WO2010024197A1 - Microchip and blood analysis system - Google Patents

Microchip and blood analysis system Download PDF

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Publication number
WO2010024197A1
WO2010024197A1 PCT/JP2009/064633 JP2009064633W WO2010024197A1 WO 2010024197 A1 WO2010024197 A1 WO 2010024197A1 JP 2009064633 W JP2009064633 W JP 2009064633W WO 2010024197 A1 WO2010024197 A1 WO 2010024197A1
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WIPO (PCT)
Prior art keywords
blood
microchip
flow path
cross
analysis system
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PCT/JP2009/064633
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French (fr)
Japanese (ja)
Inventor
郁 福室
貴紀 村山
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コニカミノルタオプト株式会社
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Publication of WO2010024197A1 publication Critical patent/WO2010024197A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/491—Blood by separating the blood components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers

Definitions

  • the present invention relates to a microchip and a blood characteristic analysis system.
  • the blood vessels in the living body are constantly deformed, and the cross-sectional area is also changing with this deformation.
  • the present invention has been made in view of the above circumstances, and an object of the present invention is to provide a microchip and a blood characteristic analysis system capable of easily measuring blood characteristics in a state close to a living body as compared with the conventional art.
  • a microchip for blood characteristic analysis provided in a blood characteristic analysis system for measuring blood characteristics, Having at least one flow path through which blood passes;
  • the flow path can change a cross-sectional area or a cross-sectional shape in at least a part thereof.
  • the invention according to claim 2 is the microchip according to claim 1,
  • the flow path is characterized in that the cross-sectional area or the cross-sectional shape of at least a part of the flow path can be changed in a state in which blood is passed.
  • invention of Claim 3 is the microchip of Claim 1 or 2, Comprising:
  • the flow path is characterized in that the cross-sectional area in at least a part can be arbitrarily changed, or the cross-sectional shape can be changed to a predetermined shape.
  • the invention described in claim 4 is the microchip according to any one of claims 1 to 3, It has a drive means which drives a channel wall in at least a part of the channel.
  • the invention according to claim 5 is the microchip according to claim 4,
  • the drive means is a piezoelectric actuator or a piezoelectric ultrasonic linear actuator.
  • the invention according to claim 6 is a blood characteristic analysis system, A microchip according to any one of claims 1 to 5; Imaging means for imaging the blood flow in at least one of the internal region, the inlet region, and the outlet region of the flow path; Analysis means capable of calculating blood characteristics by analyzing a blood flow image by the imaging means; It is characterized by providing.
  • the invention according to claim 7 is the blood characteristic analysis system according to claim 6,
  • the microchip has a driving means for driving a channel wall in at least a part of the channel,
  • the blood characteristic analysis system includes control means for controlling the drive means so that at least one of pressure, velocity, pulse pressure, and pulse rate of blood flowing through the flow path is set to a predetermined value. .
  • the invention according to claim 8 is the blood characteristic analysis system according to claim 7,
  • the control means is a personal computer.
  • the deformation of blood vessels in the living body can be changed to the same micro Blood characteristics can be measured by simulating the flow path in the chip. Therefore, it is possible to easily measure blood characteristics in a state close to the living body, compared to the conventional case that requires complicated operations such as manufacturing a plurality of microchips having different cross-sectional areas of the flow paths and measuring them individually. it can.
  • the flow channel can change the cross-sectional area or the cross-sectional shape in at least a portion in a state where blood is passed
  • the cross-sectional area or cross-section of the flow channel can be changed during the same measurement.
  • the condition such as the shape can be changed, and the blood characteristic at that time can be measured just as the cross-sectional area or cross-sectional shape of the flow path is changing. Therefore, measurement of blood characteristics in a state closer to the living body can be performed easily and in a short time.
  • the flow path can be arbitrarily changed in cross-sectional area at least in part, or the cross-sectional shape can be changed to a predetermined shape.
  • the blood characteristics can be measured by more accurately simulating the above in the flow path in the same microchip. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
  • the flow path wall in at least a part of the flow path is set so that at least one of the pressure, velocity, pulse pressure, and pulse rate of the blood flowing through the flow path has a predetermined value. Since the control means for controlling the drive means for driving is provided, blood characteristics can be measured by simulating at least one of blood pressure, velocity, pulse pressure, and pulse rate in the living body. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
  • FIG. 1 It is a block diagram which shows the whole structure of the blood characteristic analysis system which concerns on this invention. It is a figure which shows a microchip, (a) is a top view, (b) is an exploded side view, (c) is the elements on larger scale of (a). It is a figure for demonstrating the flow path of a microchip, the upper figure is a top view, and the lower figure is a side view. It is a figure for demonstrating the movable part of the flow path of a microchip.
  • FIG. 1 is a block diagram showing the overall configuration of the blood characteristic analysis system 1 in the present embodiment.
  • the blood characteristic analysis system 1 guides blood from a supply tank 10 to a discharge tank 11 through a microchip (filter) 2 and measures a plurality of types of blood characteristics from information acquired in the process. To do.
  • the blood characteristic analysis system 1 is mainly based on the microchip 2, the TV camera 3 that captures the blood flow in the microchip 2, and the blood flow image captured by the TV camera 3.
  • a personal computer 7 that measures characteristics
  • a display 8 that displays a blood flow image
  • a blood flow control unit 9 that controls blood flow in the microchip 2 are provided.
  • a plurality of liquids such as physiological saline and physiologically active substances are connected to the flow path via the mixer 12 so as to be mixed with blood and guided to the microchip 2.
  • a solution bottle 13 or the like is further provided.
  • the blood mixed with a liquid such as physiological saline or a physiologically active substance is micro-controlled by the differential pressure control unit 91 in the blood flow control unit 9 by controlling the pressurization pump 15 and the decompression pump 16. By adjusting the differential pressure across the chip 2, a desired amount flows through the microchip 2.
  • the valve 10 a of the supply tank 10 and the like are integrated and controlled by the sequence control unit 17.
  • FIG. 2A is a view (plan view) of the microchip as viewed from above
  • FIG. 2B is a side view
  • FIG. 2C is a partially enlarged view of a part of the microchip.
  • the microchip 2 is formed by overlapping a rectangular glass flat plate 20 and a base plate 21 as shown in FIG.
  • the glass flat plate 20 is formed in a flat plate shape and covers the inner side surface of the base plate 21 (the upper surface in FIG. 2B).
  • the base plate 21 has depressions 210 and 211 at both ends, and a plurality of grooves 212 and so on between the depressions 210 and 211.
  • the hollow part 210 has a through-hole 210 a communicating with the supply tank 10 on the bottom surface, and an upstream storage part 22 for storing blood is formed between the glass flat plate 20.
  • the recess 211 has a through hole 211 a communicating with the discharge tank 11 on the bottom surface, and forms a downstream storage 23 for storing blood between the flat glass plate 20.
  • the plurality of grooves 212 are arranged so as to extend in parallel to the direction (X direction in the drawing) connecting the recess 210 and the recess 211, and extend in the X direction described above. It is in a state of being partitioned by the portion 213.
  • the plurality of grooves 212,... Alternately communicate with the depression 210 or the depression 211, whereby the upstream blood circuit 24 that allows blood to flow from the upstream reservoir 22 and the downstream reservoir 23.
  • a downstream blood circuit 25 that allows blood to flow into the glass plate 20 is formed.
  • FIGS. 3A and 3B are diagrams for explaining the flow path of the microchip 2.
  • the upper diagram is a plan view of the terrace portion 213 as viewed from above.
  • the lower diagram is a cross-sectional view of FIGS. 3A and 3B as viewed from the side.
  • a plurality of hexagonal bank portions 214 are arranged in the X direction on the upper end portion of the terrace portion 213, and the glass flat plate 20 is formed on the top surface. Abut.
  • the flow path 26, the upstream blood circuit 24, and the downstream blood circuit 25 (corresponding virtual lines are omitted at the positions indicated by virtual lines AA and BB in FIG. 2 (c).
  • the cross-sectional area (also referred to as a flow-path cross-sectional area) of the flow path 26 is narrower than that of the upstream blood circuit 24 and the downstream blood circuit 25. More specifically, the cross-sectional shape of the flow path 26 is a flat rectangle in accordance with the shape of red blood cells (the shape of a disk with a hollow center and an elliptical shape with a flat cross section). The size is smaller than the size of red blood cells. Thereby, it is possible to observe a state in which red blood cells pass through thin blood vessels such as capillaries while deforming their own shapes, and it is possible to simulate the smoothness of blood in the blood vessels.
  • FIG. 4 is a diagram for explaining the movable part of the microchip 2.
  • the bank portion 214 includes a movable portion 214 a that can move in the X direction and a stationary portion 214 b that is formed integrally with the base plate 21.
  • the movable portion 214a is formed in a square shape including a channel wall portion 26a at the center in the Y direction among the channel walls parallel to the Y direction (flow direction) forming the channel 26, and is moved in the X direction ( It is movable by a predetermined range in the direction orthogonal to the flow direction.
  • the cross-sectional area of a part of the flow path 26 can be arbitrarily changed.
  • the movable portion 214a is not limited to the above configuration, and may be configured to be movable in the X direction including the flow channel wall in at least a part of the flow channel 26. Furthermore, the cross-sectional shape of the flow channel 26 may be changed. The configuration may be changed. As a configuration for changing the cross-sectional shape, for example, a configuration in which the upper end of the flow path wall portion 26a is inclined in the X direction or a shape in which the flow path wall portion 26a is curved by using a shape memory material or the like can be used. Further, the movable portion 214a, the stationary portion 214b, and the actuator 27 are not shown in FIGS. 2 and 3 for simplification of illustration.
  • Actuators 27 for driving the movable portion 214a are respectively embedded in the base plate 21 corresponding to the movable portion 214a, and are connected to a drive control portion 92, which will be described later, so as to be driven and controlled (FIG. 1). reference).
  • the actuator 27 is not particularly limited, but is a piezoelectric actuator or a piezoelectric ultrasonic linear actuator. As such an actuator 27, for example, those disclosed in JP-A-7-298656, JP-A-2006-66976, or JP-A-2007-57581 can be used.
  • the blood introduced from the supply tank 10 is stored in the upstream storage section 22, passes through the flow path 26 and the downstream blood circuit 25 from the upstream blood circuit 24, is stored in the downstream storage section 23, and is discharged into the discharge tank 11. It will be discharged from.
  • blood cells in blood flowing through the flow path 26, for example, red blood cells first pass through the inlet region A upstream of the gate 215, and then deform the inner region B of the gate 215. And finally pass through the exit region C downstream of the gate 215.
  • pressure sensors E1 and E2 are provided before and after the microchip 2, and the pressure sensors E1 and E2 output the measured chip upstream pressure P1 and chip downstream pressure P2 to the blood flow control unit 9. (See FIG. 1).
  • these pressure sensors E1 and E2 only need to be able to measure the blood pressure in the vicinity of the inlet and outlet of the microchip 2.
  • pressure adjusting containers are provided before and after the microchip 2, and the pressure in each container is measured. You may make it measure.
  • 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. As shown in FIG. 1, the TV camera 3 is installed to face the glass flat plate 20 in the microchip 2, and photographs the blood flow passing through the flow path 26 through the glass flat plate 20.
  • the imaging range is a range including the entrance area A to the exit area C in the plurality of gates 215 shown in FIGS. However, this imaging range may be a range including at least one of the entrance area A, the internal area B, and the exit area C in each gate 215.
  • 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 blood properties and the like, and include those related to fluidity such as blood coagulation ability in addition to blood pressure and velocity.
  • Aggregation capacity is a quantitative value indicating the ease of occurrence of the aggregation phenomenon in which blood cells stay and bind together, and the area, number, and area ratio of each blood cell type contained in the blood cell retention part consisting of the retained blood cells. Or the number ratio.
  • 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 photographed image output from the TV camera 3 and blood characteristics calculated by the personal computer 7.
  • the blood flow control unit 9 includes a differential pressure control unit 91 that controls the differential pressure across the microchip 2 and a drive control unit 92 that controls the drive of the actuator 27, and according to a control command from the sequence control unit 17.
  • the differential pressure control unit 91 and the drive control unit 92 perform predetermined control.
  • the blood flow control unit 9 and the sequence control unit 17 may be configured integrally with the personal computer 7, and the personal computer 7 may perform the predetermined control.
  • the differential pressure control unit 91 controls the pressurization pump 15 upstream of the microchip 2 and the decompression pump 16 downstream of the microchip 2 so that the chip upstream pressure P1 and the chip downstream pressure P2 become predetermined pressures.
  • the drive control unit 92 controls the drive of the actuator 27 so that the distance w (see FIG. 4) between the opposed flow path wall portions 26a in the flow path 26 of the microchip 2 becomes a predetermined value.
  • the operation of the blood characteristic analysis system 1 when measuring blood characteristics will be described below.
  • the blood flow in the flow path 26 is photographed by the TV camera 3 while flowing the blood to the microchip 2. More specifically, the sequence controller 17 adds physiological saline or the like to the solution bottle 13 as necessary while injecting blood to be measured into the supply tank 10.
  • the sequence control unit 17 controls the pressurization pump 15 and the decompression pump 16 via the differential pressure control unit 91 to apply a predetermined differential pressure to the microchip 2 to flow blood through the microchip 2,
  • the TV camera 3 images the blood flow in the flow path 26. At this time, the distance w between the flow path wall portions 26 a in the microchip 2 is set to a desired value by the drive control unit 92.
  • the personal computer 7 calculates blood characteristics by performing image processing on the captured image
  • the calculation result and the captured image itself are displayed on the display 8.
  • the distance w between the channel wall portions 26a in the microchip 2 can be changed according to the calculated blood characteristics. Specifically, for example, the distance w between the flow path wall portions 26a is changed by controlling the actuator 27 so that the blood pressure and / or velocity is set to a predetermined value. In this way, it is possible to measure other blood characteristics by simulating blood pressure and velocity in the living body.
  • Such a change of the distance w may be performed at the time of re-measurement, or may be performed during blood flow imaging, that is, in a state where blood is passed through the flow path 26.
  • Changing the distance between the flow path walls before imaging the blood flow can be assumed to measure the blood flow according to the thickness of the blood vessel in the human body.
  • Changing the distance between the flow paths during imaging of blood flow can be assumed to measure blood flow in a state where the thickness of the blood vessel is changing in the human body.
  • the distance w between the flow path wall portions 26a may be repeatedly changed by controlling the actuator 27 in a state where blood is passed through the flow path 26. Specifically, the actuator 27 is controlled to repeatedly vary the distance w between the flow path wall portions 26a so that the pulse pressure and / or the pulse rate of the blood flowing through the flow path 26 have predetermined values. In this way, blood characteristics can be measured by simulating blood flow pulsations in the living body.
  • the pulse pressure may be measured by repeatedly varying the plurality of actuators 27 in synchronization, and the pressure change at that time may be measured as the pulse pressure by the pressure difference between the pressure sensors E1 and E2, or a piezoelectric element may be used.
  • the pulse pressure may be measured by the piezoelectric element provided inside each flow channel 26.
  • the blood characteristic is measured using the microchip 2 having the flow path 26 whose cross-sectional area or cross-sectional shape can be changed at least partially.
  • Blood characteristics can be measured by simulating the deformation of a blood vessel in a living body through the flow path 26 in the same microchip 2. Therefore, it is possible to easily measure blood characteristics in a state close to the living body, compared to the conventional case that requires complicated operations such as manufacturing a plurality of microchips having different cross-sectional areas of the flow paths and measuring them individually. it can.
  • the flow path 26 can change the cross-sectional area or cross-sectional shape in at least one part in the state which let the blood pass, conditions, such as the cross-sectional area or cross-sectional shape of the flow path 26, can be changed during the same measurement.
  • the blood characteristics at the time when the cross-sectional area or cross-sectional shape of the flow path 26 is changing can be measured. Therefore, measurement of blood characteristics in a state closer to the living body can be performed easily and in a short time.
  • the cross-sectional area of at least a part of the flow path 26 can be arbitrarily changed, or the cross-sectional shape can be changed to a predetermined shape, the deformation of blood vessels in the living body can be changed in the same microchip 2.
  • the blood characteristics can be measured by simulating with the path 26 more precisely. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
  • drive control for controlling the actuator 27 that drives the flow path wall portion 26a of the flow path 26 so that at least one of the pressure, velocity, pulse pressure, and pulse rate of the blood flowing through the flow path 26 has a predetermined value. Since the unit 92 is provided, blood characteristics can be measured by simulating at least one of blood pressure, velocity, pulse pressure, and pulse rate in the living body. Therefore, it is possible to measure blood characteristics in a state closer to the living body.

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Abstract

A microchip for conveniently measuring blood characteristics in a state as close as possible to the in vivo situation.  A microchip (2) for blood analysis to be employed in a blood analysis system (1) for measuring blood characteristics which comprises at least one microchannel (26) for blood passage, wherein the cross section area or cross section shape of the microchannel (26) can be altered at least in a part thereof.

Description

マイクロチップ及び血液特性解析システムMicrochip and blood characteristic analysis system
　本発明は、マイクロチップ及び血液特性解析システムに関する。 The present invention relates to a microchip and a blood characteristic analysis system.
　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。この血液の流動性はサラサラ度などとも称され、流動性が高くサラサラであるほど健康であることを意味している。 In recent years, with increasing interest in health, blood fluidity has attracted attention as a health barometer. This fluidity of blood is also called smoothness and the like, and the higher the fluidity, the better the health.
　この血液の流動性を調べる方法としては、微細な溝を有するマイクロチップに血液を通過させて、通過に要する時間を計測する技術が知られている（例えば、特許文献１参照）。この技術では、マイクロチップ上板の透明ガラスを介してカメラでマイクロチップ通過時の血球を観察することにより、血液の流動性を視覚的に捉えることが可能となっている。また、この特許文献１に記載の技術以外にも、同様の装置で撮影した血流画像を解析することにより、流動性を含む様々な血液特性を計測する技術が提案されている（例えば、特許文献２～４参照）。 As a method for examining the blood fluidity, a technique is known in which blood is passed through a microchip having a fine groove and the time required for passage is measured (for example, see Patent Document 1). In this technique, blood fluidity can be visually grasped by observing blood cells passing through the microchip with a camera through the transparent glass on the upper plate of the microchip. In addition to the technique described in Patent Document 1, a technique for measuring various blood characteristics including fluidity by analyzing a blood flow image photographed by a similar device has been proposed (for example, patents). Reference 2-4).
　ところで、本来、生体内の血管は常に変形しており、この変形に伴って断面積も変化している。 By the way, the blood vessels in the living body are constantly deformed, and the cross-sectional area is also changing with this deformation.
特許第２６８５５４４号公報Japanese Patent No. 2685544 特許第２５３２７０７号公報Japanese Patent No. 2532707 特開２００５－２６５６３４号公報JP 2005-265634 A 特開２００６－１４５３４５号公報JP 2006-145345 A
　しかしながら、上記特許文献１～４に記載の技術では、血液を通過させる流路の断面積や断面形状が一定であったために、生体内の血流を十分に模擬できていなかった。なお、上記従来の技術によってこの血管の変形を模擬しようとすると、流路の断面積が異なる複数のマイクロチップを製作してそれぞれで計測する等の煩雑な作業を要してしまう。 However, in the techniques described in Patent Documents 1 to 4, the cross-sectional area and cross-sectional shape of the flow path through which blood passes are constant, so that the blood flow in the living body cannot be sufficiently simulated. Note that, when trying to simulate the deformation of the blood vessel by the above-described conventional technique, a complicated operation such as manufacturing a plurality of microchips having different cross-sectional areas of the flow paths and measuring each of them is required.
　本発明は、上記事情を鑑みてなされたもので、従来に比べ、生体内に近い状態での血液特性の計測を簡便に行うことができるマイクロチップ及び血液特性解析システム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 microchip and a blood characteristic analysis system capable of easily measuring blood characteristics in a state close to a living body as compared with the conventional art.
　前記の課題を解決するために、請求項１に記載の発明は、
　血液特性を計測する血液特性解析システムに備えられる血液特性解析用のマイクロチップであって、
　血液が通過する少なくとも１つの流路を有し、
　前記流路は、少なくとも一部分における断面積又は断面形状が変更可能であることを特徴とする。 In order to solve the above-mentioned problem, the invention according to claim 1
A microchip for blood characteristic analysis provided in a blood characteristic analysis system for measuring blood characteristics,
Having at least one flow path through which blood passes;
The flow path can change a cross-sectional area or a cross-sectional shape in at least a part thereof.
　請求項２に記載の発明は、請求項１に記載のマイクロチップであって、
　前記流路は、血液を通過させた状態で、少なくとも一部分における断面積又は断面形状が変更可能であることを特徴とする。 The invention according to claim 2 is the microchip according to claim 1,
The flow path is characterized in that the cross-sectional area or the cross-sectional shape of at least a part of the flow path can be changed in a state in which blood is passed.
　請求項３に記載の発明は、請求項１又は２に記載のマイクロチップであって、
　前記流路は、少なくとも一部分における断面積が任意に変更可能であるか、或いは断面形状が所定の形状に変更可能であることを特徴とする。 Invention of Claim 3 is the microchip of Claim 1 or 2, Comprising:
The flow path is characterized in that the cross-sectional area in at least a part can be arbitrarily changed, or the cross-sectional shape can be changed to a predetermined shape.
　請求項４に記載の発明は、請求項１～３のいずれか一項に記載のマイクロチップであって、
　前記流路の少なくとも一部分における流路壁を駆動する駆動手段を有することを特徴とする。 The invention described in claim 4 is the microchip according to any one of claims 1 to 3,
It has a drive means which drives a channel wall in at least a part of the channel.
　請求項５に記載の発明は、請求項４に記載のマイクロチップであって、
　前記駆動手段は、圧電アクチュエータ又は圧電超音波リニアアクチュエータであることを特徴とする。 The invention according to claim 5 is the microchip according to claim 4,
The drive means is a piezoelectric actuator or a piezoelectric ultrasonic linear actuator.
　請求項６に記載の発明は、血液特性解析システムであって、
　請求項１～５のいずれか一項に記載のマイクロチップと、
　前記流路の内部領域、入口領域、及び出口領域の少なくとも１つの領域における血液の流れを撮影する撮影手段と、
　前記撮影手段による血流画像を解析して血液特性を算出可能な解析手段と、
を備えることを特徴とする。 The invention according to claim 6 is a blood characteristic analysis system,
A microchip according to any one of claims 1 to 5;
Imaging means for imaging the blood flow in at least one of the internal region, the inlet region, and the outlet region of the flow path;
Analysis means capable of calculating blood characteristics by analyzing a blood flow image by the imaging means;
It is characterized by providing.
　請求項７に記載の発明は、請求項６に記載の血液特性解析システムであって、
　前記マイクロチップは、前記流路の少なくとも一部分における流路壁を駆動する駆動手段を有し、
　当該血液特性解析システムは、前記流路を流れる血液の圧力、速度、脈圧、及び脈拍数の少なくとも１つを所定の値とするよう前記駆動手段を制御する制御手段を備えることを特徴とする。 The invention according to claim 7 is the blood characteristic analysis system according to claim 6,
The microchip has a driving means for driving a channel wall in at least a part of the channel,
The blood characteristic analysis system includes control means for controlling the drive means so that at least one of pressure, velocity, pulse pressure, and pulse rate of blood flowing through the flow path is set to a predetermined value. .
　請求項８に記載の発明は、請求項７に記載の血液特性解析システムであって、
　前記制御手段は、パソコンであることを特徴とする。 The invention according to claim 8 is the blood characteristic analysis system according to claim 7,
The control means is a personal computer.
　請求項１に記載の発明によれば、少なくとも一部分における断面積又は断面形状が変更可能な流路を有するマイクロチップを用いて血液特性が計測されるので、生体内の血管の変形を同一のマイクロチップ内の流路で模擬して血液特性の計測を行うことができる。したがって、流路の断面積が異なる複数のマイクロチップを製作してそれぞれで計測する等の煩雑な作業を要した従来に比べ、生体内に近い状態での血液特性の計測を簡便に行うことができる。 According to the first aspect of the present invention, since blood characteristics are measured using a microchip having a flow path whose cross-sectional area or cross-sectional shape can be changed at least in part, the deformation of blood vessels in the living body can be changed to the same micro Blood characteristics can be measured by simulating the flow path in the chip. Therefore, it is possible to easily measure blood characteristics in a state close to the living body, compared to the conventional case that requires complicated operations such as manufacturing a plurality of microchips having different cross-sectional areas of the flow paths and measuring them individually. it can.
　請求項２に記載の発明によれば、前記流路は、血液を通過させた状態で、少なくとも一部分における断面積又は断面形状が変更可能であるので、同一計測中に流路の断面積又は断面形状といった条件を変えることができるとともに、流路の断面積又は断面形状が変化している正にそのときの血液特性を計測することができる。したがって、より生体内に近い状態での血液特性の計測を簡便・短時間に行うことができる。 According to the second aspect of the present invention, since the flow channel can change the cross-sectional area or the cross-sectional shape in at least a portion in a state where blood is passed, the cross-sectional area or cross-section of the flow channel can be changed during the same measurement. The condition such as the shape can be changed, and the blood characteristic at that time can be measured just as the cross-sectional area or cross-sectional shape of the flow path is changing. Therefore, measurement of blood characteristics in a state closer to the living body can be performed easily and in a short time.
　請求項３に記載の発明によれば、前記流路は、少なくとも一部分における断面積が任意に変更可能であるか、或いは断面形状が所定の形状に変更可能であるので、生体内の血管の変形を同一のマイクロチップ内の流路でより精密に模擬して血液特性の計測を行うことができる。したがって、より生体内に近い状態での血液特性の計測を行うことができる。 According to the third aspect of the present invention, the flow path can be arbitrarily changed in cross-sectional area at least in part, or the cross-sectional shape can be changed to a predetermined shape. The blood characteristics can be measured by more accurately simulating the above in the flow path in the same microchip. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
　請求項７に記載の発明によれば、前記流路を流れる血液の圧力、速度、脈圧、及び脈拍数の少なくとも１つを所定の値とするよう、流路の少なくとも一部分における流路壁を駆動する駆動手段を制御する制御手段を備えるので、生体における血液の圧力、速度、脈圧、及び脈拍数の少なくとも１つを模擬して血液特性の計測を行うことができる。したがって、より生体内に近い状態での血液特性の計測を行うことができる。 According to the seventh aspect of the present invention, the flow path wall in at least a part of the flow path is set so that at least one of the pressure, velocity, pulse pressure, and pulse rate of the blood flowing through the flow path has a predetermined value. Since the control means for controlling the drive means for driving is provided, blood characteristics can be measured by simulating at least one of blood pressure, velocity, pulse pressure, and pulse rate in the living body. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
本発明に係る血液特性解析システム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 blood characteristic analysis system which concerns on this invention. マイクロチップを示す図であり、（ａ）は平面図、（ｂ）は分解側面図、（ｃ）は（ａ）の部分拡大図である。It is a figure which shows a microchip, (a) is a top view, (b) is an exploded side view, (c) is the elements on larger scale of (a). マイクロチップの流路を説明するための図であり、上側の図は平面図、下側の図は側面図である。It is a figure for demonstrating the flow path of a microchip, the upper figure is a top view, and the lower figure is a side view. マイクロチップの流路の可動部を説明するための図である。It is a figure for demonstrating the movable part of the flow path of a microchip.
　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、本実施の形態における血液特性解析システム１の全体構成を示すブロック図である。 FIG. 1 is a block diagram showing the overall configuration of the blood characteristic analysis system 1 in the present embodiment.
　この図に示すように、血液特性解析システム１は、血液を供給槽１０からマイクロチップ（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複数種類の血液特性を計測するものである。 As shown in this figure, the blood characteristic analysis system 1 guides blood from a supply tank 10 to a discharge tank 11 through a microchip (filter) 2 and measures a plurality of types of blood characteristics from information acquired in the process. To do.
　具体的には、血液特性解析システム１は、主に、マイクロチップ２と、マイクロチップ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血液特性を計測するパソコン７と、血流画像を表示するディスプレイ８と、マイクロチップ２内の血流を制御する血流制御部９とを備えている。なお、本実施の形態における血液特性解析システム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マイクロチップ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、血流制御部９内の差圧制御部９１が加圧ポンプ１５及び減圧ポンプ１６を制御してマイクロチップ２前後の差圧を調整することにより、マイクロチップ２内を所望量だけ流れるようになっている。また、上述の血流制御部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 characteristic analysis system 1 is mainly based on the microchip 2, the TV camera 3 that captures the blood flow in the microchip 2, and the blood flow image captured by the TV camera 3. A personal computer 7 that measures characteristics, a display 8 that displays a blood flow image, and a blood flow control unit 9 that controls blood flow in the microchip 2 are provided. In the blood characteristic analysis system 1 according to the present embodiment, a plurality of liquids such as physiological saline and physiologically active substances are connected to the flow path via the mixer 12 so as to be mixed with blood and guided to the microchip 2. A solution bottle 13 or the like is further provided. The blood mixed with a liquid such as physiological saline or a physiologically active substance (hereinafter referred to as blood) is micro-controlled by the differential pressure control unit 91 in the blood flow control unit 9 by controlling the pressurization pump 15 and the decompression pump 16. By adjusting the differential pressure across the chip 2, a desired amount flows through the microchip 2. In addition to the blood flow 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（ａ）（ｂ）（ｃ）は、図１に示されたマイクロチップ２を図示したものである。図２（ａ）はマイクロチップを上面から見た図（平面図）であり、図２（ｂ）は側面図、図２（ｃ）はマイクロチップの一部を拡大した部分拡大図である。 2 (a), 2 (b) and 2 (c) illustrate the microchip 2 shown in FIG. 2A is a view (plan view) of the microchip as viewed from above, FIG. 2B is a side view, and FIG. 2C is a partially enlarged view of a part of the microchip.
　マイクロチップ２は、図２に示すように、矩形状のガラス平板２０及びベース板２１を重ね合わせて形成されている。 The microchip 2 is formed by overlapping a rectangular glass flat plate 20 and a base plate 21 as shown in FIG.
　ガラス平板２０は、平板状に形成されており、ベース板２１の内側面（図２（ｂ）では上側の面）を覆っている。 The glass flat plate 20 is formed in a flat plate shape and covers the inner side surface of the base plate 21 (the upper surface in FIG. 2B).
　ベース板２１は、両端部に窪み部２１０，２１１を、これら窪み部２１０，２１１の間に複数の溝部２１２，…を有している。 The base plate 21 has depressions 210 and 211 at both ends, and a plurality of grooves 212 and so on between the depressions 210 and 211.
　このうち、窪み部２１０は、供給槽１０と連通する貫通口２１０ａを底面に有しており、血液を貯留する上流側貯留部２２をガラス平板２０との間に形成している。 Among these, the hollow part 210 has a through-hole 210 a communicating with the supply tank 10 on the bottom surface, and an upstream storage part 22 for storing blood is formed between the glass flat plate 20.
　同様に、窪み部２１１は、排出槽１１と連通する貫通口２１１ａを底面に有しており、血液を貯留する下流側貯留部２３をガラス平板２０との間に形成している。 Similarly, the recess 211 has a through hole 211 a communicating with the discharge tank 11 on the bottom surface, and forms a downstream storage 23 for storing blood between the flat glass plate 20.
　また、複数の溝部２１２，…は、窪み部２１０と窪み部２１１とを結ぶ方向（図中のＸ方向）に対して平行に延在するよう配設され、上述のＸ方向に延在するテラス部２１３によって仕切られた状態となっている。これら複数の溝部２１２，…は、互い違いに窪み部２１０、または窪み部２１１に連通しており、これにより、上流側貯留部２２から血液を流入させる上流側血液回路２４と、下流側貯留部２３に血液を流入させる下流側血液回路２５とを、ガラス平板２０との間に形成している。 Further, the plurality of grooves 212,... Are arranged so as to extend in parallel to the direction (X direction in the drawing) connecting the recess 210 and the recess 211, and extend in the X direction described above. It is in a state of being partitioned by the portion 213. The plurality of grooves 212,... Alternately communicate with the depression 210 or the depression 211, whereby the upstream blood circuit 24 that allows blood to flow from the upstream reservoir 22 and the downstream reservoir 23. A downstream blood circuit 25 that allows blood to flow into the glass plate 20 is formed.
　図３（ａ）（ｂ）は、マイクロチップ２の流路を説明するための図であり、図３（ａ）（ｂ）ともに、上側の図は、テラス部２１３を上から見た平面図であり、下側の図は、図３（ａ）（ｂ）を側面から見た断面図である。 FIGS. 3A and 3B are diagrams for explaining the flow path of the microchip 2. In FIGS. 3A and 3B, the upper diagram is a plan view of the terrace portion 213 as viewed from above. The lower diagram is a cross-sectional view of FIGS. 3A and 3B as viewed from the side.
　テラス部２１３の上端部には、図２（ｃ）や図３（ａ）（ｂ）に示すように、六角形状の土手部２１４がＸ方向に複数配列されており、頂面でガラス平板２０に当接している。 As shown in FIG. 2C and FIG. 3A and FIG. 3B, a plurality of hexagonal bank portions 214 are arranged in the X direction on the upper end portion of the terrace portion 213, and the glass flat plate 20 is formed on the top surface. Abut.
　これら複数の土手部２１４，…は互いとの間にゲート２１５を形成しており、このゲート２１５は、Ｘ方向の直交方向（以下、Ｙ方向とする）に血液を流す微細な流路２６を、ガラス平板２０との間に形成している。つまり、この流路２６は、表面に微細な溝としてのゲート２１５を有するベース板２１と、このベース板２１の表面に当接する平面部を有するガラス平板２０とを接合することによって、これらゲート２１５及び平面部で形成される空間となっている。なお、特に限定はされないが、図２（ｃ）の仮想線Ａ－Ａ，Ｂ－Ｂに示す位置で流路２６や上流側血液回路２４，下流側血液回路２５（対応する仮想線は省略している）を切断した場合に、流路２６は上流側血液回路２４や下流側血液回路２５の内部よりも断面積（流路断面積ともいう）が狭くなっている。より詳細には、流路２６の断面形状は赤血球の形状（真ん中が窪んだ円盤形状であり、断面が扁平な楕円形状）に合わせて扁平な長方形をなしており、この流路２６の断面のサイズは赤血球のサイズより小さくなっている。これにより、毛細血管などの細い血管を赤血球が自身の形状を変形させながら通過していく状態が観察でき、また、血管中での血液のサラサラ度を模擬的に再現することができる。 The plurality of bank portions 214,... Form a gate 215 between them, and the gate 215 has a fine channel 26 that allows blood to flow in a direction orthogonal to the X direction (hereinafter referred to as the Y direction). And the glass flat plate 20. That is, the flow path 26 joins the gate plate 215 by joining the base plate 21 having the gate 215 as a fine groove on the surface and the glass flat plate 20 having the flat portion contacting the surface of the base plate 21. And a space formed by a plane portion. Although not particularly limited, the flow path 26, the upstream blood circuit 24, and the downstream blood circuit 25 (corresponding virtual lines are omitted at the positions indicated by virtual lines AA and BB in FIG. 2 (c). The cross-sectional area (also referred to as a flow-path cross-sectional area) of the flow path 26 is narrower than that of the upstream blood circuit 24 and the downstream blood circuit 25. More specifically, the cross-sectional shape of the flow path 26 is a flat rectangle in accordance with the shape of red blood cells (the shape of a disk with a hollow center and an elliptical shape with a flat cross section). The size is smaller than the size of red blood cells. Thereby, it is possible to observe a state in which red blood cells pass through thin blood vessels such as capillaries while deforming their own shapes, and it is possible to simulate the smoothness of blood in the blood vessels.
　図４はマイクロチップ２の可動部を説明するための図である。 FIG. 4 is a diagram for explaining the movable part of the microchip 2.
　土手部２１４は、図４に示すように、Ｘ方向に移動可能な可動部２１４ａ、及びベース板２１と一体に形成された静止部２１４ｂから形成されている。可動部２１４ａは、流路２６を形成するＹ方向（流れ方向）に平行な流路壁のうち、Ｙ方向中央の流路壁部分２６ａを含んで方形状に形成され、アクチュエータ２７によりＸ方向（流れ方向に直交方向）へ所定範囲だけ移動可能になっている。この可動部２１４ａの移動により、流路２６の一部分の断面積を任意に変化させることができる。 As shown in FIG. 4, the bank portion 214 includes a movable portion 214 a that can move in the X direction and a stationary portion 214 b that is formed integrally with the base plate 21. The movable portion 214a is formed in a square shape including a channel wall portion 26a at the center in the Y direction among the channel walls parallel to the Y direction (flow direction) forming the channel 26, and is moved in the X direction ( It is movable by a predetermined range in the direction orthogonal to the flow direction. By the movement of the movable portion 214a, the cross-sectional area of a part of the flow path 26 can be arbitrarily changed.
　なお、可動部２１４ａは、上記構成に限定されず、流路２６の少なくとも一部分における流路壁を含んでＸ方向へ移動可能に構成されていればよく、更には、流路２６の断面形状を変化させる構成であってもよい。この断面形状を変化させる構成としては、例えば、流路壁部分２６ａの上端をＸ方向へ傾かせるものや、形状記憶材等の使用により流路壁部分２６ａを湾曲させるもの等が可能である。また、可動部２１４ａ、静止部２１４ｂ、及びアクチュエータ２７は、図示の簡略化のため、図２及び図３では図示を省略している。 The movable portion 214a is not limited to the above configuration, and may be configured to be movable in the X direction including the flow channel wall in at least a part of the flow channel 26. Furthermore, the cross-sectional shape of the flow channel 26 may be changed. The configuration may be changed. As a configuration for changing the cross-sectional shape, for example, a configuration in which the upper end of the flow path wall portion 26a is inclined in the X direction or a shape in which the flow path wall portion 26a is curved by using a shape memory material or the like can be used. Further, the movable portion 214a, the stationary portion 214b, and the actuator 27 are not shown in FIGS. 2 and 3 for simplification of illustration.
　可動部２１４ａを駆動するアクチュエータ２７は、可動部２１４ａに対応してベース板２１内にそれぞれ埋設されており、後述の駆動制御部９２と接続されて駆動制御されるようになっている（図１参照）。このアクチュエータ２７は、特に限定はされないが、圧電アクチュエータ又は圧電超音波リニアアクチュエータである。このようなアクチュエータ２７としては、例えば特開平７－２９８６５６号公報、特開２００６－６６９７６号公報、又は特開２００７－５７５８１号公報に開示のもの等を用いることができる。 Actuators 27 for driving the movable portion 214a are respectively embedded in the base plate 21 corresponding to the movable portion 214a, and are connected to a drive control portion 92, which will be described later, so as to be driven and controlled (FIG. 1). reference). The actuator 27 is not particularly limited, but is a piezoelectric actuator or a piezoelectric ultrasonic linear actuator. As such an actuator 27, for example, those disclosed in JP-A-7-298656, JP-A-2006-66976, or JP-A-2007-57581 can be used.
　以上のマイクロチップ２の構造をふまえ、図１にもどり、本願実施例の説明を行う。 Based on the structure of the microchip 2 described above, returning to FIG. 1, the embodiment of the present application will be described.
　供給槽１０から導入された血液は上流側貯留部２２で貯留され、上流側血液回路２４から流路２６、下流側血液回路２５を通過した後、下流側貯留部２３に貯留されて排出槽１１から排出されることとなる。（より詳細には、図３に示すように、流路２６を流れる血液中の血球、例えば赤血球は、まずゲート２１５上流の入口領域Ａを通った後、ゲート２１５の内部領域Ｂを変形しながら通過し、最後にゲート２１５下流の出口領域Ｃを通過することとなる。）
　なお、このマイクロチップ２の前後には、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、計測したチップ上流圧力Ｐ１，チップ下流圧力Ｐ２を血流制御部９へ出力するようになっている（図１参照）。但し、これら圧力センサＥ１，Ｅ２は、マイクロチップ２の入口，出口近傍での血液の圧力を計測できればよく、例えばマイクロチップ２の前後にそれぞれ圧力調整容器を設けて、この各容器内の圧力を計測するようにしてもよい。 The blood introduced from the supply tank 10 is stored in the upstream storage section 22, passes through the flow path 26 and the downstream blood circuit 25 from the upstream blood circuit 24, is stored in the downstream storage section 23, and is discharged into the discharge tank 11. It will be discharged from. (In more detail, as shown in FIG. 3, blood cells in blood flowing through the flow path 26, for example, red blood cells, first pass through the inlet region A upstream of the gate 215, and then deform the inner region B of the gate 215. And finally pass through the exit region C downstream of the gate 215.)
In addition, pressure sensors E1 and E2 are provided before and after the microchip 2, and the pressure sensors E1 and E2 output the measured chip upstream pressure P1 and chip downstream pressure P2 to the blood flow control unit 9. (See FIG. 1). However, these pressure sensors E1 and E2 only need to be able to measure the blood pressure in the vicinity of the inlet and outlet of the microchip 2. For example, pressure adjusting containers are provided before and after the microchip 2, and the pressure in each container is measured. You may make it measure.
　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、図１に示すように、マイクロチップ２におけるガラス平板２０に対向して設置され、流路２６を通過する血液の流れをガラス平板２０越しに撮影する。その撮影範囲は、図２、図３で示されている複数のゲート２１５における入口領域Ａ～出口領域Ｃを含む範囲となっている。但し、この撮影範囲は、各ゲート２１５における入口領域Ａ、内部領域Ｂ、出口領域Ｃのうちの少なくとも１つの領域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. As shown in FIG. 1, the TV camera 3 is installed to face the glass flat plate 20 in the microchip 2, and photographs the blood flow passing through the flow path 26 through the glass flat plate 20. The imaging range is a range including the entrance area A to the exit area C in the plurality of gates 215 shown in FIGS. However, this imaging range may be a range including at least one of the entrance area A, the internal area B, and the exit area C in each gate 215. 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、血液の圧力や速度等の他、血液の凝集能といった流動性に関するものを含む。凝集能とは、血球が滞留して集塊状に結合する凝集現象の発生しやすさを表す定量値であり、滞留した血球からなる血球滞留部に含まれる各血球種の面積、個数、面積割合、又は個数割合などで表される。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 blood properties and the like, and include those related to fluidity such as blood coagulation ability in addition to blood pressure and velocity. Aggregation capacity is a quantitative value indicating the ease of occurrence of the aggregation phenomenon in which blood cells stay and bind together, and the area, number, and area ratio of each blood cell type contained in the blood cell retention part consisting of the retained blood cells. Or the number ratio. 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が出力した撮影画像や、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 photographed image output from the TV camera 3 and blood characteristics calculated by the personal computer 7.
　血流制御部９は、マイクロチップ２前後の差圧を制御する差圧制御部９１と、アクチュエータ２７の駆動を制御する駆動制御部９２とを備え、シーケンス制御部１７からの制御指令に応じてこれら差圧制御部９１及び駆動制御部９２が所定の制御を行うようになっている。なお、血流制御部９及びシーケンス制御部１７をパソコン７と一体に構成し、このパソコン７が前記所定の制御を行うようにしてもよい。 The blood flow control unit 9 includes a differential pressure control unit 91 that controls the differential pressure across the microchip 2 and a drive control unit 92 that controls the drive of the actuator 27, and according to a control command from the sequence control unit 17. The differential pressure control unit 91 and the drive control unit 92 perform predetermined control. The blood flow control unit 9 and the sequence control unit 17 may be configured integrally with the personal computer 7, and the personal computer 7 may perform the predetermined control.
　差圧制御部９１は、チップ上流圧力Ｐ１及びチップ下流圧力Ｐ２が所定の圧力となるように、マイクロチップ２上流の加圧ポンプ１５とマイクロチップ２下流の減圧ポンプ１６とをそれぞれ制御する。 The differential pressure control unit 91 controls the pressurization pump 15 upstream of the microchip 2 and the decompression pump 16 downstream of the microchip 2 so that the chip upstream pressure P1 and the chip downstream pressure P2 become predetermined pressures.
　駆動制御部９２は、マイクロチップ２の流路２６において、対向する流路壁部分２６ａ間の距離ｗ（図４参照）が所定値となるように、アクチュエータ２７の駆動を制御する。 The drive control unit 92 controls the drive of the actuator 27 so that the distance w (see FIG. 4) between the opposed flow path wall portions 26a in the flow path 26 of the microchip 2 becomes a predetermined value.
　図１を主に用いて、以下に、血液特性を計測する際の血液特性解析システム１の動作について説明する。 Referring mainly to FIG. 1, the operation of the blood characteristic analysis system 1 when measuring blood characteristics will be described below.
　まずマイクロチップ２へ血液を流しつつ、流路２６内の血流をＴＶカメラ３で撮影する。より詳細には、シーケンス制御部１７が供給槽１０へ計測対象の血液を注入させつつ、必要に応じて溶液びん１３へ生理食塩水等を加えさせる。そして、シーケンス制御部１７が差圧制御部９１を介して加圧ポンプ１５及び減圧ポンプ１６を制御することによりマイクロチップ２に所定の差圧を作用させて当該マイクロチップ２に血液を流す一方、ＴＶカメラ３が流路２６内の血流を撮影する。この際、マイクロチップ２内の流路壁部分２６ａ間の距離ｗは、駆動制御部９２により所望の値に設定されている。 First, the blood flow in the flow path 26 is photographed by the TV camera 3 while flowing the blood to the microchip 2. More specifically, the sequence controller 17 adds physiological saline or the like to the solution bottle 13 as necessary while injecting blood to be measured into the supply tank 10. The sequence control unit 17 controls the pressurization pump 15 and the decompression pump 16 via the differential pressure control unit 91 to apply a predetermined differential pressure to the microchip 2 to flow blood through the microchip 2, The TV camera 3 images the blood flow in the flow path 26. At this time, the distance w between the flow path wall portions 26 a in the microchip 2 is set to a desired value by the drive control unit 92.
　次に、パソコン７が撮影画像を画像処理することによって血液特性を算出した後、算出結果や撮影画像そのものをディスプレイ８に表示させる。 Next, after the personal computer 7 calculates blood characteristics by performing image processing on the captured image, the calculation result and the captured image itself are displayed on the display 8.
　ここで、算出された血液特性に応じてマイクロチップ２内の流路壁部分２６ａ間の距離ｗを変更させることができる。具体的には、例えば血液の圧力及び／又は速度を所定の値とするよう、アクチュエータ２７を制御して流路壁部分２６ａ間の距離ｗを変更させる。このようにすれば、生体における血液の圧力や速度を模擬して他の血液特性の計測を行うことができる。ｗの値としては、赤血球の血球径（約８μｍ）より小さい値であればよく、最も小さい値は、血管が詰まった状態を示す、ｗ＝０である。なお、このような距離ｗの変更は、再計測の際に行ってもよいし、血流の撮影中、つまり流路２６に血液を通過させた状態で行ってもよい。血流の撮影前に流路壁間の距離を変更するということは、人体の中で、血管の太さに応じた血流を測定することを想定することができる。血流の撮影中に流路間の距離を変更することは、人体の中で、血管の太さが変化しているような状態での血流を測定することを想定できる。 Here, the distance w between the channel wall portions 26a in the microchip 2 can be changed according to the calculated blood characteristics. Specifically, for example, the distance w between the flow path wall portions 26a is changed by controlling the actuator 27 so that the blood pressure and / or velocity is set to a predetermined value. In this way, it is possible to measure other blood characteristics by simulating blood pressure and velocity in the living body. The value of w may be a value smaller than the blood cell diameter of red blood cells (about 8 μm), and the smallest value is w = 0, which indicates a state where the blood vessel is clogged. Such a change of the distance w may be performed at the time of re-measurement, or may be performed during blood flow imaging, that is, in a state where blood is passed through the flow path 26. Changing the distance between the flow path walls before imaging the blood flow can be assumed to measure the blood flow according to the thickness of the blood vessel in the human body. Changing the distance between the flow paths during imaging of blood flow can be assumed to measure blood flow in a state where the thickness of the blood vessel is changing in the human body.
　また、流路２６に血液を通過させた状態で、アクチュエータ２７を制御して流路壁部分２６ａ間の距離ｗを反復変動させてもよい。具体的には、流路２６を流れる血液の脈圧及び／又は脈拍数を所定の値とするよう、アクチュエータ２７を制御して流路壁部分２６ａ間の距離ｗを反復変動させる。このようにすれば、生体内における血流の脈動を模擬して血液特性の計測を行うことができる。なお、脈圧の測定は、複数のアクチュエータ２７を同期させて反復変動させ、その際の圧力変化を圧力センサＥ１，Ｅ２の差圧により脈圧として測定するようにしてもよく、あるいは圧電素子を各流路２６の内部に設けて、当該圧電素子により脈圧を測定するようにしてもよい。 Further, the distance w between the flow path wall portions 26a may be repeatedly changed by controlling the actuator 27 in a state where blood is passed through the flow path 26. Specifically, the actuator 27 is controlled to repeatedly vary the distance w between the flow path wall portions 26a so that the pulse pressure and / or the pulse rate of the blood flowing through the flow path 26 have predetermined values. In this way, blood characteristics can be measured by simulating blood flow pulsations in the living body. The pulse pressure may be measured by repeatedly varying the plurality of actuators 27 in synchronization, and the pressure change at that time may be measured as the pulse pressure by the pressure difference between the pressure sensors E1 and E2, or a piezoelectric element may be used. The pulse pressure may be measured by the piezoelectric element provided inside each flow channel 26.
　以上のように、本実施の形態における血液特性解析システム１によれば、少なくとも一部分における断面積又は断面形状が変更可能な流路２６を有するマイクロチップ２を用いて血液特性が計測されるので、生体内の血管の変形を同一のマイクロチップ２内の流路２６で模擬して血液特性の計測を行うことができる。したがって、流路の断面積が異なる複数のマイクロチップを製作してそれぞれで計測する等の煩雑な作業を要した従来に比べ、生体内に近い状態での血液特性の計測を簡便に行うことができる。 As described above, according to the blood characteristic analysis system 1 in the present embodiment, the blood characteristic is measured using the microchip 2 having the flow path 26 whose cross-sectional area or cross-sectional shape can be changed at least partially. Blood characteristics can be measured by simulating the deformation of a blood vessel in a living body through the flow path 26 in the same microchip 2. Therefore, it is possible to easily measure blood characteristics in a state close to the living body, compared to the conventional case that requires complicated operations such as manufacturing a plurality of microchips having different cross-sectional areas of the flow paths and measuring them individually. it can.
　また、流路２６は、血液を通過させた状態で、少なくとも一部分における断面積又は断面形状が変更可能であるので、同一計測中に流路２６の断面積又は断面形状といった条件を変えることができるとともに、流路２６の断面積又は断面形状が変化している正にそのときの血液特性を計測することができる。したがって、より生体内に近い状態での血液特性の計測を簡便・短時間に行うことができる。 Moreover, since the flow path 26 can change the cross-sectional area or cross-sectional shape in at least one part in the state which let the blood pass, conditions, such as the cross-sectional area or cross-sectional shape of the flow path 26, can be changed during the same measurement. At the same time, the blood characteristics at the time when the cross-sectional area or cross-sectional shape of the flow path 26 is changing can be measured. Therefore, measurement of blood characteristics in a state closer to the living body can be performed easily and in a short time.
　また、流路２６は、少なくとも一部分における断面積が任意に変更可能であるか、或いは断面形状が所定の形状に変更可能であるので、生体内の血管の変形を同一のマイクロチップ２内の流路２６でより精密に模擬して血液特性の計測を行うことができる。したがって、より生体内に近い状態での血液特性の計測を行うことができる。 In addition, since the cross-sectional area of at least a part of the flow path 26 can be arbitrarily changed, or the cross-sectional shape can be changed to a predetermined shape, the deformation of blood vessels in the living body can be changed in the same microchip 2. The blood characteristics can be measured by simulating with the path 26 more precisely. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
　また、流路２６を流れる血液の圧力、速度、脈圧、及び脈拍数の少なくとも１つを所定の値とするよう、流路２６の流路壁部分２６ａを駆動するアクチュエータ２７を制御する駆動制御部９２を備えるので、生体における血液の圧力、速度、脈圧、及び脈拍数の少なくとも１つを模擬して血液特性の計測を行うことができる。したがって、より生体内に近い状態での血液特性の計測を行うことができる。 Further, drive control for controlling the actuator 27 that drives the flow path wall portion 26a of the flow path 26 so that at least one of the pressure, velocity, pulse pressure, and pulse rate of the blood flowing through the flow path 26 has a predetermined value. Since the unit 92 is provided, blood characteristics can be measured by simulating at least one of blood pressure, velocity, pulse pressure, and pulse rate in the living body. Therefore, it is possible to measure blood characteristics in a state closer to the living body.
　なお、本発明は上記実施の形態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。 In addition, this invention is not limited to the said embodiment, Of course, it can change suitably.
　１　血液特性解析システム
　２　マイクロチップ
　３　ＴＶカメラ（撮影手段）
　２６　流路
　２７　アクチュエータ（駆動手段）
　７０　演算処理部（解析手段）
　９２　駆動制御部（制御手段）
　Ａ　入口領域
　Ｂ　内部領域
　Ｃ　出口領域 1 Blood characteristic analysis system 2 Microchip 3 TV camera (photographing means)
26 Flow path 27 Actuator (drive means)
70 Arithmetic processing part (analysis means)
92 Drive control unit (control means)
A Entrance area B Internal area C Exit area

Claims (8)

  1. 　血液特性を計測する血液特性解析システムに備えられる血液特性解析用のマイクロチップであって、
    　血液が通過する少なくとも１つの流路を有し、
    　前記流路は、少なくとも一部分における断面積又は断面形状が変更可能であることを特徴とするマイクロチップ。     A microchip for blood characteristic analysis provided in a blood characteristic analysis system for measuring blood characteristics,
    Having at least one flow path through which blood passes;
    The microchip according to claim 1, wherein a cross-sectional area or a cross-sectional shape of at least a part of the flow path is changeable.
  2. 　前記流路は、血液を通過させた状態で、少なくとも一部分における断面積又は断面形状が変更可能であることを特徴とする請求項１に記載のマイクロチップ。 2. The microchip according to claim 1, wherein the flow path is capable of changing a cross-sectional area or a cross-sectional shape in at least a part in a state in which blood is passed.
  3. 　前記流路は、少なくとも一部分における断面積が任意に変更可能であるか、或いは断面形状が所定の形状に変更可能であることを特徴とする請求項１又は２に記載のマイクロチップ。 3. The microchip according to claim 1, wherein a cross-sectional area of at least a part of the flow path can be arbitrarily changed, or a cross-sectional shape thereof can be changed to a predetermined shape.
  4. 　前記流路の少なくとも一部分における流路壁を駆動する駆動手段を有することを特徴とする請求項１～３のいずれか一項に記載のマイクロチップ。 The microchip according to any one of claims 1 to 3, further comprising a driving unit that drives a channel wall in at least a part of the channel.
  5. 　前記駆動手段は、圧電アクチュエータ又は圧電超音波リニアアクチュエータであることを特徴とする請求項４に記載のマイクロチップ。 5. The microchip according to claim 4, wherein the driving means is a piezoelectric actuator or a piezoelectric ultrasonic linear actuator.
  6. 　請求項１～５のいずれか一項に記載のマイクロチップと、
    　前記流路の内部領域、入口領域、及び出口領域の少なくとも１つの領域における血液の流れを撮影する撮影手段と、
    　前記撮影手段による血流画像を解析して血液特性を算出可能な解析手段と、
    を備えることを特徴とする血液特性解析システム。     A microchip according to any one of claims 1 to 5;
    Imaging means for imaging the blood flow in at least one of the internal region, the inlet region, and the outlet region of the flow path;
    Analyzing means capable of calculating blood characteristics by analyzing a blood flow image by the imaging means;
    A blood characteristic analysis system comprising:
  7. 　前記マイクロチップは、前記流路の少なくとも一部分における流路壁を駆動する駆動手段を有し、
    　当該血液特性解析システムは、前記流路を流れる血液の圧力、速度、脈圧、及び脈拍数の少なくとも１つを所定の値とするよう前記駆動手段を制御する制御手段を備えることを特徴とする請求項６に記載の血液特性解析システム。     The microchip has a driving means for driving a channel wall in at least a part of the channel,
    The blood characteristic analysis system includes control means for controlling the drive means so that at least one of pressure, velocity, pulse pressure, and pulse rate of blood flowing through the flow path is set to a predetermined value. The blood characteristic analysis system according to claim 6.
  8. 　前記制御手段は、パソコンであることを特徴とする請求項７に記載の血液特性解析システム。 The blood characteristic analysis system according to claim 7, wherein the control means is a personal computer.
PCT/JP2009/064633 2008-09-01 2009-08-21 Microchip and blood analysis system WO2010024197A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002505439A (en) * 1998-03-02 2002-02-19 セントラル リサーチ ラボラトリーズ リミティド Flow rate changing device and flow rate changing method for changing the flow rate of fluid along a path
JP2002214243A (en) * 2001-01-19 2002-07-31 Nec Corp Liquid flow control method and mechanism and biosensor provided with liquid flow control mechanism
JP2006125990A (en) * 2004-10-28 2006-05-18 Konica Minolta Medical & Graphic Inc Bio-substance examination device and microreactor
WO2006095615A1 (en) * 2005-03-07 2006-09-14 Kuraray Co., Ltd. Microchannel array and method for producing the same, and blood measuring method employing it
JP2008008891A (en) * 2006-05-30 2008-01-17 Honda Motor Co Ltd Apparatus for controlling flow rate in microflow path, microchip apparatus comprising flow rate control apparatus, and flow rate control method

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002505439A (en) * 1998-03-02 2002-02-19 セントラル リサーチ ラボラトリーズ リミティド Flow rate changing device and flow rate changing method for changing the flow rate of fluid along a path
JP2002214243A (en) * 2001-01-19 2002-07-31 Nec Corp Liquid flow control method and mechanism and biosensor provided with liquid flow control mechanism
JP2006125990A (en) * 2004-10-28 2006-05-18 Konica Minolta Medical & Graphic Inc Bio-substance examination device and microreactor
WO2006095615A1 (en) * 2005-03-07 2006-09-14 Kuraray Co., Ltd. Microchannel array and method for producing the same, and blood measuring method employing it
JP2008008891A (en) * 2006-05-30 2008-01-17 Honda Motor Co Ltd Apparatus for controlling flow rate in microflow path, microchip apparatus comprising flow rate control apparatus, and flow rate control method

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