WO2010010805A1 - マイクロチップ、血液特性解析システム及び血液特性解析方法 - Google Patents
マイクロチップ、血液特性解析システム及び血液特性解析方法 Download PDFInfo
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- WO2010010805A1 WO2010010805A1 PCT/JP2009/062282 JP2009062282W WO2010010805A1 WO 2010010805 A1 WO2010010805 A1 WO 2010010805A1 JP 2009062282 W JP2009062282 W JP 2009062282W WO 2010010805 A1 WO2010010805 A1 WO 2010010805A1
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- 238000000034 method Methods 0.000 title claims abstract description 8
- 238000004159 blood analysis Methods 0.000 title abstract 3
- 210000004369 blood Anatomy 0.000 claims abstract description 151
- 239000008280 blood Substances 0.000 claims abstract description 151
- 230000017531 blood circulation Effects 0.000 claims abstract description 83
- 238000004458 analytical method Methods 0.000 claims description 71
- 238000011144 upstream manufacturing Methods 0.000 claims description 20
- 238000003384 imaging method Methods 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 4
- 210000004204 blood vessel Anatomy 0.000 abstract description 42
- 230000004888 barrier function Effects 0.000 abstract 4
- 210000000601 blood cell Anatomy 0.000 description 10
- 239000011521 glass Substances 0.000 description 9
- 208000007536 Thrombosis Diseases 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 238000004364 calculation method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
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- 229910052710 silicon Inorganic materials 0.000 description 2
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- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000005357 flat glass Substances 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- 238000000059 patterning Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229920002120 photoresistant polymer Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
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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
- G01N33/4905—Determining clotting time of blood
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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
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1429—Signal processing
- G01N15/1433—Signal processing using image recognition
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1027—Determining speed or velocity of a particle
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
- G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
Definitions
- the present invention relates to a microchip, a blood characteristic analysis system, and a blood characteristic analysis method.
- blood properties such as blood fluidity and blood cell deformability are attracting attention as a health barometer.
- the fluidity of blood is also called smoothness, which means that the higher the fluidity, the better the health.
- the flow channel shape is varied from the viewpoint of accurately quantifying the blood characteristics by bringing the blood flow of the human body close to the state in the blood vessel. More specifically, in the device described in Patent Document 3, the flow path width is narrowed in the blood flow direction in some of the flow paths, and in the device described in Patent Document 4, a plurality of obstacles are provided in some of the flow paths. Arranged.
- the size and shape may change in the direction of blood flow when the blood collides.
- the obstacle in the flow path has a uniform shape in the blood flow direction (the obstacles adjacent to each other in the blood flow direction have the same shape), and the human body Therefore, it is impossible to accurately analyze blood characteristics simulating the inside of blood vessels.
- the present invention has been made in view of the above circumstances, and provides a microchip, a blood characteristic analysis system, and a blood characteristic analysis method capable of analyzing blood characteristics by imitating blood vessels more accurately than in the past.
- the task is to do.
- the invention according to claim 1 is a microchip for blood characteristic analysis provided in a blood characteristic analysis system for measuring blood characteristics, It has a plurality of flow paths that allow blood to pass through, A plurality of first obstacles for locally changing the direction of blood flow are provided in the blood flow direction on the wall surface defining the flow channel of only some of the plurality of flow channels. , Among the plurality of first obstacles, the obstacles adjacent to each other in the blood flow direction have different shapes.
- the invention according to claim 2 is a microchip for blood characteristic analysis provided in a blood characteristic analysis system for measuring blood characteristics, It has a plurality of flow paths that allow blood to pass through, Among the plurality of flow paths, a plurality of second obstacles for locally changing the direction of blood flow are provided in the blood flow direction on the wall surface defining the flow path of only some of the flow paths. , The plurality of second obstacles have a random shape.
- the invention according to claim 3 is the microchip according to claim 1 or 2
- a third obstacle that locally changes the direction of the blood flow in the direction of blood flow is formed on the wall surface that defines the other part of the plurality of flow paths except the part of the flow paths. There are several at regular intervals.
- the plurality of third obstacles have the same shape as each other.
- the invention described in claim 4 is the microchip according to any one of claims 1 to 3,
- the obstacle is provided so as to protrude inside the flow path.
- the invention according to claim 5 is the microchip according to any one of claims 1 to 4, wherein the inner wall portion of the plurality of flow paths has a cross section that widens from the upstream side to the downstream side in the blood flow direction. Or narrow.
- the invention according to claim 6 is the microchip according to any one of claims 1 to 5, Of the plurality of flow paths, the wall surface defining the flow path where the obstacle is not provided is formed flat.
- the invention according to claim 7 is the microchip according to any one of claims 1 to 6,
- the wall surface defining the plurality of flow paths has a circular cross section.
- the invention according to claim 8 is a blood characteristic analysis system for measuring blood characteristics, A microchip according to any one of claims 1 to 7; Imaging means for imaging blood flow in the plurality of flow paths of the microchip; Analyzing means for calculating a blood characteristic by analyzing a photographed image by the photographing means; It is characterized by providing.
- the invention according to claim 9 is the blood characteristic analysis system according to claim 8,
- the analysis means includes A blood characteristic is calculated by analyzing a photographed image in a predetermined channel among the plurality of channels.
- the invention according to claim 10 is the blood characteristic analysis system according to claim 8,
- the analysis means includes Of the plurality of flow paths, the photographed images in the partial flow paths and the flow paths other than the partial flow paths are analyzed, and blood characteristics are compared.
- the invention according to claim 11 is the blood characteristic analysis system according to any one of claims 8 to 10,
- the photographing means includes The blood flow in the part of the plurality of channels and in a channel other than the part of the channels is photographed.
- the invention described in claim 12 is a blood characteristic analysis method for analyzing blood characteristics using the microchip according to any one of claims 1 to 7, An imaging step for imaging blood flow in the plurality of flow paths of the microchip; An analysis step of calculating a blood characteristic by analyzing a photographed image by the photographing step; It is characterized by having.
- the invention described in claim 13 is the blood property analysis method according to claim 12, In the analysis step, A blood characteristic is calculated by analyzing a photographed image in a predetermined channel among the plurality of channels.
- the invention described in claim 14 is the blood characteristic analysis method according to claim 12, In the analysis step, Of the plurality of flow paths, the photographed images in the partial flow paths and the flow paths other than the partial flow paths are analyzed, and blood characteristics are compared.
- the invention according to claim 15 is the blood property analysis method according to any one of claims 12 to 14, In the shooting process, The blood flow in the part of the plurality of channels and in a channel other than the part of the channels is photographed.
- the first obstacle that locally changes the direction of blood flow is provided on the wall surface that defines only a part of the plurality of channels. Are provided in the direction of blood flow, so that the shape of the flow path varies between the partial flow path and the other flow paths. Therefore, the blood characteristics can be accurately analyzed by comparing both a blood vessel without an obstacle and a blood vessel with an obstacle.
- the obstacles adjacent in the blood flow direction are configured to have different shapes. This is because multiple obstructions (thrombus, etc.) that occur in the blood vessels of the human body do not maintain the same shape and may move or change shape due to new blood flow. Are configured so as to be closer to the state of blood vessels in the human body. Thereby, compared with the case where the shape is the same between the obstacles adjacent to the blood flow direction, the blood characteristic can be analyzed by bringing the blood flow closer to the state in the blood vessel.
- the second obstacle that locally changes the direction of blood flow is provided on the wall surface that defines only a part of the plurality of channels. Are provided in the direction of blood flow, so that the shape of the flow path varies between the partial flow path and the other flow paths. Therefore, the blood characteristics can be accurately analyzed by comparing both a blood vessel without an obstacle and a blood vessel with an obstacle.
- the plurality of second obstacles are configured to have a random shape. This is because multiple obstructions (thrombus, etc.) that occur in the blood vessels of the human body do not maintain the same shape and may move or change shape due to new blood flow. It is configured so as to be random, and closer to the state of the blood vessels of the human body. Thereby, compared with the case where an obstacle is formed with regularity, a blood flow can be made closer to the state in a blood vessel, and a blood characteristic can be analyzed.
- the flow direction of the blood flow is locally changed on the wall surface that defines the other part of the plurality of passages except the part of the passages.
- a plurality of obstacles 3 are provided at regular intervals in the direction of blood flow, and the plurality of third obstacles have the same shape as each other. In addition, it is possible to observe changes in flow due to blood clots.
- the blood flow can be made closer to the state in the blood vessel and the blood characteristics can be analyzed.
- the inner wall portions of the plurality of flow paths become wider or narrower from the upstream side to the downstream side in the blood flow direction, so that the blood flow is more in the state in the blood vessel. Get closer. Therefore, it is possible to perform a more accurate analysis of blood characteristics simulating the inside of a blood vessel.
- the wall surface defining the flow path in which the obstacle is not provided among the plurality of flow paths is formed flat, the blood flow is allowed to flow in a normal blood vessel. Can be close to the state. Therefore, the blood characteristics can be analyzed more accurately by comparing both a blood vessel without an obstacle and a blood vessel with an obstacle.
- the wall surface defining the plurality of flow paths has a circular cross section, the blood characteristics can be analyzed by bringing the blood flow closer to the state in the blood vessel.
- the eighth and twelfth aspects of the present invention since the blood flow in the plurality of flow paths of the microchip is photographed and the photographed image is analyzed to calculate the blood characteristics, the state of the blood flowing through the microchip Can be photographed, and blood characteristics can be calculated.
- a blood image is calculated by analyzing a captured image in a predetermined flow path among the plurality of flow paths. Compared with the case of calculating the characteristics, the analysis can be facilitated.
- blood images are analyzed by analyzing each of the captured images of the some of the channels and the channels other than the some channels. Since the comparison is made, it is possible to analyze blood characteristics when, for example, a thrombus or atherosclerosis occurs in a blood vessel.
- 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 top view for demonstrating the flow path of a microchip. It is a top view for demonstrating the flow path of a microchip. It is a conceptual diagram for demonstrating 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 through a microchip (filter) 2 to a discharge tank 11, and measures blood characteristics from information acquired in the process. is there.
- 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 for measuring characteristics and a display 8 for displaying a blood flow image 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 physiologically active substance (hereinafter referred to as blood) is controlled by the differential pressure control unit 14 by controlling the pump 15 to adjust the differential pressure across the microchip 2.
- a desired amount flows through the chip 2.
- the valve 10 a of the supply tank 10 and the like are integrated and controlled by the sequence control unit 16.
- 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.
- a plurality of substantially hexagonal bank portions 214,... are arranged in the X direction on the upper end portion of the terrace portion 213, and abut the glass flat plate 20 at the top surface. ing.
- each gate 215 has a fine flow channel 26 that allows blood to flow in a direction orthogonal to the X direction (hereinafter referred to as the Y direction).
- the glass flat plate 20 the side surface of the bank portion 214 that forms the flow path 26 (gate 215) extends in the Y direction, so that the inner wall portion of the flow path 26 (the obstacle S described later) If provided, the base end portion) has a uniform cross section in the blood flow direction (Y direction), and in this embodiment, the cross section is rectangular.
- the width of the gate 215 is formed to be narrower than the blood cell diameter of blood cells such as erythrocytes (about 8 ⁇ m).
- the cross-sectional area is narrower than the inside of the side blood circuit 24 and the downstream blood circuit 25.
- 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. As a result, it is possible to observe a state in which red blood cells pass through a thin blood vessel such as a capillary blood vessel while deforming its own shape, and it is possible to simulate the degree of dryness of blood in the blood vessel.
- the plurality of bank portions 214 are composed of a first bank portion 214A and a second bank portion 214B.
- the first bank portion 214A is disposed adjacent to one or two other first bank portions 214A in the X direction.
- a plurality of obstacles (first obstacles) S,... For locally changing the direction of blood flow are provided on the opposing surfaces of the first bank portions 214A, that is, the wall surfaces defining the flow path 26.
- These obstacles S,... Project toward the inside of the flow path 26 and are arranged in a plurality along the Y direction, and the obstacles S adjacent in the Y direction have different shapes. Accordingly, a plurality of obstacles S,... Having different shapes are provided in the blood flow direction (Y direction) in the flow path 26 (hereinafter referred to as the obstacle flow path 26A) interposed between the first bank portions 214A. It is in the state.
- the side surfaces of the first bank portion 214A are formed flat. Further, the plurality of obstacles S,... In the first bank portion 214A increase from the upstream side to the downstream side in the blood flow direction (Y direction).
- the second bank portion 214B is disposed to face the surface of the first bank portion 214A opposite to the obstacle S and the side surface of the other second bank portion 214B.
- the entire side peripheral surface of the second bank portion 214B is formed flat, so that the second bank portion 214B and another bank portion 214 adjacent to the X direction (the first bank portion 214A or the second bank portion).
- 214B) is not provided with the obstacle S in the flow path 26 (hereinafter referred to as the comparison flow path 26B) interposed between them, in other words, the wall surface defining the flow path 26B is It is formed flat.
- the blood introduced from the supply tank 10 is stored in the upstream storage section 22, and after passing through the flow path 26 and the downstream blood circuit 25 from the upstream blood circuit 24, the downstream storage section 23 and discharged from the discharge tank 11. More specifically, as shown in FIG. 3A, blood cells in blood flowing through the flow path 26, such as red blood cells, first pass through the inlet region A upstream of the gate 215 and then the inner region B of the gate 215. And finally pass through the exit region C downstream of the gate 215.
- the base plate 21 in such a microchip 2 for example, after patterning a negative mold of the base plate 21 on a substrate such as silicon with a photoresist “SU-8” or the like, this mold is used. And a method of mold-molding and releasing polydimethylsiloxane, silicon, etc.
- the microchip has been described by taking a glass chip as an example.
- the microchip may be a resin chip.
- the base plate and / or the cover flat plate of the chip may be formed by injection molding performed by injecting molten resin.
- Pressure sensors E1 and E2 are provided before and after the microchip 2 described above, and the pressure sensors E1 and E2 output the measured pressures P1 and P2 to the differential pressure control unit 14, respectively. (See FIG. 1).
- 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 facing the glass flat plate 20 in the microchip 2, and photographs the blood flow passing through the obstacle flow path 26 ⁇ / b> A and the comparison flow path 26 ⁇ / b> B through the glass flat plate 20. To do.
- the imaging range is a range including an entrance area A to an exit area C (see FIG. 3A) in the plurality of gates 215. 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.
- Such a TV camera 3 is a camera capable of shooting a moving image, although not particularly limited.
- the personal computer 7 is connected to the TV camera 3 and includes an arithmetic processing unit 70 that calculates blood characteristics from image information output from the TV camera 3.
- the arithmetic processing unit 70 is an analyzing means in the present invention, and analyzes the captured images of the TV camera 3 in the obstacle channel 26A and the comparison channel 26B, respectively, and compares the blood characteristics.
- the blood characteristic is a characteristic value relating to blood fluidity, such as the velocity of blood cells in blood or the ability to aggregate blood.
- the agglutination ability is a quantitative value representing the ease of occurrence of the agglutination phenomenon in which blood cells stay and bind together, and the area, number, and number of each blood cell type contained in the blood cell retention part consisting of the retained blood cells, It is represented by area ratio or number ratio.
- a calculation processing unit 70 a conventionally known one 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 in the flow path 26 is photographed by the TV camera 3 while flowing the blood to the microchip 2. More specifically, the sequence control unit 16 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 controller 16 applies a predetermined differential pressure to the microchip 2 to flow blood through the microchip 2, while the TV camera 3 captures the blood flow in the obstacle channel 26A and the comparison channel 26B. .
- the personal computer 7 processes the captured image to calculate the blood characteristics of the obstacle channel 26A and the comparison channel 26B, the calculation result and the captured image itself are displayed on the display 8. At this time, the personal computer 7 calculates the difference between the blood characteristic in the obstacle channel 26A and the blood characteristic in the comparison channel 26B, thereby comparing the blood characteristics of the two and displaying the comparison result.
- the direction of blood flow is locally applied to the wall surface that defines only the obstacle channel 26A among the plurality of channels 26. Since a plurality of obstacles S to be changed are provided in the direction of blood flow, the shape of the flow path varies between the obstacle flow path 26A and the other comparison flow path 26B. Therefore, the blood characteristics can be accurately analyzed by comparing both a blood vessel without an obstacle and a blood vessel with an obstacle.
- the shapes of the obstacles S adjacent to each other in the blood flow direction are different from each other, the shapes of the obstacles S adjacent to each other in the blood flow direction are the same.
- blood characteristics can be analyzed by bringing the blood flow closer to the state in the blood vessel.
- the captured images in the obstacle flow path 26A and the comparison flow path 26B are analyzed and the blood characteristics are compared. For example, when a blood clot or atherosclerosis occurs in the blood vessel Analysis of blood characteristics can be performed.
- the TV camera 3 captures the blood flow in the plurality of obstacle channels 26A and the comparison channel 26B, the blood characteristics can be easily analyzed as compared with the case where only one of the channels is captured. Can do.
- the plurality of obstacles S in the first bank portion 214A and the second bank portion 214B are described as increasing from the upstream side to the downstream side in the blood flow direction (Y direction).
- it may be configured to decrease from the upstream side toward the downstream side. This is based on the assumption that the obstacle is large in the upstream direction of blood flow in the blood vessel state of the human body, and the state of the blood vessel in such a case can be analyzed.
- the shapes may be irregularly changed. This assumes a state in which the size of the obstacle is irregular in the blood flow direction in the state of the blood vessel of the human body, and the state of the blood vessel in such a case can be analyzed.
- each obstacle S may have a random shape. Also in this case, the same effect as the above embodiment can be obtained.
- the inner wall portion of the flow channel 26 has been described as having a uniform cross section in the blood flow direction (Y direction). However, as shown in FIG.
- the cross section may be widened or narrowed.
- the analysis can be performed assuming that the state of the blood vessel in the human body becomes wider from the upstream side in the blood flow direction toward the downstream side.
- the analysis is performed assuming that the state of the human blood vessel becomes narrow from the upstream side to the downstream side in the blood flow direction it can.
- blood characteristics can be analyzed by bringing the blood flow closer to the state in the blood vessel, and changes in the flow due to changes in the blood vessel width can be observed.
- the obstacle channel 26 ⁇ / b> A and the comparison channel 26 ⁇ / b> B are formed as the channels 26 interposed between the plurality of bank portions 214.
- the microchip 2 is provided with the obstacle channel 26 ⁇ / b> A.
- the type of the flow path is not limited to the comparison flow path 26B.
- a channel 26C in which the same type of obstacles (third obstacles) Sd having the same shape are provided on the wall surface at regular intervals is provided along with the obstacle channel 26A.
- the flow path 26C and the comparison flow path 26B may be provided together with the obstacle flow path 26A.
- each type of flow channel 26 is not a flow channel having a uniform cross-sectional shape, but is downstream from the upstream side in the blood flow direction, as shown in FIGS.
- a channel 26 (see FIG. 6B) whose cross section is wider (or narrower) toward the side
- a channel 26 (see FIG. 6D) whose cross section is circular
- any one of the flow paths 26 having a shape that becomes wider (or narrower) from the upstream side toward the downstream side may be used.
- the analysis can be performed on the assumption that a thrombus has occurred in the blood vessel, and the change in the flow due to the thrombus. Can be observed.
- the cross-sectional shape of the wall surface defining the flow path 26 is circular, the blood characteristics can be analyzed by bringing the blood flow closer to the state in the blood vessel.
- the blood characteristics may be calculated. In this case, analysis can be facilitated.
- the photographing by the TV camera 3 and the calculation of the blood characteristic are performed in parallel.
- a blood flow image is recorded in a recording means (not shown), and after all photographing is completed, the blood characteristic is recorded. May be calculated.
- the photographing conditions can be changed as necessary, and it becomes possible to more accurately grasp phenomena such as agglomeration.
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Abstract
Description
血液を通過させる複数の流路を備え、
これら複数の流路のうち、一部の流路のみの当該流路を画定する壁面には、血流の方向を局所的に変更する第1の障害物が血流方向に複数設けられており、
前記複数の第1の障害物のうち、前記血流方向に隣り合う障害物同士では、互いに形状が異なることを特徴とする。
血液を通過させる複数の流路を備え、
これら複数の流路のうち、一部の流路のみの当該流路を画定する壁面には、血流の方向を局所的に変更する第2の障害物が血流方向に複数設けられており、
前記複数の第2の障害物は、ランダムな形状を有することを特徴とする。
前記複数の流路のうち、前記一部の流路を除く他の一部の流路を画定する壁面には、血流の方向を局所的に変更する第3の障害物が血流方向に一定間隔で複数設けられており、
前記複数の第3の障害物は、互いに同一形状を有していることを特徴とする。
前記障害物は、流路の内部に突起して設けられていることを特徴とする。
前記複数の流路の内壁部は、血流方向の上流側から下流側に向かって断面が広くなる、或いは狭くなることを特徴とする。
前記複数の流路のうち、前記障害物の設けられていない流路を画定する壁面は、平坦に形成されていることを特徴とする。
前記複数の流路を画定する壁面は、断面が円形状であることを特徴とする。
請求項1~7の何れか一項に記載のマイクロチップと、
前記マイクロチップの前記複数の流路内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撮影画像を解析して血液特性を算出する解析手段と、
を備えることを特徴とする。
前記解析手段は、
前記複数の流路のうち、所定の流路における撮影画像を解析して、血液特性を算出することを特徴とする。
前記解析手段は、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける撮影画像をそれぞれ解析して、血液特性を比較することを特徴とする。
前記撮影手段は、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける血液の流れを撮影することを特徴とする。
前記マイクロチップの前記複数の流路内における血液の流れを撮影する撮影工程と、
前記撮影工程による撮影画像を解析して血液特性を算出する解析工程と、
を有することを特徴とする。
前記解析工程では、
前記複数の流路のうち、所定の流路における撮影画像を解析して、血液特性を算出することを特徴とする。
前記解析工程では、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける撮影画像をそれぞれ解析して、血液特性を比較することを特徴とする。
前記撮影工程では、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける血液の流れを撮影することを特徴とする。
2 マイクロチップ
3 TVカメラ(撮影手段)
26 流路
26A 障害物流路(一部の流路)
26B 比較流路(障害物の設けられていない流路)
26C 流路(他の一部の流路)
70 演算処理部(解析手段)
S 障害物(第1の障害物,第2の障害物)
Sd 同型障害物(第3の障害物)
Claims (15)
- 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、
血液を通過させる複数の流路を備え、
これら複数の流路のうち、一部の流路のみの当該流路を画定する壁面には、血流の方向を局所的に変更する第1の障害物が血流方向に複数設けられており、
前記複数の第1の障害物のうち、前記血流方向に隣り合う障害物同士では、互いに形状が異なることを特徴とするマイクロチップ。 - 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、
血液を通過させる複数の流路を備え、
これら複数の流路のうち、一部の流路のみの当該流路を画定する壁面には、血流の方向を局所的に変更する第2の障害物が血流方向に複数設けられており、
前記複数の第2の障害物は、ランダムな形状を有することを特徴とするマイクロチップ。 - 請求項1または2に記載のマイクロチップにおいて、
前記複数の流路のうち、前記一部の流路を除く他の一部の流路を画定する壁面には、血流の方向を局所的に変更する第3の障害物が血流方向に一定間隔で複数設けられており、
前記複数の第3の障害物は、互いに同一形状を有していることを特徴とするマイクロチップ。 - 請求項1~3の何れか一項に記載のマイクロチップにおいて、
前記障害物は、流路の内部に突起して設けられていることを特徴とするマイクロチップ。 - 請求項1~4の何れか一項に記載のマイクロチップにおいて、
前記複数の流路の内壁部は、血流方向の上流側から下流側に向かって断面が広くなる、或いは狭くなることを特徴とするマイクロチップ。 - 請求項1~5の何れか一項に記載のマイクロチップにおいて、
前記複数の流路のうち、前記障害物の設けられていない流路を画定する壁面は、平坦に形成されていることを特徴とするマイクロチップ。 - 請求項1~6の何れか一項に記載のマイクロチップにおいて、
前記複数の流路を画定する壁面は、断面が円形状であることを特徴とするマイクロチップ。 - 血液特性を計測する血液特性解析システムであって、
請求項1~7の何れか一項に記載のマイクロチップと、
前記マイクロチップの前記複数の流路内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撮影画像を解析して血液特性を算出する解析手段と、
を備えることを特徴とする血液特性解析システム。 - 請求項8記載の血液特性解析システムにおいて、
前記解析手段は、
前記複数の流路のうち、所定の流路における撮影画像を解析して、血液特性を算出することを特徴とする血液特性解析システム。 - 請求項8記載の血液特性解析システムにおいて、
前記解析手段は、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける撮影画像をそれぞれ解析して、血液特性を比較することを特徴とする血液特性解析システム。 - 請求項8~10の何れか一項に記載の血液特性解析システムにおいて、
前記撮影手段は、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける血液の流れを撮影することを特徴とする血液特性解析システム。 - 請求項1~7の何れか一項に記載のマイクロチップを用いて血液特性を解析する血液特性解析方法であって、
前記マイクロチップの前記複数の流路内における血液の流れを撮影する撮影工程と、
前記撮影工程による撮影画像を解析して血液特性を算出する解析工程と、
を有することを特徴とする血液特性解析方法。 - 請求項12記載の血液特性解析方法において、
前記解析工程では、
前記複数の流路のうち、所定の流路における撮影画像を解析して、血液特性を算出することを特徴とする血液特性解析方法。 - 請求項12記載の血液特性解析方法において、
前記解析工程では、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける撮影画像をそれぞれ解析して、血液特性を比較することを特徴とする血液特性解析方法。 - 請求項12~14の何れか一項に記載の血液特性解析方法において、
前記撮影工程では、
前記複数の流路のうち、前記一部の流路と、当該一部の流路以外の流路とにおける血液の流れを撮影することを特徴とする血液特性解析方法。
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US13/054,990 US20110124986A1 (en) | 2008-07-23 | 2009-07-06 | Microchip, Blood Analysis System and Blood Analysis Method |
JP2010521667A JP5182373B2 (ja) | 2008-07-23 | 2009-07-06 | マイクロチップ、血液特性解析システム及び血液特性解析方法 |
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JP2005092083A (ja) * | 2003-09-19 | 2005-04-07 | Shigeto Deki | 微細構造体の製造方法 |
JP2005265634A (ja) * | 2004-03-18 | 2005-09-29 | National Food Research Institute | 樹脂製マイクロチャネルアレイ及び製造方法及びこれを用いた血液測定方法 |
WO2007046450A1 (ja) * | 2005-10-18 | 2007-04-26 | Fujimori Kogyo Co., Ltd. | 血栓観測装置および血栓観測方法 |
US20080085551A1 (en) * | 2006-10-10 | 2008-04-10 | Postech Academy-Industry Foundation | Microfluidic biochip for blood typing based on agglutination reaction |
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US20020125192A1 (en) * | 2001-02-14 | 2002-09-12 | Lopez Gabriel P. | Nanostructured devices for separation and analysis |
JP2003215136A (ja) * | 2002-01-29 | 2003-07-30 | Kowa Spinning Co Ltd | 流体観察用プレート |
JP2005092083A (ja) * | 2003-09-19 | 2005-04-07 | Shigeto Deki | 微細構造体の製造方法 |
JP2005265634A (ja) * | 2004-03-18 | 2005-09-29 | National Food Research Institute | 樹脂製マイクロチャネルアレイ及び製造方法及びこれを用いた血液測定方法 |
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WO2012145833A1 (en) | 2011-04-27 | 2012-11-01 | Morega Systems Inc. | Adaptive video server with virtual file system and methods for use therewith |
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