WO2010047191A1 - Device for measuring blood cell deformability - Google Patents

Device for measuring blood cell deformability Download PDF

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Publication number
WO2010047191A1
WO2010047191A1 PCT/JP2009/065813 JP2009065813W WO2010047191A1 WO 2010047191 A1 WO2010047191 A1 WO 2010047191A1 JP 2009065813 W JP2009065813 W JP 2009065813W WO 2010047191 A1 WO2010047191 A1 WO 2010047191A1
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WO
WIPO (PCT)
Prior art keywords
blood
gate
deformability
blood cell
volume
Prior art date
Application number
PCT/JP2009/065813
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French (fr)
Japanese (ja)
Inventor
修司 一谷
Original Assignee
コニカミノルタオプト株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by コニカミノルタオプト株式会社 filed Critical コニカミノルタオプト株式会社
Priority to CN200980141499.5A priority Critical patent/CN102187217B/en
Priority to JP2010534755A priority patent/JP5093357B2/en
Publication of WO2010047191A1 publication Critical patent/WO2010047191A1/en

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    • G01N15/1433—
    • G01N2015/012—
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Electro-optical investigation, e.g. flow cytometers
    • G01N2015/1493—Particle size
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Electro-optical investigation, e.g. flow cytometers
    • G01N2015/1493—Particle size
    • G01N2015/1495—Deformation of particles

Definitions

  • the present invention relates to a blood cell deformability measuring apparatus.
  • the deformation index is defined using the major and minor diameters of elliptical red blood cells from the diffraction image.
  • a method for calculating the deformation index as a quantitative value of the deformability of red blood cells has been proposed (see, for example, Patent Documents 1 and 2).
  • Patent Documents 1 and 2 are methods that can be applied only to red blood cells that retain an elliptical shape, and cannot be applied to amoeba-like white blood cells that can be deformed into various shapes.
  • moving blood cells can be displayed as an image, it is difficult to visually grasp how the blood cells move while deforming because the blood cells flow at a uniform speed on the image.
  • the present invention has been made in view of the above circumstances, and can measure each deformability when red blood cells and white blood cells pass through capillaries and can easily grasp the state of blood cells moving while deforming. It is an object to provide a measuring device.
  • a blood cell deformability measuring device for flowing blood from an upstream terrace having a width wider than the blood cell diameter toward a gate having a width narrower than the blood cell diameter, and measuring the deformability of the blood cells in the blood, Imaging means for imaging the flow of blood passing through the upstream terrace and the gate; From the blood flow image obtained by the imaging means, speed calculation means for calculating the speed of blood cells passing through the upstream terrace or the gate; From the blood flow image obtained by the imaging means, volume calculating means for calculating the volume of blood cells passing through the gate; Deformability calculating means for calculating the deformability of the blood cell from the velocity of the blood cell and the volume of the blood cell; It is characterized by providing.
  • the invention according to claim 2 is the blood cell deformability measuring device according to claim 1,
  • the deformability calculating means calculates D 1 or D 2 satisfying the following formula (1) or formula (2) as the deformability of the blood cell.
  • the invention according to claim 4 is the blood cell deformability measuring apparatus according to any one of claims 1 to 3, It has blood flow image display means for displaying a blood flow image obtained by the photographing means on a display screen.
  • the invention according to claim 5 is the blood cell deformability measuring apparatus according to any one of claims 1 to 4, A plurality of the gates; Occlusion state calculation means for calculating the occlusion ratio of the gate occluded by the blood cells, wherein the blood cell speed obtained by the speed calculation means is zero,
  • the deformability calculating means calculates the deformability of the blood cell from the occlusion ratio of the gate and the volume of the blood cell closed by the volume calculating means.
  • the invention according to claim 6 is the blood cell deformability measuring device according to claim 5,
  • the occlusion state calculating means calculates the occlusion ratio of the gate that is occluded by blood cells of the volume according to the volume of the blood cells,
  • the deformability calculation means calculates a D 1 satisfies the following equation (3).
  • the invention according to claim 7 is the blood cell deformability measuring device according to claim 5 or 6,
  • the plurality of gates are arranged in the blood flow direction and are formed in a plurality of different widths so as to gradually narrow from the upstream side to the downstream side in the blood flow direction, or orthogonal to the blood flow direction.
  • the occlusion state calculating means detects, as a maximum occlusion width, the largest one of the widths of the gates occluded by the blood cells, from the blood flow image obtained by the imaging means,
  • the deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means.
  • the invention according to claim 8 is the blood cell deformability measuring apparatus according to claim 5 or 6,
  • the plurality of gates form a plurality of sets for each width
  • the blockage state calculating means obtains the blockage rate of the gate blocked by the blood cells according to the width of the gate, and detects the width of the gate that maximizes the blockage rate as the maximum blockage width
  • the deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means.
  • the invention according to claim 9 is the blood cell deformability measuring device according to claim 5 or 6,
  • the occlusion state calculating means detects, as a maximum occlusion width, the width of the gate at the occlusion position of the blood cell in the gate occluded with the blood cell from the blood flow image obtained by the imaging means,
  • the deformability calculating means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell closed by the volume means.
  • the invention according to claim 10 is the blood cell deformability measuring apparatus according to any one of claims 7 to 9,
  • the deformability calculating means calculates D 2 or D 3 satisfying the following formula (4) or formula (5) as the deformability of the blood cell.
  • the invention according to claim 11
  • a blood cell deformability measuring apparatus for flowing blood to a plurality of gates formed with a narrower width than the blood cell diameter and measuring the deformability of the blood cells in the blood, Photographing means for photographing the flow of blood passing through the gate; From the blood flow image obtained by the imaging means, an occlusion state calculation means for calculating the occlusion ratio of the gate occluded by the blood cells, From the blood flow image obtained by the imaging means, a volume calculation means for calculating the volume of the blood cell
  • the invention according to claim 12 is the blood cell deformability measuring device according to claim 11,
  • the occlusion state calculating means calculates the occlusion ratio of the gate that is occluded by blood cells of the volume according to the volume of the blood cells,
  • the deformability calculation means calculates a D 1 satisfies the following equation (3).
  • the invention according to claim 13 is the blood cell deformability measuring device according to claim 11 or 12, It has blood flow image display means for displaying a blood flow image obtained by the photographing means on a display screen.
  • the invention according to claim 14 is the blood cell deformability measuring device according to any one of claims 11 to 13,
  • the plurality of gates are arranged in the blood flow direction and are formed in a plurality of different widths so as to gradually narrow from the upstream side to the downstream side in the blood flow direction, or orthogonal to the blood flow direction.
  • the occlusion state calculating means detects, as a maximum occlusion width, the largest one of the widths of the gates occluded by the blood cells, from the blood flow image obtained by the imaging means,
  • the deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means.
  • the invention according to claim 15 is the blood cell deformability measuring apparatus according to any one of claims 11 to 13,
  • the plurality of gates form a plurality of sets for each width
  • the blockage state calculating means obtains the blockage rate of the gate blocked by the blood cells according to the width of the gate, and detects the width of the gate that maximizes the blockage rate as the maximum blockage width
  • the deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means.
  • the invention according to claim 16 is the blood cell deformability measuring apparatus according to any one of claims 11 to 13,
  • the occlusion state calculating means detects, as a maximum occlusion width, the width of the gate at the occlusion position of the blood cell in the gate occluded with the blood cell from the blood flow image obtained by the imaging means,
  • the deformability calculating means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell closed by the volume means.
  • the invention according to claim 17 is the blood cell deformability measuring apparatus according to any one of claims 14 to 16,
  • the deformability calculating means calculates D 2 or D 3 satisfying the following formula (4) or formula (5) as the deformability of the blood cell.
  • the deformability of the blood cell is calculated from the velocity of the blood cell and the volume of the blood cell. Therefore, the deformability of the blood cell is not limited to the red blood cell having an elliptical shape, and even if it is an amoeba-like white blood cell. Can be measured. Further, since the deformability of blood cells passing through a gate having a width narrower than the blood cell diameter is calculated, the deformability when blood cells pass through the capillaries can be measured by simulating capillaries by the gate.
  • the invention since the deformability of the blood cell is calculated from the occlusion ratio or the maximum occlusion width of the gate and the volume of the blood cell, the invention is not limited to the red blood cell having an elliptical shape, but an amoeba-like shape. Even leukocytes can be measured for deformability. Further, since the deformability of blood cells passing through a gate having a width narrower than the blood cell diameter is calculated, the deformability when blood cells pass through the capillaries can be measured by simulating capillaries by the gate.
  • the gate having a plurality of sets for each width, the maximum obtained as the gate width at which the blocking ratio for each width of the gate is maximized. Since the deformability of the blood cell is calculated from the occlusion width, the deformability is calculated using more gates, and a more stable calculation result is obtained.
  • FIG. 3A is a plan view of the flow path portion
  • FIG. 3B is a side sectional view.
  • It is a flowchart of deformability measurement in an embodiment. It is a figure which shows an example of the velocity map of a blood cell. It is a graph of a deformability. It is a flowchart of the deformability measurement in the modification of embodiment. It is a figure which shows a mode that white blood cells pass a gate. It is a graph which shows the time change of the density
  • FIG. 11 (a) is a graph showing the distribution range of measurement results of soft blood cells, with the vertical and horizontal axes representing changes in the vertical and horizontal widths of blood cells
  • FIG. 11 (b) shows the distribution ranges of measurement results of hard blood cells. It is the shown graph.
  • FIG. 12A is a graph showing measurement results of soft blood cells
  • FIG. 12B is a graph showing measurement results of hard blood cells, with the vertical width and the horizontal axis representing the change width and area of the vertical width of the blood cells.
  • FIG. 15 (a) is a processing image diagram in edge extraction processing
  • FIG. 15 (b) is a processing image diagram in monochrome / binarization processing
  • FIG. 15 (c) is a processing image diagram in noise processing
  • FIG. d) It is a process image figure in a morphological process
  • FIG.15 (e) is a process image figure in a blood cell residence part determination process. It is a figure which shows a mode that some gates are obstruct
  • FIG. 20 (a) is a figure which shows the state in which the blood containing many soft blood cells was poured
  • FIG. 20 (a) is a figure which shows the state in which the blood containing many soft blood cells was poured
  • FIG.20 (b) contains many hard blood cells.
  • FIG. 20 (b) contains many hard blood cells.
  • FIG. 20 (b) contains many hard blood cells.
  • FIG. 20 (b) contains many hard blood cells.
  • FIG. 1 is a block diagram showing an overall configuration of a blood cell deformability measuring apparatus 1 according to the present invention.
  • the blood cell deformability measuring apparatus 1 guides blood from a supply tank 10 through a filter 2 to a discharge tank 11, and measures the deformability of blood cells in the blood from information acquired in the process.
  • blood cells indicate red blood cells and / or white blood cells.
  • the blood cell deformability measuring apparatus 1 mainly includes a filter 2, a TV camera 3 for photographing a blood flow in the filter 2, and a deformability based on a blood flow image photographed by the TV camera 3.
  • a personal computer (PC) 7 that measures the blood flow
  • a display 8 that displays a blood flow image
  • a differential pressure control unit 9 that controls the blood flow in the filter 2.
  • a plurality of liquids such as physiological saline and physiologically active substances that are connected to the flow path via the mixer 12 so as to be mixed with blood and guided to the filter 2.
  • a solution bottle 13 or the like is further provided.
  • the differential pressure control unit 9 controls the pressurization pump 15 and the decompression pump 16 to adjust the differential pressure across the filter 2. By doing so, the filter 2 flows by a desired amount.
  • the valve 10 a of the supply tank 10 and the like are integrated and controlled by the sequence control unit 17.
  • FIG. 2 is a sectional view of the filter 2.
  • the filter 2 includes a base plate 21, silicon single crystal substrates 22 and 22, an outer plate 23, and a glass flat plate 24.
  • the base plate 21 is formed in a flat plate shape, and has an introduction hole 21a that communicates the upper surface near the center and the outer surface, and a discharge hole 21b that communicates the upper surface near one side end and the outer surface. .
  • the introduction hole 21a and the discharge hole 21b are connected to the supply tank 10 and the discharge tank 11 from the outer surface of the base plate 21 via a blood tube (not shown).
  • the two silicon single crystal substrates 22 and 22 are both formed in a substantially flat plate shape, and are arranged in parallel on the upper surface of the base plate 21 with a predetermined gap therebetween.
  • An introduction hole 21 a of the base plate 21 is opened in the gap between the two silicon single crystal substrates 22 and 22.
  • a protruding portion 22a extends in the direction in which the silicon single crystal substrates 22 and 22 are juxtaposed (the X direction in the drawing).
  • a plurality of hexagonal bank portions 22b are arranged in the X direction with the top surface in contact with the glass flat plate 24 (see FIG. 3).
  • the outer plate 23 is fixed to the upper surface end of the base plate 21 so as to surround the silicon single crystal substrates 22 and 22.
  • a predetermined gap is provided between the outer plate 23 and the silicon single crystal substrates 22, 22, and a discharge hole 21 b of the base plate 21 is opened in this gap.
  • the glass flat plate 24 is formed in a flat plate shape and is fixed to the upper surface of the outer plate 23. Further, between the lower surface of the glass flat plate 24 and the upper surface of the raised portion 22a, a channel portion 25 of a fine channel group is formed.
  • FIGS. 3A and 3B are diagrams for explaining the flow path section 25.
  • FIG. 3A is a view (plan view) of the flow path portion 25 as viewed from above, and
  • FIG. 3B is a side sectional view.
  • the flow path portion 25 includes a plurality of gates 25a formed between a plurality of bank portions 22b at the upper end of the raised portion 22a, and the gate 25a.
  • the upper terrace 25b is a space on the center side of the filter 2 (upper side in the drawing) and the downstream terrace 25c is a space outside the filter 2 (lower side in the drawing) with respect to the gate 25a.
  • the width t of the gate 25a is narrower than the blood cell diameter (about 8 ⁇ m) of the red blood cells R in the present embodiment.
  • the height h of the gate 25a is formed to be narrower than the blood cell diameter of the red blood cells R (about 8 ⁇ m).
  • the width t and height h may be formed narrower than the blood cell diameter of white blood cells W (about 10 to 20 ⁇ m).
  • the lengths la, lb, and lc in the width direction (Y direction in the drawing) of the raised portion 22a in the upstream terrace 25b, the gate 25a, and the downstream terrace 25c are all formed to be about 30 ⁇ m.
  • the upstream terrace 25b should just be formed in the width
  • the blood introduced from the supply tank 10 through the introduction hole 21a passes through the flow path portion 25 and is then discharged to the discharge tank 11 through the discharge hole 21b. More specifically, blood cells in blood flowing through the flow path section 25, for example, red blood cells R, first pass through the upstream terrace 25b, pass through the gate 25a, and finally pass through the downstream terrace 25c. It becomes.
  • pressure sensors E1 and E2 are provided upstream and downstream of the filter 2, and the pressure sensors E1 and E2 are configured to provide a difference between the measured filter upstream pressure P1 and filter downstream pressure P2.
  • the pressure is output to the pressure control unit 9.
  • the TV camera 3 is a digital CCD camera, for example, and is a high-speed camera having a resolution sufficient for photographing a blood flow.
  • the TV camera 3 is installed opposite to the glass flat plate 24 in the filter 2 and photographs the blood flow passing through the flow path portion 25 over the glass flat plate 24.
  • the photographing range may be a range including at least the plurality of gates 25a and the upstream terrace 25b.
  • the blood flow image obtained by the TV camera 3 is output to the personal computer 7 and displayed on the display 8.
  • the TV camera 3 is not particularly limited, but is a camera capable of shooting a moving image.
  • the personal computer 7 is connected to the TV camera 3 and includes an arithmetic processing unit 70 capable of calculating a plurality of types of blood characteristics from image information output from the TV camera 3.
  • the blood characteristics are various characteristic values indicating the properties of blood and the like, and include those relating to fluidity such as blood cell velocity and volume as well as blood cell deformability.
  • the arithmetic processing unit 70 can detect the gate 25a clogged with blood cells. As such an arithmetic processing part 70, a conventionally well-known thing can be used.
  • the display 8 is connected to the personal computer 7 and displays a blood flow image output from the TV camera 3 and blood characteristics calculated by the personal computer 7.
  • the differential pressure control unit 9 is connected to the sequence control unit 17, the pressure pump 15, and the pressure reduction pump 16, and controls the differential pressure before and after the filter 2 in accordance with a control command from the sequence control unit 17. Yes. More specifically, the differential pressure control unit 9 controls the pressure pump 15 upstream of the filter 2 and the pressure reduction pump 16 downstream of the filter 2 so that the filter upstream pressure P1 and the filter downstream pressure P2 become predetermined pressures. To do. Note that the differential pressure control unit 9 and the sequence control unit 17 may be configured integrally with the personal computer 7.
  • FIG. 4 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1.
  • the blood flow passing through the flow path portion 25 is imaged (step S1). Specifically, first, blood to be measured is poured into the supply tank 10, and physiological saline or the like is added to the solution bottle 13 as necessary. Then, a predetermined differential pressure is applied to the filter 2 by the differential pressure control unit 9 so that blood flows through the filter 2, and at the same time, the blood flow passing through the flow path unit 25 is photographed with the TV camera 3. The photographed blood flow image is displayed on the display 8.
  • the blood flow image is processed by the arithmetic processing unit 70, and a blood cell velocity map is created (step S2).
  • a blood cell velocity map is created (step S2).
  • FIG. As shown, blood cells are detected at each intersection of the grid set on the blood flow image of the upstream terrace 25b, and a velocity map is obtained that calculates the velocity vector of the blood cells at the intersection where the blood cells are detected.
  • the created velocity map may not be obtained from the velocity vector of blood cells passing through the upstream terrace 25b, but may be obtained from the velocity vector of blood cells passing through the gate 25a.
  • the blood cell type of the blood cell detected on the speed map is determined by the arithmetic processing unit 70 (step S3).
  • the red blood cell R is determined as a white portion in the red hue range.
  • the white blood cells W may be discriminated using luminance, or may be discriminated as white portions with few holes or white portions with a small number of edges per unit area using the fact that they are larger than other blood cell types.
  • the blood cell type is discriminated using a known method described in, for example, JP-A-10-48120, JP-A-10-90163, and JP-A-10-274652. Can do. If the blood to be measured includes only one of red blood cells R and white blood cells W, this blood cell type discrimination step is omitted.
  • the blood cell velocity S is calculated by the arithmetic processing unit 70 (step S4).
  • the average value of the velocity vector of the blood cell calculated in step S2 is calculated by dividing into the red blood cell R and the white blood cell W determined in step S3, so that the average value of the red blood cell R and the white blood cell W is obtained as the average value.
  • a speed S is calculated.
  • the blood cell volume V is calculated by the arithmetic processing unit 70 (step S5).
  • the area of a blood cell passing through the gate 25a is calculated using a known method described in Japanese Patent Laid-Open No. 5-79970, and the area V is multiplied by the height h of the gate 25a to obtain the volume V of the blood cell. Calculated.
  • step S6 the deformability of the blood cell is calculated by the arithmetic processing unit 70 (step S6).
  • the speed S and the volume V of the blood cell of the blood cell which is calculated in step S4 and step S5, D 1 satisfies the following equation (1) is calculated as a deformability of blood cells.
  • ⁇ ⁇ / (S ⁇ V) (1)
  • ⁇ is a predetermined coefficient set in a measurement test performed in advance. More specifically, ⁇ is calculated by the blood cell deformability measuring apparatus 1 with the deformability of red blood cells measured by another apparatus as positive. The coefficient is set so that the deformability is calculated from the velocity S of the red blood cells and the volume V of the blood cells. If ⁇ is not constant with respect to the product S ⁇ V of blood cell velocity S and volume V in a measurement test performed in advance, ⁇ may be used as a lookup table for the product S ⁇ V. .
  • D 2 satisfying the following equation (2) may be calculated as the deformability of the blood cell.
  • D 2 1 / (S ⁇ V) / (1 / (S 0 ⁇ V 0 )) (2) here, S 0 : velocity of blood cells in the blood when a predetermined reference blood is passed to the upstream terrace 25b or the gate 25a, V 0 : The volume of blood cells in the blood when the predetermined reference blood is passed to the gate 25a, and the predetermined reference blood is blood of a standard health level.
  • D 1 calculated as deformability shows that blood cells stiff greater the value.
  • D 2 indicates that the blood cell has a standard hardness when the value is 1, and indicates that the blood cell is harder as it is larger than 1 and softer as it is smaller.
  • D 1 or D 2 calculated as deformability is arranged as a graph relating to the blood cell volume V as shown in FIG. 6, and the graph for each blood cell type of red blood cells R and white blood cells W is displayed on the display 8. Is done.
  • FIG. 6 is an example in which measurement results for two types of blood A and B are displayed together.
  • the blood cell deformability measuring device 1 is not limited to the red blood cell R having an elliptical shape, and is an amoeba-like white blood cell. Even if it is W, its deformability can be measured. Further, since the deformability of the blood cells passing through the gate 25a having a width smaller than the blood cell diameter is calculated, the deformability when the blood cells pass through the capillaries can be measured by simulating the capillaries by the gate 25a.
  • the blood flow passing through the gate 25a having a width narrower than the blood cell diameter is displayed on the display 8, the blood cell having the velocity S decreased can be confirmed by the gate 25a, and the blood cell has a uniform velocity on the image. Compared to the conventional flow that has flowed in step 1, it is possible to visually grasp how the blood cells move while deforming.
  • the blood cell deformability measuring apparatus 1A includes a personal computer 7A instead of the personal computer 7 in the above embodiment, and the personal computer 7A includes an arithmetic processing unit 70A instead of the arithmetic processing unit 70. Yes.
  • the arithmetic processing unit 70A is configured to be able to measure a passage time T required for blood cells to pass through the gate 25a instead of the velocity S of the blood cells in the blood.
  • the blood cell deformability measuring apparatus 1A includes a filter 2A instead of the filter 2 in the above embodiment, and the filter 2A is replaced with a flow path portion 25 as shown in FIG. 25A is provided.
  • the shape of the flow path portion 25A is equivalent to that of the flow path portion 25.
  • FIG. 7 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1A.
  • step T1 the blood flow passing through the flow path portion 25 is photographed. This step is performed in the same manner as step S1 in the above embodiment.
  • the blood flow image is processed by the arithmetic processing unit 70A, and blood cells are detected (step T2).
  • a blood cell flowing in the upstream terrace 25b is detected and tracked by using a known method described in JP-A-2001-264318.
  • step T3 the blood cell type of the blood cell detected in step T2 is determined by the arithmetic processing unit 70A (step T3). This step is performed in the same manner as step S3 in the above embodiment.
  • step T4 the blood cell volume V is calculated by the arithmetic processing unit 70A (step T4). This step is performed in the same manner as step S5 in the above embodiment.
  • the passage time T required for the blood cells to pass through the gate 25a is measured by the arithmetic processing unit 70A (step T5).
  • the passage time T is measured by detecting the density change of the image color in the gate 25a.
  • FIGS. 8A to 8D are views showing how the white blood cells W pass through the gate 25a
  • FIG. 9 is a graph showing the change over time of the color density of the blood flow image at that time.
  • the deformability of the blood cell is calculated by the arithmetic processing unit 70A (step T6).
  • D 3 satisfying the following equation (30) is calculated as the deformability of the blood cell from the blood cell volume V and the passage time T calculated in step T4 and step T5.
  • ⁇ ⁇ ⁇ T / V (30)
  • ⁇ is a predetermined coefficient set in a measurement test performed in advance, and is a coefficient set in the same manner as ⁇ in the above equation (1).
  • D 4 satisfying the following formula (40) may be calculated as the deformability of the blood cell.
  • T 0 is a transit time required for blood cells in a predetermined reference blood to pass through the gate 25a.
  • D 3 and D 4 calculated from the equations (30) and (40) are the reciprocals of the passage time T instead of the blood cell velocity S with respect to the equations (1) and (2) in the above embodiment. It is none other than D 1 and D 2 when. Therefore, D 3 and D 4 can be used for the evaluation of deformability in the same manner as D 1 and D 2 .
  • D 3 or D 4 calculated as deformability is arranged as a graph relating to blood cell volume V as shown in FIG. 6, and the graph for each blood cell type of red blood cells R and white blood cells W is displayed on the display 8. Is done. If the blood to be measured includes only one of red blood cells R and white blood cells W, the calculated values in steps T4 to T6 may be the average value of all blood cells detected in step T1. .
  • the deformability is calculated from the volume V of the blood cells passing through the gate 25a, etc.
  • the deformability can also be obtained from a blood flow image when passing through the upstream terrace 25b or the downstream terrace 25c.
  • the blood cells passing through the upstream terrace 25b or the downstream terrace 25c change their shapes in various ways depending on their deformability as shown in FIGS. 10 (a) to 10 (c), for example. Therefore, the changes in the vertical and horizontal widths of the blood cells are calculated from the blood flow image, and as shown in FIGS. 11A and 11B, the coordinates of the vertical and horizontal axes corresponding to the data of each of the plurality of blood cells are obtained. Create a plotted graph.
  • the vertical width and horizontal width of a blood cell be the length of the Y direction of a flow-path part 25, and a X direction, for example.
  • the vertical width of the blood cell passing through the upstream terrace 25b or the downstream terrace 25c and the area of the blood cell are expressed as the vertical axis and the horizontal axis.
  • the vertical width of the blood cell on the vertical axis may be the horizontal width of the blood cell.
  • the blood cell deformability measuring apparatus 1E includes a personal computer 7E instead of the personal computer 7 in the above embodiment, and the personal computer 7E includes an arithmetic processing unit 70E instead of the arithmetic processing unit 70. Yes.
  • the arithmetic processing unit 70E is configured to determine that the gate 25a where the blood cell velocity S is zero is a closed gate 25a, and to calculate the closed ratio.
  • FIG. 13 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1E
  • FIG. 14 is a flowchart when the closed gate 25a is detected.
  • blood to be measured is flowed to the filter 2E (step S10). Specifically, blood to be measured is poured into the supply tank 10 and physiological saline or the like is added to the solution bottle 13 as necessary. Then, a predetermined differential pressure is applied to the filter 2E by the differential pressure control unit 9, and blood flows through the filter 2E.
  • a blood flow passing through the flow path portion 25E is photographed, and a blood flow image is collected (step S20).
  • the TV camera 3 takes a moving image of the blood flow that passes through the flow path portion 25E.
  • the photographed blood flow image is displayed on the display 8.
  • FIGS. 15A to 15E are diagrams showing an example of the processed image in each step of FIG. However, FIGS. 15A to 15E are for facilitating the understanding of the processing in this step, and are not processed blood flow images in the gate 25a.
  • a Sobel filter is applied to the collected blood flow image in both the vertical and horizontal directions to extract the edge of the staying blood cell portion (hereinafter referred to as a blood cell staying portion).
  • the image is grayscaled and binarized with a predetermined threshold value, and the blood cell retention portion is displayed in white (step S32).
  • noise and blood flow shadows that are misrecognized as edges of the blood cell retention portion are removed from the white portion (step S33).
  • a white portion having an area smaller than a preset threshold is set as noise, and a white portion whose length ratio between the X direction and the Y direction is outside a predetermined range is blackened as a blood flow shadow.
  • step S34 The image from which noise or the like has been removed is expanded and contracted by morphological processing, and the gaps in the white portion are filled (step S34). And the white part which remained so far is determined as a blood cell retention part (step S35).
  • the blood cell retention part is detected, and the gate 25a having the blood cell retention part is detected as the closed gate 25a.
  • the volume V of the blood cell retention part is calculated by the arithmetic processing part 70E (step S40).
  • the area of the blood cell retention portion in the gate 25a is calculated using a known method described in JP-A-5-79970, and this area is multiplied by the height h of the gate 25a, whereby the gate 25a is The volume V of the blood cell retention part being obstructed is calculated.
  • the blood cell type of the blood cell retention part is determined by the arithmetic processing unit 70E (step S50).
  • the red blood cell R is determined as a white portion in the red hue range.
  • the white blood cells W may be discriminated using luminance, or may be discriminated as white portions with few holes or white portions with a small number of edges per unit area using the fact that they are larger than other blood cell types.
  • the blood to be measured contains only one of red blood cells R and white blood cells W, this blood cell type discrimination step is omitted.
  • the blockage rate C of the gate 25a is calculated by the arithmetic processing unit 70E (step S60).
  • the ratio of the gate 25a blocked by the blood cell retention part of the volume V is calculated as the blockage ratio C for each volume V of the blood cell retention part.
  • the occlusion ratio C is preferably a ratio with respect to the total number of gates 25a. However, when all the gates 25a are not included in the blood flow image, the ratio is as a ratio with respect to the number of gates 25a included in the blood flow image. Also good.
  • the deformability of the blood cell is calculated by the arithmetic processing unit 70E (step S70).
  • a graph as shown in FIG. 17 is drawn with the horizontal axis and the vertical axis respectively from the volume V and the blockage rate C of the blood cell retention portion calculated in step S40 and step S60, and the blockage rate C of the graph is shown.
  • the deformability of the blood cell is calculated by multiplying the reciprocal of the integrated value by a predetermined coefficient. That, D 1 satisfies the following equation (3) is calculated as a deformability of blood cells.
  • ⁇ 2 is a predetermined coefficient set in a measurement test performed in advance. More specifically, ⁇ 2 is calculated by the blood cell deformability measuring apparatus 1E with the red blood cell deformability measured by another apparatus as positive. The coefficient is set so that the deformability is calculated from the volume V and the occlusion ratio C of the erythrocytes. In the measurement test performed in advance, if ⁇ 2 is not constant with respect to the integral value of the blocking ratio C with respect to the volume V, a lookup table for the integral value may be used.
  • step S60 when the blockage ratio C averaged about all the blood cell retention parts was calculated by step S60, you may calculate D1A which satisfy
  • ⁇ 2 A is a predetermined coefficient set in a measurement test performed in advance, and is a coefficient set in the same manner as ⁇ 2 in the above equation (3).
  • D 1 or D 1A calculated as the deformability indicates that the larger the value, the softer the blood cell and the higher the deformability.
  • the deformability of the blood cells is calculated from the blockage ratio C of the gate 25a and the volume V of the blood cell retention portion. Therefore, the blood cell deformability measuring device 1E is not limited to the red blood cells R having an elliptical shape. Even if it is an amoeba-like leukocyte W, its deformability can be measured. Further, since the deformability of the blood cells passing through the gate 25a having a width smaller than the blood cell diameter is calculated, the deformability when the blood cells pass through the capillaries can be measured by simulating the capillaries by the gate 25a.
  • the flow of blood passing through the gate 25a having a narrower width than the blood cell diameter is displayed on the display 8, the blood cells whose speed has been reduced by the gate 25a can be confirmed, and the blood cells are displayed at a uniform speed on the image. Compared to the conventional flow, it is possible to visually grasp how the blood cells move while deforming.
  • the blood cell deformability measuring apparatus 1F includes a filter 2F instead of the filter 2E in the above embodiment, and the filter 2F is replaced with a flow path portion 25E as shown in FIG. A flow path portion 25F is provided.
  • the flow path portion 25F has a plurality of gates 25aF formed between a plurality of bank portions 22bF,.
  • the widths of the plurality of gates 25aF are narrower than the blood cell diameter and are different from each other.
  • the width is gradually changed in the arrangement direction of the bank portions 22bF.
  • FIG. 19 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1F.
  • step T1 blood to be measured is flowed to the filter 2F (step T1), and a blood flow image of the flow path portion 25E is collected (step T2).
  • steps S10 and S20 blood to be measured is flowed to the filter 2F (step T1), and a blood flow image of the flow path portion 25E is collected (step T2).
  • the blood flow image is processed by the arithmetic processing unit 70E, and the blood flow image of the gate 25aF is extracted for each different width (step T3).
  • the blood flow image is divided and extracted by each gate 25aF.
  • step T4 After the gate 25aF closed by the blood cell retention part is detected by the arithmetic processing unit 70E (step T4), the volume V of the blood cell retention part is calculated (step T5), and then the blood cell retention part Are determined (step T6). These steps are performed in the same manner as steps S30 to S50 in the above embodiment.
  • the arithmetic processing unit 70E detects the maximum width of the gate 25aF blocked by the blood cell retention part as the maximum blocking width L (step T7).
  • the deformability of the blood cell is calculated by the arithmetic processing unit 70E (step T8).
  • D satisfying the following equation (4) from the maximum occlusion width L of the blood cell retention portion calculated in step T7 and the volume V of the blood retention portion that occludes the gate 25aF corresponding to the maximum occlusion width L: 2 is calculated as the deformability of blood cells.
  • ⁇ is a predetermined coefficient set in a measurement test performed in advance, and is a coefficient set in the same manner as ⁇ 2 in the above equation (3).
  • the D 3 that satisfies the following equation (5) may be calculated as a deformability of blood cells.
  • L 0 is the volume of the blood cell in the maximum occlusion width L for each volume of the blood cell in the gate 25aF blocked by the blood cell in the blood when a predetermined reference blood is passed to the gate 25aF. It is a value when it is V in Formula (4), and the predetermined reference blood is blood of a standard health level.
  • D 2 calculated as deformability shows that blood cells stiff greater the value.
  • D 3 indicates that the blood cell has a standard hardness when the value is 1, and indicates that the blood cell is harder as it is larger than 1 and softer as it is smaller. If the D 3 is calculated, since deformability is shown as a relative value with respect to blood cells of the standard health, it is possible to understand the degree of uniquely deformability regardless of the volume V of the blood cell trapping portion.
  • the gate 25aF is described as having a width that gradually changes in the arrangement direction of the bank portion 22bF.
  • FIGS. A plurality of stages of gates 25a 1 ,... Having respective widths gradually narrowing in the blood flow direction (Y direction in the figure) may be provided.
  • the gates 25a 1 to 25a 4 formed between the four bank portions 22b 1 to 22b 4 having different arrangement intervals at each stage are provided in the direction of blood flow.
  • Each step has a width that gradually decreases.
  • the blood cell deformability measuring apparatus 1B includes a filter 2B instead of the filter 2E in the above embodiment, and the filter 2B is replaced with a flow path portion 25E as shown in FIG. A flow path portion 25B is provided.
  • the flow path portion 25B has a plurality of gates 25aB formed between a plurality of bank portions 22bB,.
  • the plurality of gates 25aB are formed to have a width narrower than the blood cell diameter and form a plurality of sets for each width.
  • three gates 25aB constitute a set of the bank portion 22bB. It is gradually changing in the arrangement direction.
  • the blood cell deformability measuring apparatus 1B having the above configuration can calculate the deformability of blood cells by the same operation as the blood cell deformability measuring apparatus 1F in the third modified example.
  • the maximum blocking width L is detected (step T7), as shown in FIG. 22, the blocking ratio C of the gate 25aB is obtained for each width of the gate 25aB, and the width of the gate 25aB at which the blocking ratio C is maximized. Is preferably detected as the maximum closing width L.
  • the number of gates 25aB closed is determined according to the width of the gate 25aB, and the gate 25aB width obtained by averaging the blockage numbers or the width of the gate 25aB having the maximum blockage number is maximum blocked.
  • the width L may be detected.
  • the size of blood cells contained in the blood flowing through the gate 25aB is not uniform but has a distribution variation, so that a distribution peak occurs at an intermediate gate width.
  • the blood cell deformability measuring apparatus 1B it has the gate 25aB that forms a plurality of sets for each width as well as the same effect as that of the above-described embodiment. Since the deformability of blood cells can be calculated from the maximum occlusion width L obtained as the width of the gate 25aB where the occlusion ratio C by width of 25aB is the maximum, the deformability is calculated using more gates 25aB, and is more stable. A calculation result is obtained.
  • the blood cell deformability measuring apparatus 1C includes a filter 2C instead of the filter 2E in the above embodiment, and the filter 2C is replaced with a flow path portion 25E as shown in FIG. A flow path portion 25C is provided.
  • the flow path portion 25C has a plurality of gates 25aC formed between a plurality of bank portions 22bC,... Which are tapered in the blood flow direction (Y direction in the drawing). .
  • the width of the plurality of gates 25aC is gradually narrowed in the blood flow direction and narrower than the blood cell diameter.
  • the blood cell deformability measuring apparatus 1C having the above configuration can calculate the deformability of blood cells by the same operation as the blood cell deformability measuring apparatus 1F in the third modified example.
  • the width of the gate 25aC at the position where the blood cell retention portion is retained is the maximum occlusion width L. Detect as.
  • the blood flow image in the gate 25aC formed with a width narrowing in the blood flow direction can be obtained as well as the same effect as the above embodiment. Since it is displayed on the display 8, it is easy to visually grasp the width of the gate 25aC blocked by the blood cell retention portion.
  • red blood cells R and / or white blood cells W is calculated, but among leukocytes W, granulocytes, lymphocytes and monocytes are further discriminated, Each of these deformability may be calculated. In this way, more detailed blood diagnosis can be performed.
  • a known method described in, for example, JP-A-2001-174456 may be used.
  • Blood cell deformability measuring device 3 TV camera (photographing means) 7, 7A, 7E PC (blood flow image display means) 8 Display (display screen) 25, 25A, 25B, 25C, 25E, 25F Channel portion 25a Gate 25b Upstream terrace 70, 70A Arithmetic processing section (speed calculation means, volume calculation means, deformability calculation means) 70E arithmetic processing unit (speed calculation means, volume calculation means, deformability calculation means, blockage state calculation means, blockage ratio calculation means, blockage width detection means) S Blood cell velocity T Passing time V Blood cell volume C Blockage ratio L Maximum blockage width

Abstract

A device for measuring blood cell deformability comprising, in order to measure the deformability of each of erythrocytes and leukocytes passing through a capillary blood vessel, a TV camera (3) for photographing a blood flow passing through an upstream terrace (25b) being wider than the blood cell diameter and a gate (25a) being narrower than the blood cell diameter, and a computing unit (70) for calculating, from a blood flow image photographed by the TV camera (3), the speed (S) of a blood cell passing through the upstream terrace (25b) or the gate (25a) and the volume (V) of the blood cell passing through the gate (25a), and further calculating the deformability of the blood cell from the blood cell speed (S) and the blood cell volume (V).

Description

血球変形能計測装置Blood cell deformability measuring device
　本発明は、血球変形能計測装置に関する。 The present invention relates to a blood cell deformability measuring apparatus.
　近年、健康に対する関心の高まりとともに、健康のバロメータとして血液の流動性が注目されるようになっている。この血液の流動性を調べる方法としては、微細な溝を有するフィルタに血液を通過させて、通過に要する時間を計測する方法が知られている。 In recent years, with increasing interest in health, blood fluidity has attracted attention as a health barometer. As a method for examining the blood fluidity, a method is known in which blood is passed through a filter having fine grooves and the time required for passage is measured.
　ところで、血液の流動性には、血液中の血球の変形能（変形し易さ）や凝集度，粘性などの複数のパラメータが複合的に作用している。したがって、血液の流動性をより詳細に評価するためにはこれら各パラメータの定量化が必要となるが、なかでも代表的なパラメータである血球の変形能を定量化する方法は確立されていなかった。 By the way, a plurality of parameters such as deformability (easiness of deformation), aggregation degree, and viscosity of blood cells in blood act in a complex manner on blood fluidity. Therefore, in order to evaluate blood fluidity in more detail, it is necessary to quantify each of these parameters, but a method for quantifying the deformability of blood cells, which is a typical parameter, has not been established. .
　そこで、浸透圧又は粘度の異なる複数の血液試料液を混合して平衡状態に至る様子を撮像し、その回析像から楕円形状の赤血球の長径及び短径を用いて変形指数を定義することで、当該変形指数を赤血球の変形能の定量値として算出する方法が提案されている（例えば、特許文献１，２参照）。 Therefore, by mixing multiple blood sample solutions with different osmotic pressures or viscosities and imaging the state of reaching an equilibrium state, the deformation index is defined using the major and minor diameters of elliptical red blood cells from the diffraction image. A method for calculating the deformation index as a quantitative value of the deformability of red blood cells has been proposed (see, for example, Patent Documents 1 and 2).
特開平８－１２２３２８号公報JP-A-8-122328 特開平９－３１８５２３号公報JP 9-318523 A
　しかしながら、上記特許文献１，２に記載の方法は、楕円形状を保持する赤血球のみに適用し得る方法であり、様々な形状に変形可能なアメーバ状の白血球には適用できなかった。 However, the methods described in Patent Documents 1 and 2 are methods that can be applied only to red blood cells that retain an elliptical shape, and cannot be applied to amoeba-like white blood cells that can be deformed into various shapes.
　また、血球径より狭い幅の流路を使用していないため、血球が毛細血管を通過するときの変形能は計測できなかった。 In addition, since a flow path having a width narrower than the blood cell diameter is not used, the deformability when the blood cell passes through the capillary vessel cannot be measured.
　加えて、移動する血球を画像表示できるものの、画像上は血球が一様な速度で流れているため、血球が変形しつつ移動する様子を視覚的に捉えにくかった。 In addition, although moving blood cells can be displayed as an image, it is difficult to visually grasp how the blood cells move while deforming because the blood cells flow at a uniform speed on the image.
　本発明は、上記事情を鑑みてなされたもので、赤血球及び白血球が毛細血管を通過するときの各変形能を計測できるとともに、血球が変形しつつ移動する様子を視覚的に捉え易い血球変形能計測装置の提供を課題とする。 The present invention has been made in view of the above circumstances, and can measure each deformability when red blood cells and white blood cells pass through capillaries and can easily grasp the state of blood cells moving while deforming. It is an object to provide a measuring device.
　前記の課題を解決するために、請求項１に記載の発明は、
　血球径よりも広い幅の上流テラスから血球径よりも狭い幅のゲートへ向けて血液を流し、当該血液中の血球の変形能を計測する血球変形能計測装置であって、
　前記上流テラス及び前記ゲートを通過する血液の流れを撮影する撮影手段と、
　前記撮影手段によって得られた血流画像から、前記上流テラス又は前記ゲートを通過する血球の速度を算出する速度算出手段と、
　前記撮影手段によって得られた血流画像から、前記ゲートを通過する血球の体積を算出する体積算出手段と、
　前記血球の速度及び前記血球の体積から、前記血球の変形能を算出する変形能算出手段と、
　を備えることを特徴とする。 In order to solve the above-mentioned problem, the invention according to claim 1
A blood cell deformability measuring device for flowing blood from an upstream terrace having a width wider than the blood cell diameter toward a gate having a width narrower than the blood cell diameter, and measuring the deformability of the blood cells in the blood,
Imaging means for imaging the flow of blood passing through the upstream terrace and the gate;
From the blood flow image obtained by the imaging means, speed calculation means for calculating the speed of blood cells passing through the upstream terrace or the gate;
From the blood flow image obtained by the imaging means, volume calculating means for calculating the volume of blood cells passing through the gate;
Deformability calculating means for calculating the deformability of the blood cell from the velocity of the blood cell and the volume of the blood cell;
It is characterized by providing.
　請求項２に記載の発明は、請求項１に記載の血球変形能計測装置であって、
　前記変形能算出手段は、前記血球の変形能として、以下の式（１）又は式（２）を満たすＤ１又はＤ２を算出することを特徴とする。 The invention according to claim 2 is the blood cell deformability measuring device according to claim 1,
The deformability calculating means calculates D 1 or D 2 satisfying the following formula (1) or formula (2) as the deformability of the blood cell.
　　Ｄ１＝α／（Ｓ×Ｖ）　　　　　　　　　　　　　　　…（１）
　　Ｄ２＝１／（Ｓ×Ｖ）／（１／（Ｓ０×Ｖ０））　　　　…（２）
（但し、
　α：所定の係数
　Ｓ：前記上流テラス又は前記ゲートを通過する血球の速度
　Ｖ：前記ゲートを通過する血球の体積
　Ｓ０：所定の基準血液を前記上流テラス又は前記ゲートへ通過させたときの当該血液中の血球の速度
　Ｖ０：所定の基準血液を前記ゲートへ通過させたときの当該血液中の血球の体積）
　請求項３に記載の発明は、請求項１又は２に記載の血球変形能計測装置であって、
　前記速度算出手段は、前記血球の速度として、前記血球が前記ゲートを通過するのに要する通過時間の逆数を算出することを特徴とする。 D 1 = α / (S × V) (1)
D 2 = 1 / (S × V) / (1 / (S 0 × V 0 )) (2)
(However,
α: a predetermined coefficient S: velocity of blood cells passing through the upstream terrace or the gate V: volume of blood cells passing through the gate S 0 : the time when a predetermined reference blood is passed through the upstream terrace or the gate Velocity of blood cells in blood V 0 : volume of blood cells in the blood when a predetermined reference blood is passed through the gate)
The invention according to claim 3 is the blood cell deformability measuring apparatus according to claim 1 or 2,
The velocity calculation means calculates the reciprocal of the transit time required for the blood cells to pass through the gate as the velocity of the blood cells.
　請求項４に記載の発明は、請求項１から３の何れか一項に記載の血球変形能計測装置であって、
　前記撮影手段によって得られた血流画像を表示画面に表示する血流画像表示手段を有することを特徴とする。 The invention according to claim 4 is the blood cell deformability measuring apparatus according to any one of claims 1 to 3,
It has blood flow image display means for displaying a blood flow image obtained by the photographing means on a display screen.
　請求項５に記載の発明は、請求項１から４の何れか一項に記載の血球変形能計測装置であって、
　前記ゲートは複数であり、
　前記速度算出手段により得られた血球の速度がゼロである前記血球で閉塞された前記ゲートの閉塞割合を算出する閉塞状態算出手段を備え、
　前記変形能算出手段は、前記ゲートの閉塞割合及び前記体積算出手段が算出した前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 The invention according to claim 5 is the blood cell deformability measuring apparatus according to any one of claims 1 to 4,
A plurality of the gates;
Occlusion state calculation means for calculating the occlusion ratio of the gate occluded by the blood cells, wherein the blood cell speed obtained by the speed calculation means is zero,
The deformability calculating means calculates the deformability of the blood cell from the occlusion ratio of the gate and the volume of the blood cell closed by the volume calculating means.
　請求項６に記載の発明は、請求項５に記載の血球変形能計測装置であって、
　前記閉塞状態算出手段は、前記血球の体積別に当該体積の血球で閉塞された前記ゲートの閉塞割合を算出し、
　前記変形能算出手段は、前記血球の変形能として、以下の式（３）を満たすＤ１を算出することを特徴とする。 The invention according to claim 6 is the blood cell deformability measuring device according to claim 5,
The occlusion state calculating means calculates the occlusion ratio of the gate that is occluded by blood cells of the volume according to the volume of the blood cells,
The deformability calculation means, as a deformability of the blood cells, and calculates a D 1 satisfies the following equation (3).
　　Ｄ１＝α２／∫ＣｄＶ　　　　　　　　　　　　　　…（３）
（但し、
　α２：所定の係数
　Ｃ：前記ゲートの閉塞割合
　Ｖ：前記ゲートを閉塞させた前記血球の体積）
　請求項７に記載の発明は、請求項５又は６に記載の血球変形能計測装置であって、
　複数の前記ゲートは、血流方向に複数配設されるとともに血流方向上流側から下流側に向けて除々に狭くなるように複数の異なる幅に形成されるか、或いは血流方向に直交する方向に複数配設されるとともに複数の異なる幅で形成されており、
　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートの幅のうち最大のものを最大閉塞幅として検出し、
　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 D 1 = α2 / ∫CdV (3)
(However,
α2: Predetermined coefficient C: Blocking ratio of the gate V: Volume of the blood cell blocking the gate)
The invention according to claim 7 is the blood cell deformability measuring device according to claim 5 or 6,
The plurality of gates are arranged in the blood flow direction and are formed in a plurality of different widths so as to gradually narrow from the upstream side to the downstream side in the blood flow direction, or orthogonal to the blood flow direction. It is formed with a plurality of different widths and a plurality of different widths in the direction,
The occlusion state calculating means detects, as a maximum occlusion width, the largest one of the widths of the gates occluded by the blood cells, from the blood flow image obtained by the imaging means,
The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. Features.
　請求項８に記載の発明は、請求項５又は６に記載の血球変形能計測装置であって、
　複数の前記ゲートは幅毎に複数の組を形成しており、
　前記閉塞状態算出手段は、前記血球で閉塞された前記ゲートの閉塞割合を前記ゲートの幅別に求め、当該閉塞割合が最大となる前記ゲートの幅を最大閉塞幅として検出し、
　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 The invention according to claim 8 is the blood cell deformability measuring apparatus according to claim 5 or 6,
The plurality of gates form a plurality of sets for each width,
The blockage state calculating means obtains the blockage rate of the gate blocked by the blood cells according to the width of the gate, and detects the width of the gate that maximizes the blockage rate as the maximum blockage width,
The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. Features.
　請求項９に記載の発明は、請求項５又は６に記載の血球変形能計測装置であって、
　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートにおける当該血球の閉塞位置での当該ゲートの幅を最大閉塞幅として検出し、
　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積手段が算出した前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 The invention according to claim 9 is the blood cell deformability measuring device according to claim 5 or 6,
The occlusion state calculating means detects, as a maximum occlusion width, the width of the gate at the occlusion position of the blood cell in the gate occluded with the blood cell from the blood flow image obtained by the imaging means,
The deformability calculating means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell closed by the volume means.
　請求項１０に記載の発明は、請求項７から９のいずれか一項に記載の血球変形能計測装置であって、
　前記変形能算出手段は、前記血球の変形能として、以下の式（４）又は式（５）を満たすＤ２又はＤ３を算出することを特徴とする。 The invention according to claim 10 is the blood cell deformability measuring apparatus according to any one of claims 7 to 9,
The deformability calculating means calculates D 2 or D 3 satisfying the following formula (4) or formula (5) as the deformability of the blood cell.
　　Ｄ２＝β×Ｌ／Ｖ　　　　　　　　　　　　　　　…（４）
　　Ｄ３＝Ｌ／Ｌ０　　　　　　　　　　　　　　　　…（５）
（但し、
　β：所定の係数
　Ｌ：前記ゲートの最大閉塞幅
　Ｌ０：所定の基準血液を前記ゲートへ通過させたときに、当該血液中の血球で閉塞されたゲートにおける当該血球の体積別の最大閉塞幅のうち、血球の体積が式（４）におけるＶであるときの値
　Ｖ：前記ゲートを閉塞させた前記血球の体積）
　前記の課題を解決するために、請求項１１に記載の発明は、
　血球径より狭い幅に形成された複数のゲートへ血液を流し、当該血液中の血球の変形能を計測する血球変形能計測装置であって、
　前記ゲートを通過する血液の流れを撮影する撮影手段と、
　前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートの閉塞割合を算出する閉塞状態算出手段と、
　前記撮影手段によって得られた血流画像から、前記ゲートを閉塞させた前記血球の体積を算出する体積算出手段と、
　前記ゲートの閉塞割合及び前記血球の体積から、前記血球の変形能を算出する変形能算出手段と、
　を備えることを特徴とする。 D 2 = β × L / V (4)
D 3 = L / L 0 (5)
(However,
β: Predetermined coefficient L: Maximum occlusion width of the gate L 0 : Maximum occlusion width for each blood cell volume at the gate occluded with blood cells in the blood when a predetermined reference blood is passed through the gate Value when the volume of blood cells is V in the formula (4) V: volume of the blood cells with the gate blocked)
In order to solve the above-mentioned problem, the invention according to claim 11
A blood cell deformability measuring apparatus for flowing blood to a plurality of gates formed with a narrower width than the blood cell diameter and measuring the deformability of the blood cells in the blood,
Photographing means for photographing the flow of blood passing through the gate;
From the blood flow image obtained by the imaging means, an occlusion state calculation means for calculating the occlusion ratio of the gate occluded by the blood cells,
From the blood flow image obtained by the imaging means, a volume calculation means for calculating the volume of the blood cell with the gate blocked,
Deformability calculating means for calculating the deformability of the blood cell from the blockage ratio of the gate and the volume of the blood cell;
It is characterized by providing.
　請求項１２に記載の発明は、請求項１１に記載の血球変形能計測装置であって、
　前記閉塞状態算出手段は、前記血球の体積別に当該体積の血球で閉塞された前記ゲートの閉塞割合を算出し、
　前記変形能算出手段は、前記血球の変形能として、以下の式（３）を満たすＤ１を算出することを特徴とする。 The invention according to claim 12 is the blood cell deformability measuring device according to claim 11,
The occlusion state calculating means calculates the occlusion ratio of the gate that is occluded by blood cells of the volume according to the volume of the blood cells,
The deformability calculation means, as a deformability of the blood cells, and calculates a D 1 satisfies the following equation (3).
　　Ｄ１＝α２／∫ＣｄＶ　　　　　　　　　　　　　　…（３）
（但し、
　α２：所定の係数
　Ｃ：前記ゲートの閉塞割合
　Ｖ：前記ゲートを閉塞させた前記血球の体積）
　請求項１３に記載の発明は、請求項１１又は１２に記載の血球変形能計測装置であって、
　前記撮影手段によって得られた血流画像を表示画面に表示する血流画像表示手段を有することを特徴とする。 D 1 = α2 / ∫CdV (3)
(However,
α2: Predetermined coefficient C: Blocking ratio of the gate V: Volume of the blood cell blocking the gate)
The invention according to claim 13 is the blood cell deformability measuring device according to claim 11 or 12,
It has blood flow image display means for displaying a blood flow image obtained by the photographing means on a display screen.
　請求項１４に記載の発明は、請求項１１から１３のいずれか一項に記載の血球変形能計測装置であって、
　複数の前記ゲートは、血流方向に複数配設されるとともに血流方向上流側から下流側に向けて除々に狭くなるように複数の異なる幅に形成されるか、或いは血流方向に直交する方向に複数配設されるとともに複数の異なる幅で形成されており、
　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートの幅のうち最大のものを最大閉塞幅として検出し、
　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 The invention according to claim 14 is the blood cell deformability measuring device according to any one of claims 11 to 13,
The plurality of gates are arranged in the blood flow direction and are formed in a plurality of different widths so as to gradually narrow from the upstream side to the downstream side in the blood flow direction, or orthogonal to the blood flow direction. It is formed with a plurality of different widths and a plurality of different widths in the direction,
The occlusion state calculating means detects, as a maximum occlusion width, the largest one of the widths of the gates occluded by the blood cells, from the blood flow image obtained by the imaging means,
The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. Features.
　請求項１５に記載の発明は、請求項１１から１３のいずれか一項に記載の血球変形能計測装置であって、
　複数の前記ゲートは幅毎に複数の組を形成しており、
　前記閉塞状態算出手段は、前記血球で閉塞された前記ゲートの閉塞割合を前記ゲートの幅別に求め、当該閉塞割合が最大となる前記ゲートの幅を最大閉塞幅として検出し、
　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 The invention according to claim 15 is the blood cell deformability measuring apparatus according to any one of claims 11 to 13,
The plurality of gates form a plurality of sets for each width,
The blockage state calculating means obtains the blockage rate of the gate blocked by the blood cells according to the width of the gate, and detects the width of the gate that maximizes the blockage rate as the maximum blockage width,
The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. Features.
　請求項１６に記載の発明は、請求項１１から１３のいずれか一項に記載の血球変形能計測装置であって、
　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートにおける当該血球の閉塞位置での当該ゲートの幅を最大閉塞幅として検出し、
　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積手段が算出した前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする。 The invention according to claim 16 is the blood cell deformability measuring apparatus according to any one of claims 11 to 13,
The occlusion state calculating means detects, as a maximum occlusion width, the width of the gate at the occlusion position of the blood cell in the gate occluded with the blood cell from the blood flow image obtained by the imaging means,
The deformability calculating means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell closed by the volume means.
　請求項１７に記載の発明は、請求項１４から１６のいずれか一項に記載の血球変形能計測装置であって、
　前記変形能算出手段は、前記血球の変形能として、以下の式（４）又は式（５）を満たすＤ２又はＤ３を算出することを特徴とする。 The invention according to claim 17 is the blood cell deformability measuring apparatus according to any one of claims 14 to 16,
The deformability calculating means calculates D 2 or D 3 satisfying the following formula (4) or formula (5) as the deformability of the blood cell.
　　Ｄ２＝β×Ｌ／Ｖ　　　　　　　　　　　　　　　…（４）
　　Ｄ３＝Ｌ／Ｌ０　　　　　　　　　　　　　　　　…（５）
（但し、
　β：所定の係数
　Ｌ：前記ゲートの最大閉塞幅
　Ｌ０：所定の基準血液を前記ゲートへ通過させたときに、当該血液中の血球で閉塞されたゲートにおける当該血球の体積別の最大閉塞幅のうち、血球の体積が式（４）におけるＶであるときの値
　Ｖ：前記ゲートを閉塞させた前記血球の体積） D 2 = β × L / V (4)
D 3 = L / L 0 (5)
(However,
β: Predetermined coefficient L: Maximum occlusion width of the gate L 0 : Maximum occlusion width for each blood cell volume at the gate occluded with blood cells in the blood when a predetermined reference blood is passed through the gate Value when the volume of blood cells is V in the formula (4) V: volume of the blood cells with the gate blocked)
　請求項１に記載の発明によれば、血球の速度及び血球の体積から血球の変形能を算出するので、楕円形状を保持する赤血球に限定されず、アメーバ状の白血球であってもその変形能を計測することができる。また、血球径より狭い幅のゲートを通過する血球の変形能が算出されるので、ゲートによって毛細血管を模擬して血球が毛細血管を通過するときの変形能を計測することができる。 According to the first aspect of the present invention, the deformability of the blood cell is calculated from the velocity of the blood cell and the volume of the blood cell. Therefore, the deformability of the blood cell is not limited to the red blood cell having an elliptical shape, and even if it is an amoeba-like white blood cell. Can be measured. Further, since the deformability of blood cells passing through a gate having a width narrower than the blood cell diameter is calculated, the deformability when blood cells pass through the capillaries can be measured by simulating capillaries by the gate.
　更に、請求項４、１３に記載の発明によれば血球径より狭い幅のゲートを通過する血液の流れが表示画面に表示されるので、ゲートにより速度が低下した血球を確認することができ、画像上は血球が一様な速度で流れていた従来に比べて、血球が変形しつつ移動する様子を視覚的に捉え易くすることができる。 Furthermore, according to the inventions of claims 4 and 13, since the flow of blood passing through a gate having a narrower width than the blood cell diameter is displayed on the display screen, it is possible to check blood cells whose speed has been reduced by the gate, Compared with the conventional technique in which blood cells flow at a uniform speed on the image, it is possible to make it easier to visually grasp how the blood cells move while deforming.
　請求項５、１１に記載の発明によれば、ゲートの閉塞割合又は最大閉塞幅と血球の体積とから血球の変形能を算出するので、楕円形状を保持する赤血球に限定されず、アメーバ状の白血球であってもその変形能を計測することができる。また、血球径より狭い幅のゲートを通過する血球の変形能が算出されるので、ゲートによって毛細血管を模擬して血球が毛細血管を通過するときの変形能を計測することができる。更に、血球径より狭い幅のゲートを通過する血液の流れが表示画面に表示されるので、ゲートにより速度が低下した血球を確認することができ、画像上は血球が一様な速度で流れていた従来に比べて、血球が変形しつつ移動する様子を視覚的に捉え易くすることができる。 According to the inventions of claims 5 and 11, since the deformability of the blood cell is calculated from the occlusion ratio or the maximum occlusion width of the gate and the volume of the blood cell, the invention is not limited to the red blood cell having an elliptical shape, but an amoeba-like shape. Even leukocytes can be measured for deformability. Further, since the deformability of blood cells passing through a gate having a width narrower than the blood cell diameter is calculated, the deformability when blood cells pass through the capillaries can be measured by simulating capillaries by the gate. Furthermore, since the flow of blood passing through a gate narrower than the blood cell diameter is displayed on the display screen, blood cells whose speed has been reduced by the gate can be confirmed, and blood cells are flowing at a uniform speed on the image. Compared with the conventional art, it is possible to visually grasp the state in which the blood cell moves while being deformed.
　また、請求項８、１５に記載の発明によれば、幅毎に複数の組を形成しているゲートを有し、当該ゲートの幅別の閉塞割合が最大となるゲートの幅として求めた最大閉塞幅から血球の変形能を算出するので、より多くのゲートを用いて変形能が算出され、より安定した算出結果が得られる。 According to the invention described in claims 8 and 15, the gate having a plurality of sets for each width, the maximum obtained as the gate width at which the blocking ratio for each width of the gate is maximized. Since the deformability of the blood cell is calculated from the occlusion width, the deformability is calculated using more gates, and a more stable calculation result is obtained.
　また、請求項９、１６に記載の発明によれば、血流方向に狭くなる幅に形成されたゲート内の血流画像が表示画面に表示されるので、血球で閉塞されているゲートの幅が視覚的に捉え易い。 According to the invention described in claims 9 and 16, since the blood flow image in the gate formed in a width narrowing in the blood flow direction is displayed on the display screen, the width of the gate blocked by the blood cells is displayed. Is easy to catch visually.
血球変形能計測装置の全体構成を示すブロック図である。It is a block diagram which shows the whole structure of a blood cell deformability measuring apparatus. フィルタの断面図である。It is sectional drawing of a filter. 図３（ａ）流路部の平面図であり、図３（ｂ）側断面図である。FIG. 3A is a plan view of the flow path portion, and FIG. 3B is a side sectional view. 実施の形態における変形能計測のフローチャートである。It is a flowchart of deformability measurement in an embodiment. 血球の速度マップの一例を示す図である。It is a figure which shows an example of the velocity map of a blood cell. 変形能のグラフである。It is a graph of a deformability. 実施の形態の変形例における変形能計測のフローチャートである。It is a flowchart of the deformability measurement in the modification of embodiment. 白血球がゲートを通過する様子を示す図である。It is a figure which shows a mode that white blood cells pass a gate. 白血球がゲートを通過するときの血流画像の色の濃度の時間変化を示すグラフである。It is a graph which shows the time change of the density | concentration of the color of the blood-flow image when a leukocyte passes a gate. 上流テラス又は下流テラスでの血球の変形例を示す図である。It is a figure which shows the modification of the blood cell in an upstream terrace or a downstream terrace. 血球の縦幅及び横幅の各変化を縦軸及び横軸として図１１（ａ）柔らかい血球の計測結果の分布範囲を示したグラフであり、図１１（ｂ）硬い血球の計測結果の分布範囲を示したグラフである。FIG. 11 (a) is a graph showing the distribution range of measurement results of soft blood cells, with the vertical and horizontal axes representing changes in the vertical and horizontal widths of blood cells, and FIG. 11 (b) shows the distribution ranges of measurement results of hard blood cells. It is the shown graph. 血球の縦幅の変化幅及び面積を縦軸及び横軸として図１２（ａ）柔らかい血球の計測結果を示したグラフであり、図１２（ｂ）硬い血球の計測結果を示したグラフである。FIG. 12A is a graph showing measurement results of soft blood cells, and FIG. 12B is a graph showing measurement results of hard blood cells, with the vertical width and the horizontal axis representing the change width and area of the vertical width of the blood cells. 第１の変形例における変形能計測のフローチャートである。It is a flowchart of the deformability measurement in a 1st modification. 閉塞ゲートが検知される際のフローチャートである。It is a flowchart at the time of a blockade gate being detected. 図１４の各ステップにおける処理画像の一例を示す図である。図１５（ａ）エッジ抽出処理における処理画像図であり、図１５（ｂ）モノクロ・二値化処理における処理画像図であり、図１５（ｃ）ノイズ処理における処理画像図であり、図１５（ｄ）モルフォロジー処理における処理画像図であり、図１５（ｅ）血球滞留部判定処理における処理画像図である。It is a figure which shows an example of the process image in each step of FIG. 15 (a) is a processing image diagram in edge extraction processing, FIG. 15 (b) is a processing image diagram in monochrome / binarization processing, FIG. 15 (c) is a processing image diagram in noise processing, and FIG. d) It is a process image figure in a morphological process, FIG.15 (e) is a process image figure in a blood cell residence part determination process. 白血球で一部のゲートが閉塞している様子を示す図である。It is a figure which shows a mode that some gates are obstruct | occluded with leukocytes. 血球の体積に対する閉塞割合の変化を示すグラフである。It is a graph which shows the change of the obstruction | occlusion ratio with respect to the volume of a blood cell. 第２の変形例における流路部を示す図である。It is a figure which shows the flow-path part in a 2nd modification. 第２の変形例における変形能計測のフローチャートである。It is a flowchart of the deformability measurement in the 2nd modification. 第２の変形例における流路部の別例を示す図であり、図２０（ａ）柔らかい血球を多く含む血液が流された状態を示す図であり、図２０（ｂ）硬い血球を多く含む血液が流された状態を示す図である。It is a figure which shows another example of the flow-path part in a 2nd modification, FIG. 20 (a) is a figure which shows the state in which the blood containing many soft blood cells was poured, and FIG.20 (b) contains many hard blood cells. It is a figure which shows the state in which the blood was poured. 第３の変形例における流路部を示す図である。It is a figure which shows the flow-path part in a 3rd modification. ゲートの幅に対する閉塞割合の変化を示すグラフである。It is a graph which shows the change of the obstruction | occlusion ratio with respect to the width | variety of a gate. ゲートの幅に対する閉塞個数の変化を示すグラフである。It is a graph which shows the change of the blockage number with respect to the width | variety of a gate. 第４の変形例における流路部を示す図である。It is a figure which shows the flow-path part in a 4th modification.
　以下、本発明の実施の形態について、図を参照して説明する。 Hereinafter, embodiments of the present invention will be described with reference to the drawings.
　図１は、本発明に係る血球変形能計測装置１の全体構成を示すブロック図である。 FIG. 1 is a block diagram showing an overall configuration of a blood cell deformability measuring apparatus 1 according to the present invention.
　この図に示すように、血球変形能計測装置１は、血液を供給槽１０からフィルタ２に通して排出槽１１へ導き、その過程で取得される情報から血液中の血球の変形能を計測するものである。なお、本実施の形態においては、血球とは赤血球及び／又は白血球を指すものとする。 As shown in this figure, the blood cell deformability measuring apparatus 1 guides blood from a supply tank 10 through a filter 2 to a discharge tank 11, and measures the deformability of blood cells in the blood from information acquired in the process. Is. In the present embodiment, blood cells indicate red blood cells and / or white blood cells.
　具体的には、血球変形能計測装置１は、主に、フィルタ２と、フィルタ２内の血液の流れを撮影するＴＶカメラ３と、ＴＶカメラ３で撮影された血流画像に基づいて変形能を計測するパソコン（ＰＣ）７と、血流画像を表示するディスプレイ８と、フィルタ２内の血流を制御する差圧制御部９とを備えている。なお、本実施の形態における血球変形能計測装置１には、生理食塩水や生理活性物質などの液体を血液と混合してフィルタ２に導けるよう、ミクサー１２を介して流路に連結された複数の溶液びん１３等が更に具備されている。そして、生理食塩水や生理活性物質などの液体と混合した血液（以下、血液という）は、差圧制御部９が加圧ポンプ１５及び減圧ポンプ１６を制御してフィルタ２前後の差圧を調整することにより、フィルタ２内を所望量だけ流れるようになっている。また、上述の差圧制御部９やミクサー１２の他、供給槽１０のバルブ１０ａ等は、シーケンス制御部１７によって統合制御されている。 Specifically, the blood cell deformability measuring apparatus 1 mainly includes a filter 2, a TV camera 3 for photographing a blood flow in the filter 2, and a deformability based on a blood flow image photographed by the TV camera 3. A personal computer (PC) 7 that measures the blood flow, a display 8 that displays a blood flow image, and a differential pressure control unit 9 that controls the blood flow in the filter 2. In the blood cell deformability measuring apparatus 1 according to the present embodiment, a plurality of liquids such as physiological saline and physiologically active substances that are connected to the flow path via the mixer 12 so as to be mixed with blood and guided to the filter 2. A solution bottle 13 or the like is further provided. For blood mixed with a liquid such as physiological saline or physiologically active substance (hereinafter referred to as blood), the differential pressure control unit 9 controls the pressurization pump 15 and the decompression pump 16 to adjust the differential pressure across the filter 2. By doing so, the filter 2 flows by a desired amount. In addition to the differential pressure control unit 9 and the mixer 12 described above, the valve 10 a of the supply tank 10 and the like are integrated and controlled by the sequence control unit 17.
　図２は、フィルタ２の断面図である。フィルタ２は、図２に示すように、ベース板２１、シリコン単結晶基板２２，２２、外側板２３及びガラス平板２４を含んで構成されている。 FIG. 2 is a sectional view of the filter 2. As shown in FIG. 2, the filter 2 includes a base plate 21, silicon single crystal substrates 22 and 22, an outer plate 23, and a glass flat plate 24.
　ベース板２１は、平板状に形成されており、中央近傍の上面と外側面とを連通する導入孔２１ａ、及び一側端寄りの上面と外側面とを連通する排出孔２１ｂを有している。これら導入孔２１ａ及び排出孔２１ｂは、ベース板２１の外側面から血液チューブ（図示せず）を介して供給槽１０及び排出槽１１に連結されている。 The base plate 21 is formed in a flat plate shape, and has an introduction hole 21a that communicates the upper surface near the center and the outer surface, and a discharge hole 21b that communicates the upper surface near one side end and the outer surface. . The introduction hole 21a and the discharge hole 21b are connected to the supply tank 10 and the discharge tank 11 from the outer surface of the base plate 21 via a blood tube (not shown).
　２つのシリコン単結晶基板２２，２２は、いずれも略平板状に形成されており、互いに所定の隙間を介した状態でベース板２１の上面に並設されている。この２つのシリコン単結晶基板２２，２２間の隙間には、ベース板２１の導入孔２１ａが開口している。また、シリコン単結晶基板２２，２２の上端部には、隆起部２２ａが当該シリコン単結晶基板２２，２２の並設方向（図中のＸ方向）に延在しており、この隆起部２２ａの上端部には、六角形状の土手部２２ｂが頂面をガラス平板２４に当接させてＸ方向に複数配列されている（図３参照）。 The two silicon single crystal substrates 22 and 22 are both formed in a substantially flat plate shape, and are arranged in parallel on the upper surface of the base plate 21 with a predetermined gap therebetween. An introduction hole 21 a of the base plate 21 is opened in the gap between the two silicon single crystal substrates 22 and 22. Further, at the upper end portions of the silicon single crystal substrates 22 and 22, a protruding portion 22a extends in the direction in which the silicon single crystal substrates 22 and 22 are juxtaposed (the X direction in the drawing). At the upper end, a plurality of hexagonal bank portions 22b are arranged in the X direction with the top surface in contact with the glass flat plate 24 (see FIG. 3).
　外側板２３は、シリコン単結晶基板２２，２２の周囲を囲んでベース板２１の上面端に固定されている。外側板２３とシリコン単結晶基板２２，２２との間には所定の隙間が設けられ、この隙間にベース板２１の排出孔２１ｂが開口している。 The outer plate 23 is fixed to the upper surface end of the base plate 21 so as to surround the silicon single crystal substrates 22 and 22. A predetermined gap is provided between the outer plate 23 and the silicon single crystal substrates 22, 22, and a discharge hole 21 b of the base plate 21 is opened in this gap.
　ガラス平板２４は、平板状に形成されており、外側板２３の上面に固定されている。また、ガラス平板２４の下面と隆起部２２ａの上面との間には、微細な流路群の流路部２５が形成されている。 The glass flat plate 24 is formed in a flat plate shape and is fixed to the upper surface of the outer plate 23. Further, between the lower surface of the glass flat plate 24 and the upper surface of the raised portion 22a, a channel portion 25 of a fine channel group is formed.
　図３（ａ），（ｂ）は、流路部２５を説明するための図である。図３（ａ）は流路部２５を上面から見た図（平面図）であり、図３（ｂ）は側断面図である。 FIGS. 3A and 3B are diagrams for explaining the flow path section 25. FIG. 3A is a view (plan view) of the flow path portion 25 as viewed from above, and FIG. 3B is a side sectional view.
　流路部２５は、図３（ａ），（ｂ）に示すように、隆起部２２ａ上端部の複数の土手部２２ｂ，…に挟まれて形成される複数のゲート２５ａと、当該ゲート２５ａよりもフィルタ２中央側（図中の上側）の空間である上流テラス２５ｂと、ゲート２５ａよりもフィルタ２外側（図中の下側）の空間である下流テラス２５ｃとから構成されている。このうちのゲート２５ａの幅ｔは、本実施の形態においては、赤血球Ｒの血球径（約８μｍ）よりも狭く形成されている。また、ゲート２５ａの高さｈも同様に赤血球Ｒの血球径（約８μｍ）よりも狭く形成されている。但し、計測対象の血球が白血球Ｗのみであれば、当該幅ｔ、高さｈは白血球Ｗの血球径（約１０～２０μｍ）よりも狭く形成されていればよい。また、特に限定はされないが、上流テラス２５ｂ，ゲート２５ａ，下流テラス２５ｃにおける隆起部２２ａ幅方向（図中のＹ方向）の各長さｌａ，ｌｂ，ｌｃは、いずれも約３０μｍに形成されている。なお、上流テラス２５ｂは、通過する血球が大きく変形しないように、血球径よりも広い幅に形成されていればよい。 As shown in FIGS. 3A and 3B, the flow path portion 25 includes a plurality of gates 25a formed between a plurality of bank portions 22b at the upper end of the raised portion 22a, and the gate 25a. The upper terrace 25b is a space on the center side of the filter 2 (upper side in the drawing) and the downstream terrace 25c is a space outside the filter 2 (lower side in the drawing) with respect to the gate 25a. Of these, the width t of the gate 25a is narrower than the blood cell diameter (about 8 μm) of the red blood cells R in the present embodiment. Similarly, the height h of the gate 25a is formed to be narrower than the blood cell diameter of the red blood cells R (about 8 μm). However, if the blood cells to be measured are only white blood cells W, the width t and height h may be formed narrower than the blood cell diameter of white blood cells W (about 10 to 20 μm). Although not particularly limited, the lengths la, lb, and lc in the width direction (Y direction in the drawing) of the raised portion 22a in the upstream terrace 25b, the gate 25a, and the downstream terrace 25c are all formed to be about 30 μm. Yes. In addition, the upstream terrace 25b should just be formed in the width | variety wider than a blood cell diameter so that the passing blood cell may not deform | transform large.
　以上の構成を具備するフィルタ２においては、供給槽１０から導入孔２１ａを通じて導入された血液は、流路部２５を通過した後、排出孔２１ｂを通じて排出槽１１へ排出されることとなる。そして、より詳細には、流路部２５を流れる血液中の血球、例えば赤血球Ｒは、まず上流テラス２５ｂを通過した後、ゲート２５ａを変形しながら通過し、最後に下流テラス２５ｃを通過することとなる。 In the filter 2 having the above configuration, the blood introduced from the supply tank 10 through the introduction hole 21a passes through the flow path portion 25 and is then discharged to the discharge tank 11 through the discharge hole 21b. More specifically, blood cells in blood flowing through the flow path section 25, for example, red blood cells R, first pass through the upstream terrace 25b, pass through the gate 25a, and finally pass through the downstream terrace 25c. It becomes.
　また、フィルタ２の上流及び下流には、図１に示すように、圧力センサＥ１，Ｅ２が設けられており、この圧力センサＥ１，Ｅ２は、計測したフィルタ上流圧力Ｐ１，フィルタ下流圧力Ｐ２を差圧制御部９へ出力するようになっている。 Further, as shown in FIG. 1, pressure sensors E1 and E2 are provided upstream and downstream of the filter 2, and the pressure sensors E1 and E2 are configured to provide a difference between the measured filter upstream pressure P1 and filter downstream pressure P2. The pressure is output to the pressure control unit 9.
　ＴＶカメラ３は、例えばデジタルＣＣＤカメラであり、血液の流れを撮影するのに十分な解像度を有した高速カメラである。このＴＶカメラ３は、フィルタ２におけるガラス平板２４に対向して設置され、流路部２５を通過する血液の流れをガラス平板２４超しに撮影する。但し、その撮影範囲は、少なくとも複数のゲート２５ａ及び上流テラス２５ｂを含む範囲であればよい。ＴＶカメラ３によって得られた血流画像は、パソコン７に出力されるとともに、ディスプレイ８に表示されるようになっている。なお、ＴＶカメラ３は、特に限定はされないが、動画が撮影可能なカメラである。 The TV camera 3 is a digital CCD camera, for example, and is a high-speed camera having a resolution sufficient for photographing a blood flow. The TV camera 3 is installed opposite to the glass flat plate 24 in the filter 2 and photographs the blood flow passing through the flow path portion 25 over the glass flat plate 24. However, the photographing range may be a range including at least the plurality of gates 25a and the upstream terrace 25b. The blood flow image obtained by the TV camera 3 is output to the personal computer 7 and displayed on the display 8. The TV camera 3 is not particularly limited, but is a camera capable of shooting a moving image.
　パソコン７は、ＴＶカメラ３と接続されており、当該ＴＶカメラ３が出力した画像情報から複数種類の血液特性をそれぞれ算出可能な演算処理部７０を備えている。なお、血液特性とは、血液の性状等を示す種々の特性値であり、血液中の血球の速度や体積の他、血球の変形能といった流動性に関するものを含む。また演算処理部７０は、血球が詰まって閉塞したゲート２５ａを検知できるようになっている。このような演算処理部７０としては、従来より公知のものを用いることができる。 The personal computer 7 is connected to the TV camera 3 and includes an arithmetic processing unit 70 capable of calculating a plurality of types of blood characteristics from image information output from the TV camera 3. The blood characteristics are various characteristic values indicating the properties of blood and the like, and include those relating to fluidity such as blood cell velocity and volume as well as blood cell deformability. The arithmetic processing unit 70 can detect the gate 25a clogged with blood cells. As such an arithmetic processing part 70, a conventionally well-known thing can be used.
　ディスプレイ８は、パソコン７と接続されており、ＴＶカメラ３が出力した血流画像や、パソコン７によって算出された血液特性を表示するようになっている。 The display 8 is connected to the personal computer 7 and displays a blood flow image output from the TV camera 3 and blood characteristics calculated by the personal computer 7.
　差圧制御部９は、シーケンス制御部１７，加圧ポンプ１５及び減圧ポンプ１６と接続されており、シーケンス制御部１７からの制御指令に応じてフィルタ２前後の差圧を制御するようになっている。より詳細には、差圧制御部９は、フィルタ上流圧力Ｐ１及びフィルタ下流圧力Ｐ２が所定の圧力となるように、フィルタ２上流の加圧ポンプ１５とフィルタ２下流の減圧ポンプ１６とをそれぞれ制御する。なお、この差圧制御部９やシーケンス制御部１７は、パソコン７と一体に構成してもよい。 The differential pressure control unit 9 is connected to the sequence control unit 17, the pressure pump 15, and the pressure reduction pump 16, and controls the differential pressure before and after the filter 2 in accordance with a control command from the sequence control unit 17. Yes. More specifically, the differential pressure control unit 9 controls the pressure pump 15 upstream of the filter 2 and the pressure reduction pump 16 downstream of the filter 2 so that the filter upstream pressure P1 and the filter downstream pressure P2 become predetermined pressures. To do. Note that the differential pressure control unit 9 and the sequence control unit 17 may be configured integrally with the personal computer 7.
　［実施形態］
　続いて、血球変形能計測装置１の動作について、主に図４を参照して説明する。図４は、血球変形能計測装置１による変形能計測のフローチャートである。 [Embodiment]
Next, the operation of the blood cell deformability measuring apparatus 1 will be described mainly with reference to FIG. FIG. 4 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1.
　まず、図４に示すように、流路部２５を通過する血流が撮影される（ステップＳ１）。具体的には、最初に、供給槽１０へ計測対象の血液が注がれるとともに、必要に応じて溶液びん１３へ生理食塩水等が加えられる。そして、差圧制御部９によりフィルタ２に所定の差圧が加えられて血液がフィルタ２に流されると同時に、流路部２５を通過する血流がＴＶカメラ３で動画撮影される。撮影された血流画像はディスプレイ８に表示される。 First, as shown in FIG. 4, the blood flow passing through the flow path portion 25 is imaged (step S1). Specifically, first, blood to be measured is poured into the supply tank 10, and physiological saline or the like is added to the solution bottle 13 as necessary. Then, a predetermined differential pressure is applied to the filter 2 by the differential pressure control unit 9 so that blood flows through the filter 2, and at the same time, the blood flow passing through the flow path unit 25 is photographed with the TV camera 3. The photographed blood flow image is displayed on the display 8.
　次に、演算処理部７０により血流画像が処理され、血球の速度マップが作成される（ステップＳ２）。ここでは、例えば特開平２－２５７９３１号公報、特開平６－１８５３９号公報、特開２００１－２６４３１８号公報及び特開２００６－２２３７６１号公報等に記載の公知の方法を用いることで、図５に示すように、上流テラス２５ｂの血流画像上に設定した格子の各交点において血球の検出が行われ、血球が検出された交点での当該血球の速度ベクトルを求めた速度マップが作成される。なお、作成される速度マップは、上流テラス２５ｂを通過する血球の速度ベクトルを求めたものでなくとも、ゲート２５ａを通過する血球の速度ベクトルを求めたものであってもよい。 Next, the blood flow image is processed by the arithmetic processing unit 70, and a blood cell velocity map is created (step S2). Here, for example, by using a known method described in JP-A-2-257931, JP-A-6-18539, JP-A-2001-264318, JP-A-2006-223761, etc., FIG. As shown, blood cells are detected at each intersection of the grid set on the blood flow image of the upstream terrace 25b, and a velocity map is obtained that calculates the velocity vector of the blood cells at the intersection where the blood cells are detected. Note that the created velocity map may not be obtained from the velocity vector of blood cells passing through the upstream terrace 25b, but may be obtained from the velocity vector of blood cells passing through the gate 25a.
　次に、図４に示すように、演算処理部７０により、速度マップ上で検出された血球の血球種が判別される（ステップＳ３）。赤血球Ｒは赤の色相範囲にある白色部分として判別する。白血球Ｗは、輝度を利用して判別してもよいし、他の血球種より大きいことを利用し、穴の少ない白色部分や単位面積当たりのエッジ数が少ない白色部分として判別してもよい。 Next, as shown in FIG. 4, the blood cell type of the blood cell detected on the speed map is determined by the arithmetic processing unit 70 (step S3). The red blood cell R is determined as a white portion in the red hue range. The white blood cells W may be discriminated using luminance, or may be discriminated as white portions with few holes or white portions with a small number of edges per unit area using the fact that they are larger than other blood cell types.
　また、上述の判別方法以外にも、例えば特開平１０－４８１２０号公報、特開平１０－９０１６３号公報及び特開平１０－２７４６５２号公報等に記載の公知の方法を用いて血球種を判別することができる。なお、計測対象の血液が赤血球Ｒ及び白血球Ｗのいずれか一方のみを含むものであれば、この血球種判別ステップは省略される。 In addition to the discrimination method described above, the blood cell type is discriminated using a known method described in, for example, JP-A-10-48120, JP-A-10-90163, and JP-A-10-274652. Can do. If the blood to be measured includes only one of red blood cells R and white blood cells W, this blood cell type discrimination step is omitted.
　次に、演算処理部７０により血球の速度Ｓが算出される（ステップＳ４）。ここでは、ステップＳ３で判別された赤血球Ｒと白血球Ｗとに分けて、ステップＳ２で算出された血球の速度ベクトルの各平均値を算出することにより、当該各平均値として赤血球Ｒ及び白血球Ｗの速度Ｓが算出される。 Next, the blood cell velocity S is calculated by the arithmetic processing unit 70 (step S4). Here, the average value of the velocity vector of the blood cell calculated in step S2 is calculated by dividing into the red blood cell R and the white blood cell W determined in step S3, so that the average value of the red blood cell R and the white blood cell W is obtained as the average value. A speed S is calculated.
　次に、演算処理部７０により血球の体積Ｖが算出される（ステップＳ５）。ここでは、例えば特開平５－７９９７０号公報に記載の公知の方法を用いてゲート２５ａを通過する血球の面積を算出し、この面積にゲート２５ａの高さｈを乗じることで血球の体積Ｖが算出される。 Next, the blood cell volume V is calculated by the arithmetic processing unit 70 (step S5). Here, for example, the area of a blood cell passing through the gate 25a is calculated using a known method described in Japanese Patent Laid-Open No. 5-79970, and the area V is multiplied by the height h of the gate 25a to obtain the volume V of the blood cell. Calculated.
　次に、演算処理部７０により血球の変形能が算出される（ステップＳ６）。ここでは、ステップＳ４及びステップＳ５で算出された血球の速度Ｓ及び血球の体積Ｖから、以下の式（１）を満たすＤ１が血球の変形能として算出される。 Next, the deformability of the blood cell is calculated by the arithmetic processing unit 70 (step S6). Here, the speed S and the volume V of the blood cell of the blood cell which is calculated in step S4 and step S5, D 1 satisfies the following equation (1) is calculated as a deformability of blood cells.
　　Ｄ１＝α／（Ｓ×Ｖ）　　　　　　　　　　　　　　　…（１）
　ここで、αは、予め行われた計測試験で設定された所定の係数であり、より詳細には、他の装置で計測された赤血球の変形能を正として、血球変形能計測装置１で算出された赤血球の速度Ｓ及び血球の体積Ｖから当該変形能が算出されるよう設定された係数である。なお、予め行われた計測試験において、血球の速度Ｓと体積Ｖとの積Ｓ×Ｖに対してαが一定とならない場合には、αを当該積Ｓ×Ｖに対するルックアップテーブルとすればよい。 D 1 = α / (S × V) (1)
Here, α is a predetermined coefficient set in a measurement test performed in advance. More specifically, α is calculated by the blood cell deformability measuring apparatus 1 with the deformability of red blood cells measured by another apparatus as positive. The coefficient is set so that the deformability is calculated from the velocity S of the red blood cells and the volume V of the blood cells. If α is not constant with respect to the product S × V of blood cell velocity S and volume V in a measurement test performed in advance, α may be used as a lookup table for the product S × V. .
　また、このステップでは、以下の式（２）を満たすＤ２を血球の変形能として算出してもよい。
Ｄ２＝１／（Ｓ×Ｖ）／（１／（Ｓ０×Ｖ０））　　　　　　…（２）
　ここで、
Ｓ０：所定の基準血液を上流テラス２５ｂ又はゲート２５ａへ通過させたときの当該血液中の血球の速度、
Ｖ０：所定の基準血液をゲート２５ａへ通過させたときの当該血液中の血球の体積であり、所定の基準血液とは、標準的な健康度の血液である。 In this step, D 2 satisfying the following equation (2) may be calculated as the deformability of the blood cell.
D 2 = 1 / (S × V) / (1 / (S 0 × V 0 )) (2)
here,
S 0 : velocity of blood cells in the blood when a predetermined reference blood is passed to the upstream terrace 25b or the gate 25a,
V 0 : The volume of blood cells in the blood when the predetermined reference blood is passed to the gate 25a, and the predetermined reference blood is blood of a standard health level.
　ここで、変形能として算出されたＤ１は、その値が大きいほど血球が硬いことを示す。また、Ｄ２は、その値が１のときに血球が標準的な硬さであることを示し、１より大きいほど硬く、小さいほど柔らかいことを示す。Ｄ２が算出された場合には、標準的な健康度の血球に対する相対値として変形能が示されるので、血球の体積Ｖによらず一意に変形能の程度を理解することができる。 Here, D 1 calculated as deformability, shows that blood cells stiff greater the value. Further, D 2 indicates that the blood cell has a standard hardness when the value is 1, and indicates that the blood cell is harder as it is larger than 1 and softer as it is smaller. When the D 2 is calculated, since the deformability as a relative value with respect to blood cells of the standard health is shown, it is possible to understand the degree of uniquely deformability regardless of the volume V of the blood cell.
　そして、変形能として算出されたＤ１又はＤ２は、図６に示すように、血球の体積Ｖに関するグラフとして整理され、赤血球Ｒ及び白血球Ｗの各血球種についての当該グラフがディスプレイ８に表示される。なお、図６は、２種類の血液Ａ，Ｂについての計測結果を併せて表示した例である。 Then, D 1 or D 2 calculated as deformability is arranged as a graph relating to the blood cell volume V as shown in FIG. 6, and the graph for each blood cell type of red blood cells R and white blood cells W is displayed on the display 8. Is done. FIG. 6 is an example in which measurement results for two types of blood A and B are displayed together.
　以上のように、血球変形能計測装置１によれば、血球の速度Ｓ及び血球の体積Ｖから血球の変形能を算出するので、楕円形状を保持する赤血球Ｒに限定されず、アメーバ状の白血球Ｗであってもその変形能を計測することができる。また、血球径より狭い幅のゲート２５ａを通過する血球の変形能が算出されるので、ゲート２５ａによって毛細血管を模擬して血球が毛細血管を通過するときの変形能を計測することができる。更に、血球径より狭い幅のゲート２５ａを通過する血液の流れがディスプレイ８に表示されるので、ゲート２５ａにより速度Ｓが低下した血球を確認することができ、画像上は血球が一様な速度で流れていた従来に比べて、血球が変形しつつ移動する様子を視覚的に捉え易くすることができる。 As described above, according to the blood cell deformability measuring device 1, the blood cell deformability is calculated from the blood cell velocity S and the blood cell volume V. Therefore, the blood cell deformability measuring device 1 is not limited to the red blood cell R having an elliptical shape, and is an amoeba-like white blood cell. Even if it is W, its deformability can be measured. Further, since the deformability of the blood cells passing through the gate 25a having a width smaller than the blood cell diameter is calculated, the deformability when the blood cells pass through the capillaries can be measured by simulating the capillaries by the gate 25a. Further, since the blood flow passing through the gate 25a having a width narrower than the blood cell diameter is displayed on the display 8, the blood cell having the velocity S decreased can be confirmed by the gate 25a, and the blood cell has a uniform velocity on the image. Compared to the conventional flow that has flowed in step 1, it is possible to visually grasp how the blood cells move while deforming.
　［第１の変形例］
　続いて、上記実施の形態に係る血球変形能計測装置１の第１の変形例としての血球変形能計測装置１Ａについて説明する。なお、上記実施の形態と同様の構成要素には同一の符号を付し、その説明を省略する。 [First Modification]
Subsequently, a blood cell deformability measuring apparatus 1A as a first modification of the blood cell deformability measuring apparatus 1 according to the above embodiment will be described. In addition, the same code | symbol is attached | subjected to the component similar to the said embodiment, and the description is abbreviate | omitted.
　血球変形能計測装置１Ａは、図１に示すように、上記実施の形態におけるパソコン７に代えてパソコン７Ａを備えており、パソコン７Ａは、演算処理部７０に代えて演算処理部７０Ａを備えている。演算処理部７０Ａは、血液中の血球の速度Ｓに代えて、血球がゲート２５ａを通過するのに要する通過時間Ｔを計測可能に構成されている。また血球変形能計測装置１Ａは、図１に示すように、上記実施の形態におけるフィルタ２に代えてフィルタ２Ａを備えており、フィルタ２Ａは、図２に示すように、流路部２５に代えて流路部２５Ａを備えている。但し、流路部２５Ａの形状は流路部２５と同等である。 As shown in FIG. 1, the blood cell deformability measuring apparatus 1A includes a personal computer 7A instead of the personal computer 7 in the above embodiment, and the personal computer 7A includes an arithmetic processing unit 70A instead of the arithmetic processing unit 70. Yes. The arithmetic processing unit 70A is configured to be able to measure a passage time T required for blood cells to pass through the gate 25a instead of the velocity S of the blood cells in the blood. Further, as shown in FIG. 1, the blood cell deformability measuring apparatus 1A includes a filter 2A instead of the filter 2 in the above embodiment, and the filter 2A is replaced with a flow path portion 25 as shown in FIG. 25A is provided. However, the shape of the flow path portion 25A is equivalent to that of the flow path portion 25.
　続いて、血球変形能計測装置１Ａの動作について、主に図７を参照して説明する。 Subsequently, the operation of the blood cell deformability measuring apparatus 1A will be described mainly with reference to FIG.
　図７は、血球変形能計測装置１Ａによる変形能計測のフローチャートである。 FIG. 7 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1A.
　まず、図７に示すように、流路部２５を通過する血流が撮影される（ステップＴ１）。このステップは、上記実施の形態におけるステップＳ１と同様に行われる。 First, as shown in FIG. 7, the blood flow passing through the flow path portion 25 is photographed (step T1). This step is performed in the same manner as step S1 in the above embodiment.
　次に、演算処理部７０Ａにより血流画像が処理され、血球が検出される（ステップＴ２）。ここでは、例えば特開２００１－２６４３１８号公報に記載の公知の方法を用いて、上流テラス２５ｂを流れる血球を検出して追尾する。 Next, the blood flow image is processed by the arithmetic processing unit 70A, and blood cells are detected (step T2). Here, for example, a blood cell flowing in the upstream terrace 25b is detected and tracked by using a known method described in JP-A-2001-264318.
　次に、演算処理部７０Ａにより、ステップＴ２で検出された血球の血球種が判別される（ステップＴ３）。このステップは、上記実施の形態におけるステップＳ３と同様に行われる。 Next, the blood cell type of the blood cell detected in step T2 is determined by the arithmetic processing unit 70A (step T3). This step is performed in the same manner as step S3 in the above embodiment.
　次に、演算処理部７０Ａにより血球の体積Ｖが算出される（ステップＴ４）。このステップは、上記実施の形態におけるステップＳ５と同様に行われる。 Next, the blood cell volume V is calculated by the arithmetic processing unit 70A (step T4). This step is performed in the same manner as step S5 in the above embodiment.
　次に、演算処理部７０Ａにより、血球がゲート２５ａを通過するのに要する通過時間Ｔが計測される（ステップＴ５）。ここでは、ゲート２５ａ内の画像色の濃度変化を検知することにより通過時間Ｔが計測される。 Next, the passage time T required for the blood cells to pass through the gate 25a is measured by the arithmetic processing unit 70A (step T5). Here, the passage time T is measured by detecting the density change of the image color in the gate 25a.
　この通過時間Ｔの具体的な計測方法について、図８，９を参照して説明する。図８（ａ）～（ｄ）は白血球Ｗがゲート２５ａを通過する様子を示す図であり、図９はそのときの血流画像の色の濃度の時間変化を示すグラフである。 A specific method for measuring the passage time T will be described with reference to FIGS. FIGS. 8A to 8D are views showing how the white blood cells W pass through the gate 25a, and FIG. 9 is a graph showing the change over time of the color density of the blood flow image at that time.
　図８（ａ）～（ｄ）に示すように、例えば白血球Ｗがゲート２５ａを通過するときの、ゲート２５ａ内の任意の位置に設定された計測ラインＰでの血流画像の色の濃度の時間変化を計測すると、図９に示すようなグラフが得られる。 As shown in FIGS. 8A to 8D, for example, when the white blood cell W passes through the gate 25a, the color density of the blood flow image on the measurement line P set at an arbitrary position in the gate 25a. When the time change is measured, a graph as shown in FIG. 9 is obtained.
　より詳細には、まず、図８（ａ）に示すように白血球Ｗが計測ラインＰよりも上流にあるときには、血流画像の色は薄い（図９の点Ｃ１）。そして、白血球Ｗ前縁が計測ラインＰに差し掛かると色は濃くなりだし（図９の点Ｃ２）、図８（ｂ）に示すように白血球Ｗ前縁が計測ラインＰを通過しきると色は少し薄くなる（図９の点Ｃ３）。これは、白血球Ｗを包む膜の方が白血球Ｗ内部よりも色が濃いためである。続けて、図８（ｃ）に示すように白血球Ｗ後縁が計測ラインＰに差し掛かると再び色が濃くなり（図９の点Ｃ４）、白血球Ｗ後縁が計測ラインＰを通過するにつれて今度は色が薄くなっていく。そして、白血球Ｗ後縁が計測ラインＰを通過し終えるところで濃度の変化が殆ど無くなり（図９の点Ｃ５）、図８（ｄ）に示すように白血球Ｗ後縁が計測ラインＰを完全に通過しきると、濃度の変化が完全に無くなるとともに白血球Ｗ通過前の濃度まで回復する（図９の点Ｃ６）。 More specifically, first, as shown in FIG. 8A, when the white blood cell W is upstream of the measurement line P, the color of the blood flow image is light (point C 1 in FIG. 9). When the leading edge of the white blood cell W reaches the measurement line P, the color starts to become dark (point C 2 in FIG. 9), and when the leading edge of the white blood cell W passes through the measurement line P as shown in FIG. Becomes a little thinner (point C 3 in FIG. 9). This is because the membrane that wraps the leukocytes W is darker than the inside of the leukocytes W. Next, as shown in FIG. 8C, when the trailing edge of the white blood cell W reaches the measurement line P, the color becomes dark again (point C 4 in FIG. 9), and as the trailing edge of the white blood cell W passes the measurement line P. This time the color will fade. When the trailing edge of the white blood cell W finishes passing through the measurement line P, the density change is almost eliminated (point C 5 in FIG. 9), and the trailing edge of the white blood cell W completely passes the measurement line P as shown in FIG. 8 (d). When it completely passes, the concentration change is completely eliminated and the concentration before passing through the leukocytes W is recovered (point C 6 in FIG. 9).
　以上の色の濃度の変化点のうち、白血球Ｗ前縁が計測ラインＰに差し掛かる点Ｃ２から、白血球Ｗ後縁が計測ラインＰを通過し終える点Ｃ５までの時間として、通過時間Ｔが計測される。なお、血流画像にエッジを強調する処理を施しておくと、血球通過時の色の濃度変化をより顕著にすることができる。また、赤血球Ｒの通過時間Ｔを計測する場合には、赤の色相の変化を検知すればよく、この検知によりステップＴ３における赤血球Ｒの判別を兼ねることもできる。 Of the change point of the concentration of more colors, from the point C 2 leukocytes W leading edge approaches the measurement line P, as the time point to C 5 leukocytes W trailing edge passing completely through the measurement line P, the transit time T Is measured. In addition, if the process which emphasizes an edge is given to a blood-flow image, the color density change at the time of blood-cell passage can be made more remarkable. Further, when the passage time T of the red blood cell R is measured, it is only necessary to detect a change in the red hue, and this detection can also serve as the determination of the red blood cell R in step T3.
　次に、図７に示すように、演算処理部７０Ａにより血球の変形能が算出される（ステップＴ６）。ここでは、ステップＴ４及びステップＴ５で算出された血球の体積Ｖ及び通過時間Ｔから、以下の式（３０）を満たすＤ３が血球の変形能として算出される。 Next, as shown in FIG. 7, the deformability of the blood cell is calculated by the arithmetic processing unit 70A (step T6). Here, D 3 satisfying the following equation (30) is calculated as the deformability of the blood cell from the blood cell volume V and the passage time T calculated in step T4 and step T5.
　　Ｄ３＝β×Ｔ／Ｖ　　　　　　　　　　　　　　　…（３０）
　ここで、βは、予め行われた計測試験で設定された所定の係数であり、上述の式（１）におけるαと同様に設定された係数である。 D 3 = β × T / V (30)
Here, β is a predetermined coefficient set in a measurement test performed in advance, and is a coefficient set in the same manner as α in the above equation (1).
　また、このステップでは、以下の式（４０）を満たすＤ４を血球の変形能として算出してもよい。 In this step, D 4 satisfying the following formula (40) may be calculated as the deformability of the blood cell.
　　Ｄ４＝Ｔ／Ｖ／（Ｔ０／Ｖ０）　　　　　　…（４０）
　ここで、Ｔ０は、所定の基準血液中の血球がゲート２５ａを通過するのに要する通過時間である。 D 4 = T / V / (T 0 / V 0 ) (40)
Here, T 0 is a transit time required for blood cells in a predetermined reference blood to pass through the gate 25a.
　ここで、式（３０），（４０）から算出されるＤ３，Ｄ４は、上記実施の形態での式（１），（２）に対し血球の速度Ｓに代えて通過時間Ｔの逆数を代入したときのＤ１，Ｄ２に他ならない。したがって、Ｄ３，Ｄ４は、Ｄ１，Ｄ２と同様に変形能の評価に用いることができる。 Here, D 3 and D 4 calculated from the equations (30) and (40) are the reciprocals of the passage time T instead of the blood cell velocity S with respect to the equations (1) and (2) in the above embodiment. It is none other than D 1 and D 2 when. Therefore, D 3 and D 4 can be used for the evaluation of deformability in the same manner as D 1 and D 2 .
　そして、変形能として算出されたＤ３又はＤ４は、図６に示すように、血球の体積Ｖに関するグラフとして整理され、赤血球Ｒ及び白血球Ｗの各血球種についての当該グラフがディスプレイ８に表示される。なお、計測対象の血液が赤血球Ｒ及び白血球Ｗのいずれか一方のみを含むものであれば、ステップＴ４～Ｔ６での各算出値を、ステップＴ１で検出された全ての血球の平均値としてもよい。 Then, D 3 or D 4 calculated as deformability is arranged as a graph relating to blood cell volume V as shown in FIG. 6, and the graph for each blood cell type of red blood cells R and white blood cells W is displayed on the display 8. Is done. If the blood to be measured includes only one of red blood cells R and white blood cells W, the calculated values in steps T4 to T6 may be the average value of all blood cells detected in step T1. .
　以上のように、血球変形能計測装置１Ａによれば、上記実施の形態と同様の効果を奏することができる。 As described above, according to the blood cell deformability measuring apparatus 1A, the same effects as those in the above embodiment can be obtained.
　また、ゲート２５ａを通過する血球の体積Ｖ等から変形能を算出するものとして記載したが、上流テラス２５ｂ又は下流テラス２５ｃを通過するときの血流画像から変形能を求めることもできる。上流テラス２５ｂ又は下流テラス２５ｃを通過する血球は、例えば図１０（ａ）～（ｃ）に示すように、その変形能に応じて様々に形状を変化させる。そこで、この血球の縦幅及び横幅の変化を血流画像から算出し、図１１（ａ），（ｂ）に示すように、複数の血球それぞれのデータに対応する縦軸及び横軸の座標にプロットとしたグラフを作成する。そして、このグラフにプロットした各データの分布範囲から、血球の縦幅及び横幅の各変化幅が交差する部分（図中のハッチング部で分布範囲）の面積を変形能として算出することで、当該変形能が小さいほど硬い血球として評価することができる。なお、血球の縦幅及び横幅は、例えば流路部２５のＹ方向及びＸ方向の長さとすればよい。 In addition, although it has been described that the deformability is calculated from the volume V of the blood cells passing through the gate 25a, etc., the deformability can also be obtained from a blood flow image when passing through the upstream terrace 25b or the downstream terrace 25c. The blood cells passing through the upstream terrace 25b or the downstream terrace 25c change their shapes in various ways depending on their deformability as shown in FIGS. 10 (a) to 10 (c), for example. Therefore, the changes in the vertical and horizontal widths of the blood cells are calculated from the blood flow image, and as shown in FIGS. 11A and 11B, the coordinates of the vertical and horizontal axes corresponding to the data of each of the plurality of blood cells are obtained. Create a plotted graph. Then, from the distribution range of each data plotted in this graph, by calculating the area of the portion where the change widths of the vertical and horizontal widths of blood cells intersect (distribution range in the hatched portion in the figure) as the deformability, The smaller the deformability, the harder the blood cell can be evaluated. In addition, what is necessary is just to let the vertical width and horizontal width of a blood cell be the length of the Y direction of a flow-path part 25, and a X direction, for example.
　その他にも、例えば図１２（ａ），（ｂ）に示すように、上流テラス２５ｂ又は下流テラス２５ｃを通過する血球の縦幅の変化幅、及び当該血球の面積を、縦軸及び横軸としたグラフを作成してもよい。このグラフから、例えば、図１２（ｂ）よりも血球の縦幅の変化幅が大きい図１２（ａ）の方が、より柔らかい血球を示しているとして変形能を評価することができる。なお、縦軸の血球の縦幅は、血球の横幅としてもよい。 In addition, for example, as shown in FIGS. 12A and 12B, the vertical width of the blood cell passing through the upstream terrace 25b or the downstream terrace 25c and the area of the blood cell are expressed as the vertical axis and the horizontal axis. You may create a graph. From this graph, for example, the deformability can be evaluated assuming that FIG. 12A, in which the change in the vertical width of the blood cell is larger than that in FIG. 12B, shows a softer blood cell. The vertical width of the blood cell on the vertical axis may be the horizontal width of the blood cell.
　また、その他の点についても、本発明は上記実施の形態及びその変形例に限定されるものではなく、適宜変更可能であるのは勿論である。 Also, with respect to other points, the present invention is not limited to the above-described embodiment and its modifications, and can of course be changed as appropriate.
　［第２の変形例］
　続いて、上記実施の形態に係る血球変形能計測装置１の第２の変形例としての血球変形能計測装置１Ｅについて説明する。なお、上記実施の形態と同様の構成要素には同一の符号を付し、その説明を省略する。 [Second Modification]
Subsequently, a blood cell deformability measuring apparatus 1E as a second modification of the blood cell deformability measuring apparatus 1 according to the above embodiment will be described. In addition, the same code | symbol is attached | subjected to the component similar to the said embodiment, and the description is abbreviate | omitted.
　血球変形能計測装置１Ｅは、図１に示すように、上記実施の形態におけるパソコン７に代えてパソコン７Ｅを備えており、パソコン７Ｅは、演算処理部７０に代えて演算処理部７０Ｅを備えている。演算処理部７０Ｅは、血球の速度Ｓがゼロであるゲート２５ａを閉塞したゲート２５ａと判断し、閉塞した割合を算出可能に構成されている。 As shown in FIG. 1, the blood cell deformability measuring apparatus 1E includes a personal computer 7E instead of the personal computer 7 in the above embodiment, and the personal computer 7E includes an arithmetic processing unit 70E instead of the arithmetic processing unit 70. Yes. The arithmetic processing unit 70E is configured to determine that the gate 25a where the blood cell velocity S is zero is a closed gate 25a, and to calculate the closed ratio.
　続いて、血球変形能計測装置１Ｅの動作について、主に図１３，図１４を参照して説明する。 Subsequently, the operation of the blood cell deformability measuring apparatus 1E will be described mainly with reference to FIGS.
　図１３は血球変形能計測装置１Ｅによる変形能計測のフローチャートであり、図１４は閉塞しているゲート２５ａが検知される際のフローチャートである。 13 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1E, and FIG. 14 is a flowchart when the closed gate 25a is detected.
　まず、図１３に示すように、計測対象の血液がフィルタ２Ｅへ流される（ステップＳ１０）。具体的には、供給槽１０へ計測対象の血液が注がれるとともに、必要に応じて溶液びん１３へ生理食塩水等が加えられる。そして、差圧制御部９によりフィルタ２Ｅに所定の差圧が加えられて血液がフィルタ２Ｅに流される。 First, as shown in FIG. 13, blood to be measured is flowed to the filter 2E (step S10). Specifically, blood to be measured is poured into the supply tank 10 and physiological saline or the like is added to the solution bottle 13 as necessary. Then, a predetermined differential pressure is applied to the filter 2E by the differential pressure control unit 9, and blood flows through the filter 2E.
　次に、流路部２５Ｅを通過する血流が撮影され、血流画像が採取される（ステップＳ２０）。ここでは、流路部２５Ｅを通過する血流がＴＶカメラ３で動画撮影される。撮影された血流画像はディスプレイ８に表示される。 Next, a blood flow passing through the flow path portion 25E is photographed, and a blood flow image is collected (step S20). Here, the TV camera 3 takes a moving image of the blood flow that passes through the flow path portion 25E. The photographed blood flow image is displayed on the display 8.
　次に、演算処理部７０Ｅにより血流画像が処理され、ゲート２５ａ内で滞留している血球が検出されることにより、血球が詰まって閉塞しているゲート２５ａが検知される（ステップＳ３０）。このステップは、図１４及び図１５（ａ）～（ｅ）に示す各ステップ及び処理画像を経て行われる。ここで、図１５（ａ）～（ｅ）は、図１４の各ステップにおける処理画像の一例を示す図である。但し、図１５（ａ）～（ｅ）は、当該ステップでの処理の理解を容易にするためのものであり、ゲート２５ａ内の血流画像を処理したものではない。 Next, the blood flow image is processed by the arithmetic processing unit 70E, and the blood cells staying in the gate 25a are detected, whereby the gate 25a clogged with the blood cells is detected (step S30). This step is performed through each step and processed image shown in FIGS. 14 and 15A to 15E. Here, FIGS. 15A to 15E are diagrams showing an example of the processed image in each step of FIG. However, FIGS. 15A to 15E are for facilitating the understanding of the processing in this step, and are not processed blood flow images in the gate 25a.
　図１４に示すように、まず、採取された血流画像に対し垂直及び水平の両方向へＳｏｂｅｌフィルタをかけることで、滞留している血球部分（以下、血球滞留部という）のエッジが抽出される（ステップＳ３１）。そして、この画像がグレースケール化されるとともに所定の閾値で二値化され、血球滞留部が白色で表示される（ステップＳ３２）。 As shown in FIG. 14, first, a Sobel filter is applied to the collected blood flow image in both the vertical and horizontal directions to extract the edge of the staying blood cell portion (hereinafter referred to as a blood cell staying portion). (Step S31). The image is grayscaled and binarized with a predetermined threshold value, and the blood cell retention portion is displayed in white (step S32).
　二値化の後、血球滞留部のエッジとして誤認識されたノイズや血流の影が白色部分から除去される（ステップＳ３３）。ここでは、予め設定した閾値より小さい面積の白色部分をノイズとするとともに、Ｘ方向とＹ方向との長さの比が所定範囲外となる白色部分を血流の影として、それぞれ黒色化する。 After binarization, noise and blood flow shadows that are misrecognized as edges of the blood cell retention portion are removed from the white portion (step S33). Here, a white portion having an area smaller than a preset threshold is set as noise, and a white portion whose length ratio between the X direction and the Y direction is outside a predetermined range is blackened as a blood flow shadow.
　ノイズ等が除去された画像は、モルフォロジー処理により膨張伸縮処理されて、白色部分の隙間が塗り潰される（ステップＳ３４）。そして、ここまで残った白色部分が血球滞留部として判定される（ステップＳ３５）。 The image from which noise or the like has been removed is expanded and contracted by morphological processing, and the gaps in the white portion are filled (step S34). And the white part which remained so far is determined as a blood cell retention part (step S35).
　こうして血球滞留部が検出され、当該血球滞留部のあるゲート２５ａが、閉塞しているゲート２５ａとして検知される。 Thus, the blood cell retention part is detected, and the gate 25a having the blood cell retention part is detected as the closed gate 25a.
　次に、図１３に示すように、演算処理部７０Ｅにより血球滞留部の体積Ｖが算出される（ステップＳ４０）。ここでは、例えば特開平５－７９９７０号公報に記載の公知の方法を用いてゲート２５ａ内の血球滞留部の面積を算出し、この面積にゲート２５ａの高さｈを乗じることで、ゲート２５ａを閉塞させている血球滞留部の体積Ｖが算出される。 Next, as shown in FIG. 13, the volume V of the blood cell retention part is calculated by the arithmetic processing part 70E (step S40). Here, for example, the area of the blood cell retention portion in the gate 25a is calculated using a known method described in JP-A-5-79970, and this area is multiplied by the height h of the gate 25a, whereby the gate 25a is The volume V of the blood cell retention part being obstructed is calculated.
　次に、演算処理部７０Ｅにより、血球滞留部の血球種が判別される（ステップＳ５０）。赤血球Ｒは赤の色相範囲にある白色部分として判別する。白血球Ｗは、輝度を利用して判別してもよいし、他の血球種より大きいことを利用し、穴の少ない白色部分や単位面積当たりのエッジ数が少ない白色部分として判別してもよい。 Next, the blood cell type of the blood cell retention part is determined by the arithmetic processing unit 70E (step S50). The red blood cell R is determined as a white portion in the red hue range. The white blood cells W may be discriminated using luminance, or may be discriminated as white portions with few holes or white portions with a small number of edges per unit area using the fact that they are larger than other blood cell types.
　なお、計測対象の血液が赤血球Ｒ及び白血球Ｗのいずれか一方のみを含むものであれば、この血球種判別ステップは省略される。 If the blood to be measured contains only one of red blood cells R and white blood cells W, this blood cell type discrimination step is omitted.
　次に、演算処理部７０Ｅによりゲート２５ａの閉塞割合Ｃが算出される（ステップＳ６０）。ここでは、血球滞留部の体積Ｖ別に当該体積Ｖの血球滞留部で閉塞されたゲート２５ａの割合が、閉塞割合Ｃとして算出される。なお、閉塞割合Ｃはゲート２５ａの総数に対する割合とするのが好ましいが、血流画像に全てのゲート２５ａが含まれていない場合には、血流画像に含まれているゲート２５ａ数に対する割合としてもよい。 Next, the blockage rate C of the gate 25a is calculated by the arithmetic processing unit 70E (step S60). Here, the ratio of the gate 25a blocked by the blood cell retention part of the volume V is calculated as the blockage ratio C for each volume V of the blood cell retention part. The occlusion ratio C is preferably a ratio with respect to the total number of gates 25a. However, when all the gates 25a are not included in the blood flow image, the ratio is as a ratio with respect to the number of gates 25a included in the blood flow image. Also good.
　また、このステップでは、閉塞割合Ｃを所定範囲の体積Ｖ別に算出してもよいし、体積Ｖ別に算出せずに全ての血球滞留部についての平均を算出してもよい。後者の場合において、例えば図１６に示すように、１８個のゲート２５ａのうちの８個が白血球Ｗに閉塞されているときには、閉塞割合Ｃ＝８／１８＝０．４４と算出される。 In this step, the occlusion ratio C may be calculated for each volume V in a predetermined range, or an average for all blood cell retention portions may be calculated without calculating for each volume V. In the latter case, for example, as shown in FIG. 16, when eight of the eighteen gates 25a are blocked by the white blood cells W, the blocking ratio C = 8/18 = 0.44 is calculated.
　次に、演算処理部７０Ｅにより血球の変形能が算出される（ステップＳ７０）。ここでは、ステップＳ４０及びステップＳ６０で算出された血球滞留部の体積Ｖ及び閉塞割合Ｃから、それぞれを横軸及び縦軸とした図１７に示すようなグラフが描かれ、当該グラフの閉塞割合Ｃを積分した値の逆数に所定の係数を乗じることにより血球の変形能が算出される。つまり、以下の式（３）を満たすＤ１が血球の変形能として算出される。 Next, the deformability of the blood cell is calculated by the arithmetic processing unit 70E (step S70). Here, a graph as shown in FIG. 17 is drawn with the horizontal axis and the vertical axis respectively from the volume V and the blockage rate C of the blood cell retention portion calculated in step S40 and step S60, and the blockage rate C of the graph is shown. The deformability of the blood cell is calculated by multiplying the reciprocal of the integrated value by a predetermined coefficient. That, D 1 satisfies the following equation (3) is calculated as a deformability of blood cells.
　　Ｄ１＝α２／∫ＣｄＶ　　　　　　　　　　　　　　…（３）
　ここで、α２は、予め行われた計測試験で設定された所定の係数であり、より詳細には、他の装置で計測された赤血球の変形能を正として、血球変形能計測装置１Ｅで算出された赤血球の体積Ｖ及び閉塞割合Ｃから当該変形能が算出されるよう設定された係数である。なお、予め行われた計測試験において、体積Ｖに関する閉塞割合Ｃの積分値に対してα２が一定とならない場合には、当該積分値に対するルックアップテーブルとすればよい。 D 1 = α2 / ∫CdV (3)
Here, α2 is a predetermined coefficient set in a measurement test performed in advance. More specifically, α2 is calculated by the blood cell deformability measuring apparatus 1E with the red blood cell deformability measured by another apparatus as positive. The coefficient is set so that the deformability is calculated from the volume V and the occlusion ratio C of the erythrocytes. In the measurement test performed in advance, if α2 is not constant with respect to the integral value of the blocking ratio C with respect to the volume V, a lookup table for the integral value may be used.
　また、ステップＳ６０で、全ての血球滞留部について平均した閉塞割合Ｃを算出していた場合には、以下の式（３ａ）を満たすＤ１Ａを血球の変形能として算出してもよい。 Moreover, when the blockage ratio C averaged about all the blood cell retention parts was calculated by step S60, you may calculate D1A which satisfy | fills the following formula | equation (3a) as a deformability of a blood cell.
　　Ｄ１Ａ＝α２Ａ／Ｃ　　　　　　　　　　　　　　　　　…（３ａ）
　ここで、α２Ａは、予め行われた計測試験で設定された所定の係数であり、上述の式（３）におけるα２と同様に設定された係数である。 D 1A = α2 A / C (3a)
Here, α2 A is a predetermined coefficient set in a measurement test performed in advance, and is a coefficient set in the same manner as α2 in the above equation (3).
　ここで、変形能として算出されたＤ１又はＤ１Ａは、その値が大きいほど血球が柔らかく変形能が高いことを示す。 Here, D 1 or D 1A calculated as the deformability indicates that the larger the value, the softer the blood cell and the higher the deformability.
　以上のように、血球変形能計測装置１Ｅによれば、ゲート２５ａの閉塞割合Ｃと血球滞留部の体積Ｖとから血球の変形能を算出するので、楕円形状を保持する赤血球Ｒに限定されず、アメーバ状の白血球Ｗであってもその変形能を計測することができる。また、血球径より狭い幅のゲート２５ａを通過する血球の変形能が算出されるので、ゲート２５ａによって毛細血管を模擬して血球が毛細血管を通過するときの変形能を計測することができる。更に、血球径より狭い幅のゲート２５ａを通過する血液の流れがディスプレイ８に表示されるので、ゲート２５ａにより速度が低下した血球を確認することができ、画像上は血球が一様な速度で流れていた従来に比べて、血球が変形しつつ移動する様子を視覚的に捉え易くすることができる。 As described above, according to the blood cell deformability measuring apparatus 1E, the deformability of the blood cells is calculated from the blockage ratio C of the gate 25a and the volume V of the blood cell retention portion. Therefore, the blood cell deformability measuring device 1E is not limited to the red blood cells R having an elliptical shape. Even if it is an amoeba-like leukocyte W, its deformability can be measured. Further, since the deformability of the blood cells passing through the gate 25a having a width smaller than the blood cell diameter is calculated, the deformability when the blood cells pass through the capillaries can be measured by simulating the capillaries by the gate 25a. Furthermore, since the flow of blood passing through the gate 25a having a narrower width than the blood cell diameter is displayed on the display 8, the blood cells whose speed has been reduced by the gate 25a can be confirmed, and the blood cells are displayed at a uniform speed on the image. Compared to the conventional flow, it is possible to visually grasp how the blood cells move while deforming.
　［第３の変形例］
　続いて、上記実施の形態に係る血球変形能計測装置１Ｅの第３の変形例としての血球変形能計測装置１Ｆについて説明する。なお、上記実施の形態と同様の構成要素には同一の符号を付し、その説明を省略する。 [Third Modification]
Subsequently, a blood cell deformability measuring apparatus 1F as a third modification of the blood cell deformability measuring apparatus 1E according to the above embodiment will be described. In addition, the same code | symbol is attached | subjected to the component similar to the said embodiment, and the description is abbreviate | omitted.
　血球変形能計測装置１Ｆは、図１に示すように、上記実施の形態におけるフィルタ２Ｅに代えてフィルタ２Ｆを備えており、フィルタ２Ｆは、図２に示すように、流路部２５Ｅに代えて流路部２５Ｆを備えている。 As shown in FIG. 1, the blood cell deformability measuring apparatus 1F includes a filter 2F instead of the filter 2E in the above embodiment, and the filter 2F is replaced with a flow path portion 25E as shown in FIG. A flow path portion 25F is provided.
　流路部２５Ｆは、図１８に示すように、配列間隔が異なる複数の土手部２２ｂＦ，…に挟まれて形成される複数のゲート２５ａＦを有している。この複数のゲート２５ａＦの幅は、血球径よりも狭いとともに互いに異なっており、本第３の変形例においては、土手部２２ｂＦの配列方向に徐々に変化している。 As shown in FIG. 18, the flow path portion 25F has a plurality of gates 25aF formed between a plurality of bank portions 22bF,. The widths of the plurality of gates 25aF are narrower than the blood cell diameter and are different from each other. In the third modification, the width is gradually changed in the arrangement direction of the bank portions 22bF.
　続いて、血球変形能計測装置１Ｆの動作について、主に図１９を参照して説明する。 Subsequently, the operation of the blood cell deformability measuring apparatus 1F will be described mainly with reference to FIG.
　図１９は、血球変形能計測装置１Ｆによる変形能計測のフローチャートである。 FIG. 19 is a flowchart of deformability measurement by the blood cell deformability measuring apparatus 1F.
　まず、図１９に示すように、計測対象の血液がフィルタ２Ｆへ流され（ステップＴ１）、流路部２５Ｅの血流画像が採取される（ステップＴ２）。これらのステップは、上記実施の形態におけるステップＳ１０及びステップＳ２０と同様に行われる。 First, as shown in FIG. 19, blood to be measured is flowed to the filter 2F (step T1), and a blood flow image of the flow path portion 25E is collected (step T2). These steps are performed in the same manner as steps S10 and S20 in the above embodiment.
　次に、演算処理部７０Ｅにより血流画像が処理され、異なる幅ごとにゲート２５ａＦの血流画像を抽出する（ステップＴ３）。本第３の変形例においては、各ゲート２５ａＦで血流画像を分割して抽出する。 Next, the blood flow image is processed by the arithmetic processing unit 70E, and the blood flow image of the gate 25aF is extracted for each different width (step T3). In the third modification, the blood flow image is divided and extracted by each gate 25aF.
　次に、演算処理部７０Ｅにより、血球滞留部で閉塞されているゲート２５ａＦが検知された後（ステップＴ４）、当該血球滞留部の体積Ｖが算出され（ステップＴ５）、次いで、当該血球滞留部の血球種が判別される（ステップＴ６）。これらのステップは、上記実施の形態におけるステップＳ３０～Ｓ５０と同様に行われる。 Next, after the gate 25aF closed by the blood cell retention part is detected by the arithmetic processing unit 70E (step T4), the volume V of the blood cell retention part is calculated (step T5), and then the blood cell retention part Are determined (step T6). These steps are performed in the same manner as steps S30 to S50 in the above embodiment.
　次に、演算処理部７０Ｅにより、血球滞留部で閉塞されているゲート２５ａＦの幅のうち最大のものが最大閉塞幅Ｌとして検出される（ステップＴ７）。 Next, the arithmetic processing unit 70E detects the maximum width of the gate 25aF blocked by the blood cell retention part as the maximum blocking width L (step T7).
　次に、演算処理部７０Ｅにより血球の変形能が算出される（ステップＴ８）。ここでは、ステップＴ７で算出された血球滞留部の最大閉塞幅Ｌ、及び当該最大閉塞幅Ｌに対応するゲート２５ａＦを閉塞させた血液滞留部の体積Ｖから、以下の式（４）を満たすＤ２が血球の変形能として算出される。 Next, the deformability of the blood cell is calculated by the arithmetic processing unit 70E (step T8). Here, D satisfying the following equation (4) from the maximum occlusion width L of the blood cell retention portion calculated in step T7 and the volume V of the blood retention portion that occludes the gate 25aF corresponding to the maximum occlusion width L: 2 is calculated as the deformability of blood cells.
　　Ｄ２＝β×Ｌ／Ｖ　　　　　　　　　　　　　　　…（４）
　ここで、βは、予め行われた計測試験で設定された所定の係数であり、上述の式（３）におけるα２と同様に設定された係数である。 D 2 = β × L / V (4)
Here, β is a predetermined coefficient set in a measurement test performed in advance, and is a coefficient set in the same manner as α2 in the above equation (3).
　また、このステップでは、以下の式（５）を満たすＤ３を血球の変形能として算出してもよい。 Further, in this step, the D 3 that satisfies the following equation (5) may be calculated as a deformability of blood cells.
　　Ｄ３＝Ｌ／Ｌ０　　　　　　　　　　　　　　　　…（５）
　ここで、Ｌ０は、所定の基準血液をゲート２５ａＦへ通過させたときに、当該血液中の血球で閉塞されたゲート２５ａＦにおける当該血球の体積別の最大閉塞幅Ｌのうち、血球の体積が式（４）におけるＶであるときの値であり、所定の基準血液とは、標準的な健康度の血液である。 D 3 = L / L 0 (5)
Here, L 0 is the volume of the blood cell in the maximum occlusion width L for each volume of the blood cell in the gate 25aF blocked by the blood cell in the blood when a predetermined reference blood is passed to the gate 25aF. It is a value when it is V in Formula (4), and the predetermined reference blood is blood of a standard health level.
　ここで、変形能として算出されたＤ２は、その値が大きいほど血球が硬いことを示す。また、Ｄ３は、その値が１のときに血球が標準的な硬さであることを示し、１より大きいほど硬く、小さいほど柔らかいことを示す。Ｄ３が算出された場合には、標準的な健康度の血球に対する相対値として変形能が示されるので、血球滞留部の体積Ｖによらず一意に変形能の程度を理解することができる。 Here, D 2 calculated as deformability, shows that blood cells stiff greater the value. Further, D 3 indicates that the blood cell has a standard hardness when the value is 1, and indicates that the blood cell is harder as it is larger than 1 and softer as it is smaller. If the D 3 is calculated, since deformability is shown as a relative value with respect to blood cells of the standard health, it is possible to understand the degree of uniquely deformability regardless of the volume V of the blood cell trapping portion.
　以上のように、血球変形能計測装置１Ｆによれば、上記実施の形態と同様の効果を奏することができる。 As described above, according to the blood cell deformability measuring apparatus 1F, the same effects as those of the above embodiment can be obtained.
　なお、本第３の変形例においては、ゲート２５ａＦは、土手部２２ｂＦの配列方向に徐々に変化する幅を有するものとして記載したが、例えば図２０（ａ），（ｂ）に示すように、血流方向（図中のＹ方向）に徐々に狭くなる各幅を有する複数段のゲート２５ａ１，…を設けてもよい。図２０（ａ），（ｂ）に示す例では、各段で配列間隔の異なる４段の土手部２２ｂ１～２２ｂ４にそれぞれ挟まれて形成されるゲート２５ａ１～２５ａ４が、血流方向への段毎に徐々に狭くなる幅をそれぞれ有している。このようなゲート２５ａ１～２５ａ４を用いた場合には、より上流で多くの血球を滞留させている方が硬い血球を多く有する血液として評価することができる。なお、図２０（ａ）は、柔らかい血球を多く含む血液が流された状態を示す図であり、図２０（ｂ）は、硬い血球を多く含む血液が流された状態を示す図である。 In the third modified example, the gate 25aF is described as having a width that gradually changes in the arrangement direction of the bank portion 22bF. However, for example, as shown in FIGS. A plurality of stages of gates 25a 1 ,... Having respective widths gradually narrowing in the blood flow direction (Y direction in the figure) may be provided. In the example shown in FIGS. 20 (a) and 20 (b), the gates 25a 1 to 25a 4 formed between the four bank portions 22b 1 to 22b 4 having different arrangement intervals at each stage are provided in the direction of blood flow. Each step has a width that gradually decreases. When such gates 25a 1 to 25a 4 are used, it is possible to evaluate as a blood having a lot of hard blood cells if more blood cells are retained more upstream. 20A is a diagram showing a state in which blood containing a lot of soft blood cells is flowed, and FIG. 20B is a diagram showing a state in which blood containing a lot of hard blood cells is flowed.
　［第４の変形例］
　続いて、上記実施の形態に係る血球変形能計測装置１Ｅの第４の変形例としての血球変形能計測装置１Ｂについて説明する。なお、上記実施の形態と同様の構成要素には同一の符号を付し、その説明を省略する。 [Fourth Modification]
Subsequently, a blood cell deformability measuring apparatus 1B as a fourth modification of the blood cell deformability measuring apparatus 1E according to the above embodiment will be described. In addition, the same code | symbol is attached | subjected to the component similar to the said embodiment, and the description is abbreviate | omitted.
　血球変形能計測装置１Ｂは、図１に示すように、上記実施の形態におけるフィルタ２Ｅに代えてフィルタ２Ｂを備えており、フィルタ２Ｂは、図２に示すように、流路部２５Ｅに代えて流路部２５Ｂを備えている。 As shown in FIG. 1, the blood cell deformability measuring apparatus 1B includes a filter 2B instead of the filter 2E in the above embodiment, and the filter 2B is replaced with a flow path portion 25E as shown in FIG. A flow path portion 25B is provided.
　流路部２５Ｂは、図２１に示すように、一定個数毎に配列間隔が変わる複数の土手部２２ｂＢ，…に挟まれて形成される複数のゲート２５ａＢを有している。この複数のゲート２５ａＢは、血球径より狭い幅に形成されるとともに幅毎に複数の組を形成しており、本第４の変形例においては、３個で組を構成して土手部２２ｂＢの配列方向に徐々に変化している。 As shown in FIG. 21, the flow path portion 25B has a plurality of gates 25aB formed between a plurality of bank portions 22bB,. The plurality of gates 25aB are formed to have a width narrower than the blood cell diameter and form a plurality of sets for each width. In the fourth modified example, three gates 25aB constitute a set of the bank portion 22bB. It is gradually changing in the arrangement direction.
　以上の構成を具備する血球変形能計測装置１Ｂは、上記第３の変形例における血球変形能計測装置１Ｆと同様の動作によって、血球の変形能を算出することができる。但し、最大閉塞幅Ｌを検出するとき（ステップＴ７）には、図２２に示すように、ゲート２５ａＢの閉塞割合Ｃをゲート２５ａＢの幅別に求め、当該閉塞割合Ｃが最大となるゲート２５ａＢの幅を最大閉塞幅Ｌとして検出するのが好ましい。 The blood cell deformability measuring apparatus 1B having the above configuration can calculate the deformability of blood cells by the same operation as the blood cell deformability measuring apparatus 1F in the third modified example. However, when the maximum blocking width L is detected (step T7), as shown in FIG. 22, the blocking ratio C of the gate 25aB is obtained for each width of the gate 25aB, and the width of the gate 25aB at which the blocking ratio C is maximized. Is preferably detected as the maximum closing width L.
　また、図２３に示すように、ゲート２５ａＢの閉塞個数をゲート２５ａＢの幅別に求め、当該閉塞個数で平均を取ったゲート２５ａＢの幅、又は当該閉塞個数が最大となるゲート２５ａＢの幅を最大閉塞幅Ｌとして検出してもよい。なお図２２、図２３においてはゲート２５ａＢを流す血液に含まれる血球の大きさは均一ではなく分布ばらつきを持っているために、中間のゲート幅で分布のピークを生じている。 Further, as shown in FIG. 23, the number of gates 25aB closed is determined according to the width of the gate 25aB, and the gate 25aB width obtained by averaging the blockage numbers or the width of the gate 25aB having the maximum blockage number is maximum blocked. The width L may be detected. In FIGS. 22 and 23, the size of blood cells contained in the blood flowing through the gate 25aB is not uniform but has a distribution variation, so that a distribution peak occurs at an intermediate gate width.
　以上のように、血球変形能計測装置１Ｂによれば、上記実施の形態と同様の効果を奏するのは勿論のこと、幅毎に複数の組を形成しているゲート２５ａＢを有し、当該ゲート２５ａＢの幅別の閉塞割合Ｃが最大となるゲート２５ａＢの幅として求めた最大閉塞幅Ｌから血球の変形能を算出できるので、より多くのゲート２５ａＢを用いて変形能が算出され、より安定した算出結果が得られる。 As described above, according to the blood cell deformability measuring apparatus 1B, it has the gate 25aB that forms a plurality of sets for each width as well as the same effect as that of the above-described embodiment. Since the deformability of blood cells can be calculated from the maximum occlusion width L obtained as the width of the gate 25aB where the occlusion ratio C by width of 25aB is the maximum, the deformability is calculated using more gates 25aB, and is more stable. A calculation result is obtained.
　［第５の変形例］
　続いて、上記実施の形態に係る血球変形能計測装置１Ｅの第５の変形例としての血球変形能計測装置１Ｃについて説明する。なお、上記実施の形態と同様の構成要素には同一の符号を付し、その説明を省略する。 [Fifth Modification]
Subsequently, a blood cell deformability measuring apparatus 1C as a fifth modification of the blood cell deformability measuring apparatus 1E according to the above embodiment will be described. In addition, the same code | symbol is attached | subjected to the component similar to the said embodiment, and the description is abbreviate | omitted.
　血球変形能計測装置１Ｃは、図１に示すように、上記実施の形態におけるフィルタ２Ｅに代えてフィルタ２Ｃを備えており、フィルタ２Ｃは、図２に示すように、流路部２５Ｅに代えて流路部２５Ｃを備えている。 As shown in FIG. 1, the blood cell deformability measuring apparatus 1C includes a filter 2C instead of the filter 2E in the above embodiment, and the filter 2C is replaced with a flow path portion 25E as shown in FIG. A flow path portion 25C is provided.
　流路部２５Ｃは、図２４に示すように、血流方向（図中のＹ方向）に先太りする複数の土手部２２ｂＣ，…に挟まれて形成される複数のゲート２５ａＣを有している。この複数のゲート２５ａＣの幅は、血流方向に徐々に狭くなるとともに血球径よりも狭く形成されている。 As shown in FIG. 24, the flow path portion 25C has a plurality of gates 25aC formed between a plurality of bank portions 22bC,... Which are tapered in the blood flow direction (Y direction in the drawing). . The width of the plurality of gates 25aC is gradually narrowed in the blood flow direction and narrower than the blood cell diameter.
　以上の構成を具備する血球変形能計測装置１Ｃは、上記第３の変形例における血球変形能計測装置１Ｆと同様の動作によって、血球の変形能を算出することができる。但し、最大閉塞幅Ｌを検出するとき（ステップＴ７）には、血球滞留部で閉塞されたゲート２５ａＣにおいて、当該血球滞留部が滞留している位置での当該ゲート２５ａＣの幅を最大閉塞幅Ｌとして検出する。 The blood cell deformability measuring apparatus 1C having the above configuration can calculate the deformability of blood cells by the same operation as the blood cell deformability measuring apparatus 1F in the third modified example. However, when detecting the maximum occlusion width L (step T7), in the gate 25aC occluded by the blood cell retention portion, the width of the gate 25aC at the position where the blood cell retention portion is retained is the maximum occlusion width L. Detect as.
　以上のように、血球変形能計測装置１Ｃによれば、上記実施の形態と同様の効果を奏するのは勿論のこと、血流方向に狭くなる幅に形成されたゲート２５ａＣ内の血流画像がディスプレイ８に表示されるので、血球滞留部で閉塞されているゲート２５ａＣの幅が視覚的に捉え易い。 As described above, according to the blood cell deformability measuring apparatus 1C, the blood flow image in the gate 25aC formed with a width narrowing in the blood flow direction can be obtained as well as the same effect as the above embodiment. Since it is displayed on the display 8, it is easy to visually grasp the width of the gate 25aC blocked by the blood cell retention portion.
　なお、本実施の形態及びその変形例においては、赤血球Ｒ及び／又は白血球Ｗの変形能が算出されるものとして記載したが、白血球Ｗのうち顆粒球、リンパ球及び単球を更に判別し、これらの各変形能が算出されるようにしてもよい。このようにすれば、より詳細の血液診断を行うことができる。顆粒球、リンパ球及び単球の判別は、例えば特開２００１－１７４４５６号公報に記載の公知の方法を用いればよい。 In the present embodiment and its modifications, it is described that the deformability of red blood cells R and / or white blood cells W is calculated, but among leukocytes W, granulocytes, lymphocytes and monocytes are further discriminated, Each of these deformability may be calculated. In this way, more detailed blood diagnosis can be performed. For discrimination between granulocytes, lymphocytes and monocytes, a known method described in, for example, JP-A-2001-174456 may be used.
　また、その他の点についても、本発明は上記実施の形態及びその変形例に限定されるものではなく、適宜変更可能であるのは勿論である。 Also, with respect to other points, the present invention is not limited to the above-described embodiment and its modifications, and can of course be changed as appropriate.
　１、１Ａ、１Ｂ、１Ｃ、１Ｅ、１Ｆ　血球変形能計測装置
　３　ＴＶカメラ（撮影手段）
　７、７Ａ、７Ｅ　パソコン（血流画像表示手段）
　８　ディスプレイ（表示画面）
　２５、２５Ａ、２５Ｂ、２５Ｃ、２５Ｅ、２５Ｆ　流路部
　２５ａ　ゲート
　２５ｂ　上流テラス
　７０、７０Ａ　演算処理部（速度算出手段、体積算出手段、変形能算出手段）
　７０Ｅ　演算処理部（速度算出手段、体積算出手段、変形能算出手段、閉塞状態算出手段、閉塞割合算出手段、閉塞幅検出手段）
　Ｓ　血球の速度
　Ｔ　通過時間
　Ｖ　血球の体積
　Ｃ　閉塞割合
　Ｌ　最大閉塞幅 1, 1A, 1B, 1C, 1E, 1F Blood cell deformability measuring device 3 TV camera (photographing means)
7, 7A, 7E PC (blood flow image display means)
8 Display (display screen)
25, 25A, 25B, 25C, 25E, 25F Channel portion 25a Gate 25b Upstream terrace 70, 70A Arithmetic processing section (speed calculation means, volume calculation means, deformability calculation means)
70E arithmetic processing unit (speed calculation means, volume calculation means, deformability calculation means, blockage state calculation means, blockage ratio calculation means, blockage width detection means)
S Blood cell velocity T Passing time V Blood cell volume C Blockage ratio L Maximum blockage width

Claims (17)

  1. 　血球径よりも広い幅の上流テラスから血球径よりも狭い幅のゲートへ向けて血液を流し、当該血液中の血球の変形能を計測する血球変形能計測装置であって、
    　前記上流テラス及び前記ゲートを通過する血液の流れを撮影する撮影手段と、
    　前記撮影手段によって得られた血流画像から、前記上流テラス又は前記ゲートを通過する血球の速度を算出する速度算出手段と、
    　前記撮影手段によって得られた血流画像から、前記ゲートを通過する血球の体積を算出する体積算出手段と、
    　前記血球の速度及び前記血球の体積から、前記血球の変形能を算出する変形能算出手段と、
    　を備えることを特徴とする血球変形能計測装置。     A blood cell deformability measuring device for flowing blood from an upstream terrace having a width wider than the blood cell diameter toward a gate having a width narrower than the blood cell diameter, and measuring the deformability of the blood cells in the blood,
    Imaging means for imaging the flow of blood passing through the upstream terrace and the gate;
    From the blood flow image obtained by the imaging means, speed calculation means for calculating the speed of blood cells passing through the upstream terrace or the gate;
    From the blood flow image obtained by the imaging means, volume calculating means for calculating the volume of blood cells passing through the gate;
    Deformability calculating means for calculating the deformability of the blood cell from the velocity of the blood cell and the volume of the blood cell;
    A blood cell deformability measuring apparatus comprising:
  2. 　前記変形能算出手段は、前記血球の変形能として、以下の式（１）又は式（２）を満たすＤ１又はＤ２を算出することを特徴とする請求項１に記載の血球変形能計測装置。
    　　Ｄ１＝α／（Ｓ×Ｖ）　　　　　　　　　　　　　　　　…（１）
    　　Ｄ２＝１／（Ｓ×Ｖ）／（１／（Ｓ０×Ｖ０））　　　　　…（２）
    （但し、
    　α：所定の係数
    　Ｓ：前記上流テラス又は前記ゲートを通過する血球の速度
    　Ｖ：前記ゲートを通過する血球の体積
    　Ｓ０：所定の基準血液を前記上流テラス又は前記ゲートへ通過させたときの当該血液中の血球の速度
    　Ｖ０：所定の基準血液を前記ゲートへ通過させたときの当該血液中の血球の体積）     2. The blood cell deformability measurement according to claim 1, wherein the deformability calculation means calculates D 1 or D 2 satisfying the following formula (1) or formula (2) as the deformability of the blood cell. apparatus.
    D 1 = α / (S × V) (1)
    D 2 = 1 / (S × V) / (1 / (S 0 × V 0 )) (2)
    (However,
    α: a predetermined coefficient S: velocity of blood cells passing through the upstream terrace or the gate V: volume of blood cells passing through the gate S 0 : the time when a predetermined reference blood is passed through the upstream terrace or the gate Velocity of blood cells in blood V 0 : volume of blood cells in the blood when a predetermined reference blood is passed through the gate)
  3. 　前記速度算出手段は、前記血球の速度として、前記血球が前記ゲートを通過するのに要する通過時間の逆数を算出することを特徴とする請求項１又は２に記載の血球変形能計測装置。 The blood cell deformability measuring apparatus according to claim 1 or 2, wherein the speed calculation means calculates the reciprocal of the transit time required for the blood cells to pass through the gate as the speed of the blood cells.
  4. 　前記撮影手段によって得られた血流画像を表示画面に表示する血流画像表示手段を有することを特徴とする請求項１から３の何れか一項に記載の血球変形能計測装置。 4. The blood cell deformability measuring apparatus according to claim 1, further comprising blood flow image display means for displaying a blood flow image obtained by the imaging means on a display screen.
  5. 　前記ゲートは複数であり、
    　前記速度算出手段により得られた血球の速度がゼロである前記血球で閉塞された前記ゲートの閉塞割合を算出する閉塞状態算出手段を備え
    　前記変形能算出手段は、前記ゲートの閉塞割合及び前記体積算出手段が算出した前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする請求項１から４の何れか一項に記載の血球変形能計測装置。     A plurality of the gates;
    A blockage state calculating unit that calculates a blockage rate of the gate blocked by the blood cell, wherein the blood cell velocity obtained by the velocity calculation unit is zero, the deformability calculation unit including the blockage rate of the gate and the volume The blood cell deformability measuring apparatus according to any one of claims 1 to 4, wherein the deformability of the blood cell is calculated from the volume of the blood cell with the gate closed by the calculation means.
  6. 　前記閉塞状態算出手段は、前記血球の体積別に当該体積の血球で閉塞された前記ゲートの閉塞割合を算出し、
    　前記変形能算出手段は、前記血球の変形能として、以下の式（３）を満たすＤ１を算出することを特徴とする請求項５に記載の血球変形能計測装置。
    　　Ｄ１＝α２／∫ＣｄＶ　　　　　　　　　　　　　　…（３）
    （但し、
    　α２：所定の係数
    　Ｃ：前記ゲートの閉塞割合
    　Ｖ：前記ゲートを閉塞させた前記血球の体積）     The occlusion state calculating means calculates the occlusion ratio of the gate that is occluded by blood cells of the volume according to the volume of the blood cells,
    The deformability calculation means, blood cell deformability measurement apparatus described as deformability of the blood cells, to claim 5, characterized in that to calculate the D 1 satisfies the following equation (3).
    D 1 = α2 / ∫CdV (3)
    (However,
    α2: Predetermined coefficient C: Blocking ratio of the gate V: Volume of the blood cell blocking the gate)
  7. 　複数の前記ゲートは、血流方向に複数配設されるとともに血流方向上流側から下流側に向けて除々に狭くなるように複数の異なる幅に形成されるか、或いは血流方向に直交する方向に複数配設されるとともに複数の異なる幅で形成されており、
    　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートの幅のうち最大のものを最大閉塞幅として検出し、
    　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする請求項５又は６に記載の血球変形能計測装置。     The plurality of gates are arranged in the blood flow direction and are formed in a plurality of different widths so as to gradually narrow from the upstream side to the downstream side in the blood flow direction, or orthogonal to the blood flow direction. It is formed with a plurality of different widths and a plurality of different widths in the direction,
    The occlusion state calculating means detects, as a maximum occlusion width, the largest one of the widths of the gates occluded by the blood cells, from the blood flow image obtained by the imaging means,
    The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. The blood cell deformability measuring apparatus according to claim 5 or 6, characterized by the above.
  8. 　複数の前記ゲートは幅毎に複数の組を形成しており、
    　前記閉塞状態算出手段は、前記血球で閉塞された前記ゲートの閉塞割合を前記ゲートの幅別に求め、当該閉塞割合が最大となる前記ゲートの幅を最大閉塞幅として検出し、
    　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする請求項５又は６に記載の血球変形能計測装置。     The plurality of gates form a plurality of sets for each width,
    The blockage state calculating means obtains the blockage rate of the gate blocked by the blood cells according to the width of the gate, and detects the width of the gate that maximizes the blockage rate as the maximum blockage width,
    The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. The blood cell deformability measuring apparatus according to claim 5 or 6, characterized by the above.
  9. 　前記ゲートは血流方向下流側に向けて狭くなる幅に形成されており、
    　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートにおける当該血球の閉塞位置での当該ゲートの幅を最大閉塞幅として検出し、
    　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積手段が算出した前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする請求項５又は６に記載の血球変形能計測装置。     The gate is formed in a width that narrows toward the downstream side in the blood flow direction,
    The occlusion state calculating means detects, as a maximum occlusion width, the width of the gate at the occlusion position of the blood cell in the gate occluded with the blood cell from the blood flow image obtained by the imaging means,
    7. The deformability calculating means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that has closed the gate calculated by the volume means. The blood cell deformability measuring apparatus according to 1.
  10. 　前記変形能算出手段は、前記血球の変形能として、以下の式（４）又は式（５）を満たすＤ２又はＤ３を算出することを特徴とする請求項７から９のいずれか一項に記載の血球変形能計測装置。
    　　Ｄ２＝β×Ｌ／Ｖ　　　　　　　　　　　　　　　…（４）
    　　Ｄ３＝Ｌ／Ｌ０　　　　　　　　　　　　　　　　…（５）
    （但し、
    　β：所定の係数
    　Ｌ：前記ゲートの最大閉塞幅
    　Ｌ０：所定の基準血液を前記ゲートへ通過させたときに、当該血液中の血球で閉塞されたゲートにおける当該血球の体積別の最大閉塞幅のうち、血球の体積が式（４）におけるＶであるときの値
    　Ｖ：前記ゲートを閉塞させた前記血球の体積）     10. The deformability calculating means calculates D 2 or D 3 satisfying the following formula (4) or formula (5) as the deformability of the blood cell: 10. The blood cell deformability measuring apparatus according to 1.
    D 2 = β × L / V (4)
    D 3 = L / L 0 (5)
    (However,
    β: Predetermined coefficient L: Maximum occlusion width of the gate L 0 : Maximum occlusion width for each blood cell volume at the gate occluded with blood cells in the blood when a predetermined reference blood is passed through the gate Value when the volume of blood cells is V in the formula (4) V: volume of the blood cells with the gate blocked)
  11. 　血球径より狭い幅に形成された複数のゲートへ血液を流し、当該血液中の血球の変形能を計測する血球変形能計測装置であって、
    　前記ゲートを通過する血液の流れを撮影する撮影手段と、
    　前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートの閉塞割合を算出する閉塞状態算出手段と、
    　前記撮影手段によって得られた血流画像から、前記ゲートを閉塞させた前記血球の体積を算出する体積算出手段と、
    　前記ゲートの閉塞割合及び前記血球の体積から、前記血球の変形能を算出する変形能算出手段と、
    　を備えることを特徴とする血球変形能計測装置。     A blood cell deformability measuring apparatus for flowing blood to a plurality of gates formed with a narrower width than the blood cell diameter and measuring the deformability of the blood cells in the blood,
    Photographing means for photographing the flow of blood passing through the gate;
    From the blood flow image obtained by the imaging means, an occlusion state calculation means for calculating the occlusion ratio of the gate occluded by the blood cells,
    From the blood flow image obtained by the imaging means, a volume calculation means for calculating the volume of the blood cell with the gate blocked,
    Deformability calculating means for calculating the deformability of the blood cell from the blockage ratio of the gate and the volume of the blood cell;
    A blood cell deformability measuring apparatus comprising:
  12. 　前記閉塞状態算出手段は、前記血球の体積別に当該体積の血球で閉塞された前記ゲートの閉塞割合を算出し、
    　前記変形能算出手段は、前記血球の変形能として、以下の式（３）を満たすＤ１を算出することを特徴とする請求項１１に記載の血球変形能計測装置。
    　　Ｄ１＝α２／∫ＣｄＶ　　　　　　　　　　　　　　…（３）
    （但し、
    　α２：所定の係数
    　Ｃ：前記ゲートの閉塞割合
    　Ｖ：前記ゲートを閉塞させた前記血球の体積）     The occlusion state calculating means calculates the occlusion ratio of the gate that is occluded by blood cells of the volume according to the volume of the blood cells,
    The deformability calculation means, blood cell deformability measurement apparatus described as deformability of the blood cells, to claim 11, characterized in that to calculate the D 1 satisfies the following equation (3).
    D 1 = α2 / ∫CdV (3)
    (However,
    α2: Predetermined coefficient C: Blocking ratio of the gate V: Volume of the blood cell blocking the gate)
  13. 　前記撮影手段によって得られた血流画像を表示画面に表示する血流画像表示手段を有することを特徴とする請求項１１又は１２に記載の血球変形能計測装置。 The blood cell deformability measuring device according to claim 11 or 12, further comprising blood flow image display means for displaying a blood flow image obtained by the imaging means on a display screen.
  14. 　複数の前記ゲートは、血流方向に複数配設されるとともに血流方向上流側から下流側に向けて除々に狭くなるように複数の異なる幅に形成されるか、或いは血流方向に直交する方向に複数配設されるとともに複数の異なる幅で形成されており、
    　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートの幅のうち最大のものを最大閉塞幅として検出し、
    　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出すことを特徴とする請求項１１から１３のいずれか一項に記載の血球変形能計測装置。     The plurality of gates are arranged in the blood flow direction and are formed in a plurality of different widths so as to gradually narrow from the upstream side to the downstream side in the blood flow direction, or orthogonal to the blood flow direction. It is formed with a plurality of different widths and a plurality of different widths in the direction,
    The occlusion state calculating means detects, as a maximum occlusion width, the largest one of the widths of the gates occluded by the blood cells, from the blood flow image obtained by the imaging means,
    The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. The blood cell deformability measuring apparatus according to any one of claims 11 to 13, characterized in that
  15. 　複数の前記ゲートは幅毎に複数の組を形成しており、
    　前記閉塞状態算出手段は、前記血球で閉塞された前記ゲートの閉塞割合を前記ゲートの幅別に求め、当該閉塞割合が最大となる前記ゲートの幅を最大閉塞幅として検出し、
    　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積算出手段が算出した前記最大閉塞幅に対応する前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする請求項１１から１３のいずれか一項に記載の血球変形能計測装置。     The plurality of gates form a plurality of sets for each width,
    The blockage state calculating means obtains the blockage rate of the gate blocked by the blood cells according to the width of the gate, and detects the width of the gate that maximizes the blockage rate as the maximum blockage width,
    The deformability calculation means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that occludes the gate corresponding to the maximum occlusion width calculated by the volume calculation means. The blood cell deformability measuring apparatus according to any one of claims 11 to 13, characterized in that
  16. 　前記ゲートは血流方向下流側に向けて狭くなる幅に形成されており、
    　前記閉塞状態算出手段は、前記撮影手段によって得られた血流画像から、前記血球で閉塞された前記ゲートにおける当該血球の閉塞位置での当該ゲートの幅を最大閉塞幅として検出し、
    　前記変形能算出手段は、前記ゲートの最大閉塞幅及び前記体積手段が算出した前記ゲートを閉塞させた前記血球の体積から、前記血球の変形能を算出することを特徴とする請求項１１から１３のいずれか一項に記載の血球変形能計測装置。     The gate is formed in a width that narrows toward the downstream side in the blood flow direction,
    The occlusion state calculating means detects, as a maximum occlusion width, the width of the gate at the occlusion position of the blood cell in the gate occluded with the blood cell from the blood flow image obtained by the imaging means,
    The deformability calculating means calculates the deformability of the blood cell from the maximum occlusion width of the gate and the volume of the blood cell that has closed the gate calculated by the volume means. The blood cell deformability measuring device according to any one of the above.
  17. 　前記変形能算出手段は、前記血球の変形能として、以下の式（４）又は式（５）を満たすＤ２又はＤ３を算出することを特徴とする請求項１４～１６のいずれか一項に記載の血球変形能計測装置。
    　　Ｄ２＝β×Ｌ／Ｖ　　　　　　　　　　　　　　　…（４）
    　　Ｄ３＝Ｌ／Ｌ０　　　　　　　　　　　　　　　　…（５）
    （但し、
    　β：所定の係数
    　Ｌ：前記ゲートの最大閉塞幅
    　Ｌ０：所定の基準血液を前記ゲートへ通過させたときに、当該血液中の血球で閉塞されたゲートにおける当該血球の体積別の最大閉塞幅のうち、血球の体積が式（４）におけるＶであるときの値
    　Ｖ：前記ゲートを閉塞させた前記血球の体積）     The deformability calculating means calculates D 2 or D 3 satisfying the following formula (4) or formula (5) as the deformability of the blood cell: The blood cell deformability measuring apparatus according to 1.
    D 2 = β × L / V (4)
    D 3 = L / L 0 (5)
    (However,
    β: Predetermined coefficient L: Maximum occlusion width of the gate L 0 : Maximum occlusion width for each blood cell volume at the gate occluded with blood cells in the blood when a predetermined reference blood is passed through the gate Value when the volume of blood cells is V in the formula (4) V: volume of the blood cells with the gate blocked)
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WO2010137470A1 (en) * 2009-05-29 2010-12-02 コニカミノルタオプト株式会社 Device for measuring deformability and method for measuring deformability
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