WO2008053743A1 - Microchip and analyzer using the same - Google Patents
Microchip and analyzer using the same Download PDFInfo
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- WO2008053743A1 WO2008053743A1 PCT/JP2007/070603 JP2007070603W WO2008053743A1 WO 2008053743 A1 WO2008053743 A1 WO 2008053743A1 JP 2007070603 W JP2007070603 W JP 2007070603W WO 2008053743 A1 WO2008053743 A1 WO 2008053743A1
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- Prior art keywords
- capillary
- cavity
- capillary cavity
- sample liquid
- microchip
- Prior art date
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Classifications
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- 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
- B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0605—Metering of fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0621—Control of the sequence of chambers filled or emptied
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
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- 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
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- 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
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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- 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
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L9/00—Supporting devices; Holding devices
- B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
- B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
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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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00158—Elements containing microarrays, i.e. "biochip"
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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
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/04—Details of the conveyor system
- G01N2035/0439—Rotary sample carriers, i.e. carousels
- G01N2035/0446—Combinations of the above
- G01N2035/0449—Combinations of the above using centrifugal transport of liquid
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
Definitions
- the present invention relates to a microchip for electrochemically or optically analyzing a biological fluid.
- a biosensor for analyzing a specific component in a sample solution for example, in a dalcose in blood and a sensor.
- a blood glucose level or the like is obtained by measuring a current value obtained by a reaction with a reagent such as glucose oxidase supported on the carrier.
- microchip As an optical analysis method, a method of analysis using a microchip in which a liquid channel is formed is known.
- the microchip can control the fluid using a rotating device with a horizontal axis, and it uses centrifugal force to measure the sample liquid, separate the cytoplasmic material, transfer and distribute the separated fluid, Since mixing / stirring can be performed, various biochemical analyzes can be performed.
- FIG. 13 shows a portion of the distribution unit 400.
- the inlet port 409 is connected to the capillary cavity 404a via the upper portion 402.
- Capillary cavity 404a is connected to capillary cavity 404b via conduit portion 405a.
- the capillaries 404b, 404c, 404d, 404e, 404f are connected via the conduit portions 405b, 405c, 4 05d, 405e. ing.
- Capillary cavity 404f is connected to outlet port 410 via upper portion 403.
- the upper portion 402, the conduit portions 405a to 405e, and the upper portion 403 are provided with a force S of vent holes 406a to 406g.
- the sample entered from the inlet port 409 is transferred to the outlet port 410 by capillary force, and after filling each capillary cavity 404a to 404f with the sample solution, the respective capillary cavity 404a is caused by the centrifugal force generated by the rotation of this biosensor.
- Samples in ⁇ 404f are aerated and separated at positions 406a ⁇ 406g, passed through each Norebu 408a ⁇ 408f and each connected micro-duct 407a ⁇ 407f to the next processing chamber (not shown) Be transported.
- Patent Document 1 Japanese Patent Publication No. 4 504758
- Patent Document 2 Special Table 2004-No. 529333 Noriyuki
- the present invention solves the above-described conventional problems, and provides a microchip that can prevent air bubbles from being mixed into the capillary cavity and can collect a sample solution any number of times until the capillary cavity is satisfied.
- the purpose is to do.
- the microchip according to claim 1 of the present invention includes an injection port for collecting a sample solution, and at least one capillary cavity capable of collecting a certain amount of sample solution by capillary force through the injection port. , Communicated with the capillary cavity and rotated around the axis.
- a microchip having a holding chamber that receives the sample liquid in the capillary cavity that is transferred by the centrifugal force generated by the capillary force, and is connected to one side of the capillary cavity that connects the inlet and the holding chamber. It is characterized by the provision of a cavity that does not generate air and communicates with the atmosphere.
- the microchip according to claim 2 of the present invention includes a storage chamber for storing a sample liquid, at least one capillary cavity capable of collecting a constant amount of the sample liquid from the storage chamber by capillary force,
- a microchip including a holding chamber that communicates with the capillary cavity and receives a sample solution in the capillary cavity that is transferred by a centrifugal force generated by rotation around an axis. It is a special feature of the present invention to provide a cavity that communicates with the atmosphere without generating a capillary force on one side of the capillary cavity that connects the two.
- the microchip according to claim 3 of the present invention is the microchip according to claim 1 or 2, wherein the capillary cavity and the cavity have a rectangular cross-sectional shape, and the cavity has a cross-sectional dimension in the thickness direction.
- the cavity whose size is larger than the cross-sectional dimension of the capillary cavity is formed on one or both side surfaces of the capillary cavity.
- the microchip according to claim 4 of the present invention is the microchip according to claim 1 or 2, wherein a part of the cross-sectional shape of the capillary cavity has an arc shape, and the cross-sectional shape of the cavity is a rectangular shape. And the cavity whose cross-sectional dimension in the thickness direction of the cavity is larger than the cross-sectional dimension of the capillary cavity is formed on one or both side surfaces of the capillary cavity.
- the microchip according to claim 5 of the present invention is the microchip according to claim 3 or claim 4, wherein a cross-sectional dimension in the thickness direction of the cavity is 5011 m or more larger than the capillary cavity! / It is characterized by.
- the microchip according to claim 6 of the present invention is the microchip according to claim 1 or 2, wherein the capillary cavity and a part of the cross-sectional shape of the cavity have an arc shape, and the cavity is the capillary. It is formed on one or both sides of the cavity.
- the microchip according to claim 7 of the present invention is characterized in that in claim 1 or claim 2, the wall surface of the cavity is a hydrophobic surface.
- the microchip according to claim 8 of the present invention is capable of collecting a certain amount of sample liquid by capillary force through the inlet through which the sample liquid is collected and the inlet through the inlet.
- a first capillary cavity capable of communicating with the outer peripheral end of the first capillary cavity and receiving a sample liquid in the first capillary cavity that is transferred by a centrifugal force generated by rotation around an axis.
- a second capillary cavity communicating with the first capillary cavity and capable of collecting a predetermined amount of sample liquid by capillary force via the first capillary cavity;
- a second pipe that communicates with the outer peripheral end of the second capillary cavity and receives the sample liquid in the second capillary cavity that is transferred by centrifugal force generated by rotation around the axis.
- a holding chamber that has a cavity communicating with the atmosphere without generating a capillary force on one side of the first capillary cavity and the second capillary cavity.
- the boundary between the capillary cavity and the second capillary cavity has a curved shape that is located on the inner peripheral side of the first holding chamber and the second holding chamber and protrudes in the inner peripheral direction. And it has a wall surface in the outer peripheral side of the said boundary part, It is characterized by the above-mentioned.
- the microchip according to claim 9 of the present invention is capable of collecting a certain amount of sample liquid by capillary force through the inlet through which the sample liquid is collected and the inlet through the inlet.
- a first capillary cavity capable of communicating with the outer peripheral end of the first capillary cavity and receiving a sample liquid in the first capillary cavity that is transferred by a centrifugal force generated by rotation around an axis.
- a holding chamber a second capillary cavity that communicates with the first capillary cavity and can collect a predetermined amount of sample liquid by capillary force via the first capillary cavity; and the second capillary cavity.
- a second container for receiving the sample liquid in the second capillary cavity which is communicated with the outer peripheral end of the capillary capillary and is transferred by centrifugal force generated by rotation around the axis.
- N— 2 holding chambers for receiving the sample liquid in the N-2 capillary cavities to be sent respectively, and the first capillary cavity, the second capillary cavity, and the second capillary tube
- One side surface of the N-2 capillary cavities formed continuously from the cavity to the Nth capillary cavity has a cavity that communicates with the atmosphere without generating a capillary force.
- the boundary between the capillary cavity and the second capillary cavity has a curved shape that is located on the inner peripheral side of the first holding chamber 1 and the second holding chamber and protrudes in the inner peripheral direction.
- the N ⁇ 2 boundary portions of the N ⁇ 2 capillary cavities formed in sequence from the second capillary cavity to the Nth capillary cavity are connected to the second holding channel.
- N ⁇ from the first bar to the Nth holding chamber 1 have curved shapes that are located on the inner peripheral side of the two holding chambers 1 and project in the inner peripheral direction. It is characterized by having a wall surface on the outer peripheral side of the N ⁇ 1 boundary part up to the N ⁇ 1 boundary part.
- the microchip according to claim 10 of the present invention is capable of collecting a predetermined amount of sample liquid from the storage chamber by a capillary force in communication with the storage chamber storing the sample liquid and the storage chamber.
- the fourth capillary cavity communicates with the outer peripheral end of the fourth capillary cavity and receives the sample liquid in the fourth capillary cavity that is transferred by the centrifugal force generated by the rotation around the axis.
- a fifth capillary cavity communicating with the fourth capillary cavity and capable of collecting a certain amount of sample liquid by capillary force via the fourth capillary cavity; 5th holding
- maintenance which receives the sample liquid in the said 2nd capillary cavity which is connected with the outer peripheral edge part of 5 capillary capillary, and is transferred by the centrifugal force generated by the rotation around an axial center And a cavity communicating with the atmosphere without generating a capillary force is provided on one side surface of the fourth capillary cavity and the fifth capillary cavity, and the fourth capillary cavity and the fifth capillary cavity are provided with the fifth capillary cavity and the fifth capillary cavity.
- the boundary with the capillary cavity has a curved shape protruding in the inner peripheral direction at a position on the inner peripheral side with respect to the storage chamber and the fourth holding chamber, and a wall surface on the outer peripheral side of the boundary It is characterized by having.
- the microchip according to claim 11 of the present invention is capable of collecting a certain amount of sample liquid from the storage chamber by a capillary force in communication with the storage chamber for storing the sample liquid and the storage chamber.
- the second capillary cavity communicates with the outer peripheral end of the second capillary cavity and receives the sample liquid in the second capillary cavity that is transferred by the centrifugal force generated by the rotation around the axis.
- a second holding chamber a third capillary cavity that communicates with the second capillary cavity and can collect a certain amount of sample liquid by capillary force via the second capillary cavity; and A third holding chamber that communicates with the outer peripheral end of the third capillary cavity and receives the sample liquid in the third capillary cavity that is transferred by centrifugal force generated by rotation around the axis; N—2 capillary cavities formed in sequence from 3 capillary cavities to Nth (N is a positive integer greater than or equal to 3) capillary cavities, and the N ⁇ 2 An N-2 holding chamber that communicates with the outer periphery of the capillary cavity and receives the sample liquid in the N-2 capillary cavities respectively transferred by the centrifugal force generated by rotation around the axis.
- One side surface of the N-2 capillary cavities formed from the second capillary cavity, the third capillary cavity, and the third capillary cavity to the Nth capillary cavity continuously.
- Each of which has a cavity communicating with the atmosphere without generating a capillary force, and a second boundary between the second capillary cavity and the third capillary cavity is formed by the second capillary cavity and the second capillary cavity.
- each has a curved shape protruding in the inner circumferential direction at a position on the inner peripheral side with respect to the third capillary cavity, and sequentially from the third capillary cavity, the Nth
- the N—2 boundary portion of the two capillary cavities formed up to the capillary cavity is more than the N—two holding chambers from the third holding chamber one to the Nth holding chamber one.
- Each has a curved shape protruding in the inner circumferential direction at a position on the inner circumferential side, and a wall surface is disposed on the outer circumferential side of the N-1 boundary portions from the second boundary portion to the N-1 boundary portion. It is characterized by having.
- An analyzer according to claim 12 of the present invention is an analyzer to which the microchip according to claim 1 is attached, and holds the microchip in a state where its injection port faces the axial center side.
- a rotation driving means for rotating the sample around the sample chamber, and a sample liquid collected from the inlet by the rotation driving means and held in the capillary cavity is transferred to the holding chamber, and then the sample in the holding chamber.
- An analysis means for analyzing the liquid, and the capillary cavity is filled from the inlet of the microchip. After the sample solution is collected in step (b), the sample solution in the capillary cavity is removed by the centrifugal force generated by the rotation of the microchip by the rotation driving means, and the capillary cavity and the cavity not containing the sample solution are removed. It is configured to be transferred to the holding chamber via.
- the analysis device is an analysis device to which the microchip according to claim 2 is mounted, wherein the rotation drive means for rotating the microchip about an axis, and the rotation Analysis means for analyzing the sample liquid in the holding chamber after the sample liquid collected from the storage chamber by the driving means and held in the capillary cavity is transferred to the holding chamber. After collecting the sample liquid from the chamber until the capillary cavity is filled, the sample liquid in the capillary cavity is removed from the capillary cavity by the centrifugal force generated by the rotation of the microchip by the rotation driving means. It is characterized in that it is configured such that liquid enters and is transferred to the holding chamber 1 via the cavity.
- the microchip of the present invention it is possible to prevent air bubbles from being mixed into the capillary cavity for collecting the sample liquid, and therefore it is possible to collect the sample liquid as many times as necessary until the capillary cavity is satisfied. . Therefore, since measurement errors due to insufficient sampling of the sample liquid can be eliminated, the measurement accuracy of the microchip can be improved.
- FIG. 1 is an external view of a microchip according to a first embodiment of the present invention.
- FIG. 2 is an exploded perspective view of the microchip in the same embodiment.
- FIG. 3 is an external perspective view when mounted on a microchip holding member in the same embodiment.
- FIG. 4 is an enlarged perspective view showing the periphery of the injection port in the same embodiment.
- FIG. 5 is a block diagram of the analyzer according to the embodiment.
- FIG. 6 is a plan view showing the microchannel configuration of the same embodiment
- FIG. 7 Explanatory diagram of “sample solution injection process” to “measuring chamber filling process” in the same embodiment.
- FIG. 8 The capillary cavity and the cross-sectional shape of the cavity in the microchip of the first embodiment of the present invention are shown.
- Illustration FIG. 9 is a plan view of the microchip according to the second embodiment of the present invention.
- FIG. 11 Enlarged view explaining the “sample liquid distribution process” in the same embodiment
- FIG. 1 shows the microchip 3 in an external view.
- FIG. 2 is an exploded perspective view showing the configuration of the microchip 3.
- the microchip 3 is formed by bonding the upper substrate 1 and the lower substrate 2, and a microchannel structure having fine irregularities is formed on one surface of the lower substrate 2, and the sample liquid Each function works such as transporting and maintaining a predetermined amount of liquid.
- FIG. 3 is an external perspective view showing a state in which the microchip 3 is mounted on the microchip holding member 101.
- One microchip 3 is mounted on the microchip holding member 101, and the analyzer ( The microchip holding member 101 and the microchip 3 are rotated in a predetermined direction of the shaft center 11 by the rotation driving means on the side (not shown).
- FIG. 4 is an enlarged view showing the periphery of the inlet 14 of the microchip 3.
- the inlet 14 protrudes in the direction of the axis 11 from one side surface of the microchip body.
- the recess 12 is gently curved so that the sectional area force of the opening on the axial center side of the recess is equal to or larger than the sectional area of the opening on the outer peripheral side of the recess.
- FIG. 5 is a schematic diagram showing a configuration of an analyzer 1000 to which the microchip 3 of Embodiment 1 is attached.
- the present microchip 3 is mounted on the upper part of the microchip holding member 101 mounted on the rotating shaft of the motor 102 which is the rotational driving means of the analyzer 1000, and the motor 102 is driven to rotate.
- the microchip holding member 101 to which the microchip 3 is attached can be driven to rotate around the axis.
- This analyzer transfers the liquid in the microchip by using the centrifugal force generated by the rotation around the axis by the configuration of the chamber and the flow path in the microchip 3 depending on the application. Or a centrifuge that centrifuges.
- the force for attaching the microphone tip 3 to the analyzer 1000 may have a fan shape, a cube shape, or other shapes.
- a plurality of microchips 3 may be mounted on the analyzer 1000 at the same time.
- the laser light from the laser light source 103 is attached to the microchip holding member 101 of the analyzer 1000 while the microchip holding member 101 is driven to rotate in the C direction by the motor 102. Irradiate towards the microchip.
- the laser light source 103 is screwed into a feed screw 105 driven by a traverse motor 104, and the servo control circuit 106 drives the traverse motor 104 so that the laser light source 103 can be placed at an arbitrary measurement location.
- the laser light source 103 can be moved in the radial direction of the microchip holding member 101.
- a photo detector (PD) 107 that detects the amount of transmitted light that has passed through the micro chip holding member 101 out of the laser light emitted from the laser light source 103, and a photo detector (PD ) Adjustment circuit to adjust the output gain of 107 10
- a / D converter 109 that digitally converts the output of the adjustment circuit 108, a transmitted light signal processing circuit 110 that processes data digitally converted by the A / D converter 109, and a transmitted light signal processing circuit 110 It has a memory 113 for storing data, a microcomputer (CPU) 111 for controlling them, and a display unit 112 for displaying the analyzed results.
- the optical scanning technique for the optical disc is not particularly used.
- the area in which the position information is recorded on the microchip 3 is used.
- a tracking actuator (not shown) provided inside the laser light source 103 that is driven only by the traverse motor 104, the optical path of the laser light is combined with the surface direction of the microchip as necessary. It may be configured such that the microchip tracks can be accurately traced while being driven and controlled in position.
- FIG. 6 is a plan view showing the microchannel configuration of the microchip of the first embodiment.
- FIG. 7 is a diagram for explaining the “filling process of the measurement chamber” from the “microchip sample solution injection process” according to the first embodiment.
- FIGS. 8 (a) to 8 (d) show examples of the cross-sectional shapes of the capillary cavity and cavity in the microchip, respectively, and FIG. 8 (a) shows the capillary cavity 4 and cavity 15 and 16 of the same embodiment.
- FIG. 8 (b) is a cross-sectional view when the cross-sectional shape is a rectangular shape
- FIG. 8 (b) is a cross-sectional view when the cross-sectional shapes of the capillary cavities 4 and 15 of the embodiment are arc-shaped
- Fig. 8 (c) is the same embodiment.
- Fig. 8 (d) is a cross-sectional view when the cross-sectional shape of the capillary cavity 4 is an arc shape and the cross-sectional shape of the cavity 15 is a rectangular shape.
- Fig. 8 (e) shows a cross-sectional view of the shape and shape of the capillaries with the same thickness.
- Fig. 8 (e) shows that the capillaries 4 and 15 and 16 of the same embodiment have a rectangular cross-section, and the capillaries 15 and 16 have a thickness of capillaries.
- Section when greater than 4 FIG 8 (f) are cross-sectional shape of the capillary Kiyabi tee 4 and Kiyabiti 15 of the embodiment is an arc shape, size les than a thickness of the capillary key Yabiti 4 Kiyabiti 15 is a cross-sectional view of.
- the microchannel configuration of the microchip 3 of Embodiment 1 is An inlet 14 for collecting the sample liquid, a capillary cavity 4 for holding a predetermined amount of the sample liquid injected into the inlet 14, cavities 15 and 16 for discharging the air in the capillary cavity 4, and an analysis reagent (not shown) 1), a measurement chamber 7 for measuring the mixture of the sample solution and the analysis reagent, a flow path 6 communicating with the retention chamber 5 and the measurement chamber 7, and a measurement chamber 1 and a flow path 8 communicating with the air opening hole 9.
- the capillary cavity 4, the flow path 6, and the flow path 8 have a depth of 50 m to 300.
- the sample liquid flows with a capillary force, it is not limited to this dimension. Absent. Also, the depth of the holding chamber 5, the measurement cell 7, and the cavities 15, 16 is 0.3 mm to 5 mm. This is due to the amount of sample solution and the conditions for measuring the absorbance (optical path length, It can be adjusted by measuring wavelength, sample solution reaction concentration, reagent type, and the like.
- the wall surfaces of the capillary cavities 4, the flow paths 6, and the flow paths 8 are subjected to hydrophilic treatment, and the hydrophilic treatment methods include plasma and corona.
- the hydrophilic treatment methods include plasma and corona.
- hydrophilic means that the contact angle with water is less than 90 °, more preferably less than 40 °.
- the microchip 3 is detached from the microchip holding member 101 and protrudes in the direction of the axis 11 from one side surface of the microchip 3.
- the sample liquid is spotted on the injection port 14, the sample liquid is injected into the capillary cavity 4 by a capillary phenomenon as shown in FIG. 7 (a) immediately after the spotting.
- the sample liquid is a capillary that flows through the side surface of the capillary cavity 4 in advance.
- the center of the capillary cavity 4 becomes a capillary stream that flows in advance, and the capillary cavity 4 is filled. Therefore, even if the sample liquid to be spotted at the inlet 14 is insufficient during the filling of the capillary cavity 4 or the sample liquid is separated from the inlet 14 during the filling, it is spotted again from the inlet. In this way, the sample solution flows in the center of the capillary cavity 4 first, so it is held in the capillary cavity.
- the capillary cavity 4 and the cavity 15 and 16 have a cross section in the thickness direction on one or both sides of the rectangular capillary cavity 4 formed on the lower substrate.
- a configuration in which arc-shaped cavities 15 and 16 are provided, as shown in FIG. 8 (c) the cross-sectional dimension in the thickness direction is capillary cavity 4 on one or both sides of the arc-shaped capillary cavity 4 formed on the lower substrate.
- FIG. 8 A configuration in which rectangular cavities 15 and 16 are provided that are larger than the cross-sectional dimension of Fig. 8 (d), and one side or both sides of an arcuate capillary cavity 4 formed on the lower substrate as shown in Fig. 8 (d)
- the capillary cavity 4 and rectangular cavity 15 and 16 having the same cross-sectional dimension in the thickness direction are provided, and the walls of the cavities 15 and 16 have a hydrophobic surface or a hydrophobic treatment (the contact angle with water is 9 as the standard for hydrophobicity). 0 ° or more is desirable, but 70 ° or more may also be applied), as shown in FIG.
- the cross-sectional dimensions of the cavities 15 and 16 in the thickness direction should be 50 m or more larger than the cross-sectional dimensions of the capillary cavity 4 Thus, the sample solution can be prevented from flowing into the cavities 15 and 16.
- the upper substrate 1 must be rigid to maintain the cross-sectional dimension in the thickness direction of the capillary cavity.
- the distance from the surface of the substrate 1 to the cavities 15 and 16 is preferably about 0.5 to 1 mm.
- Hydrophilic treatment applies hydrophilic treatment to the walls of other cavities 15, 16, etc., where it is desirable to use only the wall of capillary cavity 4. Otherwise, the sample solution will flow into the cavity.
- the microchip 3 is attached to the analyzer 1000, and the microchip 3 is rotated by the rotation driving means of the analyzer 1000, as shown in Fig. 7 (b).
- the sample solution in the capillary cavity 4 is transferred by centrifugal force into the holding chamber 15 where the analysis reagent is previously supported.
- the sample liquid that has flowed into the holding chamber 5 is mixed with the analysis reagent carried in the holding chamber 15 by swinging due to the rotation acceleration of the analyzer 1000 or by diffusion of the liquid while the rotation is stopped. However, it is also possible to mix by applying an external force that directly vibrates the holding chamber 15 itself.
- the sample liquid in the channel 6 is transferred into the measurement chamber 7 by the rotation of the analyzer, and the analyzer 1000 reacts the sample liquid with the analysis reagent.
- the concentration of the component can be measured.
- FIG. 9 is a plan view showing a microchannel configuration of the microchip of the second embodiment.
- FIG. 10 is a diagram for explaining the “filling process of the measurement chamber” from the “microchip sample solution injection process” to the second embodiment.
- FIG. 11 is an enlarged view for explaining the “sample solution distribution process of the microphone port chip” according to the second embodiment of the present invention.
- the microchannel configuration of the microchip 3 of Embodiment 2 holds the injection port 14 for collecting the sample solution and a predetermined amount of the sample solution injected into the injection port 14.
- the first capillary cavity 17, the second capillary cavity 19 that holds a predetermined amount of sample solution via the first capillary cavity 17, and the predetermined amount of sample liquid via the second capillary cavity 19 Only the third capillary cavity 21 that holds the sample, the cavity 15 and 16 that discharges the air inside the capillary cavity 17 and 19, and the sample liquid in the first capillary cavity 17 that receives the sample liquid and contains the solid solution
- the storage chamber for separating the solution component and the solid component into the holding chamber 5 as the first holding chamber 5 and the sample solution in the second capillary cavity 19 are received, and the ratio of the solution component to the solid component in the sample solution is determined.
- Submerged Measurement chamber 25 as a third holding chamber 1 for performing minute measurement, and a fourth capillary for holding a predetermined amount of solution components of the sample solution separated in the holding chamber 5 via the flow path 26
- the tube capillary 28, the fifth capillary cavity 30 that retains a predetermined amount of the solution components via the fourth capillary cavity 28, and the sample liquid in the fourth capillary cavity 28 are received, and the sample liquid and Measurement chamber 34 as the fourth holding chamber for measuring the mixture with the analytical reagent and the fifth holding for receiving the sample liquid in the fifth capillary cavity 30 and measuring the mixture of the sample liquid and the analytical reagent
- a measurement chamber 38 as a chamber, a valve 31 communicating with the end of the fourth capillary cavity 28, a flow path 33 communicating with the measurement chamber 34, a measurement chamber 34, and an air release hole 36 are
- the depth of the channel 33, the channel 35, the channel 37, and the channel 39 is 50 ⁇ m to 300 ⁇ m, but if the sample liquid flows by capillary force, it is limited to this dimension. It is not a thing.
- the depth of the holding chamber 1, the measuring cell 7, the diluent storage chamber 23, the cavities 15, 16, the measuring chamber 25, the valves 31, 32, the measuring chamber 36, and the measuring chamber 38 is 0. It is formed from 3mm to 5mm. It can be adjusted according to the conditions for measuring the degree of measurement (optical path length, measurement wavelength, sample solution reaction concentration, reagent type, etc.).
- the 4th capillary cavity 28, the 5th capillary cavity 30, the flow path 33, the flow path 35, the flow path 37, and the flow path 39 are subjected to hydrophilic treatment, and the hydrophilic treatment methods include plasma, corona, A surface treatment method using an active gas such as ozone or fluorine, or a surface treatment using a surfactant or a hydrophilic polymer can be mentioned.
- hydrophilic means that the contact angle with water is less than 90 °, more preferably less than 40 °.
- the microchip 3 is removed from the microchip holding member 101, and the axis 11 is formed from one side surface of the microchip 3.
- the sample solution is spotted on the inlet 14 projecting in the direction, immediately after the spotting, the sample solution is injected into the first capillary cavity 17 by a predetermined amount by capillary action as shown in FIG.
- a predetermined amount is injected into the second capillary cavity 19 through the first capillary cavity 17 and further into the third capillary cavity 21 through the second capillary cavity 19. Only injected.
- the both sides of the first capillary cavity 17, the second capillary cavity 19, and the side surfaces in the inner circumferential direction of the third capillary cavity 21 are provided in the respective capillary cavities. Since the cavities 15 and 16 for exhausting air are provided, the sample liquid becomes a capillary flow that precedes the central part of the capillary cavity where the side part of the capillary cavity flows first. Fill the capillary cavity.
- the inlet is again introduced. Since the sample liquid flows first through the center of the capillary cavity, it comes into contact with the center of the sample liquid held in the capillary cavity, and the air is placed on the side where the cavities 15 and 16 are located. Since it is filled while discharging in the direction, bubbles do not occur and each capillary cavity can be spotted repeatedly until it can hold a predetermined amount of sample liquid. Is possible.
- the microchip 3 is attached to the analyzer 1000, and the microchip 3 is rotated by the rotation driving means of the analyzer 1000, thereby rotating the inlet by centrifugal force as shown in Fig. 10 (b).
- the sample liquid in the first capillary cavity 17 held between 14 and the first distribution position 18 as the boundary is broken at the first distribution position 18 and transferred to the holding chamber 5.
- the sample liquid in the second capillary cavity 19 is held between the first distribution position 18 and the second distribution position 20 as a boundary! /.
- the second distribution position 20, which is the boundary with the cavity 21 has a curved shape projecting in the inner peripheral direction at a position on the inner peripheral side of the holding chamber 5, the measurement chamber 7, and the measurement chamber 25.
- the first capillary cavity 17, the second capillary cavity 19, and the third capillary cavity 21 are provided with cavities 15 and 16, each capillary cavity is caused by centrifugal force.
- FIG. 14 (a), 14 (b), and 14 (c) show the A-A 'and C-C' lines shown in Fig. 9, respectively. , Shows a cross-sectional view along the DD line.
- the first distribution position 18 as the boundary between the first capillary cavity 17 and the second capillary cavity 19 is located on the inner periphery of the holding chamber 5 and the measurement chamber 7 as the second holding chamber 7. It has a curved shape located on the side and protruding in the inner circumferential direction, and has a wall surface B1 on the outer circumferential side.
- the second distribution position 20 as the boundary portion of the third capillary cavity 21 formed successively from the measurement chamber 7 as the holding chamber 1 is the holding chamber 5 and the second
- the measuring chamber 17 as the holding chamber 1 has a curved shape that is located on the inner peripheral side and protrudes in the inner peripheral direction, and has a wall surface B2 on the outer peripheral side.
- the sample liquid in the capillary cavity when distributed, it can be distributed without generating a pressure difference between the capillary cavities and a siphon effect. Accuracy can be improved.
- the number of sample liquid distributions can be adjusted according to the number of measurement items.
- N distributions are required, N capillary cavities are provided and mixed into each capillary cavity.
- the present invention is not limited to the contents described in the second embodiment.
- the first capillary cavity 17 that communicates with the inlet 14 is changed from one place.
- the force that fills the capillary cavity continuously in the direction of the sample liquid Fill the sample liquid with the capillary cavity continuously from both the first capillary cavity 17 in both the left and right directions from two or more locations. Les.
- the sample liquid that has flowed into the holding chamber 5 and the measurement chamber 7 is separated into a solution component and a solid component by centrifugal force.
- the sample liquid and the diluted liquid flowing into the measurement chamber 25 are mixed by the oscillation due to the rotation acceleration of the analyzer 1000 and the diffusion of the liquid while the rotation is stopped. It is also possible to mix by applying such external force.
- a valve 32 having a cross-sectional dimension in the thickness direction larger than that of the fourth capillary cavity 28 is provided, and flows into the fourth capillary cavity 28. Capillary flow of the sample solution is stopped at valve 32.
- a valve 33 having a cross-sectional dimension in the thickness direction larger than that of the fifth capillary cavity 30 is provided at the end of the fifth capillary cavity 30 and is introduced into the fifth capillary cavity 30. Capillary flow of the sample solution is stopped at valve 33.
- a cavity 16 for discharging the air in each capillary cavity is provided on the inner circumferential side surface of the fourth capillary cavity 28 and the fifth capillary cavity 30! /
- the sample liquid becomes a capillary flow in which the side surface portion on the outer peripheral side of the capillary cavity flows first, and fills the inside of each capillary cavity. Therefore, as the sample liquid is filled from the holding chamber 5 into the capillary cavities, air is exhausted in the direction of the side surface on the inner circumference side where the cavities 16 are located, so that bubbles are formed in the capillary cavities. It does not occur, and each capillary cavity can be filled with the sample solution.
- the microchip 3 is rotated by the rotation driving means of the analyzer 1000, as shown in FIG. 10 (d).
- the sample liquid in the fourth capillary cavity 28 held between the third distribution position 27 and the fourth distribution position 29 as a boundary portion by the centrifugal force at the third distribution position 27, And the fourth distribution position 29 is broken, transferred to the measurement chamber 34 via the valve 32 and the flow path 33, and further held between the fourth distribution position 29 and the valve 32.
- the sample liquid in the capillary cavity 30 is broken at the fourth distribution position 29 and transferred to the measurement chamber 38 via the valve 33 and the flow path 37.
- the third distribution position 27 that is the boundary between the flow path 26 and the fourth capillary cavity 28, the fourth capillary cavity 28, and the fifth capillary cavity 30
- the fourth distribution position 29, which is the boundary has a curved shape protruding in the inner peripheral direction at a position on the inner peripheral side of the measurement chamber 34 and the measurement chamber 38, and further includes a fourth distribution position 29. Since the cavity 16 is provided on the side of the capillary cavity 28 and the fifth capillary cavity 30, the third distribution position 27 is used when the sample liquid in each capillary cavity is transferred to the outer circumference by centrifugal force. Since the centrifugal force acts on the sample liquid from the innermost peripheral position of the fourth distribution position 29 and the sample liquid is broken, a pressure difference between the capillary cavities and a siphon effect are generated. , Each sample solution can be accurately distributed .
- the number of sample liquid distributions can be adjusted according to the number of measurement items.
- N distributions are necessary, N capillary cavities are provided and mixed into the respective capillary cavities. Since the chamber 1 and the holding chamber 1 such as the measurement chamber can be communicated with each other, the contents are not limited to those described in the second embodiment.
- the force S for filling the capillary cavity continuous in one direction from one location of the holding chamber 15 with the sample solution S, and the left and right from two or more locations of the holding chamber 15.
- the capillary cavity may be continued in both directions to fill the sample solution.
- the sample solution transferred to the measurement chamber 34 and the measurement chamber 38 is measured by measuring the absorbance of the reaction state between the sample solution and the analysis reagent by a measuring instrument (not shown) attached to the analyzer.
- the concentration of the component can be measured by measuring by, for example.
- the sample liquid is blood
- the hematocrit value ratio of plasma to blood cells
- the concentration of hemoglobin contained in the red blood cells is measured with the measurement chamber 25. Measurement can be performed using plasma in which lipid components such as glucose and cholesterol contained in plasma are separated in a holding chamber 5.
- the microchip which is effective in the present invention, prevents the bubbles from being mixed into the capillary cavity for collecting the sample liquid, and allows the sample liquid to be collected any number of times until the capillary cavity is satisfied.
- Sample liquid collection method and distribution transfer method in a microphone mouth chip that has the effect of improving the distribution accuracy of the sample liquid and is used for the measurement of components of biological fluids with an electrochemical sensor or an optical sensor. Useful as such.
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Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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US12/447,564 US8512638B2 (en) | 2006-10-31 | 2007-10-23 | Microchip and analyzer using the same |
JP2008542054A JP5247460B2 (ja) | 2006-10-31 | 2007-10-23 | マイクロチップ |
EP07830337.7A EP2096444B1 (en) | 2006-10-31 | 2007-10-23 | Microchip and analyzer using the same |
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JP2006295159 | 2006-10-31 | ||
JP2006-295159 | 2006-10-31 |
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PCT/JP2007/070603 WO2008053743A1 (en) | 2006-10-31 | 2007-10-23 | Microchip and analyzer using the same |
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US (1) | US8512638B2 (ja) |
EP (1) | EP2096444B1 (ja) |
JP (1) | JP5247460B2 (ja) |
WO (1) | WO2008053743A1 (ja) |
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JP2019537033A (ja) * | 2016-10-24 | 2019-12-19 | エンティア リミテッド | キュベット |
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Also Published As
Publication number | Publication date |
---|---|
JP5247460B2 (ja) | 2013-07-24 |
US8512638B2 (en) | 2013-08-20 |
EP2096444A1 (en) | 2009-09-02 |
EP2096444A4 (en) | 2010-07-07 |
US20100074801A1 (en) | 2010-03-25 |
EP2096444B1 (en) | 2016-12-07 |
JPWO2008053743A1 (ja) | 2010-02-25 |
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