Particle detection device, information processing device, information processing method, and particle detection method

Abstract

A particle detection apparatus comprising: a plurality of optical detectors configured to detect light from a particle, wherein at least one optical detector has a different applied voltage coefficient than the other optical detectors; and a processor comprising a processing device and a memory storing instructions that, when executed by the processing device, cause the processor to: correct optical data obtained from the particle according to a difference between the applied voltage coefficient of the plurality of optical detectors and a predetermined applied voltage coefficient.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of Japanese priority patent application JP2019-186782, filed on October 10, 2019, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This technology relates to a particle detection apparatus. More specifically, this technology relates to an information processing apparatus, a particle detection apparatus, an information processing method, and a particle detection method for optically detecting the properties of particles. Background Technology

[0004] In recent years, technologies have been developed to allow biological microparticles, such as cells or microorganisms, or microbeads, to flow in flow paths and to detect particles individually or to analyze or sort the detected particles during the flow process, as a result of improvements in analytical techniques.

[0005] As a representative example of this technique used to analyze or sort particles, the analytical technique known as flow cytometry has been rapidly improved. Flow cytometry is an analytical technique used to analyze or sort particles by circulating them in a fluid in an aligned state and irradiating them with a laser beam or similar device to detect the fluorescence or scattered light emitted from each particle.

[0006] For example, when fluorescence is detected in cells, cells labeled with fluorescent dyes are irradiated with excitation light (such as a laser beam) of appropriate wavelength and intensity. The fluorescence emitted from the fluorescent dyes is then focused using a lens or similar means, light within a suitable wavelength range is selected using a wavelength-selective element such as a filter or dichroic mirror, and the selected light is detected using a light-receiving element such as a photomultiplier tube (PMT). At this point, by combining multiple wavelength-selective elements and multiple light-receiving elements, rays from various fluorescent dyes on the labeled cells can also be detected and analyzed simultaneously. Furthermore, by combining rays of excitation light with multiple wavelengths, the number of analyzable fluorescent dyes can be increased.

[0007] Examples of methods for detecting fluorescence in flow cytometry include methods that select multiple rays in discontinuous wavelength ranges using wavelength-selective elements such as filters and detect the intensity of light in each wavelength range, and methods for detecting the intensity of light in a continuous wavelength range as a fluorescence spectrum. In spectral flow cytometry capable of detecting fluorescence spectra, fluorescence emitted from particles is spectrally dispersed using spectral elements such as prisms or gratings. The spectrally dispersed fluorescence is then detected using an array of light-receiving elements obtained by configuring multiple light-receiving elements different within the detection wavelength range. As an array of light-receiving elements, a PMT array or a photodiode array obtained by arranging light-receiving elements such as PMTs or photodiodes in one dimension, or an array obtained by arranging multiple independent detection channels of light-receiving elements such as two-dimensional light-receiving elements (e.g., CCD or CMOS), can be used.

[0008] In particle analysis, such as flow cytometry, optical techniques are often used to illuminate the particles to be analyzed with light, such as lasers, and detect the fluorescence or scattered light emitted from the particles. Then, using a computer and software for analysis, a histogram is extracted based on the detected optical data, and the analysis is performed.

[0009] In the optical analysis of particles, in some cases, quality control (QC) is performed before the optical detection of the particles used as the actual target to be inspected, for purposes such as verifying the accuracy of the optical detection, confirming and standardizing the operation of the equipment, etc. This QC typically involves using multiple beads labeled with fluorescent dyes that have different fluorescence intensities (e.g., 3-peak beads, 6-peak beads, 8-peak beads, etc.), or beads of a type that obtain a wide range of spectra (e.g., alignment check beads or superrainbow fluorescent particles), etc.

[0010] As a technique for performing fluorescence compensation in the detection of multiple fluorescent dyes, for example, PTL1 discloses a technique in which, by developing a procedure for calculating the centroid value of a fluorescence group associated with the fluorescently labeled cells to be tested from a two-dimensional correlation plot of the fluorescently labeled cells to be tested obtained by flow cytometry, and performing a correction calculation on the fluorescence value of the fluorescently labeled cells to be tested corresponding to the centroid value by using fluorescence value and predetermined determinant clusters, fluorescence compensation can be performed between multiple fluorescent dyes or in the detection of fluorescence by using multiple laser beams, and even after the processing of the cells to be tested has been completed, fluorescence compensation can be performed without reprocessing the sample.

[0011] Reference List

[0012] Patent documents

[0013] PTL1: JP 2003-83894 A

[0014] PTL2: WO 2017 / 126170 A1. Summary of the Invention

[0015] [Technical Issues]

[0016] Optical detectors, such as PMTs, exhibit individual-level sensitivity variations, and even when using the same optical detector, sensitivity differences arise over time. An example of this sensitivity variation is the change in the sensitivity of the optical detector itself. In some cases, even when the same voltage value is set, the sensitivity can change by tens of times or more due to individual differences or the passage of time. This is directly and primarily reflected in differences in the device's output level. Therefore, even when performing the same settings between devices, or even when performing the same settings within a device as in previous detections, differences in output levels will occur.

[0017] Therefore, for example in PTL 2, by using the applied voltage coefficient corresponding to the characteristic quantity of the predetermined output pulse, it is possible to correct the level difference of the output from detection units that are set to the same applied voltage coefficient with high precision. However, this technique is a method for commonly changing the applied voltage coefficient of all detectors, and there is a need for further improvement.

[0018] Therefore, this technology is expected to primarily provide a technique for accurately correcting differences between output levels from a detection unit configured to differ in the applied voltage coefficient.

[0019] [Solution to the problem]

[0020] According to the present technology, firstly, a particle detection device is provided, including an optical detector configured to detect light from particles, wherein at least one optical detector has an applied voltage coefficient different from that of the other optical detectors; and

[0021] A processor, including a processing device and a memory storing instructions, which, when executed by the processing device, cause the processor to: correct optical data obtained from particles based on the difference between applied voltage coefficients of a plurality of optical detectors and predetermined applied voltage coefficients.

[0022] According to the present technology, an information processing apparatus is provided, comprising: a processor, including a processing device and a memory storing instructions, wherein when the instructions are executed by the processing device, the instructions cause the processor to: correct optical data of light detected from a particle by a plurality of optical detectors based on the difference between the applied voltage coefficients of a plurality of optical detectors and a predetermined applied voltage coefficient, wherein at least one optical detector has an applied voltage coefficient different from the other optical detectors.

[0023] According to the present technology, a further information processing method is provided, comprising: correcting optical data of light detected from a particle by a plurality of optical detectors based on the difference between the applied voltage coefficients of a plurality of optical detectors and a predetermined applied voltage coefficient, wherein at least one optical detector has an applied voltage coefficient different from that of the other optical detectors.

[0024] According to the present technology, a particle detection method is also provided, comprising: detecting light from a particle, wherein at least one optical detector has an applied voltage coefficient different from other optical detectors; and correcting optical data obtained from the particle based on the difference between the applied voltage coefficients of a plurality of optical detectors and a predetermined applied voltage coefficient.

[0025] In this technology, it is assumed that "particles" encompass a wide range, including biologically related microparticles such as cells, microorganisms or liposomes, synthetic particles such as latex particles, gel particles or industrial particles, etc.

[0026] Biologically relevant microparticles include chromosomes, liposomes, mitochondria, organelles, etc., that make up various cells. Cells include animal cells (e.g., blood cells) and plant cells. Microorganisms include bacteria such as *Escherichia coli*, viruses such as tobacco mosaic virus, fungi such as yeast, etc. Furthermore, biologically relevant microparticles may also include biologically relevant polymers, such as nucleic acids, proteins, or complexes of nucleic acids and proteins. Additionally, industrial particles can be, for example, organic or inorganic polymer materials, metals, etc. Organic polymer materials include polystyrene, styrene-divinylbenzene copolymer, polymethyl methacrylate, etc. Inorganic polymer materials include glass, silica, magnetic materials, etc. Metals include gold colloids, aluminum, etc. These particles are generally spherical in shape. However, in this art, the shape of these particles can be aspherical, and the size, mass, etc., of each of these particles are not specifically limited. Attached Figure Description

[0027] Figure 1 This is a schematic conceptual diagram illustrating a first embodiment of a particle detection device 2 that can be used with an information processing device 1 according to the present technology.

[0028] Figure 2 This is a schematic conceptual diagram illustrating a first embodiment of a particle detection system 3 that can be used with an information processing device 1 according to the present technology.

[0029] Figure 3 This is a schematic conceptual diagram illustrating a second embodiment of a particle detection device 2 that can be used with an information processing device 1 according to the present technology.

[0030] Figure 4This is a schematic conceptual diagram illustrating a second embodiment of a particle detection system 3 that can be used with an information processing device 1 according to the present technology.

[0031] Figure 5 This is a graph that instead shows an example of a linear relationship under the assumption that the vertical axis represents Log HV and the horizontal axis represents St.

[0032] Figure 6 This is a graph that instead shows an example of a linear relationship under the assumption that the vertical axis represents Log HV and the horizontal axis represents St.

[0033] Figure 7A This is a graph that replaces the diagram showing the level of optical data obtained from the particles when the applied voltage coefficients (St values) of all detectors are set uniformly, and Figure 7B It is a graph that replaces the diagram showing the level of optical data obtained from the particles when a voltage coefficient (St value) is applied for each wavelength of the excitation light.

[0034] Figure 8A This is a graph showing the characteristic portions obtained from a fluorescent reference particle (single dye) when the same applied voltage coefficient (e.g., St value: 3) is set for wavelengths 1 and 2. Figure 8B It is a graph showing the characteristic portion obtained from the fluorescent reference particle (single dye) when a voltage coefficient (St value) is applied to each wavelength setting of the excitation light.

[0035] Figure 9A This is an alternative graph showing the optical data levels obtained from actual samples with the same applied voltage coefficient (e.g., St value: 3) set for wavelengths 1 and 2. Figure 9B This is a graph that replaces the diagram showing the level of optical data obtained from actual samples when a voltage coefficient (St value) is applied to each wavelength setting of the excitation light.

[0036] Figure 10A This is a graph that instead shows a characteristic portion obtained from a fluorescent reference particle (single dye) when all PMTs are set with the same applied voltage coefficient (e.g., St value: 3) for each wavelength. Figure 10B This is a graph showing the characteristic portion obtained from the fluorescent reference particle (single dye) when the applied voltage coefficient (St value) of PMT 1 and 2 has been increased at wavelength 1.

[0037] Figure 11 This is a flowchart illustrating an example of the processing flow performed on fluorescent reference particle (single dye) data.

[0038] Figure 12 This is a flowchart illustrating an example of the processing flow performed on actual sample data.

[0039] Figure 13 This is a flowchart illustrating a variation of the process performed on actual sample data.

[0040] Figure 14 This is a graph illustrating an example of a door setup. Detailed Implementation

[0041] Preferred embodiments of the present technology are described below with reference to the accompanying drawings. The embodiments described below indicate examples of representative embodiments of the present technology and should not be construed as limiting the scope of the present technology. Note that the descriptions will proceed in the following order.

[0042] 1. Information processing device 1, particle detection device 2, and particle detection system 3

[0043] (1) Flow path P

[0044] (2) Light irradiation unit 21

[0045] (3) Optical detection unit 22

[0046] (4) Information processing device 1 (information processing unit 11)

[0047] (4-1) Correction Unit 111

[0048] (4-2) Set unit 12(112)

[0049] (4-3) Fluorescence separation processing unit 13(113)

[0050] (4-4) Memory 14(114)

[0051] (4-5) Display unit 15 (115)

[0052] (4-6) User Interface 16(116)

[0053] (5) Sorting Unit 23

[0054] 2. Information processing methods and particle detection methods

[0055] 3. Computer program

[0056] <1. Information processing device 1, particle detection device 2, and particle detection system 3>

[0057] The information processing apparatus 1 according to this technology is an apparatus for processing optical data detected when detecting fluorescence emitted by particles in a sample liquid flowing from a flow path P, and includes at least a correction unit 111. Furthermore, it may, as needed, include a setting unit 12, a fluorescence separation processing unit 13, a memory 14, a display unit 15, a user interface 16, etc.

[0058] Figure 1 This is a schematic conceptual diagram illustrating a first embodiment of a particle detection device 2 that can be used with an information processing device 1 according to the present technology. Figure 2 This is a schematic conceptual diagram illustrating a first embodiment of a particle detection system 3 that can be used with an information processing device 1 according to the present technology. Figure 3 This is a schematic conceptual diagram illustrating a second embodiment of a particle detection device 2 that can be used with an information processing device 1 according to the present technology. Figure 4 This is a schematic conceptual diagram illustrating a second embodiment of a particle detection system 3 that can be used with the information processing apparatus 1 according to the present technology. The particle detection apparatus 2 and particle detection system according to the present technology include at least an optical detection unit 22 and an information processing unit 11, and the information processing unit 11 includes at least a correction unit 111. Furthermore, as needed, it may include a flow path P, a light irradiation unit 21, a setting unit 112, a fluorescence separation processing unit 113, a memory 114, a display unit 115, a user interface 116, a sorting unit 23, etc.

[0059] It should be noted that the calibration unit 111, setting unit 12 (112), fluorescence separation processing unit 13 (113), memory 14 (114), display unit 15 (115), user interface 16 (116), etc., can be located within the information processing unit 11, such as according to the... Figure 1 The particle detection device 2 of the first embodiment is shown. Alternatively, as in... Figure 2 As shown, the particle detection system 3 may include an information processing device 1 and a particle detection device 2. The information processing device 1 includes a calibration unit 111, a setting unit 12, a fluorescence separation processing unit 13, a memory 14, a display unit 15, and a user interface 16. Furthermore, according to... Figure 3 As shown in the particle detection device 2 of the second embodiment, the information processing unit 11, the setting unit 12, the fluorescence separation processing unit 13, the memory 14, the display unit 15, and the user interface 16 can be arranged independently of each other. Alternatively, as... Figure 4 As shown, in the particle detection system 3, the independent information processing unit 11, setting unit 12, fluorescence separation processing unit 13, memory 14, display unit 15 and user interface 16 can be connected to the optical detection unit 22 of the particle detection device 2 via a network.

[0060] Furthermore, the information processing unit 11 (correction unit 111), setting unit 12 (112), fluorescence separation processing unit 13 (113), memory 14 (114), and display unit 15 (115) can be located in a cloud environment and can be connected to the particle detection device 2 via a network. More preferably, the correction unit 111 and setting unit 12 (112) can be located in the information processing unit 11, and the fluorescence separation processing unit 13 (113), memory 14 (114), and display unit 15 (115) can be located in a cloud environment and can be connected to the particle detection device 2 via a network. In this case, the records of correction processing performed by the correction unit 111, the records of setting conditions of the setting unit 12 (112), and the records of fluorescence separation processing performed by the fluorescence separation processing unit 13 (113) can be stored in the memory 14 (114), and the various types of information stored in the memory 14 (114) can be shared by multiple users.

[0061] The details of each unit are described below along the time series of the detection.

[0062] (1) Flow path P

[0063] The particle detection device 2 according to this technology can analyze or sort particles by detecting optical data obtained from particles arranged in a row in a flow cell (flow path P).

[0064] The flow path P can be pre-set in the particle detection device 2, or a commercially available flow path P, a disposable chip with a flow path P, etc. can be set in the particle detection device 2 to perform analysis or sorting.

[0065] The form of the flow path P is not specifically limited and can be designed freely. For example, not only as... Figure 1 , Figure 2 ,and Figure 4 As shown, a flow path P is formed in a two-dimensional or three-dimensional substrate T made of plastic, glass, etc., and as... Figure 3 As shown, the flow path P used in existing flow cytometers can be used in particle detection device 2.

[0066] Furthermore, if the flow path P has a form capable of forming laminar flow and can be freely designed, the flow path width, flow path depth, and flow path cross-sectional shape of the flow path P are not specifically limited. For example, microchannels with a flow path width of 1 mm or less can also be used in the particle detection device 2. Specifically, microchannels with a flow path width ranging from about 10 μm to about 1 mm (inclusive) can be appropriately used in this technology.

[0067] There are no specific limitations on the method used to supply particles, and the particles can flow in the flow path P according to the form of the flow path P to be used. For example, it is described that the particles are formed in... Figure 1 , Figure 2 ,and Figure 4 The diagram illustrates the flow path P in the substrate T. A sample liquid containing particles is introduced into the sample liquid flow path P11, and sheath fluid is introduced into each of the two sheath fluid flow paths P12a and P12b. The sample liquid flow path P11 and the sheath fluid flow paths P12a and P12b are joined together to form a main flow path P13. The laminar flow of sample liquid supplied to the sample liquid flow path P11 and the laminar flow of sheath fluid supplied to the sheath fluid flow paths P12a and P12b are connected to each other in the main flow path P13, and a sheath flow can be formed where the laminar flow of sample liquid is sandwiched between the laminar flows of sheath fluid.

[0068] Particles induced to flow through flow path P can be labeled with one or more types of dyes (such as fluorescent dyes). Examples of fluorescent dyes that can be used in this technique include Cascade Blue, Pacific Blue, FITC, phycoerythrin (PE), propidium iodide (PI), Texas Red (TR), piperidine chlorophyll protein (PerCP), allophycocyanin (APC), 4',6-diamidinyl-2-phenylindole (DAPI), Cy3, Cy5, Cy7, Brilliant Violet (BV421), etc.

[0069] (2) Light irradiation unit 21

[0070] The particle detection device 2 and particle detection system 3 according to the present invention may include a light irradiation unit 21. The light irradiation unit 21 irradiates particles flowing through the flow path P with light. The light irradiation unit 21 can be omitted from the particle detection device 2 according to the present invention, and particles flowing through the flow path P can be irradiated with light by using an external light irradiation device or the like.

[0071] The light irradiation unit 21 may include multiple light sources to be irradiated with excitation light rays having different wavelengths from each other.

[0072] There is no specific limitation on the type of light emitted from the light irradiation unit 21; however, in order to reliably generate fluorescence or scattered light from the particles, light with constant direction, wavelength, and intensity is desirable. Examples include lasers, LEDs, etc. When using a laser, the type of laser is not specifically limited. However, one or more types of lasers, such as argon ion (Ar) lasers, helium-neon (He-Ne) lasers, dye lasers, krypton (Cr) lasers, semiconductor lasers, and solid-state lasers obtained by combining semiconductor lasers and wavelength conversion optical elements, can be freely combined and used.

[0073] (3) Optical detection unit 22

[0074] Optical detection unit 22 optically detects particles flowing in flow path P. In this technology, optical detection unit 22 includes multiple optical detectors. Furthermore, the optical detection unit may include a signal processing unit for converting electrical signals obtained from the multiple optical detectors into digital signals. The digital signals obtained by the signal processing unit can be transmitted to an information processing unit. Signal data can be processed as optical data in the information processing unit. Optical data may include fluorescence data. More specifically, optical data may include fluorescence intensity data (front, height, area, width) and light intensity data. Different applied voltage coefficients (hereinafter also referred to as "St values") can be set for the multiple optical detectors. Here, the applied voltage coefficient (St value) is a value calculated based on the voltage applied to the optical detector and characteristic quantities of the optical data from the optical detector. For example, a plot is drawn using Log high voltage (HV) and Log height median as axes based on the correspondence between characteristic quantities (such as median height) obtained from the optical detectors and HV, as shown below. Figure 5 and Figure 6 As shown, a linear function is obtained. At this point, the median Log height can be defined as the applied voltage coefficient (St value). It should be noted that optical data (front, height, area, width) are used instead of feature quantities.

[0075] Multiple optical detectors can each receive light emitted from a particle due to irradiation by excitation light having different wavelengths. Alternatively, multiple optical detectors can receive light emitted from a particle due to irradiation by excitation light having the same wavelength.

[0076] In this technology, since the optical detector can detect light signals from particles, there are no specific limitations on the specific optical detection method used in the optical detection unit 22, and the optical detection method used in known optical detectors can be freely selected and adopted. For example, one or a free combination of two or more optical detection methods can be used in fluorescence detection instruments, scattered light detection instruments, transmitted light detection instruments, reflected light detection instruments, diffraction light detection instruments, ultraviolet spectrometers, infrared spectrometers, Raman spectrometers, FRET detection instruments, FISH detection instruments, various other spectroscopic detection instruments, PMT arrays or photodiode arrays obtained by one-dimensional arrangement of light receiving elements such as PMTs or photodiodes, and two-dimensional light receiving elements such as CCDs or CMOS with multiple independently arranged detection channels.

[0077] Furthermore, since light signals from particles can be detected, the location of the optical detection unit 22 in the particle detection device 2 according to this technology is not specifically limited and can be freely designed. For example, as Figures 1 to 4 As shown, preferably, the optical detection unit 22 is arranged on a side different from the side of the light irradiation unit 21, wherein the flow path P is located between the optical detection unit 22 and the light irradiation unit 21. This is because by arranging the optical detection unit 22 on a side different from the side of the light irradiation unit 21, the flow path P is located between the optical detection unit 22 and the light irradiation unit 21, allowing the light irradiation unit 21 and the optical detection unit 22 to be arranged in a configuration with a high degree of freedom. Furthermore, for example, fluorescence is also emitted in a direction different from the incident direction of the irradiation light; therefore, the optical detection unit 22 can be arranged relative to the flow path P on the same side as the side of the light irradiation unit 21, or on the side where the optical detection unit 22 and the light irradiation unit 21 form a 90-degree angle.

[0078] (4) Information processing device 1 (information processing unit 11)

[0079] In this technology, the information processing device 1 (information processing unit 11) performs information processing on optical data from fluorescence, which has been detected from particles by the optical detection unit 22. Details of the information processing method are described below.

[0080] (4-1) Correction Unit 111

[0081] The correction unit 111 performs correction to match the optical data from the fluorescence with the output level detected under the same applied voltage coefficient, wherein the fluorescence is detected from the particles by multiple optical detectors, which are configured to be different in terms of the applied voltage coefficient.

[0082] For example, when the applied voltage coefficient (St value) of all detectors is set uniformly, as in the prior art, the applied voltage is controlled to avoid saturation while preferentially supplying bright dye. In this case, such as... Figure 7A As shown, in dark dye (in Figure 7A In the case of wavelength 2), the level is low, and therefore the S / N value decreases in some cases. Conversely, as... Figure 7B As shown, by employing this technique and increasing the applied voltage coefficient (St value) to be set in the optical detector for detecting light emitted from particles due to irradiation with excitation light of wavelength 2, the level at wavelength 2 can be increased. As described above, by increasing the applied voltage coefficient (St value) in regions with low staining levels, a state with a good S / N ratio can be generated in all regions.

[0083] It is important to note that, in Figure 7BIn the present invention, a voltage coefficient (St value) is applied for each wavelength of the excitation light. However, in the case where light emitted from the particle by the excitation light at the same wavelength is received by multiple optical detectors, as described later, it is possible to set the applied voltage coefficient (St value) for each optical detector.

[0084] Next, a recalculation is performed to match the optical data detected as described above with the output level detected at the same applied voltage coefficient (St value). In this case, preferably, a correction is performed to match the output level detected at the minimum applied voltage coefficient. When recalculating the level from each state, the correlation between the applied voltage coefficient (St value) and the output level has already been calculated by normalization, and therefore the correlation can be used.

[0085] This correction method according to the present technology can be used to detect fluorescent reference particles that emit fluorescence with a predetermined wavelength bandwidth, and can also be used to detect particles to be analyzed.

[0086] As described above, by employing this technique, even if the applied voltage coefficient (St value) has been changed before detecting a fluorescent reference particle or the particle to be analyzed emitting fluorescence with a predetermined wavelength bandwidth, it is not necessary to perform detection again, and the fluorescence separation process (demixing) described later can be performed. Furthermore, similarly, for the compensation described later, it is not necessary to perform correction again. Moreover, when the intensity of light in a continuous wavelength range is detected as a fluorescence spectrum, there is an advantage that the applied voltage does not need to be manually controlled.

[0087] The following example illustrates a more specific method using flow cytometry performed with two different excitation beams.

[0088] (a) Multiple optical detectors are configured to have different applied voltage coefficients for each excitation light.

[0089] (a-1) Detection of fluorescent reference particles (single staining agent)

[0090] For example, such as Figure 8A As shown, when the same applied voltage coefficient (e.g., St value: 3) is set for wavelengths 1 and 2, and the level of the characteristic portion is lower in the case of wavelength 1, if the applied voltage coefficient (St value) for wavelength 1 is increased (e.g., St value: 5), then as... Figure 8B As shown, at wavelength 1, the level of the characteristic region increases, the S / N ratio improves, and the characteristic region becomes more prominent. This improves the separation performance of the fluorescent reference particle (single staining agent).

[0091] Next, corrections are performed to match the levels corresponding to the same applied voltage coefficient (the same St value) (e.g., the lowest St value), and the relative spectral shape of the fluorescent reference particle (single dye) is calculated. Figure 8A and Figure 8B In the example, the data for wavelength 1 was calculated as a St value corresponding to 3, and the continuous spectral shape of the fluorescent reference particle (single dye) was calculated.

[0092] (a-2) Detection of particles to be analyzed (actual sample)

[0093] For example, such as Figure 9A As shown, when the same applied voltage coefficient (e.g., St value: 3) is set for wavelengths 1 and 2, and the level is lower for wavelength 1, the applied voltage coefficient (St value) for wavelength 1 is increased (e.g., St value: 5), and the actual sample is detected in this state (see...). Figure 9B ).

[0094] Next, corrections are performed to match the levels corresponding to the same applied voltage coefficient (the same St value) (e.g., the lowest St value), and the spectrum of the actual sample is calculated. Figure 9A and Figure 9B In the example, data at wavelength 1 is calculated as a St value corresponding to 3, and the spectrum of the actual sample is calculated.

[0095] (a-3) Fluorescence separation treatment (demixing)

[0096] By using the spectral shape of the fluorescent reference particle (single staining agent) obtained in (a-1) above, fluorescence separation processing (demixing) is performed on the spectrum of the actual sample obtained in (a-2) above.

[0097] After fluorescence separation (demixing), the level at wavelength 1 can be recalculated to correspond to the St value at wavelength 5, and the results can be displayed.

[0098] (b) Setting the applied voltage coefficient (St value) for each optical detector

[0099] In (a) above, a voltage coefficient (St value) is applied to each wavelength of the excitation light. However, when light emitted from a particle due to irradiation with the excitation light at the same wavelength is received from a particle by multiple optical detectors, it is possible to apply a voltage coefficient (St value) to each of the multiple optical detectors separately. For example, the following description is provided by changing the applied voltage coefficient (St value) for each PMT.

[0100] (b-1) Detection of fluorescent reference particles (single staining agent)

[0101] For example, such as Figure 10A As shown, when the same applied voltage coefficient (e.g., St value: 3) is set for all PMTs at various wavelengths, and the characteristic levels of PMTs 1 and 2 are low at wavelength 1, if the applied voltage coefficient (St value) of PMTs 1 and 2 at wavelength 1 is increased (e.g., St value: 5), then as... Figure 10B As shown, at wavelength 1, the level of the characteristic region increases, the S / N ratio improves, and the characteristic region becomes more prominent. This improves the separation performance of the fluorescent reference particle (single dye).

[0102] Next, corrections are performed to match the levels corresponding to the same applied voltage coefficient (the same St value) (e.g., the lowest St value), and the relative spectral shape of the fluorescent reference particle (single dye) is calculated. Figure 10A and Figure 10B In the example, the data for PMT 1 and 2 at wavelength 1 were calculated as St values ​​corresponding to 3, and the continuous spectral shape of the fluorescent reference particle (single dye) was calculated.

[0103] (b-2) Detection of particles to be analyzed (actual sample)

[0104] Similar to the relationship between (a-1) and (a-2) above, the applied voltage coefficient (St value) of PMT 1 and 2 increases (e.g., St value: 5) in the case of wavelength 1, and the actual sample is detected in this state.

[0105] Next, corrections are performed to match the levels corresponding to the same applied voltage coefficient (the same St value) (e.g., the lowest St value), and the spectrum of the actual sample is calculated. Figure 10A and Figure 10B In the example, the data of PMT 1 and 2 at wavelength 1 are calculated as St values ​​corresponding to 3, and the spectrum of the actual sample is calculated.

[0106] (b-3) Fluorescence separation treatment (demixing)

[0107] By using the spectral shape of the fluorescent reference particle (single staining agent) obtained in (b-1) above, the spectrum obtained in (b-2) of the above actual sample is subjected to fluorescence separation processing (demixing).

[0108] After fluorescence separation (demixing), the level at wavelength 1 can be recalculated to correspond to a St value of 5, and the results can be displayed.

[0109] To summarize the above descriptions, the processing procedures performed on fluorescent reference particle (single dye) data and the processing procedures performed on actual sample data are as follows: Figure 11 and Figure 12 As shown in the figure. It should be noted that in the processing performed on actual sample data, variations different from the above-described example of the processing procedure performed on actual sample data can also be used (see...). Figure 13 ).

[0110] (The process for processing fluorescent reference particle (single dye) data (see...) Figure 11 ))

[0111] First, a voltage coefficient (St value) is applied for each wavelength of the excitation light or for each optical detector setting, and fluorescence (S1) from the fluorescent reference particle (single dye) is detected.

[0112] Next, the obtained data is corrected to match the level corresponding to the same applied voltage coefficient (the same St value) (e.g., the lowest St value), and a recalculation is performed (S2).

[0113] The continuous spectral shape of the fluorescent reference particle (single dye) obtained from the recalculation is stored as the spectral shape of the fluorescent reference particle (single dye) (S3).

[0114] (The process of processing actual sample data (see)) Figure 12 ))

[0115] First, a voltage coefficient (St value) is applied for each wavelength of the excitation light or for each optical detector setting, and fluorescence from the actual sample is detected (S4).

[0116] Next, the obtained data is corrected to match the level corresponding to the same applied voltage coefficient (the same St value) (e.g., the lowest St value), and a recalculation is performed (S5).

[0117] By using the spectral shape of the fluorescent reference particle (single staining agent) stored in S3 above, fluorescence separation processing (demixing) is performed on the spectrum obtained from the recalculation of the actual sample (S6).

[0118] After fluorescence separation (demixing), the spectral data of the actual sample are recalculated to correspond to the applied voltage coefficient (St value) set in S4 above (S7).

[0119] The results (S8) show the recalculated spectral data of the actual sample.

[0120] (Variations on the processing flow performed on actual sample data (see)) Figure 13 ))

[0121] First, a voltage coefficient (St value) is applied for each wavelength of the excitation light or for each optical detector setting, and fluorescence from the actual sample is detected (S4).

[0122] Next, the spectral shape of the fluorescent reference particle (single staining agent) stored in S3 is recalculated to correspond to the applied voltage coefficient (St value) set in S4 (S9). Since the applied voltage coefficient (St value) set in S4 varies depending on the wavelength of the excitation light or the optical detector, the data of the fluorescent reference particle (single staining agent) stored in S3 is corrected by using the difference from the lowest applied voltage coefficient (lowest St value), thus recalculating the spectral shape. Using this method, even without storing the applied voltage coefficient (St value) of the fluorescent reference particle (single staining agent), the fluorescent reference particle (single staining agent) can be corrected to correspond to the actual sample data. When the applied voltage coefficient (St value) of the fluorescent reference particle (single staining agent) is already stored in memory, the spectral shape of the fluorescent reference particle (single staining agent) stored in S3 is recalculated to correspond to the applied voltage coefficient (St value) set in S4.

[0123] By using the spectral shape of the fluorescent reference particle (single staining agent) recalculated in S9 above, the spectrum obtained in S4 of the actual sample is subjected to fluorescence separation processing (demixing) (S10).

[0124] The results (S11) show the spectral data of the actual sample after fluorescence separation (demixing).

[0125] As shown in this variation, fluorescence separation processing is performed by using optical data obtained from the actual sample by multiple optical detectors set to be different in terms of applied voltage coefficients, and by recalculating the values ​​obtained by correcting the optical data obtained from the fluorescent reference particles (single dye) to match the output levels detected at the same applied voltage coefficient, and by matching the values ​​obtained by matching the output levels detected at different applied voltage coefficients in the detection of fluorescence emitted from the actual sample. This allows the results to be displayed without performing the recalculation process on the spectral data of the actual sample again after the fluorescence separation processing (demixing) to correspond to the applied voltage coefficient (St value) already set in S4 above (processing in S7).

[0126] (4-2) Set unit 12(112)

[0127] The information processing apparatus 1, particle detection apparatus 2, and particle detection system 3 according to the present technology may include a setting unit 12 (112). The setting unit 12 (112) sets the applied voltage value (St value) according to the output level of the optical detector in the optical detection unit 22. In the present technology, the setting unit 12 (112) may be omitted, and the user can manually set the applied voltage coefficient (St value). However, by providing the setting unit 12 (112), the applied voltage coefficient (St value) can be automatically set according to the output level of the optical detector.

[0128] (4-3) Fluorescence separation processing unit 13(113)

[0129] The information processing apparatus 1, particle detection apparatus 2, and particle detection system 3 according to this technology may include a fluorescence separation processing unit 13 (113). The fluorescence separation processing unit 13 (113) performs fluorescence separation processing (demixing) by using values ​​obtained by correcting optical data obtained from fluorescent reference particles (single dye) to match the output level detected at the same applied voltage coefficient, and values ​​obtained by correcting optical data obtained from the particles to be analyzed (actual samples) to match the output level detected at the same applied voltage coefficient. (See the flowchart of the processing performed on actual sample data described above.) Figure 12 )]).

[0130] Furthermore, the fluorescence separation processing unit 13 (113) performs fluorescence separation processing (demixing) by using optical data already obtained from the particles to be analyzed (actual sample) by multiple optical detectors and by performing a recalculated value on the output level obtained by correcting the optical data obtained from the fluorescent reference particles (single dye) to match the detection of fluorescence emitted from the particles to be analyzed (actual sample) at different applied voltage coefficients (see [variation of the process for processing actual sample data (see [...]). Figure 13 )]).

[0131] It should be noted that in this technology, the fluorescence separation processing unit 13 (113) can be omitted, and fluorescence separation processing (demixing) can be performed by using an external information processing device or the like.

[0132] (4-4) Memory 14(114)

[0133] The information processing device 1, particle detection device 2, and particle detection system 3 according to this technology may include a memory 14 (114) for storing various types of data. The memory 14 (114) may store any matters related to detection, such as optical data related to particles detected by the optical detection unit 22, records of correction processing performed by the correction unit 111, records of setting conditions in the setting unit 12 (112), or records of fluorescence separation processing (demixing) performed by the fluorescence separation processing unit 13 (113).

[0134] Furthermore, as described above, in this technology, the memory 14 (114) can be set up in a cloud environment, and thus each user can share various types of information that have been recorded in the memory 14 (114) in the cloud via a network.

[0135] Specifically, the normalized data obtained in this technology is stored in a cloud-based storage device 14 (114) and shared by users with different devices. This enables the data to be reused, which can contribute to improved usability.

[0136] More specifically, for example, the normalized waveform data (spectral reference data) of the fluorescent reference particle (single staining agent) is recorded in a cloud-based memory 14 (114), allowing users to share the waveform data. This enables each user to select the spectral reference data of the fluorescence to be used in the experiment from the cloud-based memory 14 (114) and perform fluorescence separation processing between the spectral reference data and the experimental data of each device. With this configuration, each user does not need to detect the fluorescent reference particle (single staining agent) every time.

[0137] Furthermore, the spectral reference data before normalization, together with the applied voltage coefficient (St value), can be pre-recorded in a cloud-based memory 14 (114), and a process for correcting the applied voltage coefficient (St value) corresponding to the experimental data obtained in each device can be performed before the fluorescence separation process.

[0138] It should be noted that in this technology, memory 14 (114) can be omitted, and various types of data can be stored by using external storage devices, etc.

[0139] (4-5) Display unit 15 (115)

[0140] The information processing device 1, particle detection device 2, and particle detection system 3 according to this technology may include a display unit 15 (115) for displaying various types of information. The display unit 15 (115) may display any matters related to detection, such as optical data related to particles detected by the optical detection unit 22, various types of data corrected by the correction unit 111, or the results of fluorescence separation processing (demixing) performed by the fluorescence separation processing unit 13 (113).

[0141] In this technology, the display unit 15 (115) can be omitted, and an external display device can be connected. For example, a monitor, printer, etc. can be used as the display unit 15 (115).

[0142] (4-6) User Interface 16(116)

[0143] The information processing apparatus 1, particle detection apparatus 2, and particle detection system 3 according to this technology may further include a user interface 16 (116), which serves as a part for a user to perform operations. The user can access and control each unit via the user interface 16 (116).

[0144] In this technology, the user interface 16 (116) can be omitted, and an external operating device can be connected. For example, a mouse, keyboard, etc. can be used as the user interface 16 (116).

[0145] (5) Sorting Unit 23

[0146] The information processing apparatus 1, particle detection apparatus 2, and particle detection system 3 according to this technology may include a sorting unit 23. The sorting unit 23 sorts particles based on optical data detected by the optical detection unit 22. For example, the sorting unit 23 may sort particles on the downstream side of the flow path P based on analysis results of particle size, shape, internal structure, etc., which have been analyzed from the optical data. The classification method according to each embodiment is described below.

[0147] For example, in Figure 2 and Figure 3 In the illustrated embodiment, by applying vibration to all or part of the main flow path P13 using, for example, a vibrating element 23a vibrating at a predetermined frequency, droplets are generated from the outlet of the main flow path P13. Note that the vibrating element 23a used in this case is not specifically limited, and known vibrating elements can be freely selected and used. Examples include piezoelectric vibrating elements, etc. Furthermore, by adjusting the amount of liquid supplied to the sample liquid flow path P11, the sheath fluid flow paths P12a and P12b, and the main flow path P13, the diameter of the outlet, the frequency of the vibrating element, etc., the size of the droplets can be adjusted, and droplets each comprising a fixed number of particles can be generated.

[0148] Next, based on the particle size, shape, internal structure, etc., analyzed according to the optical data detected by the optical detection unit 22, a positive or negative charge is applied (see...). Figure 2 and Figure 3 (Ref. 23b). Then, the path of the charged droplets is changed in the desired direction by the applied voltage to the counter electrode 23c, and the charged droplets are classified.

[0149] In addition, for example, in Figure 4 In the illustrated embodiment, three branch flow paths—the sorting flow path P14 and the disposal flow paths P15a and P15b—are disposed downstream of the main flow path P13 formed on the substrate T. Particles determined to meet predetermined optical characteristics and used as sorting targets are introduced into the sorting flow path P14, while particles determined not to meet predetermined optical characteristics and not used as sorting targets are allowed to flow into either of the two disposal flow paths P15a and P15b and are not introduced into the sorting flow path P14. This enables sorting.

[0150] Using known methods, particles intended for sorting can be introduced into the sorting flow path P14. For example, by generating a negative pressure in the sorting flow path P14 using a vibrating element 23a (such as a piezoelectric element) and drawing a sample liquid, including particles intended for sorting or sheath fluid, into the sorting flow path P14 using this negative pressure, particles intended for sorting can be drawn into the sorting flow path P14. Furthermore, although not shown, particles intended for sorting can be introduced into the sorting flow path P14 by controlling or changing the laminar flow direction using valve electromagnetic force, fluid flow (gas or liquid), etc.

[0151] exist Figure 4 In the illustrated embodiment, the sample liquid storage unit B1, sheath fluid storage unit B2, sorting liquid storage unit B3, and waste liquid storage units B4a and B4b are respectively connected to the sample liquid flow path P11, the sheath fluid flow path P12a and P12b, the sorting flow path P14, and the disposal flow path P15a and P15b, thus forming a completely enclosed sorting device. For example, when the particles used as the sorting target are, for example, cells used in cell preparation, a completely enclosed device (isolated from the external environment) is preferably designed to maintain a sterile environment and prevent contamination. Figure 4 The implementation method is shown below.

[0152] The information processing device 1, particle detection device 2, and particle detection system 3 described above according to this technology can be applied to automatic leveling, compensation, gate setting, etc., as described below.

[0153] (Automatic horizontal adjustment)

[0154] The optical data acquired changes due to the high voltage (HV) of the optical detector. In the prior art, the optical data level is manually set according to the user's perception to match the target value, and samples are prepared for this purpose. Conversely, in the normalized state, the applied voltage coefficient (St value) causing saturation can be calculated based on the already set applied voltage coefficient (St value) and the acquired optical data level. This allows the applied voltage coefficient (St value) to be adjusted to the target level using data that has already been detected once, and can be set to obtain the desired optical data level. Figure 14 The process of automatic horizontal adjustment is shown in the figure.

[0155] like Figure 14 As shown, first, a voltage coefficient (St value) is applied for each wavelength of the excitation light, and then the fluorescence from the particles is detected.

[0156] Next, the maximum value at each wavelength is obtained from the specified data. In this case, the specified data refers to the data from multiple samples in the gate.

[0157] Then, the applied voltage coefficient (St value) is reset in such a way that the maximum value at each wavelength matches the target value (e.g., half of the saturation).

[0158] It should be noted that Figure 14 The example shown illustrates the application of a voltage coefficient (St value) for each wavelength of the excitation light. However, when applying a voltage coefficient (St value) for each optical detector, the target value can be obtained by applying a voltage coefficient (St value) for each optical detector.

[0159] (Compensation Application)

[0160] After setting the high voltage (HV) of the optical detector, compensation is set based on the ratio of dye spillage. Therefore, if the high voltage (HV) of the optical detector changes, compensation needs to be set again. However, by changing the normalized applied voltage coefficient (St value), the change in the optical data level can also be calculated, thus allowing recompensation to be performed automatically.

[0161] For example, if the applied voltage coefficient (St value) of the optical detector is changed after compensation has already been performed, the compensation can be recalculated based on the applied voltage coefficient (St value).

[0162] As a specific example, the compensation coefficients are determined in such a way that the applied voltage coefficient (St value) of PMT 1 is 3 and the applied voltage coefficient (St value) of PMT 2 is 3, as described in Table 1 below.

[0163] [Table 1]

[0164]

[0165] Subsequently, for example, in order to improve the S / N ratio, it is assumed that the applied voltage coefficient (St value) of PMT 2 has become 4.

[0166] In the prior art, compensation has been set again. However, the amount of change in optical data level caused by the change in the applied voltage coefficient (St value) is known (in the case where the optical data level of St value 4 is ten times that of St value 3), so the compensation coefficient can be obtained by performing a calculation such that FITC-PMT2_PE_St4 = 7 * 10 = 70 (see Table 2).

[0167] Furthermore, in PE-PMT1_FITC, the level of PE-PMT2_PE_St4 is actually ten times larger, but the level of PE-PMT1_FITC_St3 is relatively lower. Therefore, by performing calculations, a compensation coefficient can be obtained such that PE_PMT1 = 30 / 10 = 3 (see Table 2).

[0168] [Table 2]

[0169]

[0170] (In the case of a door being installed)

[0171] If the applied voltage coefficient (St value) is varied for each wavelength of the excitation light, the optical data level changes. Therefore, the gate set in the initial experiment is recalculated. Thus, the gate is redefined due to the change in the level. For example, in Figure 14 In this example, in PMT1_FITC_St3 / PMT2_PE_St3, the level on both axes is 1 / 10 of the level in PMT1_FITC_St4 / PMT2_PE_St4. As mentioned above, this allows the door to be reset by multiplying by 1 / 10.

[0172] As described above, by employing this technology, even when the setting of the voltage to be applied is changed, the output level can be prevented from deviating from the gate in the case of a method for individually setting the voltage to be applied to each optical detector and detecting the intensity of light in each wavelength range.

[0173] <2. Information Processing Methods and Particle Detection Methods>

[0174] The information processing method according to this technology is a method for processing detected optical data when detecting fluorescence emitted by particles in a sample liquid flowing from a flow path P, and at least performs correction processing. Furthermore, setting processing, fluorescence separation processing, storage processing, display processing, etc., can be performed as needed. In the particle detection method according to this technology, at least optical detection processing and information processing are performed, and at least correction processing is performed during information processing. Furthermore, light irradiation processing, setting processing, fluorescence separation processing, storage processing, display processing, sorting processing, etc., can be performed as needed. It should be noted that each processing is the same as the processing performed by each unit of the information processing device 1, particle detection device 2, and particle detection system 3 according to this technology already described above; therefore, detailed descriptions of each processing are omitted here.

[0175] <3. Computer Programs>

[0176] The computer program according to this technology is a program used in processing the detected optical data in the detection of fluorescence emitted by particles in a sample liquid flowing from a flow path P, and is a program that enables the computer to have a correction function that corrects the optical data of fluorescence detected from particles by multiple optical detectors that have been set to be different in terms of applied voltage coefficients, so as to match the output level detected at the same applied voltage coefficient.

[0177] The computer program according to this technology is recorded on a suitable recording medium. Furthermore, the computer program according to this technology can be stored in a cloud environment, etc., and users can download the computer program from a personal computer, etc., via a network and use the computer program. It should be noted that the correction function in the computer program according to this technology is the same as the correction function of the correction unit 111 of the information processing device 1, particle detection device 2, and particle detection system 3 described above, therefore its description is omitted here.

[0178] It should be noted that this technology can also be implemented using the configurations described below.

[0179] (1) An information processing device, comprising:

[0180] The correction unit performs correction on the optical data of fluorescence detected from the particles by multiple optical detectors to match the output level detected at the same applied voltage coefficient, wherein the multiple optical detectors are configured to be different in terms of applied voltage coefficient. (2)

[0182] According to the information processing device in (1),

[0183] The applied voltage coefficient is calculated based on the voltage applied to each of the plurality of optical detectors and the characteristic quantities of optical data from each of the plurality of optical detectors. (3)

[0185] The information processing device according to any one of (1) to (2),

[0186] The correction unit performs correction on the optical data to match the output level detected at the minimum applied voltage coefficient. (4)

[0188] The information processing apparatus according to any one of (1) to (3) further includes:

[0189] The setting unit sets the applied voltage coefficient according to the output level of each of the plurality of optical detectors. (5)

[0191] Information processing apparatus according to any one of (1) to (4),

[0192] The particles include fluorescent reference particles that emit fluorescence with a predetermined wavelength bandwidth. (6)

[0194] According to the information processing device in (5),

[0195] Here, "particle" refers to the particle to be analyzed. (7)

[0197] The information processing apparatus according to (6) further includes:

[0198] The fluorescence separation processing unit performs fluorescence separation processing by using the following:

[0199] The value obtained by performing the correction on the optical data obtained from the fluorescent reference particle, and

[0200] The value obtained by performing the correction on the optical data obtained from the particle to be analyzed. (8)

[0202] The information processing apparatus according to (5) further includes:

[0203] The fluorescence separation processing unit performs fluorescence separation processing by using the following:

[0204] Optical data obtained from particles analyzed by multiple optical detectors set to differ in applied voltage coefficients, and

[0205] The values ​​obtained by recalculating the optical data obtained from the fluorescent reference particle through correction are matched with the output levels detected at the applied voltage coefficients, which have been set to be different in the detection of fluorescence emitted by the particle to be analyzed. (9)

[0207] A particle detection device, comprising:

[0208] An optical detection unit includes multiple optical detectors for detecting fluorescence emitted from particles; and

[0209] The information processing unit processes the optical data obtained from the optical detection unit.

[0210] The information processing unit includes:

[0211] The correction unit performs correction on the optical data detected by the multiple optical detectors to match the output level detected under the same applied voltage coefficient, although the multiple optical detectors differ in the applied voltage coefficient. (10)

[0213] According to the particle detection device in (9),

[0214] The plurality of optical detectors respectively receive rays of light emitted from the particles due to irradiation by excitation light having different wavelengths from each other. (11)

[0216] According to the particle detection device in (9) or (10),

[0217] The correction unit performs the correction on the optical data detected by multiple optical detectors to match the output levels detected under the same applied voltage coefficient, wherein the multiple optical detectors are configured to have different applied voltage coefficients for each excitation light ray having different wavelengths. (12)

[0219] According to any one of (9) to (11), the particle detection device

[0220] In this system, multiple optical detectors receive light emitted from the particles due to irradiation by excitation light of the same wavelength. (13)

[0222] According to the particle detection device in (12),

[0223] A voltage coefficient is applied to each of the plurality of optical detectors. (14)

[0225] An information processing method, comprising:

[0226] The optical data of fluorescence detected from particles by multiple optical detectors are corrected to match the output level detected under the same applied voltage coefficient, wherein the multiple optical detectors have been configured to be different in terms of applied voltage coefficient. (15)

[0228] A particle detection method, comprising:

[0229] Fluorescence emitted from particles was detected using multiple optical detectors; and

[0230] Process the optical data obtained in the detection.

[0231] The processing includes

[0232] The optical data detected by multiple optical detectors are corrected to match the output level detected under the same applied voltage coefficient, and the multiple optical detectors are set to be different in terms of applied voltage coefficient. (16)

[0234] A computer program that enables a computer to perform correction on optical data from fluorescence detected from particles by a plurality of optical detectors to match the output levels detected under the same applied voltage coefficient, wherein the plurality of optical detectors have been configured to be different in terms of the applied voltage coefficient. (17)

[0236] A particle detection device, comprising:

[0237] Multiple optical detectors are configured to detect light from particles, wherein at least one optical detector has an applied voltage coefficient different from the others; and

[0238] A processor, including a processing device and a memory storing instructions, which, when executed by the processing device, cause the processor to:

[0239] The optical data obtained from the particles is corrected based on the difference between the applied voltage coefficient of the plurality of optical detectors and the predetermined applied voltage coefficient. (18)

[0241] According to the particle detection apparatus of (17), the applied voltage coefficient is determined based on the relationship between the voltage applied to each of the plurality of optical detectors and the characteristic quantity of the optical data obtained from each of the plurality of optical detectors. (19)

[0243] According to the particle detection device of (17) or (18), the predetermined applied voltage coefficient is the smallest applied voltage coefficient among the applied voltage coefficients of a plurality of optical detectors. (20)

[0245] The particle detection apparatus according to any one of (17) to (19) further includes: a memory configured to store correction data obtained by correcting the optical data. (twenty one)

[0247] According to any one of (17) to (20) of the particle detection device, the processor resets the applied voltage coefficient based on the optical data of each of the plurality of optical detectors. (twenty two)

[0249] The particle detection apparatus according to any one of (17) to (21) further comprises a memory that stores optical data with applied voltage coefficients for each of a plurality of optical detectors. (twenty three)

[0251] According to any one of (17) to (22) a particle detection device, wherein the particle is a particle to be analyzed, and the processor performs fluorescence separation processing using optical data obtained from a single dye particle and correction data obtained by correcting and adjusting the optical data of the particle to be analyzed. (twenty four)

[0253] According to the particle detection device of (23), the fluorescence separation process is performed by using correction data obtained by correcting the optical data of the single dye particles. (25)

[0255] A particle detection apparatus according to any one of (17) to (24), wherein each of the plurality of optical detectors detects light emitted from a particle by irradiating an excitation light at a different wavelength from each other. (26)

[0257] According to any one of (17) to (24) of the particle detection apparatus, wherein two or more of the plurality of optical detectors are detected by irradiating light emitted from the particle by excitation light having the same wavelength. (27)

[0259] An information processing device, comprising:

[0260] A processor, including a processing device and a memory storing instructions, which, when executed by the processing device, cause the processor to:

[0261] The optical data of light detected from particles by the plurality of optical detectors are corrected based on the difference between the applied voltage coefficients of the plurality of optical detectors and a predetermined applied voltage coefficient.

[0262] At least one of the optical detectors has an applied voltage coefficient that differs from that of the other optical detectors. (28)

[0264] According to the information processing apparatus of (27), wherein the particles are single-staining particles, and the processor performs fluorescence separation processing by using optical data obtained from the particles to be analyzed and data corrected by correcting the optical data of the single-staining particles. (29)

[0266] According to the information processing device of (28),

[0267] The optical data of the single dye particles are corrected to adjust the output level of the particles to be analyzed, which are detected under the predetermined applied voltage coefficient. (30)

[0269] According to the information processing device of (28) or (29), fluorescence separation processing is performed by using correction data of the optical data of the particle to be analyzed. (31)

[0271] An information processing method, comprising:

[0272] The optical data of light detected from particles by the plurality of optical detectors are corrected based on the difference between the applied voltage coefficients of the plurality of optical detectors and a predetermined applied voltage coefficient.

[0273] At least one of the optical detectors has an applied voltage coefficient that differs from that of the other optical detectors. (32)

[0275] A particle detection method, comprising:

[0276] Detecting light from particles, wherein at least one optical detector has an applied voltage coefficient different from that of the other optical detectors;

[0277] The optical data obtained from the particles are corrected based on the difference between the applied voltage coefficients of the plurality of optical detectors and a predetermined applied voltage coefficient.

[0278] Those skilled in the art will understand that various modifications, combinations, sub-combinations and alterations may be made depending on design requirements and other factors, as long as they are within the scope of the appended claims or their equivalents.

[0279] [List of Reference Numbers]

[0280] 1. Information processing device

[0281] 2. Particle detection device

[0282] 3. Particle Detection System

[0283] P flow pathway

[0284] 21 Light Illumination Units

[0285] 22 Optical Detection Units

[0286] 11 Information Processing Unit

[0287] 111 Calibration Unit

[0288] 12, 112 Setting Unit

[0289] 13,113 Fluorescence Separation Processing Unit

[0290] 14,114 memory

[0291] 15, 115 display units

[0292] 16,116 User Interface

[0293] 23 sorting units.

Claims

1. A particle detection device, comprising: A plurality of optical detectors are configured to detect light from particles, each of the plurality of optical detectors having a corresponding applied voltage coefficient, wherein at least one of the plurality of optical detectors has an applied voltage coefficient higher than a predetermined applied voltage coefficient of the plurality of optical detectors; as well as A processor, including a processing device and a memory storing instructions that, when executed by the processing device, cause the processor to function. The optical data obtained from the particle by the plurality of optical detectors is corrected based on the difference between the corresponding applied voltage coefficient of each of the plurality of optical detectors and the predetermined applied voltage coefficient.

2. The particle detection device according to claim 1, in, Based on the predetermined applied voltage coefficient, the applied voltage coefficient of each of the plurality of optical detectors is determined according to the characteristic quantity of the optical data obtained from each of the plurality of optical detectors.

3. The particle detection device according to claim 1, The predetermined applied voltage coefficient is the smallest applied voltage coefficient among the corresponding applied voltage coefficients of the plurality of optical detectors.

4. The particle detection device according to claim 1 further includes a memory configured to store correction data obtained by correcting the optical data.

5. The particle detection apparatus of claim 1, wherein the processor resets the applied voltage coefficient based on optical data from each of the plurality of optical detectors.

6. The particle detection apparatus of claim 1 further includes a memory configured to store optical data and applied voltage coefficients for each of the plurality of optical detectors.

7. The particle detection device according to claim 1, wherein, The particle is the particle to be analyzed, and the processor performs fluorescence separation processing using optical data obtained from the single dye particle and correction data obtained by correcting the optical data of the particle to be analyzed.

8. The particle detection device according to claim 7, wherein, The fluorescence separation process is performed using correction data obtained by correcting the optical data of the single dye particles.

9. The particle detection device according to claim 1, Each of the plurality of optical detectors detects light emitted from the particle by irradiating excitation light at different wavelengths from each other.

10. The particle detection device according to claim 1, Two or more of the plurality of optical detectors detect light emitted from the particle by irradiating the particle with excitation light of the same wavelength.

11. An information processing apparatus, comprising: A processor, including a processing device and a memory storing instructions that, when executed by the processing device, cause the processor to function. Each of a plurality of optical detectors has a corresponding applied voltage coefficient. Optical data of light detected from particles by the plurality of optical detectors are corrected based on the difference between the corresponding applied voltage coefficients of the plurality of optical detectors and a predetermined applied voltage coefficient. At least one of the plurality of optical detectors has an applied voltage coefficient that is higher than the predetermined applied voltage coefficient of the plurality of optical detectors.

12. The information processing apparatus according to claim 11, The particles are single-stain particles, and the processor performs fluorescence separation processing using optical data obtained from the particles to be analyzed and correction data obtained by correcting the optical data of the single-stain particles.

13. The information processing apparatus according to claim 12, The optical data of the single dye particles are corrected to adjust the output level of the particles to be analyzed as detected under the predetermined applied voltage coefficient.

14. The information processing apparatus according to claim 12, The fluorescence separation process is performed using correction data obtained by correcting the optical data of the particles to be analyzed.

15. An information processing method, comprising: Each of a plurality of optical detectors has a corresponding applied voltage coefficient. Optical data of light detected from particles by the plurality of optical detectors are corrected based on the difference between the corresponding applied voltage coefficients of the plurality of optical detectors and a predetermined applied voltage coefficient. At least one of the plurality of optical detectors has an applied voltage coefficient that is higher than the predetermined applied voltage coefficient of the plurality of optical detectors.

16. A particle detection method, comprising: Each of a plurality of optical detectors has a corresponding applied voltage coefficient, and light from a particle is detected using the plurality of optical detectors, wherein at least one of the plurality of optical detectors has an applied voltage coefficient higher than a predetermined applied voltage coefficient of the plurality of optical detectors; as well as The optical data obtained from the particle is corrected based on the difference between the corresponding applied voltage coefficient of the plurality of optical detectors and the predetermined applied voltage coefficient.

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