WO2010137470A1 - Device for measuring deformability and method for measuring deformability - Google Patents

Device for measuring deformability and method for measuring deformability Download PDF

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WO2010137470A1
WO2010137470A1 PCT/JP2010/058180 JP2010058180W WO2010137470A1 WO 2010137470 A1 WO2010137470 A1 WO 2010137470A1 JP 2010058180 W JP2010058180 W JP 2010058180W WO 2010137470 A1 WO2010137470 A1 WO 2010137470A1
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red blood
deformability
blood cells
hematocrit
velocity
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PCT/JP2010/058180
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French (fr)
Japanese (ja)
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修司 一谷
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コニカミノルタオプト株式会社
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Priority to CN201080022844.6A priority Critical patent/CN102449480B/en
Priority to JP2011515974A priority patent/JP5541280B2/en
Publication of WO2010137470A1 publication Critical patent/WO2010137470A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials

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  • the present invention relates to a deformability measuring apparatus and a deformability measuring method.
  • the deformability of the blood cells can be quantified using the velocity of the blood cells.
  • the moving distance of each blood cell is obtained from a plurality of blood flow images obtained by continuously photographing blood vessels, and the velocity of each blood cell is determined from the moving distance and the frame rate value of the camera.
  • a calculation method has been proposed (see, for example, Patent Document 1).
  • a method for measuring the velocity of fine particles other than blood cells can be applied to blood cells to determine the velocity.
  • red blood cells in blood have a characteristic that the speed changes depending on the hematocrit value of blood.
  • the present invention has been made in view of the above circumstances, and an object of the present invention is to provide a deformability measuring apparatus and a deformability measuring method capable of measuring the deformability of erythrocytes with high reliability independent of the hematocrit value.
  • the invention according to claim 1 is a deformability measuring apparatus, Speed calculating means for calculating the speed of red blood cells in the blood flowing through a flow path having a narrower width than the blood cell diameter of red blood cells; As the hematocrit value of the blood, hematocrit measuring means for obtaining a volume ratio of red blood cells occupying the blood, Deformability calculating means for calculating the deformability of the red blood cells by correcting the speed of the red blood cells calculated by the speed calculating means based on the hematocrit value obtained by the hematocrit measuring means; It is characterized by providing.
  • the deformability measuring apparatus of Claim 1 is the deformability measuring apparatus of Claim 1, Comprising:
  • the deformability calculating means calculates the red blood cell deformability D that satisfies the following formula (1) or formula (2).
  • Invention of Claim 4 is a deformability measuring apparatus of Claim 3, Comprising: An imaging means for imaging blood flowing through the flow path, The speed calculation means uses the blood flow image photographed by the photographing means, tracks the red blood cells in the blood flow image, calculates the speed of the red blood cells, The hematocrit measurement means uses the blood flow image used to calculate the velocity of the red blood cells, extracts a region containing red blood cells from the blood flow image based on a difference in concentration, and obtains the hematocrit value. .
  • the invention according to claim 5 is a deformability measuring method, A speed calculating step for calculating the speed of red blood cells in the blood flowing through a flow path having a narrower width than the blood cell diameter of red blood cells; As the hematocrit value of the blood, a hematocrit measurement step for determining the volume ratio of red blood cells in the blood, Based on the hematocrit value obtained in the hematocrit measurement step, a deformability calculation step for calculating the deformability of the red blood cells by correcting the speed of the red blood cells calculated in the speed calculation step; It is characterized by providing.
  • Invention of Claim 6 is a deformability measuring method of Claim 5, Comprising: In the deformability calculation step, the deformability D of the red blood cells satisfying the following formula (1) or formula (2) is calculated.
  • Invention of Claim 8 is a deformability measuring method of Claim 7, Comprising: Comprising a photographing step of photographing blood flowing through the flow path; In the velocity calculating step, using the blood flow image taken in the imaging step, tracking the red blood cells in the blood flow image to calculate the velocity of the red blood cells, In the hematocrit measurement step, the blood flow image used for calculating the velocity of the red blood cells is used, and a region containing red blood cells is extracted from the blood flow image based on a difference in concentration to obtain the hematocrit value. .
  • the speed of the red blood cells is corrected based on the hematocrit value of the blood containing the red blood cells, so the deformability of red blood cells is calculated while taking into account the influence of the hematocrit value. can do. Therefore, it is possible to measure the deformability of erythrocytes with high reliability independent of the hematocrit value.
  • the blood extracted for the measurement operation for calculating the velocity and the hematocrit value are thereby obtained. It is possible to prevent the hematocrit values from being different from each other for blood extracted for measurement work. Since red blood cells are not uniformly contained in blood, hematocrit values may be different from each other even if they are extracted from the same blood. According to the invention, it is possible to prevent such a case from occurring and reliably correct the speed of the red blood cells based on the corresponding hematocrit value, so that it is possible to measure the deformability of the red blood cells with higher reliability.
  • FIG. 1 is a block diagram showing an overall configuration of a deformability measuring apparatus 1 according to the first embodiment of the present invention.
  • the deformability measuring device 1 guides blood from the supply tank 10 through the filter 2 to the discharge tank 11, calculates the blood cell velocity in the blood from the information acquired in the process, Blood is supplied from the supply tank 10 to the hematocrit measuring device 4 to measure the hematocrit value, and the deformability (ease of deformation) of red blood cells is obtained from the velocity of the blood cells and the hematocrit value.
  • the deformability measuring apparatus 1 mainly includes a filter 2, a TV camera 3, a hematocrit measuring instrument 4, a personal computer (PC) 7, a display 8, and a differential pressure control unit 9.
  • the deformability measuring apparatus 1 according to the first embodiment is connected to a flow path via a mixer 12 so that a liquid such as physiological saline or a physiologically active substance can be mixed with blood and guided to the filter 2.
  • a plurality of solution bottles 13 and the like are further provided.
  • the blood mixed with a liquid such as physiological saline or a physiologically active substance (hereinafter referred to as blood) is operated by the differential pressure control unit 9 with the pressure pump 15 and the pressure reduction pump 16 with the first valve 10a opened.
  • this blood is sent to the hematocrit measuring instrument 4 by a desired amount when the differential pressure control unit 9 drives the pressurizing pump 15 with the second valve 10b opened.
  • the differential pressure control unit 9, the mixer 12, the first valve 10 a, and the second valve 10 b 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 of arrow X (hereinafter referred to as X direction) at the upper end portions of the silicon single crystal substrates 22 and 22, and the upper end portion of the protruding portion 22a has a hexagonal shape.
  • a plurality of banks 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.
  • 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 thereof.
  • 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 gate 25a is formed in a width t narrower than the blood cell diameter (about 8 ⁇ m) of the red blood cell R in the first embodiment.
  • the lengths la, lb, and lc in the direction of the arrow Y (hereinafter referred to as the Y direction) on the upstream terrace 25b, the gate 25a, and the downstream terrace 25c are all formed to be about 30 ⁇ m. .
  • the blood introduced from the supply tank 10 through the introduction hole 21a passes through the flow path portion 25 from the center side to the outside of the filter 2 and then is discharged through the discharge hole 21b. It will be discharged into the tank 11. More specifically, blood cells, for example, red blood cells R, in the blood flowing through the flow path section 25 first pass through the upstream terrace 25b, pass through the gate 25a while being deformed, and finally pass through the downstream terrace 25c. .
  • 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 and a shutter speed sufficient for photographing a blood flow.
  • the TV camera 3 is installed to face the glass flat plate 24 in the filter 2 and photographs the blood flowing through the flow path portion 25 over the glass flat plate 24.
  • 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 hematocrit measuring device 4 measures the volume ratio of the red blood cells R in the blood as the hematocrit value of the blood.
  • the hematocrit measuring instrument 4 includes a high-speed centrifuge (not shown), and measures a hematocrit value by a so-called micro hematocrit method. Specifically, the blood supplied from the supply tank 10 through the second valve 10b is sealed in a glass capillary, centrifuged with a high-speed centrifuge, and then the value when packed to a certain volume by this centrifugation is not shown. The hematocrit value is measured by reading with a reader.
  • the hematocrit measuring device 4 may be any device as long as it can measure the hematocrit value, and may use a known method described in, for example, Japanese Patent Application Laid-Open No. 11-118794.
  • the personal computer 7 includes an arithmetic processing unit 70.
  • the arithmetic processing unit 70 analyzes the blood flow image input from the TV camera 3 to calculate the velocity of the red blood cell R, and corrects the velocity based on the hematocrit value measured by the hematocrit measuring device 4.
  • the deformability of red blood cells R is calculated.
  • an arithmetic processing unit 70 for example, a CPU (Central Processing ⁇ ⁇ Unit) capable of calculating the deformability of the red blood cell R with a required accuracy can be used.
  • a CPU Central Processing ⁇ ⁇ Unit
  • the display 8 displays a blood flow image input from the TV camera 3, an analysis image analyzed by the personal computer 7, and the like.
  • the differential pressure control unit 9 is connected to the sequence control unit 17, the pressurization pump 15 and the decompression 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 the deformability measuring method by the deformability measuring apparatus 1.
  • step S1 blood to be measured is passed through the filter 2 (step S1). 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, the first valve 10 a is opened by the sequence control unit 17 and 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.
  • the blood flowing through the flow path portion 25 is photographed by the TV camera 3 (step S2).
  • the TV camera 3 takes a moving image of the blood flow so that the same red blood cell R flowing through the gate 25a can be captured in at least two frames.
  • step S3 the speed of red blood cells R in the blood flowing through the gate 25a is calculated (step S3).
  • This step is performed by the arithmetic processing unit 70 of the personal computer 7 analyzing the blood flow image obtained in step S2. Specifically, the arithmetic processing unit 70 uses the blood flow images of a plurality of frames to track the red blood cells R in the blood flow images, thereby obtaining the moving distance of the same red blood cells R flowing through the gate 25a.
  • the speed of the red blood cell R is calculated by dividing by the shutter speed.
  • imaging of blood flow and calculation of velocity in steps S2 and S3 are not limited to the above methods, and the methods described in Patent Documents 1 and 2 and Non-Patent Document 1 described above may be used.
  • the speed is measured by measuring the passage time when a predetermined amount of blood is flowed to the gate 25a without taking the blood flow at S2, and dividing the flow amount of blood by the cross-sectional area and the passage time of the gate 25a. You may use the method of calculating
  • step S4 blood to be measured is set in the hematocrit measuring instrument 4 (step S4).
  • the first valve 10a is closed and the second valve 10b is opened by the sequence control unit 17, and the pressurizing pump 15 is further driven, so that the same blood flowed to the filter 2 in step S1 is hematocritized. It is sent to the measuring device 4 and set.
  • the hematocrit value of the blood set in the hematocrit measuring device 4 is measured (step S5).
  • the measured hematocrit value is output to the personal computer 7.
  • the process related to the measurement of the hematocrit value in steps S4 and S5 may be performed before the process related to the calculation of the speed in steps S2 and S3, or may be performed in parallel.
  • step S6 the deformability of the red blood cell R is calculated.
  • the arithmetic processing unit 70 calculates the deformability of the red blood cell R by correcting the speed of the red blood cell R calculated in step S3 based on the hematocrit value measured in step S5.
  • the arithmetic processing unit 70 calculates the deformability D of the red blood cell R as a value satisfying the following formula (1) or formula (2).
  • V V / V 0 (1)
  • V V ⁇ V 0 (2)
  • V is the velocity of the red blood cell R calculated in step S3
  • V 0 is the red blood cell R in the reference blood when the reference blood having the hematocrit value H measured in step S5 is flowed to the gate 25a.
  • Speed the reference blood refers to the blood of a healthy person
  • the hematocrit value H and the velocity V 0 of the red blood cell R in the reference blood have a relationship as shown in FIG. 5, for example. Therefore, by storing a conversion formula or conversion table corresponding to the relationship between the hematocrit value H of FIG.
  • the hematocrit value H measured in step S5 is stored. From this, the velocity V 0 of the red blood cell R in the reference blood can be obtained.
  • the blood to be measured can be identified as being closer to the reference blood as it is closer.
  • the velocity V 0 of the red blood cell R in the reference blood generally has a constant velocity range ⁇ V 0 with respect to the same hematocrit value H as shown in FIG.
  • the average value may be the speed V 0 .
  • the deformability range ⁇ D corresponding to the speed range ⁇ V 0 the blood to be measured is determined as being within the reference blood range and being good if within the deformability range ⁇ D. You may make it do.
  • the deformability D shown on the vertical axis in FIG. 6 is a unit and a scale when calculated using the above formula (1).
  • the deformability measuring apparatus 1 in the first embodiment described above when calculating the deformability D of the red blood cell R, the velocity V of the red blood cell R is corrected based on the hematocrit value H of the blood containing the red blood cell R. Therefore, the deformability D of the red blood cell R can be calculated while considering the influence of the hematocrit value H. Therefore, it is possible to measure the deformability D of the red blood cell R with high reliability that does not depend on the hematocrit value H.
  • FIG. 7 is a block diagram showing the overall configuration of the deformability measuring apparatus 1A.
  • the deformability measuring apparatus 1A is different from the deformability measuring apparatus 1 in the first embodiment in that it does not include the hematocrit measuring instrument 4 and the second valve 10b, and instead of the personal computer 7. And a personal computer 7A.
  • the personal computer 7A includes an arithmetic processing unit 70A in place of the arithmetic processing unit 70 in the first embodiment.
  • the arithmetic processing unit 70A analyzes the blood flow image input from the TV camera 3 to calculate the velocity V of the red blood cell R and the hematocrit value H of the red blood cell R, and also calculates the red blood cell R from the speed V and the hematocrit value H of the red blood cell R.
  • the deformability D is calculated.
  • FIG. 8 is a flowchart of the deformability measuring method by the deformability measuring apparatus 1A.
  • step T1 blood to be measured is passed through the filter 2 (step T1), the blood flowing through the flow path section 25 is photographed (step T2), and then the speed of the red blood cells R in the blood flowing through the gate 25a is obtained. V is calculated (step T3).
  • steps T1 to T3 are performed in the same manner as steps S1 to S3 in the first embodiment.
  • the processing unit 70A performs the same processing as the processing unit 70 in the first embodiment, whereby the velocity V of the red blood cell R is calculated.
  • the hematocrit value H of the blood to be measured is calculated (step T4).
  • the arithmetic processing unit 70A uses the blood flow image used for calculating the velocity V of the red blood cell R, and calculates the red blood cell R from the blood flow image based on the difference in density between the red blood cell R portion and the non-red blood cell portion.
  • the hematocrit value H which is the volume ratio of blood cells in the blood, is obtained by extracting the included region.
  • the arithmetic processing unit 70A calculates a ratio of the region in the entire blood flow image by setting a region where the density of the image color is equal to or greater than a predetermined threshold as a region including the red blood cells R. Such a region is preferably in the region of the upstream terrace 25b upstream of the gate 25a.
  • the velocity V and the hematocrit value H of the red blood cells R are calculated using the blood flow image captured in step T2, that is, the blood flow imaging in step T2.
  • the velocity V and the hematocrit value H of the red blood cell R are calculated through the same measurement work common to each other.
  • step T5 the deformability D of the red blood cell R is calculated (step T5).
  • the arithmetic processing unit 70A uses the velocity V and hematocrit value H of the red blood cells R calculated in steps T3 and T4, and is the same as the arithmetic processing unit 70 in step S6 in the first embodiment. By performing the processing, the deformability D of the red blood cell R is calculated.
  • the velocity V of the red blood cell R can be obtained through the same measurement work common to each other as well as the same effect as that of the first embodiment. Since the hematocrit value H is calculated, it is possible to prevent the hematocrit value H from being different between the blood extracted for the measurement operation for calculating the velocity V and the blood extracted for the measurement operation for obtaining the hematocrit value H. Since the red blood cells R are not uniformly contained in the blood, the hematocrit values H may be different from each other even if the same blood is extracted separately.
  • the deformability measuring apparatus 1A According to the deformability measuring apparatus 1A, such a case can be prevented and the velocity V of the red blood cell R can be reliably corrected based on the corresponding hematocrit value H. Therefore, the deformability of the red blood cell R is more reliable. D can be measured.
  • the velocity V of the red blood cell R is corrected based on the hematocrit value H.
  • the velocity V of the red blood cell R or the amount of hemoglobin may be corrected, or a combination thereof may be used. It may be corrected.
  • the conversion equation or conversion table for converting the age or hemoglobin amount in the healthy person into the velocity of the red blood cell R is stored in the arithmetic processing units 70 and 70A, so that the red blood cell R as in the case of the hematocrit value H is stored. Can be corrected.
  • 1,1A Deformability measuring device 3 TV camera (photographing means) 4 Hematocrit measuring instrument (hematocrit measuring means) 25a Gate (flow path) 70 arithmetic processing unit (speed calculation means, deformability calculation means) 70A arithmetic processing unit (speed calculation means, hematocrit measurement means, deformability calculation means) D Deformability of red blood cells H Hematocrit value R Red blood cells V Red blood cell velocity V 0 Red blood cell velocity in reference blood

Abstract

Erythrocyte deformability can be measured at a high reliability without depending on hematocrit values. For this, a calculation unit (70) calculates the velocity (V) of erythrocytes (R) in blood that is flowing through a gate (25a), the width (t) of which is narrower than the cell diameter of the erythrocytes (R), and determines the ratio by volume of the erythrocytes (R) in the blood as the hematocrit value (H) of the blood. Further, the calculation unit (70) corrects the velocity (V) of the erythrocytes (R) on the basis of the hematocrit value (H) and thus determines the deformability (D) of the erythrocytes (R).

Description

変形能計測装置及び変形能計測方法Deformability measuring device and deformability measuring method
 本発明は、変形能計測装置及び変形能計測方法に関する。 The present invention relates to a deformability measuring apparatus and a deformability measuring method.
 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。この血液の流動性には、血液中の血球の変形能(変形しやすさ)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。そのため、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であり、なかでも代表的なパラメータである血球の変形能についての定量化方法の確立が望まれている。 In recent years, with increasing interest in health, blood fluidity has attracted attention as a health barometer. A plurality of parameters such as the deformability (ease of deformation), the degree of aggregation, and the viscosity of blood cells in the blood act in a complex manner on the blood fluidity. Therefore, in order to evaluate blood fluidity in more detail, it is necessary to quantify each of these parameters, and in particular, establishment of a quantification method for blood cell deformability, which is a representative parameter, is desired. Yes.
 ここで、血球は変形しやすいものほど速く流れることから、この血球の変形能は当該血球の速度を用いて定量化することができる。血球の速度を計測する方法としては、血管を連続撮影して得られた複数の血流画像から血球個々の移動距離を求め、この移動距離とカメラのフレームレートの値とから血球個々の速度を算出する方法が提案されている(例えば、特許文献1参照)。その他にも、血球以外の微細な粒子の速度を計測する方法(例えば、特許文献2又は非特許文献1参照)を血球に適用し、その速度を求めることが可能である。 Here, since blood cells are more likely to deform and flow faster, the deformability of the blood cells can be quantified using the velocity of the blood cells. As a method of measuring the velocity of blood cells, the moving distance of each blood cell is obtained from a plurality of blood flow images obtained by continuously photographing blood vessels, and the velocity of each blood cell is determined from the moving distance and the frame rate value of the camera. A calculation method has been proposed (see, for example, Patent Document 1). In addition, a method for measuring the velocity of fine particles other than blood cells (see, for example, Patent Document 2 or Non-Patent Document 1) can be applied to blood cells to determine the velocity.
 ところで、血液中の赤血球は、血液のヘマトクリット値に依存して速度が変化する特性を有している。 By the way, red blood cells in blood have a characteristic that the speed changes depending on the hematocrit value of blood.
特開2006-223761号公報JP 2006-223761 A 特開2002-148270号公報JP 2002-148270 A
 しかしながら、上記特許文献1,2及び非特許文献1に記載の方法で算出した赤血球の速度をそのまま当該赤血球の変形能としたのでは、ヘマトクリット値の影響を考慮できていないため、ヘマトクリット値に依存しない信頼性の高い変形能を求めることができない。 However, if the red blood cell velocity calculated by the methods described in Patent Documents 1 and 2 and Non-Patent Document 1 is used as the deformability of the red blood cells as it is, the influence of the hematocrit value cannot be taken into account, and thus depends on the hematocrit value. Unable to obtain a reliable deformability.
 本発明は、上記事情を鑑みてなされたもので、ヘマトクリット値に依存しない信頼性の高い赤血球の変形能を計測することのできる変形能計測装置及び変形能計測方法の提供を課題とする。 The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a deformability measuring apparatus and a deformability measuring method capable of measuring the deformability of erythrocytes with high reliability independent of the hematocrit value.
 前記の課題を解決するために、請求項1に記載の発明は、変形能計測装置であって、
 赤血球の血球径よりも狭い幅の流路を流れる血液中の赤血球の速度を算出する速度算出手段と、
 前記血液のヘマトクリット値として、当該血液中に占める赤血球の容積割合を求めるヘマトクリット計測手段と、
 前記ヘマトクリット計測手段で求められた前記ヘマトクリット値に基づいて、前記速度算出手段で算出された前記赤血球の速度を補正することにより、前記赤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 problems, the invention according to claim 1 is a deformability measuring apparatus,
Speed calculating means for calculating the speed of red blood cells in the blood flowing through a flow path having a narrower width than the blood cell diameter of red blood cells;
As the hematocrit value of the blood, hematocrit measuring means for obtaining a volume ratio of red blood cells occupying the blood,
Deformability calculating means for calculating the deformability of the red blood cells by correcting the speed of the red blood cells calculated by the speed calculating means based on the hematocrit value obtained by the hematocrit measuring means;
It is characterized by providing.
 請求項2に記載の発明は、請求項1に記載の変形能計測装置であって、
 前記変形能算出手段は、以下の式(1)又は式(2)を満たす前記赤血球の変形能Dを算出することを特徴とする。
Invention of Claim 2 is the deformability measuring apparatus of Claim 1, Comprising:
The deformability calculating means calculates the red blood cell deformability D that satisfies the following formula (1) or formula (2).
  D=V/V               …(1)
  D=V-V               …(2)
(但し、V:前記速度算出手段で算出された前記赤血球の速度
    V:前記ヘマトクリット計測手段で求められた前記ヘマトクリット値を有する基準血液を前記流路へ流したときの当該基準血液中の赤血球の速度)
 請求項3に記載の発明は、請求項1又は2に記載の変形能計測装置であって、
 前記速度算出手段及び前記ヘマトクリット計測手段は、互いに共通する同一の計測作業を通じて、前記赤血球の速度及び前記ヘマトクリット値を算出する又は求めることを特徴とする。
D = V / V 0 (1)
D = V−V 0 (2)
(However, V: velocity of the red blood cells calculated by the velocity calculation means V 0 : red blood cells in the reference blood when the reference blood having the hematocrit value obtained by the hematocrit measurement means is flowed into the flow path. Speed)
Invention of Claim 3 is a deformability measuring apparatus of Claim 1 or 2, Comprising:
The velocity calculation means and the hematocrit measurement means calculate or obtain the velocity of the red blood cells and the hematocrit value through the same measurement work common to each other.
 請求項4に記載の発明は、請求項3に記載の変形能計測装置であって、
 前記流路を流れる血液を撮影する撮影手段を備え、
 前記速度算出手段は、前記撮影手段で撮影された血流画像を用い、当該血流画像中の赤血球を追跡して当該赤血球の速度を算出し、
 前記ヘマトクリット計測手段は、前記赤血球の速度の算出に用いた血流画像を用い、濃度の違いに基づいて当該血流画像から赤血球を含む領域を抽出して前記ヘマトクリット値を求めることを特徴とする。
Invention of Claim 4 is a deformability measuring apparatus of Claim 3, Comprising:
An imaging means for imaging blood flowing through the flow path,
The speed calculation means uses the blood flow image photographed by the photographing means, tracks the red blood cells in the blood flow image, calculates the speed of the red blood cells,
The hematocrit measurement means uses the blood flow image used to calculate the velocity of the red blood cells, extracts a region containing red blood cells from the blood flow image based on a difference in concentration, and obtains the hematocrit value. .
 請求項5に記載の発明は、変形能計測方法であって、
 赤血球の血球径よりも狭い幅の流路を流れる血液中の赤血球の速度を算出する速度算出工程と、
 前記血液のヘマトクリット値として、当該血液中に占める赤血球の容積割合を求めるヘマトクリット計測工程と、
 前記ヘマトクリット計測工程で求められた前記ヘマトクリット値に基づいて、前記速度算出工程で算出された前記赤血球の速度を補正することにより、前記赤血球の変形能を算出する変形能算出工程と、
 を備えることを特徴とする。
The invention according to claim 5 is a deformability measuring method,
A speed calculating step for calculating the speed of red blood cells in the blood flowing through a flow path having a narrower width than the blood cell diameter of red blood cells;
As the hematocrit value of the blood, a hematocrit measurement step for determining the volume ratio of red blood cells in the blood,
Based on the hematocrit value obtained in the hematocrit measurement step, a deformability calculation step for calculating the deformability of the red blood cells by correcting the speed of the red blood cells calculated in the speed calculation step;
It is characterized by providing.
 請求項6に記載の発明は、請求項5に記載の変形能計測方法であって、
 前記変形能算出工程では、以下の式(1)又は式(2)を満たす前記赤血球の変形能Dを算出することを特徴とする。
Invention of Claim 6 is a deformability measuring method of Claim 5, Comprising:
In the deformability calculation step, the deformability D of the red blood cells satisfying the following formula (1) or formula (2) is calculated.
  D=V/V               …(1)
  D=V-V               …(2)
(但し、V:前記速度算出工程で算出された前記赤血球の速度
    V:前記ヘマトクリット計測工程で求められた前記ヘマトクリット値を有する基準血液を前記流路へ流したときの当該基準血液中の赤血球の速度)
 請求項7に記載の発明は、請求項5又は6に記載の変形能計測方法であって、
 前記速度算出工程及び前記ヘマトクリット計測工程では、互いに共通する同一の計測作業を通じて、前記赤血球の速度及び前記ヘマトクリット値を算出する又は求めることを特徴とする。
D = V / V 0 (1)
D = V−V 0 (2)
(However, V: velocity of the red blood cells calculated in the velocity calculation step V 0 : red blood cells in the reference blood when the reference blood having the hematocrit value determined in the hematocrit measurement step is flowed to the flow path) Speed)
Invention of Claim 7 is the deformability measuring method of Claim 5 or 6, Comprising:
In the velocity calculation step and the hematocrit measurement step, the velocity of the red blood cells and the hematocrit value are calculated or obtained through the same measurement work common to each other.
 請求項8に記載の発明は、請求項7に記載の変形能計測方法であって、
 前記流路を流れる血液を撮影する撮影工程を備え、
 前記速度算出工程では、前記撮影工程で撮影された血流画像を用い、当該血流画像中の赤血球を追跡して当該赤血球の速度を算出し、
 前記ヘマトクリット計測工程では、前記赤血球の速度の算出に用いた血流画像を用い、濃度の違いに基づいて当該血流画像から赤血球を含む領域を抽出して前記ヘマトクリット値を求めることを特徴とする。
Invention of Claim 8 is a deformability measuring method of Claim 7, Comprising:
Comprising a photographing step of photographing blood flowing through the flow path;
In the velocity calculating step, using the blood flow image taken in the imaging step, tracking the red blood cells in the blood flow image to calculate the velocity of the red blood cells,
In the hematocrit measurement step, the blood flow image used for calculating the velocity of the red blood cells is used, and a region containing red blood cells is extracted from the blood flow image based on a difference in concentration to obtain the hematocrit value. .
 本発明によれば、赤血球の変形能を算出する際に、当該赤血球を含む血液のヘマトクリット値に基づいて当該赤血球の速度を補正するので、ヘマトクリット値の影響を考慮しつつ赤血球の変形能を算出することができる。したがって、ヘマトクリット値に依存しない信頼性の高い赤血球の変形能を計測することができる。 According to the present invention, when calculating the deformability of red blood cells, the speed of the red blood cells is corrected based on the hematocrit value of the blood containing the red blood cells, so the deformability of red blood cells is calculated while taking into account the influence of the hematocrit value. can do. Therefore, it is possible to measure the deformability of erythrocytes with high reliability independent of the hematocrit value.
 また更に、互いに共通する同一の計測作業を通じて、赤血球の速度を算出し、ヘマトクリット値を求めるようにした際には、それによって、速度を算出する計測作業用に抽出した血液と、ヘマトクリット値を求める計測作業用に抽出した血液とで、ヘマトクリット値が互いに異なることを防止できる。赤血球は血液中に一様に含有されていないため、同一の血液であってもそこから別々に抽出されたもの同士では、ヘマトクリット値が互いに異なる場合がある。当該発明によれば、このような場合が生じるのを防止し、確実に対応するヘマトクリット値に基づいて赤血球の速度を補正できるので、より信頼性の高い赤血球の変形能を計測することができる。 Furthermore, when the red blood cell velocity is calculated and the hematocrit value is obtained through the same measurement operation common to each other, the blood extracted for the measurement operation for calculating the velocity and the hematocrit value are thereby obtained. It is possible to prevent the hematocrit values from being different from each other for blood extracted for measurement work. Since red blood cells are not uniformly contained in blood, hematocrit values may be different from each other even if they are extracted from the same blood. According to the invention, it is possible to prevent such a case from occurring and reliably correct the speed of the red blood cells based on the corresponding hematocrit value, so that it is possible to measure the deformability of the red blood cells with higher reliability.
第1の実施形態における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 the deformability measuring apparatus in 1st Embodiment. フィルタの断面図である。It is sectional drawing of a filter. (a)流路部の平面図であり、(b)側断面図である。(A) It is a top view of a flow-path part, (b) It is a sectional side view. 第1の実施形態における変形能計測方法のフローチャートである。It is a flowchart of the deformability measuring method in 1st Embodiment. 健常者におけるヘマトクリット値と赤血球の速度との関係を示すグラフである。It is a graph which shows the relationship between the hematocrit value and the speed | rate of erythrocytes in a healthy subject. 健常者におけるヘマトクリット値と赤血球の変形能との関係を示すグラフである。It is a graph which shows the relationship between the hematocrit value in a healthy subject, and the deformability of erythrocytes. 第2の実施形態における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 the deformability measuring apparatus in 2nd Embodiment. 第2の実施形態における変形能計測方法のフローチャートである。It is a flowchart of the deformability measuring method in 2nd Embodiment.
 以下、本発明の実施形態について、図を参照して説明する。 Hereinafter, embodiments of the present invention will be described with reference to the drawings.
 [第1の実施形態]
 図1は、本発明の第1の実施形態に係る変形能計測装置1の全体構成を示すブロック図である。この図に示すように、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速度を算出するとともに、血液を供給槽10からヘマトクリット測定器4へ供給してヘマトクリット値を測定し、これら血球の速度とヘマトクリット値とから赤血球の変形能(変形しやすさ)を求めるものである。
[First Embodiment]
FIG. 1 is a block diagram showing an overall configuration of a deformability measuring apparatus 1 according to the first embodiment of the present invention. As shown in this figure, the deformability measuring device 1 guides blood from the supply tank 10 through the filter 2 to the discharge tank 11, calculates the blood cell velocity in the blood from the information acquired in the process, Blood is supplied from the supply tank 10 to the hematocrit measuring device 4 to measure the hematocrit value, and the deformability (ease of deformation) of red blood cells is obtained from the velocity of the blood cells and the hematocrit value.
 具体的には、変形能計測装置1は、主に、フィルタ2、TVカメラ3、ヘマトクリット測定器4、パソコン(PC)7、ディスプレイ8及び差圧制御部9を備えている。なお、本第1の実施形態における変形能計測装置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された血液(以下、血液という)は、第1バルブ10aが開放された状態で、差圧制御部9が加圧ポンプ15及び減圧ポンプ16を駆動してフィルタ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。同時に、この血液は、第2バルブ10bが開放された状態で、差圧制御部9が加圧ポンプ15を駆動することにより、ヘマトクリット測定器4へ所望量だけ送られるようになっている。また、上述の差圧制御部9、ミクサー12、第1バルブ10a及び第2バルブ10b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 deformability measuring apparatus 1 mainly includes a filter 2, a TV camera 3, a hematocrit measuring instrument 4, a personal computer (PC) 7, a display 8, and a differential pressure control unit 9. The deformability measuring apparatus 1 according to the first embodiment is connected to a flow path via a mixer 12 so that a liquid such as physiological saline or a physiologically active substance can be mixed with blood and guided to the filter 2. A plurality of solution bottles 13 and the like are further provided. The blood mixed with a liquid such as physiological saline or a physiologically active substance (hereinafter referred to as blood) is operated by the differential pressure control unit 9 with the pressure pump 15 and the pressure reduction pump 16 with the first valve 10a opened. Is driven to adjust the differential pressure across the filter 2 so as to flow through the filter 2 by a desired amount. At the same time, this blood is sent to the hematocrit measuring instrument 4 by a desired amount when the differential pressure control unit 9 drives the pressurizing pump 15 with the second valve 10b opened. The differential pressure control unit 9, the mixer 12, the first valve 10 a, and the second valve 10 b 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が矢印Xの方向(以下、X方向という)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, a protruding portion 22a extends in the direction of arrow X (hereinafter referred to as X direction) at the upper end portions of the silicon single crystal substrates 22 and 22, and the upper end portion of the protruding portion 22a has a hexagonal shape. A plurality of banks 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)は、流路部25を上面から見た図(平面図)であり、図3(b)は、その側断面図である。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。 3A is a view (plan view) of the flow path portion 25 as viewed from above, and FIG. 3B is a side sectional view thereof. 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.
 このうち、ゲート25aは、本第1の実施形態においては、赤血球Rの血球径(約8μm)よりも狭い幅tに形成されている。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における矢印Yの方向(以下、Y方向という)の各長さla,lb,lcは、いずれも約30μmに形成されている。 Among these, the gate 25a is formed in a width t narrower than the blood cell diameter (about 8 μm) of the red blood cell R in the first embodiment. Although not particularly limited, the lengths la, lb, and lc in the direction of the arrow Y (hereinafter referred to as the Y direction) on the upstream terrace 25b, the gate 25a, and the downstream terrace 25c are all formed to be about 30 μm. .
 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、当該フィルタ2の中央側から外側へ向かって流路部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。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 from the center side to the outside of the filter 2 and then is discharged through the discharge hole 21b. It will be discharged into the tank 11. More specifically, blood cells, for example, red blood cells R, in the blood flowing through the flow path section 25 first pass through the upstream terrace 25b, pass through the gate 25a while being deformed, and finally pass through the downstream terrace 25c. .
 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及びシャッタースピード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を流れる血液をガラス平板24超しに撮影する。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 and a shutter speed sufficient for photographing a blood flow. The TV camera 3 is installed to face the glass flat plate 24 in the filter 2 and photographs the blood flowing through the flow path portion 25 over the glass flat plate 24. 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.
 ヘマトクリット測定器4は、血液のヘマトクリット値として、血液中に占める赤血球Rの容積割合を測定するものである。このヘマトクリット測定器4は、図示しない高速遠心機を備えており、いわゆるミクロヘマトクリット法によりヘマトクリット値を測定する。具体的には、供給槽10から第2バルブ10bを通じて供給された血液をガラス製毛細管に封入し、高速遠心機で遠心した後、この遠心によって一定容積まで詰め込まれたときの値を図示しない専用の読み取り器で読むことでヘマトクリット値を測定する。但し、ヘマトクリット測定器4は、ヘマトクリット値が測定できるものであればよく、例えば特開平11-118794号公報等に記載の公知の方法を用いるものであってもよい。 The hematocrit measuring device 4 measures the volume ratio of the red blood cells R in the blood as the hematocrit value of the blood. The hematocrit measuring instrument 4 includes a high-speed centrifuge (not shown), and measures a hematocrit value by a so-called micro hematocrit method. Specifically, the blood supplied from the supply tank 10 through the second valve 10b is sealed in a glass capillary, centrifuged with a high-speed centrifuge, and then the value when packed to a certain volume by this centrifugation is not shown. The hematocrit value is measured by reading with a reader. However, the hematocrit measuring device 4 may be any device as long as it can measure the hematocrit value, and may use a known method described in, for example, Japanese Patent Application Laid-Open No. 11-118794.
 パソコン7は、演算処理部70を備えている。この演算処理部70は、TVカメラ3から入力された血流画像を解析して赤血球Rの速度を算出するとともに、ヘマトクリット測定器4で測定されたヘマトクリット値に基づいて当該速度を補正することにより、赤血球Rの変形能を算出する。このような演算処理部70としては、例えば、上記赤血球Rの変形能を所要の精度で算出可能なCPU(Central Processing Unit)を用いることができる。 The personal computer 7 includes an arithmetic processing unit 70. The arithmetic processing unit 70 analyzes the blood flow image input from the TV camera 3 to calculate the velocity of the red blood cell R, and corrects the velocity based on the hematocrit value measured by the hematocrit measuring device 4. The deformability of red blood cells R is calculated. As such an arithmetic processing unit 70, for example, a CPU (Central Processing 可能 な Unit) capable of calculating the deformability of the red blood cell R with a required accuracy can be used.
 ディスプレイ8は、TVカメラ3から入力された血流画像や、パソコン7によって解析された解析画像等を表示する。 The display 8 displays a blood flow image input from the TV camera 3, an analysis image analyzed by the personal computer 7, and the like.
 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 pressurization pump 15 and the decompression 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.
 続いて、変形能計測装置1を用いて赤血球Rの変形能を計測する変形能計測方法について、主に図4を参照して説明する。図4は、変形能計測装置1による変形能計測方法のフローチャートである。 Subsequently, a deformability measuring method for measuring the deformability of the red blood cell R using the deformability measuring apparatus 1 will be described mainly with reference to FIG. FIG. 4 is a flowchart of the deformability measuring method by the deformability measuring apparatus 1.
 この図に示すように、まず、フィルタ2へ計測対象の血液を流す(ステップS1)。具体的には、供給槽10へ計測対象の血液を注ぐとともに、必要に応じて溶液びん13へ生理食塩水等を加える。そして、シーケンス制御部17により第1バルブ10aが開放されるとともに差圧制御部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へ流される。 As shown in this figure, first, blood to be measured is passed through the filter 2 (step S1). 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, the first valve 10 a is opened by the sequence control unit 17 and 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.
 次に、TVカメラ3により、流路部25を流れる血液を撮影する(ステップS2)。このとき、TVカメラ3は、ゲート25aを流れる同一の赤血球Rを少なくとも2フレームで捉えられるように血流を動画撮影する。 Next, the blood flowing through the flow path portion 25 is photographed by the TV camera 3 (step S2). At this time, the TV camera 3 takes a moving image of the blood flow so that the same red blood cell R flowing through the gate 25a can be captured in at least two frames.
 次に、ゲート25aを流れる血液中の赤血球Rの速度を算出する(ステップS3)。このステップは、パソコン7の演算処理部70がステップS2で得られた血流画像を解析することにより行われる。具体的には、演算処理部70は、複数フレームの血流画像を用い、当該血流画像中の赤血球Rを追跡することにより、ゲート25aを流れる同一の赤血球Rの移動距離を求め、これをシャッタースピードで除すことにより当該赤血球Rの速度を算出する。 Next, the speed of red blood cells R in the blood flowing through the gate 25a is calculated (step S3). This step is performed by the arithmetic processing unit 70 of the personal computer 7 analyzing the blood flow image obtained in step S2. Specifically, the arithmetic processing unit 70 uses the blood flow images of a plurality of frames to track the red blood cells R in the blood flow images, thereby obtaining the moving distance of the same red blood cells R flowing through the gate 25a. The speed of the red blood cell R is calculated by dividing by the shutter speed.
 なお、ステップS2及びS3での血流の撮影及び速度の算出は、上記の方法に限定されず、上述した特許文献1,2及び非特許文献1に記載の方法を用いてもよいし、ステップS2での血流の撮影を行わずに、ゲート25aへ所定量の血液を流したときの通過時間を計測し、流した血液量をゲート25aの断面積と通過時間とで除すことにより速度を求める方法を用いてもよい。 Note that imaging of blood flow and calculation of velocity in steps S2 and S3 are not limited to the above methods, and the methods described in Patent Documents 1 and 2 and Non-Patent Document 1 described above may be used. The speed is measured by measuring the passage time when a predetermined amount of blood is flowed to the gate 25a without taking the blood flow at S2, and dividing the flow amount of blood by the cross-sectional area and the passage time of the gate 25a. You may use the method of calculating | requiring.
 次に、ヘマトクリット測定器4に計測対象の血液をセットする(ステップS4)。このステップでは、シーケンス制御部17により第1バルブ10aが閉じられるとともに第2バルブ10bが開放され、更に加圧ポンプ15が駆動されて、ステップS1でフィルタ2へ流されたものと同じ血液がヘマトクリット測定器4へ送られてセットされる。 Next, blood to be measured is set in the hematocrit measuring instrument 4 (step S4). In this step, the first valve 10a is closed and the second valve 10b is opened by the sequence control unit 17, and the pressurizing pump 15 is further driven, so that the same blood flowed to the filter 2 in step S1 is hematocritized. It is sent to the measuring device 4 and set.
 次に、ヘマトクリット測定器4にセットされた血液のヘマトクリット値を測定する(ステップS5)。測定されたヘマトクリット値はパソコン7へ出力される。なお、ステップS4及びS5のヘマトクリット値の測定に係る工程は、ステップS2及びS3の速度の算出に係る工程よりも前に行ってもよいし、並行して行ってもよい。 Next, the hematocrit value of the blood set in the hematocrit measuring device 4 is measured (step S5). The measured hematocrit value is output to the personal computer 7. In addition, the process related to the measurement of the hematocrit value in steps S4 and S5 may be performed before the process related to the calculation of the speed in steps S2 and S3, or may be performed in parallel.
 次に、赤血球Rの変形能を算出する(ステップS6)。このステップでは、演算処理部70は、ステップS5で測定されたヘマトクリット値に基づいて、ステップS3で算出された赤血球Rの速度を補正することにより、赤血球Rの変形能を算出する。 Next, the deformability of the red blood cell R is calculated (step S6). In this step, the arithmetic processing unit 70 calculates the deformability of the red blood cell R by correcting the speed of the red blood cell R calculated in step S3 based on the hematocrit value measured in step S5.
 具体的には、演算処理部70は、以下の式(1)又は式(2)を満たす値として赤血球Rの変形能Dを算出する。 Specifically, the arithmetic processing unit 70 calculates the deformability D of the red blood cell R as a value satisfying the following formula (1) or formula (2).
  D=V/V               …(1)
  D=V-V               …(2)
 但し、Vは、ステップS3で算出された赤血球Rの速度であり、Vは、ステップS5で測定されたヘマトクリット値Hを有する基準血液をゲート25aへ流したときの当該基準血液中の赤血球Rの速度である。ここで、基準血液とは、健常者の血液をいい、この基準血液におけるヘマトクリット値Hと赤血球Rの速度Vとは、例えば、図5に示すような関係となる。したがって、この図5のヘマトクリット値Hと赤血球Rの速度Vとの関係に相当する変換式又は変換テーブルを予め演算処理部70に記憶させておくことで、ステップS5で測定されたヘマトクリット値Hから基準血液中の赤血球Rの速度Vを求めることができる。
D = V / V 0 (1)
D = V−V 0 (2)
However, V is the velocity of the red blood cell R calculated in step S3, and V 0 is the red blood cell R in the reference blood when the reference blood having the hematocrit value H measured in step S5 is flowed to the gate 25a. Speed. Here, the reference blood refers to the blood of a healthy person, and the hematocrit value H and the velocity V 0 of the red blood cell R in the reference blood have a relationship as shown in FIG. 5, for example. Therefore, by storing a conversion formula or conversion table corresponding to the relationship between the hematocrit value H of FIG. 5 and the velocity V 0 of the red blood cell R in the arithmetic processing unit 70 in advance, the hematocrit value H measured in step S5 is stored. From this, the velocity V 0 of the red blood cell R in the reference blood can be obtained.
 こうして算出された変形能Dによれば、式(1)を用いた場合には当該変形能Dが1に近いほど基準血液に近いものであり、式(2)を用いた場合には0に近いほど基準血液に近いものであるとして、計測対象の血液を判別することができる。 According to the deformability D calculated in this way, the closer the deformability D is to 1, the closer to the reference blood when the equation (1) is used, and 0 when the equation (2) is used. The blood to be measured can be identified as being closer to the reference blood as it is closer.
 なお、基準血液(健常者の血液)における赤血球Rの速度Vは、一般に、図5に示すように、同一のヘマトクリット値Hに対して一定の速度範囲ΔVを有している。この速度範囲ΔVを考慮する場合には、その平均値を速度Vとしてもよい。また、図6に示すように、速度範囲ΔVに相当する変形能範囲ΔDを用いて、この変形能範囲ΔD内であれば基準血液の範囲内であり良好であるとして計測対象の血液を判別するようにしてもよい。なお、図6の縦軸に示す変形能Dは、上記の式(1)を用いて算出された場合の単位及び目盛となっている。 Note that the velocity V 0 of the red blood cell R in the reference blood (blood of a healthy person) generally has a constant velocity range ΔV 0 with respect to the same hematocrit value H as shown in FIG. When this speed range ΔV 0 is considered, the average value may be the speed V 0 . Further, as shown in FIG. 6, using the deformability range ΔD corresponding to the speed range ΔV 0 , the blood to be measured is determined as being within the reference blood range and being good if within the deformability range ΔD. You may make it do. In addition, the deformability D shown on the vertical axis in FIG. 6 is a unit and a scale when calculated using the above formula (1).
 以上の第1の実施形態における変形能計測装置1によれば、赤血球Rの変形能Dを算出する際に、当該赤血球Rを含む血液のヘマトクリット値Hに基づいて当該赤血球Rの速度Vを補正するので、ヘマトクリット値Hの影響を考慮しつつ赤血球Rの変形能Dを算出することができる。したがって、ヘマトクリット値Hに依存しない信頼性の高い赤血球Rの変形能Dを計測することができる。 According to the deformability measuring apparatus 1 in the first embodiment described above, when calculating the deformability D of the red blood cell R, the velocity V of the red blood cell R is corrected based on the hematocrit value H of the blood containing the red blood cell R. Therefore, the deformability D of the red blood cell R can be calculated while considering the influence of the hematocrit value H. Therefore, it is possible to measure the deformability D of the red blood cell R with high reliability that does not depend on the hematocrit value H.
 [第2の実施形態]
 続いて、本発明の第2の実施形態に係る変形能計測装置1Aについて説明する。なお、上記第1の実施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 Embodiment]
Subsequently, a deformability measuring apparatus 1A according to a second embodiment of the present invention will be described. In addition, the same code | symbol is attached | subjected to the component similar to the said 1st Embodiment, and the description is abbreviate | omitted.
 図7は、変形能計測装置1Aの全体構成を示すブロック図である。 FIG. 7 is a block diagram showing the overall configuration of the deformability measuring apparatus 1A.
 この図に示すように、変形能計測装置1Aは、上記第1の実施形態における変形能計測装置1に対し、ヘマトクリット測定器4及び第2バルブ10bを備えていないことに加え、パソコン7に代えてパソコン7Aを備えている。 As shown in this figure, the deformability measuring apparatus 1A is different from the deformability measuring apparatus 1 in the first embodiment in that it does not include the hematocrit measuring instrument 4 and the second valve 10b, and instead of the personal computer 7. And a personal computer 7A.
 パソコン7Aは、上記第1の実施形態における演算処理部70に代えて演算処理部70Aを備えている。演算処理部70Aは、TVカメラ3から入力された血流画像を解析して赤血球Rの速度V及びこの血液のヘマトクリット値Hを算出するとともに、これら赤血球Rの速度V及びヘマトクリット値Hから赤血球Rの変形能Dを算出する。 The personal computer 7A includes an arithmetic processing unit 70A in place of the arithmetic processing unit 70 in the first embodiment. The arithmetic processing unit 70A analyzes the blood flow image input from the TV camera 3 to calculate the velocity V of the red blood cell R and the hematocrit value H of the red blood cell R, and also calculates the red blood cell R from the speed V and the hematocrit value H of the red blood cell R. The deformability D is calculated.
 続いて、変形能計測装置1Aを用いて赤血球Rの変形能Dを計測する変形能計測方法について、図8を参照して説明する。図8は、変形能計測装置1Aによる変形能計測方法のフローチャートである。 Subsequently, a deformability measuring method for measuring the deformability D of the red blood cell R using the deformability measuring apparatus 1A will be described with reference to FIG. FIG. 8 is a flowchart of the deformability measuring method by the deformability measuring apparatus 1A.
 この図に示すように、まず、フィルタ2へ計測対象の血液を流し(ステップT1)、流路部25を流れる血液を撮影した後(ステップT2)、ゲート25aを流れる血液中の赤血球Rの速度Vを算出する(ステップT3)。これらのステップT1~T3は、上記第1の実施形態におけるステップS1~S3と同様に行われる。なお、ステップT3では、演算処理部70Aが上記第1の実施形態における演算処理部70と同様の処理を行うことにより赤血球Rの速度Vが算出される。 As shown in this figure, first, blood to be measured is passed through the filter 2 (step T1), the blood flowing through the flow path section 25 is photographed (step T2), and then the speed of the red blood cells R in the blood flowing through the gate 25a is obtained. V is calculated (step T3). These steps T1 to T3 are performed in the same manner as steps S1 to S3 in the first embodiment. In step T3, the processing unit 70A performs the same processing as the processing unit 70 in the first embodiment, whereby the velocity V of the red blood cell R is calculated.
 次に、計測対象の血液のヘマトクリット値Hを算出する(ステップT4)。このステップでは、演算処理部70Aは、赤血球Rの速度Vの算出に用いた血流画像を用い、赤血球Rの部分とそうでない部分との濃度の違いに基づいて当該血流画像から赤血球Rを含む領域を抽出して血液中に占める血球の容積割合であるヘマトクリット値Hを求める。具体的には、演算処理部70Aは、画像色の濃度が所定の閾値以上の領域を赤血球Rが含まれる領域として、当該領域が血流画像全体に占める割合を算出する。このような領域としては、ゲート25aよりも上流の上流テラス25bの領域内であることが好ましい。 Next, the hematocrit value H of the blood to be measured is calculated (step T4). In this step, the arithmetic processing unit 70A uses the blood flow image used for calculating the velocity V of the red blood cell R, and calculates the red blood cell R from the blood flow image based on the difference in density between the red blood cell R portion and the non-red blood cell portion. The hematocrit value H, which is the volume ratio of blood cells in the blood, is obtained by extracting the included region. Specifically, the arithmetic processing unit 70A calculates a ratio of the region in the entire blood flow image by setting a region where the density of the image color is equal to or greater than a predetermined threshold as a region including the red blood cells R. Such a region is preferably in the region of the upstream terrace 25b upstream of the gate 25a.
 このように、ステップT3及びT4では、いずれもステップT2で撮影された血流画像を用いて赤血球Rの速度V及びヘマトクリット値Hを算出しており、つまり、ステップT2での血流の撮影という互いに共通する同一の計測作業を通じて、赤血球Rの速度V及びヘマトクリット値Hを算出している。 As described above, in steps T3 and T4, the velocity V and the hematocrit value H of the red blood cells R are calculated using the blood flow image captured in step T2, that is, the blood flow imaging in step T2. The velocity V and the hematocrit value H of the red blood cell R are calculated through the same measurement work common to each other.
 次に、赤血球Rの変形能Dを算出する(ステップT5)。このステップT5では、演算処理部70Aが、ステップT3及びT4で算出された赤血球Rの速度V及びヘマトクリット値Hを用いて、上記第1の実施形態におけるステップS6での演算処理部70と同様の処理を行うことにより赤血球Rの変形能Dが算出される。 Next, the deformability D of the red blood cell R is calculated (step T5). In step T5, the arithmetic processing unit 70A uses the velocity V and hematocrit value H of the red blood cells R calculated in steps T3 and T4, and is the same as the arithmetic processing unit 70 in step S6 in the first embodiment. By performing the processing, the deformability D of the red blood cell R is calculated.
 以上の第2の実施形態における変形能計測装置1Aによれば、上記第1の実施形態と同様の効果が得られるのはもちろんのこと、互いに共通する同一の計測作業を通じて、赤血球Rの速度V及びヘマトクリット値Hが算出されるので、速度Vを算出する計測作業用に抽出した血液と、ヘマトクリット値Hを求める計測作業用に抽出した血液とで、ヘマトクリット値Hが互いに異なることを防止できる。赤血球Rは血液中に一様に含有されていないため、同一の血液であってもそこから別々に抽出されたもの同士では、ヘマトクリット値Hが互いに異なる場合がある。変形能計測装置1Aによれば、このような場合が生じるのを防止し、確実に対応するヘマトクリット値Hに基づいて赤血球Rの速度Vを補正できるので、より信頼性の高い赤血球Rの変形能Dを計測することができる。 According to the deformability measuring apparatus 1A in the second embodiment described above, the velocity V of the red blood cell R can be obtained through the same measurement work common to each other as well as the same effect as that of the first embodiment. Since the hematocrit value H is calculated, it is possible to prevent the hematocrit value H from being different between the blood extracted for the measurement operation for calculating the velocity V and the blood extracted for the measurement operation for obtaining the hematocrit value H. Since the red blood cells R are not uniformly contained in the blood, the hematocrit values H may be different from each other even if the same blood is extracted separately. According to the deformability measuring apparatus 1A, such a case can be prevented and the velocity V of the red blood cell R can be reliably corrected based on the corresponding hematocrit value H. Therefore, the deformability of the red blood cell R is more reliable. D can be measured.
 なお、本発明は上記第1及び第2の実施形態に限定して解釈されるべきではなく、適宜変更・改良が可能であることはもちろんである。 It should be noted that the present invention should not be construed as being limited to the first and second embodiments described above, and of course can be modified or improved as appropriate.
 例えば、上記第1及び第2の実施形態では、ヘマトクリット値Hに基づいて赤血球Rの速度Vを補正しているが、被験者の年齢やヘモグロビン量などで補正してもよいし、これらを組み合わせて補正してもよい。この場合には、健常者における年齢又はヘモグロビン量を赤血球Rの速度に変換する変換式又は変換テーブルを演算処理部70,70Aに記憶させておくことで、ヘマトクリット値Hの場合と同様に赤血球Rの速度Vを補正することができる。 For example, in the first and second embodiments, the velocity V of the red blood cell R is corrected based on the hematocrit value H. However, the velocity V of the red blood cell R or the amount of hemoglobin may be corrected, or a combination thereof may be used. It may be corrected. In this case, the conversion equation or conversion table for converting the age or hemoglobin amount in the healthy person into the velocity of the red blood cell R is stored in the arithmetic processing units 70 and 70A, so that the red blood cell R as in the case of the hematocrit value H is stored. Can be corrected.
 1,1A 変形能計測装置
 3 TVカメラ(撮影手段)
 4 ヘマトクリット測定器(ヘマトクリット計測手段)
 25a ゲート(流路)
 70 演算処理部(速度算出手段、変形能算出手段)
 70A 演算処理部(速度算出手段、ヘマトクリット計測手段、変形能算出手段)
 D 赤血球の変形能
 H ヘマトクリット値
 R 赤血球
 V 赤血球の速度
 V 基準血液中の赤血球の速度
1,1A Deformability measuring device 3 TV camera (photographing means)
4 Hematocrit measuring instrument (hematocrit measuring means)
25a Gate (flow path)
70 arithmetic processing unit (speed calculation means, deformability calculation means)
70A arithmetic processing unit (speed calculation means, hematocrit measurement means, deformability calculation means)
D Deformability of red blood cells H Hematocrit value R Red blood cells V Red blood cell velocity V 0 Red blood cell velocity in reference blood

Claims (8)

  1.  赤血球の血球径よりも狭い幅の流路を流れる血液中の赤血球の速度を算出する速度算出手段と、
     前記血液のヘマトクリット値として、当該血液中に占める赤血球の容積割合を求めるヘマトクリット計測手段と、
     前記ヘマトクリット計測手段で求められた前記ヘマトクリット値に基づいて、前記速度算出手段で算出された前記赤血球の速度を補正することにより、前記赤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変形能計測装置。
    Speed calculating means for calculating the speed of red blood cells in the blood flowing through a flow path having a narrower width than the blood cell diameter of red blood cells;
    As the hematocrit value of the blood, hematocrit measuring means for obtaining a volume ratio of red blood cells occupying the blood,
    Deformability calculating means for calculating the deformability of the red blood cells by correcting the speed of the red blood cells calculated by the speed calculating means based on the hematocrit value obtained by the hematocrit measuring means;
    A deformability measuring apparatus comprising:
  2.  前記変形能算出手段は、以下の式(1)又は式(2)を満たす前記赤血球の変形能Dを算出することを特徴とする請求項1に記載の変形能計測装置。
      D=V/V               …(1)
      D=V-V               …(2)
    (但し、V:前記速度算出手段で算出された前記赤血球の速度
        V:前記ヘマトクリット計測手段で求められた前記ヘマトクリット値を有する基準血液を前記流路へ流したときの当該基準血液中の赤血球の速度)
    The deformability measuring apparatus according to claim 1, wherein the deformability calculating means calculates the deformability D of the red blood cells satisfying the following formula (1) or formula (2).
    D = V / V 0 (1)
    D = V−V 0 (2)
    (However, V: velocity of the red blood cells calculated by the velocity calculation means V 0 : red blood cells in the reference blood when the reference blood having the hematocrit value obtained by the hematocrit measurement means is flowed into the flow path. Speed)
  3.  前記速度算出手段及び前記ヘマトクリット計測手段は、互いに共通する同一の計測作業を通じて、前記赤血球の速度及び前記ヘマトクリット値を算出する又は求めることを特徴とする請求項1又は2に記載の変形能計測装置。 3. The deformability measuring apparatus according to claim 1, wherein the velocity calculation unit and the hematocrit measurement unit calculate or obtain the velocity of the red blood cell and the hematocrit value through the same measurement operation common to each other. .
  4.  前記流路を流れる血液を撮影する撮影手段を備え、
     前記速度算出手段は、前記撮影手段で撮影された血流画像を用い、当該血流画像中の赤血球を追跡して当該赤血球の速度を算出し、
     前記ヘマトクリット計測手段は、前記赤血球の速度の算出に用いた血流画像を用い、濃度の違いに基づいて当該血流画像から赤血球を含む領域を抽出して前記ヘマトクリット値を求めることを特徴とする請求項3に記載の変形能計測装置。
    An imaging means for imaging blood flowing through the flow path,
    The speed calculation means uses the blood flow image photographed by the photographing means, tracks the red blood cells in the blood flow image, calculates the speed of the red blood cells,
    The hematocrit measurement means uses the blood flow image used to calculate the velocity of the red blood cells, extracts a region containing red blood cells from the blood flow image based on a difference in concentration, and obtains the hematocrit value. The deformability measuring apparatus according to claim 3.
  5.  赤血球の血球径よりも狭い幅の流路を流れる血液中の赤血球の速度を算出する速度算出工程と、
     前記血液のヘマトクリット値として、当該血液中に占める赤血球の容積割合を求めるヘマトクリット計測工程と、
     前記ヘマトクリット計測工程で求められた前記ヘマトクリット値に基づいて、前記速度算出工程で算出された前記赤血球の速度を補正することにより、前記赤血球の変形能を算出する変形能算出工程と、
     を備えることを特徴とする変形能計測方法。
    A speed calculating step for calculating the speed of red blood cells in the blood flowing through a flow path having a width smaller than the blood cell diameter of red blood cells;
    As the hematocrit value of the blood, a hematocrit measurement step for determining the volume ratio of red blood cells in the blood,
    Based on the hematocrit value obtained in the hematocrit measurement step, a deformability calculation step for calculating the deformability of the red blood cells by correcting the speed of the red blood cells calculated in the speed calculation step;
    A deformability measuring method comprising:
  6.  前記変形能算出工程では、以下の式(1)又は式(2)を満たす前記赤血球の変形能Dを算出することを特徴とする請求項5に記載の変形能計測方法。
      D=V/V               …(1)
      D=V-V               …(2)
    (但し、V:前記速度算出工程で算出された前記赤血球の速度
        V:前記ヘマトクリット計測工程で求められた前記ヘマトクリット値を有する基準血液を前記流路へ流したときの当該基準血液中の赤血球の速度)
    6. The deformability measuring method according to claim 5, wherein in the deformability calculation step, the deformability D of the red blood cells satisfying the following formula (1) or formula (2) is calculated.
    D = V / V 0 (1)
    D = V−V 0 (2)
    (However, V: velocity of the red blood cells calculated in the velocity calculation step V 0 : red blood cells in the reference blood when the reference blood having the hematocrit value determined in the hematocrit measurement step is flowed to the flow path) Speed)
  7.  前記速度算出工程及び前記ヘマトクリット計測工程では、互いに共通する同一の計測作業を通じて、前記赤血球の速度及び前記ヘマトクリット値を算出する又は求めることを特徴とする請求項5又は6に記載の変形能計測方法。 The deformability measuring method according to claim 5 or 6, wherein, in the velocity calculating step and the hematocrit measuring step, the velocity of the red blood cells and the hematocrit value are calculated or obtained through the same measurement work common to each other. .
  8.  前記流路を流れる血液を撮影する撮影工程を備え、
     前記速度算出工程では、前記撮影工程で撮影された血流画像を用い、当該血流画像中の赤血球を追跡して当該赤血球の速度を算出し、
     前記ヘマトクリット計測工程では、前記赤血球の速度の算出に用いた血流画像を用い、濃度の違いに基づいて当該血流画像から赤血球を含む領域を抽出して前記ヘマトクリット値を求めることを特徴とする請求項7に記載の変形能計測方法。
    Comprising a photographing step of photographing blood flowing through the flow path;
    In the velocity calculating step, using the blood flow image taken in the imaging step, tracking the red blood cells in the blood flow image to calculate the velocity of the red blood cells,
    In the hematocrit measurement step, the blood flow image used for calculating the velocity of the red blood cells is used, and a region containing red blood cells is extracted from the blood flow image based on a difference in concentration to obtain the hematocrit value. The deformability measuring method according to claim 7.
PCT/JP2010/058180 2009-05-29 2010-05-14 Device for measuring deformability and method for measuring deformability WO2010137470A1 (en)

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