Laser measurement device and laser measurement method

Abstract

This laser measurement device is provided with: a flow cell that includes a sample flow path through which a fluid containing a sample subjected to measurement passes; a surface-emitting laser that emits toward the sample flow path a laser beam having a beam pattern having at least two bright portions with a dark portion in between in a fluid flowing direction; and a photodetector that detects light emitted from the sample when the sample passes through a region in which the beam pattern is formed in the sample flow path.

Description

Laser measurement device and laser measurement method

[0001] The present disclosure relates to a laser measurement device and a laser measurement method.

[0002] Patent Document 1 discloses a method of forming a striped pattern area in a sample flow path of a flow cell (flow path device) by irradiating the flow cell with two laser beams having different optical axes, receiving scattered light or fluorescence emitted from particles passing through the striped pattern area with a sensor, and measuring the size of the particles based on the output of the sensor.

[0003] JP 2022-77967 A JP 2022-154929 A

[0004] Y. Kurosaka et al., "Effects of non-lasing band in two-dimensional photonic-crystal lasers clarified using omnidirectional bandstructure," Opt. Express 20, 21773-21783 (2012)

[0005] In the above-described method, the width of the stripe pattern (the distance between adjacent stripes) functions as a scale for size measurement. Therefore, in order to accurately measure particle size using the above-described method, the width of the stripe pattern must be adjusted with high precision. However, since the above-described method forms the stripe pattern using two laser beams with different optical axes, even a slight misalignment of the optical axes of the laser beams changes the width of the stripe pattern. Therefore, in order to obtain a highly accurate stripe pattern, advanced and complex alignment work is required for the light sources or the optical components described above to accurately position the two laser beams (e.g., two laser beams emitted from two light sources, or two laser beams formed by splitting laser beam from one light source with an optical component such as a beam splitter). Furthermore, even a slight misalignment of the optical axis of the laser beam due to vibrations or the like occurring during measurement may result in inaccurate calculation of the particle size.

[0006] Therefore, an object of one aspect of the present disclosure is to provide a laser measurement apparatus and a laser measurement method that can easily and accurately form a beam pattern suitable for particle measurement using a flow channel device.

[0007] The present disclosure includes the following laser measurement devices [1] to

[18] and laser measurement methods

[19] .

[0008] [1] A laser measurement apparatus comprising: a flow path device including a sample flow path through which a fluid containing particles to be measured passes; a light source that emits laser light toward the sample flow path, the laser light having a beam pattern in which at least two bright areas are arranged with a dark area sandwiched between them along the flow direction of the fluid; and a sensor that detects light emitted from the particles when the particles pass through an area in the sample flow path where the beam pattern is formed.

[0009] The laser measurement device forms a beam pattern in the sample flow channel of a flow channel device, in which light and dark areas are alternately arranged along the flow direction of the flow channel device. Particle measurement (e.g., particle size measurement) can be performed effectively based on the light emitted from the particles when they pass through the region where such a beam pattern is formed. Furthermore, the laser measurement device can easily and accurately form the beam pattern by using a single light source configured in advance to form the beam pattern. That is, to form the beam pattern, sophisticated and complex alignment adjustments of multiple light sources (i.e., the optical axes of the laser beams emitted from each light source) or optical components such as a beam splitter for splitting a single laser beam emitted from a single light source into two laser beams are not required. As a result, the laser measurement device can easily and accurately form a beam pattern suitable for particle measurement using a flow channel device.

[0010] [2] The laser measurement device of [1], wherein the light source has a surface-emitting laser including: a light-emitting unit; and a phase modulation layer optically coupled to the light-emitting unit, the phase modulation layer including a base layer and a plurality of modified refractive index areas having a refractive index different from that of the base layer.

[0011] According to the configuration [2] above, by using a surface-emitting laser having a phase modulation layer as a light source, the above-mentioned beam pattern can be suitably and easily formed in the sample flow channel.

[0012] [3] A laser measurement device according to [2], wherein the center of gravity of each of the plurality of modified refractive index areas is positioned relative to each of the plurality of periodically arranged lattice points in accordance with a phase distribution corresponding to the beam pattern.

[0013] According to the configuration [3] above, the above-mentioned beam pattern can be suitably and easily formed in the sample flow channel by the surface-emitting laser, while eliminating the need for a slit member, which will be described later.

[0014] [4] The laser measurement device of [2], wherein the phase modulation layer is a photonic crystal layer in which the plurality of modified refractive index areas are periodically arranged, and the light source further has a slit member that forms the laser light having the beam pattern by passing light emitted from the surface-emitting laser.

[0015] [5] The laser measurement device of [1], wherein the light source has: a vertical cavity surface emitting laser; and a slit member that forms the laser light having the beam pattern by passing light emitted from the surface emitting laser.

[0016] According to the configuration [4] or [5] above, the combination of the surface-emitting laser and the slit member makes it possible to suitably and easily form the above-mentioned beam pattern in the sample flow channel.

[0017] [6] The laser measurement device according to any one of [1] to [5], wherein the light source is fixed to a side wall of the flow path device.

[0018] According to the configuration [6] above, it is possible to suppress attenuation of the laser light outside the flow path device, and it is also possible to facilitate positioning of the light source relative to the flow path device and to reduce the size of the laser measurement device (module).

[0019] [7] The laser measurement device according to any one of [1] to [6], wherein the light source forms a striped beam pattern in which a plurality of the bright portions extending in a direction intersecting the flow direction are arranged along the flow direction.

[0020] According to the configuration [7] above, it is possible to determine the size of the particle based on the amplitude modulation of the emitted light detected by the sensor.

[0021] [8] The laser measurement device of [7], wherein the light source has a surface-emitting laser including a light-emitting section and a phase modulation layer optically coupled to the light-emitting section, the phase modulation layer including a base layer and a plurality of modified refractive index regions having a refractive index different from that of the base layer, and the surface-emitting laser forms the striped beam pattern by interfering with light emitted from each of a plurality of regions different from each other in an in-plane direction of the light emission surface of the surface-emitting laser.

[0022] According to the configuration [8] above, a fine striped beam pattern (i.e., a pattern with a fine pitch between multiple bright areas) can be formed with high precision in a space relatively close to the light-emitting surface of the surface-emitting laser. This makes it possible to appropriately measure the size of minute particles such as cells while miniaturizing the laser measurement device (module) by arranging the surface-emitting laser close to the flow path device.

[0023] [9] The laser measurement device according to any one of [1] to [8], wherein the light source includes a plurality of light source units arranged along the flow direction.

[0024]

[10] The laser measurement device according to any one of [1] to [8], wherein the light source includes a plurality of light source units arranged along a direction intersecting the flow direction.

[0025] According to the configurations [9] and

[10] above, by combining the beam patterns of the multiple light source units, a beam pattern can be formed in the flow path device that enables more advanced particle measurement than that possible with the beam pattern of a single light source unit. According to the configuration [9] above, by arranging the multiple light source units along the flow direction, the mounting surface of the light source units relative to the flow path device can be shared, thereby making it possible to make the laser measurement device (module) more compact. According to the configuration

[10] above, by distributing the multiple light source units around the sample flow path, the degree of freedom in arranging the light source units can be improved.

[0026]

[11] The laser measurement device of [9] or

[10] , wherein each of the plurality of light source units is configured to form a striped beam pattern in the sample flow path, in which a plurality of the bright portions extending in a direction intersecting the flow direction are arranged at predetermined intervals along the flow direction, and the beam patterns of each of the plurality of light source units are arranged so as not to overlap each other in a passage area through which the particles pass in the sample flow path.

[0027] According to the configuration

[11] above, by selecting two or more light source units that emit laser light from among a plurality of light source units, the spacing (pitch) between the bright areas formed in the passage area can be easily and appropriately adjusted according to the size range of the particles to be measured.

[0028]

[12] The laser measurement device of [9] or

[10] , wherein the plurality of light source units form a first bright portion of brightness with a first intensity in a region of a first range in a first direction intersecting the flow direction, and form a second bright portion of brightness with a second intensity different from the first intensity in a region of a second range different from the first range in the first direction.

[0029] According to the configuration

[12] above, it is possible to identify the region in the sample flow path through which the particles to be measured have passed (i.e., the region of the first range or the region of the second range) based on the intensity of the emitted light detected by the sensor.

[0030]

[13] The laser measurement device of any of [1] to

[12] , wherein the light source includes a first light source unit that emits the laser light of a first wavelength and a second light source unit that emits the laser light of a second wavelength different from the first wavelength, and the sensor detects a first signal corresponding to first emitted light emitted in response to the laser light of the first wavelength being irradiated onto the particle, and a second signal corresponding to second emitted light emitted in response to the laser light of the second wavelength being irradiated onto the particle.

[0031] According to the configuration

[13] above, more advanced particle measurement can be performed based on measurement results corresponding to each of a plurality of wavelengths different from each other.

[0032]

[14] The laser measurement device of

[13] , wherein the first light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a direction intersecting the flow direction are arranged at a first interval along the flow direction, and the second light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a direction intersecting the flow direction are arranged at a second interval along the flow direction that is different from the first interval.

[0033] According to the configuration of

[14] above, by varying the pitch between the bright areas for each wavelength, when the particles to be measured have different size ranges, it is possible to measure the particle size corresponding to each range based on the measurement results of each wavelength (i.e., the measurement results of the first signal or the measurement results of the second signal).

[0034]

[15] The laser measurement device of

[13] , wherein the first beam pattern formed by the first light source unit and the second beam pattern formed by the second light source unit have the same shape and are arranged at positions offset from each other along the flow direction.

[0035] According to the configuration of

[15] above, the velocity (flow velocity) of particles in the sample flow path can be easily and accurately measured based on the time lag between the waveform corresponding to the measurement result of the first wavelength (measurement result of the first signal) and the waveform corresponding to the measurement result of the second wavelength (measurement result of the second signal), and the amount of positional deviation between the first beam pattern and the second beam pattern.

[0036]

[16] The laser measurement device of

[13] , wherein the pattern shape of the first beam pattern formed by the first light source unit is different from the pattern shape of the second beam pattern formed by the second light source unit.

[0037] According to the configuration of

[16] above, it is possible to obtain measurement results (time waveforms) corresponding to different pattern shapes for each wavelength, making it possible to perform more advanced particle measurement (waveform analysis).

[0038]

[17] The laser measurement device of

[13] , wherein the first light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a first direction intersecting the flow direction are arranged along the flow direction, and the second light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a second direction intersecting the first direction are arranged along the flow direction.

[0039] According to the configuration of

[17] above, it becomes possible to perform more advanced particle shape estimation from the measurement results (time waveform) for each wavelength.

[0040]

[18] The laser measurement device according to any one of [1] to

[17] , wherein the light source modulates the intensity of the laser light over time.

[0041] According to the configuration of

[18] above, it is possible to easily grasp the background noise occurring during measurement from the measurement results (time waveform).

[0042]

[19] A laser measurement method using the laser measurement device of any one of [1] to

[18] , comprising: a step of emitting the laser light from the light source to the flow path device, to form a beam pattern in a sample flow path through which a fluid containing particles to be measured passes within the flow path device, in which at least two bright areas are arranged with a dark area sandwiched between them along the flow direction of the fluid; a step of detecting emitted light emitted from the particles when the particles pass through an area in which the beam pattern is formed; and a step of determining at least one of the shape and size of the particles based on the detected emitted light.

[0043] The above laser measurement method can achieve the same effect as the laser measurement device described in [1] above. That is, since a beam pattern suitable for particle measurement using a flow path device can be formed with high accuracy and ease, at least one of the shape and size of particles can be determined with high accuracy based on the detection results of the emitted light obtained by the beam pattern.

[0044] According to one aspect of the present disclosure, it is possible to provide a laser measurement device and a laser measurement method that can easily and accurately form a beam pattern suitable for particle measurement using a flow channel device.

[0045] FIG. 1 is a diagram schematically showing the configuration of a laser measurement device of an embodiment. FIG. 2 is an enlarged view of portion A in FIG. 1. FIG. 3 is an enlarged view of portion A in FIG. 1 viewed from a direction facing the surface-emitting laser. FIG. 4 is a cross-sectional view of a flow cell taken along line IV-IV in FIG. 2. FIG. 5 is a partially cutaway perspective view showing an example of a surface-emitting laser. FIG. 6 is a cross-sectional view showing an example of a layered structure of a surface-emitting laser. FIG. 7 is a plan view showing an example of a phase modulation layer. FIG. 8 is an enlarged view of a unit constituent region. FIG. 9 is a plan view showing a first example of a phase distribution of a phase modulation layer. FIG. 10 is a diagram showing how two beams are emitted from the two regions shown in FIG. 9. FIG. 11 is a perspective view showing a second example of a phase distribution of a phase modulation layer. FIG. 12 is a diagram showing a first measurement example. In Fig. 13, (A) is a graph showing the light intensity of the surface-emitting laser, (B) is a graph showing the measurement results of the emitted light from sample Sa in Fig. 12, (C) is a graph showing the measurement results of the emitted light from sample Sb in Fig. 12, and (D) is a graph showing the measurement results of the emitted light from sample Sc in Fig. 12. Fig. 14 is a diagram showing a second measurement example. In Fig. 15, (A) is a graph showing the measurement results of the emitted light from sample Sd in Fig. 14, (B) is a graph showing the measurement results of the emitted light from sample Se in Fig. 14, (C) is a graph showing the measurement results of the emitted light from sample Sf in Fig. 14, (D) is a graph showing the measurement results of the emitted light from sample Sg in Fig. 14, (E) is a graph showing the measurement results of the emitted light from sample Sh in Fig. 14, and (F) is a graph showing the measurement results of the emitted light from sample Si in Fig. 14. Fig. 16 is a diagram showing a third measurement example. Fig. 17 is a diagram showing an example of a beam pattern formed by a combination of multiple surface-emitting lasers in a third measurement example. Fig. 18 is a diagram showing a fourth measurement example. In Fig. 19, (A) is a graph showing the measurement results of emitted light from sample Sj in Fig. 18, and (B) is a graph showing the measurement results of emitted light from sample Sk in Fig. 18. Fig. 20 is a diagram showing a fifth measurement example. Fig. 21 is a graph showing the measurement results of emitted light from sample S in Fig. 20. Fig. 22 is a diagram showing a sixth measurement example. Fig. 23 is a diagram showing a seventh measurement example. Fig. 24 is a diagram showing an eighth measurement example.25A is a graph showing the measurement results of light emitted from sample Sl in FIG. 24, and (B) is a graph showing the measurement results of light emitted from sample Sm in FIG. 24. In FIG. 26A is a graph showing the measurement results using laser light, which is continuous light, and (B) is a graph showing the measurement results of the ninth measurement example. FIG. 27 is a graph showing another example of the measurement results of the ninth measurement example. FIG. 28 is an enlarged view of range Rb in FIG. 27. FIG. 29 is a diagram showing a modified arrangement of multiple surface-emitting lasers. FIG. 30 is a diagram showing a schematic configuration of a first modified example of a laser measurement device. FIG. 31 is a diagram showing a schematic configuration of a second modified example of a laser measurement device. FIGS. 32A and 32B are diagrams showing another example of a beam pattern. FIG. 33 is a diagram showing a first modified example of a light source. FIG. 34 is a diagram showing a second modified example of a light source. FIG. 35 is a plan view showing an example in which a refractive index approximately periodic structure is applied to a specific region of a phase modulation layer. FIG. 36 is a diagram showing a phase shift in spherical coordinates (r, θ). ｒｏｔ ,θ ｔｉｌｔ 37 is a plan view showing a reciprocal lattice space relating to a phase modulation layer of a light emitting device that performs M-point oscillation. FIG. 38 is a conceptual diagram showing an example of a phase distribution. FIG. 39 is a diagram for schematically explaining the peripheral structure of a light line LL. FIG. 40 is a diagram for explaining a coordinate conversion from (ξ, η, ζ) to coordinates (ξ, η, ζ) in an XYZ orthogonal coordinate system. FIG. 39 is a diagram for explaining a phase distribution φ ２ Fig. 41 is a conceptual diagram for explaining a state in which a diffraction vector is added to the in-plane wave vector in four directions, which is obtained by removing the wave number spread from the wave number vector. Fig. 42 is a plan view showing another form of the phase modulation layer (first region and second region). Fig. 43 is a diagram showing the arrangement of modified refractive index areas in the phase modulation layer (first region and second region) shown in Fig. 42.

[0046] Hereinafter, an embodiment of the present disclosure will be described in detail with reference to the drawings. In the following description, the same or equivalent elements will be designated by the same reference numerals, and redundant description will be omitted.

[0047] [Overall Configuration of Laser Measurement Apparatus] A laser measurement apparatus 1 according to an embodiment of the present disclosure will be described with reference to Figures 1 to 4. The laser measurement apparatus 1 is an apparatus for performing particle measurement (e.g., measurement of particle shape, size, etc.) by flow cytometry. As shown in Figure 1, the laser measurement apparatus 1 includes a flow cell 2 (a flow path device), a surface-emitting laser 3 (a light source), a photodetector 4 (a sensor), a control unit 5, an optical system 6, and a pump 7.

[0048] 1 shows a configuration in which the laser measurement device 1 includes a single surface-emitting laser 3 as a light source, but when forming the beam patterns of the third to eighth measurement examples described below, the laser measurement device 1 may include multiple surface-emitting lasers 3A to 3D (light source units) (two surface-emitting lasers 3A and 3B in the fourth to eighth measurement examples). Also, while FIG. 1 shows a configuration in which the laser measurement device 1 includes a single photodetector 4 as a sensor, when forming the beam patterns of the fifth to eighth measurement examples described below, the laser measurement device 1 may include multiple (two) photodetectors 4A and 4B corresponding to the multiple (two) surface-emitting lasers 3A and 3B, respectively. The configurations of the light source and sensor corresponding to each measurement example will be described when explaining each measurement example.

[0049] The flow cell 2 includes a sample flow path 21 through which a fluid containing a sample S (see FIGS. 2 to 4 ), which is a particle to be measured, passes. The sample S is, for example, a minute particle such as a cell, an extracellular vesicle, or a biological substance. The fluid containing the sample S is pumped into the sample flow path 21 by a pump 7. In this embodiment, the flow cell 2 has a tubular sidewall 22 that surrounds the sample flow path 21 and extends in one direction (the Z-axis direction). As an example, the sidewall 22 is formed in the shape of a square ring when viewed from the direction of fluid flow (the Z-axis direction) in the flow cell 2. The sidewall 22 is formed of a material that is transparent to the laser light L1 emitted from the surface-emitting laser 3 and the emitted light L2 emitted from the sample S. In other words, the sidewall 22 transmits the laser light L1 and the emitted light L2. Examples of transparent materials include glass, quartz, and synthetic resin.

[0050] Within the sample flow channel 21, a flow of sample suspension containing the sample S (sample flow) and a flow of sheath liquid (sheath flow) formed around the sample flow are formed. In this embodiment, the sample flow and the sheath flow within the sample flow channel 21 are not distinguished from each other in the illustration. The fluid forming the sample flow and the sheath flow is, for example, water. When the width of the sample flow is set to a relatively small value by controlling the pressure of the sample flow and the pressure of the sheath flow, each sample S flows sequentially through approximately the center of the sample flow channel 21. On the other hand, when the width of the sample flow is set to a relatively large value, the sample S also flows to positions other than the approximately center of the sample flow channel 21 (i.e., positions shifted from the center of the sample flow channel 21 toward the side wall 22).

[0051] For convenience, in the specification and drawings, the direction along the flow direction of the fluid in the flow cell 2 is referred to as the Z-axis direction, the direction perpendicular to the side surface 22a of the side wall 22 on which the surface-emitting laser 3 is attached (in other words, the direction perpendicular to the light emission surface 3a of the surface-emitting laser 3) is referred to as the X-axis direction, and the direction perpendicular to both the Z-axis direction and the X-axis direction is referred to as the Y-axis direction.

[0052] The surface-emitting laser 3 emits laser light L1 so as to form a beam pattern P in the sample flow path 21, in which at least two bright regions Pa are arranged with a dark region Pb sandwiched between them along the flow direction (Z-axis direction) of the fluid in the flow cell 2 (see FIG. 12 ). In other words, the beam pattern P includes a portion in which bright regions Pa and dark regions Pb alternate along the Z-axis direction. FIGS. 1 to 3 schematically show the laser light L1 forming the beam pattern P1 ( FIG. 12 ) of a first measurement example, which will be described later. As an example, the surface-emitting laser 3 is fixed to the sidewall 22 of the flow cell 2. More specifically, the surface-emitting laser 3 is fixed to the flow cell 2 so that the light-emitting surface 3a of the surface-emitting laser 3 faces one side surface 22a of the sidewall 22 (the outer surface opposite the inner surface on the sample flow path 21 side). The surface-emitting laser 3 is attached to the side surface 22a by, for example, direct bonding using semiconductor process technology, bonding with an adhesive, screwing, or the like. A configuration example of the surface-emitting laser 3 will be described later. However, the surface-emitting laser 3 does not have to be fixed to the flow cell 2 (side wall 22), and may be disposed at a position away from the flow cell 2. For example, the surface-emitting laser 3 may be disposed at a position away from the flow cell 2, for example, within a range of 20 mm or less, in order to adjust the size of the beam pattern P (for example, the pitch between adjacent bright portions Pa of the striped beam pattern P1).

[0053] The photodetector 4 is a sensor that detects emitted light L2 emitted from the sample S when the sample S passes through the region in the sample flow path 21 where the beam pattern P is formed. Examples of the emitted light L2 include scattered light and fluorescence. In this embodiment, the photodetector 4 detects the scattered light as the emitted light L2. Scattered light includes forward scattered light that travels in the same direction as the irradiation direction of the laser light L1 onto the sample S, and side scattered light that travels in a direction perpendicular to the irradiation direction. In this embodiment, the photodetector 4 is configured to detect the forward scattered light as the emitted light L2. That is, in order to detect the forward scattered light from the sample S, the photodetector 4 is disposed in a position facing the surface-emitting laser 3 across the sample flow path 21.

[0054] The control unit 5 acquires the measurement results (time waveform) of the signal intensity detected by the photodetector 4, and performs various analytical processes (e.g., determining (estimating) the shape and size of the sample S in each measurement example described below) based on the measurement results. The control unit 5 can be configured, for example, by one or more computer devices equipped with a processor, memory, auxiliary storage device, etc.

[0055] The optical system 6 is composed of a plurality of optical members arranged to efficiently guide only the emitted light L2 to the photodetector 4. The optical system 6 is arranged between the flow cell 2 and the photodetector 4. The optical system 6 has a collimating lens 61, a light-shielding plate 62, a condensing lens 63, and an optical filter 64. The collimating lens 61, the light-shielding plate 62, the condensing lens 63, and the optical filter 64 are arranged in this order from the flow cell 2 side toward the photodetector 4 side.

[0056] The collimating lens 61 is a lens for collimating the emission light L2 emitted from the sample S. The light blocking plate 62 is a member for blocking the laser light L1 to prevent the laser light L1 from entering the photodetector 4. The condensing lens 63 is a lens for collecting the emission light L2 collimated by the collimating lens 61 onto the light receiving surface of the photodetector 4. The optical filter 64 is a filter member configured to transmit only the emission light L2. For example, the optical filter 64 is a bandpass filter configured to transmit only the wavelength band corresponding to the emission light L2.

[0057] [Configuration Example of Surface-Emitting Laser] A configuration example of the surface-emitting laser 3 will be described with reference to Figures 5 to 11. In Figures 5 to 11, an XYZ Cartesian coordinate system is defined in which the axis extending in the thickness direction of the surface-emitting laser 3 at the center of the surface-emitting laser 3 is the Z-axis. Note that the XYZ Cartesian coordinate system in Figures 5 to 11 is unrelated to the XYZ Cartesian coordinate systems in other figures (i.e., the XYZ Cartesian coordinate system in which the flow direction of the fluid in the flow cell 2 defined above is defined as the Z-axis direction).

[0058] The surface-emitting laser 3 is a laser light source that forms a standing wave in the XY plane and outputs a phase-controlled plane wave in a direction intersecting its thickness direction. The surface-emitting laser 3 is a Si-iPM laser, and can output an optical image of any shape in a direction perpendicular to the main surface 10a of the semiconductor substrate 10 (Z-axis direction), a direction tilted relative to this, or a direction including both. The surface-emitting laser 3 may be a Si-iPMSEL (registered trademark) manufactured by Hamamatsu Photonics KK

[0059] 5 and 6 , the surface-emitting laser 3 includes an active layer 12 as a light-emitting section provided on a semiconductor substrate 10, a pair of cladding layers 11 and 13 sandwiching the active layer 12, and a contact layer 14 provided on the cladding layer 13. The semiconductor substrate 10, the cladding layers 11 and 13, and the contact layer 14 are made of compound semiconductors such as GaAs-based semiconductors, InP-based semiconductors, or nitride-based semiconductors. The energy bandgaps of the cladding layers 11 and 13 are larger than the energy bandgaps of the active layer 12. The thickness directions of the semiconductor substrate 10, the cladding layer 11, the active layer 12, the cladding layer 13, and the contact layer 14 coincide with the Z-axis direction.

[0060] The surface-emitting laser 3 further includes a phase modulation layer 15 optically coupled to the active layer 12. In this embodiment, the phase modulation layer 15 is provided between the active layer 12 and the cladding layer 13. The thickness direction of the phase modulation layer 15 coincides with the Z-axis direction. The phase modulation layer 15 may be provided between the cladding layer 11 and the active layer 12. An optical guide layer may be provided, if necessary, between at least one of the active layer 12 and the cladding layer 13 and the active layer 12 and the cladding layer 11. The optical guide layer may include a carrier barrier layer for efficiently confining carriers in the active layer 12.

[0061] The phase modulation layer 15 is configured to include a base layer 15a made of a first refractive index medium and a plurality of modified refractive index areas 15b made of a second refractive index medium having a refractive index different from that of the first refractive index medium and present in the base layer 15a. The plurality of modified refractive index areas 15b include a lattice-like, approximately periodic structure. When the equivalent refractive index of the mode is n and the lattice spacing is a, the wavelength λ selected by the phase modulation layer 15 is ０ is λ ０ This wavelength λ is expressed as ０ is a wavelength included in the emission wavelength range of the active layer 12. The phase modulation layer 15 is configured to modulate the wavelength λ ０ A band edge wavelength in the vicinity of the phase modulation layer 15 can be selected and output to the outside. In this case, the M-point band edge of a square lattice, which is free from zero-order optical noise in the vertical direction, can be used as the photonic band edge. Alternatively, the photonic band edge may be the J-point band edge of a triangular lattice. The light incident on the phase modulation layer 15 forms a predetermined mode in accordance with the arrangement of the modified refractive index regions 15b in the phase modulation layer 15, and is emitted to the outside from the surface of the surface-emitting laser 3 as laser light.

[0062] The surface-emitting laser 3 further includes an electrode 16 provided on the contact layer 14 and an electrode 17 provided on the back surface 10b of the semiconductor substrate 10. The electrode 16 forms ohmic contact with the contact layer 14. The electrode 17 forms ohmic contact with the semiconductor substrate 10. The electrode 17 has an opening 17a in the central region of the back surface 10b. The electrode 16 is provided in the central region of the surface of the contact layer 14. The portion of the contact layer 14 other than the electrode 16 is covered with a protective film 18 (see FIG. 6 ). The contact layer 14 not in contact with the electrode 16 may be removed to limit the current range. The back surface 10b of the semiconductor substrate 10, except for the region where the electrode 17 is provided, is covered with an anti-reflection film 19, including the inside of the opening 17a. The anti-reflection film 19 in the region other than the opening 17a may be removed.

[0063] In the surface-emitting laser 3, when a driving current is supplied between the electrodes 16 and 17, recombination of electrons and holes occurs in the active layer 12, causing the active layer 12 to emit light. The electrons and holes that contribute to this light emission, as well as the light generated in the active layer 12, are efficiently confined between the cladding layers 11 and 13. The light emitted from the active layer 12 enters the phase modulation layer 15 and forms a predetermined mode according to the lattice structure inside the phase modulation layer 15. The laser light emitted from the phase modulation layer 15 is directly output from the back surface 10b through the opening 17a to the outside of the surface-emitting laser 3. Alternatively, the laser light emitted from the phase modulation layer 15 is reflected by the electrode 16, and then output from the back surface 10b through the opening 17a to the outside of the surface-emitting laser 3. That is, in this example, the back surface 10b of the surface-emitting laser 3 functions as the light-emitting surface 3a. At this time, the signal light contained in the laser light is emitted in any direction, including a direction perpendicular to the main surface 10a and directions inclined relative to that direction. It is this signal light that constitutes the light emitted from the surface-emitting laser 3. The signal light is mainly the first-order diffracted light or the −1st-order diffracted light of the laser light (hereinafter referred to as +1st-order light and −1st-order light, respectively), or both.

[0064] FIG. 7 is a plan view of the phase modulation layer 15. In FIG. 7, a virtual square lattice is set in the XY plane for the phase modulation layer 15. One side of the square lattice is parallel to the X axis, and the other side is parallel to the Y axis. Square-shaped unit constituent regions R, each centered on a lattice point O of the square lattice, are two-dimensionally arranged across multiple columns along the X axis and multiple rows along the Y axis. The XY coordinates of each unit constituent region R are defined by the center of gravity of the respective unit constituent region R. These center of gravity positions coincide with the lattice point O of the virtual square lattice. For example, only one modified refractive index region 15b is provided in each unit constituent region R. The planar shape of the modified refractive index region 15b is, for example, circular. The lattice point O may be located outside the modified refractive index region 15b or may be included inside the modified refractive index region 15b.

[0065] FIG. 8 is an enlarged view of the unit constituent region R. As shown in the figure, each modified refractive index area 15b has a center of gravity G. Here, the angle between the vector from lattice point O toward the center of gravity G and the X-axis is defined as γ(x, y). x represents the position of the xth lattice point on the X-axis, and y represents the position of the yth lattice point on the Y-axis. When the rotation angle γ is 0°, the direction of the vector connecting lattice point O and the center of gravity G coincides with the positive direction of the X-axis. Furthermore, the length of the vector connecting lattice point O and the center of gravity G is defined as r(x, y). As an example, r(x, y) is constant throughout the phase modulation layer 15, regardless of x and y. The planar size of each modified refractive index area 15b does not need to be constant and may be set individually.

[0066] In this embodiment, the surface-emitting laser 3 is configured as an iPMSEL. That is, the center of gravity G of each of the multiple modified refractive index areas 15b is located relative to each of the multiple periodically arranged lattice points O in accordance with a phase distribution corresponding to the beam pattern (beam pattern P of various measurement examples described below). In other words, the center of gravity G of each modified refractive index area 15b is located relative to the corresponding lattice point O in accordance with the phase modulation amount of a predetermined phase distribution. That is, as shown in FIG. 7 , the direction of the vector connecting the lattice point O and the center of gravity G, in other words, the rotation angle γ of the center of gravity G of the modified refractive index area 15b around the lattice point O, is set individually for each lattice point O in accordance with the phase distribution φ(x, y) corresponding to the desired shape of the emitted light.

[0067] As described above, in this embodiment, the surface-emitting laser 3 is a surface-emitting laser configured to be capable of outputting an optical image of any shape according to the setting of the phase distribution φ(x, y) of the phase modulation layer 15. By using such a surface-emitting laser 3, it is possible to form, in the sample flow channel 21, beam patterns P of various measurement examples, which will be described later.

[0068] For example, in order to suitably form a striped beam pattern P1 according to a first measurement example described later (i.e., a pattern in which a plurality of linear bright areas Pa and a plurality of linear dark areas Pb are alternately arranged as shown in FIG. 12 ), the surface-emitting laser 3 may be configured as follows. That is, the surface-emitting laser 3 may form the striped beam pattern P1 by causing interference between light beams emitted from a plurality of different regions in the in-plane direction of the light-emitting surface 3 a (i.e., the direction along the XY plane in FIGS. 5 to 11 ). With the above configuration, a fine striped beam pattern P1 (i.e., a pattern in which the pitch between the plurality of bright areas Pa is minute) can be formed with high precision in a space relatively close to the light-emitting surface 3 a of the surface-emitting laser 3. As a result, by disposing the surface-emitting laser 3 in close proximity to the flow cell 2, it is possible to miniaturize the laser measurement device 1 (module) while suitably measuring the size of microparticles such as cells.

[0069] Below, two examples (first example and second example) of phase distribution for forming a striped beam pattern P1 in a space at a relatively short distance (for example, about 1 mm) from the light emission surface 3 a of the surface-emitting laser 3 will be described. However, the phase distribution for forming the beam pattern P1 is not limited to the following first and second examples. Furthermore, when forming a beam pattern other than a striped pattern, the phase distribution of the phase modulation layer 15 is set according to the shape of the beam pattern.

[0070] 9 and 10 , a first example of the phase distribution of the phase modulation layer 15 will be described. In the first example, the phase distribution of the phase modulation layer 15 has regions (corresponding to a first region 151 and a second region 152 described later) including a one-dimensional lens pattern whose phase changes in one direction (for example, the X-axis direction) on both sides of the optical axis in that direction. Due to the one-dimensional lens pattern, a first beam emitted from a region on one side of the optical axis (corresponding to the first region 151 described later) and a second beam emitted from a region on the other side of the optical axis (corresponding to the second region 152 described later) intersect with each other at a certain position (a first position) and then separate.

[0071] FIG. 9 is a plan view showing an example of the phase distribution of the phase modulation layer 15. The phase distribution of the phase modulation layer 15 may have a first region 151 on one side of the optical axis OX in one direction (the X-axis direction in the illustrated example) and a second region 152 on the other side of the optical axis OX in the same direction. In this case, the optical axis OX is located between the first region 151 and the second region 152. The distance from the first region 151 to the optical axis OX is equal to the distance from the second region 152 to the optical axis OX. In other words, the planar shapes of the first region 151 and the second region 152 are symmetrical with respect to a line passing through the optical axis OX and extending in the Y-axis direction. The optical axis OX is the central axis of the light emitted from the surface-emitting laser 3, and is typically the center line of the surface-emitting laser 3 along the Z-axis direction. The first region 151 and the second region 152 have planar shapes such as rectangular shapes and extend in a direction intersecting the X-axis direction (the Y-axis direction in the illustrated example). The longitudinal direction of the first region 151 is parallel to the longitudinal direction of the second region 152. A gap SP including the optical axis OX is provided between the first region 151 and the second region 152. The width of the gap SP in the X-axis direction is arbitrary.

[0072] The first region 151 and the second region 152 include a one-dimensional lens pattern whose phase changes in the arrangement direction of the first region 151 and the second region 152, i.e., in the X-axis direction. FIG. 10 is a diagram showing how beams 241 and 242 are emitted from the first region 151 and the second region 152 shown in FIG. A beam 241 (first beam), which is +1st-order light, is emitted from the first region 151. A beam 242 (second beam), which is +1st-order light, is emitted from the second region 152. The beams 241 and 242 cross each other at a first position 25 and then separate. The first position 25 is defined as the center position of a region 26 (shown by dots in the figure) in the XZ plane where the beams 241 and 242 overlap. When the width of the first region 151 in the X-axis direction is equal to the width of the second region 152 in the same direction, the region 26 has a diamond shape when viewed from the Y-axis direction. A focused spot 261 is formed in the region 26, extending in the light emission direction with the first position 25 as its center. The first position 25 may be located on the optical axis OX or may be spaced apart from the optical axis OX.

[0073] According to the above configuration, by causing interference in the region 26 where the beams 241 and 242 overlap, it is possible to form a striped light image extending in the Y-axis direction (i.e., a beam pattern including multiple linear bright areas arranged in the X-axis direction).

[0074] (Second Example of Phase Distribution) A second example of the phase distribution of the phase modulation layer 15 will be described with reference to FIG. 11 . As shown in FIG. 11 , in the second example, the phase modulation layer 15 has a light extraction region 15P formed therein, including a first region 151 and a second region 152 spaced apart from the first region 151, according to the arrangement of a plurality of modified refractive index regions 15b. In the light extraction region 15P, a plurality of modified refractive index regions 15b are arranged so that light resonating in the in-plane direction of the XY plane is diffracted in the out-of-plane direction in the first region 151 and the second region 152. In addition, in the intermediate region 155, a plurality of modified refractive index regions 15b are arranged so that light resonating in the in-plane direction is not diffracted in the out-of-plane direction. The first region 151 and the second region 152 are formed as elongated linear regions in the Y-axis direction. This realizes a pseudo-double slit in which the first region 151 and the second region 152 each serve as a slit, making it possible to form interference fringes in the Fresnel region due to interference of the emitted light. That is, it is possible to form a fine striped pattern (beam pattern P1) at a relatively short distance from the light exit surface 3a.

[0075] [Measurement Examples] Various beam patterns P will be described below, along with measurement examples corresponding to each beam pattern P.

[0076] (First Measurement Example) A first measurement example using a striped beam pattern P1 will be described with reference to FIGS. 12 and 13 . In the first measurement example, the surface-emitting laser 3 is configured to form multiple (for example, five) linear bright regions Pa extending in a direction (Y-axis direction) intersecting the flow direction (Z-axis direction) of the flow cell 2 and the emission direction (X-axis direction) of the laser light L1. As shown in FIG. 12 , the beam pattern P1 has a pattern shape in which linear bright regions (bright regions Pa) and linear dark regions (dark regions Pb) are alternately arranged along the Z-axis direction when viewed from the X-axis direction. FIG. 13A shows a graph in which the horizontal axis represents the coordinate corresponding to the x-axis direction in FIG. 12 and the vertical axis represents the intensity of the beam pattern P1 formed by the laser light L1. As shown in FIG. 13A , the beam pattern P1 has peaks at positions corresponding to each of the five bright regions Pa.

[0077] As shown in Figure 12, we consider a sample Sa having an elongated shape in the Z-axis direction, a spherical sample Sb, and a sample Sc having an elongated shape in the Y-axis direction. Although Figure 12 illustrates multiple samples Sa to Sc simultaneously present in the sample flow path 21, each sample Sa to Sc is measured separately. That is, each sample Sa to Sc passes through the region where the beam pattern P1 is formed at different times. This also applies to the second measurement example in Figure 14, the fourth measurement example in Figure 18, and the seventh measurement example in Figure 24.

[0078] (B) of Figure 13 is a graph (time waveform) showing the measurement results of emitted light L2 from sample Sa in Figure 12, (C) is a graph showing the measurement results of emitted light L2 from sample Sb in Figure 12, and (D) is a graph showing the measurement results of emitted light L2 from sample Sc in Figure 12. In each graph, the horizontal axis represents time, and the vertical axis represents the signal intensity of emitted light L2 (in this embodiment, forward scattered light) detected by the photodetector 4.

[0079] In the measurement results (time waveforms) of each of the samples Sa to Sc shown in Figure 13 (B) to (D), peaks are observed corresponding to the timing at which each of the samples Sa to Sc passes through the position where it overlaps with the five bright areas Pa. Here, the light intensity at the peak (mountain) of the time waveform is defined as I ｍａｘ and the light intensity at the bottom (valley) is expressed as I ｍｉｎ Then, the modulation depth M of the measurement result can be calculated by the following formula (0).

[0080] M = (I ｍａｘ -I ｍｉｎ ) / (I ｍａｘ +I ｍｉｎ ) ... (0)

[0081] According to the first measurement example, the control unit 5 can determine the size (length in the Z-axis direction) of the sample S based on the amplitude modulation of the signal intensity of the emitted light L2 represented in the measurement result (time waveform). More specifically, as shown in (C) and (D) of Figures 13A and 13B, for samples Sb and Sc having a short length in the Z-axis direction, the samples Sb and Sc do not overlap with multiple bright portions Pa at the same time (or the period in which they do not overlap with the bright portions Pa is relatively long), so the modulation depth M calculated by the above formula (0) is relatively large. On the other hand, as shown in (B) of Figure 13A, for sample Sa having a long length in the Z-axis direction, there is a period in which the sample Sa overlaps with multiple bright portions Pa at the same time (or the period in which they do not overlap with the bright portions Pa is relatively short), so the modulation depth M calculated by the above formula (0) is relatively small. Therefore, according to the first measurement example, the control unit 5 can determine the size (length in the Z-axis direction) of the sample S based on the magnitude of the modulation depth M. For example, the control unit 5 can determine the size of the sample S based on the modulation depth M obtained from the measurement results of each sample S by using information indicating the correspondence between the modulation depth M obtained by the above formula (0), the spacing (pitch) between adjacent bright areas Pa, and the size of the sample S (length in the Z-axis direction) (for example, a modulation curve such as that shown in Figure 7 of Patent Document 1).

[0082] The range (size range) of the size (length in the Z-axis direction) of the sample S that can be measured by the striped beam pattern P1 depends on the distance (pitch) between adjacent bright areas Pa in the beam pattern P1. Specifically, the smaller the size of the sample S to be measured, the shorter the pitch must be to determine the size of the sample S. Therefore, in the first measurement example, it is necessary to select and use a surface-emitting laser 3 configured to form a beam pattern P1 having a pitch that corresponds to the size range of the sample S to be measured. The pitch between adjacent bright areas Pa is set, for example, to be equal to or greater than 1 μm and equal to or less than 100 μm.

[0083] 14 and 15, a second measurement example using a dot-shaped beam pattern P2 will be described. As shown in Fig. 14, the beam pattern P2 has a pattern shape in which a plurality of bright portions Pa are scattered in a dot shape when viewed from the X-axis direction. As an example, such a dot-shaped beam pattern P2 can be formed by using the Si-iPM laser disclosed in Patent Document 2 as the surface-emitting laser 3.

[0084] In the example of Fig. 14, each bright portion Pa is formed in a square shape when viewed from the X-axis direction. Furthermore, the multiple bright portions Pa are arranged in a diamond lattice pattern when viewed from the X-axis direction. That is, if the rows in which the bright portions Pa are arranged in the Z-axis direction are defined as rows x1 to x4 from the upstream side to the downstream side, the positions in the Y-axis direction of the multiple bright portions Pa arranged in the odd-numbered rows (x1, x3) are shifted from the positions in the Y-axis direction of the multiple bright portions Pa arranged in the even-numbered rows (x2, x4). As a result, the beam pattern P2 has a shape in which a dark portion Pb is arranged between two adjacent bright portions Pa in the Z-axis direction (in other words, a shape in which the bright portions Pa and the dark portions Pb are arranged alternately along the Z-axis direction). More specifically, in the flow paths in the odd-numbered columns that flow through positions overlapping with the bright portions Pa (in FIG. 14 , the flow paths through which samples Sd and Sf pass, the flow path through which the upper half of sample Sh passes, and the flow paths through which the upper and lower portions of sample Si pass when sample Si is divided into thirds), bright portions Pa are formed in the odd-numbered columns, and dark portions Pb are formed in the regions between the bright portions Pa of adjacent odd-numbered columns. On the other hand, in the flow paths in the even-numbered columns that flow through positions overlapping with the bright portions Pa (in FIG. 14 , the flow paths through which samples Se and Sg pass, the flow path through which the lower half of sample Sh passes, and the flow path through which the central portion of sample Si passes when sample Si is divided into thirds), bright portions Pa are formed in the even-numbered columns, and dark portions Pb are formed in the regions between the bright portions Pa of adjacent even-numbered columns.

[0085] 14, consider samples Sd and Se that are elongated in the Z-axis direction, spherical samples Sf and Sg, sample Sh that is elongated in the Y-axis direction, and sample Si that is longer than sample Sh in the Y-axis direction. Here, it is assumed that the sample flows of each of samples Sd to Si are set to flow straight along the Z-axis direction.

[0086] 15A is a graph showing the measurement results of emitted light L2 from sample Sd, (B) is a graph showing the measurement results of emitted light L2 from sample Se, (C) is a graph showing the measurement results of emitted light L2 from sample Sf, (D) is a graph showing the measurement results of emitted light L2 from sample Sg, (E) is a graph showing the measurement results of emitted light L2 from sample Sh, and (F) is a graph showing the measurement results of emitted light L2 from sample Si. In each graph, the horizontal axis represents time, and the vertical axis represents the signal intensity of emitted light L2 detected by photodetector 4. Furthermore, times t1 to t4 on the horizontal axis of each graph represent the times when each sample Sd to Si passed through positions corresponding to columns x1 to x4 in FIG.

[0087] The samples Sd and Se, which are longer in the Z-axis direction, overlap with one bright portion Pa for a longer period than the samples Sf to Si, which are shorter in the Z-axis direction. For this reason, as shown in Figures 15A and 15B, the time waveforms of samples Sd and Se have peak waveforms that are longer in the time direction (horizontal axis direction) than the time waveforms of samples Sf and Sg (see Figures 15C and 15D).

[0088] The sample Sh, which is long in the Y-axis direction, is large enough to overlap one bright portion Pa provided in the odd-numbered column and one bright portion Pa provided in the even-numbered column. Therefore, as shown in Fig. 15(E), peak waveforms are observed not only at times t1 and t3 when the sample passes through the odd-numbered column (x1, x3), but also at times t2 and t4 when the sample passes through the even-numbered column (x2, x4).

[0089] Sample Si, which is long in the Y-axis direction, is large enough to overlap two bright portions Pa provided in the odd-numbered columns and one bright portion Pa provided in the even-numbered column. For this reason, as shown in Fig. 15(F), peak waveforms are observed in both the odd-numbered columns and the even-numbered columns, similar to sample Sh, and the peaks corresponding to the odd-numbered columns (peaks at times t1 and t3) are higher than the peaks corresponding to the even-numbered columns (peaks at times t2 and t4).

[0090] As described above, according to the second measurement example, the control unit 5 can determine not only the length of the sample S in the Z-axis direction but also the length of the sample S in the Y-axis direction based on the measurement results (time waveforms) of each sample S. That is, the control unit 5 can determine the length of the sample S along the Z-axis direction based on the width of the peak waveform in the time direction represented in the measurement results (time waveforms). Furthermore, the control unit 5 can determine the length of the sample S in the Y-axis direction based on the position where the peak is observed (either the odd-numbered column or the even-numbered column, or both the odd-numbered column and the even-numbered column) and the peak difference between the odd-numbered column and the even-numbered column.

[0091] 16 and 17 , a third measurement example will be described, in which various beam patterns can be formed by combining multiple surface-emitting lasers 3A to 3D. As shown in FIG. 16 , in the third measurement example, the laser measurement device 1 includes, as light sources, multiple (four, for example) surface-emitting lasers 3A to 3D (multiple light source units) arranged along the Z-axis direction. In the third measurement example, the surface-emitting lasers 3A to 3D all have the same configuration as the surface-emitting laser 3 described above. Note that the surface-emitting lasers 3A and 3B used in the fourth and subsequent measurement examples are unrelated to the surface-emitting lasers 3A and 3B used in the third measurement example, and are configured to form beam patterns corresponding to the respective measurement examples.

[0092] As in the first measurement example, each of the multiple surface-emitting lasers 3A to 3D is configured to form striped beam patterns PA to PD (see the left part of FIG. 17 ) in the sample flow path 21, in which multiple linear bright areas Pa extending in the Y-axis direction are arranged at predetermined intervals along the Z-axis direction. Furthermore, in a passing region Ra through which the sample S passes in the sample flow path 21, the beam patterns PA to PD of the multiple surface-emitting lasers 3A to 3D are arranged so as not to overlap with each other. In this example, flow control is performed so that the sample S passes through the center of the sample flow path 21 in the Y-axis direction, and therefore the passing region Ra is a region that includes the center of the sample flow path 21 in the Y-axis direction and has a predetermined length in the Z-axis direction.

[0093] FIG. 17 is a diagram showing each of the beam patterns PA to PD when viewed from the X-axis direction (where the Z-axis direction corresponds to the left-right direction in the figure and the Y-axis direction corresponds to the up-down direction in the figure). As shown in the left part of FIG. 17, the bright portions Pa of each of the beam patterns PA to PD are shifted from each other in the Z-axis direction in the passing region Ra and are arranged so as not to overlap each other. The pitch p (the distance between adjacent bright portions Pa) of each of the beam patterns PA to PD is constant. In addition, the beam pattern PB is spaced a distance d from the beam pattern PA in the Z-axis direction. ＡＢ Similarly, the beam patterns PC and PD are shifted from the beam pattern PA by a distance d ＡＣ , d ＡＤ Here, the distance d ＡＢ is half the length of the pitch p, and the distance d ＡＣ is a quarter of the pitch p, and the distance d ＡＤ is 3 / 4 the length of the pitch p.

[0094] 17, when laser light L1 is emitted only from the surface-emitting laser 3A, it is possible to set a beam pattern PA in which the distance between adjacent bright portions Pa is "pitch p." Note that it is also possible to set a beam pattern (any of beam patterns PB to PC) in which the distance between adjacent bright portions Pa is "pitch p" by emitting laser light L1 only from one of the surface-emitting lasers 3B, 3C, and 3D.

[0095] 17, when laser light L1 is emitted from two surface-emitting lasers 3A and 3B, it is possible to set a beam pattern (beam pattern PA+PB) in which the distance between adjacent bright portions Pa is "half the pitch p." Note that, by emitting laser light L1 from surface-emitting lasers 3C and 3D, it is also possible to set a beam pattern (beam pattern PC+PD) in which the distance between adjacent bright portions Pa is "half the pitch p."

[0096] As shown in the lower right part of Figure 17, when laser light L1 is emitted from four surface-emitting lasers 3A to 3D, a beam pattern (beam pattern PA+PB+PC+PD) can be set in which the distance between adjacent bright areas Pa is "1 / 4 of the pitch p."

[0097] As described above, according to the third measurement example, by selecting two or more surface-emitting lasers that emit laser light L1 from the plurality of surface-emitting lasers 3A to 3D, it is possible to easily and appropriately adjust the interval (pitch) between the bright portions Pa formed in the passage region Ra in accordance with the range of sizes of the measurement target sample S. The two or more surface-emitting lasers that emit laser light L1 may be configured to be switchable by the control unit 5, for example.

[0098] (Fourth Measurement Example) A fourth measurement example will be described with reference to Figures 18 and 19. The fourth measurement example is similar to the third measurement example in that a plurality of surface-emitting lasers (light source units) are used as light sources. In the fourth measurement example, the laser measurement device 1A includes two surface-emitting lasers 3A and 3B as light sources. Both of the surface-emitting lasers 3A and 3B have the same configuration as the surface-emitting laser 3 described above.

[0099] The multiple surface-emitting lasers 3A, 3B are configured to form a first bright portion Pa1 with a first brightness intensity in a region R1 of a first range in the Y-axis direction (first direction) in at least a portion of the sample flow path 21, and to form a second bright portion Pa2 with a second brightness intensity different from the first brightness in a region R2 of a second range different from the first range in the Y-axis direction. For example, the first range is a region outside the center in the Y-axis direction, and the second range is a region in the center in the Y-axis direction. Furthermore, one surface-emitting laser 3A is configured to form a low-intensity first bright portion Pa1 in the region R1, and the other surface-emitting laser 3B is configured to form a high-intensity second bright portion Pa2 in the region R2. That is, the light intensity of the laser light L1 of the surface-emitting laser 3B that forms the second bright portion Pa2 is greater than the light intensity of the laser light L1 of the surface-emitting laser 3A that forms the first bright portion Pa1.

[0100] When viewed from the X-axis direction, the first bright portion Pa1 and the second bright portion Pa2 are both formed in a linear shape extending in the Y-axis direction. That is, the surface-emitting laser 3A forms a beam pattern PA in which the low-intensity first bright portion Pa1 and the dark portion Pb are alternately arranged along the Z-axis direction. On the other hand, the surface-emitting laser 3B forms a beam pattern PB in which the high-intensity second bright portion Pa2 and the dark portion Pb are alternately arranged along the Z-axis direction.

[0101] As shown in Figure 18, sample Sj passes through region R1 in sample flow path 21. Sample Sk passes through region R2 in sample flow path 21. Samples Sj and Sk have the same shape and size. Figure 19 (A) is a graph showing the measurement results of emitted light L2 from sample Sj, and (B) is a graph showing the measurement results of emitted light L2 from sample Sk. In each graph, the horizontal axis represents time, and the vertical axis represents the signal intensity of emitted light L2 detected by photodetector 4.

[0102] As shown in FIG. 19 , the signal intensity of the emitted light L2 emitted from the sample Sk passing through the high-intensity second bright portion Pa2 ( FIG. 19B ) is greater than the signal intensity of the emitted light L2 emitted from the sample Sj passing through the low-intensity first bright portion Pa1 ( FIG. 19A ). Therefore, according to the fourth measurement example, the control unit 5 can identify the region in the sample flow path 21 through which the measurement target sample S passed (either region R1 or R2 in the example of FIG. 18 ) based on the intensity of the emitted light L2 detected by the photodetector 4. For example, consider a case where, in order to accurately measure the sample S, it is necessary to control the flow in the flow cell 2 so that the sample S passes through the center (region R2) of the sample flow path 21. According to the fourth measurement example, in such a case, it is easy to confirm whether the flow in the flow cell 2 is being appropriately controlled (i.e., whether only measurement results corresponding to the sample S passing through region R2 are being obtained).

[0103] 20 and 21 , a fifth measurement example will be described. In the fifth measurement example, the laser measurement device 1 includes two light sources: a surface-emitting laser 3A (first light source unit) and a surface-emitting laser 3B (second light source unit). The surface-emitting laser 3A is configured to emit laser light L1 of a first wavelength. The surface-emitting laser 3B is configured to emit laser light L1 of a second wavelength different from the first wavelength.

[0104] The wavelength of the emitted light L2 emitted from the sample S in response to irradiation with the laser light L1 of the first wavelength is a wavelength corresponding to the first wavelength (e.g., the same wavelength as the first wavelength). Similarly, the wavelength of the emitted light L2 emitted from the sample S in response to irradiation with the laser light L1 of the second wavelength is a wavelength corresponding to the second wavelength (e.g., the same wavelength as the second wavelength). Therefore, in the fifth measurement example, the laser measurement device 1 includes a photodetector 4A (first sensor) that detects a first signal corresponding to the emitted light L2 (first emitted light) emitted in response to irradiation of the sample S with the laser light L1 of the first wavelength, and a photodetector 4B (second sensor) that detects a second signal corresponding to the emitted light L2 (second emitted light) emitted in response to irradiation of the sample S with the laser light L1 of the second wavelength. Note that an optical filter 64A configured to transmit only the first emitted light may be arranged upstream of the photodetector 4A. Similarly, an optical filter 64B configured to transmit only the second emitted light may be arranged upstream of the photodetector 4B. With this configuration, it is possible to separately acquire the measurement result corresponding to the first wavelength (first signal) and the measurement result corresponding to the second wavelength (second signal).

[0105] It should be noted that the XYZ Cartesian coordinate system in Fig. 20 indicates the direction of the illustrated flow cell 2, and the arrangement of the surface-emitting lasers 3A, 3B and photodetectors 4A, 4B in Fig. 20 does not correspond to their actual arrangement with respect to the flow cell 2. In reality, in Fig. 20, the surface-emitting lasers 3A, 3B are arranged further back than the flow cell 2, and the photodetectors 4A, 4B are arranged further forward than the flow cell 2. The same applies to Figs. 22 to 24.

[0106] As shown in Fig. 20 , the beam pattern PA (first beam pattern) formed by the surface-emitting laser 3A and the beam pattern PB (second beam pattern) formed by the surface-emitting laser 3B have the same shape and are arranged at positions offset from each other along the Z-axis direction. In the example of Fig. 20 , the beam pattern PA has a striped pattern shape in which four linear bright portions PAa are arranged at a pitch p. Like the beam pattern PA, the beam pattern PB also has a striped pattern shape in which four linear bright portions PBa are arranged at a pitch p. The beam pattern PB is offset downstream from the beam pattern PA by a distance half the pitch p.

[0107] 21 is a graph showing a waveform WA corresponding to the measurement results of the first emitted light emitted by the sample S when it passes through the beam pattern PA of the first wavelength (i.e., the measurement results of the first emitted light detected by the photodetector 4A), and a waveform WB corresponding to the measurement results of the second emitted light emitted by the sample S when it passes through the beam pattern PB of the second wavelength (i.e., the measurement results of the second emitted light detected by the photodetector 4B). In FIG. 21 , the horizontal axis represents time, and the vertical axis represents the signal intensity of the emitted light L2 detected by each of the photodetectors 4A and 4B. As shown in FIG. 21 , the two beam patterns PA and PB have the same shape, and therefore, waveforms WA and WB of the same shape are obtained. Furthermore, because the beam pattern PB is located downstream of the beam pattern PA by half the pitch p, a time difference Δt occurs between the waveform WA and the waveform WB according to the difference in distance.

[0108] According to the fifth measurement example, the control unit 5 can easily and accurately measure the velocity (flow rate) of the sample S in the sample flow path 21 based on the time shift (time difference Δt) between the waveform WA corresponding to the measurement result of the first wavelength (measurement result of the photodetector 4A) and the waveform WB corresponding to the measurement result of the second wavelength (measurement result of the photodetector 4B), and the positional deviation amount (half the pitch p in the example of FIG. 21 ) between the beam pattern PA and the beam pattern PB. For example, the control unit 5 can calculate the time difference Δt by performing pattern matching between the waveform WA and the waveform WB to determine the relative movement amount of the waveform WB with respect to the waveform WA required to superimpose the waveform WA on the waveform WB. Alternatively, as shown in FIG. 21 , corresponding points (e.g., points corresponding to the first peaks) on the waveforms WA and WB may be identified and the time difference Δt between these points may be calculated. The control unit 5 then divides the positional shift (p / 2) of the beam patterns PA and PB by the time difference Δt to easily and accurately determine the flow velocity of the sample S during the measurement of the waveforms WA and WB. Measurements similar to those in the fifth measurement example may also be performed by, for example, providing multiple (e.g., two) light source units with the same wavelength, configuring the beam patterns of the multiple light source units to be formed at positions offset from each other along the Z-axis, and varying the light emission timing of each of the multiple light source units (e.g., alternately flashing the light pulses so that the timings of the light pulses do not overlap), and detecting the output (signal intensity) of each of the multiple photodetectors. While this configuration requires control of the light emission timing, it is possible to omit the optical filter located before the photodetector.

[0109] (Sixth Measurement Example) The sixth measurement example will be described with reference to FIG. 22 . The sixth measurement example differs from the fifth measurement example in the following respects. That is, in the sixth measurement example, the surface-emitting laser 3A forms a beam pattern PA in which a plurality of linear bright portions PAa extending in the Y-axis direction are arranged at a first interval (pitch p1) along the Z-axis direction. On the other hand, the surface-emitting laser 3B forms a beam pattern PB in which a plurality of linear bright portions PBa extending in the Y-axis direction are arranged at a second interval (pitch p2) along the Z-axis direction that is different from the first interval. In the example of FIG. 22 , the pitch p2 is ⅓ of the pitch p1. Therefore, in FIG. 22 , the bright portions PBa are also formed so as to overlap the positions where the bright portions PAa are formed.

[0110] According to the sixth measurement example, by varying the pitch between the bright portions for each wavelength (i.e., by varying the pitch p1 between adjacent bright portions PAa and the pitch p2 between adjacent bright portions PBa), when the sample S to be measured (i.e., a group of samples that may flow through the flow cell 2) has different size ranges, it is possible to measure the sample size corresponding to each size range based on the measurement results for each wavelength (i.e., the measurement results of the photodetector 4A or the measurement results of the photodetector 4B). That is, according to the sixth measurement example, it is possible to simultaneously accommodate both the size range measurable by the pitch p1 and the size lens measurable by the pitch p2. In the third modification described above, by selecting a combination of multiple surface-emitting lasers 3A to 3D, the measurable size lens can be adjusted (changed), but it is not possible to simultaneously accommodate multiple different arbitrary size ranges. For example, in the third modification, by combining the beam pattern PA and the beam pattern PC, two different pitches "p / 4" and "3p / 4" can be partially formed, but there are limitations on the combinations of the two pitches that can be realized (in the above example, even if the positions of the two beam patterns PA and PB are shifted, only combinations in which the sum of the two pitches is "p" can be realized). In contrast, according to the sixth modification, a beam pattern of any pitch can be formed for each wavelength, making it possible to flexibly and simultaneously accommodate two different size ranges.

[0111] (Seventh Measurement Example) The seventh measurement example will be described with reference to Fig. 23 . The seventh measurement example differs from the sixth measurement example in the following respects. That is, in the seventh measurement example, the pattern shape of the beam pattern PA formed by the surface-emitting laser 3A (a stripe pattern in the example of Fig. 23 ) differs from the pattern shape of the beam pattern PB formed by the surface-emitting laser 3B (a dot pattern in the example of Fig. 23 ). Here, "pattern shape" refers to the type of shape of the bright parts that make up the beam pattern (for example, the type of pattern, such as lines (stripes) or dots).

[0112] According to the seventh measurement example, measurement results (time waveforms) corresponding to different pattern shapes can be obtained for each wavelength, enabling more advanced particle measurement (waveform analysis). More specifically, by separating the wavelengths of the beam patterns PA and PB, measurement results corresponding to different pattern shapes can be simultaneously and distinctly acquired. In this way, by obtaining waveforms for each of multiple pattern shapes, the amount of information available for waveform analysis can be increased.

[0113] (Eighth Measurement Example) The eighth measurement example will be described with reference to FIGS. 24 and 25 . The eighth measurement example is similar to the fifth to seventh measurement examples in that a surface-emitting laser 3A emitting laser light L1 of a first wavelength and a surface-emitting laser 3B emitting laser light L1 of a second wavelength are used as light sources. Meanwhile, in the eighth measurement example, the surface-emitting laser 3A is configured to form a striped beam pattern PA in which a plurality of bright portions PAa extending in a first direction D1 intersecting the Z-axis direction are arranged along the Z-axis direction. The surface-emitting laser 3B is configured to form a striped beam pattern PB in which a plurality of bright portions PBa extending in a second direction D2 intersecting the first direction D1 are arranged along the Z-axis direction. As an example, the angle at which the first direction D1 is inclined with respect to the Z-axis direction is the inverse of the sign of the angle at which the second direction D2 is inclined with respect to the Z-axis direction. That is, the beam pattern PA and the beam pattern PB have shapes that are line-symmetric with respect to an axis AX parallel to the Z-axis direction.

[0114] According to the eighth measurement example, more advanced particle shape estimation can be performed from the measurement results (time waveforms) for each wavelength. An example of the shape estimation will be described below with reference to FIGS. 24 and 25 . Here, as shown in FIG. 24 , a spherical sample S1 and a non-spherical (ellipsoidal) sample Sm are considered. (A) of FIG. 25 is a graph showing a waveform WA corresponding to the measurement results of the first emitted light emitted from the sample S1 when it passes through the beam pattern PA of the first wavelength (i.e., the measurement results of the first emitted light detected by the photodetector 4A), and a waveform WB corresponding to the measurement results of the second emitted light emitted from the sample S1 when it passes through the beam pattern PB of the second wavelength (i.e., the measurement results of the second emitted light detected by the photodetector 4B). (B) of Figure 25 is a graph showing a waveform WA corresponding to the measurement result of the first emitted light emitted by the sample Sm when it passes through the beam pattern PA of the first wavelength (i.e., the measurement result of the first emitted light detected by the photodetector 4A), and a waveform WB corresponding to the measurement result of the second emitted light emitted by the sample Sm when it passes through the beam pattern PB of the second wavelength (i.e., the measurement result of the second emitted light detected by the photodetector 4B).

[0115] In the case of a spherical sample S1 (i.e., a sample having a shape that is line-symmetric with respect to an axis parallel to the Z-axis direction), the time during which the sample S1 flowing through the sample flow path 21 overlaps with one bright portion PAa (i.e., the period during which emitted light L2 detected by photodetector 4A is emitted) is the same as the time during which the sample S1 overlaps with one bright portion PBa (i.e., the period during which emitted light L2 detected by photodetector 4B is emitted). Therefore, as shown in Figure 25(A), waveforms WA and WB having the same shape but shifted in time are observed for the sample S1.

[0116] On the other hand, in the case of a non-spherical sample like sample Sm (a sample that does not have a shape that is line-symmetrical with respect to an axis parallel to the Z-axis direction, as shown in FIG. 24 ), the time during which sample Sm flowing through sample flow path 21 overlaps with one bright portion PAa is not the same as the time during which sample Sm overlaps with one bright portion PBa. In the example of FIG. 24 , the time during which sample Sm overlaps with one bright portion PBa is shorter than the time during which sample Sm overlaps with one bright portion PAa. Therefore, as shown in FIG. 25B , for sample Sm, the time width of waveform WA is shorter than the time width of waveform WB.

[0117] Therefore, in the above example, the control unit 5 can determine (estimate) that the sample S is spherical (or has a shape close to spherical) if it can determine, based on the waveforms WA and WB obtained by the photodetectors 4A and 4B, that the time widths of the waveforms WA and WB are identical or similar based on a predetermined criterion. On the other hand, the control unit 5 can determine (estimate) that the sample S has a shape that deviates from a spherical shape as the difference between the time widths of the waveforms WA and WB increases. In the example of FIG. 24 , if the sample Sm flows through the sample flow path 21 with its longitudinal direction parallel to the Z-axis or Y-axis, the time widths of the waveforms WA and WB may also be identical for the sample Sm, as with the sample Sl. However, since it is considered rare for a non-spherical sample to flow through the sample flow path 21 while maintaining such an orientation, it is considered possible to determine (estimate) the shape of the sample (whether spherical or non-spherical) with a certain degree of accuracy using the above measurement method.

[0118] (Ninth Measurement Example) A ninth measurement example will be described with reference to FIGS. 26 to 28 . In the ninth measurement example, the surface-emitting laser 3 is configured to time-modulate the laser light L1. As an example, the surface-emitting laser 3 is configured to blink the laser light L1 by switching the laser light L1 ON / OFF. For example, the surface-emitting laser 3 blinks the laser light L1, which forms the same beam pattern P1 as in the first measurement example ( FIG. 12 ), at a predetermined frequency. Note that the ninth measurement example does not necessarily require switching the laser light L1 between an ON state (a state in which the laser light L1 having a predetermined intensity is output) and an OFF state (a state in which the intensity is 0%, i.e., a state in which the laser light L1 is not output). For example, the surface-emitting laser 3 may be configured to constantly emit the laser light L1 and time-modulate a period of sufficiently high intensity (corresponding to the ON state) and a period of sufficiently low intensity (corresponding to the OFF state).

[0119] 26A is a graph showing the measurement results of the emitted light L2 when the laser light L1 is not blinking. FIG. 26B is a graph showing the measurement results of the emitted light L2 in the ninth modification (i.e., when the laser light L1 is blinking). Note that a certain amount of background noise occurs during both measurements. It is difficult to identify the background noise from the time waveform shown in FIG. 26A. On the other hand, in the time waveform shown in FIG. 26B, the background noise N can be easily measured by connecting the lower ends of each waveform element measured in a pulsed manner.

[0120] FIG. 27 is a graph showing the measurement results of the emitted light L2 when the blinking frequency is 20 kHz (emission interval: 50 μs), the pitch between the bright areas Pa of the beam pattern P1 (see FIG. 12) is set to 5 μm, and the laser light L1 is pulsed short (when the pulse width of one pulse is set to several ns). FIG. 28 is an enlarged view of the range Rb in FIG. 27. Note that in the example of FIG. 27, background noise is absent or negligibly small. When the laser light L1 is pulsed short in this manner, as shown in FIG. 28, the photodetector 4 can obtain a measurement value W1 corresponding to the emitted light L2 and a measurement value W2 corresponding to the delayed fluorescence of the sample S. That is, it is possible to simultaneously measure the emitted light L2 (forward scattered light) and delayed fluorescence. As a result, when performing fluorescence measurement (i.e., when delayed fluorescence is the measurement target), it is possible to measure the background light derived from the excitation light (laser light L1) and the delayed fluorescence of the measurement target separately, thereby improving the detection limit of the fluorescence measurement. The control unit 5 can also measure the sample size as described above based on the detection result (measurement value W1) of the emitted light L2, and identify the sample S based on the fluorescence lifetime obtained from the measurement value W2 of the delayed fluorescence. Furthermore, by using a striped beam pattern P1 as in this example, it is possible to obtain measurement results similar to the range Rb in Figure 27 for the number of stripes. By integrating and averaging the measurement values ​​W2 obtained by repeated measurements in this way, it is possible to accurately calculate the fluorescence lifetime.

[0121] [Effects] In the laser measurement device 1 described above, a beam pattern P is formed in the sample flow path 21 of the flow cell 2, in which bright areas Pa and dark areas Pb are alternately arranged along the flow direction (Z-axis direction) of the flow cell 2. When the sample S to be measured passes through the region where the beam pattern P is formed, particle measurement (e.g., measurement of the size of the sample S) can be suitably performed based on the emitted light L2 (forward scattered light in this embodiment) emitted from the sample S. Furthermore, the laser measurement device 1 can easily and accurately form the beam pattern P (e.g., the striped beam pattern P1 in FIG. 12 ) by using a single light source (surface-emitting laser 3) configured in advance to form the beam pattern P. That is, forming the beam pattern P does not require sophisticated and complex alignment adjustment of multiple light sources (i.e., the optical axes of the laser beams emitted from each light source) or optical components such as a beam splitter for splitting one laser beam emitted from one light source into two laser beams. As described above, the laser measurement device 1 can easily and accurately form a beam pattern P suitable for particle measurement using the flow cell 2.

[0122] Furthermore, by using a surface-emitting laser 3 having a phase modulation layer 15 as a light source, the above-mentioned beam pattern P can be suitably and easily formed in the sample flow path 21. In this embodiment, the surface-emitting laser 3 has the center of gravity G of each of the multiple modified refractive index areas 15b arranged at a relative position in accordance with a phase distribution corresponding to the beam pattern P with respect to each of the multiple periodically arranged lattice points O. In other words, the surface-emitting laser 3 is configured as an iPMSEL. With this configuration, the beam pattern P can be suitably and easily formed in the sample flow path 21 by the surface-emitting laser 3, without requiring the slit member 50 used in a modified light source described later.

[0123] The light source (surface-emitting lasers 3, 3A to 3D) is fixed to a side wall 22 (one side surface 22a in this embodiment) of the flow cell 2. With the above configuration, it is possible to suppress attenuation of the laser light L1 outside the flow cell 2. Furthermore, it is possible to facilitate positioning of the surface-emitting lasers 3, 3A to 3D relative to the flow cell 2, and to achieve a reduction in the size of the laser measurement device 1 (module).

[0124] In the technique described in Patent Document 1, two laser beams must be collimated before entering the flow cell. However, collimating the laser beams from the light source requires a certain optical path length, which may result in an increase in the size of the measurement device. In contrast, in this embodiment, by using a surface-emitting laser 3 to which the first and second examples of the phase distribution described above are applied as a light source, it is possible to form a fine striped beam pattern P1 in a space relatively close to the light-emitting surface 3a (e.g., about 1 mm). As a result, even if the distance from the light-emitting surface 3a to the sample flow path 21 is shortened by fixing the surface-emitting laser 3 to the sidewall 22 of the flow cell 2, the fine striped beam pattern P1 can be appropriately formed in the sample flow path 21. In other words, according to this embodiment, it is possible to easily and accurately form a fine striped beam pattern in the sample flow path 21 while miniaturizing the laser measurement device 1.

[0125] In the third to eighth measurement examples, the light source includes a plurality of surface-emitting lasers 3A to 3D (two surface-emitting lasers 3A and 3B in the fifth to eighth measurement examples). These multiple surface-emitting lasers (light source units) are arranged along the flow direction (Z-axis direction). According to the above configuration, by combining the beam patterns of the multiple surface-emitting lasers, it is possible to form a beam pattern within the flow cell 2 that enables more advanced particle measurement (e.g., the measurements in the third to eighth measurement examples described above) than is possible with the beam pattern of a single surface-emitting laser. Furthermore, by arranging the multiple surface-emitting lasers along the Z-axis direction, it is possible to share a common mounting surface (one side surface 22a of the side wall 22 in this embodiment) for the surface-emitting lasers 3A to 3D relative to the flow cell 2, thereby making it possible to make the laser measurement device 1 (module) more compact.

[0126] Furthermore, as in the fifth to eighth measurement examples, a configuration including a surface-emitting laser 3A emitting laser light L1 of a first wavelength and a surface-emitting laser 3B emitting laser light L1 of a second wavelength as the light source, and a photodetector 4A corresponding to the surface-emitting laser 3A and a photodetector 4B corresponding to the surface-emitting laser 3B as the sensor allows for more advanced particle measurement based on measurement results corresponding to each of a plurality of different wavelengths. In the above embodiments (fifth to eighth measurement examples), the laser measurement device 1 includes multiple (two) physically different photodetectors 4A, 4B for each wavelength. However, the laser measurement device 1 may also include a single photodetector capable of distinguishing and detecting measurement results (first and second signals) for each wavelength. An example of such a photodetector is a sensor that combines multiple pixels with a filter configured to transmit different wavelengths for each pixel.

[0127] Furthermore, by using the laser measurement device 1, the following laser measurement method can be suitably implemented. That is, the laser measurement method includes the following steps: a first step of emitting laser light L1 from the surface-emitting laser 3 to the flow cell 2 to form a beam pattern P in a sample flow path 21 through which a fluid containing a sample S to be measured passes within the flow cell 2, the beam pattern P including at least two bright portions Pa arranged with a dark portion Pb sandwiched therebetween along the fluid flow direction (Z-axis direction); a second step of detecting emitted light L2 emitted from the sample S as the sample S passes through the region where the beam pattern P is formed; and a third step of determining at least one of the shape and size of the sample S based on the detected emitted light L2. When the laser measurement device 1 is used, the detection of the emitted light L2 in the second step is performed by the photodetector 4. Furthermore, the determination process in the third step is performed by the control unit 5. According to the above laser measurement method, a beam pattern P suitable for particle measurement using the flow cell 2 can be formed with high precision and easily by the surface-emitting laser 3, and therefore at least one of the shape and size of particles can be accurately determined based on the detection result of the emitted light L2 obtained by the beam pattern P.

[0128] [Modifications] Although several embodiments and modifications of the present disclosure have been described above, the present disclosure is not limited to the configurations shown in the above-described embodiments and modifications. The materials and shapes of each configuration are not limited to the specific materials and shapes described above, and various materials and shapes other than those described above can be used. Furthermore, some of the configurations included in the above-described embodiments and modifications may be omitted or modified as appropriate, and can be combined in any manner.

[0129] In the third to eighth measurement examples, a configuration using multiple surface-emitting lasers 3A to 3D as light sources has been described. However, the arrangement of the multiple surface-emitting lasers 3A to 3D is not limited to the arrangement along the Z-axis direction on the same side surface 22a of the side wall 22 as shown in FIG. 16 . For example, as shown in FIG. 29 , multiple (here, two) surface-emitting lasers 3A and 3B may be arranged along a direction intersecting the Z-axis direction (e.g., the circumferential direction of the side wall 22 perpendicular to the Z-axis direction). In this manner, the multiple (two) surface-emitting lasers 3A and 3B may be provided on different side surfaces 22a and 22b of the side wall 22 (in this example, adjacent side surfaces perpendicular to each other). Furthermore, when forward scattered light from the sample S is detected as emitted light L2 as in the above embodiment, a photodetector 4A for detecting forward scattered light (emission light L2) emitted from the sample S by the laser light L1 (beam pattern) from the surface-emitting laser 3A may be arranged in a position facing the surface-emitting laser 3A across the flow cell 2. Similarly, a photodetector 4B for detecting forward scattered light (emitted light L2) emitted from the sample S by the laser light L1 (beam pattern) from the surface-emitting laser 3B may be disposed at a position facing the surface-emitting laser 3B across the flow cell 2. According to the above configuration, by distributing a plurality of surface-emitting lasers around the sample flow path 21, the degree of freedom in arranging the surface-emitting lasers can be improved.

[0130] FIG. 30 is a schematic diagram showing the configuration of a laser measurement apparatus 1A according to a first modification. As in the laser measurement apparatus 1A, the photodetector 4 may be disposed at a position shifted in the Z-axis direction from the front position of the surface-emitting laser 3 (i.e., the position where the laser light L1 is incident). Even in this case, the photodetector 4 can detect a portion of the forward scattered light (emitted light L2) emitted at a constant emission angle. Furthermore, to improve the light-receiving efficiency of the photodetector 4, the photodetector 4 may be fixed to the side wall 22 of the flow cell 2. According to this configuration, the optical system 6 in the laser measurement apparatus 1 shown in FIG. 1 can be omitted, and by fixing the photodetector 4 to the flow cell 2, the laser measurement apparatus 1A (module) can be further miniaturized.

[0131] FIG. 31 is a schematic diagram showing the configuration of a laser measurement device 1B according to a second modification. The laser measurement device 1B includes a photodetector 4C having a larger light-receiving surface than the laser measurement devices 1 and 1A. More specifically, the photodetector 4C has a larger light-receiving surface than the light-shielding plate 62 for blocking the laser light L1. As an example, the photodetector 4C has a light-receiving surface located outside the light-shielding plate 62 when viewed from the X-axis direction. Furthermore, like the photodetector 4 of the laser measurement device 1, the photodetector 4C is disposed at a position away from the flow cell 2. According to the laser measurement device 1B, the photodetector 4C can detect the emitted light L2, which diverges at a relatively large angle, at a position relatively far from the sample S where the laser light L1 and the emitted light L2 do not overlap. This allows the amount of emitted light L2 received by the photodetector 4C to be increased compared to the laser measurement device 1A according to the first modification. Furthermore, according to the laser measurement device 1B, similar to the laser measurement device 1A, the optical system 6 other than the light-shielding plate 62 in the laser measurement device 1 can be omitted, thereby making it possible to further reduce the size of the laser measurement device 1B (module).

[0132] In the above embodiment, a striped (linear) pattern and a dotted (spotted) pattern were exemplified as the pattern shapes of the beam pattern formed in the sample flow channel 21. However, the pattern shapes of the beam pattern are not limited to these two shapes. For example, a beam pattern having a shape such that a plurality of bright portions Pa extending in the Y-axis direction and having a bend C are arranged along the Z-axis direction, as in the beam pattern PM1 of FIG. 32A , rather than being linear, may be used. Furthermore, a striped beam pattern having bright portions Pa configured such that the curvature gradually changes toward the downstream side, as in the beam pattern PM2 of FIG. 32B , may be used. Such a beam pattern PM2 corrects for the difference in flow velocity between the center and outer edges of the sample flow channel 21 in the Y-axis direction, making it possible to obtain a signal that is purely dependent on the size (particle diameter) of the sample S, regardless of the position in the Y-axis direction of the sample flow channel 21 through which the sample S passes.

[0133] In the above embodiment, forward scattered light emitted from the sample S in response to irradiation with the laser light L1 is detected as the emitted light L2, but light other than scattered light (e.g., fluorescence) may be detected as the emitted light L2, or side scattered light may be detected as the emitted light L2. When side scattered light is detected as the emitted light L2, the photodetector 4 need only be disposed in the emission direction of the side scattered light with respect to the sample S, rather than facing the surface-emitting laser 3. Furthermore, while detecting forward scattered light as emitted light L2 for determining the shape or size of particles, the side scattered light may also be detected as information for analyzing the type of particle. In this case, a photodetector for detecting side scattered light may be provided separately from the photodetector 4 for detecting the emitted light L2 (forward scattered light).

[0134] In the above embodiment, a flow cell is used as an example of a flow path device, but the flow path device may also include a micro-flow path (sample flow path) other than a flow cell, such as a micro-flow path chip used in fields such as μTAS.

[0135] Furthermore, in the above embodiment, a configuration has been described in which the surface-emitting laser 3 configured as an iPMSEL is used as a light source (or, in the case where the light source includes a plurality of light source units, each light source unit), but the light source may be realized by combining a surface-emitting laser other than an iPMSEL with a slit member. That is, in the above embodiment, as an example of the surface-emitting laser 3, a configuration has been described in which a pseudo-double slit is realized by the first region 151 and the second region 152 (see FIG. 9 ) and interference fringes are formed by interference of the emitted light, but such a double slit may also be realized by a physical slit member. Below, modified examples (first modified example and second modified example) of a light source using such a mechanism will be described.

[0136] (First Modification of Light Source) A first modification of the light source (a combination of a surface-emitting laser 31 and a slit member 50) will be described with reference to Fig. 33 . As shown in Fig. 33 , the surface-emitting laser 31 has a configuration similar to that of the surface-emitting laser 3 shown in Fig. 6 , but differs from the surface-emitting laser 3 mainly in the following points. That is, the surface-emitting laser 31 has a phase modulation layer 15A instead of the phase modulation layer 15. In addition, a slit member 50 is provided at a position facing the light emission surface 3a of the surface-emitting laser 31. In this example, the slit member 50 is provided integrally with the surface-emitting laser 31 on the anti-reflection film 19 provided on the back surface 10b within the opening 17a of the electrode 17.

[0137] As described above, in the phase modulation layer 15, the center of gravity G of each of the multiple modified refractive index areas 15 b is located at a relative position with respect to each of the multiple periodically arranged lattice points O in accordance with the phase distribution corresponding to the beam pattern P. In contrast, the phase modulation layer 15A is configured as a photonic crystal layer in which the multiple modified refractive index areas 15 b are periodically arranged. That is, in the phase modulation layer 15A, the center of gravity G of each of the multiple modified refractive index areas 15 b coincides with the position of each of the multiple periodically arranged lattice points O. In other words, the surface-emitting laser 31 is configured as a photonic crystal surface-emitting laser (PCSEL) that emits coherent (longitudinal and horizontal single mode) light from the back surface 10 b.

[0138] The slit member 50 is a member for forming laser light L1 having a predetermined beam pattern P by passing light emitted from the surface-emitting laser 31. In the example of FIG. 33 , the slit member 50 is a plate-like member having two openings 50a and 50b (slits). That is, in the example of FIG. 33 , instead of a pseudo double slit formed by the first region 151 and the second region 152 (see FIG. 9 ), a double slit is realized by the physical openings 50a and 50b of the slit member 50. As a result, the first modified example of the light source (the surface-emitting laser 31 and the slit member 50) is configured to form interference fringes (for example, the striped beam pattern P1 according to the first measurement example shown in FIG. 12 ) due to interference of the emitted light passing through the openings 50a and 50b.

[0139] According to the first modified example of the light source described above, the above-mentioned beam pattern (for example, a striped beam pattern P1) can be suitably and easily formed in the sample flow path 21 by combining the surface-emitting laser 31 (PCSEL) and the slit member 50. The number and shape of the openings provided in the slit member 50 may be set according to the shape of the desired beam pattern. Furthermore, although in the example of FIG. 33 , the surface-emitting laser 31 is formed integrally with the slit member 50, the surface-emitting laser 31 and the slit member 50 may be arranged to be spaced apart from each other, as in the second modified example of the light source shown in FIG. 34 .

[0140] (Second Modification of Light Source) A second modification of the light source (a combination of a surface-emitting laser 32 and a slit member 50) will be described with reference to FIG. 34 . The surface-emitting laser 32 is configured as a vertical cavity surface-emitting laser (VCSEL). As shown in FIG. 34 , the surface-emitting laser 32 has a semiconductor substrate 321, a first DBR layer 322, an active layer 323, and a second DBR layer 327 instead of the semiconductor substrate 10, cladding layer 11, active layer 12, cladding layer 13, contact layer 14, and phase modulation layer 15 of the surface-emitting laser 3. The semiconductor substrate 321 is, for example, an n-type semiconductor substrate. The first DBR layer 322 is, for example, a layer formed of an n-type multilayer film reflector (DBR), and is formed on the semiconductor substrate 321. The active layer 323 is disposed between the first DBR layer 322 and the second DBR layer 327, and includes, from the first DBR layer 322 side toward the second DBR layer 327 side, a first guide layer 324, a quantum well layer 325, and a second guide layer 326. The second DBR layer 327 is a layer formed of, for example, a P-type multilayer reflector (DBR), and is formed on the active layer 323.

[0141] Like the surface-emitting laser 31, the surface-emitting laser 32 configured as a VCSEL emits coherent light from a region within the opening 17a of the electrode 17 on the rear surface (the surface on which the anti-reflection film 19 is provided) of the semiconductor substrate 321. The width of the opening 17a is set to, for example, several μm or less in order to emit such coherent light. Furthermore, the surface-emitting laser 32 may be formed with a current confinement structure for suitably emitting coherent light.

[0142] The slit member 50 is a plate-like member having double slits (openings 50a and 50b) formed therein, similar to the first modified example described above. In the second modified example, as an example, the surface-emitting laser 32 and the slit member 50 are arranged to be spaced apart from each other. In order to form the striped beam pattern P1 described above, the distance between the emission surface of the surface-emitting laser 32 (the surface of the electrode 17 opposite to the semiconductor substrate 321 side) and the slit member 50 may be set to, for example, about several hundred μm.

[0143] According to the first or second modified example of the light source described above, a predetermined beam pattern (for example, a striped beam pattern P1) can be suitably and easily formed by combining a surface-emitting laser (PCSEL or VCSEL) and the slit member 50.

[0144] Furthermore, the configuration of the surface-emitting laser 3 configured as an iPMSEL (particularly the configuration of each modified refractive index area 15b) is not limited to the configuration described in the above embodiment. Other configuration examples of the surface-emitting laser 3 will be described in detail below.

[0145] FIG. 35 is a plan view showing an example in which a substantially periodic refractive index structure is applied to a specific region of the phase modulation layer 15 shown in FIG. 11 . In the example shown in FIG. 35 , a substantially periodic structure (e.g., the structure shown in FIG. 7 ) for emitting a desired optical image is formed within the square inner region RIN. Meanwhile, a circular modified refractive index region 15b is disposed in the outer region ROUT surrounding the inner region RIN, in which the lattice point positions of the square lattice coincide with the center of gravity position. The lattice spacing a of the virtually set square lattice is identical within the inner region RIN and the outer region ROUT. In the structure shown in FIG. 38 , light is distributed within the outer region ROUT as well, thereby suppressing the generation of high-frequency noise (so-called window function noise) caused by a sudden change in light intensity around the periphery of the inner region RIN. Furthermore, light leakage in a direction perpendicular to the thickness direction can be suppressed, which is expected to reduce the threshold current. However, the present invention is not limited to this example, and the substantially periodic structure for emitting a desired optical image (for example, the structure shown in FIG. 7) may be formed in the entire area of ​​the first region 151 and the second region 152.

[0146] In order to obtain a desired distribution of the light-converging points U, the rotation angle distribution α(x, y) of the modified refractive index area 15b in the phase modulation layer 15 (first area 151 and second area 152) is determined by the following procedure.

[0147] As a first prerequisite, in an XYZ orthogonal coordinate system defined by a Z axis coinciding with the normal direction and an XY plane coinciding with one surface of the phase modulation layer 15 including the multiple modified refractive index areas 15b, a square M １ ×N １ pieces (M １, N １ A virtual square lattice composed of unit constituent regions R (where R is an integer of 1 or more) is set on the XY plane.

[0148] As a second prerequisite, the coordinates (ξ, η, ζ) in the XYZ orthogonal coordinate system are determined by the length r of the moving radius and the tilt angle θ from the Z axis, as shown in FIG. ｔｉｌｔ and the rotation angle θ from the X-axis specified on the XY plane ｒｏｔ and the spherical coordinates (r, θ ｒｏｔ ,θ ｔｉｌｔ ) satisfy the relationships shown in the following formulas (1) to (3). ｒｏｔ ,θ ｔｉｌｔ ) to coordinates (ξ, η, ζ) in the XYZ Cartesian coordinate system, and the coordinates (ξ, η, ζ) represent a designed light image on a predetermined plane set in the XYZ Cartesian coordinate system, which is real space.

[0149]

[0150]

[0151]

[0152] The light emitted from the surface-emitting laser 3 is reflected at an angle θ ｔｉｌｔ and θ ｒｏｔ When the set of bright spots is directed in the direction specified by the angle θ ｔｉｌｔ and θ ｒｏｔ is the normalized wave number defined by the following equation (4) and corresponds to the X axis. ｘ The coordinate value kx on the axis and the normalized wave number defined by the following equation (5) which corresponds to the Y axis and is K ｘ K perpendicular to the axis ｙ The normalized wave number is a wave number normalized by setting the wave number 2π / a, which corresponds to the lattice spacing of a virtual square lattice, to 1.0. ｘ axis and K ｙ In the wavenumber space defined by the axes, specific wavenumber ranges including the beam pattern corresponding to the optical image are each a square-shaped M ２ ×N ２ pieces (M ２, N ２ is an integer of 1 or more). ２ is an integer M １ Similarly, the integer N ２ is an integer N １ The formulas (4) and (5) are disclosed in, for example, Non-Patent Document 1.

[0153]

[0154] a: lattice constant of a virtual square lattice λ: oscillation wavelength of the surface emitting laser 3

[0155] The third prerequisite is that in wave number space, K ｘ Axial coordinate component kx (0 or more M ２ -1 or less integer) and K ｙ Axial coordinate component ky (0 or more N ２ The image region FR(kx, ky) specified by the coordinate component x (0 to M) in the X-axis direction is １ -1 or less) and the coordinate component y (0 or more N １ The complex amplitude F(x, y) obtained by performing a two-dimensional inverse discrete Fourier transform on a unit constituent region R(x, y) on the X-Y plane specified by x and y (an integer equal to or less than -1) is given by the following equation (6), where j is the imaginary unit. The complex amplitude F(x, y) is defined by the following equation (7), where the amplitude term is A(x, y) and the phase term is φ(x, y). As a fourth prerequisite, the unit constituent region R(x, y) is defined by the s-axis and t-axis, which are parallel to the X-axis and Y-axis, respectively, and are orthogonal to each other at the lattice point O(x, y) that is the center of the unit constituent region R(x, y).

[0156]

[0157]

[0158] Under the above first to fourth preconditions, the first region 151 and the second region 152 may be configured to satisfy the following fifth and sixth conditions. That is, the fifth condition is satisfied when the center of gravity G is located away from the lattice point O(x, y) within the unit constituent region R(x, y). The sixth condition is satisfied when the line segment length r from the lattice point O(x, y) to the corresponding center of gravity G is ２ (x, y) is M １ pieces x N １ With the angle α(x, y) between the s-axis and the line segment connecting the lattice point O(x, y) and the corresponding center of gravity G, set to a common value in each of the unit constituent regions R, the angle α(x, y) is satisfied by arranging the corresponding modified refractive index area 15b within the unit constituent region R(x, y) so that the following relationship is satisfied: α(x, y) = C × φ(x, y) + B, where C is a proportionality constant, e.g., 180° / π, and B is an arbitrary constant, e.g., 0.

[0159] Next, we will explain the M-point oscillation of the surface-emitting laser 3. For the surface-emitting laser 3 to oscillate at the M-point band edge, the lattice spacing a of a virtual square lattice, the emission wavelength λ of the active layer 12, and the equivalent refractive index n of the mode should satisfy the condition λ = (√2)n × a. FIG. 37 is a plan view showing the reciprocal lattice space related to the phase modulation layer of a light-emitting device that performs M-point oscillation. Point P in the figure represents a reciprocal lattice point. Arrow B1 in the figure represents the fundamental reciprocal lattice vector, and arrows K1, K2, K3, and K4 represent four in-plane wave vectors. Each of the in-plane wave vectors K1 to K4 has a wave number spread SP due to the rotation angle distribution α(x, y).

[0160] The magnitude of the in-plane wave vectors K1 to K4 (i.e., the magnitude of the standing wave in the in-plane direction) is smaller than the magnitude of the primitive reciprocal lattice vector B1. Therefore, the vector sum of the in-plane wave vectors K1 to K4 and the primitive reciprocal lattice vector B1 does not become 0, and the wave number in the in-plane direction cannot become 0 due to diffraction, so diffraction does not occur in the direction perpendicular to the plane (Z-axis direction). If this continues, the M-point oscillation surface-emitting laser 3 will not output not only the zeroth-order light in the direction perpendicular to the plane (Z-axis direction), but also +1st-order light and −1st-order light in directions inclined with respect to the Z-axis direction.

[0161] For example, by applying the following technique to the phase modulation layer 15 (first region 151 and second region 152) in the M-point oscillation surface-emitting laser 3, it is possible to output a portion of the +1st-order light and the -1st-order light without outputting the 0th-order light. That is, as shown in Figure 38, by adding a diffraction vector V1 having a certain magnitude and direction to the in-plane wave vectors K1 to K4, the magnitude of at least one of the in-plane wave vectors K1 to K4 (in the figure, the in-plane wave vector K3) is made smaller than 2π / λ (λ: wavelength of the light output from the active layer 12). In other words, at least one of the in-plane wave vectors K1 to K4 after the diffraction vector V1 is added is contained within a light line LL, which is a circular region with a radius of 2π / λ.

[0162] In Fig. 38, the in-plane wave vectors K1 to K4 indicated by dashed lines represent the wave vectors before the addition of the diffraction vector V1, while the in-plane wave vectors K1 to K4 indicated by solid lines represent the wave vectors after the addition of the diffraction vector V1. The light line LL corresponds to the total reflection condition, and wave vectors whose magnitude falls within the light line LL have a component in the direction perpendicular to the surface (Z-axis direction). In one example, the direction of the diffraction vector V1 is along the Γ-M1 axis or the Γ-M2 axis. The magnitude of the diffraction vector V1 is in the range of 2π / (√2)a-2π / λ to 2π / (√2)a+2π / λ, and in one example, is 2π / (√2)a.

[0163] Next, we consider the magnitude and direction of the diffraction vector V1 for placing at least one of the in-plane wave vectors K1 to K4 within the light line LL. The following formulas (8) to (11) show the in-plane wave vectors K1 to K4 before the diffraction vector V1 is added.

[0164]

[0165]

[0166]

[0167] The spreads Δkx and Δky of the wave vectors satisfy the following formulas (12) and (13), respectively. ｍａｘ and the maximum value of the spread in the y-axis direction Δky ｍａｘ is defined by the angular spread of the optical image of the design.

[0168]

[0169]

[0170] When the diffraction vector V1 is expressed as in the following formula (14), the in-plane wave vectors K1 to K4 after the diffraction vector V1 is added are expressed as the following formulas (15) to (18).

[0171]

[0172]

[0173]

[0174]

[0175]

[0176] In the formulas (15) to (18), if it is considered that any of the in-plane wave vectors K1 to K4 falls within the light line LL, the relationship of the following formula (19) holds.

[0177] That is, by adding a diffraction vector V1 that satisfies the formula (19), any of the in-plane wave vectors K1 to K4 falls within the light line LL, and a part of the +1st order light and the -1st order light is output.

[0178] The reason why the size (radius) of the light line LL is set to 2π / λ is as follows. FIG. 39 is a diagram for schematically explaining the structure surrounding the light line LL. The diagram shows the boundary between the device and air in the Z direction. The magnitude of the wave vector of light in a vacuum is 2π / λ, but when light propagates through a device medium as shown in FIG. 39, the magnitude of the wave vector Ka in the medium with a refractive index n is 2πn / λ. In this case, in order for light to propagate through the boundary between the device and air, the wave number components parallel to the boundary must be continuous (law of conservation of wave number).

[0179] In Figure 39, when the wave vector Ka and the Z axis form an angle θ, the length of the wave vector Kb projected onto the plane (i.e., the in-plane wave vector) is (2πn / λ) sin θ. On the other hand, since the refractive index n of a medium is generally greater than 1, the law of conservation of wave numbers no longer holds when the angle at which the in-plane wave vector Kb in the medium is greater than 2π / λ. In this case, the light is totally reflected and cannot be extracted to the air side. The magnitude of the wave vector corresponding to this total reflection condition is the magnitude of the light line LL, i.e., 2π / λ.

[0180] As an example of a specific method of adding a diffraction vector V1 to the in-plane wave vectors K1 to K4, a phase distribution φ according to a desired output light shape is １ (x, y), the phase distribution φ ２ In this case, the phase distribution φ(x, y) of the phase modulation layer 15 (first region 151 and second region 152) is expressed as φ(x, y)=φ １ (x, y) + φ ２ It is expressed as (x, y). １ As mentioned above, (x, y) corresponds to the phase of the complex amplitude when the desired shape of the emitted light is Fourier transformed. ２ (x, y) is the phase distribution for adding the diffraction vector V1 that satisfies the above equation (19).

[0181] FIG. 40 shows the phase distribution φ ２ 1 is a diagram conceptually illustrating an example of (x, y) in which a first phase value φ Ａ and a first phase value φ Ａ a second phase value φ different from Ｂ In one example, the phase values ​​φ Ａ is 0 (rad), and the phase value φ Ｂ is π (rad), where the first phase value φ Ａ and a second phase value φ Ｂ and change in increments of π. Such an arrangement of phase values ​​makes it possible to suitably realize a diffraction vector V1 along the Γ-M1 axis or the Γ-M2 axis. In the case of a checkerboard arrangement, V1 = (±π / a, ±π / a), and the diffraction vector V1 exactly cancels out one of the in-plane wave vectors K1 to K4 in FIG. 9. Therefore, the axis of symmetry between the +1st-order light and the -1st-order light coincides with the Z direction, i.e., the direction perpendicular to the in-plane direction of the phase modulation layer 15. In general, the angular distribution θ2(x, y) of the diffraction vector V is expressed as the dot product of the diffraction vector V(Vx, Vy) and the position vector r(x, y), and is given by the following equation: θ2(x, y) = V r = Vx x + Vy y

[0182] Therefore, when V = V1, the phase values ​​are 0 and π for a position vector r(xa, ya) (x and y are both integers). On the other hand, as described above, the diffraction vector V1 may be shifted from (±π / a, ±π / a) as long as at least one of the in-plane wave vectors K1 to K4 falls within the range in which the light line LL is included.

[0183] In this embodiment, when the wavenumber spread based on the angular spread of the output light is contained in a circle of radius Δk centered at a certain point in wavenumber space, it can also be simply considered as follows: By adding a diffraction vector V1 to the four-directional in-plane wavenumber vectors K1 to K4, the magnitude of at least one of the four-directional in-plane wavenumber vectors K1 to K4 is made smaller than 2π / λ (light line LL). This can be considered as meaning that by adding the diffraction vector V1 to the four-directional in-plane wavenumber vectors K1 to K4 minus the wavenumber spread Δk, the magnitude of at least one of the four-directional in-plane wavenumber vectors K1 to K4 is made smaller than the value {(2π / λ) - Δk} obtained by subtracting the wavenumber spread Δk from 2π / λ.

[0184] FIG. 41 is a diagram conceptually illustrating the above-mentioned idea. As shown in the figure, when a diffraction vector V1 is added to in-plane wave vectors K1 to K4 excluding the wave number spread Δk, the magnitude of at least one of the in-plane wave vectors K1 to K4 becomes smaller than {(2π / λ)-Δk}. In FIG. 12, region LL2 is a circular region with a radius of {(2π / λ)-Δk}. In FIG. 41, the in-plane wave vectors K1 to K4 indicated by dashed lines represent the wave vectors before the addition of the diffraction vector V1, and the in-plane wave vectors K1 to K4 indicated by solid lines represent the wave vectors after the addition of the diffraction vector V1. Region LL2 corresponds to the total reflection condition taking into account the wave number spread Δk, and wave vectors whose magnitude falls within region LL2 also propagate in the direction perpendicular to the plane (the Z-axis direction).

[0185] In this embodiment, the magnitude and direction of the diffraction vector V1 for placing at least one of the in-plane wave vectors K1 to K4 within the region LL2 will be described. The following formulas (20) to (23) show the in-plane wave vectors K1 to K4 before the diffraction vector V1 is added.

[0186]

[0187]

[0188]

[0189]

[0190] Here, when the diffraction vector V1 is expressed as in the above-mentioned formula (14), the in-plane wave vectors K1 to K4 after the diffraction vector V1 is added are expressed by the following formulas (24) to (27).

[0191]

[0192]

[0193]

[0194]

[0195] In formulas (24) to (27), if it is considered that any of the in-plane wave vectors K1 to K4 falls within region LL2, the relationship of the following formula (28) holds. That is, by adding a diffraction vector V1 that satisfies formula (28), any of the in-plane wave vectors K1 to K4 excluding the wave number spread Δk falls within region LL2. Even in such a case, it is possible to output a part of the +1st-order light and the -1st-order light without outputting the 0th-order light.

[0196]

[0197] FIG. 42 is a plan view showing another form of the phase modulation layer 15 (first region 151 and second region 152). FIG. 43 is a diagram showing the arrangement of the modified refractive index areas 15b in the phase modulation layer 15 (first region 151 and second region 152) shown in FIG. 42. As shown in FIGS. 42 and 43, the center of gravity G of each modified refractive index area 15b of the phase modulation layer 15 may be arranged on a straight line D. The straight line D passes through a lattice point O corresponding to each unit constituent region R and is inclined with respect to each side of the square lattice. In other words, the straight line D is inclined with respect to both the X-axis and the Y-axis. The inclination angle of the straight line D with respect to one side of the square lattice (the X-axis) is β.

[0198] In this case, the tilt angle β is constant within the phase modulation layer 15 (the first region 151 and the second region 152). The tilt angle β satisfies 0°<β<90°, and in one example, β=45°. Alternatively, the tilt angle β satisfies 180°<β<270°, and in one example, β=225°. When the tilt angle β satisfies 0°<β<90° or 180°<β<270°, the straight line D extends from the first quadrant to the third quadrant of the coordinate plane defined by the X-axis and the Y-axis. The tilt angle β satisfies 90°<β<180°, and in one example, β=135°. Alternatively, the tilt angle β satisfies 270°<β<360°, and in one example, β=315°. When the tilt angle β satisfies 90°<β<180° or 270°<β<360°, the straight line D extends from the second quadrant to the fourth quadrant of the coordinate plane defined by the X-axis and the Y-axis. Thus, the tilt angle β is an angle excluding 0°, 90°, 180°, and 270°.

[0199] Here, the distance between the lattice point O and the center of gravity G is r(x, y). x is the position of the xth lattice point on the X axis, and y is the position of the yth lattice point on the Y axis. When the distance r(x, y) is a positive value, the center of gravity G is located in the first quadrant (or the second quadrant). When the distance r(x, y) is a negative value, the center of gravity G is located in the third quadrant (or the fourth quadrant). When the distance r(x, y) is 0, the lattice point O and the center of gravity G coincide with each other. The tilt angles are preferably 45°, 135°, 225°, or 275°. At these tilt angles, only two of the four wave vectors (e.g., in-plane wave vectors (±π / a, ±π / a)) forming the standing wave at point M are phase-modulated, and the other two are not, thereby forming a stable standing wave.

[0200] The distance r(x, y) between the center of gravity G of each modified refractive index area and the lattice point O corresponding to each unit constituent area R is set individually for each modified refractive index area 15b according to the phase distribution φ(x, y) corresponding to the desired output light shape. In the present disclosure, this arrangement of the center of gravity G is referred to as the second arrangement. The phase distribution φ(x, y) and the distance distribution r(x, y) have specific values ​​for each position determined by the values ​​of x and y, but are not necessarily expressed by a specific function. The distribution of distance r(x, y) is determined from the phase distribution φ(x, y) extracted from the complex amplitude distribution obtained by performing an inverse Fourier transform on the desired output light shape.

[0201] That is, when the phase φ(x, y) at a certain coordinate (x, y) is φ0, the distance r(x, y) is set to 0, when the phase φ(x, y) is π+φ0, the distance r(x, y) is set to the maximum value R0, and when the phase φ(x, y) is -π+φ0, the distance r(x, y) is set to the minimum value -R0. For phases φ(x, y) in between, the distance r(x, y) is set so that r(x, y) = {φ(x, y) - φ0} × R0 / π. The initial phase φ0 can be set arbitrarily.

[0202] If the lattice spacing of a virtual square lattice is a, then the maximum value R of r(x, y) falls within the range of the following equation (29), for example: When determining the complex amplitude distribution from a desired optical image, it is possible to improve the reproducibility of the beam pattern by applying an iterative algorithm such as the GS method, which is commonly used in calculations for generating holograms.

[0203]

[0204] In this second embodiment, a desired light output shape (such as the number and positions of light-focusing points) can be obtained by determining the distribution of the distances r(x, y) of the modified refractive index areas 15b of the phase modulation layer 15 (first region 151 and second region 152). Under the same first to fourth preconditions as those in the first embodiment, the phase modulation layer 15 (first region 151 and second region 152) is configured to satisfy the following condition. That is, the corresponding modified refractive index area 15b is disposed within the unit constituent region R(x, y) so that the distance r(x, y) from the lattice point O(x, y) to the center of gravity G of the corresponding modified refractive index area 15b satisfies the following relationship: To obtain a desired light output shape, the light output shape may be subjected to an inverse Fourier transform, and a distribution of the distances r(x, y) corresponding to the phase φ(x, y) of the complex amplitude may be provided to the multiple modified refractive index areas 15b. The phase φ(x, y) and the distance r(x, y) may be proportional to each other. r(x, y) = C × (φ(x, y) - φ0) C: proportional constant, for example, R0 / π φ0: any constant, for example, 0

[0205] In this second embodiment, too, in a light-emitting device that oscillates at point M, the following innovation is applied to the phase modulation layer 15 (first region 151 and second region 152), so that the zeroth-order light is not output into the light line LL, and a portion of the +1st-order light and the −1st-order light is output. Specifically, as shown in FIG. 38 , a diffraction vector V1 having a certain magnitude and direction is added to the in-plane wave vectors K1 to K4, so that the magnitude of at least one of the in-plane wave vectors K1 to K4 is made smaller than 2π / λ. In other words, at least one of the in-plane wave vectors K1 to K4 after the diffraction vector V1 is added is contained within the light line LL, which is a circular region with a radius of 2π / λ. By adding the diffraction vector V1 that satisfies the above-mentioned formula (19), one of the in-plane wave vectors K1 to K4 is contained within the light line LL, and a portion of the +1st-order light and the −1st-order light is output.

[0206] 41 , by adding a diffraction vector V1 to the four-directional in-plane wave vectors K1 to K4 minus the wave number spread Δk (i.e., the four-directional in-plane wave vectors in an M-point oscillation square lattice PCSEL), the magnitude of at least one of the four-directional in-plane wave vectors K1 to K4 may be made smaller than the value obtained by subtracting the wave number spread Δk from 2π / λ, i.e., {(2π / λ)−Δk}. That is, by adding a diffraction vector V1 that satisfies the above-described formula (28), any of the in-plane wave vectors K1 to K4 falls within the region LL2, and a portion of the +1st-order light and a portion of the −1st-order light are output.

[0207] As a result, in the light extraction region 15P, light emitted from the active layer 12 and resonating in the in-plane direction of the XY plane in the phase modulation layer 15 is diffracted in the out-of-plane direction of the XY plane (direction intersecting the XY plane) in the first region 151 and the second region 152, and a portion of the +1st order light and the −1st order light are output only from the first region 151 and the second region 152. As a result, as shown in Figure 15, a pseudo double slit is formed in the phase modulation layer 15, with the first region 151 and the second region 152 serving as slits, and interference fringes due to interference of the emitted light can be formed in the Fresnel region.

[0208] 1, 1A...laser measurement device, 2...flow cell (flow path device), 3, 3A to 3D, 31, 32...surface-emitting laser (light source, light source unit), 3a...light emission surface, 4, 4A, 4B...photodetector (sensor), 15, 15A...phase modulation layer, 15a...base layer, 15b...modified refractive index area, 21...sample flow path, 22...side wall, L1...laser light, L2...emitted light, P, P1, P2, PC, PD, PM1, PM2...beam pattern, PA...beam pattern (first beam pattern), PB...beam pattern (second beam pattern), Pa, PAa, PBa...bright area, Pb...dark area, Ra...passage area, S, Sa to Sm...sample (particle).

Claims

1. A laser measurement device comprising: a flow path device including a sample flow path through which a fluid containing particles to be measured passes; a light source that emits laser light toward the sample flow path, the light having a beam pattern in which at least two bright areas are arranged with a dark area sandwiched between them along the flow direction of the fluid; and a sensor that detects light emitted from the particles when the particles pass through an area in the sample flow path in which the beam pattern is formed.

2. The laser measurement device described in claim 1, wherein the light source has a surface-emitting laser including: a light-emitting section; and a phase modulation layer optically coupled to the light-emitting section, the phase modulation layer including a base layer and a plurality of modified refractive index areas having a refractive index different from that of the base layer.

3. A laser measurement device as described in claim 2, wherein the center of gravity of each of the multiple modified refractive index areas is positioned at a relative position in accordance with a phase distribution corresponding to the beam pattern with respect to each of a multiple number of periodically arranged lattice points.

4. The laser measurement device described in claim 2, wherein the phase modulation layer is a photonic crystal layer in which the multiple modified refractive index areas are periodically arranged, and the light source further has a slit member that forms the laser light having the beam pattern by passing light emitted from the surface-emitting laser.

5. The laser measurement device as described in claim 1, wherein the light source comprises: a vertical cavity surface emitting laser; and a slit member that forms the laser light having the beam pattern by passing light emitted from the surface emitting laser.

6. The laser measurement device according to any one of claims 1 to 5, wherein the light source is fixed to a side wall of the flow path device.

7. A laser measurement device according to any one of claims 1 to 6, wherein the light source forms a striped beam pattern in which a plurality of bright areas extending in a direction intersecting the flow direction are arranged along the flow direction.

8. The laser measurement device according to claim 7, wherein the light source has a surface-emitting laser including a light-emitting section, and a phase modulation layer optically coupled to the light-emitting section, the phase modulation layer including a base layer and a plurality of modified refractive index regions having a refractive index different from that of the base layer, and the surface-emitting laser forms the striped beam pattern by interfering with light emitted from each of a plurality of mutually different regions in an in-plane direction of the light emission surface of the surface-emitting laser.

9. A laser measurement device according to any one of claims 1 to 8, wherein the light source includes a plurality of light source units arranged along the flow direction.

10. A laser measurement device according to any one of claims 1 to 8, wherein the light source includes a plurality of light source units arranged along a direction intersecting the flow direction.

11. A laser measurement device as described in claim 9 or 10, wherein each of the plurality of light source units is configured to form a striped beam pattern within the sample flow path in which a plurality of the bright sections extending in a direction intersecting the flow direction are arranged at predetermined intervals along the flow direction, and in a passing region within the sample flow path through which the particles pass, the beam patterns of each of the plurality of light source units are arranged so as not to overlap with each other.

12. A laser measurement device as described in claim 9 or 10, wherein the multiple light source units form a first bright portion of brightness with a first intensity in a first range region in a first direction intersecting the flow direction, and form a second bright portion of brightness with a second intensity different from the first intensity in a second range region different from the first range in the first direction.

13. A laser measurement device as described in any one of claims 1 to 12, wherein the light source includes a first light source unit that emits the laser light of a first wavelength and a second light source unit that emits the laser light of a second wavelength different from the first wavelength, and the sensor detects a first signal corresponding to first emitted light emitted in response to the laser light of the first wavelength being irradiated onto the particle, and a second signal corresponding to second emitted light emitted in response to the laser light of the second wavelength being irradiated onto the particle.

14. The laser measurement device described in claim 13, wherein the first light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a direction intersecting the flow direction are arranged at a first interval along the flow direction, and the second light source unit forms a striped beam pattern in which the bright portions extending in a direction intersecting the flow direction are arranged at a second interval different from the first interval along the flow direction.

15. A laser measurement device as described in claim 13, wherein the first beam pattern formed by the first light source unit and the second beam pattern formed by the second light source unit have the same shape and are arranged at offset positions from each other along the flow direction.

16. The laser measurement device according to claim 13, wherein a pattern shape of the first beam pattern formed by the first light source unit is different from a pattern shape of the second beam pattern formed by the second light source unit.

17. The laser measurement device described in claim 13, wherein the first light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a first direction intersecting the flow direction are arranged along the flow direction, and the second light source unit forms a striped beam pattern in which a plurality of the bright portions extending in a second direction intersecting the first direction are arranged along the flow direction.

18. A laser measurement device according to any one of claims 1 to 17, wherein the light source modulates the intensity of the laser light over time.

19. A laser measurement method using the laser measurement device according to any one of claims 1 to 18, comprising the steps of: emitting the laser light from the light source to the flow path device, thereby forming a beam pattern in a sample flow path through which a fluid containing particles to be measured passes within the flow path device, in which at least two bright areas are arranged with a dark area sandwiched between them along the flow direction of the fluid; detecting light emitted from the particle when the particle passes through a region in which the beam pattern is formed; and determining at least one of the shape and size of the particle based on the detected emitted light.

Images