Flow analysis device for flow channels

Abstract

To allow for quickly performing a flow analysis even when an LDV is used to analyze a flow in a flow channel.SOLUTION: An irradiation direction of a first laser beam L1 and a second laser beam L2 to a blood chamber 100 is defined as an X-direction. A flow analyzer 1 provided herein comprises an X-direction scanning unit 30 configured to scan the first and second laser beams L1, L2 such that an intersection of the first and second laser beams L1, L2 in the blood chamber 100 moves in the X-direction.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a flow analyzer for analyzing the flow state of blood flowing through a blood chamber of a blood circuit used in, for example, blood purification therapy, and particularly to the technical field of a structure that measures flow velocity by utilizing the coherence of laser light. [Background technology]

[0002] The blood circuits used in blood purification therapy are composed of blood chambers, tubes, and other components. Analysis of blood flow within the blood chamber is particularly important for investigating ways to suppress blood clotting within the chamber. Factors thought to cause blood clotting within the blood chamber include partial blood stagnation and velocity changes, among other factors. Understanding these factors and analyzing the mechanism of blood clotting could enable the design of a blood chamber that is less prone to clotting. However, because blood is an opaque liquid, determining its behavior within the blood chamber by appearance is difficult. Furthermore, the complex parameter settings required for simulation analysis make sufficient analysis difficult.

[0003] It is also generally known that the flow velocity of a fluid inside a circular pipe can be measured, for example, using a two-dimensional velocimeter. Particle Image Velocimetry (PIV) is a widely used two-dimensional velocimeter with high spatial resolution. When using PIV to visualize a flow inside a circular pipe, for example, a sheet of laser light is incident on the pipe so that it passes through the central axis, and tracer particles moving on the surface of the sheet light are photographed with a high-speed camera.

[0004] Another known flow velocity measurement technique with high spatial resolution is laser Doppler velocimetry (LDV), which is used in laser Doppler blood flow meters (see, for example, Patent Documents 1 and 2). The laser Doppler blood flow meters in Patent Documents 1 and 2 include an optical system that splits laser light emitted from a laser light source into two beams, which are then incident on a rod lens or cylindrical lens to form a light sheet, and refracts the light sheet so that it is incident on a measurement target. Scattered light from tracer particles in the fluid at the intersection region where the two light sheets intersect is two-dimensionally focused and converted into an electrical signal by a photoelectric conversion element. This electrical signal, called a Doppler burst signal, contains frequency components proportional to the velocity of the tracer particles in the fluid. Therefore, the flow velocity of the fluid at the intersection region is calculated from the power spectrum obtained by performing a fast Fourier transform or the like on the Doppler burst signal. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2009 / 081883 Brochure [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-59856 Summary of the Invention [Problem to be solved by the invention]

[0006] In particle image velocimetry, velocity components along two axes can be obtained by projecting a laser beam through the central axis of a circular pipe. However, the velocity component along the remaining axis (i.e., perpendicular to the plane of the light sheet) cannot be obtained. Visualizing flow velocities along all three axes requires stereo PIV, which uses two high-speed cameras and a thick light sheet. Therefore, stereo PIV is considered the preferred method for measuring vortices along the inner wall of a circular pipe. While stereo PIV is convenient for blood, where red blood cells act as tracer particles, its application is limited to peripheral blood vessels and thin artificial channels. This is due to the inherent inability of PIV to be applied to opaque fluids.

[0007] Therefore, if a laser Doppler blood flowmeter based on LDV techniques is used, and a near-infrared laser light source is used, which can minimize the light absorption rate of hemoglobin and water molecules in the blood, it may be possible to apply it to thick artificial channels that are difficult to measure with PIV. However, the technology for obtaining flow velocity images using LDV is still immature, and there is no measurement technology available for visualizing flow velocities inside circular pipes. Of course, existing LDV systems can measure the flow velocity at any single point in an artificial channel, so it would not be impossible to obtain a wide range of velocity distributions if a long period of time were spent. However, in reality, the measurement time is limited, making it difficult to analyze the flow of blood inside a blood chamber.

[0008] The present invention has been made in consideration of the above points, and its purpose is to enable flow analysis of blood in a blood chamber to be performed in a short time even when using LDV. [Means for solving the problem]

[0009] In order to achieve the above object, in the present invention, sheet-shaped first and second laser lights are incident so that they intersect with each other at a predetermined position within the flow path, the blood flow velocity is calculated from the beat frequency contained in the scattered light at the intersection region of the laser lights, and the intersection position of the first and second laser lights within the flow path is scanned in the irradiation direction of the laser lights.

[0010] The first invention is a flow analysis device for analyzing the flow state of a fluid flowing in a flow channel, the device comprising: a laser light source that emits laser light in a near-infrared region; a laser light branching unit that branches the laser light emitted from the laser light source into a first laser light and a second laser light; a first optical system that refracts the first laser light and the second laser light branched by the laser light branching unit so that they intersect with each other at a predetermined position in the flow channel; a second optical system that shapes the first laser light and the second laser light branched by the laser light branching unit into sheet-like shapes; and a flow analysis device for analyzing the flow state of a fluid flowing in a flow channel, the device comprising: a laser light source that emits laser light in a near-infrared region; a laser light branching unit that branches the laser light emitted from the laser light source into a first laser light and a second laser light; a first optical system that refracts the first laser light and the second laser light branched by the laser light branching unit so that they intersect with each other at a predetermined position in the flow channel; the first laser beam and the second laser beam being incident on the flow path; a focusing optical system that focuses the scattered light of the first laser beam and the second laser beam in a linear shape; a light receiving element disposed at a focusing position of the focusing optical system; a photoelectric conversion element that converts the scattered light incident on the light receiving element into an electrical signal; a flow velocity calculation unit that obtains the frequency of an optical beat contained in the scattered light at the linear irradiation site based on the electrical signal and calculates the flow velocity of the fluid at the linear irradiation site from the obtained frequency; and an X-direction scanning unit that scans the first laser beam and the second laser beam so that, when the irradiation direction of the first laser beam and the second laser beam to the flow path is defined as the X direction, an intersection position of the first laser beam and the second laser beam within the flow path moves in the X direction.

[0011] According to this configuration, laser light emitted from a laser light source is split into a first laser light and a second laser light, which then become a sheet-like laser light and enter the flow path so that they intersect at a predetermined position. Particles in the fluid flowing through the linear irradiation area where the first and second laser lights intersect generate scattered light from the laser light. This scattered light is linearly focused by a focusing optical system, received by a light-receiving element, and converted into an electrical signal by a photoelectric conversion element. The scattered light has a beat proportional to the velocity of particles in the fluid in the flow path, and the flow velocity of the fluid at the linear irradiation area can be calculated based on the frequency of the beat. This calculation method is well known and can be used, for example, methods described in Patent Documents 1 and 2.

[0012] Because the laser light is in the near-infrared region, if the fluid is blood, for example, the light absorption rate by hemoglobin and water molecules in the blood is low, so the light reaches not only the surface portion of the flow channel but also the deeper portions, expanding the measurement range. The wavelength of the laser light can be, for example, in the range of 760 nm to 2500 nm, and is particularly preferably set in the range of 780 nm to 820 nm. A wavelength within this range can further reduce the absorption rate of the laser light by hemoglobin and water.

[0013] Then, by scanning the first laser light and the second laser light in the direction of irradiation onto the flow channel, it becomes possible to obtain the flow velocity of the fluid over the entire length of the flow channel from the front side to the depth direction in a short time.

[0014] Examples of components constituting the flow path include, but are not limited to, a blood chamber and a blood tube. The flow path can be formed, for example, from a cylindrical member, a rectangular cylindrical member, a conical member, a pyramidal member, or a member having a shape similar to these. These members must be translucent to the first laser beam and the second laser beam. The fluid may be, for example, blood or a blood simulant.

[0015] The second invention is characterized in that it includes a Y-direction scanning unit that scans the first laser light and the second laser light so that the intersection position of the first laser light and the second laser light within the flow path moves in the Y direction when the longitudinal direction of the linear irradiation area is the Y direction.

[0016] According to this configuration, by scanning the first laser light and the second laser light not only in the X direction but also in the longitudinal direction of the linear irradiation area, the flow velocity of the fluid can be obtained over a wider range.

[0017] A third invention is characterized in that it includes a control device that controls the X-direction scanning unit, and the control device stops scanning by the X-direction scanning unit while the scattered light is received by the light receiving element.

[0018] That is, when the first laser beam and the second laser beam are being scanned, the frequency of the scattered light is a frequency that also takes into account the scanning speed, which may result in an error in the flow velocity of the fluid, but in the present invention, when the scanning of the first laser beam and the second laser beam is stopped, the light-receiving element receives scattered light from the components of the fluid flowing through the linear irradiation site, and the flow velocity of the fluid can be obtained based on this. This means that the scanning speed of the first laser beam and the second laser beam no longer affects the flow velocity of the fluid, making it possible to obtain an accurate flow velocity.

[0019] A fourth invention is characterized in that the X-direction scanning unit includes a movable member to which the laser light source, the laser beam branching unit, the first optical system, the second optical system, the light-collecting optical system, and the light-receiving element are attached, and an X-direction driving device that drives the movable member in the X direction.

[0020] That is, if the relative positional relationship between the optical system and the laser light source, or the relative positional relationship between the focusing optical system and the light-receiving element deviates from its initial state, this could result in, for example, a decrease in measurement accuracy. However, in the present invention, the laser light source, laser light branching unit, first optical system, second optical system, focusing optical system, and light-receiving element are attached to a movable member, and the movable member is driven in the X direction by an X-direction driving device. Therefore, when scanning with the first laser light and the second laser light, the relative positional relationship between the optical system and the laser light source, or the relative positional relationship between the focusing optical system and the light-receiving element does not deviate from its initial state, and measurement accuracy can be improved.

[0021] A fifth aspect of the present invention is characterized in that the device further comprises a visible light irradiation unit that irradiates the linear irradiation area in the flow channel with visible light.

[0022] That is, for example, when adjusting the irradiation positions of the first laser beam and the second laser beam, the operator cannot visually check the irradiation positions because the first laser beam and the second laser beam are light in the near-infrared region. In the present invention, visible light is irradiated onto the linear irradiation site in the flow channel, so the irradiation positions of the first laser beam and the second laser beam can be visually confirmed.

[0023] The sixth invention is characterized in that the visible light irradiation unit is arranged on the opposite side of the flow path across the focusing optical system, and is configured to irradiate the linear irradiation area with visible light through the focusing optical system.

[0024] According to this configuration, the focus of the visible light emitted from the visible light emitting unit can be adjusted to the linearly irradiated area by using the light collecting optical system.

[0025] The seventh invention is characterized in that the focusing optical system comprises a first focusing lens arranged on the light receiving element side and a second focusing lens arranged on the flow path side, and the first optical system is composed of the second focusing lens.

[0026] According to this configuration, the first laser beam and the second laser beam split by the laser beam splitter can be refracted by the second condenser lens constituting the condensing optical system and made incident on the flow path. In other words, the second condenser lens constituting the condensing optical system can be used as the first optical system, thereby simplifying the configuration of the optical system.

[0027] The eighth invention is characterized in that the second focusing lens is arranged to face the incident side of the first laser light and the second laser light in the flow path, the first focusing lens and the second focusing lens are arranged to face each other, and the first focusing lens is formed to avoid the optical paths of the first laser light and the second laser light.

[0028] With this configuration, the focusing optical system is disposed so as to face the incident side of the flow path of the first laser beam and the second laser beam, so that the laser light source, laser beam branching unit, first optical system, second optical system, focusing optical system, and light receiving element can be integrated into a compact flow analysis device. In this case, the first laser beam and the second laser beam do not enter the first focusing lens, so they can be refracted in a predetermined direction by the second focusing lens.

[0029] A ninth aspect of the present invention is characterized in that a portion of the outer periphery of the first condenser lens corresponding to the optical paths of the first laser light and the second laser light is cut away.

[0030] According to this configuration, the first condenser lens can be provided so as to avoid the optical paths of the first laser light and the second laser light, by a simple configuration in which a part of the first condenser lens is removed. [Effects of the Invention]

[0031] According to the present invention, near-infrared laser light is branched into first and second laser light sheets, which are then made to intersect with each other at a predetermined position within the flow path. When calculating the flow velocity of the fluid based on the frequency of the optical beat of the light scattered by particles in the fluid flowing through the linear irradiation area, the first and second laser light are scanned in the direction of irradiation onto the fluid, so that fluid flow analysis can be performed in a short time using LDV. [Brief explanation of the drawings]

[0032] [Figure 1] 1 is a schematic diagram of a blood chamber flow analysis device according to an embodiment of the present invention. [Figure 2] FIG. 1 is a block diagram of a flow analysis device in a blood chamber. [Figure 3] FIG. 10 is a diagram illustrating the state in which the blood chamber is irradiated with laser light. [Figure 4] FIG. 2 is a perspective view of a first condenser lens and a second condenser lens. [Figure 5] 3A and 3B are diagrams illustrating examples of the configuration of a light receiving element and a photoelectric conversion element. [Figure 6] FIG. 1 shows the travel of a laser beam within a blood chamber. [Figure 7] 10 is a graph used to correct the intersection position of laser light. [Figure 8] 1 is a graph showing the relationship between spectral density and frequency. [Figure 9] FIG. 10 is a diagram showing the flow analysis results. DETAILED DESCRIPTION OF THE INVENTION

[0033] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. Note that the following description of the preferred embodiments is merely exemplary in nature and is not intended to limit the present invention, its applications, or its uses.

[0034] 1 shows a fluid flow analysis device 1 according to an embodiment of the present invention. The flow analysis device 1 is a device used to analyze the flow state of blood flowing through a flow path formed in a blood chamber 100 of a blood circuit used, for example, in blood purification therapy. In this example, the device is described as a flow analysis device 1 for a blood chamber, but is not limited to this, and can also be used as a flow analysis device for a fluid containing particles that generate scattered light when irradiated with laser light, as described below.

[0035] The blood purification therapy is hemodialysis involving extracorporeal circulation. In addition to blood chamber 100, the blood circuit includes an inflow tube for introducing blood into blood chamber 100 and an outflow tube for discharging blood from blood chamber 100 (not shown). As shown in FIG. 3, blood chamber 100 includes a cylindrically molded, transparent resin main body 101, a first closure member 102 for closing one end of main body 101, and a second closure member 103 for closing the other end of main body 101. First closure member 102 includes inflow tube 102a to which the inflow tube is connected. A mesh (not shown) is provided within inflow tube 102a to prevent solids such as coagulated blood from returning to the body. Second closure member 103 includes outflow tube 103a to which the outflow tube is connected. Therefore, in this embodiment, blood flowing in from the top of blood chamber 100 is discharged from the bottom. Furthermore, since inflow pipe portion 102a is oriented horizontally, a swirling flow is generated along the sidewall within blood chamber 100. The inner diameter of main body cylindrical portion 101 is set to, for example, about 15 mm to 20 mm. The material of main body cylindrical portion 101 is, for example, vinyl chloride.

[0036] (Overall configuration of flow analysis device 1) The flow analysis device 1 is configured to be capable of so-called laser Doppler flow velocity measurement, and includes a device main body 2, a control device 3, a keyboard 4, a mouse 5, and a display unit 6, as shown in FIG. 1. The control device 3 can be configured, for example, as the main body of a personal computer or a microcomputer. The keyboard 4 and mouse 5 are used to operate the control device 3, enter various settings, input information, etc. The display unit 6 is configured, for example, as a liquid crystal display, and is controlled by the control device 3, and is configured to be able to display in color information, various data, images, etc. input via the keyboard 4 and mouse 5.

[0037] The device main body 2 includes a base material 20. The base material 20 is made of a plate material or the like extending horizontally, and is fixed so as not to move vertically or horizontally. In addition to the base material 20, the device main body 2 includes a laser output device 21, a laser beam branching unit 22, a first rod lens 23, a second rod lens 24, a focusing optical system 25, a light receiving element 26, and a photoelectric conversion element 27. The device main body 2 further includes an X-direction scanning unit 30 and a Y-direction scanning unit 31 that scan the laser beam. The X-direction scanning unit 30 and the Y-direction scanning unit 31 can be configured, for example, by an electric stage or the like.

[0038] In the description of this embodiment, the longitudinal direction of base material 20 is defined as the X direction, the vertical direction as the Y direction, and the lateral direction of base material 20 as the Z direction, but these definitions are for the sake of convenience of description only. The Y direction coincides with the longitudinal direction of blood chamber 100.

[0039] Y-direction scanning unit 31 is attached to scanning unit mounting plate 20a, which protrudes upward from one longitudinal end of base member 20. Y-direction scanning unit 31 includes blood chamber fixing member 31a to which blood chamber 100 is fixed, guide rails 31b that guide blood chamber fixing member 31a in the vertical direction, and Y-direction driving device 31c shown in FIG. 2. Y-direction driving device 31c is connected to and controlled by control device 3. Examples of Y-direction driving device 31c that can be used include, but are not limited to, well-known linear actuators and actuators that combine a stepping motor and a feed screw mechanism. Any device that can move blood chamber fixing member 31a in the vertical direction will suffice. Blood chamber fixing member 31a can move only in the Y direction via guide rails 31b. The amount and timing of movement of blood chamber fixing member 31a are set by control signals output from control device 3.

[0040] An X-direction scanning unit 30 is attached to the top surface of the base material 20 at a position away from the scanning unit mounting plate 20a. The X-direction scanning unit 30 includes a movable member 30a, a fixed member 30b, and an X-direction driving device 30c. The fixed member 30b is fixed to the top surface of the base material 20 and includes a guide rail 30d extending in the X direction. The movable member 30a may be formed of a plate material extending in the X and Z directions and is movable only in the X direction along the guide rail 30d. The X-direction driving device 30c is connected to and controlled by the control device 3. The X-direction driving device 30c may be, for example, a well-known linear actuator or an actuator combining a stepping motor and a feed screw mechanism, but is not limited to these and may be any device that can move the movable member 30a in the X direction.

[0041] The laser output device 21, laser beam branching unit 22, first rod lens 23, second rod lens 24, focusing optical system 25, and light-receiving element 26 are attached to the movable member 30a by, for example, a bracket or a base (not shown). The laser output device 21 serves as a laser light source that emits laser beams in the near-infrared region. The wavelength of the laser beams in the near-infrared region can be, for example, in the range of 760 nm to 2500 nm. In this embodiment, near-infrared laser beams with a wavelength of 808 nm are irradiated, but this is not limited thereto. For example, near-infrared laser beams in the range of 780 nm to 820 nm can also be irradiated. The wavelength range around 800 nm is low in both hemoglobin and water. Generally, this wavelength range can penetrate blood to a depth approximately 10 times greater than visible light (wavelengths 400 to 700 nm). However, because laser beams inevitably attenuate in blood, it is preferable to use a high-output laser output device 21. In this embodiment, the output at the emission end of the laser output device 21 is set to 141 mW, but this is not limitative.

[0042] The emission direction of laser output device 21 is the X direction and toward blood chamber 100. Collimating lens 21a is provided at the emission end of laser output device 21. In addition, polarizing filter 21b for passing p-polarized linearly polarized light is also provided at the emission end of laser output device 21, closer to blood chamber 100 than collimating lens 21a. After passing through collimating lens 21a, the laser light emitted from laser output device 21 is incident on polarizing filter 21b. In this embodiment, p-polarized light is used, but the polarization direction is not limited to this.

[0043] Laser beam branching unit 22 is a beam splitter that branches the laser beam emitted from laser output unit 21, and is a conventionally well-known component. Laser beam branching unit 22 is disposed opposite polarizing filter 21b on the side closer to blood chamber 100 than polarizing filter 21b. Laser beam branching unit 22 emits a first laser beam L1 that travels in the X direction toward blood chamber 100, and a second laser beam L2 that travels in the Z direction.

[0044] A mirror 28 is attached to movable member 30a. Mirror 28 is positioned so that second laser light L2 emitted from laser light branching unit 22 is incident on it, and second laser light L2 reflected by mirror 28 becomes parallel to first laser light L1 and travels toward blood chamber 100. First laser light L1 and second laser light L2 are lights that pass at the same height and travel horizontally. Furthermore, the optical paths of first laser light L1 and second laser light L2 are separated in the Z direction.

[0045] A condensing optical system 25 is installed between laser beam branching unit 22 and blood chamber 100. Condensing optical system 25 includes first condensing lens 25a and second condensing lens 25b, which are arranged so that their optical axes face the X direction and so that they face each other. First condensing lens 25a and second condensing lens 25b can each be configured as an achromatic lens formed by cementing lenses made of materials with different refractive indices. First condensing lens 25a is arranged on the laser output device 21 side, and second condensing lens 25b is arranged on the blood chamber 100 side.

[0046] 4, a portion of the outer periphery of the first condenser lens 25a corresponding to the optical path of the first laser beam L1 and a portion corresponding to the optical path of the second laser beam L2 are removed. That is, the outer periphery of the first condenser lens 25a is provided with cutouts 25c, 25c at two locations spaced apart in the Z direction, each formed by removing a portion of the first condenser lens 25a. By providing these cutouts 25c, 25c, the first condenser lens 25a is formed so as to avoid the optical paths of the first laser beam L1 and the second laser beam L2. The first laser beam L1 and the second laser beam L2 pass beside the first condenser lens 25a and travel straight in the X direction.

[0047] On the other hand, second condenser lens 25b is formed to be located on the optical paths of first laser light L1 and second laser light L2. Second condenser lens 25b is a lens that refracts first laser light L1 and second laser light L2 branched by laser light branching unit 22 so that they intersect with each other at a predetermined position within blood chamber 100. Therefore, second condenser lens 25b is a lens that constitutes the first optical system of the present invention, and by using second condenser lens 25b that constitutes condensing optical system 25 as the first optical system, the configuration of the optical system can be simplified. The intersection position of first laser light L1 and second laser light L2 can be set arbitrarily by the position of second condenser lens 25b and the optical design of second condenser lens 25b. In this embodiment, as shown in FIG. 1, first laser light L1 and second laser light L2 intersect at a position approximately 150 mm away from second condenser lens 25b.

[0048] The first rod lens 23 and the second rod lens 24 are arranged closer to the blood chamber 100 than the second collecting lens 25b, with a gap between them in the Z direction. The first laser light L1 that has passed through the second collecting lens 25b is incident on the first rod lens 23, and the second laser light L2 that has passed through the second collecting lens 25b is incident on the second rod lens 24. The first rod lens 23 is a lens that converts the first laser light L1 into a sheet-like light (first sheet light) extending in the Y direction. The second rod lens 24 is a lens that converts the second laser light L2 into a sheet-like light (second sheet light) extending in the Y direction. The first rod lens 23 and the second rod lens 24 constitute the second optical system of the present invention. In this embodiment, the surfaces of optical components such as the first collecting lens 25a, the second collecting lens 25b, the first rod lens 23, and the second rod lens 24 are coated with an anti-reflection film for the wavelength of the laser light to suppress attenuation of the wavelength of the laser light. Furthermore, a cylindrical lens or the like can be used instead of the rod lens, and any configuration is possible as long as the optical system can generate sheet-like light.

[0049] As shown in FIG. 3, by forming the light into a sheet shape extending in the Y direction, the portion where the first laser light and the second laser light intersect with each other is formed as a single linear portion of high light intensity extending in the Y direction, and this portion becomes the linear irradiation area A. The thickness of the sheet light in the linear irradiation area A can be adjusted by the collimator lens 21a, and in this embodiment, the thickness of the sheet light in the linear irradiation area A is set to 0.2 mm. In the linear irradiation area A, a continuous vertical interference fringe is formed in the Y direction due to the phase difference between the incident wavefronts of the first laser light L1 and the second laser light L2. The thickness of the sheet light can be set, for example, in the range of 0.1 mm to 1.0 mm.

[0050] When light is irradiated onto particles (tracer particles) with a diameter larger than the wavelength of the light, scattered light is emitted from the particles due to Mie scattering. Examples of particles with a diameter larger than the wavelength of near-infrared laser light include red blood cells, which are components of blood. Therefore, when first laser light L1 and second laser light L2 are incident on the blood chamber 100 in which blood is flowing, scattered light due to Mie scattering is emitted from the red blood cells. This scattered light is scattered in various directions according to the theory of Mie scattering. At this time, the scattered light from the linear irradiation area A contains an optical beat (beat). The frequency of the optical beat is proportional to the speed at which the red blood cells pass through the linear irradiation area A.

[0051] Of the scattered light emitted from the particles, light that travels toward second collecting lens 25b of collecting optical system 25 passes through second collecting lens 25b and first collecting lens 25a in this order and is collected. Light receiving element 26 shown in Figure 1 is disposed at the position where the scattered light is collected. Therefore, first collecting lens 25a of collecting optical system 25 is disposed on the side of light receiving element 26, and second collecting lens 25b is disposed so as to face the incident side of blood chamber 100 on which first laser light L1 and second laser light L2 are incident.

[0052] 5, the light receiving element 26 can be configured, for example, as an optical fiber array made up of a plurality of optical fibers 26a, and in this embodiment, one end portions 26b (end portions serving as light receiving portions) of the plurality of optical fibers 26a are arranged so as to be adjacent to one another in a straight line in the Y direction. The scattered light from the linear irradiation site A is focused by the focusing optical system 25 in a straight line at the point where the one end portions 26b of the optical fibers 26a are aligned.

[0053] The optical fiber 26a constituting the light receiving element 26 can be, for example, a plastic fiber (EsKa SH-1001) with a diameter of 0.25 mm. The optical fiber 26a may also be a glass fiber. To improve spatial resolution, it is preferable to use an optical fiber 26a with a smaller diameter.

[0054] The number of optical fibers 26a is not particularly limited, but in this embodiment, it is 32. The end portions 26b of the optical fibers 26a can be arranged without gaps and held by a holding member (not shown). The numerical aperture NA of the end portions 26b of the optical fibers 26a is 0.5, which is smaller than the numerical apertures of the first and second condenser lenses 25a and 25b. Therefore, to prevent stray light from entering the end portions 26b of the optical fibers 26a, a single slit 26c (shown in FIG. 1) that is long in the Y direction is disposed in front of the end portions 26b of the optical fibers 26a. The width of the single slit 26c is set to match the numerical apertures of the first and second condenser lenses 25a and 25b. A polarizing filter 26e is disposed between the single slit 26c and the end portions 26b of the optical fibers 26a. It is desirable that the polarization directions of the polarizing filter 21b and the polarizing filter 26 are the same.

[0055] 5, the other end 26d of the optical fiber 26a is coupled (connected) to an avalanche photodiode (APD) 27 using a zirconia ferrule. The avalanche photodiode 27 is a photoelectric conversion element that converts scattered light incident on the light receiving element 26 into an electrical signal, and one is provided for each optical fiber 26a. Therefore, in this embodiment, 32 avalanche photodiodes 27 are provided.

[0056] Control device 3 is equipped with flow velocity calculation unit 3a. The scattered light has an optical bead (beat) due to the flow of blood in blood chamber 100. Flow velocity calculation unit 3a is configured to obtain the optical beat frequency generated by the flow of blood in blood chamber 100 based on the electrical signals output from each avalanche photodiode 27, and to calculate the blood flow velocity at linear irradiation site A from the obtained frequency. The calculation method used by flow velocity calculation unit 3a can be, for example, the methods disclosed in Patent Documents 1 and 2, or the method described below.

[0057] The flow velocity can be determined with the optical fiber 26a as a unit, using the spatial resolution determined by the magnification of the focusing optical system 25. For example, if an optical fiber 26a with a diameter of 0.25 mm is used and the magnification of the focusing optical system 25 is 1, the spatial resolution is 0.25 mm.

[0058] The laser beam splitter 22 may also include an acousto-optic element (AOM) that splits the continuous wave laser beam from the laser output device 21 into a first laser beam L1 and a second laser beam L2 having slightly different frequencies. The direction of blood flow can also be identified by applying modulation using the acousto-optic element. However, if it is not necessary to identify the flow direction, frequency modulation using the acousto-optic element may not be necessary.

[0059] Because the wavelengths of the first laser light L1 and the second laser light L2 are outside the visible light range, the linear irradiation area A cannot be seen with the naked eye. In this embodiment, as shown in FIG. 5, a visible light irradiation unit 29 is provided that irradiates the linear irradiation area A in the blood chamber 100 with visible light. The visible light irradiation unit 29 has an optical fiber 29a similar to the optical fiber 26a described above and a visible light emitting unit 29b that emits visible light. One end 29c of the optical fiber 29a is arranged so as to be aligned with one end 26b of the optical fiber 26a. The other end of the optical fiber 29a is connected to a visible light emitting unit 29b equipped with a light emitting element such as a light emitting diode (LED), and the light emitted from the visible light emitting unit 29b is incident on the other end of the optical fiber 29a. Therefore, visible light is irradiated from one end 29c of the optical fiber 29a. Visible light irradiator 29 is disposed on the opposite side of focusing optical system 25 from blood chamber 100, and visible light irradiated from one end 29c of optical fiber 29a is coupled through focusing optical system 25 at linear irradiation site A and irradiated onto linear irradiation site A. As a result, a point of light is visible on linear irradiation site A, and the initial position of blood chamber 100 can be determined based on this point of light. The light irradiated from visible light irradiator 29b is not particularly limited, but can be, for example, red, green, blue, etc., and a color that is easily distinguishable from natural light is preferable.

[0060] (laser light scanning) 1, the movable member 30a can be moved in both the positive and negative directions of the X direction. The movable member 30a is equipped with a laser output device 21, a laser beam branching unit 22, a first rod lens 23, a second rod lens 24, a focusing optical system 25, and a light-receiving element 26, so that the laser beam emitting system and the light-receiving system can be moved in the X direction without changing the relative positional relationship of each component. This causes a linear irradiation area A, which is the intersection of the first laser beam L1 and the second laser beam L2 emitted from the laser output device 21, to move in the X direction.

[0061] The scanning of the laser beam will be described in detail with reference to FIG. 6. FIG. 6 shows a horizontal cross section of the blood chamber 100 irradiated with the first laser beam L1 and the second laser beam L2, with point O being a point on the center line of the blood chamber 100. Although simulated blood is assumed to be flowing within the blood chamber 100, blood may be flowing. The simulated blood is a liquid in which tracer particles are dispersed in a 45 wt% glycerin aqueous solution to simulate the viscosity of blood. Polyethylene particles with a diameter of 10 μm were used as the tracer particles. 10 mg of polyethylene particles were added per liter of the glycerin aqueous solution. A roller-type tube pump (MF-01, manufactured by JMS) actually used in dialysis treatment was used as the pump to deliver the simulated blood. The flow rate of the simulated blood delivered by the pump was set to a range of 150 to 300 ml / min, which is typical for dialysis treatment.

[0062] Here, light entering the inside of blood chamber 100 from the outside is refracted twice at the interface between air and blood chamber 100 and the interface between blood chamber 100 and the artificial blood. The refractive index n1 of air is 1.0, the refractive index n2 of the nearly colorless and transparent vinyl chloride material of blood chamber 100 is 1.52, and the refractive index n3 of the artificial blood is 1.32. Therefore, the irradiation angle of the light changes by two degrees. Furthermore, in this embodiment, the first laser beam L1 and the second laser beam L2 are scanned in the X direction. Therefore, the angles of incidence of the first laser beam L1 and the second laser beam L2 on blood chamber 100 change depending on the position of movable member 30a of X-direction scanning unit 30. Therefore, the displacement of movable member 30a in the X direction is not the same as the displacement of the intersection of the first laser beam L1 and the second laser beam L2 in the X direction.

[0063] This will be explained based on Fig. 6. In Fig. 6, if the imaginary intersection point of the first laser light L1 and the second laser light L2 when they travel straight without refracting (when they travel straight through the air) is P1, the actual intersection point of the first laser light L1 and the second laser light L2 is P2. When point S in Fig. 6 is taken as the reference position, the relationship between the distance d from point S to point P1 and the distance d1 from point S to point P2 can be represented by a curve displayed on the graph shown in Fig. 7.

[0064] 7, the control device 3 can obtain the position of the intersection of the first laser beam L1 and the second laser beam L2 from the displacement of the movable member 30a of the X-direction scanning unit 30. The data constituting the graph shown in FIG. 7 can be obtained in advance based on the refractive index and the incident angle of the laser beam, etc., and stored in the memory unit 3b of the control device 3 shown in FIG. 2. The displacement of the movable member 30a of the X-direction scanning unit 30 can be obtained based on the drive amount by a well-known displacement sensor or the X-direction driving device 30c, etc.

[0065] However, if movable member 30a of X-direction scanning unit 30 is moved so that the intersection of first laser beam L1 and second laser beam L2 always passes along straight line B extending in the X direction through center point O of blood chamber 100, the incident angles of first laser beam L1 and second laser beam L2 onto blood chamber 100 will always be the same, and the displacement of the intersection of first laser beam L1 and second laser beam L2 on the X axis can be found by simple geometric calculation. Similarly, the intersection angle of first laser beam L1 and second laser beam L2 (the intersection angle is a parameter necessary for calculating the flow velocity) can also be found by simple geometric calculation, although it is not always constant.

[0066] If one were to obtain a velocity distribution by scanning the intersection of the laser beams along the Z axis, the angles of incidence of the first laser beam L1 and the second laser beam L2 on blood chamber 100 would not necessarily be the same, so not only would the calculations be complicated to determine the intersection position and intersection angle of the laser beams, but in order to move the intersection of the laser beams on a linear trajectory that passes through the center line of blood chamber 100, it would ultimately be necessary to control two axes using an X-direction drive device as well. Therefore, scanning in the Z-axis direction would complicate the configuration and make control cumbersome, so scanning in the X direction as described above is preferred.

[0067] The Y-direction scanning unit 31 is used when measuring a measurement target with a long dimension in the Y direction. The operation of the two-axis motorized stages of the X-direction scanning unit 30 and the Y-direction scanning unit 31 is automatically controlled by the control device 3. After measuring 45 times while moving the movable member 30a of the X-direction scanning unit 30 in the X direction, the blood chamber fixing member 31a of the Y-direction scanning unit 31 is moved in the Y direction, and this is repeated 10 times to measure the flow velocity of the simulated blood in one blood chamber 100. Therefore, in this case, the total number of measurements is 450. Furthermore, since 32 channels are simultaneously measured per measurement, the total number of measurement points is 14,400. For example, if 1.5 seconds of time-series data is recorded at all points, the total measurement time, including the time required to save the data to the memory unit 3b, is approximately 38 minutes. The simplest way to shorten the measurement time is to increase the number of simultaneously measured channels from the current 32 channels, i.e., to increase the number of optical fibers 26a that make up the light-receiving element 26.

[0068] The number of measurements described above is an example; the number of measurements can be reduced if the diameter of blood chamber 100 is small, and the number of measurements can also be reduced if the vertical dimension of blood chamber 100 is short. On the other hand, the resolution can be improved by making the measurement points more minute. Settings such as the number of measurements and the measurement range can be input into control device 3 using keyboard 4, mouse 5, etc., and the input results displayed on display unit 6 can be confirmed.

[0069] The control device 3 is configured to stop scanning by the X-direction scanning unit 30 while the light-receiving element 26 receives the scattered light. The time during which the light-receiving element 26 receives the scattered light can be set to approximately 1.5 seconds, as described above. By stopping scanning by the X-direction scanning unit 30 during this time, the linear irradiation area A of the first laser light L1 and the second laser light L2 does not move. That is, if the first laser light L1 and the second laser light L2 are scanning during the light-receiving time, the frequency of the scattered light will be a frequency that also takes into account the scanning speed of the first laser light L1 and the second laser light L2, which may result in an error in the blood flow velocity. However, in this embodiment, when the scanning of the first laser light L1 and the second laser light L2 is stopped, the light-receiving element 26 can receive scattered light from components of blood flowing through the linear irradiation area A, and the blood flow velocity can be obtained based on this. This prevents the scanning speed of the first laser light L1 and the second laser light L2 from affecting the blood flow velocity, thereby obtaining an accurate flow velocity. The time for receiving the scattered light by the light receiving element 26 can be set arbitrarily, for example, within the range of 0.1 to 3 seconds.

[0070] (Signal Processing) The avalanche photodiode 27 converts photons incident from the optical fiber 26a into carriers. However, because the amplitude of this current is very weak (less than 1 pA), the control device 3 is equipped with an amplifier 3c, which converts the signal into a voltage signal with a maximum amplitude of approximately 1 V. The control device 3 also includes a high-pass filter 3d, to which the signal amplified by the amplifier 3c is input. The high-pass filter 3d is a high-order Butterworth filter with a cutoff frequency of 100 Hz. This high-pass filter 3d is used to remove pedestal components. The control device 3 also includes 32 AD converters 3e, to which 32-channel voltage signals are respectively input. The AD converters 3e can have a resolution of 12 bits and a sampling frequency of 10 MHz. The time-series voltage data simultaneously A / D-converted by the AD converters 3e can be stored in the memory unit 3b. The amplifiers 3c, high-pass filters 3d, and AD converters 3e may be provided outside the control device 3.

[0071] One method involves fast Fourier transform (FFT) of time-series voltage data and determining the flow velocity from the frequency position of peaks in the spectrum. However, large tracer particles are required to obtain sufficient scattered light intensity. For example, polyethylene particles with a diameter of 30 μm or greater are required. This is because the scattered light intensity is proportional to the square of the particle diameter. However, the inlet tube 102a of the blood chamber 100 contains a mesh, and particles with a diameter of 30 μm would clog the mesh. Therefore, in the blood simulant described above, 10 μm particles are added at a high concentration to a glycerin solution, thereby increasing the number of particles per unit volume. Of course, increasing the number of particles increases the scattered light intensity, but because scattered light from many particles is received simultaneously, it can be difficult to identify clear peaks in the spectrum.

[0072] It is difficult to observe a clear peak in a typical spectrum obtained when measuring an arbitrary point inside blood chamber 100, but by checking the spectrum before and after flowing a fluid such as a glycerin aqueous solution from the fluid delivery pump, it can be confirmed that when fluid flows, increasing the flow rate of the fluid delivery pump causes a slight increase in the high frequency side, as shown in Figure 8. The expected value of the optical beat frequency can be calculated from such a spectrum, and the following equation, which uses a weighted integral of the wavenumber, can be used to obtain the flow velocity v from the expected value of the beat frequency.

[0073] TIFF0007742068000001.tif26164

[0074] Here, d is the fringe interval of the laser light, and P(f) is the power spectral density. The integration start frequency f1 was set to 100 Hz, which is the cutoff frequency of the high-pass filter. The end frequency f Z was set at 25 kHz. As a result, the above formula is the same as that used to calculate the flow velocity using a laser Doppler flowmeter.

[0075] For example, if 1.5 seconds of time-series data is recorded per channel, the typical size of the binary data per 2D flow velocity image will be approximately 30 Gbytes. Performing FFT on all of this data would require a huge amount of analysis time.

[0076] Therefore, analysis time can be shortened by using parallel calculations with a graphics processing unit (Nvidia GTX-1080Ti). The processing time required to perform FFT processing on 30 Gbytes of binary data and convert it into flow velocity is approximately 9 minutes, which is approximately one-third the processing time required when performing parallel calculations with 8 threads using a CPU (Intel Core i7 6700K). Therefore, it is preferable that the control device 3 is equipped with the above-mentioned graphics processing unit.

[0077] Although sensitivity variations occur due to individual differences in quantum efficiency of the avalanche photodiodes 27, it is preferable to prepare a large number of avalanche photodiodes 27, measure the power spectrum obtained when the same optical signal is input to all of the avalanche photodiodes 27, and select and use 32 avalanche photodiodes 27 with uniform characteristics.

[0078] (Measurement results) Fig. 9 shows an example of a measurement result display screen displayed on the display unit 3 shown in Fig. 3. In this graph, the vertical axis represents the flow velocity value, and the display format changes color depending on the flow velocity value. This display format can be realized by processing by the control device 3.

[0079] The liquid used in the experiment was the aforementioned simulated blood, and the flow rate of the pump was 250 ml / min. Because a roller-type tube pump was used in the experiment, pulsation occurred within the blood chamber 100, coinciding with the roller's rotation period. Therefore, the flow rate also changed in response to the pulsation, and the flow rate was calculated as the time average value over two roller rotation periods (approximately 2.0 seconds for a flow rate of 250 ml / min). Because the blood chamber 100 used had a horizontal inlet tube 102a, the flow rate was slow in the center of the tube and fast on both sides. This velocity distribution suggests the generation of a swirling flow within the chamber. From this graph, it can be seen that the flow rate at the center of the vortex was approximately 4 mm / s and the flow rate around the periphery of the vortex was approximately 10 mm / s. Generally, blood clotting within the blood chamber is thought to occur more easily in areas with slow flow rates or large changes in flow rate. Therefore, this velocity distribution can be used to predict areas where blood clotting is likely to occur.

[0080] (Effects of the embodiment) As described above, in blood chamber flow analysis device 1 according to this embodiment, laser light emitted from laser output device 21 is split into first laser light L1 and second laser light L2, which then become sheet-shaped laser light beams and enter blood chamber 100 so as to intersect with each other at a predetermined position. Blood cells in the blood flowing through linear irradiation area A, where first laser light L1 and second laser light L2 intersect with each other, generate scattered light from the laser light. This scattered light is linearly focused by focusing optical system 25, received by light-receiving element 26, and converted into an electrical signal by photoelectric conversion element 27. The scattered light has a beat frequency proportional to the blood flow velocity within blood chamber 100, and the blood flow velocity at linear irradiation area A can be calculated based on this beat frequency. Because the laser light is in the near-infrared region, it has low light absorption by hemoglobin and water molecules in the blood. Therefore, it reaches not only the surface but also the deeper portions of blood chamber 100, thereby expanding the measurement range.

[0081] Then, by scanning the first laser light L1 and the second laser light L2 in the X direction, which is the irradiation direction onto the blood chamber 100, using the X direction scanning unit 30, the blood flow velocity can be obtained in a short time from the front side of the blood chamber 100 to the entire depth direction.

[0082] The above-described embodiments are merely examples in all respects and should not be construed as limiting. Furthermore, all modifications and variations within the scope of the claims are within the scope of the present invention.

[0083] For example, the light receiving element 26 and the photoelectric conversion element 27 may be a photomultiplier tube, or an image sensor (solid-state imaging element) such as a CCD or C-MOS. The solid-state imaging element may be a line sensor.

[0084] In addition to cylindrical members such as the blood chamber described above, the flow path can also be formed from rectangular cylindrical members, conical members, pyramidal members, or members with shapes similar to these. [Industrial Applicability]

[0085] As described above, the flow analysis device in accordance with the present invention can be used to analyze the flow state of blood flowing in the blood chamber of a blood circuit, for example. [Explanation of symbols]

[0086] 1 Flow analysis device 3. Control device 3a Flow velocity calculation section 21 Laser output device (laser light source) 22 Laser beam splitter 23 First rod lens (second optical system) 24 Second rod lens (second optical system) 25 Condensing optical system 25a First focusing lens 25b Second condenser lens (first optical system) 26 Photodetector 27 Avalanche photodiode (photoelectric conversion element) 29 Visible light irradiation section 30 X-direction scanning unit 30a Movable member 30c X-direction drive unit 31 Y-direction scanning unit 100 Blood Chamber A Linear irradiation area L1 First laser beam L2 Second laser beam

Claims

1. 1. A flow analysis device for analyzing the flow state of a fluid flowing in a flow channel, the fluid containing particles that generate scattered light when irradiated with laser light in the near-infrared region, a chamber fixing member to which a chamber forming the flow path is fixed; a laser light source that emits laser light in the near-infrared region; a laser beam splitter that splits the laser beam emitted from the laser light source into a first laser beam and a second laser beam; a first optical system that refracts the first laser beam and the second laser beam branched by the laser beam branching unit so that the first laser beam and the second laser beam intersect with each other at a predetermined position within the flow path; a second optical system that forms the first laser beam and the second laser beam branched by the laser beam branching unit into a sheet shape; a focusing optical system that focuses scattered light of the first laser light and the second laser light by particles in a fluid moving through a linear irradiation region where the first laser light and the second laser light intersect with each other, into a linear beam; a light receiving element disposed at a light collecting position of the light collecting optical system; a photoelectric conversion element that converts the scattered light incident on the light receiving element into an electrical signal; a flow velocity calculation unit that obtains a frequency of an optical beat included in the scattered light at the linear irradiation site based on the electrical signal, and calculates a flow velocity of the fluid at the linear irradiation site from the obtained frequency; an X-direction scanning unit that scans the first laser light and the second laser light such that, when an irradiation direction of the first laser light and the second laser light to the flow path is an X direction, an intersection position of the first laser light and the second laser light in the flow path moves in the X direction; the X-direction scanning unit includes a movable member to which the laser light source, the laser beam branching unit, the first optical system, the second optical system, the light-collecting optical system, and the light-receiving element are attached, and an X-direction driving device that drives the movable member in the X direction; the second optical system is attached to the movable member so that the first laser light and the second laser light each have a sheet shape extending in a fluid flow direction, A flow analysis device for a flow channel, characterized in that the longitudinal direction of the chamber fixed to the chamber fixing member is the direction in which the sheet-like first laser light and second laser light extend.

2. 2. The flow analysis device for a flow channel according to claim 1, A flow analysis device for a flow path, characterized in that it is equipped with a Y-direction scanning unit that scans the first laser light and the second laser light so that the intersection position of the first laser light and the second laser light within the flow path moves in the Y direction when the longitudinal direction of the linear irradiation area is the Y direction.

3. 3. The flow analysis device for a flow channel according to claim 1, a control device for controlling the X-direction scanning unit, The flow analysis device in a flow channel, wherein the control device stops scanning by the X-direction scanning unit while the scattered light is received by the light receiving element.

4. 4. The flow analysis device for a flow channel according to claim 1, The flow analysis device for a flow channel, further comprising: a visible light irradiation unit that irradiates the linear irradiation portion in the flow channel with visible light.

5. 5. The flow analysis device for a flow channel according to claim 4, The visible light irradiation unit is arranged on the opposite side of the flow path from the focusing optical system, and is configured to irradiate the linear irradiation area with visible light through the focusing optical system.

6. 6. The flow analysis device for a flow channel according to claim 1, the light-collecting optical system includes a first condensing lens disposed on the light-receiving element side and a second condensing lens disposed on the flow path side, 10. An apparatus for analyzing flow in a flow channel, wherein the first optical system is composed of the second condenser lens.

7. 7. The flow analysis device for a flow channel according to claim 6, the second condenser lens is disposed to face an incident side of the flow channel on which the first laser light and the second laser light are incident, the first condenser lens and the second condenser lens are disposed so as to face each other, 10. A flow analysis device for a flow channel, wherein the first condenser lens is formed so as to avoid the optical paths of the first laser light and the second laser light.

8. 8. The flow analysis device for a flow channel according to claim 7, 10. A flow analysis device for a flow channel, wherein a portion of the outer periphery of the first condenser lens corresponding to the optical paths of the first laser light and the second laser light is removed.

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