Information processing device, information processing method, and program

Abstract

The present invention suppresses accuracy degradation that is caused by optical filters. An information processing device according to an embodiment comprises: an irradiation unit (101) that irradiates a sample with light; an optical system (11a, 11b, 11c) that splits fluorescent light from the sample using two or more optical filters; a plurality of photodetectors (12a, 12b) that detect intensities of respective rays of the fluorescent light split by the optical system; and a processing unit (103) that analyzes the sample on the basis of the intensity of the ray of the fluorescent light detected by each of the photodetectors. The processing unit determines whether or not setting conditions of the two or more optical filters are appropriate on the basis of first optical intensities of rays obtained by irradiating two or more types of test samples with light from the irradiation unit and passing the light through the optical system, the first optical intensities being detected by the respective photodetectors for each test sample.

Description

Technical Field

[0001] The present disclosure relates to an information processing apparatus, an information processing method, and a program.

Background Art

[0002] Conventionally, as a method for analyzing (or analyzing; in the present disclosure, analysis includes analysis) proteins of biological-related microparticles such as cells, microorganisms, and liposomes, there is flow cytometry. The apparatus used for this flow cytometry is called a flow cytometer (FCM). In a flow cytometer, laser light of a specific wavelength is irradiated onto microparticles flowing in a row in a flow path, and light such as fluorescence, forward scattered light, and side scattered light emitted from each microparticle is converted into an electrical signal by a photodetector and digitized, and statistical analysis is performed on the result, whereby the type, size, structure, etc. of each microparticle are determined.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] A flow cytometer having a plurality of detection systems usually includes a plurality of optical filters. Here, in the case of a flow cytometer capable of changing the wavelength band, it is necessary to manually set the optical filters in a predetermined arrangement. However, at that time, if there are human errors or poor mounting in the setting of the optical filters, or if the optical filters are damaged or deteriorated, etc., there will be a problem that accurate analysis or analysis cannot be performed.

[0005] Therefore, this disclosure proposes an information processing apparatus, an information processing method, and a program that can suppress the reduction in accuracy caused by optical filters. [Means for solving the problem]

[0006] To solve the above problems, an information processing device according to the present disclosure comprises an irradiation unit that irradiates a sample with light, an optical system that separates fluorescence from the sample using two or more optical filters, a plurality of photodetectors that detect the intensity of each of the fluorescence separated by the optical system, and a processing unit that analyzes the sample based on the intensity of the fluorescence detected by each of the photodetectors, wherein the processing unit determines whether the setting state of the two or more optical filters is appropriate based on the first light intensity for each of the test samples detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto two or more test samples. [Brief explanation of the drawing]

[0007] [Figure 1] This is a schematic diagram showing an example of the configuration of a biological sample analyzer, which is an example of an information processing system according to the first embodiment of this disclosure. [Figure 2] This is a schematic diagram showing a schematic configuration example of an optical system according to the first embodiment of this disclosure. [Figure 3] Figure 2 shows a graph illustrating two-dimensional plots of forward and side-scattered light scattered by AlignCheck beads and SortCal beads, respectively, detected by the optical system shown as an example. [Figure 4] Figure 2 shows a graph illustrating the fluorescence spectrum of AlignCheck beads detected by the optical system shown in the example. [Figure 5] Figure 2 shows a graph illustrating the fluorescence spectrum of SortCal beads detected by the optical system shown in the example. [Figure 6] This figure shows an example of the level ratio obtained from the setup beads when the optical filter is correctly set up for the optical system illustrated in Figure 2. [Figure 7] This flowchart shows an example of a verification flow relating to the first example of the first embodiment of the present disclosure. [Figure 8] This is a schematic diagram showing an example of an optical system in the detection unit of a biological sample analyzer used in verification according to the first embodiment of this disclosure. [Figure 9] This figure shows the level ratio and CV obtained when the filter setting is normal under the measurement conditions shown in Figure 8. [Figure 10] This figure shows an example of the reference level ratio and CV used in the verification according to the first embodiment of this disclosure. [Figure 11] This figure shows an example of the level ratio and CV obtained in case 1 of the verification according to the first embodiment of this disclosure. [Figure 12] This figure shows an example of the level ratio and CV obtained in case 2 of the verification according to the first embodiment of this disclosure. [Figure 13] This figure shows an example of the level ratio and CV obtained in case 3 of the verification according to the first embodiment of this disclosure. [Figure 14] This figure shows an example of a list of optical filter patterns provided to the user as selection candidates in a second embodiment of this disclosure. [Figure 15] This figure shows an example of an optical filter and socket with a QR code (registered trademark) attached according to a second embodiment of this disclosure. [Figure 16] This figure shows an example of a notification screen that is displayed to a user according to the third embodiment of this disclosure. [Figure 17] This is a hardware configuration diagram showing an example of a computer that implements the functions of the information processing device related to this disclosure. [Modes for carrying out the invention]

[0008] Embodiments of the present disclosure will be described in detail below with reference to the drawings. In the following embodiments, the same parts will be denoted by the same reference numerals to avoid redundant descriptions.

[0009] The present disclosure will be described in accordance with the item order shown below. 0. Introduction 1. First Embodiment 1.1 Example of System Configuration of Biological Sample Analyzer 1.2 Example of Schematic Configuration of Optical System 1.3 Examples of Test Samples 1.4 Schematic Example of Verification Procedure 1.5 Examples of Reference Level Ratios 1.6 Method for Verifying the Setting State of Mounted Optical Filters 1.6.1 Example of Verification Flow 1.6.1.1 First Example 1.6.1.2 Second Example 1.7 Specific Examples of Verification Results 1.7.1 Case 1 1.7.2 Case 2 1.7.3 Case 3 1.8 Summary 2. Second Embodiment 2.1 Overall Flow 3. Third Embodiment 4. Variants 5. Hardware Configuration

[0010] 0. Introduction Flow cytometers have detection optics. Usually, fluorescence emitted from a sample is wavelength - demultiplexed or wavelength - limited by an optical filter arranged on the optical path through which it propagates, and is finally detected by an optoelectronic device such as a photomultiplier tube (PMT) or a photodiode (PD).

[0011] Here, when there are multiple detection systems in the device, multiple optical filters are also required. In the case of a specification that can change the wavelength band of the fluorescence to be analyzed, it is necessary to remove, insert, or replace the optical filter from the outside. However, in the process of setting the optical filter, there is a possibility of misapplying the optical filter due to human error, and there is also a possibility of improper mounting such as the optical filter not being correctly mounted.

[0012] Thus, if the optical filter is not set up correctly, the fluorescence emitted from the sample cannot be measured accurately, making accurate analysis difficult. Furthermore, if the optical filter is damaged or its optical properties have changed due to aging or other factors, the fluorescence emitted from the sample cannot be measured accurately, which can also make accurate analysis difficult.

[0013] One way to verify whether optical filters are set up in the correct position is to attach an RFID (Radio Frequency Identifier) ​​to each optical filter and detect which filter is located where. However, this method has the problem that if the detection accuracy decreases due to reasons such as the optical filter not being inserted in the correct position or the optical filter's characteristics degrading, it is impossible to identify the cause.

[0014] Therefore, in the following embodiment, we propose an information processing system, information processing method, and program that can suppress a decrease in detection accuracy caused by optical filters, such as setting errors in optical filters or damage or deterioration of optical filters, thereby suppressing a decrease in the accuracy of analysis and interpretation.

[0015] Specifically, in the following embodiment, the setting state of the optical filter is detected, and based on the obtained setting state, it is determined whether the optical filter is set correctly, and whether the characteristics of the optical filter have changed due to damage, contamination, aging, etc. The setting state of the optical filter here may include whether the optical filter is set in the correct position, whether the optical filter is inserted to the correct position, whether the orientation of the optical filter is correct, and whether the characteristics of the optical filter have changed due to damage, contamination, aging, etc.

[0016] 1. First Embodiment Hereinafter, an information processing system, information processing method, and program according to the first embodiment of this disclosure will be described in detail with reference to the drawings.

[0017] 1.1 Example System Configuration of a Biological Sample Analysis Device Figure 1 shows an example configuration of a biological sample analyzer, which is an example of an information processing system according to this embodiment. The biological sample analyzer 100 shown in Figure 1 includes a light irradiation unit 101 that irradiates light onto a biological sample S flowing through a flow path C, a detection unit 102 that detects the light generated by the irradiation, and an information processing unit (also simply called a processing unit) 103 that processes information related to the light detected by the detection unit 102. Examples of the biological sample analyzer 100 include, for example, a flow cytometer and an imaging flow cytometer. The biological sample analyzer 100 may also include a sorting unit 104 that sorts specific biological particles P within the biological sample S. An example of the biological sample analyzer 100 including the sorting unit 104 is, for example, a cell sorter.

[0018] (Biological sample) The biological sample S may be a liquid sample containing biological particles P. These biological particles P are, for example, cells or non-cellular biological particles. The cells may be living cells, and more specifically, blood cells such as red blood cells and white blood cells, and germ cells such as sperm and fertilized eggs. The cells may be directly collected from a sample such as whole blood, or they may be cultured cells obtained after culturing. Examples of non-cellular biological particles include extracellular vesicles, particularly exosomes and microvesicles. The biological particles P may be labeled with one or more labeling substances (for example, dyes (particularly fluorescent dyes) and fluorescent dye-labeled antibodies). The biological sample analyzer 100 of this disclosure may also analyze particles other than biological particles, and beads, etc., may be analyzed for calibration purposes.

[0019] (Flow channel) The channel C may be configured to allow a biological sample S to flow, particularly in such a way that the biological particles P contained in the biological sample S are arranged in a substantially straight line. The channel structure including channel C may be designed to form a laminar flow, and in particular, to form a laminar flow in which the flow of the biological sample S (sample flow) is surrounded by the flow of sheath fluid. The design of the channel structure may be appropriately selected by those skilled in the art, and known designs may be adopted. The channel C may be formed in a flow channel structure such as a microchip (a chip with a channel on the order of micrometers) or a flow cell. The width of the channel C is 1 mm (millimeter) or less, and in particular may be 10 μm (micrometers) or more and 1 mm or less. The channel C and the channel structure including it may be formed from materials such as plastic or glass.

[0020] The apparatus of this disclosure may be configured such that light from the light irradiation unit 101 irradiates a biological sample S, particularly biological particles P, flowing through the channel C. The apparatus of this disclosure may be configured such that the light irradiation point (interrogation point) for the biological sample S is located within the channel structure in which the channel C is formed, or it may be configured such that the light irradiation point is located outside the channel structure. An example of the former is a configuration in which the light irradiates the channel C in a microchip or flow cell. In the latter case, the light irradiates the biological particles P after they have exited the channel structure (particularly its nozzle), for example, a Jet-in-Air type flow cytometer.

[0021] (Light irradiation area) The light irradiation unit 101 includes a light source unit that emits light and a light guide optical system that guides the light to the channel C. The light source unit includes one or more light sources. The type of light source may be, for example, a laser light source or an LED (Light Emitting Diode). The wavelength of the light emitted from each light source may be any of the wavelengths of ultraviolet light, visible light, or infrared light. The light guide optical system includes optical components such as a beam splitter group, a mirror group, or an optical fiber. The light guide optical system may also include a lens group for focusing the light, for example, an objective lens. There may be one or more light irradiation points on the biological sample S. The light irradiation unit 101 may be configured to focus light irradiated from one or more different light sources onto a single irradiation point.

[0022] (Detection unit) The detection unit 102 includes at least one photodetector that detects light generated by light irradiation of particles by the light irradiation unit 101. The light to be detected is, for example, fluorescence or scattered light (e.g., one or more of forward scattered light, back scattered light, and side scattered light), transmitted light, or reflected light. Each photodetector includes one or more light-receiving elements, for example, a light-receiving element array. Each photodetector may include one or more PMTs (photomultiplier tubes) and / or photodiodes such as APDs (Avalanche Photodiodes) and MPPCs (Multi-Pixel Photon Counters) as light-receiving elements. The photodetector may include, for example, a PMT array in which multiple PMTs are arranged in a one-dimensional direction. The detection unit 102 may also include an image sensor such as a CCD (Charge Coupled Device) or CMOS (Complementary Metal-Oxide-Semiconductor). The detection unit 102 can acquire biological particle information regarding biological particles P using the image sensor.

[0023] As described above, bioparticle information may include at least one of the following: a bioparticle image of the bioparticle, bioparticle feature quantities, bioparticle attribute information, etc. Furthermore, the bioparticle image of the bioparticle may include, for example, bright-field images, dark-field images, fluorescence images, etc.

[0024] The detection unit 102 includes a detection optical system that directs light of a predetermined detection wavelength to a corresponding photodetector. The detection optical system includes a spectroscopic unit such as a prism or diffraction grating, or a wavelength separation unit such as a dichroic mirror or optical filter. The detection optical system may be configured to spectrally analyze light from biological particles P, for example, and to detect light in different wavelength ranges using multiple photodetectors, more than the number of fluorescent dyes. A flow cytometer including such a detection optical system is called a spectral flow cytometer. Alternatively, the detection optical system may be configured to separate light corresponding to the fluorescence wavelength range of a fluorescent dye from light from biological particles P, for example, and to detect the separated light using a corresponding photodetector.

[0025] Furthermore, the detection unit 102 may include a signal processing unit that converts the electrical signal obtained by the photodetector into a digital signal. The signal processing unit may include an A / D converter as the device that performs the conversion. The digital signal obtained by the conversion by the signal processing unit may be transmitted to the information processing unit 103. The digital signal may be treated by the information processing unit 103 as data related to light (hereinafter also referred to as "light data"). The light data may be, for example, light data including fluorescence data. More specifically, the light data may be light intensity data, and the light intensity may be light intensity data of light including fluorescence (which may include feature quantities such as Area, Height, and Width).

[0026] (Information Processing Department) The information processing unit 103 includes, for example, a processing unit that performs processing of various data (e.g., optical data) and a storage unit that stores various data. When the processing unit obtains optical data corresponding to a fluorescent dye from the detection unit 102, it can perform fluorescence leakage correction (compensation processing) on ​​the optical intensity data. In the case of a spectral flow cytometer, the processing unit also performs fluorescence separation processing on the optical data to obtain optical intensity data corresponding to the fluorescent dye.

[0027] The fluorescence separation process may be performed, for example, according to the unmixing method described in Japanese Patent Application Publication No. 2011-232259. If the detection unit 102 includes an image sensor, the processing unit may acquire morphological information of the biological particle P based on the image acquired by the image sensor. The storage unit may be configured to store the acquired optical data. The storage unit may further be configured to store spectral reference data used in the unmixing process.

[0028] If the biological sample analyzer 100 includes a sorting unit 104 described later, the information processing unit 103 may determine whether to sort biological particles P based on optical data and / or morphological information. Based on the result of this determination, the information processing unit 103 controls the sorting unit 104, and the sorting unit 104 may sort the biological particles P.

[0029] The information processing unit 103 may be configured to output various types of data (e.g., optical data and images). For example, the information processing unit 103 may output various types of data (e.g., two-dimensional plots, spectral plots, etc.) generated based on the optical data. The information processing unit 103 may also be configured to accept input of various types of data, for example, by accepting gating processing on a plot by a user. The information processing unit 103 may include an output unit (e.g., a display) or an input unit (e.g., a keyboard) for executing such output or input.

[0030] The information processing unit 103 may be configured as a general-purpose computer, for example, as an information processing device equipped with a CPU (Central Processing Unit), RAM (Random Access Memory), and ROM (Read-only memory). The information processing unit 103 may be contained within the housing that houses the light irradiation unit 101 and the detection unit 102, or it may be located outside of that housing. Furthermore, various processing or functions performed by the information processing unit 103 may be implemented by a server computer or cloud connected via a network.

[0031] (Preparative separation section) The sorting unit 104 can sort biological particles P according to, for example, the determination result by the information processing unit 103. The sorting method may involve generating droplets containing biological particles P by vibration, applying an electric charge to the droplets to be sorted, and controlling the direction of movement of the droplets with electrodes. The sorting method may also involve controlling the direction of movement of biological particles P within a flow channel structure. The flow channel structure may be provided with, for example, a control mechanism using pressure (injection or suction) or electric charge. An example of such a flow channel structure is a chip (for example, the chip described in Japanese Patent Application Publication No. 2020-76736) having a flow channel structure in which a flow channel C branches downstream into a recovery flow channel and a waste liquid flow channel, and specific biological particles P are recovered into the recovery flow channel.

[0032] 1.2 Example of a schematic configuration of an optical system Next, a schematic example of the optical system configuration in the biological sample analyzer 100 according to this embodiment will be described. Figure 2 is a schematic diagram showing a schematic example of the optical system configuration according to this embodiment. However, the optical system shown in Figure 2 is the simplest possible configuration, and the optical system mounted on the biological sample analyzer 100 may be more complex.

[0033] As shown in Figure 2, the detection unit 102 of the biological sample analyzer 100 includes, as an optical system, an optical filter (hereinafter also simply called a filter) 11c that separates light emitted or scattered from biological particles P when light is irradiated, a filter 11a that transmits light of a specific wavelength band from the light that has passed through the filter 11c, a photodetector 12a that detects the light that has passed through the filter 11a, a filter 11b that transmits light of a specific wavelength band from the light reflected by the filter 11c, and a photodetector 12b that detects the light that has passed through the filter 11b.

[0034] Filter 11c may be an optical filter that transmits light in a specific wavelength band and reflects light in other wavelength bands, such as a dichroic mirror. Filters 11a and 11b may be optical filters that transmit light in a specific wavelength band and reflect light in other wavelength bands.

[0035] The photodetector 12a is a photodetector with adjustable gain, such as a photomultiplier tube, and detects the intensity of light transmitted through filters 11c and 11a. Similarly, the photodetector 12b is a photodetector, such as a photomultiplier tube, and detects the intensity of light reflected by filter 11c and transmitted through filter 11b.

[0036] 1.3 Examples of test samples In this embodiment, two or more test samples with different characteristics may be used to detect the setting state of the optical filter. In this embodiment, a flow cytometer is given as an example of an information processing device (biological sample analyzer), so check beads having a size and shape similar to the minute particles such as cells that the flow cytometer is testing can be used as test samples. Therefore, in this embodiment, an example is given in which AlignCheck beads and SortCal beads are used as setup beads.

[0037] Figures 3 to 5 show the characteristics of AlignCheck beads and SortCal beads detected by the optical system exemplified in Figure 2. Figure 3 is a graph showing two-dimensional plots of forward scattered light and side scattered light scattered by AlignCheck beads and SortCal beads, respectively, detected by the optical system exemplified in Figure 2. Figure 4 is a graph showing the fluorescence spectrum of AlignCheck beads detected by the optical system exemplified in Figure 2, and Figure 5 is a graph showing the fluorescence spectrum of SortCal beads detected by the optical system exemplified in Figure 2. In Figure 3, the horizontal axis represents the light intensity of forward scattered light, and the vertical axis represents the light intensity of side scattered light. In Figures 4 and 5, the horizontal axis represents the channels when the wavelength band from 400 nm to 800 nm is divided into 32 channels, and the vertical axis represents the light intensity of fluorescence detected for each channel.

[0038] AlignCheck beads and SortCal beads differ in size. Therefore, by using a scattering plot as shown in Figure 3, it is possible to separate their respective fluorescence signals. That is, as shown in Figure 3, the scattering plots for AlignCheck beads and SortCal beads are distributed at different positions in the 2D graph. By applying a gate to each distribution, it is possible to separate the events obtained from AlignCheck beads from the events obtained from SortCal beads. This makes it possible to separately extract the fluorescence signal obtained by detecting the fluorescence emitted from AlignCheck beads and the fluorescence signal obtained by detecting the fluorescence emitted from SortCal beads.

[0039] In this explanation, "event" may refer to a dataset containing the light intensity signals (also called fluorescence signals and detection signals) of fluorescence, forward scattered light, and side scattered light detected by each bead. Furthermore, timestamps or identification IDs may be used to associate these signals.

[0040] Furthermore, as shown in Figures 4 and 5, AlignCheck beads and SortCal beads exhibit high fluorescence characteristics in the 400 nm to 800 nm range. Moreover, these two beads have a wide fluorescence wavelength band, different wavelength spectra, and different fluorescence light intensities (hereinafter simply referred to as levels). For these reasons, AlignCheck beads and SortCal beads are suitable as test samples. Therefore, in this embodiment, these beads are used to verify whether the optical filter settings are appropriate by examining the level ratio of the fluorescence signals in each wavelength band (corresponding to one or more channels). However, the test samples are not limited to AlignCheck beads and SortCal beads; various samples capable of separating observed fluorescence with sufficient accuracy can be used. The level ratio to be examined may be the relative level ratio of the fluorescence signals in each wavelength band, or the absolute level ratio. When using the absolute level ratio, it is also possible to use the absolute level of each fluorescence signal to determine whether the optical filter settings are appropriate.

[0041] 1.4 Outline example of verification procedure In this embodiment, the verification procedure is as follows: For example, in the optical system illustrated in Figure 2, first, the gain of the photodetector 12a is adjusted so that the level of the fluorescence signal obtained from the SortCal beads reaches a specified value. For example, if a photomultiplier tube is used as the photodetector 12a, the HV (High Voltage) applied to the photomultiplier tube is adjusted so that the level of the fluorescence signal obtained from the SortCal beads reaches a specified value.

[0042] In this explanation, "level" refers to a value indicating the light intensity of fluorescence, and may be, for example, the amplitude of the fluorescence signal obtained by detecting fluorescence in a certain channel (hereinafter also referred to as Height), or the average of the Heights of the fluorescence signals detected in two or more consecutive channels.

[0043] Next, in this embodiment, the level ratio of the AlignCheck beads and SortCal beads detected by the photodetector 12a is calculated, and the calculated level ratio is evaluated to determine the setting status of the filters 11a and 11c, that is, whether the filters 11a and 11c are set correctly, whether the characteristics of the filters 11a and 11c have changed, etc.

[0044] Similarly, with respect to the photodetector 12b, the setting status of filters 11b and 11c is determined by evaluating the level ratio from the gain adjustment.

[0045] 1.5 Examples of level ratios to use as a reference The evaluation of the level ratio may be performed based on a comparison between a pre-prepared reference level ratio (hereinafter referred to as the reference level ratio) and the level ratio obtained from actual measurements. In this case, the reference level ratio used as a basis for verifying whether the setting state of the optical filter is appropriate may be, for example, the level ratio obtained using a test sample with the optical filter correctly set for the optical system of the biological sample analyzer 100. This reference level ratio may be, for example, obtained in advance by the provider or maintenance management of the biological sample analyzer 100 and set in the actual device, or it may be obtained and set by the user.

[0046] Figure 6 shows an example of the level ratio obtained when AlignCheck beads and SortCal beads are used as test samples and filters 11a to 11c are correctly set for the optical system exemplified in Figure 2. In this explanation, for example, the case in which the wavelength band from 500 nm to 800 nm is divided into two channels, with the shorter wavelength side detected in channel Ch1 and the longer wavelength side detected in channel Ch2 is used as an example.

[0047] As shown in Figure 6, in this example, for instance, the height (level) of the SortCal bead in the wavelength band of channel Ch1 is 7667, and the height (level) of the AlignCheck bead in the same channel band is 820. Therefore, the reference level ratio for channel Ch1 is calculated to be 9.35. Similarly, the reference level ratio for channel Ch2 is calculated to be 12.48.

[0048] The level ratios obtained in this way are used, for example, to verify whether the settings of the optical filters are appropriate. For example, if the measured level ratio of channel Ch1 is not within a predetermined range based on the reference level ratio for channel Ch1 (=9.35) when filters 11a to 11c are set up for the optical system illustrated in Figure 2, it can be determined that the settings of filters 11a and 11c are not appropriate. Similarly, if the measured level ratio of channel Ch2 is not within a predetermined range based on the reference level ratio for channel Ch2 (=12.48), it can be determined that the settings of filters 11b and 11c are not appropriate.

[0049] 1.6 Method for verifying the setting status of the installed optical filter Next, we will explain in detail how to verify whether the settings of the installed optical filter are appropriate when actually using the biological sample analyzer 100.

[0050] The setting of the optical filter is verified by actually running beads through it and basing the verification on the output obtained. The following example uses a setup bead set that includes AlignCheck and SortCal beads.

[0051] Here, the setup bead composition ratio is AlignCheck beads:SortCal beads = 1:2. In addition, the detection parameters will include the bead level ratio, as well as the coefficient of variation (CV) or robust CV (rCV).

[0052] If the wavelength band obtained changes due to incorrect insertion of the optical filter, the level ratio obtained from each bead will change. If the optical filter is set up incorrectly due to incorrect insertion, the amount of incident light to the photodetector will decrease. As a result, it is thought that the CV and rCV will deteriorate due to shot noise. Therefore, by verifying the CV or rCV in addition to the level ratio of the beads, more accurate verification becomes possible.

[0053] 1.6.1 Example Verification Flow Next, we will describe the verification flow for verifying the setting status of the optical filter. In this embodiment, we will illustrate two verification flows based on whether or not the gain of the photodetector is adjustable.

[0054] 1.6.1.1 Example 1 First, as an example, we will describe a verification flow for a case where the gain of the photodetector can be adjusted. Examples of photodetectors with adjustable gain include photomultiplier tubes.

[0055] Figure 7 is a flowchart showing an example of a verification flow according to the first example of this embodiment. Before executing the verification flow shown in Figure 7, it is assumed that an optical filter corresponding to the sample to be analyzed, different from the setup beads, is set in the optical system of the detection unit 102 of the biological sample analyzer 100.

[0056] As shown in Figure 7, in this verification flow, first, a predetermined number of events (for example, 1000) are acquired (step S101). Specifically, setup beads are flowed through channel C (see Figure 1), and the fluorescence emitted by irradiating the beads flowing through channel C with light from the light irradiation unit 101 is detected. A set of detection signals, including a fluorescence signal, a detection signal for forward scattered light, and a detection signal for side scattered light, is detected as one event. Note that one event may correspond to one bead. The predetermined number may be, for example, a number that can reduce statistical errors to some extent and does not impose an excessive burden as a preparation procedure performed before the actual measurement.

[0057] Next, the information processing unit 103 of the biological sample analyzer 100 calculates the level of the fluorescence signal that is the predetermined number from the top in Height among the events acquired in step S101 (step S102). Here, the predetermined number may be, for example, the 10th number from the top, i.e., if 1000 events are acquired, it may be the 100th number from the highest Height. However, it is not limited to this, and step S102 may be modified in various ways as long as it can identify a level that serves as a guideline for setting an appropriate gain in the detection of the setup beads.

[0058] Next, the information processing unit 103 determines whether or not gain adjustment of the photodetector is necessary based on the level calculated in step S102 (step S103). Specifically, for example, the information processing unit 103 determines whether or not the level calculated in step S102 falls within a predetermined range, and if it does not, it determines that gain adjustment is necessary (YES in step S103). On the other hand, if the level falls within the predetermined range, it determines that gain adjustment is unnecessary (NO in step S103). The predetermined range is, for example, 7 × 10 5 The range may be ±10%. However, it is not limited to this range, and various modifications are permitted as long as they allow for proper detection of the setup beads.

[0059] If gain adjustment is necessary (YES in step S103), the gain of the photodetector is adjusted (step S104) so ​​that the level calculated in step S102 falls within the predetermined range in step S103, and the operation returns to step S101 and onward. For example, if the photodetector is a photomultiplier tube, the HV applied to the photomultiplier tube may be adjusted in step S104.

[0060] If gain adjustment is not required (NO in step S103), a second predetermined number of events (e.g., 10,000) are acquired (step S105). The method for acquiring the events may be the same as in step S101, for example. The second predetermined number may be, for example, a number that can sufficiently reduce statistical errors.

[0061] Next, in the information processing unit 103, a two-dimensional plot of the event (see, for example, Figure 3) is drawn from the detection signals of forward scattered light and side scattered light in the event acquired in step S105. By applying a gate to this two-dimensional plot, the events of the SortCal bead (also called the first bead) and the events of the AlignCheck bead (also called the second bead) are separated and extracted (step S106). Note that the gate applied to the two-dimensional plot may be set manually by the user or automatically by the information processing unit 103.

[0062] Next, the information processing unit 103 calculates the median or average value of the height of the fluorescence signal for each channel for each bead extracted in step S106 (step S107), and then calculates the level ratio of the heights for each channel (step S108). In this example, the denominator used to calculate the level ratio is shown to be the median or average value of the height of the fluorescence signal of the AlignCheck bead (second bead), but it is not limited to this, and may be the median or average value of the height of the fluorescence signal of the SortCal bead (first bead).

[0063] Next, the information processing unit 103 determines whether the calculated level ratio for each channel falls within a predetermined first standard (step S109). The first standard may be, for example, a range set based on the level ratio for each channel that has been acquired in advance (see, for example, Figure 6). In this case, for example, setting the range of the first standard set for each level ratio to be within ±15% of each level ratio makes it possible to more appropriately verify the suitability of the optical filter setting. However, the values ​​are not limited to this, and may be changed in various ways as long as the verification can be performed appropriately.

[0064] If the level ratio for each channel falls within the first standard (YES in step S109), this operation proceeds to step S110. On the other hand, if the level ratio for each channel does not fall within the first standard (NO in step S109), this operation proceeds to step S112.

[0065] In step S110, the information processing unit 103 calculates the channel-specific CV or rCV for each bead extracted in step S106.

[0066] Next, the information processing unit 103 determines whether the calculated CV or rCV for each bead and channel falls within a pre-set second standard (step S111). The second standard may be, for example, a range set based on the previously acquired CV or rCV for each bead and channel. In this case, for example, if the value of CV or rCV is 4% or less, the range of the second standard may be ±2% from that value. On the other hand, if the value of CV or rCV is greater than 4%, the range of the second standard may be ±3% from that value. However, the range is not limited to these values ​​and may be changed in various ways as long as appropriate verification can be performed. In this case, the range of the second standard may be set considering the wavelength range of each channel.

[0067] If the CV or rCV for each bead and each channel falls within the second standard (YES in step S111), this operation ends. On the other hand, if the CV or rCV for each bead and each channel does not fall within the second standard (NO in step S111), this operation proceeds to step S112.

[0068] In step S112, the user is notified to check the setting status of the optical filter or to reset the optical filter. This notification may be provided to the user, for example, via a display or speaker (not shown) provided by the information processing unit 103, or it may be provided to the user's mobile terminal in the form of email or message. After step S112, this operation may end, or the system may return to step S101 and perform subsequent operations. If this operation ends, the user may check the setting status of the optical filter or reset the optical filter, and then perform this operation again from the beginning.

[0069] 1.6.1.2 Example 2 The second example will explain the case where the gain of the photodetector cannot be adjusted. Examples of photodetectors where the gain cannot be adjusted include photodiodes, APDs (Avalanche Photodiodes), and MPPCs (Multi-Pixel Photon Counters).

[0070] In cases where the photodetector gain cannot be adjusted, the verification flow may be structured by omitting the gain adjustment operations from steps S101 to S104 in the verification flow for the first example described with reference to Figure 7, and proceeding only from step S105 onwards. However, even when using photodiodes, APDs, MPPCs, etc., the verification flow for the first example described above may be performed if gain adjustment is possible. Furthermore, the operations from step S105 onwards may be the same as those described with reference to Figure 7, so a detailed explanation is omitted here.

[0071] 1.7 Specific Examples of Verification Results Next, we will explain some specific examples of the verification results obtained when actually performing verification using the verification flow according to this embodiment.

[0072] In this verification, the optical system shown in Figure 8 was used. Figure 8 is a schematic diagram showing an example of the optical system in the detection unit 102 of the biological sample analyzer 100 used in this verification. However, in Figure 8, the photodetectors corresponding to each channel are omitted.

[0073] In Figure 8, filter 11-1 is a long-pass filter (LP) that transmits light L2 with wavelength components of 639 nm or greater and reflects light L2 with wavelength components of less than 639 nm, thus splitting the incident light L1 into light L1 and L2.

[0074] Filter 11-2 is a long-pass filter that transmits light L3 with wavelength components of 572 nm or more and reflects light L9 with wavelength components of less than 572 nm, thus splitting the light L2 that has passed through filter 11-1 into light L3 and light L9.

[0075] Filter 11-3 is a bandpass filter with a bandwidth of 50 nm centered at 785 nm, and is placed on the incident surface of the photodetector, which is channel Ch6.

[0076] Filter 11-4 is a long-pass filter that transmits light L5 with wavelength components of 561 nm or more and reflects light L6 with wavelength components of less than 561 nm, and separates the light L4 reflected by filter 11-1 into light L5 and light L6.

[0077] Filter 11-5 is a bandpass filter with a bandwidth of 30 nm centered at 585 nm, and is placed on the incident surface of the photodetector, which is channel Ch3, to limit the wavelength component of the light L5 incident on the photodetector.

[0078] Filter 11-6 is a long-pass filter that transmits light L7 with wavelength components of 487.5 nm or greater and reflects light L8 with wavelength components of less than 487.5 nm, and separates the light L6 reflected by filter 11-4 into light L7 and light L8.

[0079] Filter 11-7 is a bandpass filter with a bandwidth of 50 nm centered at 525 nm, and is placed on the incident surface of the photodetector, which is channel Ch2, to limit the wavelength component of the light L7 incident on the photodetector.

[0080] Filter 11-8 is a bandpass filter with a bandwidth of 50 nm centered at 450 nm.

[0081] Filter 11-9 is a long-pass filter that transmits light L11 with wavelength components of 685 nm or greater and reflects light L10 with wavelength components of less than 685 nm, and separates the light L9 reflected by filter 11-2 into light L10 and light L11.

[0082] Filter 11-10 is a bandpass filter with a bandwidth of 30 nm centered at 665 nm, and is placed on the incident surface of the photodetector, which is channel Ch4, to limit the wavelength component of the light L10 incident on the photodetector.

[0083] Filter 11-11 is a bandpass filter with a bandwidth of 60 nm centered at 720 nm, and is placed on the incident surface of the photodetector, which is channel Ch5, to limit the wavelength component of the light L11 incident on the photodetector.

[0084] Filters 11-12 are bandpass filters with a bandwidth of 178 nm centered at 488 nm, and are placed on the incident surface of a photodetector for detecting backscattered light L12, thereby limiting the light incident on the photodetector to backscattered light L12.

[0085] Filters 11-13 are long-pass filters that transmit light with wavelengths of 600 nm or more and reflect light with wavelengths of less than 600 nm. Filter 11-14 is a band-pass filter with a bandwidth of 60 nm centered at 600 nm. Filter 11-15 is a band-pass filter with a bandwidth of 30 nm centered at 617 nm. Filters 11-13 to 11-15 are assumed to be installed in the detection unit 102 of the biological sample analyzer 100 as spare optical filters.

[0086] Furthermore, in this verification, the light emitted from the light irradiation unit 101 and irradiated onto the beads flowing through channel C was set to 488 nm (corresponding to the wavelength of backscattered light L12), and a setup bead configuration of AlignCheck beads:SortCal beads = 1:2 was used. The 10th percentile height of the fluorescence signal obtained from the SortCal beads was 7 × 10⁻¹⁴. 5 The gain of each photodetector was adjusted to fall within a range of ±10%. In the following explanation, AlignCheck beads will be abbreviated as ACB and SortCal beads as SCB. The level ratio for each channel was defined as (SCB level) / (ACB level).

[0087] Figure 9 shows the Height, level ratio, and CV for each channel obtained when filters 11-1 to 11-12 were correctly set under the measurement conditions described above. In Figure 9, Height_ACB represents the Height of the fluorescence signal obtained with AlignCheck beads, Height_SCB represents the Height of the fluorescence signal obtained with SortCal beads, Area_ACB_CV represents the CV calculated from the fluorescence signal obtained with AlignCheck beads, and Area_SCB_CV represents the CV calculated from the fluorescence signal obtained with SortCal beads. Of the values ​​shown in Figure 9, the level ratio and CV for each channel were used as a reference (first and second norms) when verifying the setting status of the optical filters.

[0088] 1.7.1 Case 1 Case 1 describes the case where filter 11-7 is swapped with the spare filter 11-14, as shown in Figure 8. Figure 10 shows the Height, level ratio, and CV for each channel acquired in Case 1. Comparing Figure 10 with Figure 9, in Case 1, the level ratio value of channel Ch2 falls outside the first specified range (8.17 ± 15%) obtained from the values ​​shown in Figure 8, and similarly, the Area_ACB_CV value of channel Ch2 falls outside the second specified range (3.6% ± 2%) obtained from the values ​​shown in Figure 8, while the other values ​​are within the specified range. From this, it can be determined that in Case 1, there is an error in filter 11-7, which is placed directly in front of the photodetector of channel Ch2.

[0089] 1.7.2 Case 2 Case 2 describes the case where filters 11-5 and 11-7 are swapped, as shown in Figure 8. Figure 11 shows the Height, level ratio, and CV for each channel obtained in Case 2. Comparing Figure 11 with Figure 9, in Case 2, the level ratio values ​​for channels Ch2 and Ch3 are within the first specified range (Ch2: 8.17±15%, Ch3: 7.87±15%) obtained from the values ​​shown in Figure 8. Therefore, it is not possible to determine from the level ratio that there is an error in the optical filters placed on the path of light incident on each channel. However, the Area_ACB_CV values ​​for channels Ch2 and Ch3 are outside the second specified range (Ch2: 3.6%±2%, Ch3: 3.9%±2%) obtained from the values ​​shown in Figure 8. From this, it can be determined that in Case 2, at least one of the filters 11-1, 11-4, 11-5, 11-6, and 11-7 placed in the optical path to the photodetectors of channels Ch2 and Ch3 is incorrect.

[0090] 1.7.3 Case 3 Case 3 describes the case where filters 11-1 and 11-4 are swapped, as shown in Figure 8. Figure 12 shows the Height, level ratio, and CV for each channel obtained in Case 3. Comparing Figure 12 with Figure 9, in Case 3, the level ratio value of channel Ch3 falls outside the first specified range (8.17 ± 15%) obtained from the values ​​shown in Figure 8, the Area_ACB_CV value of channel Ch3 also falls outside the second specified range (3.6% ± 2%) obtained from the values ​​shown in Figure 8, and furthermore, the Area_SCB_CV value of channel Ch3 also falls outside the second specified range (3.9% ± 2%) obtained from the values ​​shown in Figure 8. From this, it can be determined that in Case 3, there is an error in at least one of the filters 11-1, 11-4, and 11-5 placed on the optical path to the photodetector of channel Ch3.

[0091] 1.8 Summary As described above, according to this embodiment, it is possible to verify the setting state of the optical filter from the level ratio and CV (or rCV) obtained using a test sample. Therefore, it is possible to determine that the setting state of the optical filter is not appropriate not only when there is a human error or improper installation in the setting of the optical filter, but also when the optical filter is damaged or deteriorated. As a result, it is possible to suppress the decrease in accuracy caused by the optical filter.

[0092] 2. Second Embodiment Next, a second embodiment will be described in detail with reference to the drawings. In this embodiment, the overall operation, including the selection of an optical filter used for measuring a sample for analysis, which is a preliminary step to the verification exemplified in the first embodiment, will be explained with an example.

[0093] 2.1 Overall Flow Figure 13 is a flowchart showing an example of the overall flow according to this embodiment.

[0094] (Step S201) As shown in Figure 13, in step S201 of the overall flow, the user sets the optical filter to be used for measuring the sample in the detection unit 102 of the biological sample analyzer 100, for example, in the information processing unit 103 of the biological sample analyzer 100. The following procedure can be exemplified as the setting procedure for the optical filter. In step S201, any one of the following exemplified procedures may be performed.

[0095] • Example 1 In the first example, information on the optical filters to be used in the actual measurement and their arrangement (hereinafter referred to as the optical filter pattern) is pre-prepared in the information processing unit 103 according to one or more dyes used to stain the sample (hereinafter referred to as the dye set). After the user decides which dye to use to stain the sample, or after staining the sample, the user selects the one to use from the list of optical filter patterns provided as options by the information processing unit 103. Then, according to the selected optical filter pattern, the user sets the corresponding optical filters in each socket (socket where the optical filters are set) of the optical system in the detection unit 102 of the biological sample analyzer 100.

[0096] Here, an example of a list of optical filter patterns offered to the user as selection candidates is shown in Figure 14. As shown in Figure 14, the list indicates which optical filter is set in which slot for each optical filter pattern. Each row (record) in the list is, for example, a user interface for selection by the user, and the user can set the optical filter pattern to be used in the information processing unit 103 by selecting the row of the optical filter pattern to be used.

[0097] • Second example In the second example, as in the first example, optical filter patterns for each dye set are pre-prepared in the information processing unit 103. However, in the second example, when the user inputs the dye to be used to stain the sample into the information processing unit 103, the information processing unit 103 automatically selects an optical filter pattern from the stored optical filter patterns and presents the information of the selected optical filter pattern to the user. In the second example, the user may be given a list of optical filter patterns as an option so that they can change the automatically selected optical filter pattern. The user then sets the corresponding optical filter in each socket of the optical system in the detection unit 102 of the biological sample analyzer 100 according to the automatically selected or changed optical filter pattern.

[0098] • Third example In the third example, the user selects the optical filters to be placed in each socket of the optical system in the detection unit 102 of the biological sample analyzer 100 and inputs this information to the information processing unit 103, and also sets the optical filters in each socket of the optical system in the detection unit 102. For example, the user determines the dye set to be used to stain the sample, and then determines the type of optical filter to be used and its arrangement. The information processing unit 103 provides the user with a user interface that mimics the arrangement of the optical system in the detection unit 102. The user uses the user interface provided by the information processing unit 103 to set the optical filters to be placed in each socket of the optical system. Then, according to the arrangement of optical filters that the user has determined, the user sets the corresponding optical filters in each socket of the optical system in the detection unit 102 of the biological sample analyzer 100.

[0099] • Fourth example In the fourth example, each optical filter is assigned an identification code (an example of an identification information holder) to uniquely identify it. The identification code may be an optically readable code, such as a barcode or a QR code (registered trademark). When the user sets the optical filters in each socket, they use an optical reader, such as a barcode reader or a QR code (registered trademark) reader, to read the identification codes of the optical filters set in each socket in a predetermined order. The read identification codes are input to the information processing unit 103. The information processing unit 103 identifies which optical filter is set in which socket based on the identification codes that have been input in order.

[0100] In the fourth example, identification codes may also be attached to each socket in the optical system, in addition to the optical filters. Figure 15 shows an example where QR codes (registered trademark) are attached to both the optical filters and the sockets. As shown in Figure 15, QR codes (registered trademark) 14A-14C and 15A-15C are attached to each of the optical filters 11A-11C and each of the sockets 13A-13C. In this case, by reading each QR code (registered trademark) simultaneously, the information processing unit 103 can identify which optical filter is set in which socket, even if the user reads the socket identification codes and optical filter identification codes in any order.

[0101] In the fourth example, a reader may be provided near each socket to read the identification code of the optical filter set in each socket. In this case, when the user sets an optical filter in each socket and presses, for example, a complete button (read button), the identification code of the optical filter set in each socket may be automatically read and transmitted to the information processing unit 103.

[0102] • Case 5 In the fifth example, as in the fourth example, each optical filter is assigned an identification code. The user sets the optical filters in each socket, then uses a mobile device such as a cell phone or smartphone to photograph the entire optical system and inputs the captured image data to the information processing unit 103. Various methods of input may be used, such as attaching the image to an email and sending it, or uploading it from a dedicated application or website. The information processing unit 103 identifies the optical filters set in each socket of the optical system by analyzing the image data input by the user.

[0103] • Case 6 In the sixth example, each optical filter is fitted with a tag (an example of an identification information holder) that stores identification information to uniquely identify it. The tag may be a contactless type such as RFID, or a contact type. In addition, each socket of the optical system is provided with a reader for reading the information stored in the tag attached to the optical filter set in it. When the user sets an optical filter in each socket, information on which optical filter is set in which socket is automatically or manually input to the information processing unit 103.

[0104] In step S201, in addition to the setting information of the optical filter, lot information of the setup beads used for verification may also be input to the information processing unit 103. This lot information may be input directly by the user to the information processing unit 103, or it may be input to the information processing unit 103 using a mobile device such as a mobile phone or smartphone.

[0105] (Step S202) In step S202, for example, the setting status of the optical filter is verified by executing the verification flow described with reference to Figure 7 in the first embodiment.

[0106] (Step S203). In step S203, based on the verification results from step S202, it is determined whether the optical filter settings are appropriate. If they are not appropriate (NO in step S203), the flow returns to step S201, and the optical filter settings are repeated. On the other hand, if they are appropriate (YES in step S203), the flow ends, and measurements are performed on the sample to be analyzed.

[0107] 3. Third Embodiment Next, a third embodiment will be described in detail with reference to the drawings. In this embodiment, an example will be given to the information presented to the user when notifying the user of the setting status of the optical filter or when the setting of the optical filter needs to be redone, as described using step S112 in Figure 7 in the first embodiment. Note that the type and arrangement of the optical filter in the optical system of the detection unit 102 may be set in the information processing unit 103 by the procedure exemplified in the second embodiment, for example.

[0108] In step S112 of Figure 7, in addition to information instructing the user to "check the setting status of the optical filter or readjust the setting status of the optical filter," or instead of such information, the user may be notified of information to identify an optical filter whose setting status is presumed to be inappropriate.

[0109] The information used to identify an optical filter that is presumed to be in an inappropriate setting can be various types of information, such as information pointing to a specific optical filter, or information pointing to the optical path to the photodetector corresponding to the channel determined to be inappropriate during verification, and / or the optical filter placed on this optical path.

[0110] Figure 16 is a schematic diagram showing an example of a screen (hereinafter referred to as the notification screen) that is presented to the user as "information for identifying optical filters that are presumed to have an inappropriate setting." In this example, we illustrate Case 2 (Figure 11) in the first embodiment, that is, the case in which filters 11-5 and 11-7 are swapped.

[0111] As shown in Figure 16, in this embodiment, the notification screen provided to the user shows the optical paths to the photodetectors corresponding to channels Ch2 and Ch3, which were determined to be inappropriate during verification, using visual effects such as thick lines, accent colors, or blinking. In this example, the optical paths from filter 11-1 to channel CH2 and from filter 11-1 to channel Ch3 are shown with thick lines. Therefore, a user who is presented with this notification screen can recognize that the setting state of one or more of the filters 11-1, 11-4, 11-5, 11-6, and 11-7 located on the optical path from filter 11-1 to channels Ch2 and Ch3 is inappropriate.

[0112] The notification screen may be displayed on a display accessible to the user, such as a display included in or connected to the information processing unit 103, or a mobile device carried by the user.

[0113] 4. Variations In the embodiments described above, a flow cytometer was exemplified as the biological sample analyzer 100. However, the technology described herein is not limited to a flow cytometer and can be applied to various analytical devices that use two or more optical filters to separate light from a sample into two or more wavelength bands, such as microscopes and image cytometers. In this case, the sample is not limited to minute particles but can be various objects, such as tissue sections. Similarly, instead of setup beads, two or more objects with different fluorescence intensities and scattered light intensities can be used as test samples.

[0114] 5. Hardware Configuration The information processing unit 103 according to the above embodiment can be implemented by a computer 1000 having a configuration such as that shown in Figure 17. Figure 17 is a hardware configuration diagram showing an example of a computer 1000 that implements the functions of the information processing unit 103. The computer 1000 has a CPU 1100, RAM 1200, ROM (Read Only Memory) 1300, HDD (Hard Disk Drive) 1400, a communication interface 1500, and an input / output interface 1600. The various parts of the computer 1000 are connected by a bus 1050.

[0115] The CPU 1100 operates based on programs stored in the ROM 1300 or HDD 1400, and controls various parts. For example, the CPU 1100 loads the programs stored in the ROM 1300 or HDD 1400 into the RAM 1200 and executes processing corresponding to various programs.

[0116] ROM1300 stores boot programs such as the BIOS (Basic Input Output System) executed by CPU1100 when computer 1000 starts up, as well as programs that depend on the computer 1000's hardware.

[0117] The HDD1400 is a computer-readable recording medium that non-temporarily records programs executed by the CPU1100 and data used by such programs. Specifically, the HDD1400 is a recording medium that records programs for realizing each operation related to this disclosure, which are an example of program data 1450.

[0118] The communication interface 1500 is an interface for the computer 1000 to connect to an external network 1550 (e.g., the Internet). For example, the CPU 1100 can receive data from other devices or transmit data it has generated to other devices via the communication interface 1500.

[0119] The input / output interface 1600 includes the I / F unit 18 described above and is an interface for connecting the input / output device 1650 and the computer 1000. For example, the CPU 1100 receives data from input devices such as keyboards and mice via the input / output interface 1600. The CPU 1100 also transmits data to output devices such as displays, speakers, and printers via the input / output interface 1600. The input / output interface 1600 may also function as a media interface for reading programs recorded on a predetermined recording medium (media). Examples of media include optical recording media such as DVDs (Digital Versatile Discs) and PDs (Phase Change Rewritable Disks), magneto-optical recording media such as MOs (Magneto-Optical Disks), tape media, magnetic recording media, or semiconductor memory.

[0120] For example, when computer 1000 functions as an information processing unit 103 according to the above embodiment, the CPU 1100 of computer 1000 realizes the functions of the information processing unit 103 by executing a program loaded on RAM 1200. The HDD 1400 stores the program and the like according to this disclosure. The CPU 1100 reads and executes the program data 1450 from HDD 1400, but as another example, these programs may be obtained from other devices via an external network 1550.

[0121] While embodiments of this disclosure have been described above, the technical scope of this disclosure is not limited to the embodiments described above, and various modifications are possible without departing from the spirit of this disclosure. Furthermore, components from different embodiments and modifications may be combined as appropriate.

[0122] Furthermore, the effects described in each embodiment of this specification are merely illustrative and not limiting, and other effects may also occur.

[0123] Furthermore, this technology can also be configured as follows. (1) An illumination unit that irradiates light onto the sample, An optical system that separates the light from the aforementioned sample using two or more optical filters, Multiple photodetectors for detecting the intensity of each of the light waves separated by the aforementioned optical system, A processing unit that analyzes the sample based on the intensity of light detected by each of the aforementioned photodetectors, Equipped with, The processing unit determines whether the setting state of the two or more optical filters is appropriate based on the first light intensity for each test sample detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto two or more test samples. Information processing device. (2) The processing unit determines whether the setting state of the two or more optical filters is appropriate based on the ratio of the first light intensity for each test sample. The information processing device described in (1) above. (3) The processing unit determines whether the setting state of the two or more optical filters is appropriate, based on whether the ratio of the second light intensity for each test sample, detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto the two or more test samples with the two or more optical filters set appropriately, falls within a first predetermined range. The information processing device described in (2) above. (4) The processing unit determines whether the setting state of the two or more optical filters is appropriate based on the average or median value of the first light intensity detected by two or more of the multiple photodetectors. An information processing device as described in any one of (1) to (3) above. (5) The processing unit determines whether the setting state of the two or more optical filters is appropriate, based on the coefficient of variation or robust coefficient of variation of the first light intensity detected by each of the photodetectors. An information processing device as described in any one of (2) to (4) above. (6) The processing unit determines whether the setting state of the two or more optical filters is appropriate, based on whether the coefficient of variation of the first light intensity or the robust coefficient of variation falls within a second predetermined range, which is based on the coefficient of variation of the second light intensity or the robust coefficient of variation for each test sample detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto the two or more test samples with the two or more optical filters set appropriately. The information processing device described in (5) above. (7) If the processing unit determines that the setting state of the two or more optical filters is not appropriate, it notifies the user that the setting state of at least one of the two or more optical filters is not appropriate. An information processing device as described in any one of (1) to (6) above. (8) The processing unit notifies the user of one or more optical filters whose settings are presumed to be inappropriate, or of an optical path in which one or more optical filters whose settings are presumed to be inappropriate, based on the first light intensity for each test sample detected by each of the photodetectors. The information processing device described in (7) above. (9) The processing unit notifies the user of one or more optical filters whose setting state is presumed to be inappropriate, or the optical path in which one or more optical filters whose setting state is presumed to be inappropriate, based on the types and arrangement of the two or more optical filters in the optical system set by the user. The information processing device described in (8) above. (10) The processing unit presents the user with candidates for the types and arrangements of the two or more optical filters to be set in the optical system according to the dye used to stain the sample, and based on the types and arrangements of the two or more optical filters selected by the user from the candidates, it notifies the user of one or more optical filters whose setting state is presumed to be inappropriate, or the optical path in which one or more optical filters whose setting state is presumed to be inappropriate are arranged. The information processing device described in (9) above. (11) The processing unit automatically sets the types and arrangements of the two or more optical filters to be set in the optical system according to the dye used to stain the sample input by the user, and notifies the user of the one or more optical filters whose setting state is estimated to be inappropriate, or the optical path in which the one or more optical filters whose setting state is estimated to be inappropriate are arranged, based on the automatically set types and arrangements of the two or more optical filters. The information processing device described in (9) above. (12) Each of the optical filters has an identification information holding unit that holds identification information for uniquely identifying its own type, The processing unit notifies the user of one or more optical filters whose setting state is estimated to be inappropriate, or the optical path in which one or more optical filters whose setting state is estimated to be inappropriate, based on the type of each optical filter and the arrangement of each optical filter obtained from the identification information holding unit of each optical filter. The information processing device described in (9) above. (13) The aforementioned sample consists of fine particles, The aforementioned two or more test samples are setup beads containing two or more beads of different sizes. An information processing device as described in any one of (1) to (12) above. (14) The irradiation unit irradiates the sample or test specimen flowing through a predetermined channel with light. An information processing device as described in any one of (1) to (13) above. (15) Light was shone onto two types of test samples. The intensity of each separated light beam is detected in an optical system that separates the light from each of the two types of test samples using two or more optical filters. Based on the detected light intensity for each test sample, it is determined whether the settings of the two or more optical filters are appropriate. Information processing methods that include the following. (16) A program for operating the processor of an information processing device comprising: an illumination unit that irradiates a sample with light; an optical system that separates the light from the sample using two or more optical filters; and a plurality of photodetectors that detect the intensity of each of the light separated by the optical system, A program for the processor to determine whether the setting state of the two or more optical filters is appropriate, based on the first light intensity for each test sample detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto two or more test samples. [Explanation of Symbols]

[0124] 11A~11C, 11a~11c, 11-1~11-15 filters 12a~12c, Photodetector 13A~13C Socket 14A~14C, 15A~15C QR Code (Registered Trademark) 100 Biological Sample Analysis Device 101 Light-irradiating section 102 Detection unit 103 Information Processing Department 104 Preparation section C channel L1~L15 light P biological particles S Biological sample

Claims

1. An illumination unit that irradiates light onto the sample, An optical system for demultiplying fluorescence from the aforementioned sample using two or more optical filters, Multiple photodetectors for detecting the intensity of each of the fluorescence waves separated by the optical system, A processing unit that analyzes the sample based on the fluorescence intensity detected by each of the photodetectors, Equipped with, The processing unit determines whether the setting state of the two or more optical filters is appropriate based on the first light intensity for each test sample detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto two or more test samples. Information processing device.

2. The processing unit determines whether the setting state of the two or more optical filters is appropriate based on the ratio of the first light intensity for each test sample. The information processing apparatus according to claim 1.

3. The processing unit determines whether the setting state of the two or more optical filters is appropriate, based on whether the ratio of the second light intensity for each test sample, as detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto the two or more test samples with the two or more optical filters set appropriately, falls within a first predetermined range. The information processing apparatus according to claim 2.

4. The processing unit determines whether the setting state of the two or more optical filters is appropriate based on the average or median value of the first light intensity detected by two or more of the multiple photodetectors. The information processing apparatus according to claim 1.

5. The processing unit determines whether the setting state of the two or more optical filters is appropriate, based on the coefficient of variation or robust coefficient of variation of the first light intensity detected by each of the photodetectors. The information processing apparatus according to claim 2.

6. The processing unit determines whether the setting state of the two or more optical filters is appropriate, based on whether the coefficient of variation of the first light intensity or the robust coefficient of variation falls within a second predetermined range, which is based on the coefficient of variation of the second light intensity or the robust coefficient of variation for each test sample detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto the two or more test samples with the two or more optical filters set appropriately. The information processing apparatus according to claim 5.

7. If the processing unit determines that the setting state of the two or more optical filters is not appropriate, it notifies the user that the setting state of at least one of the two or more optical filters is not appropriate. The information processing apparatus according to claim 1.

8. The processing unit notifies the user of one or more optical filters whose setting state is presumed to be inappropriate, or an optical path in which one or more optical filters whose setting state is presumed to be inappropriate, based on the first light intensity for each test sample detected by each of the photodetectors. The information processing apparatus according to claim 7.

9. The processing unit notifies the user of one or more optical filters whose setting state is presumed to be inappropriate, or the optical path in which one or more optical filters whose setting state is presumed to be inappropriate, based on the types and arrangement of the two or more optical filters in the optical system set by the user. The information processing apparatus according to claim 8.

10. The processing unit presents the user with candidates for the types and arrangements of the two or more optical filters to be set in the optical system according to the dye used to stain the sample, and based on the types and arrangements of the two or more optical filters selected by the user from the candidates, it notifies the user of the one or more optical filters whose setting state is presumed to be inappropriate, or the optical path in which the one or more optical filters whose setting state is presumed to be inappropriate are arranged. The information processing apparatus according to claim 9.

11. The processing unit automatically sets the types and arrangements of the two or more optical filters to be set in the optical system according to the dye used to stain the sample input by the user, and based on the automatically set types and arrangements of the two or more optical filters, it notifies the user of the one or more optical filters whose setting state is estimated to be inappropriate, or the optical path in which the one or more optical filters whose setting state is estimated to be inappropriate are arranged. The information processing apparatus according to claim 9.

12. Each of the optical filters has an identification information holding unit that holds identification information for uniquely identifying its own type, The processing unit notifies the user of one or more optical filters whose setting state is presumed to be inappropriate, or the optical path in which one or more optical filters whose setting state is presumed to be inappropriate, based on the type of each optical filter and the arrangement of each optical filter obtained from the identification information holding unit of each optical filter. The information processing apparatus according to claim 9.

13. The aforementioned sample consists of fine particles, The aforementioned two or more test samples are setup beads containing two or more beads of different sizes. The information processing apparatus according to claim 1.

14. The irradiation unit irradiates the sample or test specimen flowing through a predetermined channel with light. The information processing apparatus according to claim 1.

15. Light was shone onto two types of test samples. The fluorescence from each of the two types of test samples is separated using two or more optical filters in an optical system, and the intensity of each separated fluorescence is detected. Based on the fluorescence intensity detected for each test sample, it is determined whether the settings of the two or more optical filters are appropriate. Information processing methods that include the following.

16. A program for operating the processor of an information processing device comprising: an irradiation unit that irradiates a sample with light; an optical system that separates fluorescence from the sample using two or more optical filters; and a plurality of photodetectors that detect the intensity of each of the fluorescence signals separated by the optical system, A program for the processor to determine whether the setting state of the two or more optical filters is appropriate, based on the first light intensity for each test sample detected by each of the photodetectors via the optical system when light from the irradiation unit is irradiated onto two or more test samples.

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