Raman scattered light detection device and raman scattered light detection method

Abstract

Provided is a Raman scattered light detection device and a Raman scattered light detection method, whereby Raman spectroscopic analysis of particles in a liquid can be effectively carried out.　This Raman scattered light detection device comprises: an optical system for irradiating particles in a liquid with first light; a detector that detects Raman scattered light generated from the particles irradiated with the first light; a position measurement unit that measures the position of the particles; and a position adjustment unit that aligns the focal point position of the optical system with the position of the particles on the basis of the position of the particles measured by the position measurement unit. The position measurement unit has an interferometer that acquires an interference fringe-containing image for measuring interference between a reference light and second light that is irradiated onto the particles in a direction different from that of the first light and that is reflected by the particles.

Description

Raman Scattering Light Detection Device and Raman Scattering Light Detection Method

[0001] The present invention relates to a Raman scattering light detection device and a Raman scattering light detection method.

[0002] It is sometimes necessary to analyze particles in a liquid. For example, powders may be dispersed in a liquid, and the components of the particles contained in the powders may be analyzed. As a technique for analyzing particles in a liquid, Raman spectroscopic analysis can be mentioned. Patent Document 1 discloses a technique for performing Raman spectroscopic analysis of particles in a liquid.

[0003] Japanese Patent Application Laid-Open No. 2007-292704

[0004] In order to perform Raman spectroscopic analysis, it is necessary to irradiate light to a sample using an optical system. In order to perform Raman spectroscopic analysis effectively, it is desirable to irradiate light to the sample after aligning the position of the focus of the optical system with the position of the sample. When the particles in the liquid are the sample, it is difficult to align the position of the focus of the optical system with the position of the particles because the position of the particles is not easily determined. Therefore, it is difficult to effectively perform Raman spectroscopic analysis of particles in a liquid.

[0005] An object of the present invention is to provide a Raman scattering light detection device and a Raman scattering light detection method that enable effective Raman spectroscopic analysis of particles in a liquid.

[0006] A Raman scattering light detection device according to one embodiment of the present invention includes an optical system for irradiating a first light to particles in a liquid, a detector for detecting Raman scattering light generated from the particles irradiated with the first light, a position measurement unit for measuring the position of the particles, and a position adjustment unit for aligning the position of the focus of the optical system with the position of the particles based on the position of the particles measured by the position measurement unit. The position measurement unit has an interferometer that measures interference between a second light irradiated to the particles in a direction different from the first light and reflected by the particles and a reference light.

[0007] In one embodiment of the present invention, the Raman scattering light detection device measures the position of particles in a liquid using an interferometer, aligns the focal point of the optical system for irradiating light with the position of the particles based on the measured particle position, irradiates the particles with light, and detects the Raman scattered light. Because the position of particles in a liquid is measured, the Raman scattering light detection device can accurately align the focal point of the optical system with the position of the particles. As a result, the Raman scattering light detection device can increase the intensity of the light irradiated onto the particles, increase the intensity of the generated Raman scattered light, and increase the intensity of the detected Raman scattered light.

[0008] In a Raman scattering light detection device according to one embodiment of the present invention, the interferometer generates an image including interference fringes generated by the interference of the second light and the reference light, and the position measuring unit adjusts the position of the holder that holds the liquid containing the particles with respect to the interferometer, or the length of the optical path of the reference light, and measures the position of the particles according to the position of the interference fringes in the image acquired while the position of the holder with respect to the interferometer or the length of the optical path of the reference light has been adjusted.

[0009] In one embodiment of the present invention, the Raman scattering light detection device adjusts the position of a holder that holds a liquid containing particles, or the length of the optical path of a reference light that interferes with the light reflected from the particles. Depending on the position of the holder or the length of the optical path of the reference light, the position of the interference fringes included in the image generated by the interferometer changes. Depending on the position of the interference fringes, the position of the particles is determined.

[0010] In a Raman scattering light detection device according to one embodiment of the present invention, the reference light is light separated from the second light midway through the optical path of the second light, the interferometer has a reference mirror that reflects the reference light, the reference mirror is inclined with respect to the optical path of the reflected reference light such that the length of the optical path of the reference light differs depending on the position where the reference light is reflected, the interferometer generates an image including interference fringes generated by the interference between the second light and the reference light, and the position measuring unit measures the position of the particle according to the position of the interference fringes in the image.

[0011] In one embodiment of the present invention, the reference mirror that reflects the reference light is inclined with respect to the optical path of the reflected reference light. Depending on which part of the reference mirror the reference light is reflected from, the length of the optical path of the reference light differs, the length of the optical path between the light reflected from the particle and the reference light differs, and interference fringes are included in the image generated by the interferometer. When light from the interferometer irradiates a particle, the length of the optical path of the light reflected from the particle changes, the position of the interference fringes in the image changes, and the position of the particle is determined according to the position of the interference fringes.

[0012] A Raman scattering light detection device according to one embodiment of the present invention is characterized by irradiating the particles contained in the liquid flowing through the channel with the first light and the second light.

[0013] In one embodiment of the present invention, a channel through which a liquid containing particles flows is used, and the Raman scattering light detection device irradiates the particles contained in the liquid flowing through the channel with light to generate Raman scattering light and light from an interferometer. Raman scattering light can be detected for each particle contained in the liquid flowing through the channel, and Raman spectroscopic analysis can be performed.

[0014] In a Raman scattering light detection device according to one embodiment of the present invention, the position where the second light is irradiated is upstream of the flow path compared to the position where the first light is irradiated.

[0015] In one embodiment of the present invention, the position where the second light from the interferometer is irradiated is upstream of the position where the first light is irradiated. During the process of measuring the position of particles in the liquid using the interferometer, the particles move, and by the time the process of detecting Raman scattered light begins, the particles have reached the position where the first light is irradiated. Therefore, the Raman scattered light detection device can smoothly detect the Raman scattered light of the moving particles.

[0016] A Raman scattering light detection method according to one embodiment of the present invention is characterized in that the position of a particle in a liquid is measured, the position of the focal point of an optical system for irradiating the particle with light is aligned with the position of the particle based on the measured position of the particle, a first light is irradiated onto the particle using the optical system while the position of the focal point and the position of the particle are aligned, and Raman scattered light generated from the particle irradiated with the first light is detected, and the measurement of the position of the particle is performed using an interferometer that acquires an image including interference fringes generated by a second light irradiated onto the particle in a direction different from the first light and reflected by the particle, and a reference light.

[0017] In one embodiment of the present invention, the position of particles in a liquid is measured using an interferometer, the focal point of an optical system for irradiating light is aligned with the position of the particles, light is irradiated onto the particles, and Raman scattered light is detected. Based on the measured position of the particles in the liquid, the focal point of the optical system is aligned with the position of the particles. It becomes possible to increase the intensity of the light irradiated onto the particles, increase the intensity of the generated Raman scattered light, and increase the intensity of the detected Raman scattered light, thereby enabling effective Raman spectroscopy.

[0018] The present invention offers excellent advantages, such as enabling effective Raman spectroscopy analysis of particles in liquids.

[0019] This is a block diagram showing an example configuration of a Raman scattering light detection device according to Embodiment 1. This is a block diagram showing an example configuration of the inside of the control unit. This is a flowchart showing an example of the processing procedure performed by the Raman scattering light detection device. This is a schematic diagram showing an example of a planar image and a side view image of a particle 62 including interference fringes. This is a block diagram showing an example configuration of a Raman scattering light detection device according to Embodiment 2. This is a block diagram showing an example configuration of a Raman scattering light detection device according to Embodiment 3. This is a schematic diagram showing an example of a particle image and an interference fringe image.

[0020] The present invention will be described in detail below based on the drawings illustrating its embodiments. <Embodiment 1> Figure 1 is a block diagram showing an example configuration of a Raman scattering light detection device 100 according to Embodiment 1. The Raman scattering light detection device 100 performs a Raman scattering light detection method. The Raman scattering light detection device 100 is a device for detecting Raman scattered light from particles 62 in a liquid 61 and performing Raman spectroscopic analysis. The liquid 61 contains a plurality of particles 62. For example, the plurality of particles 62 are obtained by dispersing powder in the liquid 61.

[0021] The liquid 61 containing particles 62 flows through the channel 51. The channel 51 is a structure with grooves formed in which the liquid flows. The channel 51 is configured so that the liquid flows unilaterally in a straight line or curved direction. Preferably, the channel 51 is made of a light-transmitting material. The channel 51 corresponds to a holder that holds the liquid 61 containing particles 62. As the liquid 61 flows through the channel 51, the particles 62 contained in the liquid 61 also flow through the channel 51. In the figure, the direction in which the particles 62 flow is indicated by white arrows. The direction in which the liquid 61 flows through the channel 51 is defined as the X direction. Therefore, the particles 62 generally flow along the X direction. The vertical direction is defined as the Z direction, and the direction intersecting the X and Z directions is defined as the Y direction. The Y direction is the direction intersecting Figure 1.

[0022] The flow channel 51 is mounted on a Z-stage 52 that can move along the Z-direction. The Raman scattering light detection device 100 includes a stage drive unit 53 that moves the Z-stage 52 along the Z-direction. The stage drive unit 53 is a drive mechanism configured, for example, using a motor. As the stage drive unit 53 moves the Z-stage 52, the flow channel 51 moves along the Z-direction, and the particles 62 flowing through the flow channel 51 also move along the Z-direction.

[0023] The Raman scattering light detection device 100 includes an optical system 2 for irradiating particles 62 in a liquid 61 with light. The optical system 2 includes a first light source 21, a dichroic mirror 22, and a lens 23. The first light source 21 is, for example, a laser light source. Light generated from the first light source 21 is reflected by the dichroic mirror 22, passes through the lens 23, and is irradiated onto the particles 62. The light generated from the first light source 21 and irradiated onto the particles 62 corresponds to the first light. When irradiated with light, Raman scattered light is generated from the particles 62.

[0024] The Raman scattering light detection device 100 comprises a spectrometer 31 and a detector 32 for detecting light. The detector 32 is a photodetector. The Raman scattered light generated by the particle 62 is focused by the lens 23, passes through the dichroic mirror 22, and enters the spectrometer 31. In Figure 1, the optical paths of the light irradiated onto the particle 62 and the Raman scattered light are shown by solid arrows. The spectrometer 31 spectrally separates the incident Raman scattered light. The detector 32 detects the light of each wavelength spectrally separated by the spectrometer 31.

[0025] The optical system 2 includes multiple optical components such as slits, filters, mirrors, and lenses for guiding, focusing, and separating the light and Raman scattered light irradiated onto the particle 62. The dichroic mirror 22 and lens 23 are some of the multiple optical components. In Figure 1, optical components included in the optical system 2 other than the dichroic mirror 22 and lens 23 are omitted. The arrangement of the multiple optical components shown in Figure 1 is just one example, and other arrangements are also possible. Figure 1 shows an example in which the same optical system 2 is used for both irradiating the particle 62 with light and focusing the Raman scattered light. The Raman scattered light detection device 100 may have an optical system for focusing the Raman scattered light, separate from the optical system 2 for irradiating the particle 62 with light. The Raman scattered light detection device 100 is configured to focus Raman scattered light whose optical path is along the Z direction.

[0026] The focal point of optical system 2 is the point where light from the first light source 21 converges. By aligning the focal point of optical system 2 with the position of particle 62, the intensity of the light irradiated onto particle 62 is increased, the intensity of the generated Raman scattered light is increased, and the Raman scattered light can be efficiently focused. This makes it possible to effectively perform Raman spectroscopic analysis of particle 62. However, the position of particle 62 is not fixed in liquid 61. In order to align the focal point of optical system 2 with the position of particle 62, it is necessary to measure the position of particle 62 in liquid 61.

[0027] The Raman scattering light detection device 100 includes an interferometer 4 used to measure the position of particles 62 in a liquid 61. The interferometer 4 comprises a second light source 42, an imaging unit 41, a reference mirror 43, a half mirror 44, a beam splitter 45, and a lens 46. The second light source 42 emits white light. For example, the second light source 42 is an LED (Light Emitting Diode) or a halogen lamp. The imaging unit 41 includes an image sensor and performs imaging. The light generated from the second light source 42 passes through the half mirror 44 and the beam splitter 45, then through the lens 46, and is irradiated onto the particles 62.

[0028] The interferometer 4 is configured to irradiate the particle 62 with light from the second light source 42 in a direction different from the light irradiated to the particle 62 by the optical system 2. The Raman scattering light detection device 100 is configured so that the interferometer 4 irradiates the particle 62 with light whose optical path is along the Z direction. For example, the optical system 2 is positioned to irradiate light from above the channel 51, and the interferometer 4 is positioned to irradiate light from below the channel 51. The optical system 2 and the interferometer 4 are positioned so that they irradiate light onto the particle 62 at the same location.

[0029] Light irradiated onto particle 62 is reflected by particle 62, passes through lens 46, then through beam splitter 45 and half mirror 44, and enters the imaging unit 41. By detecting the incident light, the imaging unit 41 generates an image of particle 62. Light generated from the second light source 42, irradiated onto particle 62, reflected by particle 62, and entered the imaging unit 41 corresponds to the second light. In Figure 1, the optical path of the second light is shown by a solid arrow.

[0030] A portion of the light generated from the second light source 42 becomes the reference light. The reference light is separated by the beam splitter 45, reflected by the reference mirror 43, and enters the imaging unit 41 via the beam splitter 45 and the half mirror 44. In Figure 1, the optical path of the reference light is shown by a dashed arrow. The second light, which is irradiated onto the particle 62 and reflected by the particle 62, and the reference light have different optical path lengths and interfere with each other. The image generated by the imaging unit 41 includes interference fringes generated by the interference between the second light and the reference light. The interferometer 4 measures the interference between the second light and the reference light by generating an image that includes the interference fringes.

[0031] The interferometer 4 includes multiple optical components such as filters, mirrors, and lenses for guiding, focusing, and separating the second light and the reference light. The half-mirror 44, beam splitter 45, and lens 46 are some of the multiple optical components. In Figure 1, optical components included in the interferometer 4 other than the half-mirror 44, beam splitter 45, and lens 46 are omitted. The arrangement of the multiple optical components shown in Figure 1 is just one example, and other arrangements of the multiple optical components are also possible.

[0032] The Raman scattering light detection device 100 includes a control unit 1. The first light source 21, spectrometer 31, detector 32, second light source 42, imaging unit 41, and stage drive unit 53 are connected to the control unit 1. The control unit 1 controls the operation of the first light source 21, spectrometer 31, detector 32, second light source 42, imaging unit 41, and stage drive unit 53. The control unit 1 is a control device configured using a computer. An analysis unit 33 is connected to the control unit 1, and a display unit 34 is connected to both the control unit 1 and the analysis unit 33. The analysis unit 33 is an analysis device configured using a computer. The analysis unit 33 acquires the detection result of Raman scattered light detected by the detector 32 via the control unit 1, and performs Raman spectroscopic analysis of the particle 62 based on the detection result of Raman scattered light. The detector 32 may also be directly connected to the analysis unit 33. The display unit 34 is a display device that displays images. The display unit 34 is, for example, a liquid crystal display or an EL display (Electroluminescent Display).

[0033] Figure 2 is a block diagram showing an example of the internal configuration of the control unit 1. The control unit 1 is configured using a computer such as a personal computer. The control unit 1 comprises an arithmetic unit 11, a memory 12, a reading unit 13, a storage unit 14, an operation unit 15, and an interface unit 16. The arithmetic unit 11 is a processor and is configured using, for example, a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), or a multi-core CPU. The arithmetic unit 11 may also be configured using a quantum computer. The memory 12 stores temporary data generated in connection with calculations. The memory 12 is, for example, RAM (Random Access Memory). The reading unit 13 reads information from a recording medium 10 such as an optical disc or portable memory. The storage unit 14 is non-volatile and is, for example, a hard disk or non-volatile semiconductor memory. The operation unit 15 accepts input of information such as text by receiving operations from the user. The operation unit 15 is, for example, a touch panel, a keyboard, or a pointing device.

[0034] The arithmetic unit 11 causes the reading unit 13 to read the computer program (program product) 141 recorded on the recording medium 10, and stores the read computer program 141 in the storage unit 14. The arithmetic unit 11 executes the necessary processing for the control unit 1 according to the computer program 141. The computer program 141 may be downloaded from outside the control unit 1. Alternatively, the computer program 141 may be stored in the storage unit 14 in advance. In these cases, the control unit 1 does not need to have a reading unit 13.

[0035] The computer program 141 can be deployed on a single computer, at a single site, or distributed across multiple sites and run on multiple computers interconnected by a communication network. That is, the control unit 1 may consist of multiple computers, and the computer program 141 may run on multiple computers connected via a communication network. The control unit 1 may be configured using a cloud server. The control unit 1 and the analysis unit 33 may be configured on the same computer.

[0036] The processing steps described below for performing the Raman scattering light detection method can be performed on multiple computers. Each step can also be performed on different computers. The data used during processing may be stored on multiple computers. Each step can also be performed using a virtual machine. Each step may be performed by multiple processing units. Each step may be performed by different processing units. For example, part of the processing may be performed on one computer, and other parts on other computers.

[0037] The rest of the Raman scattering light detection device 100 is connected to the interface unit 16. The user inputs various instructions, such as an instruction to start measurement, to the control unit 1 by operating the operation unit 15. The control unit 1 receives the instructions input using the operation unit 15. The control unit 1 outputs the information necessary for Raman scattering light detection and Raman spectroscopy analysis by displaying an image containing the information on the display unit 34.

[0038] The control unit 1 receives information necessary for control by receiving signals from each part of the Raman scattering light detection device 100 through the interface unit 16. The control unit 1 controls the operation of each part of the Raman scattering light detection device 100 by transmitting control signals to each part of the Raman scattering light detection device 100 through the interface unit 16.

[0039] Figure 3 is a flowchart showing an example of the procedure performed by the Raman scattering light detection device 100. In Embodiment 1, the following processes S1 to S4 are performed with the movement of the particles 62 in the flow path 51 substantially stopped. The Raman scattering light detection device 100 measures the position of the particles 62 flowing in the flow path 51 (S1). In S1, first, the interferometer 4 irradiates the particles 62 with light. At this time, the calculation unit 11 transmits a control signal from the interface unit 16 to the second light source 42, causing the control unit 1 to operate the second light source 42. The second light source 42 emits light, which irradiates the particles 62, and the light reflected by the particles 62 enters the imaging unit 41. In addition, the reference light reflected by the reference mirror 43 enters the imaging unit 41. The second light irradiated onto the particles 62 and reflected by the particles 62 interferes with the reference light.

[0040] The imaging unit 41 generates an image of the particle 62. Because the particle 62 has irregularities, the length of the optical path of the second light differs depending on which part of the particle 62 is illuminated. That is, depending on which part of the particle 62 is illuminated, the difference in the optical path lengths between the second light and the reference light differs, the brightness of the interference light resulting from the interference of the second light and the reference light differs, and interference fringes are generated. In the interferometer 4 using a white light source as the second light source 42, light of multiple wavelengths is mixed, so when the difference in the optical path lengths between the second light and the reference light becomes zero, the phases coincide at all wavelengths and the interference fringes become strongest. The larger the difference in the optical path lengths between the second light and the reference light, the lower the black and white contrast of the interference fringes. The difference in optical path lengths at which interference fringes are generated is about a few μm. The image generated by the imaging unit 41 includes interference fringes generated by the interference of the second light and the reference light. The imaging unit 41 inputs the generated image to the control unit 1. The calculation unit 11 acquires the image through the interface unit 16.

[0041] Next, the control unit 1 moves the Z-stage 52. At this time, the calculation unit 11 transmits a control signal from the interface unit 16 to the stage drive unit 53, causing the control unit 1 to move the Z-stage 52. As the Z-stage 52 moves, the position of the flow path 51 relative to the interferometer 4 is adjusted. That is, the flow path 51 moves along the Z direction, and the particles 62 move along the Z direction. As the particles 62 move, the length of the optical path of the second light changes, and the interference fringes included in the image generated by the imaging unit 41 change.

[0042] Figure 4 is a schematic diagram showing examples of planar and side images of a particle 62 containing interference fringes. The planar image is an image of the particle 62 observed from the side where the interferometer 4 is located in the Z-axis direction, and is an image generated by the imaging unit 41. The side image is an image of the particle 62 observed in the Y-axis direction. In Figure 4, the planar image is placed on the right and the side image is placed on the left. Figure 4 shows the changes in the planar and side images of the particle 62 in response to the movement of the particle 62 due to the movement of the Z-stage 52. The planar and side images obtained sequentially when the particle 62 is moved so that the optical path of the second light gradually becomes longer are arranged from top to bottom. In the figure, the brightest interference fringe is shown with a dashed line. In reality, multiple bright and dimmer fringes occur. For example, the interference light is brightest when the optical path lengths of the second light and the reference light are the same. In the second planar and side images from the top, the optical path of the second light is longer than in the top planar and side images, so the brightest interference fringe moves to a position closer to the interferometer 4. In the third planar and side view images from the top, the brightest interference fringes are generated at the edge of particle 62 closest to the interferometer 4. In the fourth image from the top, the brightest interference fringes are no longer generated because the optical path of the second beam has become too long.

[0043] The calculation unit 11 performs image processing on the image generated by the imaging unit 41 to identify the position of interference fringes in the image and, according to the position of the interference fringes, identifies the position of the particle 62 along the Z direction. For example, the position in the Z direction where the interference light is brightest is predetermined and stored in the storage unit 14. The calculation unit 11 determines that the portion of the particle 62 corresponding to the brightest interference fringe in the image is at the position where the interference light is brightest. For example, the calculation unit 11 adjusts the position of the flow path 51 so that the brightest interference fringe is generated at the end of the particle 62 closest to the interferometer 4, and identifies that the center of the particle 62 is at a position shifted in the Z direction by the average radius of the particle 62 from the position where the interference light is brightest. In this way, the Raman scattering light detection device 100 measures the position of the particle 62. The processing in S1 by the interferometer 4, Z stage 52, stage drive unit 53, and control unit 1 corresponds to the position measurement unit.

[0044] Next, the Raman scattered light detection device 100 aligns the position of the focal point of the optical system 2 with the position of the particle 62 (S2). The position of the focal point of the optical system 2 is predetermined and stored in the storage unit 14. In S2, the control unit 1 moves the Z stage 52. At this time, the calculation unit 11 transmits a control signal from the interface unit 16 to the stage drive unit 53. As the Z stage 52 moves, the position of the flow path 51 with respect to the optical system 2 is adjusted, and the particle 62 moves along the Z direction. Since the position of the particle 62 is specified in S1, in S2, the particle 62 can be moved so that the position of the focal point of the optical system 2 coincides with the position of the particle 62. For example, the calculation unit 11 moves the Z stage 52 by the magnitude of the difference between the position of the particle 62 specified in S1 and the position of the focal point of the optical system 2, so that the position of the focal point of the optical system 2 coincides with the position of the particle 62. Thus, the Raman scattered light detection device 100 aligns the position of the focal point of the optical system 2 with the position of the particle 62. The process of S2 by the Z stage 52, the stage drive unit 53, and the control unit 1 corresponds to the position adjustment unit.

[0045] Next, the Raman scattered light detection device 100 irradiates the particle 62 with light for generating Raman scattered light in a state where the position of the focal point of the optical system 2 coincides with the position of the particle 62 (S3). In S3, the control unit 1 operates the first light source 21 by the calculation unit 11 transmitting a control signal from the interface unit 16 to the first light source 21. The first light source 21 emits light, and the light is irradiated onto the particle 62. Since the position of the focal point of the optical system 2 coincides with the position of the particle 62, the intensity of the light irradiated onto the particle 62 increases.

[0046] The Raman scattered light detection device 100 detects Raman scattered light generated by the particles 62 (S4). Raman scattered light is generated from the particles 62 irradiated with light. The Raman scattered light enters the spectroscope 31 via the optical system 2. The spectroscope 31 spectroscopes the incident Raman scattered light. The detector 32 detects light of each wavelength spectroscoped by the spectroscope 31. The control unit 1 controls the wavelength of the light spectroscoped by the spectroscope 31. The detector 32 inputs a signal corresponding to the detection intensity of light of each wavelength to the control unit 1. In this way, the Raman scattered light detection device 100 detects Raman scattered light. When performing the processes of S3 to S4, the control unit 1 turns off the second light source 42. It is prevented that the light from the second light source 42 enters the optical system 2 and has an adverse effect on the detection of Raman scattered light.

[0047] The Raman scattered light detection device 100 performs Raman spectroscopic analysis based on the detected Raman scattered light (S5). In S5, the control unit 1 inputs the signal input from the detector 32 to the analysis unit 33. Thereby, the analysis unit 33 acquires information representing the detection intensity of Raman scattered light of each wavelength. The analysis unit 33 generates a Raman spectrum representing the relationship between the Raman shift and the intensity of the detected Raman scattered light based on the acquired information. The analysis unit 33 stores the generated Raman spectrum. The analysis unit 33 may display the Raman spectrum on the display unit 34. The analysis unit 33 may perform analysis regarding the particles 62 based on the Raman spectrum. For example, the analysis unit 33 may perform analysis regarding the chemical bond or crystal structure of the particles 62.

[0048] After S5 ends, the Raman scattered light detection device 100 ends the process. The Raman scattered light detection device 100 appropriately repeats the processes of S1 to S5. For example, the Raman scattered light detection device 100 executes the processes of S$ to S5 for each of the individual particles 62 included in the liquid 61. The Raman scattered light detection device 100 may perform collective analysis using the Raman scattered light detected for a plurality of particles 62.

[0049] As detailed above, the Raman scattering light detection device 100 uses an interferometer 4 to measure the position of particles 62 in the liquid 61, and based on the measured position of particles 62, aligns the focal point of the optical system 2 with the position of particles 62 and detects Raman scattered light. By using the interferometer 4, the Raman scattering light detection device 100 can appropriately measure the position of particles 62 in the liquid 61. Because it measures the position of particles 62 in the liquid 61, the Raman scattering light detection device 100 can accurately align the focal point of the optical system 2, which is used for irradiating light and focusing Raman scattered light, with the position of particles 62. By aligning the focal point of the optical system 2 with the position of particles 62, the Raman scattering light detection device 100 can increase the intensity of the light irradiated onto the particles 62, increase the intensity of the generated Raman scattered light, and increase the intensity of the detected Raman scattered light. By increasing the intensity of the detected Raman scattered light, it becomes possible to effectively perform Raman spectroscopic analysis of particles 62 in the liquid 61.

[0050] Conventionally, to increase the intensity of detectable Raman scattered light, the magnification of the lens is increased. However, when the lens magnification is increased, the depth of field becomes extremely shallow, making it difficult to focus on the sample. When using autofocus with a laser, only the sample located within the laser spot can have its position in the Z direction measured. When the position of the sample particle 62 is measured using the interferometer 4, the accuracy of the measured position of the particle 62 in the Z direction does not depend on the lens magnification. Therefore, by using the interferometer 4, the position of the particle 62 in the Z direction can be measured accurately even at low magnification with reduced lens magnification. At low magnification, the field of view is widened, making it possible to efficiently measure the position of the particle 62 under a wide field of view.

[0051] Conventional Raman scattering light detection devices include an optical system like optical system 2. When an autofocus function is added to a Raman scattering light detection device, the number of optical components such as half mirrors increases, making the optical system more complex and reducing the efficiency of detecting Raman scattered light. Furthermore, the increased complexity of the optical system leads to structural limitations. In the Raman scattering light detection device 100 according to this embodiment, the interferometer 4 is provided at a different location from the optical system 2 for detecting Raman scattered light. Therefore, the optical system 2 does not become more complex, and the efficiency of detecting Raman scattered light does not decrease. Furthermore, no structural limitations arise.

[0052] In Embodiment 1, the Raman scattering light detection device 100 was shown to move the flow path 51 in the Z direction. However, the Raman scattering light detection device 100 may also be configured to move the flow path 51 in directions other than the Z direction. For example, the flow path 51 may be placed on a stage that moves in the X and Y directions, and the position of the particles 62 may be measured and the position of the particles 62 adjusted while moving the flow path 51 in the X or Y direction.

[0053] <Embodiment 2> Figure 5 is a block diagram showing an example configuration of the Raman scattering light detection device 100 according to Embodiment 2. The Raman scattering light detection device 100 does not include a Z-stage 52 and a stage drive unit 53. Therefore, the flow path 51 is fixed. The Raman scattering light detection device 100 can adjust the focal position of the optical system 2. The Raman scattering light detection device 100 includes an optical system drive unit 35 that moves optical components included in the optical system 2. The optical system drive unit 35 is a drive mechanism configured using, for example, a motor. Any of the multiple optical components included in the optical system 2 can be moved to adjust the focal position. For example, the focal position moves when the lens 23 moves. The optical system drive unit 35 moves the focal position by moving optical components such as the lens 23.

[0054] The interferometer 4 is capable of changing the position of the reference mirror 43. The reference mirror 43 can move in a direction toward or toward the beam splitter 45. As the reference mirror 43 moves, the length of the optical path of the reference light is changed. The Raman scattering light detection device 100 includes a mirror drive unit 36 ​​for moving the reference mirror 43. The mirror drive unit 36 ​​is a drive mechanism configured, for example, using a motor or a piezoelectric element. The configuration of the other parts of the Raman scattering light detection device 100 is the same as in Embodiment 1.

[0055] In Embodiment 2, the Raman scattering light detection device 100 detects Raman scattered light from the particle 62 by performing the processes S1 to S5. Similar to Embodiment 1, the processes S1 to S4 are performed with the movement of the particle 62 in the flow path 51 substantially stopped. Similar to Embodiment 1, in S1, the interferometer 4 irradiates the particle 62 with light, the light reflected by the particle 62 enters the imaging unit 41, and the reference light reflected by the reference mirror 43 also enters the imaging unit 41. The imaging unit 41 generates an image of the particle 62. The image includes interference fringes generated by the interference between the second light irradiated onto the particle 62 and reflected by the particle 62 and the reference light. The imaging unit 41 inputs the generated image to the control unit 1.

[0056] In S1, the control unit 1 moves the reference mirror 43. At this time, the calculation unit 11 transmits a control signal from the interface unit 16 to the mirror drive unit 36, causing the control unit 1 to move the reference mirror 43. As the reference mirror 43 moves, the length of the optical path of the reference light is adjusted. As the length of the optical path of the reference light changes, the interference fringes included in the image generated by the imaging unit 41 change. In accordance with the movement of the reference mirror 43, the interference fringes change in the same way as the image shown in Figure 4.

[0057] The calculation unit 11 identifies the position of interference fringes in the image generated by the imaging unit 41 through image processing, and determines the position of the particle 62 along the Z direction according to the position of the interference fringes. For example, the position in the Z direction where the interference light is brightest when the reference mirror 43 is in its initial position is predetermined and stored in the storage unit 14. The calculation unit 11 calculates the position of the particle 62 based on this position in the Z direction, the position of the brightest interference fringe in the image, and the distance the reference mirror 43 has moved. In this way, the Raman scattering light detection device 100 measures the position of the particle 62. The processing in S1 by the interferometer 4, mirror drive unit 36, and control unit 1 corresponds to the position measurement unit.

[0058] In S2, the control unit 1 moves the focus of the optical system 2. At this time, the calculation unit 11 transmits a control signal from the interface unit 16 to the optical system drive unit 35, causing the control unit 1 to move the focus of the optical system 2 to the optical system drive unit 35. The control unit 1 moves the focus of the optical system 2 so that it aligns with the position of the particle 62 measured in S1. The initial position of the focus of the optical system 2 is predetermined and stored in the storage unit 14. For example, the calculation unit 11 aligns the position of the focus of the optical system 2 with the position of the particle 62 by moving the focus by the magnitude of the difference between the position of the particle 62 identified in S1 and the initial position of the focus of the optical system 2. In this way, the Raman scattering light detection device 100 aligns the position of the focus of the optical system 2 with the position of the particle 62. The processing in S2 by the optical system drive unit 35 and the control unit 1 corresponds to the position adjustment unit.

[0059] Subsequently, the Raman scattering light detection device 100 performs the same processing S3 to S5 as in Embodiment 1. The Raman scattering light detection device 100 repeats the processing S1 to S5 as appropriate. For example, the Raman scattering light detection device 100 performs the processing S1 to S5 for each individual particle 62 contained in the liquid 61.

[0060] In Embodiment 2, the Raman scattering light detection device 100 can measure the position of the particles 62 in the liquid 61 and increase the intensity of the detected Raman scattered light by aligning the focal point of the optical system 2 with the position of the particles 62. By increasing the intensity of the detected Raman scattered light, it becomes possible to effectively perform Raman spectroscopy analysis of the particles 62 in the liquid 61.

[0061] In embodiment 1 or 2, the wavelengths of light emitted by the first light source 21 and the second light source 42 may be different from each other. In this embodiment, the Raman scattering light detection device 100 may simultaneously perform the process of detecting Raman scattered light by irradiating the particle 62 with first light from the first light source 21 and the process of acquiring an image including interference fringes by irradiating the particle 62 with second light from the second light source 42.

[0062] <Embodiment 3> Figure 6 is a block diagram showing an example configuration of the Raman scattering light detection device 100 according to Embodiment 3. The Raman scattering light detection device 100 differs from Embodiment 2 in the configuration of the interferometer 4. Also, the Raman scattering light detection device 100 does not include a mirror drive unit 36.

[0063] The interferometer 4 comprises an imaging unit 41, a second light source 42, a reference mirror 43, half mirrors 44 and 47, a beam splitter 45, a lens 46, an infrared light source 48, and an interference fringe imaging unit 49. The infrared light source 48 is a laser light source, an SLD (Super Luminescent Diode), or an LED that emits infrared light. The interference fringe imaging unit 49 includes an image sensor and performs imaging. The imaging unit 41, the second light source 42, the infrared light source 48, and the interference fringe imaging unit 49 are connected to a control unit 1 and controlled by the control unit 1.

[0064] The interferometer 4 is configured to irradiate the particles 62 with light in a different direction than the light irradiated by the optical system 2. The Raman scattering light detection device 100 is configured so that the interferometer 4 irradiates the particles 62 with light whose optical path is aligned in the Z direction. For example, the optical system 2 is positioned to irradiate light from above the channel 51, and the interferometer 4 is positioned to irradiate light from below the channel 51.

[0065] Light generated from the second light source 42 passes through half mirrors 44 and 47 and a beam splitter 45, then through a lens 46, and irradiates the particle 62. The light irradiated onto the particle 62 is reflected by the particle 62, passes through the lens 46, then through the beam splitter 45, half mirrors 47 and 44, and enters the imaging unit 41. By detecting the incident light, the imaging unit 41 generates an image of the particle 62. In Figure 1, the optical path of the light from the second light source 42 is shown by a dashed arrow.

[0066] Light generated from the infrared light source 48 passes through the half mirror 47 and beam splitter 45, then through the lens 46, and is irradiated onto the particle 62. The light irradiated onto the particle 62 is reflected by the particle 62, passes through the lens 46, through the beam splitter 45, and is incident on the interference fringe imaging unit 49. In Embodiment 3, the light generated from the infrared light source 48, irradiated onto the particle 62, reflected by the particle 62, and incident on the interference fringe imaging unit 49 corresponds to the second light. In Figure 6, the optical path of the second light is shown by a solid arrow.

[0067] A portion of the light generated from the infrared light source 48 becomes reference light. The reference light is separated by the beam splitter 45, reflected by the reference mirror 43, passes through the beam splitter 45, and enters the interference fringe imaging unit 49. In Figure 6, the optical path of the reference light is shown by a dotted arrow. The second light, which is irradiated onto the particle 62 and reflected by the particle 62, and the reference light have different optical path lengths and interfere with each other. The interference fringe imaging unit 49 generates an image using the interference light resulting from the interference of the incident second light and the reference light.

[0068] The interferometer 4 includes multiple optical components such as filters, mirrors, and lenses for guiding, focusing, and separating the second light and the reference light. Half mirrors 44 and 47, a beam splitter 45, and a lens 46 are some of the multiple optical components. In Figure 6, optical components included in the interferometer 4 other than the half mirrors 44 and 47, the beam splitter 45, and the lens 46 are omitted. The arrangement of the multiple optical components shown in Figure 6 is just one example, and other arrangements of the multiple optical components are also possible.

[0069] Furthermore, the interferometer 4 is configured such that the second light and reference light from the infrared light source 48 are distributed in a linear fashion. The distribution of the second light and reference light is shaped linearly by optical components (not shown), such as cylindrical lenses. For example, cylindrical lenses that shape the light distribution linearly are placed on the optical paths of the second light and reference light.

[0070] The reference mirror 43 is inclined with respect to the optical path of the reflected reference light. In the example shown in Figure 6, the normal to the reflective surface of the reference mirror 43 is inclined in the XZ plane with respect to the optical path of the reflected reference light. Because the reference mirror 43 is inclined, the length of the optical path of the reference light differs depending on which part of the reference mirror 43 the reference light is reflected from. Therefore, the difference in the length of the optical paths between the second light incident on the interference fringe imaging unit 49 and the reference light differs depending on which part of the reference mirror 43 the reference light is reflected from. Consequently, interference light of different brightness levels is incident on the interference fringe imaging unit 49 in parallel, and the image generated by the interference fringe imaging unit 49 includes interference fringes.

[0071] In Figure 6, the optical system 2 and the interferometer 4 are shown to be positioned to irradiate light onto particles 62 at the same location. However, in reality, the interferometer 4 is positioned further upstream in the flow path 51. That is, in Embodiment 3, the optical system 2 and the interferometer 4 are positioned such that the position where the interferometer 4 irradiates light is further upstream than the position where the optical system 2 irradiates light.

[0072] In Embodiment 3, the Raman scattering light detection device 100 detects Raman scattered light from the particles 62 by performing the processes S1 to S5. In Embodiment 3, the processes S1 to S4 are performed while the particles 62 are flowing through the channel 51. In S1, the interferometer 4 irradiates the particles 62 with light from the second light source 42 while the particles 62 are flowing through the channel 51, and the light reflected by the particles 62 is incident on the imaging unit 41. In parallel, the interferometer 4 irradiates the particles 62 flowing through the channel 51 with light from the infrared light source 48, the light reflected by the particles 62 is incident on the interference fringe imaging unit 49, and the reference light reflected by the reference mirror 43 is incident on the interference fringe imaging unit 49. The imaging unit 41 generates an image of the particles 62, and the interference fringe imaging unit 49 generates an image including interference fringes. The imaging unit 41 and the interference fringe imaging unit 49 input the generated images to the control unit 1.

[0073] The image generated by the imaging unit 41 is called a particle image, and the image generated by the interference fringe imaging unit 49 is called an interference fringe image. Figure 7 is a schematic diagram showing examples of particle images and interference fringe images. The particle image and interference fringe image generated simultaneously are arranged side by side, and multiple images obtained sequentially over time are arranged from top to bottom. In the particle image, the horizontal axis represents the X direction, and the vertical axis represents the Y direction. In the interference fringe image, the horizontal axis represents the Z direction, and the vertical axis represents the Y direction. The particle image includes lines of light from the infrared light source 48. The interference fringe image shows the brightest interference fringe. For example, the interference light is brightest when the lengths of the optical paths of the second light and the reference light match. In reality, the interference fringe image contains multiple bright and dark fringes.

[0074] The top particle image and interference fringe image were generated when the second light from the infrared light source 48 was not irradiating the particle 62. The interference fringes in the interference fringe image are linear. As time passes, the particle 62 moves along the channel 51 and reaches a position where the second light is irradiated. The second particle image and interference fringe image from the top were generated when the second light was irradiating the tip of the particle 62. When the particle 62 is irradiated with the second light, the length of the optical path of the second light changes, so the brightest interference fringe no longer appears in the same position in the interference fringe image as before. Because the reference mirror 43 is tilted, the length of the optical path of the reference light differs depending on the position in the Z direction of the reflected portion in the reference mirror 43. Therefore, the brightest interference fringe moves in the Z direction within the interference fringe image.

[0075] As time progresses, particle 62 moves, and the second light is directed to the vicinity of the center of particle 62. The third particle image and interference fringe image from the top in Figure 7 were generated when the second light was directed to the vicinity of the center of particle 62. Compared to when the second light was directed to the tip of particle 62, the change in the length of the optical path of the second light is larger, and the brightest interference fringe in the interference fringe image moves more significantly in the Z direction. As time progresses, particle 62 moves further, and the second light is directed to the rear end of particle 62, and then the second light no longer illuminates particle 62. The fourth particle image and interference fringe image from the top were generated when the second light was directed to the rear end of particle 62, and the fifth particle image and interference fringe image from the top were generated when the second light no longer illuminated particle 62.

[0076] The magnitude of the movement of interference fringes within the interference fringe image is related to the position in the Z direction of the portion of particle 62 irradiated by the second light. The calculation unit 11 determines the position in the X direction of particle 62 moving through the flow channel 51 by image processing of the particle image. The calculation unit 11 also determines the position of the interference fringes within the interference fringe image by image processing of the interference fringe image, and determines the position of particle 62 along the Z direction according to the position of the interference fringes. For example, the correspondence between the position of the interference fringes in the interference fringe image and the position of particle 62 in the Z direction is stored in advance in the storage unit 14, and the calculation unit 11 uses the stored correspondence to determine the position of particle 62 according to the position of the interference fringes. In this way, the Raman scattering light detection device 100 measures the position of particle 62. The processing in S1 by the interferometer 4 and the control unit 1 corresponds to the position measurement unit.

[0077] In S2, similar to Embodiment 2, the control unit 1 moves the focal point of the optical system 2, so that the Raman scattering light detection device 100 aligns the position of the focal point of the optical system 2 with the position of the particle 62. The processing in S2 by the optical system drive unit 35 and the control unit 1 corresponds to the position adjustment unit. After that, the Raman scattering light detection device 100 executes the processes S3 to S5, similar to Embodiment 2. The Raman scattering light detection device 100 repeats the processes S1 to S5 as appropriate. For example, the Raman scattering light detection device 100 executes the processes S1 to S5 for each individual particle 62 flowing through the channel 51.

[0078] It is desirable that the optical system 2 and the interferometer 4 be positioned such that the position where the interferometer 4 irradiates light is upstream of the position where the optical system 2 irradiates light by a distance obtained by multiplying the time required for processing S1 and S2 by the flow velocity of the liquid 61. During processing S1 and S2, the particles 62 move, and by the time processing S3 begins, the particles 62 have reached the position where light from the optical system 2 irradiates them. Therefore, it is possible to smoothly detect the Raman scattered light of the moving particles 62. In addition, in Embodiment 3, because the interferometer 4 is positioned upstream, light from the second light source 42 is less likely to enter the optical system 2, so the second light source 42 does not need to be turned off when processing S3 to S4.

[0079] In Embodiment 3, the Raman scattering light detection device 100 can measure the position of the particles 62 in the liquid 61 and increase the intensity of the detected Raman scattered light by aligning the focal point of the optical system 2 with the position of the particles 62. By increasing the intensity of the detected Raman scattered light, it becomes possible to effectively perform Raman spectroscopic analysis of the particles 62 in the liquid 61. Furthermore, in Embodiment 3, since it is not necessary to move the flow path 51 or the reference mirror 43, it becomes possible to perform Raman spectroscopic analysis of the particles 62 in the liquid 61 more easily. By detecting Raman scattered light from each particle 62 in the order in which they flowed through the flow path 51, it also becomes possible to perform intermittent Raman spectroscopic analysis of multiple particles 62 in the liquid 61.

[0080] In conventional Raman scattering light detection systems, when using autofocus with a confocal or laser, time is required to scan the sample with light. In Embodiment 3, by using an inclined reference mirror 43, the position of the particle 62 can be measured in a shorter time. Therefore, Raman spectroscopy of the particle 62 moving through the channel 51 can be reliably performed.

[0081] The Raman scattering light detection device 100 may also be configured without an optical system drive unit 35. In this configuration, the focal point of the optical system 2 is fixed. In this configuration, the Raman scattering light detection device 100 omits the process in S2 and, when the position of the measured particle 62 aligns with the focal point of the optical system 2, irradiates the particle 62 with light and detects the Raman scattered light. In this configuration, although some particles 62 that cannot be subjected to Raman spectroscopy are generated, Raman spectroscopy of the particles 62 in the liquid 61 can be performed more easily.

[0082] In embodiments 1 to 3, an example was shown in which a liquid 61 containing particles 62 is held in a channel 51, but the holder that holds the liquid 61 may be in a form other than a channel 51. For example, the holder may be a transparent dish in which the liquid 61 containing particles 62 is stored. In embodiments 1 to 3, the wavelengths of light emitted by the first light source 21 and the second light source 42 may be different from each other. For example, the first light source 21 may be a light source that emits near-infrared light, and the second light source 42 may be a light source that emits visible light.

[0083] Embodiments 1 to 3 show examples in which the optical path of the light irradiated from the optical system 2 to the particle 62, the optical path of the detected Raman scattered light, and the optical path of the light irradiated from the interferometer 4 to the particle 62 are aligned in the Z direction. The Raman scattered light detection device 100 may be configured such that the direction of these optical paths is in a direction other than the Z direction.

[0084] In embodiments 1 to 3, the interference was measured by generating an image containing interference fringes, but the interferometer 4 may measure interference by a method other than image generation. For example, the interferometer 4 may be equipped with a two-dimensional or one-dimensional optical sensor that measures the two-dimensional or one-dimensional distribution of the intensity of incident light instead of the imaging unit 41, and the Raman scattering light detection device 100 may determine the position of the interference fringes based on the distribution of light intensity. For example, the interferometer 4 may be equipped with a plurality of optical sensors arranged in an array instead of the imaging unit 41, and the Raman scattering light detection device 100 may determine the position of the interference fringes based on the intensity of light detected by each optical sensor.

[0085] The present invention is not limited to the embodiments described above, and various modifications are possible within the scope of the claims. That is, embodiments obtained by combining technical means that have been appropriately modified within the scope of the claims are also included in the technical scope of the present invention.

[0086] The matters described in each embodiment can be combined with each other. Furthermore, the independent and dependent claims described in the claims can be combined with each other in any combination, regardless of the form of reference. Moreover, although the claims use a form in which claims referencing two or more other claims (multi-claim form), they are not limited to this. A form in which multi-claims referencing at least one multi-claim (multi-multi-claim) may also be used.

[0087] 1 Control Unit 11 Calculation Unit 14 Memory Unit 141 Computer Program 2 Optical System 21 First Light Source 31 Spectrometer 32 Detector 35 Optical System Drive Unit 36 ​​Mirror Drive Unit 4 Interferometer 41 Imaging Unit 42 Second Light Source 43 Reference Mirror 48 Infrared Light Source 49 Interference Fringe Imaging Unit 51 Flow Channel (Holder) 52 Z-Stage 53 Stage Drive Unit 61 Liquid 62 Particles

Claims

1. A Raman scattering light detection device comprising: an optical system for irradiating particles in a liquid with a first light; a detector for detecting Raman scattered light generated from the particles irradiated with the first light; a position measuring unit for measuring the position of the particles; and a position adjustment unit for aligning the position of the focal point of the optical system with the position of the particles based on the position of the particles measured by the position measuring unit, wherein the position measuring unit has an interferometer for measuring the interference between a reference light and a second light that is irradiated onto the particles in a direction different from the first light and reflected by the particles.

2. The Raman scattering light detection device according to claim 1, characterized in that the interferometer generates an image including interference fringes generated by the interference of the second light and the reference light, the position measuring unit adjusts the position of the holder that holds the liquid containing the particles with respect to the interferometer, or the length of the optical path of the reference light, and measures the position of the particles in the image obtained with respect to the adjusted position of the holder with respect to the interferometer or the length of the optical path of the reference light.

3. The Raman scattering light detection device according to claim 1, characterized in that the reference light is light separated from the second light in the middle of the optical path of the second light, the interferometer has a reference mirror that reflects the reference light, the reference mirror is inclined with respect to the optical path of the reflected reference light such that the length of the optical path of the reference light differs depending on the position where the reference light is reflected, the interferometer generates an image including interference fringes generated by the interference of the second light and the reference light, and the position measuring unit measures the position of the particle according to the position of the interference fringes in the image.

4. A Raman scattering light detection device according to any one of claims 1 to 3, characterized in that the particles contained in the liquid flowing through the channel are irradiated with the first light and the second light.

5. The Raman scattering light detection device according to claim 4, characterized in that the position where the second light is irradiated is upstream of the flow path compared to the position where the first light is irradiated.

6. A method for detecting Raman scattered light, characterized in that: the position of a particle in a liquid is measured; based on the measured position of the particle, the focal position of an optical system for irradiating the particle with light is aligned with the position of the particle; first light is irradiated onto the particle using the optical system while the focal position and the position of the particle are aligned; Raman scattered light generated from the particle irradiated with the first light is detected; and the measurement of the position of the particle is performed using an interferometer that acquires an image including interference fringes generated by a second light irradiated onto the particle in a direction different from the first light and reflected by the particle, and a reference light.

Images