Flow cytometer, biological sample analysis system and optical detection equipment

Abstract

There is provided a flow cytometer including an optical detection component that detects emitted light emitted by particles flowing in a flow path, generates the emitted light by applying light to the particles flowing in the flow path, where the optical detection device includes a plurality of light detector arrays, in each light detector array, in which the emitted light is emitted by the particles flowing in the flow path, and in which the emitted light is emitted by the particles flowing in the flow path. The photodetector elements are arranged in respective rows, and the plurality of photodetector arrays are arranged at predetermined intervals along a direction intersecting an arrangement direction of the respective rows of photodetector elements substantially parallel to each photodetector array.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of Japanese Priority Patent Application JP 2023-036453 filed Mar. 9, 2023, which is hereby incorporated by reference herein in its entirety. Technical Field

[0003] The present technology relates to flow cytometers, biological sample analysis systems, and optical detection devices. More specifically, the present disclosure relates to flow cytometers and biological sample analysis systems that perform analysis based on light generated by applying light to biological particles, as well as optical detection devices used in flow cytometers or biological sample analysis systems. Background Art

[0004] Sometimes, particle clusters, such as cells, microorganisms, and liposomes, are labeled with fluorescent dyes, particles of the clusters are irradiated with laser light, and the intensity and / or pattern of fluorescence generated by the excited fluorescent dyes is measured to measure the characteristics of the particles. A flow cytometer is an example of a particle analysis device that performs the measurements just described.

[0005] Biological sample analysis devices, such as flow cytometers, illuminate particles flowing in a stream in a line with laser light (excitation light) of a specific wavelength and detect the fluorescence and / or scattered light generated by each particle, allowing for individual analysis of multiple particles. Furthermore, the analysis results are sometimes used to separate desired biological particles. Devices with preparative separation capabilities are sometimes called cell sorters.

[0006] Such a biological sample analysis device as described above includes an optical detection device for analysis. Several technologies related to optical detection devices have been disclosed. For example, the following patent document 1 discloses a fluorescence signal acquisition device, which has multiple light sources that irradiate a measurement object containing multiple fluorescent bodies with multiple excitation light rays modulated by carrier waves with different frequencies, multiple fluorescence detection units that detect multiple fluorescent rays generated in response to the multiple excitation light rays; and a synchronous detection unit that synchronously detects the detection signals detected by the fluorescence detection units to separate the fluorescent rays corresponding to the multiple fluorescent bodies (claim 1). As the fluorescence detection unit, a photomultiplier tube is mentioned (claim 11).

[0007] [Citation List]

[0008] [Patent Document]

[0009] [Patent Document 1]

[0010] Japanese Patent Publication No. 2015-145829 Summary of the Invention

[0011] [Technical Issues]

[0012] Biological sample analysis systems such as flow cytometers detect weak fluorescence or scattered light generated from cells. To detect such weak light, a highly sensitive optical detection device is used. As an optical detection device, for example, a photomultiplier tube (also referred to as a PMT) is used as described above.

[0013] Biological sample analysis systems that perform optical detection using optical detection devices such as those described above often have increased size. This is particularly important when the biological sample analysis system is configured so that biological particles are illuminated with light using multiple light irradiation spots. For example, in the biological sample analysis apparatus just described, multiple optical detection units are provided to individually detect light from the multiple light irradiation spots. This results in an increase in the number of optical detection devices and an increase in the complexity of the configuration of the optical system for introducing light into each optical detection device, which in turn increases the size of the biological sample analysis system.

[0014] There is a need to reduce the size of biological sample analysis systems. Reducing the size of a biological sample analysis system makes it easier for its users to use it and also allows its users to more widely utilize the experimental environment. Therefore, it is desirable to reduce the size of the above-mentioned biological sample analysis system.

[0015] [Solution to the problem]

[0016] According to an embodiment of the present disclosure, there is provided a flow cytometer including an optical detection device that detects light generated by applying light to biological particles flowing in a flow path, wherein the optical detection device includes a plurality of light detector arrays, in each of which light detector elements are arranged in a row, and the plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with an arrangement direction of the light detector arrays.

[0017] The plurality of light detector arrays may be arranged in a manner corresponding to the flow direction of the flow path.

[0018] Each of the plurality of photodetector arrays may be a photodetector array in which photomultiplier tube elements are arranged in rows, a photodetector array in which avalanche photodiode elements are arranged in rows, or a photodetector array in which photomultiplier tube elements are arranged in rows or a photodetector array in which avalanche photodiode elements are arranged in rows.

[0019] Each of the plurality of photodetector arrays may be a photodetector array in which photomultiplier tube elements are arranged in rows.

[0020] Each of the photomultiplier tube elements may be a photomultiplier tube element including a dynode or a photomultiplier tube element including a semiconductor element including a multistage dynode.

[0021] The optical detection device may be a multi-pixel photon counter.

[0022] The flow cytometer may include a light irradiation section that irradiates biological particles flowing in the flow channel with light at a plurality of light irradiation positions along a flow direction of the flow channel.

[0023] Each of the plurality of light irradiation positions may be irradiated with light having wavelengths different from each other.

[0024] The flow cytometer may be configured to detect light rays originating from light application at two or more positions among a plurality of light irradiation positions by one optical detection device.

[0025] Multiple photodetector arrays may be configured such that their gains are allowed to be adjusted independently of each other.

[0026] The plurality of photodetector units included in the photodetector array may be configured so as to allow their gains to be adjusted independently of each other.

[0027] One or more of the plurality of photodetector arrays may be configured such that positions thereof in a direction intersecting with an arrangement direction of the photodetector arrays are allowed to be changed independently of each other.

[0028] One or more of the plurality of photodetector arrays may be configured such that positions thereof in the arrangement direction of the photodetector arrays are allowed to be changed independently of each other.

[0029] The optical detection device may further include a microlens array, and the microlens array may be provided such that each lens constituting the microlens array is present on each light detector element of the optical detection device.

[0030] The flow cytometer may include a propagation light path along which light generated by the light application propagates to the optical detection device, and the propagation light path may include one or more optical fibers.

[0031] The flow cytometer may further include a light irradiation unit and a propagation light path, wherein the light irradiation unit irradiates the biological particles flowing in the flow path with light at multiple light irradiation positions along the flow direction of the flow path, and the light generated by the light application of the light irradiation unit is propagated along the propagation light path to the optical detection device.

[0032] The propagation optical path may include a plurality of optical fiber core optical paths, and the plurality of optical fiber core optical paths may be arranged at light incident side ends thereof in a manner corresponding to intervals between the plurality of light irradiation positions.

[0033] The flow cytometer may further include a light irradiation unit and a propagation light path, wherein the light irradiation unit irradiates the biological particles flowing in the flow path with light at multiple light irradiation positions along the flow direction of the flow path, and the light generated by the light irradiation of the light irradiation unit is propagated along the propagation light path to the optical detection device.

[0034] The propagation optical path may include a plurality of optical fiber core optical paths, and the plurality of optical fiber core optical paths may be arranged at light exit side ends thereof in a manner corresponding to intervals between the photodetector arrays.

[0035] The flow cytometer may further include a propagation light path along which light generated by applying light to the biological particles flowing in the flow path propagates to the optical detection device, and a field stop may be inserted in the propagation light path.

[0036] At least one of the plurality of photodetector arrays may include 10 or more photodetector cells.

[0037] The plurality of light detector elements included in the optical detection device may be configured to be capable of detecting light temporally independently of one another.

[0038] In addition, according to another embodiment of the present disclosure, a biological sample analysis system is provided, which includes an optical detection device that detects light generated by applying light to biological particles flowing in a flow path, wherein the optical detection device includes a plurality of light detector arrays, in each light detector array, the light detector elements are arranged in a row, and the plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with the arrangement direction of the light detector arrays.

[0039] In addition, according to another embodiment of the present disclosure, an optical detection device is provided, which includes a plurality of light detector arrays, the light detector elements in each light detector array being arranged in a row, wherein the plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with the arrangement direction of these light detector arrays, and are used to detect light generated by applying light to biological particles flowing in a flow path.

[0040] The optical detection device may be used in combination with a light irradiation section that irradiates the biological particles with light at a plurality of light irradiation positions along the flow direction of the flow path.

[0041] The optical detection apparatus may be used in combination with a spectral optical system that spectrally disperses a plurality of light rays generated by applying light at a plurality of light irradiation positions.

[0042] Two or more of the plurality of photodetector arrays may include at least one photodetector element having a common detection wavelength range between the two or more photodetector arrays. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 is a diagram depicting an example of the configuration of a flow cytometer.

[0044] Figure 2 is a diagram depicting an example of a configuration of a flow cytometer according to an embodiment of the present disclosure.

[0045] Figure 3A is a diagram depicting an example of a configuration of an optical detection apparatus.

[0046] Figure 3B is a diagram depicting an example of a configuration of an optical detection apparatus.

[0047] Figure 4 is a diagram depicting an example of a configuration of a hybrid photodetector.

[0048] Figure 5 Schematic diagram showing the light irradiation position of the light irradiation unit.

[0049] Figure 6 is a schematic diagram showing the position change of the photodetector array.

[0050] Figure 7 FIG. 2 is a schematic diagram showing another position change of the photodetector array.

[0051] Figure 8 is a schematic diagram showing yet another position change of the photodetector array.

[0052] Figure 9 is a schematic diagram illustrating a modified example of the optical detection device.

[0053] Figure 10 is a schematic diagram illustrating another modified example of the optical detection device.

[0054] Figure 11 is a diagram depicting an example of the arrangement of a microlens array.

[0055] Figure 12 is a diagram depicting an example of the configuration of another flow cytometer according to an embodiment of the present disclosure.

[0056] Figure 13 is a diagram depicting an example of a schematic configuration of an optical fiber bundle.

[0057] Figure 14 Schematic diagram of the optical path designed by Spectral Optical Systems for light to the optical detection device.

[0058] Figure 15 is a schematic diagram depicting an incident surface in the case where light guided by the spectroscopic optical system is incident on the optical detection device.

[0059] Figure 16 is a schematic diagram illustrating a modified example of the optical detection device.

[0060] Figure 17 is a diagram depicting an example of a configuration of another flow cytometer according to an embodiment of the present disclosure.

[0061] Figure 18 is a diagram schematically depicting the overall configuration of a biological sample analysis device.

[0062] Figure 19A is a schematic diagram of an example of an optical fiber bundle.

[0063] Figure 19B is a schematic diagram of another example of an optical fiber bundle.

[0064] Figure 19C is a schematic diagram of an example of an optical fiber.

[0065] Figure 19D is a schematic diagram of another example of an optical fiber.

[0066] Figure 19E is a schematic diagram of another example of an optical fiber.

[0067] Figure 19F is a schematic diagram of another example of an optical fiber.

[0068] Figure 19G is a schematic diagram of another example of an optical fiber.

[0069] Figure 19H is a schematic diagram of another example of an optical fiber. DETAILED DESCRIPTION

[0070] Hereinafter, the preferred mode for carrying out the present disclosure is described. It should be noted that the embodiments described below represent representative embodiments of the present disclosure, and the scope of the present disclosure should not be limited to only these embodiments. It should be noted that the description of the present disclosure is given in the following order.

[0071] 1. First embodiment (flow cytometer)

[0072] (1) Basic configuration example

[0073] (2) Example of configuration of optical detection equipment

[0074] (3) Relationship with the light irradiation part

[0075] (4) Modification of the optical detection device

[0076] (4-1) Position Change

[0077] (4-2) Modification of Photodetector Array

[0078] (4-3) Microlens Array

[0079] (5) Utilization of optical fiber

[0080] (6) Other examples of configuration (use of multiple optical detection devices)

[0081] (7) Embodiments not including an objective lens

[0082] (8) Example of flow cytometer configuration

[0083] 2. Second embodiment (biological sample analysis system)

[0084] 3. Third embodiment (optical detection device)

[0085] 1. First embodiment (flow cytometer)

[0086] (1) Basic configuration example

[0087] As mentioned above, miniaturization is required for biological sample analysis systems such as flow cytometers. One of the main components of a biological sample analysis system is a detection unit, which includes an optical detection device that detects light generated by biological particles. This detection unit sometimes increases the size of the biological sample analysis system. Therefore, it is desirable to reduce the space occupied by the detection unit.

[0088] Examples of optical detection devices include image sensors such as charge-coupled devices (CCDs) and complementary metal oxide semiconductors (CMOSs). However, since these image sensors use a frame-mode readout method, it is difficult to detect light from each pixel independently. Furthermore, these image sensors lack the sensitivity to detect weak light, such as fluorescence from biological particles.

[0089] As light detectors having a higher sensitivity than that of image sensors, photomultiplier tubes and avalanche photodiodes (APDs) can be mentioned. The inventors have found that a specific optical detection device having such a light detector as just described is suitable for use with a biological sample analysis system (e.g., a flow cytometer).

[0090] Specifically, according to an embodiment of the present disclosure, a biological sample analysis system is provided, which includes an optical detection device that detects light generated by applying light to biological particles flowing in a flow path, and wherein the optical detection device includes a plurality of light detector arrays, in each of which light detector elements are arranged in a row, and the plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with an arrangement direction of these light detector arrays.

[0091] In one embodiment, the biological sample analysis system can be a flow cytometer. The optical detection device is suitable for detecting weak light, such as fluorescence and / or scattered light generated by applying light to biological particles (e.g., cells, liposomes, etc.) flowing in a flow path, and is particularly suitable for irradiating the biological particles with light at multiple locations.

[0092] The use of an optical detection device helps to reduce the size of a biological sample analysis system, and particularly helps to reduce the size of a detection portion.

[0093] Furthermore, the optical detection device can be configured so that the gain of the photodetector elements or photodetector array can be adjusted independently of each other. The signal intensity of fluorescent signals, etc., sometimes varies significantly depending on the wavelength. In such a case as just described, gain adjustment as described above can be used to maintain the dynamic range of each wavelength of light.

[0094] Furthermore, the plurality of light detector elements included in the optical detection device may be configured to be capable of detecting light temporally independently of one another. This enables the light detector elements to detect light independently of one another in real time.

[0095] Hereinafter, the present disclosure will be described in more detail with reference to the accompanying drawings.

[0096] It is considered that the detection unit used in the flow cytometer is, for example, as follows Figure 1 Constructed in the described manner. Figure 1 It is a schematic diagram of the detection unit.

[0097] Figure 1 The flow cytometer 100 shown in FIG. 1 is configured to irradiate biological particles P flowing in a flow channel C provided in a flow cell 110 with light. Figure 1 , the bioparticles P flow in the direction indicated by the dotted arrow mark.

[0098] The light irradiation section (not shown) of the flow cytometer is configured to irradiate a plurality of positions with light. Figure 1 , three light irradiation positions S1 to S3 are depicted. Specifically, the light irradiation unit is configured to irradiate each of the three light irradiation positions with light (especially laser light), and includes, for example, three laser light sources. The laser light sources emit light having different wavelengths from each other.

[0099] As biological particles P flow through the flow path C, they pass through light irradiation positions. As they pass through, the particles are irradiated with light at each light irradiation position, and light is generated from the particles by the irradiation. The generated light passes through the objective lens 120, through the flow path-side light guide optical system 130, and then reaches the optical fiber bundle 140.

[0100] The objective lens 120 is configured so that three light irradiation positions S1-S3 exist within its field of view V. The flow path-side light guide optical system 130 is a light guide optical system that guides light emitted from the objective lens 120 to the optical fiber bundle serving as the propagation light path. The aforementioned components can be configured as known in the relevant technical field, and those skilled in the art can appropriately configure them.

[0101] The optical fiber bundle 140 is a bundle having a number of optical fiber cores corresponding to the number of optical detection devices 180 (180-1, 180-2, and 180-3) described below, or may be a bundle having a number of optical fiber cores equal to or greater than the number of optical detection devices 180. The bundle may include a plurality of optical fibers bundled together, each of the plurality of optical fibers including, for example, a core, a cladding surrounding the core, and a cover surrounding the cladding. In this case, the optical fiber bundle 140 may include a number of optical fibers equal to or greater than the number of optical detection devices.

[0102] Alternatively, the bundle may include a plurality of core-clad groups, each core-clad group including a single core and a cladding surrounding the core, and a single covering layer, wherein the core-clad groups are bundled together, and the single covering layer covers the bundled core-clad groups. In this case, the optical fiber bundle 140 may include a number of core-clad groups equal to or greater than the number of optical detection devices.

[0103] In addition, instead of the optical fiber bundle, an optical fiber having a single cladding including a plurality of cores may be used. In this case, the number of cores included in the optical fiber may be equal to or greater than the number of optical detection devices.

[0104] At the flow path side end EI of the optical fiber bundle 140, the position of the optical fiber core is fixed. Figure 1 In the example, the optical fiber bundle is configured such that the three cores EC1, EC2, and EC3 are arranged at predetermined intervals. The intervals between the cores correspond to the intervals between the light irradiation positions S1 to S3 and can be, for example, calculated by multiplying the intervals between the light irradiation positions S1 to S3 by a predetermined magnification factor. Light entering the flow path side end EI travels toward the optical detection device side ends EO1 to EO3.

[0105] The optical fiber bundle 140 is split in the middle and branched into three optical fibers, and the number of the branched optical fibers corresponds to the number of the optical detection devices. Figure 1 The flow cytometer in FIG. 1 includes three optical detection devices, and correspondingly, the optical fiber bundle 140 is branched into three optical fibers.

[0106] The light emitted from the branched optical fiber 140 - 1 passes through the detector-side light guide optical system 150 - 1 and reaches the spectroscopic optical system 160 - 1 .

[0107] Although the detector-side light guide optical system 150-1 is depicted as Figure 1Although the detector-side light-guiding optical system is simplified in the illustration, the configuration of the detector-side light-guiding optical system is obviously not limited to this. It is sufficient if the detector-side light-guiding optical system is configured to allow light emitted from optical fiber 140-1 to be directed to a desired position in spectroscopic optical system 160-1. This configuration can be appropriately designed by those skilled in the art. For example, the detector-side light-guiding optical system may include one or more lenses and / or one or more reflective mirrors.

[0108] Note that, in this specification, the detector-side light guide optical systems 150 - 1 , 150 - 2 , and 150 - 3 are sometimes collectively denoted by reference numeral 150 .

[0109] Although Figure 1 While the spectral optical system 160-1 is described as a reflective diffraction grating, it is apparent that the configuration of the spectral optical system is not limited to this. As long as the spectral optical system has optical properties that allow spectral dispersion for each wavelength, and is therefore a spectrometer, its configuration can be appropriately designed by those skilled in the art. Because the spectral optical system spectrally disperses light at each wavelength, optical data for each wavelength is obtained. For example, the spectral optical system is not limited to a reflective diffraction grating and can be a transmissive diffraction grating or a prism. The prism can be a single prism or a combination of multiple prisms.

[0110] It should be noted that in this specification, the spectroscopic optical systems 160 - 1 , 160 - 2 , and 160 - 3 are sometimes collectively denoted by reference numeral 160 .

[0111] The light rays spectrally dispersed for each wavelength by the spectral optical system arrive at the telecentric condenser lens 170-1. The telecentric condenser lens parallelizes the optical axes of the spectrally dispersed light rays and emits them toward the optical detection device 180-1. Figure 1 The telecentric condenser lens is shown as a single lens, but it will be apparent to those skilled in the art that its configuration is not limited thereto. It is sufficient for the telecentric condenser lens to be configured to collimate spectrally dispersed light rays, and its configuration can be appropriately designed by those skilled in the art. For example, while the telecentric condenser lens can be a single lens, it may also include multiple lenses.

[0112] It should be noted that in this specification, the telecentric condenser lenses 170 - 1 , 170 - 2 , and 170 - 3 are sometimes collectively denoted by reference numeral 170 .

[0113] The optical detection device 180-1 is configured such that a plurality of light detector elements 181 are arranged in a row, as shown in FIG. Figure 1 As shown. Although Figure 1In the figure, five photodetector elements are arranged in a row. However, it will be apparent to those skilled in the art that the number of such elements arranged in a row is not limited to five. For example, each photodetector element may be a photodetector (PMT). The photodetector elements serve as fluorescence channels. Photons entering through the entrance window of each PMT are converted into photoelectrons on the photoelectric surface, amplified, and output as electrical signals. The output electrical signals serve as optical data for bioparticle analysis by the information processing unit described below.

[0114] Likewise, light emitted from the optical fiber 140-2 passes through the detector-side light guide optical system 150-2, the diffraction grating 160-2, and the telecentric condensing lens 170-2, and is detected by the optical detection device 180-2, as previously described with respect to the light output from the optical fiber 140-1.

[0115] Furthermore, light emitted from the optical fiber 140-3 passes through the detector-side light guide optical system 150-3, the diffraction grating 160-3, and the telecentric condensing lens 170-3, and is detected by the optical detection device 180-3, as previously described with respect to the light output from the optical fiber 140-1.

[0116] The three laser sources included in the light irradiation section are assigned to three optical detection devices 180-1 to 180-3, respectively. Optical detection device 180-1 detects light generated by applying light to biological particles at light irradiation position S1 using one laser source. Optical detection devices 180-2 and 180-3 detect light generated by applying light to biological particles at light irradiation position S2 using another laser source, and light generated by applying light to biological particles at light irradiation position S3 using another laser source, respectively. In this manner, the laser sources and optical detection devices have a one-to-one relationship.

[0117] In order to perform optical inspection by an optical inspection device, Figure 1 The illustrated arrangement of various optical components is based on a one-to-one relationship. For example, to allow light to reach each of the optical detection devices 180-1 to 180-3, a detector-side light guide system, a spectral optical system, and a telecentric focusing lens are provided along the optical path between the optical fiber and the optical detection device. In particular, the number of light guide systems, diffraction gratings, and focusing lens sets increases according to the number of optical detection devices. Consequently, the size of the flow cytometer may increase.

[0118] A flow cytometer according to an embodiment of the present disclosure includes a specific optical detection device. The specific optical detection device includes a plurality of photodetector arrays, in each of which photodetector elements are arranged in rows, and the plurality of photodetector arrays are arranged at predetermined intervals along a direction intersecting with the arrangement direction of the photodetector arrays. Therefore, the configuration of the optical system incorporated in the flow cytometer can be made compact. Specifically, the number of optical components such as the light guide optical system, the spectral optical system, and the telecentric focusing lens can be reduced, which contributes to the miniaturization of the flow cytometer.

[0119] exist Figure 2 An example of a schematic configuration of a flow cytometer according to an embodiment of the present disclosure is depicted in FIG. Figure 2 The flow cytometer 200 described in the foregoing is configured to illuminate biological particles P flowing in a flow path provided in a flow cell 210 with light. The flow cytometer includes an objective lens 220 and a flow path side light guide optical system 230. The objective lens 220 is configured so that three light irradiation positions S1 to S3 exist within its field of view V. The flow cell 210, the objective lens 220, and the flow path side light guide optical system 230 can be configured similarly to the above-mentioned respective embodiments. Figure 1 The flow cell 110 , the objective lens 120 , and the flow path side light guide optical system 130 are configured in the manner described above, and the description thereof is also applicable to the flow cytometer 200 .

[0120] Light emitted from the flow path side light guide optical system 230 passes through the field stop 240 , the detector side light guide optical system 250 , the spectral optical system 260 , and the telecentric condensing lens 270 and reaches the optical detection device 280 .

[0121] The field stop 240 may be configured to limit the observation target area, and for example, field stops A1 to A3 corresponding to respective light rays generated by light application at the light irradiation positions S1 to S3 may be provided. This makes it possible to prevent unnecessary stray light from leaking.

[0122] Light that has passed through the field stop 240 reaches the detector-side light-guiding optical system 250. The detector-side light-guiding optical system 250 is configured to guide light into the spectroscopic optical system 260. Regarding the optical components that constitute the detector-side light-guiding optical system 250, the description of the detector-side light-guiding optical system 150 given above applies. The detector-side light-guiding optical system 250 may include, for example, one or more collimating lenses for collimating light and / or one or more lenses for magnifying or shrinking the image of light. The configuration of the detector-side light-guiding optical system 250 can be appropriately designed by those skilled in the art.

[0123] like Figure 2As shown, three light rays generated by light irradiation at three light irradiation positions pass through the same detector-side light guide optical system 250. In this way, the flow cytometer according to an embodiment of the present disclosure can be configured so that one detector-side light guide optical system is used as an optical path for multiple light rays generated by light irradiation at multiple light irradiation positions.

[0124] Light exiting the detector-side light guide optical system 250 reaches the spectroscopic optical system 260. The spectroscopic optical system 260 spectrally disperses the light and allows the light to reach the telecentric condenser lens 270. The spectroscopic optical system 260 spectrally disperses the light at various wavelengths. Regarding the optical components that configure the spectroscopic optical system, the description of the spectroscopic optical system 160 given above applies. The spectroscopic optical system may be, for example, a diffraction grating (a transmission-type diffraction grating or a reflection-type diffraction grating) or a prism as described above in conjunction with the spectroscopic optical system 160.

[0125] In the case of using a prism as a spectroscopic optical system, although known materials that can be used for prisms, such as glass materials, can be appropriately used as the material constituting the prism, among these materials, it is preferable to use a material with a high internal transmittance. By using a material with a high internal transmittance, it can be expected that the loss of the amount of light entering the prism is reduced and the light is efficiently guided to the optical detection equipment. In particular, the use of a material with a high internal transmittance on the short-wave side makes it possible to reduce the influence of light attenuation that differs for each wavelength. In addition, if the surface of the prism is coated with an AR coating (anti-reflection coating: anti-reflection coating), the attenuation amount of light during spectral dispersion can be reduced.

[0126] Furthermore, using a material with high dispersibility as the material for constructing the prisms allows for appropriate separation of light entering the prisms for each wavelength, thereby reducing the number of prisms used in the optical path.

[0127] When a prism is used as a spectroscopic optical system, the size of the vertical angle and the like is adjusted according to the object for which the prism is used, thereby enabling the use of a prism designed in any shape.

[0128] like Figure 2 As shown, the three light rays generated by applying light at three light irradiation positions all pass through the same spectral optical system 260 and are spectrally dispersed by the spectral optical system. In this way, the flow cytometer according to an embodiment of the present disclosure can be configured so that one spectral optical system is used as the optical path for multiple light rays generated by applying light at multiple light irradiation positions.

[0129] The light rays spectrally dispersed by the spectral optical system 260 reach a telecentric condenser lens 270. The telecentric condenser lens 270 parallelizes the spectrally dispersed light rays and allows them to reach the optical detection device 280. The telecentric condenser lens may be configured in the manner as described above in conjunction with the telecentric condenser lens 170.

[0130] like Figure 2 As shown, the three light rays generated by applying light at the three light irradiation positions all pass through the same telecentric condenser lens 270 after passing through the spectral optical system 260, so that the advancing directions of the spectrally dispersed light rays are parallelized by the telecentric condenser lens, and the parallelized light rays reach the optical detection device. In this way, the flow cytometer according to an embodiment of the present disclosure can be configured so that a single telecentric condenser lens serves as an optical path for the multiple light rays generated by applying light at multiple light irradiation positions.

[0131] Figure 2 Also shown is the configuration of the light detector elements when viewed from the light incident surface W of the optical detection device 280. Figure 2 As shown in the area marked with reference numeral W in FIG, the optical detection device 280 includes three photodetector arrays 282-1 to 282-3, in each of which a plurality of photodetector elements 281 are arranged in a row.

[0132] exist Figure 2 In the embodiment of the present invention, five photodetector elements are arranged in a row in each photodetector array, but it is obvious to those skilled in the art that the number of such elements arranged in a row is not limited to five. The number of such elements can be appropriately selected by those skilled in the art, for example, according to the required number of fluorescence channels.

[0133] Furthermore, although the optical detection device 280 is Figure 2 Although three photodetector arrays are included in an optical detection device, the number of photodetector arrays included in one optical detection device is not limited to three. The number of photodetector arrays may vary, for example, depending on the number of light irradiation positions. For example, the optical detection device may include a number of photodetector arrays equal to the number of light irradiation positions. In some embodiments, the optical detection device may include a number of photodetector arrays that is less than or greater than the number of light irradiation positions.

[0134] The photodetector element serves as a fluorescence channel. Photons incident on the photodetector element are converted into photoelectrons on the photoelectric surface and amplified before being output as electrical signals. This output electrical signal serves as optical data for use in the information processing unit described below, for example, in biological particle analysis.

[0135] Figure 2The optical detection device 280 shown in the figure includes three light detector arrays 280-1 to 280-3, each light detector array including light detector elements arranged in a row. The light detector array 280-1 is assigned so as to detect light generated by the application of light at the light irradiation position S1; the light detector array 280-2 is assigned so as to detect light generated by the application of light at the light irradiation position S2; and the light detector array 280-3 is assigned so as to detect light generated by the application of light at the light irradiation position S3. Figure 2 As shown, the light irradiation positions S1 to S3 are arranged in a row along the flow direction, and the light detector arrays 280-1 to 280-3 are also arranged in a row in a relationship corresponding to the arrangement order of the light irradiation positions S1 to S3. In other words, the light detector arrays 280-1 to 280-3 are also arranged in a row in a manner corresponding to the flow direction of the biological particles.

[0136] It can also be considered that the three photodetector arrays are arranged at predetermined intervals along a direction intersecting with the arrangement direction of the photodetector arrays (specifically, in an orthogonal direction).

[0137] In this way, the optical detection device according to an embodiment of the present disclosure includes a plurality of light detector arrays, in each of which light detector elements are arranged in a row, and the plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with the arrangement direction of the light detector arrays.

[0138] The following reference Figure 3A and Figure 3B The optical detection device and the light detector elements included in the optical detection device are described in more detail. Figure 3A An example of the configuration of the light receiving surface side of the optical detection device is described, in which arrow marks are used to describe dimensions and dots indicate positions. Figure 3B An optical detection device housed in a housing is depicted.

[0139] Figure 3A The optical detection device 280 shown in FIG. 1 includes a plurality of detector arrays 282-1 to 282-3, in each of which light detector units 281 are arranged in a row. Figure 3A In FIG, each detector array includes 10 photodetector units, but the number of photodetector units included in each detector array is not limited to 10. In addition, although Figure 3A In the embodiment, the optical detection device 280 includes three detector arrays, but the number of detector arrays included in the optical detection device is not limited to three. Specific examples of the number of photodetector units included in each detector array and the number of detector arrays included in the optical detection device are described below.

[0140] like Figure 3BAs shown, the optical detection device 280 can be configured as a module housed in a housing 285 having a window through which the light detector array 282 is exposed. For example, the module can be connected to the information processing unit via a cable 286.

[0141] The plurality of detector arrays 282-1 to 282-3 are arranged in a manner aligned along a direction DB (also referred to as "intersecting direction DB") intersecting with the arrangement direction DA of the photodetector arrays. The arrangement direction DA and the intersecting direction DB are described below.

[0142] The plurality of detector arrays 282-1 to 282-3 are arranged such that the rows of their photodetector elements extend substantially parallel to each other, as shown in FIG. Figure 3A Specifically, the arrangement direction DA indicates a direction substantially parallel to the rows of the photodetector elements constituting the detector array.

[0143] In addition, Figure 3A , the three detector arrays 282 are arranged along an intersection direction DB. Specifically, the intersection direction DB may refer to a direction that is not parallel to the rows of light detector elements. More specifically, the multiple detector arrays 282 may be arranged so that a line connecting the center position (e.g., C1) of one detector array and the center position (e.g., C2) of another array located adjacent to (and arranged closest to) the one detector array intersects the arrangement direction DA.

[0144] exist Figure 3A , the detector array 282-1 and the detector array 282-2 are arranged so that a line interconnecting the center position C1 of the detector array 282-1 and the center position C2 of the detector array 282-2 intersects the arrangement direction DA orthogonally. Furthermore, the detector array 282-2 and the detector array 282-3 are arranged so that a line interconnecting the center position C2 of the detector array 282-2 and the center position C3 of the detector array 282-3 intersects the arrangement direction DA orthogonally. In short, the three detector arrays are arranged so that the center positions of the three detector arrays define a straight line and the straight line intersects the arrangement direction DA orthogonally.

[0145] It is to be noted that, as described below, the positions of the detector arrays may be changed in the arrangement direction, or in other words, the lines interconnecting their center positions may not necessarily intersect the arrangement direction orthogonally, and may intersect the arrangement direction to form an angle of less than 90 degrees between them, as long as this is permissible for optical detection.

[0146] One or more, two or more, or three or more of the photodetector elements comprising each of photodetector arrays 282-1, 282-2, and 282-3 can be configured to detect light of the same wavelength, and specifically can serve as the same fluorescence channel. For example, one or more, two or more, or three or more photodetector elements comprising photodetector array 283-1 can be configured to detect light in the same wavelength range as one or more, two or more, or three or more photodetector elements comprising photodetector arrays 283-2 or 283-3. For example, each photodetector array can include one or more, two or more, or three or more photodetector elements serving as the same fluorescence channel.

[0147] In this manner, one or more, two or more, or three or more photodetector elements included in each of the multiple photodetector arrays included in the optical detection device used in the embodiments of the present disclosure can be configured to detect light within the same wavelength range, and specifically, can be used as the same fluorescence channel. Furthermore, five or more, ten or more, or fifteen or more photodetector elements constituting each of the multiple photodetector arrays can be configured to detect light within the same wavelength range.

[0148] Furthermore, all photodetector arrays need not include the same number of photodetector elements. For example, the photodetector arrays may include photodetector elements that are different from each other. For example, at least one of the plurality of photodetector arrays may include five or more, 10 or more, or 15 or more photodetector elements.

[0149] For example, one-half or more, two-thirds or more, three-quarters or more, or four-fifths or more of the photodetector elements constituting each of the plurality of photodetector arrays may be configured to detect light within the same wavelength range.

[0150] In several embodiments, all photodetector elements comprising each of a plurality of photodetector arrays included in an optical detection device may be configured to detect light within the same wavelength range, and in particular may serve as the same fluorescence channel.

[0151] It should be noted that there may be one or more photodetector elements that do not detect light in the same wavelength range between photodetector arrays.

[0152] Advantages produced by examples of a flow cytometer including the optical detection device configured as described above and a method of using the optical detection device and the flow cytometer are described below.

[0153] exist Figure 1In the flow cytometer described in [1], each of the multiple optical detection devices includes a photodetector array (a plurality of photodetector units arranged in a row). In this case, in order to guide light to each optical detection device and spectrally disperse the light, it is necessary to provide a number of light guide optical systems, spectral optical systems, and telecentric focusing lenses corresponding to the number of optical detection devices.

[0154] On the other hand, Figure 2 In the flow cytometer described in [1], multiple detector arrays are incorporated into a single optical detection device. This reduces the number of light guide optical systems, spectral optical systems, and telecentric focusing lenses. This allows for miniaturization of the flow cytometer, and in particular, the detection unit.

[0155] Furthermore, for example, each detector array can acquire a spectrum of light generated from biological particles (e.g., a fluorescence spectrum). Furthermore, it is possible to acquire a spectrum of light generated by applying light from multiple excitation light sources (specifically, multiple excitation light sources having different wavelengths) to biological particles.

[0156] Furthermore, using a plurality of detector arrays arranged along a direction intersecting the arrangement direction (specifically, along an orthogonal direction), images of biological particles moving at high speed can be acquired.

[0157] For example, each of the multiple photodetector elements comprising a detector array can be configured to acquire the signal intensity of light generated by applying light to biological particles at a single light irradiation location (e.g., the signal intensity of light at the same wavelength or within the same wavelength range, specifically, the distribution of signal intensity in a direction transverse to the flow path). Furthermore, by acquiring signal intensity over a predetermined time period, distribution data of the signal intensity at each time point is obtained. By arranging the multiple distribution data along the time axis, two-dimensional image data of the biological particles can be obtained. In other words, the photodetector array is used to scan flowing particles.

[0158] Because the optical detection device includes multiple light detector arrays, the detector arrays can be configured so that they acquire light generated by applying light (excitation light) having different wavelengths to the biological particles at multiple light irradiation positions. This makes it possible to acquire multiple image data based on the light generated by applying light of each wavelength.

[0159] In this manner, a flow cytometer (and in particular an optical detection device) according to embodiments of the present disclosure may be configured to acquire images of biological particles.

[0160] Furthermore, although the optical detection device includes a plurality of detector arrays, some of the plurality of detector arrays can acquire spectra (particularly fluorescence) generated by applying light to biological particles as described above, while the remaining detector arrays can acquire image data of the biological particles in the manner described above. Because the flow cytometer according to an embodiment of the present disclosure includes the optical detection device described above, it can be configured to acquire both spectral data and image data as described above.

[0161] Furthermore, optical detection equipment can be used to obtain positional information about biological particles as they pass through light-irradiated locations. For example, positional information can be obtained by referring to signals obtained from a detector array, which is arranged orthogonally to the flow direction. To obtain positional information, for example, all multiple light-irradiated locations are illuminated with light of the same wavelength to obtain a spectrum of light in the flow direction.

[0162] (2) Example of configuration of optical detection equipment

[0163] Examples of configurations of optical detection devices are described in more detail below.

[0164] like Figure 3A As shown, an optical detection device according to an embodiment of the present disclosure includes multiple detector arrays, in each detector array, light detector elements are arranged in a row. Light detector elements can also be called light detector units. In other words, units with light detector functions can be arranged in a row.

[0165] In order to detect spectrally dispersed light of each desired wavelength, the number of photodetector elements included in each detector array is, for example, 5 or more, preferably 10 or more, and more preferably 15 or more.

[0166] From the perspective of ease of manufacture of optical detection devices, the number of photodetector elements included in each detector array is 100 or less, preferably 70 or less, and more preferably 50 or less. In several embodiments, this number can be, for example, 45 or less, 40 or less, or 35 or less. The number of photodetector elements can be, for example, 64, 48, 32, 16, 8, etc., and can particularly be 32 or 16. The number of photodetector units corresponds to the number of fluorescence channels of the flow cytometer. The number of photodetector elements included in each detector array can be varied depending on the number of channels.

[0167] Furthermore, by summing and processing the signals obtained from a plurality of consecutive photodetector elements, each detector array can be used as an array equivalent to a detector array having a smaller number of photodetector elements. By summing and processing the signals in this manner, the detector array can be considered equivalent to a detector array having a smaller number of photodetector elements. In other words, it is also possible to allow the detector array to correspond to the number of fluorescence channels without changing the number of photodetector elements.

[0168] Each photodetector element may be a photomultiplier tube or an avalanche photodiode. In other words, all photodetector elements constituting each detector array may be photomultiplier tubes or avalanche photodiodes. In some embodiments, each detector array may include photomultiplier tubes and avalanche photodiodes.

[0169] In a preferred embodiment, each light detector element may be a photomultiplier tube. In other words, each of the plurality of light detector arrays may be a light detector array comprising photomultiplier tube elements arranged in a row.

[0170] The photomultiplier tube element (hereinafter also referred to as "photomultiplier tube") may be a type including a dynode including a semiconductor element. As a photomultiplier tube including a dynode including a semiconductor element, for example, an HPD (hybrid photodetector) can be mentioned. Figure 4 An example of the configuration of the HPD is described. Figure 4 HPD 300 shown in FIG. 1 includes an incident window 301 through which light generated from biological particles enters; a photoelectric surface 302 from which electrons (photoelectrons) are emitted in response to the arrival of light; a focusing electrode section 303 that accelerates the photoelectrons; and a semiconductor element 304 (specifically, an avalanche breakdown diode) that multiplies the electrons in response to the incident electrons and outputs an electrical signal. Semiconductor element 304 can remain fixed on substrate 305. Furthermore, substrate 305 can be fixed to base 306. HPD 300 also includes a feed section 307, wiring 308 connecting feed section 307 and substrate 305, and a signal extraction section 309 that extracts signals from semiconductor element 304.

[0171] Light L incident through the incident window 301 reaches the photoelectric surface 302. When the light reaches the photoelectric surface 302, photoelectrons E are emitted from the photoelectric surface. The photoelectrons advance toward the avalanche diode 304 while being accelerated by the focusing electrode portion 303. The semiconductor element 304 is configured to function as a dynode (electron multiplying portion). The semiconductor element 304 generates electron-hole pairs according to the incident energy of the photoelectrons. If the photoelectrons enter the photoelectron incident surface of the semiconductor element, the photoelectrons are multiplied by the semiconductor element and an electrical signal is output.

[0172] A photomultiplier tube unit including a dynode including a semiconductor element is excellent in resolution per unit photoelectron and is particularly excellent in detecting weak light (especially fluorescence or scattered light) generated from biological particles.

[0173] The photomultiplier tube unit can be a type that includes multiple dynodes. As the photomultiplier tube just described, for example, a metal channel type or a microchannel plate type photomultiplier tube can be used. The photomultiplier tube just described is particularly suitable for detecting weak light generated by biological particles. In addition, the photomultiplier tube unit can be a circular cage type, a box type, a linear focus type, a box-line type, a circular line type, or a shutter type photomultiplier tube.

[0174] In another preferred embodiment, each photodetector unit can be an avalanche photodiode. In other words, the plurality of photodetector arrays can include a plurality of photodetector arrays, each of which is an avalanche photodiode arranged in a row. As an example of an optical detection device in this embodiment, a multi-pixel photon counter (MPPC) can be mentioned. However, this is not restrictive.

[0175] In a further preferred embodiment, the plurality of photodetector arrays may include both a photodetector array in which photomultiplier tube units are arranged in rows and a photodetector array in which avalanche photodiode units are arranged in rows.

[0176] For example, the MPPC outputs signals from multiple avalanche photodiodes as an accumulated signal. Simultaneously, an array of photomultiplier tube elements can output signals from each photomultiplier tube element. Therefore, preferably, the multiple photodetector arrays can be arrays of photomultiplier tube elements. Alternatively, each element of the array can include an MPPC.

[0177] Multiple photodetector arrays can be configured so that their gains can be adjusted independently of one another. Specifically, the optical detection device can be configured so that gain adjustment can be performed on an array-by-array basis. Gain adjustment can be easily performed, particularly when the photodetector elements are photomultiplier tubes or avalanche photodiodes.

[0178] When irradiating bioparticles with light from multiple laser beams of different wavelengths, the signal intensities of the fluorescence generated by the laser light application often differ. When a single laser beam and an array are associated with each other, signal output adjustment based on the laser beam intensity (or the signal intensity of the light generated by the laser beam application) can be performed by gain adjustment for each array, facilitating analysis of optical data.

[0179] Specifically, the flow cytometer according to an embodiment of the present disclosure can be configured so that the gain of each photodetector array can be adjusted. For example, the flow cytometer can be configured so that the gain of each photodetector array can be adjusted, for example, based on the signal intensity of each light (specifically, each laser) emitted from the light irradiation unit or based on the signal intensity of the light generated by light application. For example, the information processing unit described below can obtain data related to the intensity of each light or the signal intensity of the light generated by light irradiation, and then adjust the gain of each photodetector array with reference to the data.

[0180] The plurality of photodetector elements included in the photodetector array can be configured such that their gains can be adjusted independently of one another. In particular, the optical detection device can be configured such that gain adjustment can be performed for each photodetector element. Gain adjustment can be performed easily, particularly when the photodetector elements are photomultiplier tubes or avalanche photodiodes.

[0181] The signal intensity of the detected light sometimes differs depending on the position of one photodetector array in the arrangement direction. Therefore, adjusting the gain of each photodetector element in the detector array makes it possible to obtain a more appropriate analysis result.

[0182] Specifically, a flow cytometer according to an embodiment of the present disclosure may be configured to adjust the gain of each photodetector element in a detector array. For example, in a flow cytometer, the gain of each photodetector element in the detector array may be adjusted based on the signal intensity of light detected by each photodetector element. For example, an information processing unit described below may acquire data related to the signal intensity of light detected by each detector element and adjust the gain of each photodetector element based on this data.

[0183] In addition, if Figure 2 As shown in FIG3 , the optical detection device 280 includes a plurality of detector arrays 282. In each detector array, light detector units 281 are arranged in a row. The number of detector arrays included in the optical detection device 280 is not limited to Figure 2 and 3 or 10 in Fig. 3. The number of detector arrays may be equal to the number of light irradiation positions, for example, or may be equal to the number of types of laser light sources included in the light irradiation section.

[0184] For example, the number of detector arrays included in the optical detection device may be two or more, preferably, three or more, more preferably, four or more.

[0185] Although the upper limit of the number of detector arrays included in the optical detection device may not be particularly limited, it may be, for example, 20 or less, particularly 15 or less, more particularly 10 or less, 9 or less, or 8 or less.

[0186] The optical detection device may include a housing or a channel window configured to allow light generated by applying light to the biological particles to pass therethrough. The shape of the housing or channel window may be as follows: Figure 2 3 or may be a circular shape. The size L1 of the housing or the channel window may be, for example, 100 mm or less, preferably 80 mm or less, and more preferably 60 mm or less. Although the lower limit of the size L1 may not be particularly limited and may be appropriately changed according to, for example, the size and number of the photodetector array, it may be, for example, 5 mm or more, 10 mm or more, 20 mm or more, or 30 mm or more.

[0187] If the housing or access window is rectangular, dimension L1 is the length of one side or the longer side. If the housing or access window is circular, dimension L1 represents the diameter of the circle. Note that a circle includes a true circle and an ellipse. If the circular shape is an ellipse, dimension L1 represents the length of the longer diameter of the ellipse.

[0188] Multiple photodetector arrays can be arranged in the intersection direction with a pitch interval LP of, for example, 5 mm or less, and in particular can be 4 mm or less, preferably 3 mm or less, more preferably 2 mm or less, and in several embodiments, can be equal to or less than 1 mm or less.

[0189] The lower limit of the pitch interval can be determined based on the size of each photodetector unit in the intersecting direction (particularly, in the orthogonal direction). For example, when adjacent photodetector arrays are in contact with each other, the size of the photodetector array corresponds to the lower limit of the pitch interval. Therefore, although the lower limit of the pitch interval is not particularly limited, it can be, for example, 0.3 mm or more, preferably 0.4 mm or more, more preferably 0.5 mm or more, and most preferably 0.6 mm or more.

[0190] The pitch interval is the interval between two photodetector arrays adjacent to each other, and is, for example, the interval between the center positions of the sizes of two detector arrays adjacent in their intersecting direction (flow direction).

[0191] The total length LA of each of the multiple photodetector arrays in the arrangement direction of the photodetector units can be, for example, 50 mm or less, preferably 40 mm or less, more preferably 30 mm or less, in particular can be equal to 20 mm or less, or can also be 15 mm or less.

[0192] The above-mentioned total length may be, for example, 3 mm or more, preferably 5 mm or more, more preferably 7 mm or more.

[0193] The pitch interval of the photodetector cells in each photodetector array may be, for example, 0.05 mm or more, preferably 0.1 mm or more, more preferably 0.2 mm or more.

[0194] The above-mentioned pitch interval may be, for example, 5 mm or less, preferably 3 mm or less, more preferably 1 mm or less.

[0195] Although a dead zone may exist between adjacent photodetector units in each photodetector array, the width of the dead zone is preferably 100 μm or less, more preferably 80 μm or less, and most preferably 70 μm or less. Preferably, the width of the dead zone is 30% or less, preferably 25% or less, and more preferably 20% or less of the size of each photodetector unit in the arrangement direction.

[0196] In order to detect light with higher certainty, the dimension Ldb of each photodetector unit in the direction perpendicular to the arrangement direction may be 0.3 mm or more, preferably 0.4 mm or more, more preferably 0.5 mm or more, and most preferably 0.6 mm or more.

[0197] From the viewpoint of miniaturization of the optical detection apparatus, the above-mentioned dimension Ldb may be, for example, 3 mm or less, preferably 2 mm or less, and more preferably 1.5 mm or less.

[0198] Furthermore, in order to detect light with higher certainty, the dimension Lda of each light detector unit in the direction parallel to the arrangement direction may be 0.3 mm or greater, preferably 0.4 mm or greater, more preferably 0.5 mm or greater, and may also be 0.6 mm or greater.

[0199] From the viewpoint of miniaturization of the optical detection apparatus, the dimension Lda described above may be 3 mm or less, preferably, 2 mm or less, more preferably, 1.5 mm or less.

[0200] The optical detection device may be of a type having a photoelectric surface. In other words, each light detector unit may have a photoelectric surface.

[0201] The highest quantum efficiency of photoelectric conversion performed by the photoelectric surface may be, for example, 5% or more, preferably 10% or more, more preferably 15% or more.

[0202] In addition, the upper limit of the maximum quantum efficiency may not be particularly set, and may be, for example, 60% or less, 50% or less, or 40% or less.

[0203] The cathode luminance sensitivity of the photovoltaic surface is, for example, 100 μA / lm or more, preferably 200 μA / lm or more, more preferably 300 μA / lm or more, and most preferably 400 μA / lm or more.

[0204] Although the upper limit of the cathode luminance sensitivity of the photovoltaic surface may not be particularly limited, it may be, for example, 1000 μA / lm or more.

[0205] In the case where the optical detection device includes a photodetector array in which photomultiplier tube units are arranged in a row, for example, the current amplification factor of the dynode of each photomultiplier tube unit may be 10 4 or greater, preferably, 10 5 or greater, more preferably, 0.5×10 6 or greater, most preferably, 10 6 or larger.

[0206] Although the upper limit of the current amplification ratio may not be particularly limited, it may be, for example, 10 12 or smaller, 10 10 or smaller, or 10 8 or smaller.

[0207] In the case where the optical detection device includes a photodetector array in which photomultiplier tube units are arranged in a row, the dark current of the dynode of each photomultiplier tube unit is, for example, 5 nA or less, preferably 4 nA or less, and more preferably 3 nA or less per photomultiplier tube unit. The dark current is preferably as small as possible, and although the lower limit of the dark current does not need to be particularly limited, it may be, for example, 0 nA or more per photomultiplier tube unit.

[0208] Furthermore, the dynodes of the photodetector cells may be configured such that their gains may be corrected independently of each other.

[0209] The lower limit of the ratio between the gains adjustable in the elements of the array may be, for example, 1:1, 10:1 or 100:1 or more. The upper limit of the ratio may be at least 100:1, preferably 1000:1, more preferably 10000:1.

[0210] This ratio is used to correct for dispersion in the element's own gain or sensitivity, and corrects this dispersion so that when equal amounts of light are input, equal output is output. Furthermore, if there is a wavelength region where the spectral light obtained from the sample is generally dark, correction can be performed to increase the gain of the element corresponding to that wavelength region.

[0211] Each optical detection device may include an output circuit that outputs an electrical signal. For example, the output circuit may be configured so that the maximum output signal voltage of each photodetector unit is 0.01V or greater, preferably 0.03V or greater, and more preferably 0.05V or greater, averaged over time.

[0212] Furthermore, the output circuit may be configured such that the highest output signal voltage of each photodetector unit is, for example, 10 V or less, preferably 1 V or less, on a time average.

[0213] The frequency band of the output circuit may be, for example, DC-5 MHz, preferably DC-4 MHz, more preferably DC-3.5 MHz, and in several embodiments, may be DC-3 MHz, DC-2.5 MHz or DC-2 MHz.

[0214] For example, the current-voltage conversion characteristic of the output circuit may be 0.001 V / μA or greater, preferably, 0.005 V / μA or greater.

[0215] The current-voltage conversion characteristic of the output circuit may be, for example, 10 V / μA or less, preferably 1 V / μA or less.

[0216] The output circuit may include, for example, a low-pass filter to reduce ripple noise, or may include another circuit known in the relevant art for reducing such ripple noise or may perform known processing for such ripple noise reduction.

[0217] Regarding the output circuit, the crosstalk between the photodetector cells can be, for example, 3% or less, preferably 2% or less, and more preferably 1.5% or less. The crosstalk value is the ratio of the signal output of the light-incident element to the numerator when light enters only a specific element, where the signal output of the light-incident element is the denominator and the signal output of the adjacent element is the numerator.

[0218] (3) Relationship with the light irradiation part

[0219] In a preferred embodiment of the present disclosure, a flow cytometer may include a light irradiation unit that irradiates biological particles flowing in the flow path with light at multiple light irradiation positions along the flow direction of the flow path. Since the above-mentioned optical detection device includes multiple light detector arrays, using them in combination with the light irradiation unit that irradiates biological particles with light at multiple positions in the flow path makes it possible to perform detailed biological particle analysis based on light generated by light application at these positions while achieving miniaturization of the flow cytometer. Specifically, a flow cytometer according to an embodiment of the present disclosure may include a light irradiation unit that includes two or more laser sources that perform off-axis irradiation.

[0220] The light irradiation unit that irradiates the multiple light irradiation positions with light can be configured to emit light having different wavelengths to the multiple light irradiation positions. The wavelength of the applied light can be, for example, 200 nm to 1000 nm, and particularly 300 nm to 900 nm. The light irradiation unit may include multiple laser light sources, each of which emits laser light having a central wavelength within a wavelength range. The laser light emitted from the multiple laser light sources is separately applied to the multiple light irradiation positions.

[0221] In some embodiments of the present disclosure, a flow cytometer may include a light irradiation unit that irradiates biological particles flowing in the flow path with light at a light irradiation position in the flow path. The optical detection device described above can be incorporated into the flow cytometer in combination with the light irradiation unit. In other words, the flow cytometer according to an embodiment of the present disclosure may include two or more laser sources through which coaxial irradiation is performed. The wavelength of the light used for irradiation is suitable for the description of the case of off-axis irradiation.

[0222] In this embodiment, for example, two or more laser sources are combined through a predetermined optical system and used for irradiation at the above-mentioned one light irradiation position. The predetermined optical system may include, for example, one or more half mirrors and / or one or more dichroic mirrors, etc., and may be appropriately designed by those skilled in the art.

[0223] In a particularly preferred embodiment of the present disclosure, the flow cytometer may include a light irradiation section that irradiates biological particles flowing in the flow path with light at multiple light irradiation positions along the flow direction of the flow path, and can be configured so that light originating from light application at two or more positions among the multiple light irradiation positions is detected by an optical detection device, and specifically, can be configured so that light originating from light irradiation at all positions among the multiple light irradiation positions is detected by a single optical detection device.

[0224] This makes it possible to reduce the number of optical elements such as the photodetector-side light guide optical system, the diffraction grating, and the telecentric condensing lens as described above and reduce the size of the flow cytometer.

[0225] The plurality of light detector arrays included in the optical detection device may be associated with a light source (particularly a laser light source) included in the light irradiation section. Figure 5 Describe the relationship.

[0226] Figure 5Three light irradiation positions S1, S2, and S3 are depicted. The light irradiation positions are irradiated with light beams of lasers L1, L2, and L3, respectively. Specifically, the light irradiation unit is configured to emit light beams of lasers L1, L2, and L3 so as to irradiate light irradiation positions P1, P2, and P3, respectively. The light beams of lasers L1, L2, and L3 may have different wavelengths. The three light irradiation positions can be observed through a single objective lens. Furthermore, the individual light beams generated by the application of light at the three light irradiation positions can be detected by a single optical detection device.

[0227] In this manner, the flow cytometer according to the embodiment of the present disclosure can be configured so that light generated by light application at a plurality of light irradiation positions is detected by a single optical detection device.

[0228] The biological particles P flow in the flow path C and are first irradiated by the laser L1, then by the laser L2, and finally by the laser L3. With each light application, light (eg, fluorescence and / or scattered light, etc.) is generated from the biological particles.

[0229] Furthermore, the optical detection device for detecting light generated by the application of light at the location may comprise three detector arrays, e.g. Figure 2 Or as shown in FIG3 . The optical detection device includes detector arrays 282-1, 282-2, and 282-3. Detector array 282-1 can be associated with laser L1, and similarly, detector array 282-2 can be associated with laser L2, and detector array 282-3 can be associated with laser L3. More specifically, detector array 282-1 detects light generated by applying light to particles with laser L1; detector array 282-2 detects light generated by applying light to particles with laser L2; and detector array 282-3 detects light generated by applying light to particles with laser L3. In this way, the light irradiation position and the detector array can be associated with each other in advance.

[0230] Specifically, the plurality of light irradiation positions are arranged along the flow direction of the particles, and in addition, the plurality of detector arrays in the optical detection device can be arranged to be associated with the plurality of light irradiation positions. The arrangement order of the plurality of detector arrays can be the same as the arrangement order of the light irradiation positions for performing light application, and the light generated by the light application can be individually detected by the plurality of detector arrays. In other words, the plurality of detector arrays can be arranged in a manner corresponding to the flow direction of the particles.

[0231] (4) Modification of the optical detection device

[0232] (4-1) Position Change

[0233] The optical detection device described in (2) above includes a plurality of light detector arrays. Each light detector array can be configured so that its position can be changed. Such position change of the light detector array will be described with reference to an example thereof.

[0234] (4-1-1) Changes in the position of the photodetector array in the flow direction

[0235] In one embodiment, the plurality of light detector arrays may be configured so that the positions of one or more of them in the arrangement direction of the arrays can be changed independently of each other. In other words, they may be configured so that the intervals between the arrays can be adjusted. Figure 6 Describe this.

[0236] Figure 6 Three detector arrays A1 to A3 are depicted. They may be configured such that one or more of them are movable along an arrangement direction DB of the arrays.

[0237] For example, Figure 6 As shown, among the three arrays, only array A2 can be configured so that its position can be changed, and arrays A1 and A3 can be configured so that their positions cannot be changed. In particular, array A2 can be moved toward array A3 or can be moved toward array A1.

[0238] Two of the three arrays can be configured so that their positions can be changed. For example, the position of array A2 can be fixed, while the positions of arrays A1 to A3 can be variable. Arrays A1 and A3 can be configured to be movable along the array arrangement direction DB. Alternatively, while array A1 is fixed, arrays A2 and A3 can be configured to be movable along the array arrangement direction DB, or while array A3 is fixed, arrays A1 and A2 can be configured so that their positions can be moved along the arrangement direction DB.

[0239] All three arrays may be configured so that their positions are changeable. In other words, all arrays A1 to A3 may be configured so as to be movable along the arrangement direction DB.

[0240] Although the foregoing description is given with respect to an optical detection apparatus comprising three detector arrays for simplicity of description, where the optical detection apparatus comprises four or more detector arrays, they may be similarly configured such that the position of one or more thereof can be changed.

[0241] Adjusting the spacing between arrays in this manner allows for appropriate array spacing to be implemented depending on the magnification of the flow path optical system or the detector optical system, or the configuration or state of the flow path optical system or the detector optical system. For example, depending on the optical components of the flow path optical system or the detector optical system, there may be situations where maintaining the spacing between light irradiation positions makes it difficult for the light generated by the light application to reach the optical detection device. There are also situations where the positions of the light irradiation positions in the flow direction are offset. In these cases, by adjusting the array spacing as described above, more appropriate optical detection becomes possible.

[0242] (4-1-2) Change in position of the photodetector array in the arrangement direction

[0243] In another embodiment, a plurality of photodetector arrays may be configured such that the position of one or more of them in the direction in which the photodetector units are arranged can be changed independently of each other. Figure 7 Describe this.

[0244] Figure 7 Three detector arrays A1 to A3 are depicted. The detector arrays A1 to A3 may be configured such that one or more of them can be moved in the direction of arrangement of the light detector units (arrangement direction of the detector units) DA.

[0245] For example, the three arrays may be configured so that only the position of array A2 can be changed, and the positions of arrays A1 to A3 are not allowed to be changed. Specifically, array A2 can be moved along the arrangement direction of the detector units and can be moved, for example, in Figure 7 Move left or right.

[0246] The three arrays may be configured so that the positions of two of them can be changed or the positions of all three of them can be changed.

[0247] Although the foregoing description is given of an optical detection apparatus including three detector arrays for simplicity of description, where the optical detection apparatus includes four or more detector arrays, they may be similarly configured such that the position of one or more thereof can be changed.

[0248] Adjusting the position of the array in the arrangement direction of the detector cells in the manner described above enables efficient detection of light generated by light application. For example, adjusting the position according to the position of particles in the flow path of the particles enables more appropriate optical detection. Furthermore, if the wavelength of light to be detected by each detector cell is predefined, the desired light can be detected more efficiently by adjusting the position described above.

[0249] For example, when fluorescence is spectrally dispersed for each wavelength by a spectroscopic optical system, the wavelengths of the spectrally dispersed light are arranged sequentially along the arrangement direction of the detector array, from short-wavelength light to long-wavelength light. Here, fluorescence typically has a wavelength equal to or longer than the wavelength of the excitation light. Therefore, if the position in the arrangement direction remains fixed, even if fluorescence with a wavelength shorter than the wavelength of the excitation light is absent, some photodetector elements in the photodetector array may be located at a position in the detector array where fluorescence with the absent wavelength would reach. These photodetector elements can be considered to be ineffectively used for optical detection. Therefore, shifting the position of the photodetector array along the arrangement direction can reduce the number of such photodetector elements that are ineffectively used for optical detection.

[0250] For example, Figure 8 As shown on the left side of FIG, in the photodetector array A2, the photodetector elements are arranged in a row from the position where light on the short wavelength side arrives (short) to the position where light on the long wavelength side arrives (long). Here, when the wavelength of the excitation light used to generate the fluorescence detected by the photodetector array A2 is the wavelength of light having a wavelength at the position represented by Lex, there is no fluorescence on the wavelength side shorter than Lex. Therefore, the position of the photodetector array A2 is shifted toward the long wavelength side, as shown in FIG. Figure 8 This can reduce the number of light detector elements that cannot be effectively used in fluorescence detection.

[0251] (4-1-3) Position Change of the Photodetector Array in Two Directions

[0252] In another embodiment, the plurality of light detector arrays may be configured so that the position of one or more of them in the arrangement direction of the arrays can be changed independently of each other, and the position of one or more of them in the arrangement direction of the light detector units can be changed independently of each other. Figure 6 and Figure 7 Same as described.

[0253] In order to perform such a position change of the light detector array as described above, the optical detection device may include an array position adjustment unit. For example, the array position adjustment unit may be configured to perform array position adjustment using a power source (such as a piezoelectric actuator or a motor and a screw feed mechanism), or may be configured to move the array position using a tool (such as a driver) and, after adjustment, fix the position using a screw. The position of the light detector array can be controlled by the array position adjustment unit. The array position adjustment unit may be driven and controlled by the information processing unit described below.

[0254] (4-2) Modification of Photodetector Array

[0255] In FIG3 described in (2) above, all three photodetector arrays include 10 photodetector elements. Although the number of photodetector elements included in the photodetector arrays may be equal to that depicted in FIG3 , they may differ between two or more photodetector arrays. For example, Figure 9 The optical detection device 410 shown in FIG4 includes three photodetector arrays A11, A12, and A13. The number of photodetector elements included in the photodetector array A11 is 10, and the number of photodetector elements included in the photodetector array A12 and the photodetector array A13 are 12 and 14, respectively. As described above, the plurality of photodetector arrays included in the optical detection device according to an embodiment of the present disclosure may have different numbers of photodetector elements from each other. For example, the number of photodetector elements in one or two or more of the plurality of photodetector arrays included in the optical detection device may be different from the number of photodetector arrays in the optical detection device included in the other photodetector arrays.

[0256] In FIG. 3 described in (2) above, the positions of the three light detector arrays in the arrangement direction DA are identical to each other. In addition, as described in (4-1) above, the light detector arrays may be configured so that their positions can be changed in the arrangement direction. In an embodiment of the present disclosure, the positions of the plurality of light detector arrays in the arrangement direction DA may be different from each other in advance. For example, in Figure 10 The optical detection device 415 described in the embodiment includes four light detector arrays A21, A22, A23 and A24. The positions of the light detector arrays A21 and A22 in the arrangement direction DA are the same as each other. In addition, the positions of the light detector arrays A23 and A24 in the arrangement direction DA are the same as each other. At the same time, the positions of the light detector arrays A21 and A22 in the arrangement direction DA are different from the positions of the light detector arrays A23 and A24 in the arrangement direction DA. In this way, the positions of the plurality of light detector arrays included in the optical detection device according to an embodiment of the present disclosure may be different from each other in the arrangement direction. For example, the position of one or two or more light detector arrays among the plurality of light detector arrays included in the optical detection device in the arrangement direction may be different from the position of any other light detector array in the arrangement direction.

[0257] Note that the position of the photodetector array in the arrangement direction may mean the position of one of the opposite ends of the array in the arrangement direction, or may mean the center position of each array in the arrangement direction.

[0258] (4-3) Microlens Array

[0259] The optical detection device may further include a microlens array. The microlens array may be configured so that the light to be detected is focused on each light detector unit. This configuration makes it possible to more efficiently introduce light into the light detector. Figure 11 Describe microlens arrays.

[0260] like Figure 11 As shown, the microlens array MLA can be arranged so that light is focused on each photodetector element PDE. In particular, the microlens array can be configured so that there is one microlens unit LU on one photodetector element PDE.

[0261] The lens units of the microlens array may individually have a curvature in an arrangement direction DB, may have a curvature in an array arrangement direction DA (a direction from this side toward the rear of the figure), or may have a curvature in both directions.

[0262] (5) Use of optical fiber

[0263] The flow cytometer may have a propagation light path that propagates the light generated by the light application to the optical detection device, and the propagation light path may include one or more optical fibers. The number of optical fibers may be appropriately changed, for example, depending on the configuration of the optical fibers (specifically, the number of cores) and / or the light irradiation position.

[0264] For example, in the case where an optical fiber includes a core (for example, in the case of using an optical fiber including a core, a cladding surrounding the core, and a cover surrounding the cladding), for example, optical fibers equal in number to the number of light irradiation positions can be used as propagation light paths.

[0265] In the case where one optical fiber includes a plurality of cores (for example, in the case of using an optical fiber including a cladding including the plurality of cores and a cover surrounding the cladding), optical fibers smaller in number than the number of light irradiation positions can be used as propagation light paths.

[0266] In one embodiment, the propagation light path includes a plurality of optical fibers. Preferably, the plurality of optical fibers may be bundled. In other words, the propagation light path may include an optical fiber bundle. Although each optical fiber may be of a type including a single core, it may alternatively include multiple cores.

[0267] For example, a plurality of optical fibers may be bundled such that the arrangement of the cores of the optical fibers is fixed at a light-entry side terminal (an end into which light generated by application of light to biological particles enters).

[0268] Alternatively, a plurality of optical fibers may be bundled such that the arrangement of the cores of the optical fibers is fixed at a light exit-side terminal (an end at which light incident from an incident-side terminal exits).

[0269] Since the plurality of optical fibers are bundled in this manner, the plurality of optical fibers can be arranged such that their cores linearly form a row at the entrance-side terminal and / or the exit-side terminal.

[0270] In another embodiment, the propagation light path may include one optical fiber, and a plurality of core-cladding groups may be provided in the one optical fiber.

[0271] For example, a plurality of core-clad groups may be fixed so that the arrangement of the plurality of cores is fixed at the light-entry-side terminal.

[0272] Furthermore, the plurality of core-clad groups may be fixed so that the arrangement of the plurality of cores is fixed at the light exit-side terminal.

[0273] Multiple optical fibers may be bundled.

[0274] By fixing the arrangement of the cores in this manner, the plurality of cores of the optical fiber can be arranged to linearly form a row at the entrance-side terminal and / or the exit-side terminal.

[0275] In another embodiment, the propagation light path may include a single optical fiber, and multiple cores may be provided within the single optical fiber, specifically, within a single cladding. This allows the arrangement of the multiple cores to be fixed at the light-entry terminal. The arrangement of the multiple cores is also fixed at the light-exit terminal.

[0276] Since the arrangement of the cores is fixed in this manner, the plurality of cores of the optical fiber can be arranged to linearly form a row at the entrance-side terminal and / or the exit-side terminal.

[0277] Please note that in the following reference Figures 19A to 19H Examples of optical fiber configurations are described separately. Furthermore, while an example in which an optical fiber is used as a propagation optical path along which light generated by light irradiation propagates to the optical detection device in the aforementioned flow cytometer is described, any desired means that can be used as a light propagation optical path, such as a rod integrator that totally reflects incident light within its interior so that the incident light propagates, can be used. In this case, the configurations described in this specification can be used as appropriate, except that a desired light propagation means is used instead of an optical fiber.

[0278] refer to Figure 12 An example of a configuration of a flow cytometer according to an embodiment of the present disclosure having a propagation light path including an optical fiber is described. Figure 12 The flow cytometer 400 shown in Figure 2 The flow cytometer 200 shown in FIG. 1 is the same as the flow cytometer 200 shown in FIG. 1 , except that a fiber optic bundle 440 is provided in place of the field stop 240 .

[0279] The optical fiber bundle 440 may be arranged in a Figure 12The optical path between the flow cell 210 and the spectral optical system 260 is shown, and can be provided on the optical path between the flow path side light guide optical system 230 and the detector side light guide optical system 250, for example.

[0280] The optical fiber bundle 440 may be a bundle of optical fibers having a number corresponding to the number of light irradiation positions. Figure 12 In FIG. 4 , three optical fibers are bundled. The optical fiber bundle 440 may be a fiber having a structure such as that described below. Figure 19A The type of structure depicted in .

[0281] At the light entry side terminal IE of the optical fiber bundle 440, as shown Figure 12 As shown, there are three optical fiber cores CI1, CI2 and CI3 (note that Figure 12 (In the figure, the cladding and cover are omitted). The optical fiber core CI1 is the core into which light generated by applying light to the bioparticles at the light irradiation position S1 enters. Similarly, the optical fiber cores CI2 and CI3 are the cores into which light generated by applying light to the bioparticles at the light irradiation position S2 enters and light generated by applying light to the bioparticles at the light irradiation position S3 enters, respectively.

[0282] At the terminal, the arrangement intervals between the three optical fiber cores CI1, CI2, and CI3 are fixed. The arrangement intervals may correspond to the intervals between the light irradiation positions S1, S2, and S3. For example, the arrangement intervals between specific two optical fiber cores present at the light entry side terminal can be set based on the "interval between the two light irradiation positions that generate light entering the two optical fiber cores" and the "magnification of the flow path side light guide optical system." The magnification of the flow path side light guide optical system may be determined by, for example, the optical magnification of one or more optical elements (e.g., lenses, etc.) present between the flow path to be illuminated and the light entry side terminal of the optical fiber bundle.

[0283] In this way, at the light-entry side terminal, the arrangement of the plurality of optical fiber cores can be fixed, and specifically, the plurality of optical fiber cores can be arranged in such a manner that the spacing at the light-entry side terminal corresponds to the spacing between the plurality of light-irradiation positions on the flow path. In this case, the spacing between the optical fiber cores at the light-entry side terminal can be, for example, a spacing set based on (the spacing between the light-irradiation positions on the flow path) and (the magnification of the light-guiding optical system on the flow path side), and can be, for example, a spacing equivalent to "(the spacing between the light-irradiation positions on the flow path) x (the magnification of the light-guiding optical system on the flow path side)".

[0284] like Figure 12As shown, at the light exit-side terminal OE of the optical fiber bundle 440, there are three optical fiber cores CO1, CO2, and CO3. Optical fiber core CO1 is the core from which light generated by applying light to biological particles at the light irradiation position S1 is emitted. Similarly, optical fiber cores CO2 and CO3 are the cores from which light generated by applying light to biological particles at the light irradiation position S2 and the cores from which light generated by applying light to biological particles at the light irradiation position S3 is emitted, respectively.

[0285] At the terminal, the arrangement intervals between the three optical fiber cores CO1, CO2, and CO3 are fixed. The arrangement intervals may correspond to the intervals between the light detector arrays 282-1 to 282-3 of the optical detection device 280. For example, the arrangement intervals between two specific optical fiber cores present at the light exit-side terminal may be set based on "the interval between the two light detector arrays assigned to detect light emitted from the two optical fiber cores" and "the magnification of the detector-side light guide optical system." The intervals between the light detector arrays may represent the intervals in the intersection direction DB. Furthermore, the magnification of the detector-side light guide optical system may be determined by, for example, the optical magnification of one or more optical elements (e.g., lenses, etc.) present between the optical detection device and the light exit-side terminal of the optical fiber bundle.

[0286] In this manner, the arrangement of the plurality of optical fiber cores at the light exit-side terminal can be fixed, and specifically, the plurality of optical fiber cores can be arranged so as to correspond to the spacing between the photodetector arrays at the light exit-side terminal. In this case, the spacing between the optical fiber cores at the exit-side terminal can be, for example, a spacing set based on (the spacing between the photodetector arrays) and (the magnification of the detector-side light guide optical system), and can be, for example, a spacing equal to "(the spacing between the photodetector arrays) x (the magnification of the detector-side light guide optical system)".

[0287] It should be noted that the arrangement of the photodetector arrays corresponding to the light-exiting terminals of the plurality of optical fiber cores can be appropriately adjusted to match the optical path of the light from the light-exiting terminals of the optical fiber bundle 440 to the optical detection device 280. Conversely, the arrangement of the light-exiting terminals of the optical fiber cores can also be adjusted according to the arrangement of the photodetector arrays.

[0288] Here, the optical path of the light from the light exit side terminal of the optical fiber bundle 440 to the optical detection device 280 depends on the detector-side light guide optical system 250, the spectral optical system 260 and the telecentric focusing lens 270 used, their combination, or the configuration of the components.

[0289] Figure 13 A schematic example of a fiber optic bundle included in a flow cytometer according to an embodiment of the present disclosure is depicted in FIG. Figure 13The fiber bundle 450 shown is a bundle of four optical fibers. Figure 13 It is described that the optical fiber bundle 450 is divided into four optical fibers near the terminal IE and the terminal OE, but this is just a description of branching the optical fiber bundle 450 in the figure in order to illustrate the intervals between the four fiber cores, and the optical fiber bundle used in practice may not have Figure 13 Such a branch as shown in , and can be configured as Figure 12 This single linear structure is shown.

[0290] At both the light entry side terminal IE and the light exit side terminal OE of the beam, the positional relationship of the four optical fibers is fixed, in other words, the arrangement (interval) of the four optical fibers at the terminals is fixed. Figure 13 As shown, multiple cores can be arranged linearly at the light-entering terminal IE. Multiple cores can also be arranged linearly at the light-exiting terminal OE.

[0291] In addition, for example, Figure 13 The light in the optical fiber enters the cores CI1 and CI2 at the side terminals. The distance between the cores of the two specific optical fibers described above can be the linear distance between the cores CI1 and CI2 and the distance between the cores CI1 and CI2. Figure 13 The arrow mark Lci in the figure indicates the distance between the two cores. The same applies to the distance between the other two cores.

[0292] At the same time, for example, Figure 13 The light in leaves the cores CO1 and CO2 at the side terminals, the spacing can be the linear distance between the cores CO1 and CO2 and is given by Figure 13 The arrow in the figure marks the distance Lco. The same applies to the intervals between the other two cores.

[0293] In addition, the distance Lci and the distance Lco are not necessarily equal distances. In other words, the distance can be appropriately adjusted according to the optical magnification between the entrance side and the exit side.

[0294] As described above, a flow cytometer according to an embodiment of the present disclosure may include an optical fiber bundle. At opposite terminals (the light-entering terminal and the light-exiting terminal) of the optical fiber bundle, the arrangement of the cores of the plurality of optical fibers included in the optical fiber bundle may be fixed, and specifically, the arrangement intervals between the cores of the plurality of optical fibers may be fixed.

[0295] It should be noted that although Figure 12 and Figure 13 In the examples, the number of cores is three and four, respectively, but it is obvious that the number of cores is not limited to these. For example, the number of cores may be equal to the number of light irradiation positions (or the number of light detector arrays in an optical detection device), and may be, for example, two or more.

[0296] Furthermore, in some embodiments, the number of cores may be smaller than the number of light irradiation positions (or the number of light detector arrays in an optical detection device). In this case, at least one optical fiber may be shared as an optical path for light generated by applying light at two or more light irradiation positions.

[0297] In another embodiment, the number of cores may be greater than the number of light irradiation positions (or the number of light detector arrays in an optical detection device). In this case, the optical fiber used as the propagation path of the light generated by applying light to the biological particles can be appropriately switched.

[0298] In addition, although Figure 12 An example of a flow cytometer using an optical fiber bundle has been described, but optical fibers or unbundled optical fibers may be used instead of an optical fiber bundle. For example, as described above, the optical fiber may be an optical fiber having a plurality of core-cladding groups, or may be an optical fiber having a plurality of cores in a single cladding as described below.

[0299] Furthermore, when using an optical fiber such as the one described above, the plurality of optical fiber cores included in the optical fiber may be arranged so as to correspond to the spacing between the plurality of light irradiation positions on the flow path of the light-entering terminal, as described above. Furthermore, as described above, the plurality of optical fiber cores included in the optical fiber may be arranged so as to correspond to the spacing between the photodetector arrays at the light-exiting terminal.

[0300] The following describes an example of an optical fiber configuration that can be used in an embodiment of the present disclosure with reference to the accompanying drawings. As the optical fiber forming the propagation light path, one of the optical fiber bundles and optical fibers described in Examples 1 to 3 below can be used, or two or more of them can be used in combination.

[0301] (Example 1: Fiber Bundle)

[0302] Figure 19A is a schematic cross-sectional view of an example of an optical fiber bundle. Figure 19A It is a schematic diagram of a substantially vertical cross section with respect to the advancing direction of light, and the depicted components do not reflect their actual sizes.

[0303] Figure 19A The optical fiber bundle 700 shown is an optical fiber bundle having three optical fibers 701. Each optical fiber 701 has a core 703, a cladding 704 surrounding the core, and a cover 704 surrounding the cladding. In particular, the core, cladding, and cover are concentrically laminated. The materials of the core, cladding, and cover can all be known materials used in the relevant technical field.

[0304] like Figure 19AAs shown, in the optical fiber bundle 700, three optical fibers 701 are arranged in a manner that appears in a row in the above-mentioned cross section, and this arrangement is fixed by a fixing member 702. It should be noted that the arrangement may not be fixed, and for example, it may not be fixed in the middle of the bundle (i.e., the middle area of ​​the bundle excluding the light-entering side terminal and the light-exiting side terminal). The fixing member 702 may include, for example, a known material used in the relevant technical field, such as resin, rubber, or fiber.

[0305] In addition, although Figure 19A The optical fiber bundle 700 shown includes three optical fibers, but the number of optical fibers included in the optical fiber bundle is not limited to three, and may be two or more, three or more, or four or more, and the number may be, for example, the number corresponding to the number of photodetector arrays or more. Figure 19A In the embodiment, the optical fiber bundle is configured such that three optical fibers are arranged in a row on the cross section of the optical fiber bundle, but the arrangement of the optical fibers is not limited thereto. Figure 19B In the fiber bundle 800 shown, a greater number of optical fibers may be bundled. In other words, the optical fibers may not necessarily be arranged in such a manner as to Figure 19A Arranged in such a way that only one row is formed.

[0306] (Example 2: Optical fiber with multiple core-cladding groups)

[0307] Figure 19C is a schematic cross-sectional view of an example of an optical fiber. Figure 19C The optical fiber 710 depicted in FIG includes three core-cladding groups 711. Each core-cladding group represents a group formed by a core 713 and a cladding 714 surrounding the core (i.e., a structure including two elements). In addition, a cover layer 712 is provided in a manner surrounding the three core-cladding groups. The materials of the core, cladding, and cover layers can all be known materials used in the relevant technical field.

[0308] exist Figure 19C In the illustrated optical fiber 710, three core-cladding groups 711 are arranged in a row relationship in cross section, and this arrangement is fixed by a covering layer 712. It should be noted that the arrangement may not be fixed, and, for example, may not be fixed in the middle of the bundle (i.e., in the middle region between the light-entering side terminal and the light-exiting side terminal of the bundle).

[0309] In addition, although Figure 19C The optical fiber 710 shown includes three core-cladding groups 711, but the number of core-cladding groups included in the optical fiber is not limited to three, and may be two or more, three or more, or four or more, and may be a number corresponding to the number of photodetector arrays or more, for example. Figure 19CIn the embodiment, the optical fiber is configured so that three core-cladding groups appear in a row in the cross section of the optical fiber, but the arrangement of the core-cladding groups is not limited thereto. Figure 19D Multiple core-cladding layers are bundled as in the depicted optical fiber bundle 810, and in other words, the core-cladding groups may not necessarily be arranged in the same manner as in the optical fiber bundle 810. Figure 19C As depicted, they are arranged in a manner that forms only one row.

[0310] Figure 19E 1 is a schematic cross-sectional view of another example of an optical fiber. In addition to the positions of the three core-cladding groups 711 being fixed by a fixing material (e.g., resin, etc.) 715, Figure 19E The optical fiber 720 is shown with Figure 19C The optical fiber 710 shown is the same. In the embodiment of the present disclosure, an arrangement of multiple core-cladding groups 711 can be used, and the optical fiber is fixed in this manner by a fixing material. Figure 19C As shown, there may be a covering layer around the fixing material. The fixing material may be a known material used in the relevant technical field.

[0311] In addition, although Figure 19E The optical fiber 720 shown includes three core-cladding groups 711, but the number of core-cladding groups included in the optical fiber is not limited to three and may be two or more, three or more, or four or more, and the number may be, for example, the number corresponding to the number of photodetector arrays or more. Figure 19E In the embodiment, the optical fiber is configured so that three core-cladding groups appear in a row in a cross section of the optical fiber, but the arrangement of the core-cladding groups is not limited thereto. For example, a plurality of optical fibers may be arranged as follows: Figure 19F The optical fibers are bundled as shown in the optical fiber bundle 820, and the optical fibers do not need to be bundled as shown in the optical fiber bundle 820. Figure 19E Arrange in such a way as to form only one row as in .

[0312] In one embodiment, for example, the optical fiber may be subjected to a light exit end and / or a light entry end only. Figure 19E The fixing material is fixed as described in the embodiment of the present invention, and the optical fiber can be unfixed in the middle area of ​​the optical fiber. In particular, as Figure 19E or Figure 19F As shown, the optical fiber is fixed by fixing materials at the light exit end and / or the light entrance end, such as Figure 19C or Figure 19D As shown, the optical fiber may not be fixed by the fixing material in the middle region.

[0313] In another embodiment, Figure 19E The fixing by the fixing material as depicted in FIG. 1 can be performed over the entire optical fiber area including the light exit end and / or the light entry end of the optical fiber.

[0314] (Example 3: Optical fiber in which a plurality of cores are provided in a cladding)

[0315] Figure 19G is a schematic transverse cross-sectional view of another example of an optical fiber. Figure 19G The optical fiber 730 shown includes three cores 733. The three cores 733 are present in a cladding 734. In addition, a cover layer 732 is provided in a manner surrounding the cladding. The materials of the core, cladding, and cover layer can all be known materials used in the relevant technical field.

[0316] exist Figure 19G In the illustrated optical fiber 730 , three cores 733 are arranged in a row, and this arrangement is secured by a cladding 734 .

[0317] Although Figure 19G The optical fiber 730 shown includes three cores 733, but the number of cores included in the optical fiber is not limited to three, and may be two or more, three or more, or four or more, and may be equal to or more than the number corresponding to the number of photodetector arrays, for example. Figure 19G The optical fiber in is configured so that three cores appear in a row, but the arrangement of the cores is not limited thereto. Figure 19H In the optical fiber 830 depicted in FIG, multiple cores may be present in the cladding, and in other words, they may not necessarily be arranged in the same manner as in FIG. Figure 19G Arranged in such a way that only one row is formed.

[0318] (6) Designing the optical path through the spectral optical system

[0319] refer to Figure 14 An example of designing an optical path to an optical detection device through a spectral optical system in a flow cytometer according to the present disclosure is described.

[0320] Figure 14 This is a schematic diagram of the optical path from the light designed by the spectral optical system to the optical detection device. Figure 2 In the example of the configuration of the flow cytometer depicted in FIG, the optical path can be applied as an optical path from the field stop 240 to the optical detection device 280. In addition, in Figure 12 In the example of the configuration of the flow cytometer shown, the optical path may be applied as an optical path from the light exit side terminal of the optical fiber bundle 440 to the optical detection device 280 .

[0321] The light from the field stop 240, the optical fiber bundle 440, etc. is incident on the side terminal Figure 14The light incident at the light incident end X shown in FIG passes through the detector side light guide optical system 250, and the advancing direction of the light is adjusted to any direction such as a parallel direction by the detector side light guide optical system 250. The optical components that can be used as the detector side light guide optical system described in this specification can be appropriately used as the optical components configuring the detector side light guide optical system 250. Although Figure 14 An example using an optical system including two lenses is described, but this is not limitative, and those skilled in the art can freely design according to the purpose of the optical component.

[0322] The light whose path is adjusted to a desired direction by the detector-side light guide optical system 250 is spectrified for each wavelength by the spectral optical system 260. Optical components that can be used as the spectral optical system described in this specification can be appropriately used as optical components configuring the spectral optical system 260. Figure 14 An example using three prisms designed to have a vertical angle of 40 degrees is described, but this is not limitative, and those skilled in the art can freely design according to the purpose of the optical component.

[0323] The light spectrified by the spectral optical system 260 reaches the telecentric condensing lens 270. The telecentric condensing lens 270 arranges the advancing direction of the spectrified light to any direction such as a parallel direction, and makes the light reach the optical detection device 280. As for the optical components constituting the telecentric condensing lens 270, the optical components that can be used as the telecentric condensing lens described in this specification can be appropriately used. Figure 14 An example using an optical system including two lenses is described, but this is not limitative, and those skilled in the art can freely design according to the purpose of the optical component.

[0324] exist Figure 14 In the example shown, light generated by light irradiating biological particles flowing in a flow path at a plurality of light irradiation positions reaches the optical detection device 280 through the same detector-side light guide optical system 250, spectral optical system 260, and telecentric condenser lens 270. Specifically, the flow cytometer according to the present disclosure can be designed in a form in which the number of detector-side light guide optical systems 250, spectral optical systems 260, and telecentric condenser lenses 270 is smaller than the number of light irradiation positions.

[0325] Figure 15 Describes, for example, Figure 14 The optical path of light of the optical detection device shown in the example is the incident surface of the case where light enters the optical detection device.

[0326] In a case where light generated by irradiating biological particles flowing in a flow path at multiple light irradiation positions is spectrally quantified by a spectral optical system and then imaged on an incident surface of an optical detection device, the position of the spectrum of light output on the incident surface corresponding to the light irradiation position may be shifted due to aberrations of optical components, etc.

[0327] Furthermore, the width of each individual wavelength of the light that constitutes the spectrum output to the incident surface through the aforementioned spectralization varies depending on the wavelength at the time of output. Generally, short-wavelength light has a larger width when output, while long-wavelength light has a smaller width when output. Therefore, the amount of light per area outputted to the incident surface is relatively smaller when short-wavelength light is outputted compared to long-wavelength light.

[0328] exist Figure 15 In the example shown, four light spectra Y1-Y4 are output to the incident surface of the optical detection device in a relationship corresponding to four light irradiation positions. Figure 15 In FIG. 1 , it can be confirmed that the positions of the four spectrums Y1 to Y4 of the output light are shifted along the arrangement direction DA arranged in accordance with the output positions of the spectrum. It can also be confirmed that the positions of the light having the same wavelength are shifted along the arrangement direction DA.

[0329] In addition, Figure 15 It can be confirmed that, for the light rays constituting the light spectrum Y1 to Y4, the width of the light outputting short wavelengths is large, while the width of the light outputting long wavelengths is small.

[0330] The amount and direction of the positional shift of the spectrum of light output corresponding to the light irradiation position on the incident surface depends on the arrangement of the detector-side light guide optical system 250, the spectral optical system 260, and the telecentric focusing lens 270 used in the flow cytometer, or a combination thereof, or the arrangement of the optical components and the optical path. Conversely, the arrangement of the optical components or the optical path can also be adjusted according to the position where the spectrum is to be output. For example, although Figure 15 Shows the use of a prism as a spectroscopic optical system through Figure 14 The optical path for light to the optical detection device shown in FIG. 1 is the incident surface when light enters the optical detection device. However, when a diffraction grating is used as the spectral optical system instead of a prism, the effect of shifting the output position of the spectrum is typically less than when a prism is used. Therefore, by adjusting the optical components to be used and their positions in consideration of their characteristics, the position of the output spectrum on the incident surface can be adjusted.

[0331] Furthermore, the width of each wavelength of light that constitutes the output spectrum depends on the optical resolution capability of the spectroscopic optical system being used. Taking this into account, the light-receiving surface area of ​​the photodetector elements that make up the photodetector array can be adjusted to the width of each wavelength of light to be output, or the sensitivity of the photodetector elements can be adjusted based on the amount of light for each wavelength of light to be output.

[0332] exist Figure 15 In the example shown, the spectrum output to the incident surface is output at predetermined intervals along the intersection direction DB intersecting the arrangement direction DA. The intervals of the output spectrum correspond to the intervals of the spectrum input to the incident surface. Figure 14 The intervals between light rays at the light incident end X are shown. For example, when light rays enter the incident end X at intervals corresponding to the intervals between the light irradiation positions of the biological particles flowing in the flow path, the intervals between the spectra of light output to the incident surface correspond to the intervals between the light irradiation positions.

[0333] Therefore, the interval between the spectra output to the incident surface can also be adjusted by the interval between the light irradiation positions of the bioparticles flowing in the flow path and the arrangement positions of the light exit side terminals of the optical fiber bundle of the optical fiber core.

[0334] Here, the "corresponding intervals" are not limited to the same intervals and include intervals in the case where each interval is multiplied by a fixed multiplier.

[0335] Figure 16 is a schematic diagram showing an example of an optical detection device including a plurality of light detector arrays corresponding to the light output to the Figure 15 The example shows the position of the light spectrum of the incident surface of the optical detection device.

[0336] In particular, including Figure 16 The four photodetector arrays A1 to A4 in the optical detection device shown in FIG. Figure 15 The example shows that the positions of the four light spectra Y1 to Y4 are arranged in a manner that is output. Figure 16 Describes the Figure 15 , but this is not restrictive, and the number of light detector arrays or the arrangement of the light detector arrays may be adjusted according to the number of spectrums output to the incident surface of the optical detection device or the positions of the output spectrums. Conversely, the number of spectrums output to the incident surface of the optical detection device or the positions of the spectrum outputs may be adjusted according to the number of light detector arrays included in the optical detection device or according to the positions of the light detector arrays.

[0337] also, Figure 16An example of an optical detection device with a photodetector array comprising a plurality of photodetector elements having light-receiving surfaces of unequal areas is shown. In this case, the areas of the light-receiving surfaces of the photodetector elements arranged in the photodetector array are adjusted to correspond to the width of light output at each wavelength to be detected, or to correspond to the amount of light, thereby suppressing dispersion in the detection sensitivity of the photodetector array corresponding to the wavelength of light. In addition to the above configuration, for example, by adjusting the light-receiving surface areas of the photodetector elements according to the APD sensitivity of the photodetector elements in each wavelength region to be used, it is also possible to suppress dispersion in the detection sensitivity of the photodetector array for light wavelengths.

[0338] like Figure 16 As shown, by using a photodetector array including a combination of identical photodetector elements and arranging the photodetector array in a manner corresponding to the position of the spectrum of the output light, a plurality of photodetector arrays included in an optical detection device can avoid dispersion in the detection sensitivity for each wavelength.

[0339] (7) Other examples of configuration (use of multiple optical detection devices)

[0340] Figure 2 The flow cytometer depicted in the embodiment includes one optical detection device. The number of optical detection devices included in the flow cytometer according to an embodiment of the present disclosure is not limited to one and may be two or more. Specifically, in one embodiment of the present disclosure, the flow cytometer may include two or more optical detection devices, and at least one of the two or more optical detection devices may include a plurality of light detector arrays.

[0341] A flow cytometer including two or more optical detection devices facilitates efficient use of the photodetector elements of the optical detection devices and also facilitates more precise detection of spectrally dispersed light. For example, in the case of detecting fluorescence generated by applying excitation light having a specific wavelength to biological particles, in order to prevent detection of the excitation light, a notch filter for cutting off the excitation light is sometimes provided on the optical path of a light guide optical system (e.g., a detector-side light guide optical system). The notch filter does not allow light having a wavelength close to that of the excitation light to pass through. Therefore, although such an advantage of detecting fluorescence only by the notch filter is obtained, the photodetector elements assigned to detecting light having the wavelength of the excitation light cannot be effectively used. Therefore, the flow cytometer can be configured so that a plurality of optical detection devices are included therein, and the optical detection devices can be configured to detect light within wavelength ranges different from each other.

[0342] Refer to the following Figure 17 This embodiment is described.

[0343] In addition to the fact that the detector-side light-guiding optical system 250, the spectral optical system 260, the telecentric condensing lens 270, and the optical detection device 280 are changed into the detector-side light-guiding optical system 550 (551 to 554), the spectral optical system 560 (560-1 to 560-3), the telecentric condensing lens 570 (570-1 to 570-3), and the optical detection device 580 (580-1 to 580-3), Figure 17 The flow cytometer 500 shown in FIG. Figure 2 The flow cytometer configuration is the same as shown in FIG.

[0344] As described in (1) above, optical detection devices 580-1, 580-2, and 580-3 each have a plurality of photodetector arrays arranged at predetermined intervals along the flow direction. Flow cytometer 500 is configured so that the three optical detection devices individually detect light in wavelength ranges different from each other.

[0345] As an example, assume a case where excitation light having a wavelength of 390 nm, excitation light having a wavelength of 540 nm, and excitation light having a wavelength of 690 nm are applied to biological particles at three irradiation positions, and light having a wavelength ranging from 400 to 850 nm is detected.

[0346] In this case, it is assumed that the optical detection devices are allocated so that the optical detection device 580-1 detects light with a wavelength ranging from 400nm to 530nm; the optical detection device 580-2 detects light with a wavelength ranging from 550nm to 680nm; and the optical detection device 580-3 detects light with a wavelength ranging from 700nm to 850nm. In addition, the light of 530 to 550nm and the light of 680 to 700nm are cut off by the notch filter.

[0347] The light that has passed through the field stop 240 is separated into the three light rays within the above-mentioned wavelength ranges by the detector-side light guide optical system 550. Although the light guide optical system 550 can be configured as described below, its configuration can be appropriately changed according to, for example, the number of optical detection devices, the wavelength range to be detected by each optical detection device, and the like.

[0348] The light that has passed through the field stop 240 passes through a lens 551 (eg, a collimating lens, etc.) and reaches a dichroic mirror 552 .

[0349] The dichroic mirror 552 has an optical characteristic of reflecting light having a wavelength of 550 nm or less and passing light having a wavelength greater than 550 nm. Therefore, fluorescence having a wavelength of 550 nm or less reaches the spectroscopic optical system 560-1 ( Figure 14 transmission diffraction grating in ).

[0350] Light that has passed through the dichroic mirror 552 (i.e., light with a wavelength longer than 550 nm) reaches the dichroic mirror 553. The dichroic mirror 553 has an optical characteristic of reflecting light with a wavelength of 700 nm or less and allowing light with a wavelength greater than 700 nm to pass through. Therefore, fluorescence with a wavelength greater than 550 nm but equal to or less than 700 nm reaches the spectroscopic optical system 560-2 (transmission-type diffraction grating).

[0351] Light that has passed through the dichroic mirror 553 (i.e., light having a wavelength longer than 700 nm) reaches the reflective mirror 554. The reflective mirror 554 has an optical characteristic that reflects light having a wavelength of 850 nm or less. As a result, fluorescence having a wavelength greater than 700 nm but equal to or less than 850 nm reaches the spectroscopic optical system 560-3 (transmission-type diffraction grating).

[0352] It should be noted that the detector-side light guide optical system 550 may further include one or more notch filters (not shown) that cut off the excitation light. The one or more notch filters may be appropriately arranged on the optical path of the optical system.

[0353] Spectral optical system 560-1 spectrally disperses light arriving therewith, which has a wavelength ranging from 400 to 550 nm. The spectrally dispersed light is collimated by telecentric focusing lens 570-1 and reaches optical detection device 580-1. Optical detection device 580-1 includes multiple photodetector arrays. Each photodetector array includes photodetector elements arranged in a row. The photodetector arrays are arranged to detect light between 400 nm and 550 nm. More specifically, the photodetector elements at one end of the array are allocated to detect light with a wavelength of approximately 400 nm, and the photodetector elements at the ends of the array are allocated to detect light with a wavelength of 550 nm. The photodetector elements between the opposing ends detect spectrally dispersed light with a wavelength ranging from 400 nm to 550 nm.

[0354] The spectral optical system 560-2 spectrally disperses light arriving therewith having a wavelength in the range of 550nm to 700nm. The spectrally dispersed light is collimated by the telecentric focusing lens 570-2 and arrives at the optical detection device 580-2. The optical detection device 580-2 includes a plurality of photodetector arrays. Each photodetector array includes photodetector elements arranged in a row. The photodetector arrays are allocated to detect light in the range of 550 to 700nm. More specifically, the photodetector elements at one end of the array are allocated to detect light with a wavelength of approximately 550nm, and the photodetector elements at the ends of the array are allocated to detect light with a wavelength of 700nm. The photodetector elements present between the opposite ends detect the spectrally dispersed light having a wavelength in the range of 550nm to 700nm.

[0355] The spectral optical system 560-3 spectrally disperses the light reaching it and having a wavelength ranging from 700 to 850 nm. The spectrally dispersed light is collimated by the telecentric focusing lens 570-3 and reaches the optical detection device 580-3. The optical detection device 580-3 includes multiple photodetector arrays. Each photodetector array contains photodetector elements arranged in a row. The photodetector arrays are allocated to detect light with a wavelength of 700 to 850 nm. More specifically, the photodetector elements at one end of the array are allocated to detect light with a wavelength of approximately 700 nm, and the photodetector elements at multiple ends of the array are allocated to detect light with a wavelength of 850 nm. The photodetector elements between the opposite ends detect spectrally dispersed light with a wavelength ranging from 700 to 850 nm.

[0356] As described above, the detector-side light guide optical system 550 separates light into multiple wavelength ranges, allowing each to reach multiple optical detection devices. The multiple optical detection devices are configured so that their photodetector arrays utilize the total area of ​​the arrays to individually detect light rays reaching the photodetector arrays and having wavelengths within the corresponding wavelength ranges. This effectively utilizes the photodetector arrays and enables more detailed analysis.

[0357] (8) Embodiments not including an objective lens

[0358] In a general flow cytometer, an objective lens is provided through which light generated by applying light to biological particles flowing in a flow path passes. The objective lens is provided near the flow path and is provided very close to, for example, a flow cell or a cuvette.

[0359] In some embodiments, a flow cytometer according to embodiments of the present disclosure may not include an objective lens. In such embodiments, an optical detection device may be arranged on the flow path. In other words, light generated by the light application may be detected by the optical detection device without the need for any objective lens. Furthermore, in a flow cytometer configured in this manner, image data of biological particles may be acquired by the optical detection device.

[0360] (9) Example of flow cytometer configuration

[0361] A flow cytometer according to an embodiment of the present disclosure may include a light irradiation unit, a detection unit, and an information processing unit. In addition, a flow cytometer according to an embodiment of the present disclosure may further include a separation unit. The light irradiation unit, the detection unit, the information processing unit, and the separation unit may be configured in the manner described below with respect to the biological sample analysis device. The optical detection device according to an embodiment of the present disclosure may be incorporated as a component of the detection unit in a flow cytometer.

[0362] Furthermore, the biological particles irradiated with light by the flow cytometer according to the embodiment of the present disclosure can be prepared as a biological sample described below. Furthermore, the flow path in which the biological particles flow can be configured in the manner described below with respect to the biological sample analysis device.

[0363] Furthermore, the flow cytometer according to an embodiment of the present disclosure can be configured not only as a flow cytometer that performs only analysis of biological particles, but also as a flow cytometer (also known as a cell sorter) that separates predetermined biological particles based on the analysis results. The cell sorter can be configured to perform the separation process in an open space or in a closed space.

[0364] It should be noted that in the event that there is a difference between the contents described in (1) to (8) above and the contents described in this (9), priority is given to the contents described in (1) to (8) above.

[0365] Figure 18 An example of the configuration of a biological sample analysis device according to an embodiment of the present disclosure is depicted in FIG. Figure 18 The biological sample analysis device 6100 described in the document includes a light irradiation unit 6101 for irradiating a biological sample S flowing in a flow channel C with light; a detection unit 6102 for detecting light generated by applying light to the biological sample S; and an information processing unit 6103 for processing information related to the light detected by the detection unit. Examples of the biological sample analysis device 6100 include flow cytometers and imaging cytometers. The biological sample analysis device 6100 may include a separation unit 6104 for separating specific biological particles P from the biological sample. An example of a biological sample analysis device including a separation unit 6104 is a cell sorter.

[0366] (Biological Sample)

[0367] The biological sample S can be a liquid sample including biological particles. The biological particles are, for example, cells or non-cellular biological particles. The cells can be living cells, and as more specific examples, blood cells such as red blood cells or white blood cells and reproductive cells such as sperm cells or fertilized egg cells can be mentioned. In addition, the cells can be cells directly sampled from a whole blood sample, or can be cultured cells obtained after culture. As non-cellular biological particles, extracellular vesicles, in particular exosomes, microvesicles, etc. can be mentioned. The biological particles can be labeled with one or more marker substances (for example, dyes (in particular, fluorescent dyes), fluorescent dye-labeled antibodies, etc.). It should be noted that by the biological sample analysis device according to the embodiment of the present disclosure, particles other than biological particles can be analyzed, and microbeads and the like can be analyzed for calibration (calibration, calibration) and the like.

[0368] (Flow path)

[0369] The flow path C is configured so that the biological sample S flows therein. Specifically, the flow path C can be configured so as to form a flow in which the biological particles included in the biological sample are basically aligned in a row. The flow path structure including the flow path C can be designed to form a laminar flow. In particular, the flow path structure is designed to form a laminar flow in which the biological sample flow (sample flow) is wrapped by the sheath liquid flow. The design of the flow path structure can be appropriately selected by those skilled in the art, and a known flow path structure can be adopted. The flow path C can be formed in a flow path structure (flow path structure) such as a microchip (a chip including a micron-scale flow path), a flow cell, etc. The width of the flow path C is equal to or less than 1 mm, and in particular can be equal to or greater than 10 μm but equal to or less than 1 mm. The flow path C and the flow path structure including the flow path C can include materials such as plastic or glass.

[0370] The biological sample analysis device according to an embodiment of the present disclosure is configured so that the biological sample flowing in the flow path C, specifically, the biological particles in the biological sample, are irradiated with light from the light irradiation section 6101. The biological sample analysis device according to an embodiment of the present disclosure can be configured so that the irradiation point (interrogation point) of light relative to the biological sample exists in the flow path structure in which the flow path C is formed, or can be configured so that the irradiation point of light exists outside the flow path structure. As an example of the former configuration, a configuration in which the flow path C in a microchip or a flow cell is irradiated with light can be mentioned. In the latter configuration, biological particles that have left the flow path structure (specifically, its nozzle portion) are irradiated with light, and for example, an air jet type flow cytometer can be mentioned.

[0371] (Light irradiation part)

[0372] The light irradiation unit 6101 includes a light source unit that emits light and a light-guiding optical system that guides the light to the irradiation point. The light source unit includes one or more light sources. The type of light source is, for example, a laser light source or a light-emitting diode (LED). The wavelength of light emitted from each light source can be a wavelength of ultraviolet light, visible light, or infrared light. For example, the light-guiding optical system includes optical components such as a beam splitter group, a reflector group, or an optical fiber. In addition, the light-guiding optical system may include a lens group for converging light and include, for example, an objective lens. The number of irradiation points where the biological sample and the light intersect each other may be one or more. The light irradiation unit 6101 can be configured so that light emitted from one or more different light sources converges to one irradiation point.

[0373] (Testing Department)

[0374] The detection unit 6102 includes at least one light detector that detects light generated by applying light to the biological particles. The light to be detected is, for example, fluorescence or scattered light (for example, one or more of forward scattered light, back scattered light, and side scattered light). Each light detector includes one or more light receiving elements, and includes, for example, a light receiving element array. Each light detector may include one or more PMTs (photomultiplier tubes) and / or photodiodes such as APDs or MPPCs. The light detection unit includes a PMT array in which, for example, a plurality of PMTs are arranged in one-dimensional direction. In addition, the detection unit 6102 may include imaging elements such as CCDs, CMOSs, etc. The detection unit 6102 can obtain images of the biological particles (for example, bright field images, dark field images, fluorescent images, etc.) through the imaging elements.

[0375] The detection unit 6102 includes a detection optical system that allows light of a predetermined detection wavelength to reach a corresponding light detector. The detection optical system includes a spectral dispersion unit such as a prism or a diffraction grating, or a wavelength separation unit such as a dichroic mirror or an optical filter. The detection optical system is configured to, for example, spectrally disperse light generated by applying light to biological particles so that the spectrally dispersed light is detected by a plurality of light detectors, the number of which is greater than the number of fluorescent dyes used to label the biological particles. A flow cytometer that includes a detection optical system such as the one just described is referred to as a spectral flow cytometer. Furthermore, the detection optical system is configured to separate light corresponding to the fluorescence wavelength range of a specific fluorescent dye from light generated, for example, by applying light to the biological particles, and to cause the corresponding light detector to detect the separated light.

[0376] In addition, the detection unit 6102 may include a signal processing unit that converts the electrical signal obtained by the light detector into a digital signal. The signal processing unit may include an analog / digital (A / D) converter as a device for performing the conversion. The digital signal obtained by the conversion of the signal processing unit may be transmitted to the information processing unit 6103. The signal processing unit 6103 may regard the digital signal as data related to light (hereinafter also referred to as "optical data"). For example, the optical data may be optical data including fluorescence data. More specifically, the optical 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, or width).

[0377] (Information Processing Department)

[0378] The information processing unit 6103 includes, for example, a processing unit that processes various data (e.g., optical data) and a storage unit that stores the various data therein. In the case of acquiring optical data corresponding to a fluorescent dye from the detection unit 6102, the processing unit can perform fluorescence leakage correction (compensation processing) on ​​the light intensity data. In addition, in the case of a spectral flow cytometer, the processing unit performs fluorescence separation processing on the optical data and acquires light intensity data corresponding to the fluorescent dye. For example, fluorescence separation processing can be performed according to the unmixing method disclosed in Japanese Patent Laid-Open No. 2011-232259. In the case where the detection unit 6102 includes an imaging element, the processing unit can acquire shape information of biological particles with reference to the image acquired by the imaging element. The storage unit can be configured to be able to store the acquired optical data therein. The storage unit can further be configured to be able to store spectral reference data to be used in the unmixing process described above.

[0379] When the biological sample analysis device 6100 includes the extraction unit 6104 described below, the information processing unit 6103 can refer to the optical data and / or the shape information to determine whether the biological particles are to be extracted. The information processing unit 6103 then controls the extraction unit 6104 with reference to the result of the determination, and the extraction unit 6104 can extract the biological particles.

[0380] The information processing unit 6103 can be configured to output various data (e.g., optical data and images). For example, the information processing unit 6103 can output various data generated with reference to the optical data (e.g., two-dimensional graphs, spectral graphs, etc.). In addition, the information processing unit 6103 can be configured to accept input of various types of data, and, for example, accept user-controlled gating of the spectrum. The information processing unit 6103 may include an output unit (e.g., a display unit, etc.) or an input unit (e.g., a keyboard, etc.) for performing output or input.

[0381] The information processing section 6103 can be configured as a general-purpose computer and, for example, can be configured as an information processing device including a central processing unit (CPU), a random access memory (RAM), and a read-only memory (ROM). The information processing section 6103 can be included in a housing provided with the light application section 6101 and the detection section 6102, or can be provided outside the housing. In addition, various processes or functions to be implemented by the information processing section 6103 can be implemented by a server computer or cloud connected via a network.

[0382] (Separation section)

[0383] The preparative isolation section 6104 performs separation of biological particles in response to the determination result of the information processing section 6103. The separation method can be a method of generating droplets including biological particles by vibration, applying electric charge to the droplets of the separation object, and then controlling the forward direction of the droplets with electrodes. The separation method can be a method of controlling the forward direction of the biological particles to perform separation in a flow path structure. In the flow path structure, for example, a control mechanism by pressure (injection or suction) or by electric charge is provided. As an example of a flow path structure, a chip having a flow path structure (for example, a chip disclosed in Japanese Patent Laid-Open No. 2020-76736) can be cited, in which the flow path C branches to a recovery flow path and has a waste liquid flow path on its downstream side, and specific biological particles are recovered to the recovery flow path.

[0384] 2. Second embodiment (biological sample analysis system)

[0385] The optical detection device can be used not only in flow cytometers but also in analysis systems other than flow cytometers. Specifically, one embodiment of the present disclosure further provides a biological sample analysis system including the optical detection device described in 1. above.

[0386] In one embodiment, a biological sample analysis system may include an optical detection device configured to detect light generated by applying light to biological particles flowing in a flow path. As described in 1. above, the optical detection device includes a plurality of light detector arrays, each of which includes light detector elements arranged in a row. The plurality of light detector arrays may be arranged at predetermined intervals along a direction intersecting the direction in which the light detector arrays are arranged.

[0387] As described in 1. above, the biological sample analysis system may include a light irradiation unit, a detection unit, and an information processing unit. Furthermore, the system may include a separation unit. In the biological sample analysis system, the light irradiation unit, the detection unit, and the information processing unit (and optionally, the separation unit) may be combined into a single device or may be dispersed across multiple devices.

[0388] Furthermore, the biological particles to be irradiated with light do not necessarily need to be flowing in the flow path. Specifically, the biological particles to be irradiated with light can be present in an area outside the flow path, and can be, for example, biological particles present in a non-flowing sample. Furthermore, the objects to be irradiated with light can be particles other than biological particles or biological substances other than particles. For example, the optical detection device can be used in microscope systems, biological substance systems (e.g., analysis systems for nucleic acids or proteins, etc.), biological substance amplification systems (e.g., nucleic acid amplification systems, etc.), and the like.

[0389] Specifically, one embodiment of the present disclosure further provides a biological sample analysis system including an optical detection device configured to detect light generated by applying light to a biological sample.

[0390] 3. Third embodiment (optical detection device)

[0391] One embodiment of the present disclosure further provides the optical detection device described in 1. The optical detection device is suitable for analyzing biological particles. For example, the optical detection device can be used to detect light generated by applying light to biological particles.

[0392] In one embodiment, the optical detection device can be used in combination with a light irradiation unit that irradiates the bioparticles with light at multiple light irradiation positions along the flow direction of the fluid path. Specifically, one embodiment of the present disclosure further provides a combination of the light irradiation unit and the optical detection device. The light irradiation unit is as described in 1. above.

[0393] Furthermore, the optical detection device can be used in conjunction with a spectral optical system that spectrally disperses multiple light rays generated by applying light at multiple light irradiation positions. Specifically, one embodiment of the present disclosure further provides a combination of a spectral optical system and an optical detection device. The spectral optical system is as described in 1. above.

[0394] In the spectroscopic optical system, two or more photodetector arrays among the plurality of photodetector arrays may have the same detection wavelength range as each other.

[0395] It should be noted that it will be apparent to those skilled in the art that the shapes and numbers of the various optical elements (e.g., light guide optical system, spectral optical system, telecentric focusing lens, etc.) depicted in the drawings of this specification are schematic examples, and their configurations (shape, number, etc.) are not limited to those depicted in the drawings. Those skilled in the art can appropriately design each optical element so that it exhibits the desired function of the optical element. For example, a lens depicted in the drawings is not limited to a single lens and can be configured as a lens system, or in other words, a collection of two or more lenses.

[0396] The terms "substantially," "substantially," and "about" may be used to mean within ±20% of a target value in some embodiments, within ±10% of a target value in some embodiments, within ±5% of a target value in some embodiments, and within ±2% of a target value in some embodiments. The terms "approximately" and "about" may include the target value.

[0397] It should be understood by those skilled in the art that various modifications, combinations, sub-combinations and alterations may occur depending on design requirements and other factors insofar as they are within the scope of the appended claims or the equivalents thereof.

[0398] Furthermore, the present disclosure also provides the following configurations.

[0399] <1>

[0400] A flow cytometer, comprising:

[0401] an optical detection member that detects emission light emitted by particles flowing in the flow path, the emission light being generated by applying excitation light to the particles flowing in the flow path, wherein

[0402] The optical detection component includes a plurality of photodetector arrays, in each of which photodetector elements are arranged in corresponding rows, and

[0403] The plurality of photodetector arrays are arranged at predetermined intervals along a direction intersecting an arrangement direction of corresponding rows of photodetector elements of each photodetector array that is substantially parallel to the arrangement direction.

[0404] <2>

[0405] according to <1> flow cytometer, which

[0406] The arrangement of the plurality of light detector arrays corresponds to the flow direction of the flow path.

[0407] <3>

[0408] according to <1> or <2> The flow cytometer of claim 1, wherein each of the plurality of light detector elements is one of a photomultiplier tube element or an avalanche photodiode element.

[0409] <4>

[0410] according to <1> or <2> flow cytometer, in which

[0411] Each of the photodetector elements is one of a photomultiplier tube element including one dynode including a semiconductor element or a photomultiplier tube element including multiple dynodes.

[0412] <5>

[0413] according to <1> or <2> The flow cytometer, wherein the optical detection component includes a multi-pixel photon counter.

[0414] <6>

[0415] according to <1> to <5> The flow cytometer of any one of the above, further comprising:

[0416] The light irradiation unit irradiates the particles flowing in the flow channel with excitation light at a plurality of light irradiation positions along the flow direction of the flow channel.

[0417] <7>

[0418] according to <6> The flow cytometer, wherein the light irradiation section is configured to individually irradiate each of the plurality of light irradiation positions with light having wavelengths different from each other.

[0419] <8>

[0420] according to <6> or <7> The flow cytometer of the present invention is configured to detect emission light generated by applying excitation light at two or more positions among the plurality of light irradiation positions.

[0421] <9>

[0422] according to <1> to <8> The flow cytometer of any one of claims 1 to 6, wherein the respective gains of the plurality of light detector arrays can be adjusted independently of each other.

[0423] <10>

[0424] according to <1> to <9> The flow cytometer of any of claims 1 to 6, wherein the respective gains of the photodetector elements of the plurality of photodetector arrays are adjustable independently of one another.

[0425] <11>

[0426] according to <1> to <10> The flow cytometer of any one of the foregoing, wherein one or more of the plurality of light detector arrays are configured so that their respective positions can be adjusted independently of each other in a direction intersecting the arrangement direction.

[0427] <12>

[0428] according to <1> to <11> The flow cytometer of any one of the foregoing, wherein one or more of the plurality of light detector arrays are configured such that their respective positions can be adjusted independently of each other in the arrangement direction.

[0429] <13>

[0430] according to <1> to <12> The flow cytometer of any one of , wherein

[0431] The optical detection component further comprises a microlens array comprising a plurality of lenses, each lens of the plurality of lenses being arranged on a corresponding light detector element of the plurality of detector arrays.

[0432] <14>

[0433] according to <1> to <13> The flow cytometer of any one of the above, further comprising:

[0434] A light propagation path along which the emitted light propagates to the optical detection component, wherein the light propagation path includes one or more optical fibers.

[0435] <15>

[0436] according to <1> to <13> The flow cytometer of any one of the above, further comprising:

[0437] a light irradiation section that irradiates the particles flowing in the flow path with excitation light at a plurality of light irradiation positions along a flow direction of the flow path; and

[0438] The light propagation path along which the emitted light propagates to the optical detection component, wherein

[0439] The light propagation path includes multiple optical fiber cores, and

[0440] The plurality of optical fiber cores are arranged in a manner corresponding to intervals between the plurality of light irradiation positions at light input ends of the plurality of optical fiber cores.

[0441] <16>

[0442] according to <1> to <14> The flow cytometer of any one of the above, further comprising:

[0443] a light irradiation section that irradiates the particles flowing in the flow path with excitation light at a plurality of light irradiation positions along a flow direction of the flow path; and

[0444] The light propagation path along which the emitted light propagates to the optical detection component, wherein

[0445] The light propagation path includes multiple optical fiber cores, and

[0446] The plurality of optical fiber cores are arranged in a manner corresponding to intervals between respective ones of the plurality of optical detector arrays at light output ends of the plurality of optical fiber cores.

[0447] <17>

[0448] according to <1> to <13> The flow cytometer of any one of the above, further comprising:

[0449] The light propagation path along which the emitted light propagates to the optical detection component, wherein

[0450] The field stop is arranged in the light propagation path.

[0451] <18>

[0452] according to <1> to <17> The flow cytometer of any of the preceding claims, wherein at least one of the plurality of photodetector arrays comprises 10 or more photodetector elements.

[0453] <19>

[0454] according to <1> to <18> The flow cytometer of any of claims 1 to 6, wherein at least some of the plurality of light detector elements of the optical detection component are configured to detect light temporally independently of one another.

[0455] <20>

[0456] A biological sample analysis system, comprising:

[0457] an optical detection section that detects emission light emitted by particles flowing in the flow path, the emission light being generated by applying excitation light to the particles flowing in the flow path; and

[0458] An information processing unit is used to process the emitted light detected by the optical detection component, wherein

[0459] The optical detection component includes a plurality of photodetector arrays, in each of which photodetector elements are arranged in corresponding rows, and

[0460] The plurality of photodetector arrays are arranged at predetermined intervals along a direction intersecting an arrangement direction substantially parallel to a direction in which corresponding rows of photodetector elements of each of the photodetector arrays are arranged.

[0461] <21>

[0462] An optical detection device, comprising:

[0463] A plurality of photodetector arrays, in each photodetector array, photodetector elements are arranged in corresponding rows, wherein

[0464] A plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with an arrangement direction of corresponding rows of light detector elements substantially parallel to each of the light detector arrays, and the plurality of light detector arrays are used to detect emission light emitted by particles flowing in a flow path, the emission light being generated by applying excitation light to the particles flowing in the flow path.

[0465] <22>

[0466] according to <21> An optical detection apparatus, wherein the optical detection component is configured to be used in combination with a light irradiation section that irradiates the particles with excitation light at a plurality of light irradiation positions along a flow direction of a flow path.

[0467] <23>

[0468] according to <21> or <22> An optical detection device, wherein the optical detection component is configured to be used in combination with a spectral optical system that spectrally disperses multiple rays of emitted light generated by applying excitation at multiple light irradiation positions.

[0469] <24>

[0470] according to <21> to <23> The optical detection device of any one of the items , wherein two or more of the plurality of light detector arrays include at least one light detector element, and the at least one light detector element has the same detection wavelength range between the two or more light detector arrays.

[0471] [List of Reference Numbers]

[0472] 200: Flow cytometer

[0473] 210: Flow cell

[0474] 220: Objective lens

[0475] 230: Flow path side light guide optical system

[0476] 240: Field stop

[0477] 250: Detector side light guide optical system

[0478] 260: Spectral Optical System

[0479] 270: Telecentric focusing lens 280: Optical detection equipment.

Claims

1. A flow cytometer comprising an optical detection member that detects emission light emitted by particles flowing in a flow path, the emission light being generated by applying excitation light to the particles flowing in the flow path, wherein the optical detection member includes a plurality of photodetector arrays, in each of which photodetector elements are arranged in respective rows, and The plurality of photodetector arrays are arranged at predetermined intervals along a direction intersecting a direction substantially parallel to an arrangement direction of the corresponding rows of the photodetector elements of each of the photodetector arrays.

2. The flow cytometer according to claim 1, wherein The plurality of light detector arrays are arranged to correspond to a flow direction of the flow path.

3. The flow cytometer according to claim 1, wherein Each of the plurality of photodetector elements is one of a photomultiplier tube element or an avalanche photodiode element.

4. The flow cytometer according to claim 1, wherein Each photodetector element is one of a photomultiplier tube element including a dynode comprising a semiconductor element or a photomultiplier tube element including a multistage dynode.

5. The flow cytometer according to claim 1, wherein The optical detection component includes a multi-pixel photon counter.

6. The flow cytometer according to claim 1, further comprising: The light irradiation unit irradiates the particles flowing in the flow channel with the excitation light at a plurality of light irradiation positions along a flow direction of the flow channel.

7. The flow cytometer according to claim 6, wherein The light irradiation section is configured to individually irradiate light having different wavelengths to each of the plurality of light irradiation positions.

8. The flow cytometer according to claim 6, wherein The optical detection section is configured to detect emission light generated by applying the excitation light at two or more positions among the plurality of light irradiation positions.

9. The flow cytometer according to claim 1, wherein The respective gains of the plurality of photodetector arrays can be adjusted independently of each other.

10. The flow cytometer according to claim 1, wherein The respective gains of the photodetector elements of the plurality of photodetector arrays are adjustable independently of each other.

11. The flow cytometer according to claim 1, wherein One or more of the plurality of light detector arrays are configured such that respective positions thereof can be adjusted independently of each other in a direction intersecting the arrangement direction.

12. The flow cytometer according to claim 1, wherein One or more of the plurality of light detector arrays are configured such that respective positions thereof can be adjusted independently of each other in the arrangement direction.

13. The flow cytometer according to claim 1, wherein The optical detection component further comprises a microlens array comprising a plurality of lenses, each lens of the plurality of lenses being arranged on a corresponding light detector element of the plurality of detector arrays.

14. The flow cytometer according to claim 1, further comprising a light propagation path along which the emitted light propagates to the optical detection component, wherein the light propagation path comprises one or more optical fibers.

15. The flow cytometer according to claim 1, further comprising: a light irradiation unit for irradiating the particles flowing in the flow path with the excitation light at a plurality of light irradiation positions along a flow direction of the flow path; as well as A light propagation path along which the emitted light propagates to the optical detection component, wherein The light propagation path includes a plurality of optical fiber cores, and The plurality of optical fiber cores are arranged at light input ends of the plurality of optical fiber cores in a manner corresponding to intervals between the plurality of light irradiation positions.

16. The flow cytometer according to claim 1, further comprising: a light irradiation unit for irradiating the particles flowing in the flow path with the excitation light at a plurality of light irradiation positions along a flow direction of the flow path; as well as A light propagation path along which the emitted light propagates to the optical detection component, wherein The light propagation path includes a plurality of optical fiber cores, and The plurality of optical fiber cores are arranged at light output ends of the plurality of optical fiber cores in a manner corresponding to intervals between corresponding photodetector arrays of the plurality of photodetector arrays.

17. The flow cytometer according to claim 1, further comprising: A light propagation path along which the emitted light propagates to the optical detection component, wherein A field stop is arranged in the light propagation path.

18. The flow cytometer according to claim 1, wherein At least one of the plurality of photodetector arrays includes 10 or more photodetector elements.

19. The flow cytometer of claim 1, wherein at least some of the plurality of light detector elements of the optical detection component are configured to detect light temporally independently of one another.

20. A biological sample analysis system, comprising: an optical detection member that detects emission light emitted by particles flowing in a flow path, the emission light being generated by applying excitation light to the particles flowing in the flow path; as well as an information processing unit for processing the emitted light detected by the optical detection component, wherein The optical detection component includes a plurality of photodetector arrays, in each photodetector array, photodetector elements are arranged in respective rows, and The plurality of photodetector arrays are arranged at predetermined intervals along a direction intersecting a direction substantially parallel to an arrangement direction of the corresponding rows of the photodetector elements of each of the photodetector arrays.

21. An optical detection component, comprising: A plurality of photodetector arrays, in each photodetector array, photodetector elements are arranged in respective rows, wherein The plurality of light detector arrays are arranged at predetermined intervals along a direction intersecting with an arrangement direction of corresponding rows of the light detector elements of each light detector array substantially parallel to the light detector arrays, and the plurality of light detector arrays are used to detect emission light emitted by particles flowing in a flow path, the emission light being generated by applying excitation light to the particles flowing in the flow path.

22. The optical detection component according to claim 21, wherein The optical detection member is configured to be used in combination with a light irradiation section that irradiates the particles with the excitation light at a plurality of light irradiation positions along a flow direction of the flow path.

23. The optical detection component according to claim 22, wherein: The optical detection section is configured to be used in combination with a spectroscopic optical system that spectrally disperses a plurality of rays of the emission light generated by applying the excitation light at the plurality of light irradiation positions.

24. The optical detection component according to claim 21, wherein Two or more photodetector arrays of the plurality of photodetector arrays include at least one photodetector element having a same detection wavelength range between the two or more photodetector arrays.

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