JP2021025823A - Flow analyzer in flow channel - Google Patents

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

The present invention relates to a flow analyzer in a flow path, such as analyzing the flow state of blood flowing in a blood chamber of a blood circuit used in blood purification therapy or the like, and particularly utilizes the coherence of laser light. It belongs to the technical field of structures for measuring flow velocity.

The blood circuit used in blood purification therapy is composed of a blood chamber, a tube, etc. Among these, in particular, for blood flow analysis in the blood chamber, a means for suppressing blood coagulation in the blood chamber is examined. It is important to do so. Possible factors of blood coagulation in the blood chamber are, for example, partial blood retention and speed change, and if these can be grasped concretely and the mechanism of blood coagulation can be analyzed, blood coagulation will occur. Allows difficult blood chamber design. However, the behavior of blood in the blood chamber is difficult to judge by appearance because the blood is an opaque liquid, and the parameter setting is complicated in the simulation analysis, and sufficient analysis is difficult.

Further, it is generally known that the flow velocity of a fluid in a circular tube can be measured by, for example, a two-dimensional current meter. As a two-dimensional current meter having high spatial resolution, a particle image velocimetry (PIV) method is widely used. For example, when visualizing the flow in a circular tube using the particle image velocimetry method, a sheet-shaped laser beam is incident so as to pass through the central axis of the circular tube, and the tracer particles moving on the surface of the sheet light are high. The method of shooting with a speed camera is used.

Laser Doppler velocimetry (LDV) is known as another flow velocity measurement having high spatial resolution, and this technique is used as a laser Doppler blood flow meter (see, for example, Patent Documents 1 and 2). In the laser Doppler blood flow meters of Patent Documents 1 and 2, the laser light emitted from the laser light source is branched into two and incident on a rod lens or a cylindrical lens to form a sheet light, and the sheet light is measured. It is equipped with an optical system that refracts the light so that it is incident on the lens. The scattered light from the tracer particles in the fluid in the intersecting region where the two sheet lights intersect is two-dimensionally focused and converted into an electric signal by the photoelectric conversion element. Since this electric signal called the Doppler burst signal contains a frequency component proportional to the velocity of the tracer particles in the fluid, the power spectrum obtained by performing a fast Fourier transform or the like on the Doppler burst signal. It is configured to calculate the flow velocity of the fluid in the intersection region.

International Publication No. 2009/081883 Pamphlet Japanese Unexamined Patent Publication No. 2015-59856

By the way, in the case of the particle image velocimetry method, a two-axis velocity component can be obtained by incident a sheet-shaped laser beam so as to pass through the central axis of the circular tube, but the remaining one axis (that is, the sheet light). It is not possible to obtain the velocity component (in the vertical direction with respect to the surface of). In order to visualize all the flow velocimetry in the three axial directions, it is necessary to use a stereo PIV using two high-speed cameras and thick sheet light. Therefore, it is considered that the stereo PIV is selected for the measurement target in which a vortex is generated along the inner wall of the circular tube. In the case of blood, it is convenient because red blood cells act as tracer particles, but the range of application of stereo PIV is limited, and it has been limited to peripheral blood vessels and thin artificial channels. This is due to the essential specification that PIV cannot adapt to opaque fluids.

Therefore, if a laser Doppler blood flow meter to which the LDV method is applied is used and a near-infrared laser light capable of suppressing the light absorption rate by hemoglobin and water molecules in the blood is used as the light source, PIV There is a possibility that it can be applied to a thick artificial flow path that is difficult to measure. However, the technique for acquiring flow velocity imaging using LDV is immature, and there is no measurement technique for visualizing the flow velocity in the circular tube. Of course, even with the existing LDV system, the flow velocity at any one point of the artificial flow path can be measured, so it is considered that it is not impossible to obtain a wide range of velocity distribution if a long time is spent, but in reality However, since the measurement time is limited, it is difficult to analyze the flow rate of blood in the blood chamber.

The present invention has been made in view of the above points, and an object of the present invention is that when performing blood flow analysis in a blood chamber, flow analysis can be performed in a short time even by using LDV. To do so.

In order to achieve the above object, in the present invention, the sheet-shaped first laser beam and the second laser beam are incident so as to intersect each other at a predetermined position in the flow path, and the scattered light is generated in the intersecting region of the laser beam. The flow velocity of blood is calculated from the included beat frequency, and the intersection position of the first laser light and the second laser light in the flow path is scanned in the irradiation direction of the laser light. ..

The first invention is a laser light source that emits a laser beam in the near infrared region and a laser beam emitted from the laser light source in a flow analyzer in the flow path that analyzes the flow state of the fluid flowing in the flow path. The laser light branching portion that branches into the first laser light and the second laser light, and the first laser light and the second laser light branched by the laser light branching portion intersect each other at a predetermined position in the flow path. A first optical system for refracting the laser light, a second optical system for forming the first laser light and the second laser light branched by the laser light branch into a sheet, the first laser light, and the second laser light. A condensing optical system that linearly condenses the scattered light of the first laser light and the second laser light by particles in a fluid moving through linear irradiation sites where the laser light intersects each other, and the condensing optical system. The frequency of the light beat included in the light-receiving element arranged at the light-collecting position, the photoelectric conversion element that converts the scattered light incident on the light-receiving element into an electric signal, and the scattered light at the linear irradiation site is described. A flow velocity calculation unit that calculates the flow velocity of the fluid at the linear irradiation site from the obtained frequency based on an electric signal, and the irradiation direction of the first laser beam and the second laser beam to the flow path. Is the X direction, the first laser beam and the second laser beam are scanned so that the intersection position of the first laser beam and the second laser beam in the flow path moves in the X direction. It is characterized in that it is provided with an X-direction scanning unit.

According to this configuration, the laser light emitted from the laser light source is branched into the first laser light and the second laser light to become a sheet-shaped laser light, and is incident so as to intersect each other at a predetermined position in the flow path. To do. Scattered light of the laser light is generated by particles in the fluid flowing through the linear irradiation site where the first laser light and the second laser light intersect each other, and the scattered light is linearly focused by the focusing optical system. It is received by a light receiving element and converted into an electric signal by a photoelectric conversion element. Since the scattered light has a beat proportional to the velocity of the particles in the fluid in the flow path, the flow velocity of the fluid at the linear irradiation site can be calculated based on the frequency of the beat. This calculation method is a well-known method, and for example, the methods described in Patent Documents 1, 2, and the like can be used.

Since the laser light is light in the near infrared region, for example, when the fluid is blood, the absorption rate of light by hemoglobin and water molecules in the blood is low, and therefore not only the surface layer portion in the flow path but also , It reaches the back, and the measurement range is expanded. The wavelength of the laser light can be, for example, in the range of 760 nm or more and 2500 nm or less, and is particularly preferably set in the range of 780 nm or more and 820 nm or less. If the wavelength is within this range, the absorption rate of the laser light in hemoglobin and water can be further reduced.

Then, by scanning the first laser beam and the second laser beam in the irradiation direction of the flow path, it is possible to acquire the flow velocity of the fluid in a short time from the front side of the flow path to the entire depth direction. Become.

Examples of the members constituting the flow path include, but are not limited to, a blood chamber, a blood tube, and the like. The flow path can be formed of, for example, a cylindrical member, a square tubular member, a conical member, a pyramidal member, a member having a shape similar to these, or the like. It is premised that these members have the translucency of the first laser beam and the second laser beam. The fluid may be, for example, blood, pseudo-blood, or the like.

In the second invention, when the longitudinal direction of the linear irradiation site is the Y direction, the intersection position of the first laser beam and the second laser beam in the flow path moves in the Y direction. It is characterized by including a Y-direction scanning unit that scans the first laser beam and the second laser beam.

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

A third invention is characterized in that a control device for controlling the X-direction scanning unit is provided, and the control device stops scanning by the X-direction scanning unit while the scattered light is received by the light receiving element. To do.

That is, when the first laser light and the second laser light are scanned, the frequency of the scattered light becomes a frequency in which the scanning speed is also taken into consideration, and an error may occur in the flow velocity of the fluid. When the scanning of the 1st laser light and the 2nd laser light is stopped, the light receiving element receives the scattered light due to the component of the fluid flowing in the linear irradiation site, and the flow velocity of the fluid can be obtained based on this. As a result, the scanning speeds of the first laser beam and the second laser beam do not affect the flow velocity of the fluid, and an accurate flow velocity can be obtained.

In the fourth invention, the X-direction scanning unit is a movable member to which the laser light source, the laser light branching unit, the first optical system, the second optical system, the condensing optical system, and the light receiving element are attached. The movable member is provided with an X-direction drive device for driving the movable member in the X-direction.

That is, if the relative positional relationship between the optical system and the laser light source or the relative positional relationship between the condensing optical system and the light receiving element deviates from the initial state, for example, the measurement accuracy may decrease. However, in the present invention, the laser light source, the laser light branch, the first optical system, the second optical system, the condensing optical system and the light receiving element are attached to the possible member, and the movable member is driven in the X direction by the X direction drive device. Therefore, when scanning the first laser beam and the second laser beam, the relative positional relationship between the optical system and the laser light source and the relative positional relationship between the condensing optical system and the light receiving element are in the initial state. It does not deviate from the deviation, and the measurement accuracy can be improved.

A fifth aspect of the present invention is characterized in that the linear irradiation portion in the flow path is provided with a visible light irradiation unit that irradiates visible light.

That is, for example, when adjusting the irradiation positions of the first laser light and the second laser light, since the first laser light and the second laser light are light in the near infrared region, the operator can visually check where the irradiation positions are. Can not do it. In the present invention, since visible light is irradiated to the linear irradiation site in the flow path, the irradiation positions of the first laser light and the second laser light can be visually confirmed.

In the sixth invention, the visible light irradiation unit is arranged on the side opposite to the flow path with the condensing optical system interposed therebetween, and irradiates the linear irradiation portion with visible light through the condensing optical system. It is characterized by being configured in.

According to this configuration, the focus of the visible light emitted from the visible light irradiation unit can be adjusted to the linear irradiation site by using the condensing optical system.

According to a seventh aspect of the present invention, the condensing optical system includes a first condensing lens arranged on the light receiving element side and a second condensing lens arranged on the flow path side, and the first optical system It is characterized in that it is composed of the second condenser lens.

According to this configuration, the first laser light and the second laser light branched by the laser light branching portion can be refracted by the second focusing lens constituting the focusing optical system and incident on the flow path. it can. That is, since the second condensing lens constituting the condensing optical system can be used as the first optical system, the configuration of the optical system can be simplified.

In the eighth invention, the second condensing lens is arranged so as to face the incident side of the first laser light and the second laser light in the flow path, and the first condensing lens and the second condensing lens are opposed to each other. The first condensing lens is arranged so as to face each other, and the first condensing lens is formed so as to avoid the optical paths of the first laser beam and the second laser beam.

According to this configuration, the condensing optical system is arranged so as to face the incident side of the first laser light and the second laser light in the flow path, so that the laser light source, the laser light branching portion, and the first optical The system, the second optical system, the condensing optical system, and the light receiving element can be integrated into a compact flow analyzer. In this case, since the first laser light and the second laser light do not enter the first condensing lens, they can be refracted in a predetermined direction by the second condensing lens.

A ninth aspect of the present invention is characterized in that a portion of the outer peripheral portion of the first condenser lens corresponding to the optical path of the first laser beam and the second laser beam is cut off.

According to this configuration, the first condenser lens can be provided so as to avoid the optical paths of the first laser beam and the second laser beam by a simple configuration in which a part of the first condenser lens is cut off.

According to the present invention, the laser light in the near infrared region is branched into the first laser light and the second laser light to form a sheet, and the laser light is crossed at a predetermined position in the flow path to flow the linear irradiation site. When calculating the flow velocity of the fluid based on the frequency of the optical beat of the scattered light by the particles in the fluid, the first laser beam and the second laser beam are scanned in the irradiation direction of the fluid. The fluid analysis of the above can be performed in a short time by LDV.

It is a schematic block diagram of the flow analysis apparatus in a blood chamber which concerns on embodiment of this invention. It is a block diagram of the flow analyzer in a blood chamber. It is a figure explaining the state which irradiated the laser beam to the blood chamber. It is a perspective view of the 1st condensing lens and the 2nd condensing lens. It is a figure explaining the structural example of a light receiving element and a photoelectric conversion element. It is a figure which shows the running of a laser beam in a blood chamber. It is a graph used for correction of the intersection position of a laser beam. It is a graph which shows the relationship between a spectral density and a frequency. It is a figure which shows the flow analysis result.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. It should be noted that the following description of the preferred embodiment is essentially merely an example and is not intended to limit the present invention, its application or its use.

FIG. 1 shows an in-fluid flow analysis device 1 according to an embodiment of the present invention. The flow analyzer 1 is an apparatus used for analyzing the flow state of blood flowing in a flow path formed in the blood chamber 100 of a blood circuit used in, for example, blood purification therapy. In this example, the flow analysis device 1 in the blood chamber will be described, but the present invention is not limited to this, and the device may also be used as a flow analysis device for a fluid containing particles that generate scattered light by irradiation with laser light, which will be described later. Can be done.

The blood purification therapy is hemodialysis with so-called extracorporeal circulation. In addition to the blood chamber 100, the blood circuit includes an inflow side tube for inflowing blood into the blood chamber 100, an outflow side tube for flowing out blood from the blood chamber 100, and the like, although not shown. As shown in FIG. 3, the blood chamber 100 includes a main body cylinder 101 made of a transparent resin formed into a cylindrical shape, a first closing member 102 that closes one end of the main body 101, and a main body 101. It is provided with a second closing member 103 that closes the other end of the. The first closing member 102 is provided with an inflow pipe portion 102a to which an inflow side tube is connected. A mesh (not shown) is provided in the inflow pipe portion 102a to prevent solids such as coagulated blood from returning to the body. Further, the second closing member 103 is provided with an outflow pipe portion 103a to which the outflow side tube is connected. Therefore, in this embodiment, the blood that has flowed in from above the blood chamber 100 is discharged from below. Further, since the inflow pipe portion 102a faces in the horizontal direction, a swirling flow is generated along the side wall in the blood chamber 100. The inner diameter of the main body cylinder 101 is set to, for example, about 15 mm to 20 mm. The material of the main body cylinder 101 is, for example, vinyl chloride.

(Overall configuration of flow analyzer 1)
The flow analyzer 1 is configured to enable so-called laser Doppler flow velocity measurement, and includes a device main body 2 shown in FIG. 1, a control device 3, a keyboard 4, a mouse 5, and a display unit 6. The control device 3 can be composed of, for example, the main body of a personal computer, a microcomputer, or the like. The keyboard 4 and the mouse 5 are for operating the control device 3, making various settings, inputting information, and the like. The display unit 6 is composed of, for example, a liquid crystal display or the like, is controlled by the control device 3, and is configured to be capable of displaying information, various data, images, and the like input by the keyboard 4 and the mouse 5 in color. ..

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

In the description of this embodiment, the longitudinal direction of the base material 20 is defined as the X direction, the vertical direction is defined as the Y direction, and the lateral direction of the base material 20 is defined as the Z direction, but this is defined for convenience of explanation. Just do it. The Y direction coincides with the longitudinal direction of the blood chamber 100.

The Y-direction scanning portion 31 is attached to a scanning portion mounting plate 20a provided so as to project upward from one end side in the longitudinal direction of the base material 20. The Y-direction scanning unit 31 includes a blood chamber fixing member 31a to which the blood chamber 100 is fixed, a guide rail 31b for guiding the blood chamber fixing member 31a in the vertical direction, and a Y-direction driving device 31c shown in FIG. There is. The Y-direction drive device 31c is connected to the control device 3 and is controlled by the control device 3. As the Y-direction drive device 31c, for example, a well-known linear actuator, an actuator in which a stepping motor and a feed screw mechanism are combined, and the like can be used, but the present invention is not limited to these, and the blood chamber fixing member 31a is vertically oriented. Any device that can be moved will do. The blood chamber fixing member 31a can be moved only in the Y direction by the guide rail 31b. The movement amount and movement timing of the blood chamber fixing member 31a are set by a control signal output from the control device 3.

An X-direction scanning portion 30 is attached to the upper surface of the base material 20 at a portion separated from the scanning portion mounting plate 20a to the other side. The X-direction scanning unit 30 includes a movable member 30a, a fixing member 30b, and an X-direction driving device 30c. The fixing member 30b is fixed to the upper surface of the base material 20 and includes a guide rail 30d extending in the X direction. The movable member 30a can be made of a plate material or the like extending in the X direction and the Z direction, and can move only in the X direction along the guide rail 30d. The X-direction drive device 30c is connected to the control device 3 and is controlled by the control device 3. As the X-direction drive device 30c, for example, a well-known linear actuator, an actuator in which a stepping motor and a feed screw mechanism are combined, and the like can be used, but the present invention is not limited to these, and the movable member 30a is moved in the X direction. Any device that can do this will do.

The laser output device 21, the laser light branch portion 22, the first rod lens 23, the second rod lens 24, the condensing optical system 25, and the light receiving element 26 are attached to the movable member 30a by, for example, a bracket, a pedestal, or the like (not shown). Has been done. The laser output device 21 is a laser light source that emits laser light in the near infrared region. The wavelength of the laser light in the near infrared region can be, for example, in the range of 760 nm or more and 2500 nm or less. In this embodiment, the near-infrared laser light having a wavelength of 808 nm is irradiated, but the present invention is not limited to this, and for example, the near-infrared laser light in the range of 780 nm or more and 820 nm or less can be irradiated. Around 800 nm is a wavelength region where both hemoglobin and water absorption are low, and in general, it can travel in the blood to a depth of about 10 times that of visible light (wavelength 400 to 700 nm), but laser light. Is inevitably attenuated in the blood, so it is preferable to use a laser output device 21 having a high output. In this embodiment, the output at the injection end of the laser output device 21 is 141 mW, but the output is not limited to this.

The emission direction of the laser output device 21 is the X direction and the side toward the blood chamber 100. A collimating lens 21a is installed at the injection end of the laser output device 21. Further, at the ejection end of the laser output device 21, a polarizing filter 21b for passing linearly polarized p-polarized light is also installed on the side closer to the blood chamber 100 than the collimating lens 21a. The laser light emitted from the laser output device 21 passes through the collimating lens 21a and then enters the polarizing filter 21b. In this embodiment, p-polarized light is used, but the deflection direction is not limited to this.

The laser light branching unit 22 is a beam splitter that splits the laser light emitted from the laser output device 21, and is a well-known member. The laser light branching portion 22 is arranged so as to face the polarizing filter 21 on the side closer to the blood chamber 100 than the polarizing filter 21b. From the laser light branching portion 22, the first laser light L1 traveling in the X direction and toward the blood chamber 100 and the second laser light L2 traveling in the Z direction are emitted.

A mirror 28 is attached to the movable member 30a. The mirror 28 is arranged so that the second laser light L2 emitted from the laser light branching portion 22 is incident, and the second laser light L2 reflected by the mirror 28 becomes parallel to the first laser light L1. It becomes the light that travels toward the blood chamber 100. The first laser light L1 and the second laser light L2 are light that passes through the same height and travels horizontally. Further, the optical path of the first laser beam L1 and the optical path of the second laser beam L2 are separated in the Z direction.

A condensing optical system 25 is installed between the laser light branching portion 22 and the blood chamber 100. The condensing optical system 25 includes a first condensing lens 25a and a second condensing lens 25b, and the first condensing lens 25a and the second condensing lens 25b have their optical axes oriented in the X direction. They are arranged so as to face each other. The first condensing lens 25a and the second condensing lens 25b can each be composed of an achromatic lens formed by joining lenses made of materials having different refractive indexes. The first condensing lens 25a is arranged on the laser output device 21 side, and the second condensing lens 25b is arranged on the blood chamber 100 side.

As shown in FIG. 4, the portion of the outer peripheral portion of the first condensing lens 25a corresponding to the optical path of the first laser beam L1 and the portion corresponding to the optical path of the second laser beam L2 are cut off. That is, on the outer peripheral portion of the first condensing lens 25a, cutting portions 25c and 25c formed by cutting a part of the first condensing lens 25a are provided at two locations separated in the Z direction. By providing the cutting portions 25c and 25c, the first condensing lens 25a is formed so as to avoid the optical path of the first laser beam L1 and the optical path of the second laser beam L2. The first laser beam L1 and the second laser beam L2 travel straight in the X direction through the side of the first condensing lens 25a.

On the other hand, the second condensing lens 25b is formed so as to be located on the optical path of the first laser beam L1 and the optical path of the second laser beam L2. The second condensing lens 25b is a lens that refracts the first laser light L1 and the second laser light L2 branched by the laser light branching portion 22 so as to intersect each other at a predetermined position in the blood chamber 100. Therefore, the second condensing lens 25b is a lens constituting the first optical system of the present invention, and by using the second condensing lens 25b constituting the condensing optical system 25 as the first optical system, , The configuration of the optical system can be simplified. The intersecting position of the first laser beam L1 and the second laser beam L2 can be arbitrarily set by the position of the second condensing lens 25b and the optical design of the second condensing lens 25b. In this embodiment, FIG. As shown in the above, the first laser beam L1 and the second laser beam L2 intersect at a distance of about 150 mm from the second condenser lens 25b.

The first rod lens 23 and the second rod lens 24 are arranged on the blood chamber 100 side of the second condensing lens 25b at intervals in the Z direction. The first laser beam L1 that has passed through the second condenser lens 25b is incident on the first rod lens 23, and the second laser beam L2 that has passed through the second condenser lens 25b is incident on the second rod lens 24. The first rod lens 23 is a lens that changes the first laser beam L1 into sheet-shaped light (first sheet light) extending in the Y direction. The second rod lens 24 is a lens that changes the second laser beam L2 into sheet-shaped light (second sheet light) extending in the Y direction. The first rod lens 23 and the second rod lens 24 are the second optical systems of the present invention. In this embodiment, in order to suppress the attenuation of the wavelength of the laser light on the surfaces of optical components such as the first condensing lens 25a, the second condensing lens 25b, the first rod lens 23, and the second rod lens 24. , Anti-reflection film for this wavelength is coated. Further, a cylindrical lens or the like can be used instead of the rod lens, and the configuration is not limited as long as it is an optical system capable of generating sheet-like light.

As shown in FIG. 3, by forming the sheet-shaped light extending in the Y direction, the portion where the first laser light and the second laser light intersect each other has a high light intensity in a single linear shape extending in the Y direction. It is formed as a portion, and this portion becomes the linear irradiation site A. The thickness of the sheet light at the linear irradiation site A can be adjusted by the collimating lens 21a, and in this embodiment, the thickness of the sheet light at the linear irradiation site A is 0.2 mm. At the linear irradiation site A, interference fringes of vertical stripes continuous in the Y direction are formed due to the phase difference between the incident wave planes of the first laser light L1 and the second laser light L2. The thickness of the sheet light can be set in the range of, for example, 0.1 mm to 1.0 mm.

When light is irradiated to particles (tracer particles) having a diameter larger than the wavelength of light, scattered light is emitted from the particles by Mie scattering. Examples of particles having a diameter larger than the wavelength of near-infrared laser light include red blood cells, which are components of blood. Therefore, when the first laser light L1 and the 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. The scattered light is scattered in various directions according to the theory of Mie scattering. At this time, the scattered light from the linear irradiation site A includes a light beat (beat). The frequency of the optical beat is proportional to the speed at which the red blood cells pass through the linear irradiation site A.

Of the scattered light emitted from the particles, the light that travels toward the second condenser lens 25b of the condenser optical system 25 passes through the second condenser lens 25b and the first condenser lens 25a in order and is condensed. The light. The light receiving element 26 shown in FIG. 1 is arranged at a position where the scattered light is collected. Therefore, the first condensing lens 25a of the condensing optical system 25 is arranged on the light receiving element 26 side, and the second condensing lens 25b is the incident of the first laser light L1 and the second laser light L2 in the blood chamber 100. It will be arranged so as to face the side.

As shown in FIG. 5, the light receiving element 26 can be composed of, for example, an optical fiber array composed of a plurality of optical fibers 26a, and in this embodiment, one end portion (end portion serving as the light receiving portion) 26b of the plurality of optical fibers 26a. Are arranged so as to be adjacent to each other in the Y direction and arranged in a straight line. The scattered light of the linear irradiation site A is linearly focused by the condensing optical system 25 at a position where one end 26b of the optical fiber 26a is lined up.

As the optical fiber 26a constituting the light receiving element 26, for example, a plastic fiber (EsKa SH-1001) having a diameter of 0.25 mm or the like can be used. The optical fiber 26a may be a glass fiber. In order to increase the spatial resolution, it is preferable to use an optical fiber 26a having a smaller diameter.

The number of optical fibers 26a is not particularly limited, but is 32 in this embodiment. One end 26b of the optical fiber 26a can be arranged side by side without a gap and held by a holding member (not shown). The numerical aperture NA of one end 26b of the optical fiber 26a is 0.5, which is set smaller than the numerical aperture of the first condensing lens 25a and the second condensing lens 25b. Therefore, in order to prevent stray light from entering the one end 26b of the optical fiber 26a, a single slit 26c (shown in FIG. 1) long in the Y direction is arranged in front of the one end 26b of the optical fiber 26a. The width of the single slit 26c is set so as to match the numerical aperture of the first condensing lens 25a and the second condensing lens 25b. A polarizing filter 26e is arranged between the single slit 26c and one end 26b of the optical fiber 26a. It is desirable that the polarization directions of the polarizing filter 21b and the polarizing filter 26 are the same.

As shown in FIG. 5, the other end 26d of the optical fiber 26a is coupled (connected) to the 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 electric signal, and is provided for each optical fiber 26a. Therefore, in this embodiment, 32 avalanche photodiodes 27 are provided.

The control device 3 includes a flow velocity calculation unit 3a. The scattered light has a light bead (beat) due to the flow of blood in the blood chamber 100. The flow velocity calculation unit 3a obtains an optical beat frequency generated by the flow of blood in the blood chamber 100 based on an electric signal output from each avalanche photodiode 27, and from the obtained frequency at the linear irradiation site A. It is configured to calculate the flow velocity of blood. As the calculation method by the flow velocity calculation unit 3a, for example, the method disclosed in Patent Documents 1 and 2 and the method described later can be used.

The flow velocity can be obtained with a spatial resolution determined by the magnification of the condensing optical system 25 in units of the optical fiber 26a. For example, if the optical fiber 26a having a diameter of 0.25 mm is used and the magnification of the condensing optical system 25 is 1, the spatial resolution is 0.25 mm.

Further, the laser light branching unit 22 is provided with an acoustic optical element (AOM) that branches the continuously oscillating laser light from the laser output device 21 into the first laser light L1 and the second laser light L2 having slightly different frequencies. You may. By applying modulation with an acoustic optical element, the direction of blood flow can also be identified. However, when it is not necessary to identify the flow direction, it is not necessary to perform frequency modulation by the acoustic optical element.

Since the wavelengths of the first laser light L1 and the second laser light L2 are outside the visible light region, the linear irradiation site A cannot be visually observed. In this embodiment, as shown in FIG. 5, a visible light irradiation unit 29 that irradiates the linear irradiation site A in the blood chamber 100 with visible light is provided. The visible light irradiation unit 29 has an optical fiber 29a similar to the optical fiber 26a, 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 the one end 26b of the optical fiber 26a. A visible light emitting unit 29b provided with a light emitting element such as a light emitting diode (LED) is connected to the other end of the optical fiber 29a, and the light emitted from the visible light emitting unit 29b is the other end of the optical fiber 29a. It is designed to be incident on the part. Therefore, visible light is emitted from one end 29c of the optical fiber 29a. Since the visible light irradiation unit 29 is arranged on the opposite side of the condensing optical system 25 from the blood chamber 100, the visible light irradiated from one end 29c of the optical fiber 29a passes through the condensing optical system 25. It binds at the linear irradiation site A and irradiates the linear irradiation site A. As a result, a spot of light can be seen on the linear irradiation site A, and the initial position of the blood chamber 100 can be determined with reference to the spot of light. The light emitted from the visible light emitting unit 29b is not particularly limited, but a color that can be, for example, red, green, blue, or the like and is easily distinguished from natural light is preferable.

(Scanning of laser light)
By operating the X-direction drive device 30c of the X-direction scanning unit 30 shown in FIG. 1, the movable member 30a can be moved in both the plus side and the minus side in the X direction. A laser output device 21, a laser light branching portion 22, a first rod lens 23, a second rod lens 24, a condensing optical system 25, and a light receiving element 26 are attached to the movable member 30a, so that a laser light irradiation system is attached. And the light receiving system can be moved in the X direction without changing the relative positional relationship of each member. As a result, the linear irradiation portion A, which is the intersection of the first laser beam L1 and the second laser beam L2 emitted from the laser output device 21, moves in the X direction.

The scanning of the laser beam will be described in detail with reference to FIG. 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, and the point O is a point on the center line of the blood chamber 100. It is assumed that pseudo blood is flowing in the blood chamber 100, but blood may be flowing. Pseudo-blood is a liquid in which tracer particles are dispersed in a 45 wt% glycerin aqueous solution simulating the viscosity of blood. As the tracer particles, polyethylene particles having a diameter of 10 μm were used. 10 mg of polyethylene particles was added to 1 liter of an aqueous glycerin solution. A roller-type tube pump (MF-01 manufactured by JMS), which is actually used for dialysis treatment, is used as a liquid feeding pump for sending simulated blood. The flow rate of simulated blood by the liquid feed pump was set in the range of 150 to 300 ml / min, which is a typical value in dialysis treatment.

Here, the light incident from the outside to the inside of the blood chamber 100 is refracted twice at the interface between the air and the blood chamber 100 and the interface between the blood chamber 100 and the pseudo blood. Since the refractive index n1 of air is 1.0, the refractive index n2 of almost colorless and transparent vinyl chloride which is the material of the blood chamber 100 is 1.52, and the refractive index n3 of pseudo-blood is 1.32. , The irradiation angle of light will change twice. Further, in the present embodiment, since the first laser light L1 and the second laser light L2 are scanned in the X direction, the incident angles of the first laser light L1 and the second laser light L2 on the blood chamber 100 are in the X direction. It changes according to the position of the movable member 30a of the scanning unit 30, and the amount of displacement of the movable member 30a in the X direction and the amount of displacement of the intersection of the first laser beam L1 and the second laser beam L2 in the X direction are Not the same.

This will be described with reference to FIG. In FIG. 6, assuming that the virtual intersection when the first laser light L1 and the second laser light L2 go straight without refraction (when going straight in the air) is P1, the actual first laser light L1 and the second laser light L1 and the second laser light L1. The intersection of the laser beam L2 is P2. When the point S in FIG. 6 is used as the reference position, the relationship between the distance d from the point S to the point P1 and the distance d1 from the point S to the point P2 is represented by the curve displayed in the graph shown in FIG. Can be done.

In the control device 3, by using the curve shown in FIG. 7, the position of the intersection of the first laser beam L1 and the second laser beam L2 can be obtained 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, the incident angle of the laser beam, and the like, and stored in the storage unit 3b of the control device 3 shown in FIG. The displacement of the movable member 30a of the X-direction scanning unit 30 can be obtained based on a well-known displacement sensor, a drive amount by the X-direction drive device 30c, or the like.

However, move the movable member 30a of the X-direction scanning unit 30 so that the intersection of the first laser beam L1 and the second laser beam L2 always passes on the straight line B extending in the X direction through the center point O of the blood chamber 100. For example, since the angles of incidence of the first laser beam L1 and the second laser beam L2 on the blood chamber 100 are always the same, the X-axis of the intersection of the first laser beam L1 and the second laser beam L2 can be calculated by a simple geometric calculation. The amount of displacement above can be obtained. Similarly, the intersection angle of the first laser beam L1 and the second laser beam L2 (the intersection angle is a necessary parameter when calculating the flow velocity) can be obtained by a simple geometric calculation, although it is not always constant. it can.

If the intersection of the laser beams is scanned along the Z axis to obtain the velocity distribution, the angles of incidence of the first laser beam L1 and the second laser beam L2 on the blood chamber 100 are not always the same. Therefore, not only the calculation becomes complicated to specify the intersection position and the intersection angle of the laser light, but also to make the intersection of the laser light move on a straight orbit passing through the center line of the blood chamber 100. After all, it is necessary to control the two axes by also using the drive device in the X direction. Therefore, scanning in the Z-axis direction complicates the configuration and complicates control, so scanning in the X-direction described above is preferable.

The Y-direction scanning unit 31 is used when measuring a measurement target having a long dimension in the Y direction. The operation of the two-axis electric stage 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 repeated 10 times to obtain one blood. The flow velocity of pseudo blood in the chamber 100 can be measured. Therefore, in this case, the total number of measurements is 450. Moreover, since 32 channels are simultaneously measured per measurement, the total measurement points are 14,400 points. For example, when time-series data for 1.5 seconds is recorded at all points, the total measurement time is about 38 minutes including the time required to save the data in the storage unit 3b. The simplest method of shortening the measurement time is to increase the number of channels to be simultaneously measured from the current 32 channels, that is, to increase the number of optical fibers 26a constituting the light receiving element 26.

The above-mentioned number of measurements is an example, and if the diameter of the blood chamber 100 is small, the number of measurements can be reduced, and if the vertical dimension of the blood chamber 100 is short, the number of measurements can be reduced. On the other hand, the measurement points can be made finer to improve the resolution. The setting of the number of measurements, the measurement range, and the like can be input to the control device 3 by the keyboard 4, the mouse 5, and the like, and the input result displayed on the display unit 6 can be confirmed.

The control device 3 is configured to stop scanning by the X-direction scanning unit 30 while the scattered light is received by the light receiving element 26. The time for receiving the scattered light by the light receiving element 26 can be set to about 1.5 seconds as described above, but during this period, the scanning by the X-direction scanning unit 30 is stopped, so that the first laser light L1 and The linear irradiation site A of the second laser beam L2 is not moved. That is, when the first laser light L1 and the second laser light L2 are scanned during the light receiving time, the frequency of the scattered light becomes the frequency in which the scanning speeds of the first laser light L1 and the second laser light L2 are taken into consideration. Therefore, there is a possibility that an error may occur in the flow velocity of the blood, but in this embodiment, the component of the blood flowing through the linear irradiation site A when the scanning of the first laser light L1 and the second laser light L2 is stopped. The scattered light can be received by the light receiving element 26, and the flow velocity of blood can be obtained based on this. As a result, the scanning speeds of the first laser beam L1 and the second laser beam L2 do not affect the blood flow velocity, and an accurate flow velocity can be obtained. The time for receiving the scattered light by the light receiving element 26 can be arbitrarily set, and can be set in the range of, for example, 0.1 seconds to 3 seconds.

(Signal processing)
In the avalanche photodiode 27, photons incident from the optical fiber 26a are converted into carriers, but since the amplitude of this current is very weak (1 pA or less), an amplification unit 3c is provided in the control device 3, and the amplification unit 3c provides an amplification unit 3c. It is configured to convert into a voltage signal having an amplitude of about 1 V at the maximum. Further, the control device 3 is provided with a high-pass filter 3d into which the signal amplified by the amplification unit 3c is input. The high-pass filter 3d is a high-order Butterworth filter, and the cutoff frequency can be 100 Hz. The pedestal component is removed using this high-pass filter 3d. Further, the control device 3 is also provided with 32 AD conversion units 3e into which 32ch voltage signals are input. The resolution of the AD conversion unit 3e can be 12 bits, and the sampling frequency can be 10 MHz. The time-series voltage data simultaneously A / D converted by the AD conversion unit 3e can be stored in the storage unit 3b. The amplification unit 3c, the high-pass filter 3d, and the AD conversion unit 3e may be provided in addition to the control device 3.

Here, there is a method of performing a fast Fourier transform (FFT process) on the voltage data of the time series to obtain the flow velocity from the frequency position of the peak appearing on the spectrum, but in order to obtain sufficient intensity of scattered light, a large particle size is used. Tracer particles are needed. For example, in the case of polyethylene particles, particles having a diameter of 30 μm or more are required. This is because the intensity of scattered light is proportional to the square of the particle size. However, there is a mesh in the inflow tube portion 102a of the blood chamber 100, and particles having a diameter of 30 μm clog the holes in the mesh. Therefore, in the above-mentioned pseudo-blood, 10 μm particles are added to the glycerin aqueous solution at a high concentration, thereby increasing the number of particles per unit volume. Of course, as the number of particles increases, the intensity of scattered light increases, but since scattered light from many particles is received at the same time, it may be difficult to confirm a clear peak on the spectrum.

It is difficult to observe a clear peak on the typical spectrum obtained by measuring any one point in the blood chamber 100, but the spectrum can be seen before and after flowing a fluid such as an aqueous glycerin solution from the liquid feed pump. As a result, it can be confirmed that when the fluid flows, the high frequency side rises a little when the flow rate of the liquid feed pump is increased as shown in FIG. The following equation using the weighted integral of the wavenumber can be used to obtain the expected value of the optical beat frequency from such a spectrum and to obtain the flow velocity v from the expected value of the beat frequency.

Here, d is the fringe interval of the laser beam, and P (f) is the power spectral density. The integration start frequency f ₁ was set to 100 Hz, which is the cutoff frequency of the high-pass filter. In addition, the end frequency _{f Z} was set at 25kHz. As a result, the above formula becomes the same formula as calculating the flow velocity with a laser Doppler blood flow meter.

For example, when time series data for 1.5 seconds per channel is recorded, the typical size of binary data is about 30 Gbytes per two-dimensional flow velocity image. If all the huge amount of data is FFT processed in this way, a huge amount of analysis time is required.

Therefore, the analysis time can be shortened by parallel calculation using the graphic processing unit (Nvidia GTX-1080Ti). The processing time for FFT processing 30 Gbyte binary data and converting it to flow velocity is about 9 minutes, which is about 1/1/ compared to the case of parallel calculation of 8 threads using a CPU (Intel core i7 6700K). It can be shortened to 3. Therefore, it is preferable that the control device 3 includes the graphic processing unit.

In addition, although sensitivity variation occurs due to individual differences in the quantum efficiency of the avalanche photodiode 27, the power spectrum obtained when a large number of avalanche photodiodes 27 are prepared and the same optical signal input is input. It is preferable to select and use 32 avalanche photodiodes 27 having the same characteristics as measured by all avalanche photodiodes 27.

(Measurement result)
FIG. 9 shows an example of the measurement result display screen displayed on the display unit 3 shown in FIG. In this graph, the flow velocity value is set on the vertical axis, and the color is changed according to the flow velocity value. This display form can be realized by processing by the control device 3.

The liquid used in the experiment was the above-mentioned pseudo blood, and the flow rate of the liquid feed pump was 250 ml / min. Since a roller type tube pump is used in the experiment, pulsations that match the rotation cycle of the rollers are generated in the blood chamber 100. Therefore, since the flow velocity also changes in response to the pulsation, the flow velocity value is set as the time average value in two cycles of the roller (when the flow rate is 250 ml / min, it is about 2.0 seconds). Since the blood chamber 100 of the type in which the inflow tube portion 102a is laterally used is used, the flow velocity in the central portion of the circular tube is slow, and the flow velocity on both sides is high. This velocity distribution suggests that a swirling flow is occurring in the chamber, and from this graph, the flow velocity at the center of the vortex is about 4 mm / s, and the flow velocity at the outer circumference of the vortex is about 10 mm / s. You can see that. It is generally considered that blood coagulation in a blood chamber is likely to occur in a part where the flow velocity is slow or a part where the change in the flow velocity is large, and it is possible to predict the part where blood coagulation is likely to occur from such a velocity distribution. it can.

(Action and effect of the embodiment)
As described above, according to the flow analyzer 1 in the blood chamber according to this embodiment, the laser light emitted from the laser output device 21 is branched into the first laser light L1 and the second laser light L2 before the sheet. It becomes a laser beam in the shape of a laser beam, and is incident so as to intersect each other at a predetermined position in the blood chamber 100. Scattered light of the laser light is generated by blood cells in the blood flowing through the linear irradiation site A where the first laser light L1 and the second laser light L2 intersect each other, and the scattered light is linearized by the condensing optical system 25. The light is collected by the light receiving element 26, and is converted into an electric signal by the photoelectric conversion element 27. The scattered light has a beat (beat) having a frequency proportional to the flow velocity of the blood in the blood chamber 100, and the flow velocity of the blood at the linear irradiation site A can be calculated based on the frequency of this beat. Since the laser light is light in the near-infrared region, the absorption rate of light by hemoglobin and water molecules in the blood is low, and therefore, it reaches not only the surface layer portion in the blood chamber 100 but also the inner part thereof. The measurement range is expanded.

Then, by scanning the first laser beam L1 and the second laser beam L2 in the X direction, which is the irradiation direction of the blood chamber 100, by the X-direction scanning unit 30, the blood chamber 100 extends from the front side to the entire depth direction. The blood flow velocity can be obtained in a short time.

The above embodiments are merely exemplary in all respects and should not be construed in a limited way. Furthermore, all modifications and modifications that fall within the equivalent scope of the claims are within the scope of the present invention.

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

The flow path may be formed of a cylindrical member, a conical member, a pyramidal member, a member having a shape similar to these, or the like, in addition to the cylindrical member such as the blood chamber described above. it can.

As described above, the flow analyzer in the flow path according to the present invention can be used, for example, when analyzing the flow state of blood flowing in the blood chamber of the blood circuit.

1 Flow analysis device 3 Control device 3a Flow velocity calculation unit 21 Laser output device (laser light source)
22 Laser light branch 23 1st rod lens (2nd optical system)
24 2nd rod lens (2nd optical system)
25 Condensing optical system 25a First condensing lens 25b Second condensing lens (first optical system)
26 Receiver element 27 Avalanche photodiode (photoelectric conversion element)
29 Visible light irradiation unit 30 X-direction scanning unit 30a Movable member 30c X-direction driving device 31 Y-direction scanning unit 100 Blood chamber A Linear irradiation site L1 First laser light L2 Second laser light

Claims (9)

In a flow analyzer in a flow path that analyzes the flow state of a fluid flowing in the flow path,
A laser light source that emits laser light in the near infrared region,
A laser light branching portion that branches the laser light emitted from the laser light source into the first laser light and the second laser light, and
A first optical system that refracts the first laser light and the second laser light branched by the laser light branching portion so as to intersect each other at predetermined positions in the flow path.
A second optical system that forms a sheet of the first laser light and the second laser light branched by the laser light branching portion, and
Condensing the scattered light of the first laser beam and the second laser beam by particles in a fluid moving in a linear irradiation site where the first laser beam and the second laser beam intersect each other in a linear manner. Optical system and
The light receiving element arranged at the condensing position of the condensing optical system and
A photoelectric conversion element that converts the scattered light incident on the light receiving element into an electric signal, and
A flow velocity calculation unit that obtains the frequency of the light beat included in the scattered light at the linear irradiation site based on the electric signal and calculates the flow velocity of the fluid at the linear irradiation site from the obtained frequency.
When the irradiation direction of the first laser beam and the second laser beam to the flow path is the X direction, the intersection position of the first laser light and the second laser light in the flow path is the X direction. A flow analyzer in a flow path, characterized in that it includes an X-direction scanning unit that scans the first laser beam and the second laser beam so as to move to. In the flow analyzer in the flow path according to claim 1,
When the longitudinal direction of the linear irradiation site is the Y direction, the first laser beam is such that the intersection position of the first laser beam and the second laser beam in the flow path moves in the Y direction. A flow analysis device in a flow path, which comprises a Y-direction scanning unit that scans the second laser beam. In the flow analyzer in the flow path according to claim 1 or 2.
A control device for controlling the X-direction scanning unit is provided.
The control device is a flow analysis device in a flow path, characterized in that scanning by the X-direction scanning unit is stopped while the scattered light is received by the light receiving element. In the flow analyzer in the flow path according to any one of claims 1 to 3,
The X-direction scanning unit includes the laser light source, the laser light branching unit, the first optical system, the second optical system, the condensing optical system, a movable member to which the light receiving element is attached, and the movable member. A flow analyzer in a flow path including the X-direction drive device that drives in the X direction. In the flow analysis device in the flow path according to any one of claims 1 to 4.
A flow analysis device in a flow path, which comprises a visible light irradiation unit that irradiates the linear irradiation site in the flow path with visible light. In the flow analyzer in the flow path according to claim 5,
The visible light irradiation unit is arranged on the side opposite to the flow path with the condensing optical system interposed therebetween, and is configured to irradiate the linear irradiation site with visible light through the condensing optical system. A flow analyzer in a flow path characterized by. In the flow analysis device in the flow path according to any one of claims 1 to 6.
The condensing optical system includes a first condensing lens arranged on the light receiving element side and a second condensing lens arranged on the flow path side.
The first optical system is a flow analysis device in a flow path, characterized in that it is composed of the second condenser lens. In the flow analyzer in the flow path according to claim 7,
The second condensing lens is arranged so as to face the incident side of the first laser beam and the second laser beam in the flow path.
The first condensing lens and the second condensing lens are arranged so as to face each other.
The first condensing lens is a flow analysis device in a flow path, which is formed so as to avoid the optical paths of the first laser beam and the second laser beam. In the flow analyzer in the flow path according to claim 8,
A flow analysis device in a flow path, wherein a portion of the outer peripheral portion of the first condensing lens corresponding to the optical path of the first laser beam and the second laser beam is cut off.