PROM (EPROM), flash ROM, and RAM).
  • the program may be supplied to the information processing device by various types of temporary computer readable media. Examples of transitory computer-readable media include electrical signals, optical signals, and electromagnetic waves.
  • the temporary computer-readable medium can supply the program to the information processing device via a wired communication path such as an electric wire or an optical fiber, or a wireless communication path.
  • the present technology can also have the following configuration.
  • the biological particle analyzer includes a control unit that controls a vibration element to form droplets containing biological particles
  • the information processing device includes a processing unit that generates image data using device information data acquired from the biological particle analysis device,
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer.
  • Information processing system [2] The information processing system according to [1], wherein the parameters related to adjustment of the vibrating element include parameters acquired from a fluid stream image and a frequency and/or amplitude of a drive voltage supplied to the vibrating element.
  • the parameters obtained from the fluid stream image include parameters relating to the break-off point where the flux separates into droplets, parameters relating to the position of satellite droplets, and relating to the width and position of waists in the flux.
  • [4] [1] to [3], wherein the parameters related to factors that can affect the droplet state include at least one selected from temperature, pressure for fluid control, and power of light irradiated to the biological particles.
  • the data regarding the operating status of the bioparticle analyzer includes data indicating that the bioparticle analyzer is in the process of automatic adjustment before starting bioparticle collection, and data indicating that the bioparticle analyzer is in the process of bioparticle collection. and data indicating that the bioparticle analyzer is being cleaned.
  • the information processing system according to any one of [1] to [5], wherein the image data is image data in which two or more pieces of the device information data are displayed on the same time axis.
  • the device information data is a parameter obtained from a fluid stream image and a frequency and/or amplitude of a drive voltage supplied to the vibration element,
  • the information processing system according to any one of [1] to [6], wherein the image data is image data in which the device information data is displayed on the same time axis.
  • the device information data includes parameters related to factors that may affect the droplet state and data related to the operating status of the biological particle analyzer,
  • the information processing system according to any one of [1] to [7], wherein the image data is image data in which the device information data is displayed on the same time axis.
  • the information processing system further includes a client terminal, Any one of [1] to [8], wherein the processing unit generates notification information based on log information and/or error information acquired from the biological particle analyzer, and notifies the client terminal of the notification information.
  • the notification information includes at least one of information regarding auto-calibration completion, analysis completion, separation completion, warning, and error.
  • the processing unit predicts an error based on the device information data or the image data.
  • the information processing device further includes a storage unit that stores the device information data and error information acquired from the biological particle analyzer. system.
  • the processing unit generates a learned model by performing machine learning using teacher data in which the device information data and the error information are associated with each other, and the device information data is input using the learned model.
  • the information processing system according to [12] which predicts an error when an error occurs.
  • the information processing device further includes a storage unit that stores the image data and error information acquired from the biological particle analyzer. .
  • the processing unit When the processing unit generates a trained model by performing machine learning using teacher data that associates the image data and the error information, and image data is input using the trained model.
  • the information processing system according to [14], which predicts errors.
  • [16] a step in which the biological particle analyzer controls a vibrating element to form droplets containing biological particles; an information processing device generating image data using device information data acquired from the biological particle analyzer, The device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer.
  • Information processing method a step in which the biological particle analyzer controls a vibrating element to form droplets containing biological particles; an information processing device generating image data using device information data acquired from the biological particle analyzer, The device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer
  • a processing unit that generates image data using device information data acquired from a biological particle analyzer,
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer.
  • Information processing device [18] A step of generating image data using device information data obtained from a biological particle analyzer,
  • the device information data is at least one data selected from parameters related to adjustment of the vibrating element, parameters related to factors that may affect the state of the droplet, and data related to the operating status of the biological particle analyzer.

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Abstract

Le but de la présente technologie est de fournir un système de traitement d'informations apte à présenter, d'une manière facile à comprendre, des informations sur un facteur pouvant affecter les performances d'un dispositif d'analyse de particules biologiques.　La présente technologie concerne un système de traitement d'informations comprenant un dispositif d'analyse de particules biologiques et un dispositif de traitement d'informations, le dispositif d'analyse de particules biologiques comprenant une unité de commande qui commande un élément vibrant afin de former des gouttelettes contenant des particules biologiques, et le dispositif de traitement d'informations comprend une unité de traitement qui génère des données d'image à l'aide de données d'informations de dispositif acquises en provenance du dispositif d'analyse de particules biologiques. Les données d'informations de dispositif constituent au moins un élément de données choisi parmi des paramètres liés au réglage de l'élément vibrant, des paramètres associés à des facteurs pouvant affecter l'état des gouttelettes, et des données relatives à l'état de fonctionnement du dispositif d'analyse de particules biologiques.
PCT/JP2023/017247 2022-06-10 2023-05-08 Système de traitement d'informations, procédé de traitement d'informations, dispositif de traitement d'informations et programme WO2023238564A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010190909A (ja) * 2003-08-13 2010-09-02 Luminex Corp フロー・サイトメータ・タイプ測定システムの１つまたは複数のパラメータを制御するための方法
JP2018151319A (ja) * 2017-03-14 2018-09-27 ソニー株式会社 マイクロチップ、及び微小粒子測定装置
JP2021534380A (ja) * 2018-08-10 2021-12-09 サイテック バイオサイエンスィズ インコーポレイテッド 自己監視及び自己検証を行うスマートフローサイトメーター

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010190909A (ja) * 2003-08-13 2010-09-02 Luminex Corp フロー・サイトメータ・タイプ測定システムの１つまたは複数のパラメータを制御するための方法
JP2018151319A (ja) * 2017-03-14 2018-09-27 ソニー株式会社 マイクロチップ、及び微小粒子測定装置
JP2021534380A (ja) * 2018-08-10 2021-12-09 サイテック バイオサイエンスィズ インコーポレイテッド 自己監視及び自己検証を行うスマートフローサイトメーター

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