Laser measurement device and laser measurement method
The laser measurement device uses a surface-emitting laser with a phase modulation layer to form a beam pattern for accurate particle measurement, addressing the challenges of complex alignment and vibration-induced inaccuracies in existing methods.
Patent Information
- Application Number
- JP2023192945
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-11-13
- Publication Date
- 2025-05-23
AI Technical Summary
Existing laser measurement methods require advanced and complicated alignment work to form a striped pattern with high precision, which is prone to inaccuracies due to slight deviations in laser beam optical axes or vibrations during measurement.
A laser measurement device and method that uses a single light source, such as a surface-emitting laser with a phase modulation layer, to form a beam pattern with bright and dark areas alternately arranged along the flow direction, allowing for accurate particle measurement without the need for complex alignment adjustments.
The solution enables the easy and accurate formation of a beam pattern suitable for particle measurement, improving measurement precision and reducing the complexity of alignment procedures, while also minimizing the impact of vibrations.
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Figure 2025080006000001_ABST
Abstract
Description
[Technical field]
[0001] The present disclosure relates to a laser measurement device and a laser measurement method. [Background technology]
[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. [Prior art documents] [Patent documents]
[0003] [Patent Document 1] Patent Publication No. 2022-77967 Summary of the Invention [Problem to be solved by the invention]
[0004] In the above method, the width of the striped pattern (the distance between adjacent stripes) functions as a scale for size measurement. Therefore, in order to accurately measure the size of the particle by the above method, the width of the striped pattern must be adjusted with high precision. However, in the above method, the striped pattern is formed using two laser beams having different optical axes, so even a slight deviation in the optical axis of each laser beam changes the width of the striped pattern. Therefore, in order to obtain a highly accurate striped pattern, advanced and complicated alignment work is required for the light source or the optical member described above in order to position the two laser beams (for example, two laser beams emitted from two light sources, or two laser beams formed by splitting a laser beam from one light source with an optical member such as a beam splitter) with high precision. In addition, if the optical axis of the laser beam is shifted even slightly due to vibrations or the like generated during measurement, the size of the particle may not be calculated accurately.
[0005] 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 form a beam pattern suitable for particle measurement using a flow path device with high accuracy. [Means for solving the problem]
[0006] The present disclosure includes the following laser measurement devices [1] to
[18] and a laser measurement method
[19] .
[0007] [1] 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 having a beam pattern in which at least two bright portions are arranged with a dark portion sandwiched between them along a flow direction of the fluid toward the sample flow path; a sensor that detects light emitted from the particle as the particle passes through a region in the sample flow path where the beam pattern is formed.
[0008] In the above laser measurement device, a beam pattern in which light and dark areas are alternately arranged along the flow direction of the flow path device is formed in the sample flow path of the flow path device. When the particle to be measured passes through an area in which such a beam pattern is formed, particle measurement (e.g., measurement of the size of the particle, etc.) can be suitably performed based on the emitted light emitted from the particle. Furthermore, according to the above laser measurement device, the beam pattern can be formed easily and with high accuracy by using a single light source configured to form the beam pattern in advance. That is, in order to form the beam pattern, it is not necessary to perform advanced and complicated alignment adjustment of optical members such as a plurality of light sources (i.e., the optical axes of the laser beams emitted from each light source) or a beam splitter for splitting one laser beam emitted from one light source into two laser beams. As described above, according to the above laser measurement device, a beam pattern suitable for particle measurement using a flow path device can be formed easily and with high accuracy.
[0009] [2] The light source is: A light emitting portion; [1] A laser measurement device having a surface-emitting laser optically coupled to the light-emitting section and including a base layer and a phase modulation layer including a plurality of modified refractive index areas having a refractive index different from that of the base layer.
[0010] According to the above configuration [2], 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 path.
[0011] [3] A laser measurement device according to [2], wherein the center of gravity of each of the plurality of modified refractive index areas is arranged at a relative position in accordance with a phase distribution corresponding to the beam pattern with respect to each of a plurality of periodically arranged lattice points.
[0012] According to the above configuration [3], the above-mentioned beam pattern can be suitably and easily formed in the sample flow path by the surface emitting laser, while eliminating the need for a slit member described later.
[0013] [4] The phase modulation layer is a photonic crystal layer in which the multiple modified refractive index areas are periodically arranged, The laser measurement device of [2], wherein the light source further includes a slit member that forms the laser light having the beam pattern by passing the light emitted from the surface-emitting laser.
[0014] [5] The light source is: a vertical cavity surface emitting laser; and a slit member through which light emitted from the surface-emitting laser passes to form the laser light having the beam pattern.
[0015] According to the above configuration [4] or [5], the above-mentioned beam pattern can be suitably and easily formed in the sample flow path by combining the surface emitting laser with the slit member.
[0016] [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.
[0017] According to the configuration [6] above, attenuation of the laser light outside the flow path device can be suppressed. In addition, the positioning of the light source relative to the flow path device can be facilitated, and the laser measurement device (module) can be made compact.
[0018] [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 areas extending in a direction intersecting the flow direction are arranged along the flow direction.
[0019] 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.
[0020] [8] 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; The laser measurement device of [7], wherein the surface-emitting laser forms the striped beam pattern by interfering with light emitted from each of a plurality of different regions in an in-plane direction of a light emission surface of the surface-emitting laser.
[0021] According to the configuration of [8] above, a fine striped beam pattern (i.e., a pattern with a small pitch between multiple bright areas) can be formed with high accuracy in a space relatively close to the light emission surface of the surface-emitting laser. This makes it possible to appropriately measure the size of microparticles such as cells while miniaturizing the laser measurement device (module) by arranging the surface-emitting laser close to the flow path device.
[0022] [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.
[0023]
[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.
[0024] According to the configuration of [9] or
[10] above, by combining the beam patterns of the multiple light source units, a beam pattern that can perform more advanced particle measurement than that possible with the beam pattern of a single light source unit can be formed in the flow path device. According to the configuration of [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 made common, so that the laser measurement device (module) can be made compact. According to the configuration of
[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.
[0025]
[11] 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, The laser measurement device of [9] or
[10] , wherein in a passage area in the sample flow path through which the particles pass, the beam patterns of the plurality of light source units are arranged so as not to overlap with each other.
[0026] 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 passing area can be easily and appropriately adjusted according to the size range of the particles to be measured.
[0027]
[12] The laser measurement device of [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.
[0028] According to the configuration
[12] above, it is possible to identify the area in the sample flow path through which the particles to be measured have passed (i.e., the area of the first range or the area of the second range) based on the intensity of the emitted light detected by the sensor.
[0029]
[13] The light source includes a first light source unit that emits the laser light having a first wavelength, and a second light source unit that emits the laser light having a second wavelength different from the first wavelength; The sensor detects a first signal corresponding to a 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 a second emitted light emitted in response to the laser light of the second wavelength being irradiated onto the particle.
[0030] According to the configuration of
[13] above, more advanced particle measurement can be performed based on the measurement results corresponding to each of a plurality of mutually different wavelengths.
[0031]
[14] 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, The second light source unit forms a striped beam pattern in which a plurality of the bright areas 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.
[0032] According to the configuration
[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 for each wavelength (i.e., the measurement results of the first signal or the measurement results of the second signal).
[0033]
[15] The laser measurement device of
[13] , wherein a first beam pattern formed by the first light source unit and a second beam pattern formed by the second light source unit have the same shape and are positioned at offset positions from each other along the flow direction.
[0034] According to the configuration
[15] above, the velocity (flow velocity) of particles in the sample flow path can be easily and accurately measured based on the time shift 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 shift between the first beam pattern and the second beam pattern.
[0035]
[16] The laser measurement device of
[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.
[0036] 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 measurements (waveform analysis).
[0037]
[17] 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, The laser measurement device of
[13] , wherein the second light source unit forms a striped beam pattern in which a plurality of the bright areas extending in a second direction intersecting the first direction are arranged along the flow direction.
[0038] 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.
[0039]
[18] The laser measurement device according to any one of [1] to
[17] , wherein the light source time-modulates the intensity of the laser light.
[0040] According to the configuration of
[18] above, it is possible to easily grasp the background noise generated during measurement from the measurement results (time waveform).
[0041]
[19] A laser measurement method using any one of the laser measurement devices according to [1] to
[18] , forming a beam pattern in a sample flow path through which a fluid containing particles to be measured passes in the flow path device, the beam pattern including at least two bright portions arranged with a dark portion sandwiched therebetween along a flow direction of the fluid, by emitting the laser light from the light source to the flow path device; detecting light emitted from the particle as the particle passes through an area in which the beam pattern is formed; and determining at least one of a shape and a size of the particle based on the detected emitted light.
[0042] According to the above laser measurement method, it is possible to obtain 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 the particle can be determined with high accuracy based on the detection result of the emitted light obtained by the beam pattern. Effect of the Invention
[0043] According to one aspect of the present disclosure, it is possible to provide a laser measurement apparatus and a laser measurement method that can easily form a beam pattern suitable for particle measurement using a flow channel device with high accuracy. [Brief description of the drawings]
[0044] [Figure 1] FIG. 1 is a diagram illustrating a schematic configuration of a laser measurement device according to an embodiment. [Diagram 2] FIG. 2 is an enlarged view of a portion A of FIG. [Diagram 3] FIG. 3 is an enlarged view of a portion A in FIG. 1 viewed from a direction facing the surface-emitting laser. [Figure 4] FIG. 4 is a cross-sectional view of the flow cell taken along line IV-IV in FIG. [Diagram 5] FIG. 5 is a partially cutaway perspective view showing an example of a surface emitting laser. [Figure 6] FIG. 6 is a cross-sectional view showing an example of a layered structure of a surface-emitting laser. [Figure 7] FIG. 7 is a plan view showing an example of a phase modulation layer. [Figure 8] FIG. 8 is an enlarged view of a unit constituent region. [Figure 9] FIG. 9 is a plan view showing a first example of a phase distribution of the phase modulation layer. [Figure 10] FIG. 10 is a diagram showing how two beams are emitted from the two regions shown in FIG. [Figure 11] FIG. 11 is a perspective view showing a second example of the phase distribution of the phase modulation layer. [Figure 12]FIG. 12 is a diagram showing a first measurement example. [Figure 13] In Figure 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 of Figure 12, (C) is a graph showing the measurement results of the emitted light from sample Sb of Figure 12, and (D) is a graph showing the measurement results of the emitted light from sample Sc of Figure 12. [Figure 14] FIG. 14 is a diagram showing a second measurement example. [Figure 15] In Figure 15, (A) is a graph showing the measurement results of the emitted light from sample Sd of Figure 14, (B) is a graph showing the measurement results of the emitted light from sample Se of Figure 14, (C) is a graph showing the measurement results of the emitted light from sample Sf of Figure 14, (D) is a graph showing the measurement results of the emitted light from sample Sg of Figure 14, (E) is a graph showing the measurement results of the emitted light from sample Sh of Figure 14, and (F) is a graph showing the measurement results of the emitted light from sample Si of Figure 14. [Figure 16] FIG. 16 is a diagram showing a third measurement example. [Figure 17] FIG. 17 is a diagram showing an example of a beam pattern formed by a combination of a plurality of surface emitting lasers in the third measurement example. [Figure 18] FIG. 18 is a diagram showing a fourth measurement example. [Figure 19] 19, (A) is a graph showing the measurement results of the light emitted from sample Sj in FIG. 18, and (B) is a graph showing the measurement results of the light emitted from sample Sk in FIG. [Figure 20] FIG. 20 is a diagram showing the fifth measurement example. [Figure 21] FIG. 21 is a graph showing the measurement results of the emitted light from sample S of FIG. [Figure 22] FIG. 22 is a diagram showing the sixth measurement example. [Diagram 23] FIG. 23 is a diagram showing the seventh measurement example. [Figure 24] FIG. 24 is a diagram showing the eighth measurement example. [Diagram 25] 25, (A) is a graph showing the measurement results of the light emitted from sample Sl of FIG. 24, and (B) is a graph showing the measurement results of the light emitted from sample Sm of FIG. [Figure 26] In FIG. 26, (A) is a graph showing the measurement results using laser light, which is continuous light, and (B) is a graph showing the measurement results according to the ninth measurement example. [Figure 27] FIG. 27 is a graph showing another example of the measurement result of the ninth measurement example. [Figure 28] FIG. 28 is an enlarged view of the range Rb in FIG. [Figure 29] FIG. 29 is a diagram showing a modified example of the arrangement of a plurality of surface emitting lasers. [Diagram 30] FIG. 30 is a diagram illustrating a schematic configuration of a first modified example of the laser measurement device. [Diagram 31] FIG. 31 is a diagram illustrating a schematic configuration of a second modified example of the laser measurement device. [Diagram 32] FIGS. 32A and 32B are diagrams showing other examples of beam patterns. [Diagram 33] FIG. 33 is a diagram showing a first modified example of the light source. [Diagram 34] FIG. 34 is a diagram showing a second modified example of the light source. [Diagram 35] FIG. 35 is a plan view showing an example in which a substantially periodic refractive index structure is applied in a specific region of a phase modulation layer. [Diagram 36] FIG. 36 is a diagram for explaining coordinate conversion from spherical coordinates (r, θrot, θtilt) to coordinates (ξ, η, ζ) in the XYZ orthogonal coordinate system. [Figure 37] FIG. 37 is a plan view showing a reciprocal lattice space related to a phase modulation layer of a light emitting device that performs M-point oscillation. [Figure 38] FIG. 38 is a diagram conceptually illustrating an example of a phase distribution. [Figure 39] FIG. 39 is a diagram for explaining a schematic structure around the light line LL. [Diagram 40]FIG. 40 is a diagram conceptually illustrating an example of the phase distribution φ2(x, y). [Diagram 41] FIG. 41 is a conceptual diagram for explaining a state in which a diffraction vector is added to the in-plane wave vectors in four directions, from which the wave number spread is removed. [Diagram 42] FIG. 42 is a plan view showing another form of the phase modulation layer (first region and second region). [Diagram 43] FIG. 43 is a diagram showing the arrangement of modified refractive index areas in the phase modulation layer (first area and second area) shown in FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0045] Hereinafter, an embodiment of the present disclosure will be described in detail with reference to the drawings. In the following description, the same or corresponding elements are designated by the same reference numerals, and duplicated description will be omitted.
[0046] [Overall configuration of laser measurement device] A laser measurement device 1 according to an embodiment of the present disclosure will be described with reference to Fig. 1 to Fig. 4. The laser measurement device 1 is a device for performing particle measurement (e.g., measurement of particle shape, size, etc.) by flow cytometry. As shown in Fig. 1, the laser measurement device 1 includes a flow cell 2 (flow path device), a surface emitting laser 3 (light source), a photodetector 4 (sensor), a control unit 5, an optical system 6, and a pump 7.
[0047] 1 shows a configuration in which the laser measurement device 1 includes one surface-emitting laser 3 as a light source, but when forming beam patterns in the third to eighth measurement examples described later, 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 one photodetector 4 as a sensor, when forming beam patterns in the fifth to eighth measurement examples described later, 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 sources and sensors corresponding to each measurement example will be described when each measurement example is explained.
[0048] 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 material. The fluid containing the sample S is sent into the sample flow path 21 by the pump 7. In this embodiment, the flow cell 2 has a tubular side wall 22 surrounding the sample flow path 21 and extending in one direction (Z-axis direction). As an example, the side wall 22 is formed in a rectangular ring shape when viewed from the flow direction of the fluid in the flow cell 2 (Z-axis direction). The side wall 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. That is, the side wall 22 transmits the laser light L1 and the emitted light L2. Examples of the transparent material include glass, quartz, and synthetic resin.
[0049] In 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 in the sample flow channel 21 are not distinguished from each other in the drawings. The fluid forming the sample flow and the sheath flow is, for example, water. When the width of the sample flow is set to be relatively small by controlling the pressure of the sample flow and the pressure of the sheath flow, each sample S flows sequentially through the approximate center of the sample flow channel 21. On the other hand, when the width of the sample flow is set to be relatively large, the sample S also flows to positions other than the approximate 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).
[0050] 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.
[0051] The surface-emitting laser 3 is a surface-emitting laser that emits laser light L1 so that a beam pattern P in which at least two bright areas Pa are arranged with a dark area Pb sandwiched between them along the flow direction (Z-axis direction) of the fluid in the flow cell 2 is formed in the sample flow path 21 (see FIG. 12). In other words, the beam pattern P includes a portion in which bright areas Pa and dark areas Pb appear alternately along the Z-axis direction. FIGS. 1 to 3 show the laser light L1 that forms the beam pattern P1 (FIG. 12) in a first measurement example described later. As an example, the surface-emitting laser 3 is fixed to the side wall 22 of the flow cell 2. More specifically, the surface-emitting laser 3 is fixed to the flow cell 2 so that the light emission surface 3a of the surface-emitting laser 3 faces one side surface 22a of the side wall 22 (the outer surface opposite to 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 a 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 need 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).
[0052] The photodetector 4 is a sensor that detects the 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. The scattered light includes forward scattered light that travels in the same direction as the irradiation direction of the laser light L1 on 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, the photodetector 4 is disposed at a position facing the surface-emitting laser 3 across the sample flow path 21 in order to detect the forward scattered light from the sample S.
[0053] The control unit 5 acquires the measurement results (time waveform) of the signal intensity detected by the photodetector 4, and executes various analysis processes (e.g., determining (estimating) the shape and size of the sample S in each measurement example described later) based on the measurement results. The control unit 5 may be configured, for example, by one or more computer devices equipped with a processor, memory, auxiliary storage device, etc.
[0054] 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.
[0055] The collimating lens 61 is a lens for collimating the emission light L2 emitted from the sample S. The light shielding 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 condensing 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.
[0056] [Example of surface-emitting laser configuration] A configuration example of the surface-emitting laser 3 will be described with reference to Fig. 5 to Fig. 11. In Fig. 5 to Fig. 11, an XYZ orthogonal coordinate system is defined in which an axis extending in the thickness direction of the surface-emitting laser 3 at the center of the surface-emitting laser 3 is set as the Z axis. Note that the XYZ orthogonal coordinate system in Fig. 5 to Fig. 11 is unrelated to the XYZ orthogonal coordinate systems in other figures (i.e., the XYZ orthogonal coordinate system in which the flow direction of the fluid in the flow cell 2 defined above is defined as the Z axis direction).
[0057] The surface-emitting laser 3 is a laser light source that forms a standing wave in the XY plane direction and outputs a phase-controlled plane wave in a direction intersecting the thickness direction. The surface-emitting laser 3 is an S-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 inclined thereto, or a direction including both. The surface-emitting laser 3 may be an S-iPMSEL (registered trademark) manufactured by Hamamatsu Photonics KK
[0058] 5 and 6, the surface-emitting laser 3 includes an active layer 12 as a light-emitting portion provided on a semiconductor substrate 10, a pair of clad layers 11 and 13 sandwiching the active layer 12, and a contact layer 14 provided on the clad layer 13. The semiconductor substrate 10, the clad 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 band gaps of the clad layer 11 and the clad layer 13 are larger than the energy band gap of the active layer 12. The thickness directions of the semiconductor substrate 10, the clad layer 11, the active layer 12, the clad layer 13, and the contact layer 14 coincide with the Z-axis direction.
[0059] 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.
[0060] 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 =(√2)a×n. This wavelength λ 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 emission wavelength λ 0 A nearby band edge wavelength can be selected and output to the outside. In this case, the M-point band edge of a square lattice that has no 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 areas 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.
[0061] 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 makes ohmic contact with the contact layer 14. The electrode 17 makes 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 other than 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 other region other than the opening 17a may be removed.
[0062] In the surface-emitting laser 3, when a driving current is supplied between the electrode 16 and the electrode 17, recombination of electrons and holes occurs in the active layer 12, and the active layer 12 emits light. The electrons, holes, and light generated in the active layer 12 that contribute to this emission are efficiently confined between the cladding layer 11 and the cladding layer 13. The light emitted from the active layer 12 enters the inside of 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 to the outside of the surface-emitting laser 3 through the opening 17a from the back surface 10b. Alternatively, the laser light emitted from the phase modulation layer 15 is reflected at the electrode 16 and then output to the outside of the surface-emitting laser 3 through the opening 17a from the back surface 10b. That is, in this example, the back surface 10b of the surface-emitting laser 3 functions as the light emission surface 3a. At this time, the signal light included in the laser light is emitted in an arbitrary direction including a direction perpendicular to the main surface 10a and a direction inclined with respect to that direction. The emission light from the surface-emitting laser 3 is composed of this signal light. The signal light is mainly the first-order diffracted light or the -first-order diffracted light of the laser light (hereinafter, referred to as the +first-order light and the -first-order light, respectively), or both of them.
[0063] 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 with respect to 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. The square unit configuration region R centered on the lattice point O of the square lattice is two-dimensionally arranged over a plurality of columns along the X axis and a plurality of rows along the Y axis. The XY coordinates of each unit configuration region R are defined by the center-of-gravity position of each unit configuration region R. These center-of-gravity positions coincide with the lattice point O of the virtual square lattice. The birefringence region 15b is provided, for example, only one in each unit configuration region R. The planar shape of the birefringence region 15b is, for example, circular. The lattice point O may be located outside the birefringence region 15b or may be included inside the birefringence region 15b.
[0064] FIG. 8 is an enlarged view of the unitary constituent region R. As shown in the figure, each of the modified refractive index areas 15b has a center of gravity G. Here, the angle between the vector from the lattice point O toward the center of gravity G and the X-axis is γ(x, y). x indicates the position of the x-th lattice point on the X-axis, and y indicates the position of the y-th lattice point on the Y-axis. When the rotation angle γ is 0°, the direction of the vector connecting the lattice point O and the center of gravity G coincides with the positive direction of the X-axis. In addition, the length of the vector connecting the lattice point O and the center of gravity G is r(x, y). As an example, r(x, y) is constant throughout the entire phase modulation layer 15, regardless of x and y. The size of the planar shape of each modified refractive index area 15b does not need to be constant, and may be set individually.
[0065] 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 arranged at a relative position according to a phase distribution corresponding to a beam pattern (beam pattern P of various measurement examples described later) with respect to each of the multiple periodically arranged lattice points O. In other words, the center of gravity G of each modified refractive index area 15b is arranged at a relative position according to a phase modulation amount of a predetermined phase distribution with respect to the corresponding lattice point O. 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 according to the phase distribution φ(x, y) corresponding to the desired shape of the emitted light.
[0066] 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 a beam pattern P of various measurement examples described later in the sample flow path 21.
[0067] For example, in order to suitably form a striped beam pattern P1 (i.e., a pattern in which a plurality of linear bright parts Pa and a plurality of linear dark parts Pb are alternately arranged as shown in FIG. 12) according to a first measurement example described later, 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 interfering light emitted from each of a plurality of different regions in the in-plane direction of the light-emitting surface 3a (i.e., the direction along the XY plane in FIGS. 5 to 11). According to the above configuration, a fine striped beam pattern P1 (i.e., a pattern in which the pitch between the plurality of bright parts Pa is minute) can be formed with high accuracy in a space relatively close to the light-emitting surface 3a of the surface-emitting laser 3. As a result, it is possible to suitably measure the size of minute particles such as cells while miniaturizing the laser measurement device 1 (module) by disposing the surface-emitting laser 3 close to the flow cell 2.
[0068] 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 3a 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. In addition, 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.
[0069] (First example of phase distribution) A first example of the phase distribution of the phase modulation layer 15 will be described with reference to Fig. 9 and Fig. 10. 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 the one direction. Due to the one-dimensional lens pattern, a first beam emitted from a region on one side of the optical axis (corresponding to a first region 151 described later) and a second beam emitted from a region on the other side of the optical axis (corresponding to a second region 152 described later) cross each other at a certain position (first position) and then separate.
[0070] 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 (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 shape of the first region 151 and the planar shape of the second region 152 are line-symmetrical with respect to a straight 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 a planar shape such as a rectangular shape, and extend in a direction intersecting the X-axis direction (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.
[0071] 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, that is, in the X-axis direction. FIG. 10 is a diagram showing how the beams 241 and 242 are emitted from the first region 151 and the second region 152 shown in FIG. 9. The beam 241 (first beam) which is +1-order light is emitted from the first region 151. The beam 242 (second beam) which is +1-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 halftone dots in the figure) where the beams 241 and 242 overlap in the XZ plane. 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 rhombus shape when viewed from the Y-axis direction. Within the region 26, a focused spot 261 is formed that extends in the light emission direction and is centered on the first position 25. The first position 25 may be located on the optical axis OX or may be spaced apart from the optical axis OX.
[0072] According to the above configuration, by causing interference in region 26 where beams 241 and 242 overlap, 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) can be formed.
[0073] (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 including a first region 151 and a second region 152 spaced apart from the first region 151, according to the arrangement of the multiple modified refractive index regions 15b. In the light extraction region 15P, the multiple 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 the intermediate region 155, the multiple 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 long linear regions in the Y-axis direction. This makes it possible to realize a pseudo double slit in which the first region 151 and the second region 152 are each a slit, and to form interference fringes due to interference of the emitted light in the Fresnel region. 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.
[0074] [Measurement example] Various beam patterns P will be described below, along with measurement examples according to each beam pattern P.
[0075] (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 a plurality of (for example, five) linear bright areas 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 areas (bright areas Pa) and linear dark areas (dark areas Pb) are alternately arranged along the Z-axis direction when viewed from the X-axis direction. Fig. 13 (A) shows a graph in which the horizontal axis is the coordinate corresponding to the x-axis direction in Fig. 12 and the vertical axis is the intensity of the beam pattern P1 formed by the laser light L1. As shown in Fig. 13 (A), the beam pattern P1 has peaks at positions corresponding to each of the five bright areas Pa.
[0076] As shown in Fig. 12, 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 are considered here. Although Fig. 12 shows a state in which a plurality of samples Sa to Sc are 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 in which the beam pattern P1 is formed at different times. This also applies to the second measurement example in Fig. 14, the fourth measurement example in Fig. 18, and the seventh measurement example in Fig. 24.
[0077] (B) of Fig. 13 is a graph (time waveform) showing the measurement results of emitted light L2 from sample Sa of Fig. 12, (C) is a graph showing the measurement results of emitted light L2 from sample Sb of Fig. 12, and (D) is a graph showing the measurement results of emitted light L2 from sample Sc of Fig. 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.
[0078] In the measurement results (time waveforms) of the samples Sa to Sc shown in (B) to (D) of FIG. 13, 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 of the peaks (mountains) of the time waveforms is defined as I max and the light intensity at the bottom (valley) is I min Then, the modulation depth M of the measurement result can be calculated by the following formula (0).
[0079] M=(I max -I min ) / (I max +I min ) …(0)
[0080] 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 FIG. 13, in the case of samples Sb and Sc having a short length in the Z-axis direction, the samples Sb and Sc do not overlap with multiple bright parts Pa at the same time (or the period in which they do not overlap with the bright parts Pa is relatively long), so the modulation depth M obtained by the above formula (0) is relatively large. On the other hand, as shown in (B) of FIG. 13, in the case of sample Sa having a long length in the Z-axis direction, there is a period in which the sample Sa overlaps with multiple bright parts Pa at the same time (or the period in which they do not overlap with the bright parts Pa is relatively short), so the modulation depth M obtained 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 (length in the Z-axis direction) of the sample S (for example, a modulation curve such as that shown in Figure 7 of Patent Document 1).
[0081] 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 according to the size range of the sample S to be measured. The pitch between adjacent bright areas Pa is set, for example, to 1 μm or more and 100 μm or less.
[0082] (Second measurement example) A second measurement example using a dot-shaped beam pattern P2 will be described with reference to Fig. 14 and Fig. 15. As shown in Fig. 14, the beam pattern P2 has a pattern shape in which a plurality of bright parts 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 S-iPM laser disclosed in JP 2022-154929 A as the surface-emitting laser 3.
[0083] In the example of FIG. 14, each bright portion Pa is formed in a square shape when viewed from the X-axis direction. Moreover, the multiple bright portions Pa are arranged in a rhombic lattice shape 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 that flow through positions overlapping with the bright portions Pa in the odd-numbered rows (in FIG. 14, the flow paths through which the samples Sd and Sf pass, the flow paths through which the upper half of the sample Sh passes, and the flow paths through which the upper and lower parts of the sample Si pass when the sample Si is divided into thirds), bright portions Pa are formed in the odd-numbered rows, and dark portions Pb are formed in the regions between the bright portions Pa in the adjacent odd-numbered rows. On the other hand, in the flow paths that flow through positions overlapping with the bright portions Pa in the even-numbered rows (in FIG. 14, the flow paths through which the samples Se and Sg pass, the flow paths through which the lower half of the sample Sh passes, and the flow paths through which the central part of the sample Si passes when the sample Si is divided into thirds), bright portions Pa are formed in the even-numbered rows, and dark portions Pb are formed in the regions between the bright portions Pa in the adjacent even-numbered rows.
[0084] 14, samples Sd and Se having an elongated shape in the Z-axis direction, spherical samples Sf and Sg, a sample Sh having an elongated shape in the Y-axis direction, and a sample Si longer than the sample Sh in the Y-axis direction are considered. Here, it is assumed that the sample flows of the samples Sd to Si are set so as to flow straight along the Z-axis direction.
[0085] 15A is a graph showing the measurement results of the emitted light L2 from sample Sd, (B) is a graph showing the measurement results of the emitted light L2 from sample Se, (C) is a graph showing the measurement results of the emitted light L2 from sample Sf, (D) is a graph showing the measurement results of the emitted light L2 from sample Sg, (E) is a graph showing the measurement results of the emitted light L2 from sample Sh, and (F) is a graph showing the measurement results of the emitted light L2 from sample Si. In each graph, the horizontal axis indicates time, and the vertical axis indicates the signal intensity of the emitted light L2 detected by the photodetector 4. Furthermore, times t1 to t4 on the horizontal axis of each graph indicate the times when each sample Sd to Si passed through positions corresponding to columns x1 to x4 in FIG.
[0086] The samples Sd and Se, which are longer in the Z-axis direction, overlap with one bright area 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 (A) and (B) of Figures 15, in the time waveforms of samples Sd and Se, peak waveforms that are longer in the time direction (horizontal axis direction) are observed than in the time waveforms of samples Sf and Sg (see (C) and (D) of Figures 15).
[0087] 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 row and one bright portion Pa provided in the even-numbered row. Therefore, as shown in (E) of Fig. 15, peak waveforms are observed not only at times t1 and t3 when passing through the odd-numbered rows (x1, x3), but also at times t2 and t4 when passing through the even-numbered rows (x2, x4).
[0088] Sample Si, which is long in the Y-axis direction, is large enough to overlap two bright areas Pa provided in the odd-numbered rows and one bright area Pa provided in the even-numbered row. Therefore, as shown in (F) of Fig. 15, peak waveforms are observed in both the odd-numbered rows and the even-numbered rows, similar to sample Sh, and the peaks corresponding to the odd-numbered rows (peaks at time points t1 and t3) are higher than the peaks corresponding to the even-numbered rows (peaks at time points t2 and t4).
[0089] 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 waveform) 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 in the time direction of the peak waveform represented in the measurement results (time waveform). The control unit 5 can also 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 or even-numbered column, or both the odd-numbered and even-numbered columns) and the peak difference between the odd-numbered and even-numbered columns.
[0090] (Third measurement example) 16 and 17, a third measurement example in which various beam patterns can be formed by combining multiple surface-emitting lasers 3A to 3D will be described. As shown in FIG. 16, in the third measurement example, the laser measurement device 1 includes, as a light source, multiple (four, as an example) surface-emitting lasers 3A to 3D (multiple light source units) arranged along the Z-axis direction. In the third measurement example, each of the surface-emitting lasers 3A to 3D has the same configuration as the above-mentioned surface-emitting laser 3. 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 each measurement example.
[0091] Each of the multiple surface-emitting lasers 3A-3D is configured to form striped beam patterns PA-PD (see the left part of FIG. 17) in which multiple linear bright parts Pa extending in the Y-axis direction are arranged at predetermined intervals along the Z-axis direction in the same manner as in the first measurement example, in the sample flow path 21. Moreover, in a passing region Ra through which the sample S passes in the sample flow path 21, the beam patterns PA-PD of each of the multiple surface-emitting lasers 3A-3D are arranged so as not to overlap with each other. In this example, since the flow of the sample S is controlled so that it passes through the center part of the sample flow path 21 in the Y-axis direction, the passing region Ra is a region that includes the center part of the sample flow path 21 in the Y-axis direction and has a predetermined length in the Z-axis direction.
[0092] FIG. 17 is a diagram schematically showing each of the beam patterns PA to PD when viewed from the X-axis direction (when the Z-axis direction corresponds to the left-right direction in the drawing and the Y-axis direction corresponds to the up-down direction in the drawing). As shown in the left part of FIG. 17, the bright parts 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 parts Pa) of each of the beam patterns PA to PD is constant. Also, the beam pattern PB is shifted from the beam pattern PA by a distance d AB only in the Z-axis direction. Similarly, the beam patterns PC and PD are shifted from the beam pattern PA by distances d AC , d AD only in the Z-axis direction. Here, the distance d AB is half the length of the pitch p, the distance d AC is one-fourth the length of the pitch p, and the distance d AD is three-fourths the length of the pitch p.
[0093] As shown in the upper right part of FIG. 17, when only the surface-emitting laser 3A emits the laser beam L1, the beam pattern PA with the distance between adjacent bright parts Pa being "pitch p" can be set. Note that by emitting the laser beam L1 from any one of the surface-emitting lasers 3B, 3C, and 3D, a beam pattern (any one of the beam patterns PB to PC) with the distance between adjacent bright parts Pa being "pitch p" can also be set.
[0094] As shown in the middle right part of FIG. 17, when the laser beams L1 are emitted from the two surface-emitting lasers 3A and 3B, the beam pattern (beam pattern PA + PB) with the distance between adjacent bright parts Pa being "half of the pitch p" can be set. Note that by emitting the laser beam L1 from the surface-emitting lasers 3C and 3D, a beam pattern (beam pattern PC + PD) with the distance between adjacent bright parts Pa being "half of the pitch p" can also be set.
[0095] 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."
[0096] As described above, according to the third measurement example, by selecting two or more surface-emitting lasers that emit laser light L1 from the multiple surface-emitting lasers 3A to 3D, it is possible to easily and appropriately adjust the interval (pitch) between the bright parts Pa formed in the passing 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.
[0097] (4th measurement example) A fourth measurement example will be described with reference to Fig. 18 and Fig. 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.
[0098] The multiple surface-emitting lasers 3A and 3B are configured to form a first bright portion Pa1 with a brightness of a first intensity in a region R1 of a first range in the Y-axis direction (first direction) in at least a part of the region in the sample flow path 21, and to form a second bright portion Pa2 with a brightness of a second intensity different from the first intensity in a region R2 of a second range different from the first range in the Y-axis direction. As an 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. In addition, one surface-emitting laser 3A is configured to form a first bright portion Pa1 with a low intensity in the region R1, and the other surface-emitting laser 3B is configured to form a second bright portion Pa2 with a high intensity 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 set to be greater than the light intensity of the laser light L1 of the surface-emitting laser 3A that forms the first bright portion Pa1.
[0099] The first bright portion Pa1 and the second bright portion Pa2 are both formed in a line extending in the Y-axis direction when viewed from the X-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.
[0100] As shown in Fig. 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. Fig. 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 indicates time, and the vertical axis indicates the signal intensity of emitted light L2 detected by the photodetector 4.
[0101] As shown in FIG. 19, the signal intensity ((B) of FIG. 19) of the emitted light L2 emitted from the sample Sk passing through the second bright portion Pa2 with high intensity is greater than the signal intensity ((A) of FIG. 19) of the emitted light L2 emitted from the sample Sj passing through the first bright portion Pa1 with low intensity. Therefore, according to the fourth measurement example, the control unit 5 can specify the region (either region R1 or R2 in the example of FIG. 18) through which the measurement target sample S has passed in the sample flow path 21 based on the intensity of the emitted light L2 detected by the photodetector 4. For example, consider a case where it is necessary to control the flow in the flow cell 2 so that the sample S passes through the center (region R2) in the sample flow path 21 in order to measure the sample S with high accuracy. According to the fourth measurement example, in such a case, it can be easily confirmed whether the flow control in the flow cell 2 is performed appropriately (i.e., whether only the measurement result corresponding to the sample S passing through region R2 is obtained).
[0102] (5th measurement example) A fifth measurement example will be described with reference to Fig. 20 and Fig. 21. 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.
[0103] 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 (for example, 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 (for example, 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 disposed in front of the photodetector 4A. Similarly, an optical filter 64B configured to transmit only the second emitted light may be disposed in front of the photodetector 4B. With this configuration, it is possible to separately acquire a measurement result (first signal) corresponding to the first wavelength and a measurement result (second signal) corresponding to the second wavelength.
[0104] It should be noted that the XYZ orthogonal 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 the 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 in the paper than the flow cell 2, and the photodetectors 4A, 4B are arranged further forward in the paper than the flow cell 2. The same is true for Figs. 22 to 24.
[0105] 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 shifted 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. Similarly to 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 shifted downstream from the beam pattern PA by a distance half the pitch p.
[0106] FIG. 21 is a graph showing a waveform WA corresponding to the measurement result of the first emitted light emitted when the sample S 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 when the sample S 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). In FIG. 21, the horizontal axis indicates time, and the vertical axis indicates 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. In addition, since the beam pattern PB is located downstream of the beam pattern PA by half the pitch p, a time difference Δt occurs between the waveforms WA and WB according to the distance difference.
[0107] According to the fifth measurement example, the control unit 5 can easily and accurately measure the velocity (flow velocity) 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 shift 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 obtain the relative movement amount of the waveform WB with respect to the waveform WA required to overlap the waveform WA with the waveform WB. Alternatively, as shown in FIG. 21, it is also possible to specify points (for example, points corresponding to the first peak) corresponding to each other in the waveforms WA and WB and calculate the time difference Δt between the points. Then, the control unit 5 can easily and accurately obtain the flow velocity of the sample S during the measurement period of the waveforms WA and WB by dividing the positional shift amount (p / 2) of the beam patterns PA and PB by the time difference Δt. Note that, for example, a measurement similar to the fifth measurement example may be performed by preparing a plurality of (e.g., two) light source units of the same wavelength, configuring the beam patterns of the plurality of light source units to be formed at positions shifted from each other along the Z-axis direction, and making the light emission timing of each of the plurality of light source units different from each other (for example, making them blink alternately so that the timing of pulsed light emission does not overlap), and detecting the output (signal intensity) of each of the plurality of photodetectors. With such a configuration, while it becomes necessary to control the light emission timing, it becomes possible to omit the optical filter arranged in front of the photodetector.
[0108] (6th 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 points. 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) different from the first interval along the Z-axis direction. In the example of FIG. 22, the pitch p2 is 1 / 3 of the pitch p1. Therefore, in FIG. 22, the bright portions PBa are formed so as to overlap the positions where the bright portions PAa are formed.
[0109] According to the sixth measurement example, by making the pitch between the bright parts different for each wavelength (i.e., by making the pitch p1 between the adjacent bright parts PAa and the pitch p2 between the adjacent bright parts PBa different), 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 result of each wavelength (i.e., the measurement result of the photodetector 4A or the measurement result 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 example 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, even in the third modified example, 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 is a limit to the combination 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 modified example, a beam pattern of any pitch can be formed for each wavelength, so that two different size ranges can be flexibly and simultaneously handled.
[0110] (7th 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 (striped pattern in the example of Fig. 23) differs from the pattern shape of the beam pattern PB formed by the surface-emitting laser 3B (dot pattern in the example of Fig. 23). Here, "pattern shape" refers to the type of shape of the bright parts constituting the beam pattern (for example, type of pattern such as lines (stripes), dots, etc.).
[0111] According to the seventh measurement example, since it is possible to obtain measurement results (time waveforms) corresponding to different pattern shapes for each wavelength, it is possible to perform more advanced particle measurement (waveform analysis). More specifically, it is possible to simultaneously and separately obtain measurement results corresponding to beam patterns PA and PB having different pattern shapes by separating the wavelengths of the beam patterns PA and PB. In this way, by obtaining waveforms of each of a plurality of pattern shapes, it is possible to increase the amount of information that can be used for waveform analysis.
[0112] (8th measurement example) The eighth measurement example will be described with reference to FIG. 24 and FIG. 25. The eighth measurement example is similar to the fifth to seventh measurement examples in that a surface-emitting laser 3A emitting a laser beam L1 of a first wavelength and a surface-emitting laser 3B emitting a laser beam 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 angle at which the second direction D2 is inclined with respect to the Z-axis direction, with the sign reversed. That is, the beam pattern PA and the beam pattern PB have shapes that are linearly symmetric with respect to an axis AX parallel to the Z-axis direction.
[0113] According to the eighth measurement example, it becomes possible to perform more advanced particle shape estimation from the measurement results (time waveforms) for each wavelength. Hereinafter, an example of the above-mentioned shape estimation will be described with reference to Figs. 24 and 25. Here, as shown in Fig. 24, a spherical sample Sl and a non-spherical (ellipsoidal) sample Sm are considered. Fig. 25 (A) is a graph showing a waveform WA corresponding to the measurement result of the first emitted light emitted by the sample Sl when passing 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 S when passing through the beam pattern PB of the second wavelength (i.e., the measurement result 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).
[0114] In the case of a spherical sample Sl (i.e., a sample having a shape that is linearly symmetric with respect to an axis parallel to the Z-axis direction), the time that the sample Sl 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 that the sample Sl 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), for the sample Sl, waveforms WA and WB that have the same shape and are shifted in time are observed.
[0115] 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. For this reason, as shown in FIG. 25(B), for sample Sm, the time width of waveform WA is smaller than the time width of waveform WB.
[0116] Therefore, in the above example, the control unit 5 can determine (estimate) that the sample S is spherical (or has a shape close to a sphere) when it can be determined that the time width of the waveform WA and the time width of the waveform WB are the same or similar based on a predetermined criterion based on the waveforms WA and WB obtained by the photodetectors 4A and 4B. 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 width of the waveform WA and the time width of the waveform WB becomes larger. In the example of FIG. 24, when the sample Sm flows through the sample flow path 21 with the longitudinal direction of the sample Sm parallel to the Z-axis direction or the Y-axis direction, the time width of the waveform WA and the time width of the waveform WB may be the same for the sample Sm as for the sample Sl. However, it is considered that it is rare for a non-spherical sample to flow through the sample flow path 21 while maintaining such an attitude, so that the shape of the sample (whether it is spherical or non-spherical) can be determined (estimated) with a certain degree of accuracy by the above measurement method.
[0117] (9th 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 ON / OFF of the laser light L1. For example, the surface-emitting laser 3 blinks the laser light L1 forming the same beam pattern P1 as in the first measurement example (Fig. 12) at a predetermined frequency. Note that in the ninth measurement example, the surface-emitting laser 3 is not necessarily configured to switch 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 to time-modulate a period in which the intensity is sufficiently high (corresponding to the ON state) and a state in which the intensity is sufficiently low (corresponding to the OFF state).
[0118] FIG. 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 modified example (i.e., when the laser light L1 is blinking). Here, 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 pulse shape.
[0119] FIG. 27 is a graph showing the measurement results of the emitted light L2 when the blinking frequency is set to 20 kHz (emission interval: 50 μs), the pitch between the bright parts Pa of the beam pattern P1 (see FIG. 12) is set to 5 μm, and the laser light L1 is pulsed short (when one pulse width is set to several ns). FIG. 28 is a diagram showing an enlarged view of the range Rb in FIG. 27. In the example of FIG. 27, background noise does not exist or is negligibly small. When the laser light L1 is pulsed short in this way, 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 the 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, so that the detection limit of the fluorescence measurement can be improved. The control unit 5 also measures the sample size as described above based on the detection result (measurement value W1) of the emitted light L2, and can also 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 FIG. 27 for the number of stripes. By integrating and averaging the measurement values W2 measured repeatedly multiple times in this way, it is possible to calculate the fluorescence lifetime with high accuracy.
[0120] [Effects] In the laser measurement device 1 described above, a beam pattern P in which bright parts Pa and dark parts Pb are alternately arranged along the flow direction (Z-axis direction) of the flow cell 2 is formed in the sample flow path 21 of the flow cell 2. When the sample S to be measured passes through an area in which such a 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 to be measured. Furthermore, according to the laser measurement device 1, the beam pattern P can be formed with high accuracy and ease by using a single light source (surface emitting laser 3) configured to form the beam pattern P (e.g., striped beam pattern P1 in FIG. 12) in advance. That is, in order to form the beam pattern P, it is not necessary to perform advanced and complicated alignment adjustment of optical members such as a plurality of light sources (i.e., optical axes of laser light emitted from each light source) or a beam splitter for splitting one laser light emitted from one light source into two laser lights. As described above, according to the laser measurement device 1, a beam pattern P suitable for particle measurement using the flow cell 2 can be formed with high accuracy and ease.
[0121] Moreover, by using the surface-emitting laser 3 having the 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 according to a phase distribution corresponding to the beam pattern P with respect to each of the multiple periodically arranged lattice points O. That is, the surface-emitting laser 3 is configured as an iPMSEL. According to the above configuration, the beam pattern P can be suitably and easily formed in the sample flow path 21 by the surface-emitting laser 3 while eliminating the need for the slit member 50 used in the modified light source described later.
[0122] 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 reduce the size of the laser measurement device 1 (module).
[0123] In the method described in Patent Document 1, the two laser beams must be collimated before being incident on the flow cell, but a certain optical path length is required to collimate the laser beams from the light source, which may result in an increase in the size of the measurement device. In contrast, in this embodiment, the surface-emitting laser 3 to which the first and second examples of the phase distribution described above are applied is used as the light source, making it possible to form a fine striped beam pattern P1 in a space relatively close to the light emission surface 3a (for example, about 1 mm). As a result, even if the distance from the light emission surface 3a to the sample flow path 21 is shortened by fixing the surface-emitting laser 3 to the side wall 22 of the flow cell 2, the fine striped beam pattern P1 can be appropriately formed in the sample flow path 21. That is, according to this embodiment, the fine striped beam pattern can be easily and accurately formed in the sample flow path 21, while the laser measurement device 1 can be made smaller.
[0124] 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 plurality of surface-emitting lasers (light source units) are arranged along the flow direction (Z-axis direction). According to the above configuration, by combining the respective beam patterns of the plurality of surface-emitting lasers, it is possible to form a beam pattern in the flow cell 2 that can perform more advanced particle measurement (for example, the measurement in the above-mentioned third to eighth measurement examples) than the particle measurement possible with the beam pattern of a single surface-emitting laser. In addition, by arranging the plurality of surface-emitting lasers along the Z-axis direction, it is possible to share the mounting surface (one side surface 22a of the side wall 22 in this embodiment) of the surface-emitting lasers 3A to 3D relative to the flow cell 2, and therefore the laser measurement device 1 (module) can be made compact.
[0125] Also, as in the fifth to eighth measurement examples, a configuration including a surface-emitting laser 3A emitting a laser beam L1 of a first wavelength and a surface-emitting laser 3B emitting a laser beam L1 of a second wavelength as a 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 a sensor allows for more advanced particle measurement based on measurement results corresponding to a plurality of different wavelengths. In the above embodiment (fifth to eighth measurement examples), the laser measurement device 1 includes a plurality (two) of photodetectors 4A and 4B that are physically different for each wavelength, but the laser measurement device 1 may include a single photodetector that can distinguish and detect the measurement results (first signal and second signal) for each wavelength. An example of such a photodetector is a sensor that combines a plurality of pixels and a filter configured to transmit a different wavelength for each pixel.
[0126] In addition, by using the laser measurement device 1, the following laser measurement method can be suitably implemented. That is, the laser measurement method includes a first step of forming a beam pattern P in which at least two bright parts Pa are arranged with a dark part Pb sandwiched between them along the flow direction of the fluid (Z-axis direction) in a sample flow path 21 through which a fluid containing a sample S to be measured passes in the flow cell 2 by emitting laser light L1 from the surface-emitting laser 3 to the flow cell 2, a second step of detecting emitted light L2 emitted from the sample S when the sample S passes through the area in which 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. In addition, the determination process in the third step is performed by the control unit 5. According to the above laser measurement method, the beam pattern P suitable for particle measurement using the flow cell 2 can be formed with high accuracy and ease by the surface-emitting laser 3, so that at least one of the shape and size of the particle can be accurately determined based on the detection result of the emitted light L2 obtained by the beam pattern P.
[0127] [Variations] Although several embodiments and several modified examples of the present disclosure have been described above, the present disclosure is not limited to the configurations shown in the above-mentioned embodiments and modified examples. 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 adopted. In addition, some of the configurations included in the above-mentioned embodiments and modified examples may be omitted or modified as appropriate, and can be combined in any manner.
[0128] In the third to eighth measurement examples, a configuration in which a plurality of surface-emitting lasers 3A to 3D are used as light sources has been described, but the method of arranging the plurality of surface-emitting lasers 3A to 3D is not limited to the method of arranging them on the same side surface 22a of the side wall 22 along the Z-axis direction as shown in FIG. 16. For example, as shown in FIG. 29, a plurality of (two here) surface-emitting lasers 3A and 3B may be arranged along a direction intersecting the Z-axis direction (for example, the circumferential direction of the side wall 22 perpendicular to the Z-axis direction). In this manner, a plurality of (two) surface-emitting lasers 3A and 3B may be provided on different side surfaces 22a and 22b (adjacent side surfaces perpendicular to each other in this example) of the side wall 22. In addition, when detecting forward scattered light from the sample S as emitted light L2 as in the above embodiment, a photodetector 4A 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 3A may be arranged at 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.
[0129] FIG. 30 is a schematic diagram showing the configuration of a laser measurement device 1A according to a first modified example. As in the laser measurement device 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 part of the forward scattered light (emitted light L2) emitted at a constant emission angle. In addition, in order to improve the light receiving efficiency in the photodetector 4, the photodetector 4 may be fixed to the side wall 22 of the flow cell 2. According to the above configuration, the optical system 6 in the laser measurement device 1 in FIG. 1 can be omitted, and by fixing the photodetector 4 to the flow cell 2, the laser measurement device 1A (module) can be further miniaturized.
[0130] 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 shielding 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. The photodetector 4C is also disposed at a position away from the flow cell 2, similar to the photodetector 4 of the laser measurement device 1. According to the laser measurement device 1B, the emitted light L2 that advances while expanding at a relatively large angle can be detected by the photodetector 4C 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 of the first modification. Furthermore, according to the laser measurement device 1B, like 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, so that the laser measurement device 1B (module) can be made even more compact.
[0131] In the above embodiment, a striped (linear) pattern and a dotted (pointed) pattern are exemplified as the pattern shape of the beam pattern formed in the sample flow channel 21, but the pattern shape of the beam pattern is not limited to the above two shapes. For example, a beam pattern having a shape in which a plurality of bright parts Pa extending in the Y-axis direction and having a bent part C are arranged along the Z-axis direction, as in the beam pattern PM1 in FIG. 32(A), instead of a linear shape, may be used. Also, a striped beam pattern having bright parts Pa configured such that the curvature gradually changes toward the downstream side, as in the beam pattern PM2 in FIG. 32(B), may be used. According to such a beam pattern PM2, it is possible to correct the flow velocity difference between the center part and the outer edge part in the Y-axis direction of the sample flow channel 21, and to obtain a signal that is purely dependent on the size (particle diameter) of the sample S, regardless of which position in the Y-axis direction of the sample flow channel 21 the sample S passes through.
[0132] In the above embodiment, the 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 may be disposed in the emission direction of the side scattered light with respect to the sample S, not in a position facing the surface-emitting laser 3. In addition, while detecting the forward scattered light as the emitted light L2 for determining the shape or size of the particle, the side scattered light may also be detected as information for analyzing the type of particle. In this case, a photodetector for detecting the side scattered light may be provided separately from the photodetector 4 for detecting the emitted light L2 (forward scattered light).
[0133] In the above embodiment, a flow cell is used as an example of a flow path device, but the flow path device may 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.
[0134] 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 each light source unit when the light source includes a plurality of light source units), 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 the interference of the emitted light, but such a double slit may be realized by a physical slit member. Below, modified examples (first modified example and second modified example) of the light source using such a mechanism will be described.
[0135] (First modified example of light source) A first modified example 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 is mainly different from the surface-emitting laser 3 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 antireflection film 19 provided on the back surface 10b within the opening 17a of the electrode 17.
[0136] As described above, in the phase modulation layer 15, the center of gravity G of each of the multiple modified refractive index areas 15b is disposed at a relative position according to the phase distribution corresponding to the beam pattern P with respect to each of the multiple lattice points O that are periodically arranged. In contrast, the phase modulation layer 15A is configured as a photonic crystal layer in which the multiple modified refractive index areas 15b 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 15b coincides with the position of each of the multiple lattice points O that are periodically arranged. In other words, the surface-emitting laser 31 is configured as a photonic crystal surface-emitting laser (PCSEL: Photonic Crystal Surface Emitting Laser) that emits coherent (vertical and horizontal single mode) light from the back surface 10b.
[0137] The slit member 50 is a member for forming a 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, 50b (slits). That is, in the example of FIG. 33, instead of a double slit formed artificially by the first region 151 and the second region 152 (see FIG. 9), a double slit is realized by the openings 50a, 50b of the physical 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 an interference fringe (for example, a 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, 50b.
[0138] 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 a desired beam pattern. In the example of FIG. 33, the surface-emitting laser 31 is integrally formed with the slit member 50, but 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.
[0139] (Second modified example of light source) A second modified example of the light source (a combination of a surface-emitting laser 32 and a slit member 50) will be described with reference to FIG. 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, the cladding layer 11, the active layer 12, the cladding layer 13, the contact layer 14, and the 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 configured 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 has, 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 constituted by, for example, a P-type multilayer film reflector (DBR), and is formed on the active layer 323.
[0140] 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. The surface-emitting laser 32 may also be formed with a current confinement structure for suitably emitting coherent light.
[0141] The slit member 50 is a plate-like member in which double slits (openings 50a, 50b) are formed similarly 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 as described above, the distance between the emission surface of the surface-emitting laser 32 (the surface opposite to the semiconductor substrate 321 side of the electrode 17) and the slit member 50 may be set to, for example, about several hundred μm.
[0142] 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.
[0143] Moreover, 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.
[0144] FIG. 35 is a plan view showing an example in which a refractive index approximately periodic structure is applied in a specific region of the phase modulation layer 15 shown in FIG. 11. In the example shown in FIG. 35, an approximately periodic structure (for example, the structure shown in FIG. 7) for emitting a desired optical image is formed inside the square inner region RIN. Meanwhile, a circular modified refractive index region 15b in which the lattice point position of the square lattice coincides with the center of gravity position is arranged in the outer region ROUT surrounding the inner region RIN. The lattice interval a of the virtually set square lattice is the same inside the inner region RIN and in the outer region ROUT. In the case of the structure shown in FIG. 38, light is also distributed in the outer region ROUT, so that it is possible to suppress the generation of high-frequency noise (so-called window function noise) caused by a sudden change in light intensity in the periphery of the inner region RIN. In addition, it is possible to suppress light leakage in a direction perpendicular to the thickness direction, and a reduction in threshold current can be expected. However, without being limited to this example, 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.
[0145] In order to obtain a desired distribution of the light-collecting points U, the rotation angle distribution α(x, y) of the modified refractive index area 15b in the phase modulation layer 15 (the first area 151 and the second area 152) is determined by the following procedure.
[0146] As a first precondition, 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-shaped M 1 ×N 1 pieces (M 1 ,N 1 A virtual square lattice composed of unit constituent regions R (R is an integer equal to or greater than 1) is set on the XY plane.
[0147] The second prerequisite is that the coordinates (ξ, η, ζ) in the XYZ Cartesian coordinate system are expressed as the length of the moving radius r and the inclination angle θ from the Z axis, as shown in Figure 36. 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 ) satisfies the relationship 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 specified plane that is set in the XYZ Cartesian coordinate system, which is real space.
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[0151] The light emitted from the surface emitting laser 3 is reflected by the incident light at an angle θ tilt and θ rot When the set of bright points is defined as a set of bright points facing in the direction defined by the angle θ tilt and θ rotis 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 the wave number normalized by taking the wave number 2π / a, which corresponds to the lattice spacing of a virtual square lattice, as 1.0. In this case, K x Axes and K y In the wavenumber space defined by the axis, a specific wavenumber range that includes a beam pattern corresponding to a light image is a square-shaped M 2 ×N 2 pieces (M 2 ,N 2 The image area FR is composed of the integer M 2 is an integer M 1 Similarly, the integer N 2 is an integer N 1 It is not necessary that the formula (4) and the formula (5) are identical to those shown in FIG. 1. Equations (4) and (5) are disclosed in, for example, Y. Kurosaka et al., "Effects of non-lasing band in two-dimensional photonic-crystal lasers clarified using omnidirectional band structure," Opt. Express 20, 21773-21783 (2012).
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[0154] 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 to N 2 -1 or less) to define the coordinate component x(0 or more M 1 -1 or less) and the Y-axis 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 unitary constituent region R(x,y) on the XY 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 unitary 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 unitary constituent region R(x,y).
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[0157] 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 disposed away from the lattice point O(x,y) in the unit configuration 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×N 1 With the angle α(x, y) between the line segment connecting the lattice point O(x, y) and the corresponding center of gravity G and the s-axis, which is set to a common value in each unit constituent region R, the corresponding modified refractive index region 15b is positioned within the unit constituent region R(x, y) so that the angle α(x, y) between the line segment connecting the lattice point O(x, y) and the corresponding center of gravity G and the s-axis satisfies the following relationship. α(x,y)=C×φ(x,y)+B C: proportionality constant, e.g. 180° / π B: Any constant, e.g. 0
[0158] Next, the M-point oscillation of the surface-emitting laser 3 will be described. For the surface-emitting laser 3 to oscillate at the M-point (i.e., to oscillate at the M-point band edge), the lattice spacing a of the 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 a reciprocal lattice space related to a 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 a 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).
[0159] 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 is not 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, not only the 0th order light in the direction perpendicular to the plane (Z-axis direction) but also +1st order light and -1st order light in the direction inclined with respect to the Z-axis direction will not be output in the M-point oscillation surface emitting laser 3.
[0160] For example, in the M-point oscillation surface emitting laser 3, the following device is applied to the phase modulation layer 15 (first region 151 and second region 152), so that the 0th order light is not output and a part of the +1st order light and the -1st order light can be output. That is, 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 (the in-plane wave vector K3 in the figure) is made smaller than 2π / λ (λ: wavelength of 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 the light line LL, which is a circular region with a radius of 2π / λ.
[0161] In FIG. 38, the in-plane wave vectors K1 to K4 shown by dashed lines represent the wave vectors before the addition of the diffraction vector V1, and the in-plane wave vectors K1 to K4 shown 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 a wave vector having a magnitude that falls within the light line LL has 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 within the range of 2π / (√2)a-2π / λ to 2π / (√2)a+2π / λ, and in one example, is 2π / (√2)a.
[0162] Next, 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 will be considered. The following formulas (8) to (11) show the in-plane wave vectors K1 to K4 before the diffraction vector V1 is added.
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[0169] When the diffraction vector V1 is expressed as in the following formula (14), the in-plane wave number vectors K1 to K4 after the diffraction vector V1 is added become the following formulas (15) to (18).
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[0175] In formulas (15) to (18), when 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.
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[0177] The size (radius) of the light line LL is set to 2π / λ for the following reason. FIG. 39 is a diagram for explaining a schematic structure around the light line LL. This 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 a medium with a refractive index of n is 2πn / λ. At this time, 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).
[0178] In Fig. 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)sinθ. 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. At this time, 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.
[0179] 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 For (x,y), the phase distribution φ is independent of the desired output beam shape. 2 In this case, the phase distribution φ(x, y) of the phase modulation layer 15 (the first region 151 and the 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. Also, φ 2 (x, y) is the phase distribution for adding the diffraction vector V1 that satisfies the above equation (19).
[0180] Figure 40 shows the phase distribution φ 2 FIG. 1 is a diagram conceptually illustrating an example of (x, y). In the example of the diagram, 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 In this case, the first phase value φ is A and a second phase value φ B and change by π. Such an arrangement of phase values can 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 and any one of the in-plane wave vectors K1 to K4 in FIG. 9 are exactly offset. Therefore, the axis of symmetry between the +1st order light and the -1st order light coincides with the Z direction, that is, the direction perpendicular to the in-plane direction of the phase modulation layer 15. In general, the angular distribution θ of the diffraction vector V 2 (x, y) is expressed as the inner product of the diffraction vector V(Vx, Vy) and the position vector r(x, y), and is given by the following equation. θ 2 (x,y) = V r = Vx x + Vy y
[0181] Therefore, when V=V1, the phase value is 0 and π when the position vector is 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 is within the range of the light line LL.
[0182] In this embodiment, when the wave number spread based on the angular spread of the emitted light is included in a circle of radius Δk centered on a certain point in wave number space, it can be simply considered as follows. By adding the diffraction vector V1 to the in-plane wave number vectors K1 to K4 in four directions, the magnitude of at least one of the in-plane wave number vectors K1 to K4 in four directions is made smaller than 2π / λ (light line LL). This can be considered as making the magnitude of at least one of the in-plane wave number vectors K1 to K4 in four directions smaller than the value {(2π / λ)-Δk} obtained by subtracting the wave number spread Δk from 2π / λ by adding the diffraction vector V1 to the in-plane wave number vectors K1 to K4 in four directions.
[0183] FIG. 41 is a diagram conceptually illustrating the above-mentioned idea. As shown in the figure, when a diffraction vector V1 is added to the 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, the region LL2 is a circular region with a radius of {(2π / λ)-Δk}. In FIG. 41, the in-plane wave vectors K1 to K4 shown by the dashed lines represent the state before the diffraction vector V1 is added, and the in-plane wave vectors K1 to K4 shown by the solid lines represent the state after the diffraction vector V1 is added. The region LL2 corresponds to the total reflection condition considering the wave number spread Δk, and the wave vectors whose magnitude falls within the region LL2 will also propagate in the direction perpendicular to the surface (Z-axis direction).
[0184] 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.
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[0189] Here, when the diffraction vector V1 is expressed as in the above-mentioned formula (14), the in-plane wave number vectors K1 to K4 after the diffraction vector V1 is added are expressed by the following formulas (24) to (27).
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[0194] 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) is established. 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.
[0195]
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[0196] 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 FIG. 42 and FIG. 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 area 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 (X-axis) of the square lattice is β.
[0197] In this case, the tilt angle β is constant in 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 inclination 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 inclination angle β is an angle excluding 0°, 90°, 180°, and 270°.
[0198] Here, the distance between the lattice point O and the center of gravity G is r(x,y). x is the position of the x-th lattice point on the X-axis, and y is the position of the y-th 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°, and 275°. At these tilt angles, only two of the four wave vectors (for example, in-plane wave vectors (±π / a, ±π / a)) that form the standing wave at point M are phase modulated, and the other two are not phase modulated, so that a stable standing wave can be formed.
[0199] 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 shape of the emitted light. In the present disclosure, such an arrangement form of the center of gravity G is referred to as the second form. 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 the distance r(x, y) is determined by extracting the phase distribution φ(x, y) from the complex amplitude distribution obtained by performing an inverse Fourier transform on the desired shape of the emitted light.
[0200] That is, the phase φ(x,y) at a certain coordinate (x,y) is φ 0 If so, set the distance r(x,y) to 0 and the phase φ(x,y) to π+φ 0 If so, the distance r(x,y) is set to the maximum value R 0 and the phase φ(x,y) is set to -π+φ 0 If so, set the distance r(x,y) to the minimum value -R 0 For the intermediate phase φ(x,y), we set r(x,y)={φ(x,y)-φ 0}×R 0 Set the distance r(x,y) so that / π. The initial phase φ 0 can be set arbitrarily.
[0201] If the lattice spacing of a virtual square lattice is a, the maximum value of r(x,y) is R 0 is within the range of the following formula (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.
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[0203] In this second embodiment, a desired light emission shape (number, position, etc. of light-collecting points) can be obtained by determining the distribution of the distance 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 first to fourth preconditions similar to those of the first embodiment, the phase modulation layer 15 (first region 151 and second region 152) is configured to satisfy the following conditions. That is, the corresponding modified refractive index area 15b is arranged in the unit configuration area 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. When a desired light emission shape is to be obtained, the light emission shape is subjected to an inverse Fourier transform, and a distribution of the distance r(x, y) according to the phase φ(x, y) of the complex amplitude is given 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)-φ 0 ) C: Proportional constant, e.g. R 0 / π φ 0 : Any constant, e.g. 0
[0204] In the second embodiment, the light emitting device oscillating at point M is designed as follows in the phase modulation layer 15 (first region 151 and second region 152) to output a part of +1st order light and -1st order light without outputting the 0th order light into the light line LL. 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. That is, 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 part of the +1st order light and -1st order light is output.
[0205] 41, by adding a diffraction vector V1 to the in-plane wave vectors K1 to K4 in four directions minus the wave number spread Δk (i.e., the in-plane wave vectors in four directions in an M-point oscillation square lattice PCSEL), the magnitude of at least one of the in-plane wave vectors K1 to K4 in four directions may be made smaller than the value obtained by subtracting the wave number spread Δk from 2π / λ {(2π / λ)-Δk}. That is, by adding a diffraction vector V1 that satisfies the above-mentioned formula (28), any one of the in-plane wave vectors K1 to K4 falls within the region LL2, and a part of the +1st order light and the -1st order light is output.
[0206] As a result, in the light extraction region 15P, the 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 part of the +1st order light and the -1st order light is output only from the first region 151 and the second region 152. As a result, as shown in Fig. 15, a pseudo double slit is formed in the phase modulation layer 15 with each of the first region 151 and the second region 152 as a slit, and interference fringes due to interference of the output light can be formed in the Fresnel region. [Explanation of symbols]
[0207] 1, 1A... laser measurement device, 2... flow cell (flow path device), 3, 3A to 3D, 31, 32... surface emitting laser (light source, light source section), 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... passing area, S, Sa to Sm... sample (particle).
Claims
1. 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 having a beam pattern in which at least two bright portions are arranged with a dark portion sandwiched between them along a flow direction of the fluid toward the sample flow path; a sensor that detects light emitted from the particle when the particle passes through a region in the sample flow path where the beam pattern is formed; A laser measurement device comprising:
2. The light source is A light emitting portion; 2. The laser measurement device according to claim 1, further comprising a surface-emitting laser optically coupled to the light-emitting section and including a base layer and a phase modulation layer including a plurality of modified refractive index areas having a refractive index different from that of the base layer.
3. 3. The laser measurement device according to claim 2, wherein the center of gravity of each of the plurality of modified refractive index areas is arranged at a relative position in accordance with a phase distribution corresponding to the beam pattern with respect to each of a plurality of periodically arranged lattice points.
4. the phase modulation layer is a photonic crystal layer in which the multiple modified refractive index areas are periodically arranged, 3. The laser measurement device according to claim 2, wherein the light source further comprises a slit member that forms the laser light having the beam pattern by passing the light emitted from the surface emitting laser.
5. The light source is a vertical cavity surface emitting laser; 2. The laser measurement device according to claim 1, further comprising: 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 claim 1 , wherein the light source is fixed to a side wall of the flow passage device.
7. The laser measurement device according to claim 1 , 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.
8. 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; 8. The laser measurement device according to claim 7, wherein the surface-emitting laser forms the striped beam pattern by causing interference between light beams emitted from a plurality of different regions in an in-plane direction of a light emission surface of the surface-emitting laser.
9. The laser measurement device according to claim 1 , wherein the light source includes a plurality of light source units arranged along the flow direction.
10. The laser measurement device according to claim 1 , wherein the light source includes a plurality of light source units arranged along a direction intersecting the flow direction.
11. each of the plurality of light source units is configured to form, in the sample flow channel, a striped beam pattern 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; 11. The laser measurement device according to claim 9, wherein the beam patterns of the plurality of light source units are arranged so as not to overlap with each other in a passage region in the sample flow path through which the particles pass.
12. 11. The laser measurement device of claim 9, wherein the plurality of light source units form a first bright portion having a brightness of a first intensity in a first range region in a first direction intersecting the flow direction, and form a second bright portion having a brightness of a second intensity different from the first intensity in a second range region different from the first range in the first direction.
13. the light source includes a first light source unit that emits the laser light having a first wavelength and a second light source unit that emits the laser light having a second wavelength different from the first wavelength, 2. The laser measurement device of claim 1, wherein the sensor detects a first signal corresponding to a 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 a second emitted light emitted in response to the laser light of the second wavelength being irradiated onto the particle.
14. 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, 14. The laser measurement device according to claim 13, wherein 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.
15. 14. The laser measurement device according to 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 positions shifted 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 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, The laser measurement device according to claim 13 , wherein 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. The laser measurement device according to claim 1 , wherein the light source time-modulates the intensity of the laser light.
19. A laser measurement method using the laser measurement device according to claim 1, forming a beam pattern in a sample flow path through which a fluid containing particles to be measured passes in the flow path device, the beam pattern including at least two bright portions arranged with a dark portion sandwiched therebetween along a flow direction of the fluid, by emitting the laser light from the light source to the flow path device; detecting light emitted from the particle as the particle passes through an area in which the beam pattern is formed; determining at least one of a shape and a size of the particle based on the detected emitted light; A laser measurement method comprising:
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Laser interference type flow cytometry device
JP2022077967A