WO2006109397A1 - 逆流防止構造、それを用いた検査用マイクロチップおよび検査装置 - Google Patents
逆流防止構造、それを用いた検査用マイクロチップおよび検査装置 Download PDFInfo
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- WO2006109397A1 WO2006109397A1 PCT/JP2006/305109 JP2006305109W WO2006109397A1 WO 2006109397 A1 WO2006109397 A1 WO 2006109397A1 JP 2006305109 W JP2006305109 W JP 2006305109W WO 2006109397 A1 WO2006109397 A1 WO 2006109397A1
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- flow path
- backflow prevention
- reagent
- inspection
- channel
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
- F16K99/0005—Lift valves
- F16K99/0007—Lift valves of cantilever type
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/40—Static mixers
- B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
- B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
- B01F25/433—Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/40—Static mixers
- B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
- B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
- B01F25/433—Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
- B01F25/4331—Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
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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
- B01L3/502738—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 integrated valves
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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
- B01L3/502746—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
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
- F16K99/0017—Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
- F16K99/0023—Constructional types of microvalves; Details of the cutting-off member with ball-shaped valve members
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0036—Operating means specially adapted for microvalves operated by temperature variations
- F16K99/0038—Operating means specially adapted for microvalves operated by temperature variations using shape memory alloys
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0042—Electric operating means therefor
- F16K99/0044—Electric operating means therefor using thermo-electric means
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0042—Electric operating means therefor
- F16K99/0048—Electric operating means therefor using piezoelectric means
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0055—Operating means specially adapted for microvalves actuated by fluids
- F16K99/0057—Operating means specially adapted for microvalves actuated by fluids the fluid being the circulating fluid itself, e.g. check valves
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K99/0001—Microvalves
- F16K99/0034—Operating means specially adapted for microvalves
- F16K99/0055—Operating means specially adapted for microvalves actuated by fluids
- F16K99/0059—Operating means specially adapted for microvalves actuated by fluids actuated by a pilot fluid
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
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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
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
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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
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0605—Valves, specific forms thereof check valves
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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
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
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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
- B01L3/50273—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 or forces applied to move the fluids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2201/00—Properties
- C08L2201/12—Shape memory
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K2099/0073—Fabrication methods specifically adapted for microvalves
- F16K2099/008—Multi-layer fabrications
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K99/00—Subject matter not provided for in other groups of this subclass
- F16K2099/0082—Microvalves adapted for a particular use
- F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology
Definitions
- the present invention relates to a testing microchip that can be used as a microreactor in genetic testing or the like, and a testing device using the same.
- Such a system is also called ⁇ -TAS (Micro total Analysis System), bioreactor, lab “on-chips”, or biochip. Its application is expected in fields such as agricultural production.
- ⁇ -TAS Micro total Analysis System
- bioreactor Bioreactor
- lab on-chips
- biochip biochip
- the present inventors have stored a sample storage unit that stores a sample, a reagent storage unit that stores a reagent, and a sample storage unit.
- a specimen and a reagent housed in the reagent housing part are joined together to perform a predetermined test on a reaction part having a reaction channel for performing a predetermined reaction process, and a reaction processing substance obtained by the reaction of the reaction part.
- the specimen storage section, the reagent storage section, the reaction section, and the test section are continuous channels that continuously flow from the upstream side to the downstream side.
- Patent Document 3 Japanese Patent Application No. 2004-138959
- This backflow prevention part is a check valve in which the valve body closes the flow path opening by backflow pressure, or an active valve that closes the opening by pressing the valve body to the flow path opening by the valve body deforming means. It is made up of things.
- the microsphere 167 is used as a valve body, and the opening 168 formed in the substrate 162 is opened and closed by the movement of the microsphere 167, thereby allowing the liquid to flow. Allow and block passage.
- the microsphere 167 is separated from the substrate 162 by the liquid pressure and the opening 168 is opened, so that the passage of the liquid is allowed.
- the microsphere 167 is seated on the substrate 162 and the opening 168 is closed, so that the passage of the liquid is blocked.
- the flexible substrate 169 which is laminated on the substrate 162 and whose end extends to the upper side of the opening 168, is formed above the opening 168 by hydraulic pressure.
- the opening 168 is opened and closed by moving up and down.
- the end of the flexible substrate 169 is separated from the substrate 162 by the hydraulic pressure, and the opening 168 is opened. Permissible .
- the flexible substrate 169 comes into close contact with the substrate 162 and the opening 68 is closed, so that the passage of the liquid is blocked.
- a flexible substrate 163 having a valve portion 164 protruding downward is laminated on a substrate 162 having an opening 165 formed thereon.
- a valve body deforming means such as a pneumatic piston, a hydraulic piston, a piezoelectric piston, a shape memory alloy actuator, etc.
- the valve portion 164 is tightly attached to the substrate 162 so as to cover the opening 165, thereby blocking back flow in the B direction.
- the active valve is not limited to one that is operated by an external driving device, and a configuration in which the valve body is deformed by itself to close the flow path, for example, as shown in FIG.
- a structure that is deformed by energizing heating using 181 is disclosed, and a structure that is deformed by energizing heating using shape memory alloy 182 is disclosed, as shown in FIG.
- the microsphere 167 needs to be a valve body, the opening 168 must be formed in the flow path, and the microsphere 167 must be disposed.
- the structure is complicated, the manufacturing process is complicated, and the cost is high.
- the flexible substrate 169 that is laminated on the substrate 162 and whose end extends to the upper side of the opening 168 must be configured.
- the configuration is complicated, the manufacturing process is complicated, and the cost is high.
- a flexible substrate 163 having a valve portion 164 projecting downward is disposed, and the flexible substrate 163 is arranged from the upper side with air pressure, hydraulic pressure, and hydraulic piston. Since it needs to be pressed by valve element deformation means such as a piezoelectric actuator or shape memory alloy actuator, a separate drive mechanism is required, the structure is complicated, the manufacturing process is complicated, and the cost is high. At the same time, the inspection microchip will become larger.
- Patent Document 1 Japanese Patent Application Laid-Open No. 2001-322099
- Patent Document 2 JP 2004-108285 A
- Patent Document 3 Japanese Patent Application No. 2004-138959
- Non-patent document 1 “DNA chip technology and its application”, “Protein Nucleic Acid Enzyme” 43 ⁇ , No. 13 (1 998) Fumio Kimizuka, Yasunobu Kato, Kyoritsu Publishing Co., Ltd.
- the present invention is a backflow prevention structure that constitutes a backflow prevention unit that prevents backflow of liquid over a joining part where two flow paths of the microchip for inspection join. Therefore, a separate drive mechanism is not required, the manufacturing cost can be reduced without increasing the size of the inspection microchip with a simple structure, and the back flow of the liquid can be reliably prevented.
- An object of the present invention is to provide an inspection microchip that can perform an accurate inspection and has excellent reliability, and an inspection apparatus using the same.
- the present invention has been invented in order to achieve the above-described problems and objects in the prior art, and the backflow prevention structure of the present invention includes:
- the apparatus includes a backflow prevention means provided in one flow path upstream from the merging section,
- the channel resistance of the backflow preventing means is set to be larger than the total channel resistance of the total upstream and downstream channel resistances of the junction in the other channel.
- the apparatus includes a backflow prevention means provided in one flow path upstream from the merging section,
- the channel resistance of the backflow preventing means is set to be larger than the total channel resistance of the total upstream and downstream channel resistances of the junction in the other channel.
- the inspection microchip of the present invention comprises:
- a sample storage section for storing a sample
- a reagent container for storing the reagent;
- a reaction unit having a reaction channel for performing a predetermined reaction process by combining the sample stored in the sample storage unit and the reagent stored in the reagent storage unit;
- An inspection section having an inspection flow path for performing a predetermined inspection on the reaction processing substance obtained by the reaction of the reaction section,
- the apparatus includes a backflow prevention means provided in one flow path upstream from the merging section,
- the channel resistance of the backflow preventing means is set to be larger than the total channel resistance of the total upstream and downstream channel resistances of the junction in the other channel.
- FIG. 1 is a perspective view showing an embodiment of an inspection apparatus according to the present invention, comprising an inspection microchip according to the present invention and an inspection apparatus main body force for detachably mounting the inspection microchip.
- FIG. 2 is a top view showing only the entire flow path formed in the inspection microchip of FIG.
- FIG. 3 is a partially enlarged view showing a reagent storage part of the flow path of FIG.
- FIG. 4 is a partially enlarged view showing the entire flow path branched from the reagent storage section of the flow path of FIG.
- FIG. 5 (a) is a cross-sectional view showing an example of a micropump 11 using a piezo pump
- FIG. 5 (b) is a top view thereof
- FIG. It is sectional drawing which showed the Example.
- FIG. 6 is a schematic top view showing the configuration of the reagent quantification unit.
- FIG. 7 is a schematic view schematically showing an example of the flow path of the microchip for inspection showing the configuration of the backflow prevention unit of the present invention.
- FIG. 8 is a schematic view schematically showing a configuration of an example of a backflow prevention unit of the present invention.
- FIG. 9 is a schematic view schematically showing a configuration of an example of the backflow prevention unit of the present invention.
- FIG. 10 is a cross-sectional view schematically showing a configuration of a backflow prevention unit.
- FIG. 11 is a cross-sectional view schematically showing a configuration of a backflow prevention unit.
- FIG. 12 is a cross-sectional view schematically showing a configuration of a backflow prevention unit.
- FIG. 13 is a cross-sectional view schematically showing a configuration of a backflow prevention unit. Explanation of symbols
- the flow path resistance upstream of the backflow prevention means is the total flow path of the total flow path resistance upstream and downstream of the junction in the other flow path. It is set to be larger than the resistance.
- the channel resistance of the backflow preventing means is the flow upstream and downstream of the junction in the other channel. Since the total channel resistance is greater than the total channel resistance, it is possible to reliably prevent the liquid from flowing back into one of the channels upstream of the backflow prevention means.
- the liquid to be sent from one flow path is sent to the merge flow path
- the liquid is fed with a large pump pressure that can compensate for the pressure drop due to the flow path resistance of the backflow prevention means. By doing so, the liquid to be sent can be sent from the one flow path to the merge flow path through the backflow prevention means.
- the pump pressure of the liquid feed pump to one flow path to a pump pressure higher than the liquid feed pump pressure to the other flow path, and switching these liquid feed pumps, The liquid to be selectively sent from the other flow path and the other flow path can be reliably sent to the merging flow path, and the liquid from the merging flow path to one of the flow paths should be prevented from flowing back. Can be reliably prevented from flowing back.
- one flow path is used as a reagent flow path communicating with a reagent storage section in which a reagent is stored, and the other flow path is connected to a sample storage section storing a sample.
- the backflow prevention structure of the present invention can be applied as the specimen flow path.
- the pump pressure of the liquid feeding pump to the reagent channel is set to a pump pressure higher than the pump pressure of the liquid feeding pump to the sample channel, and these liquid feeding pumps are switched. Therefore, the reagent from the reagent channel, the sample from the sample channel, and the like can be selectively and reliably sent to the merge channel, and backflow is prevented to prevent contamination of the reagent container. It is possible to reliably prevent the merged liquid from the merge flow path to the reagent flow path to flow back.
- the reagent, the specimen, a mixed solution thereof, a treatment liquid, or the like is sent from the one channel to the downstream of the junction, and the liquid is stored in the downstream channel. Further, the liquid is pushed out further downstream by the liquid in the other channel.
- the liquid in the other channel may be a driving liquid for extruding the reagent and the specimen rather than the reagent.
- the present invention is characterized in that the backflow prevention means is constituted by a channel cross-sectional area force or a backflow prevention channel rather than a downstream channel cross-sectional area.
- such a backflow prevention flow path is arranged at a predetermined position of the flow path of the inspection microchip to control the pump pressure from the micropump and selectively switch the pump.
- the timing of liquid feeding can be controlled by controlling the stop and passage of liquid from the two flow paths.
- the reagent and the specimen are joined at an appropriate time, and joined and reacted at a predetermined mixing ratio, so that a predetermined test can be performed accurately.
- the present invention is characterized in that the backflow prevention means comprises a backflow prevention flow path including a baffle plate member arranged in the flow path.
- the baffle plate member arranged in the flow path increases the resistance of the backflow prevention flow path, and passes through the backflow prevention flow path from the downstream merging flow path. It is possible to reliably prevent the backflow to the upstream channel from the prevention channel.
- such a backflow prevention flow path is disposed at a predetermined position in the flow path of the microchip for inspection, and the pump pressure from the micropump is controlled, and the pump is switched selectively.
- the timing of liquid feeding can be controlled by controlling the stop and passage of liquid from the two flow paths.
- the reagent and the specimen merge at an appropriate time, and a predetermined mixing ratio is obtained. Therefore, a predetermined inspection can be performed accurately.
- the test microchip of the present invention is characterized in that the sample storage unit includes a sample pretreatment unit that performs sample pretreatment by joining the sample and the sample pretreatment liquid.
- a pretreatment suitable for an amplification reaction can be performed on a sample such as separation or concentration of an analyte (analyte), deproteinization, and the like. It is possible to provide an inspection microchip capable of performing a predetermined inspection quickly.
- the inspection apparatus of the present invention is characterized in that the above-described inspection microchip is detachably mounted and the inspection is performed in the inspection portion of the inspection microchip.
- the inspection microchip that is convenient to carry and excellent in handling is simply mounted on the inspection apparatus, and it does not require special techniques, complicated and complicated operations, and can be accurately performed. It is possible to carry out a predetermined inspection quickly and quickly.
- FIG. 1 is a perspective view showing an embodiment of an inspection apparatus according to the present invention composed of an inspection microchip according to the present invention and an inspection apparatus main body on which the inspection microchip is detachably mounted.
- FIG. FIG. 3 is a top view showing only the entire flow path formed on the test microchip in FIG. 1, FIG. 3 is a partially enlarged view showing a reagent storage part of the flow path in FIG. 2, and FIG. 4 is a reagent in the flow path in FIG. It is the elements on larger scale which show the whole flow path branched from the accommodating part.
- reference numeral 1 denotes an inspection apparatus according to the present invention as a whole.
- the inspection apparatus 1 has an inspection microchip 2 and a microchip 2 for inspection that are detachably attached to each other. And an inspection device main body 3 for carrying out the inspection.
- the inspection microchip 2 has a substantially rectangular card shape, and is composed of, for example, a single chip card made of resin, glass, silicon, ceramics, or the like. It is.
- a series of flow paths are formed in the inspection microchip 2 as shown in FIG.
- test microchip 2 for gene testing is taken as an example.
- the microchip 2 for inspection is not limited to this, and is used for inspecting various specimens.
- the arrangement, shape, dimensions, size, and the like can be variously changed according to the type of specimen, examination items, and the like.
- the test microchip 2 of this embodiment is an ICAN method (Isothermal chimera primer initiated nucleic acid amplification) [amplification of the above-mentioned amplification, and in the test microchip 2, blood
- a gene amplification reaction can be performed using a sample extracted from sputum and a reagent containing a chitin primer that has been modified specifically for hybridization with a gene targeted for detection, a DNA polymerase having strand displacement activity, and an endonuclease. (See Patent No. 3433929).
- reaction solution is subjected to a denaturation treatment and then sent to a flow path where streptavidin is adsorbed, and the amplified gene is immobilized on the flow path.
- the probe DNA whose ends are modified with fluorescein isothiocyanate (FITC) and the immobilized gene are neutralized.
- the gold colloid whose surface is modified with FITC antibody is adsorbed to a probe hybridized to the immobilized gene, and the concentration of the gold colloid is optically measured to detect the amplified gene.
- the test microchip 2 shown in FIG. 1 is composed of a single chip made of resin, and by injecting a sample such as blood, the gene amplification reaction and its reaction are performed in the test microchip 2. It is configured so that detection can be performed automatically and genetic diagnosis can be performed on multiple items simultaneously.
- test microchip 2 can be applied to the test apparatus main body 3 shown in FIG. 1 simply by dropping a blood sample of about 2 to 3 ⁇ 1 onto a chip having a length and width of several centimeters, for example. Attaching the microchip 2 for use enables the amplification reaction and its detection.
- the test microchip 2 is formed with a reagent storage unit 18 for storing a reagent used for the gene amplification reaction.
- a chitin primer modified with piotin that specifically hybridizes to a gene to be detected, a DNA polymerase having strand displacement activity , And reagent power such as endonuclease are accommodated in reagent accommodating portions 18a, 18b, 18c.
- reagents are stored in advance in these reagent storage units 18a, 18b, and 18c so that they can be inspected quickly regardless of location or time.
- the surfaces of the reagent storage portions 18a, 18b, 18c are sealed. .
- the inspection microchip 2 when the inspection microchip 2 is stored, in order to prevent the reagent from leaking into the fine flow path from the reagent storage portions 18a, 18b, 18c and causing the reagent to react, Under storage conditions, it is solid or gelled, and in use, it is encapsulated by a sealing material such as fats and oils that melts and becomes fluid at room temperature.
- a sealing material such as fats and oils that melts and becomes fluid at room temperature.
- Micropumps 11 are connected to the upstream sides of these reagent storage units 18a, 18b, and 18c by pump connection units 12, respectively. By these micropumps 11, the reagent is fed from the reagent storage portions 18a, 18b, 18c to the flow path 15a on the downstream side.
- the micropump 11 is incorporated in the inspection apparatus body 3 separate from the inspection microchip 2, and by attaching the inspection microchip 2 to the inspection apparatus body 3,
- the pump connection portion 12 is connected to the inspection microchip 2.
- FIG. 5 (a) is a cross-sectional view showing an example of a micropump 11 using a piezo pump
- FIG. 5 (b) is a top view thereof.
- the micropump 11 includes a substrate 42 on which a first liquid chamber 48, a first flow path 46, a pressurization chamber 45, a second flow path 47, and a second liquid chamber 49 are formed. I have. Then, an upper substrate 41 laminated on the substrate 42, a diaphragm 43 laminated on the upper substrate 41, a piezoelectric element 44 laminated on the opposite side of the diaphragm 43 from the pressurizing chamber 45, A drive unit (not shown) for driving the piezoelectric element 44 is provided.
- FIG. 5 (c) is a cross-sectional view showing another example of the micropump 11.
- the micropump 11 includes a silicon substrate 71, a piezoelectric element 44, and a flexible wiring force (not shown).
- the silicon substrate 71 is obtained by processing a silicon wafer into a predetermined shape by a known photolithographic technique, and by etching, a pressurizing chamber 45, a diaphragm 43, a first flow path 46, and a first liquid chamber. 48, a second flow path 47, and a second liquid chamber 49 are formed.
- the first liquid chamber 48 is provided with a port 72
- the second liquid chamber 49 is provided with a port 73, and is configured to communicate with the pump connection portion 12 of the microchip 2 for inspection via this port. It is.
- the liquid feeding direction and the liquid feeding speed can be controlled by changing the pump driving voltage and frequency.
- the reagent is transferred from the reagent storage unit 18a, 18b, 18c to the downstream channel 15a via the liquid supply control unit 13. After the liquid is fed and the mixed state is stabilized in the flow path 15a, the reagent mixed liquid is fed to the flow paths 15b and 15c to 15d branched into three.
- the flow path 15b communicates with the reaction and detection system with the sample constituting the left flow path shown in FIG.
- the flow path 15c communicates with the reaction and detection system with the positive control constituting the central flow path in FIG.
- the flow path 15d communicates with the negative detection reaction system that constitutes the flow path on the right side of FIG.
- the reagent mixed solution sent to the flow path 15b is filled in the storage portion 17a.
- a reagent filling flow path is configured between the backflow prevention unit (check valve) 16 on the upstream side of the storage unit 17a and the liquid supply control unit 13a on the downstream side,
- the reagent quantification unit is configured together with the liquid feeding control unit 13b provided in the branch flow path communicating with the micropump 11 for feeding the driving liquid.
- the reagent quantification unit is configured to mix a predetermined amount of reagent in the channel (reagent filling channel 15a) between the backflow prevention unit 16 including a check valve and the liquid feeding control unit 13a. Filled with liquid. Further, a branch channel 15b that branches from the reagent-filled channel 15a and communicates with the micropump 11 that feeds the driving liquid is provided. [0077] Then, the reagent is quantitatively fed as follows. First, the reagent 31 is filled by supplying the reagent 31 to the reagent filling channel 15a at the liquid feeding pressure without passing the reagent 31 from the liquid feeding control unit 13a to the back flow preventing unit 16 side.
- the microphone pump 11 causes the branching flow path 15b to move toward the reagent filling flow path 15a.
- the driving liquid 25 By feeding the driving liquid 25, the reagent 31 filled in the reagent filling channel 15a is pushed forward from the liquid feeding control unit 13a, and thereby the reagent 31 is quantitatively fed. It should be noted that by providing a large-volume reservoir 17a in the reagent filling channel 15a, the quantitative variation is reduced.
- the sample storage unit 20 may include a sample pretreatment unit that performs sample pretreatment by merging the sample and the sample pretreatment liquid.
- the specimen storage unit 20 has a mechanism almost the same as that of the reagent quantitative unit described above, so that the specimen is filled in a fixed quantity by the micro-bump 11, and is sent to the subsequent flow path 15e. ing.
- the specimen filled in the reservoir 17a and the reagent mixed solution filled in the reservoir 17b are sent to the channel 15e via the Y-shaped channel and mixed in the channel 15e. And ICAN reaction.
- liquid transfer of the sample and the reagent is performed by, for example, alternately driving the micropumps 11 to alternately introduce the sample and the reagent mixed solution into the flow path 15e in a ring shape. It is desirable to allow the reagent to spread and mix.
- the stop solution storage portion 21a stores a reaction stop solution in advance, and the micro pump 11 sends the reaction stop solution to the flow path 15f, thereby causing the peotidin.
- the amplification reaction can be stopped by mixing the reaction solution after the amplification reaction with the modified primer and the stop solution.
- the denatured solution in the denatured solution storage unit 21b is mixed in the flow path 15g with the mixture solution subjected to the reaction termination process, and one amplified gene is mixed. Denature into chains. So After that, the buffer solution stored in the hybridization buffer storage unit 21c is mixed in the flow path 15h, and the obtained mixed solution is used as two detection units 22a for detecting the target substance and for internal control detection. Divide into 22b and send. As a result, the gene denatured into a single strand is immobilized on the detection units 22a and 22b by the streptavidin adsorbed on the detection units 22a and 22b.
- this detection unit 22a with a single pump 11, the cleaning solution, probe DNA solution, and colloidal gold solution labeled with FITC antibody contained in each of the storage units 21d, 21f, 21e Pump in the order shown in. Similarly, the washing solution, internal control probe DNA solution, and colloidal gold solution labeled with FITC antibody are accommodated in each of the accommodating parts 21d, 21g, and 21e by the single pump 11 into the detecting part 22b. In the order shown in the figure.
- the probe DNA whose end is fluorescently labeled with FITC is allowed to hybridize with the single-stranded amplified gene immobilized on the detection units 22a and 22b, and then the gold colloid is converted via FITC.
- the combined gold colloid is irradiated with measurement light with, for example, LED force, and the presence or absence of amplification or amplification efficiency is measured by detecting transmitted light or reflected light with a light detection means such as a photodiode or a photomultiplier tube. .
- the flow path 15c communicates with the positive control that constitutes the central flow path in FIG. 2, and communicates with the detection system.
- the reaction with the negative control composing the flow path on the right side of Fig. 2 is communicated to the detection system.
- the probe is allowed to undergo an amplification reaction in the flow path with the reagent in the same manner as in the reaction and detection system of the sample in the flow path 15b described above.
- An amplification reaction is detected based on the reaction product by allowing the probe DNA accommodated in the DNA storage section to undergo hybridization in the flow path.
- the flow path as described above of the inspection microchip 2 has a backflow prevention that prevents the backflow of the liquid at the junction where the two flow paths merge.
- Many parts 16 are provided.
- the backflow prevention unit 16 is a check valve in which the valve body closes the flow path opening by backflow pressure, or an active valve that closes the opening by pressing the valve body to the flow path opening by the valve body deforming means. Power is composed. [0089]
- Patent Document 3 Japanese Patent Application No. 2004-138959
- the structure as shown in Figs. A check valve has been proposed.
- the backflow prevention unit is configured as shown in FIG.
- FIG. 7 is a schematic view schematically showing an example of the flow path of the inspection microchip showing the configuration of such a backflow prevention unit.
- the liquid feed pump 51 is driven.
- a sample supply channel 52 through which a sample is fed from the sample container is provided.
- the first reagent flow path 54 for feeding the first reagent from the first reagent container (not shown) and the liquid feed pump 55 are not shown.
- a second reagent channel 56 for feeding the second reagent from another second reagent container is not shown.
- the first reagent channel 54 and the second reagent channel 56 are communicated with the reagent supply channel 59 via the junction 57.
- sample supply channel 52 and the reagent supply channel 59 are connected to the reaction channel 6 via the junction 58.
- the backflow preventing means 70 is disposed.
- reference numeral 61 denotes an air vent
- reference numeral 62 denotes a liquid feeding control unit
- the inspection microchip 50 having such a configuration is set to have the following flow path resistance relationship.
- the flow resistance of the backflow preventing means 70 is Rl
- the flow resistance of the first reagent flow 54 is R2
- the flow resistance of the reagent supply flow 59 is R3
- R4 be the channel resistance of reaction channel 60.
- the first flow path resistance R1 of the backflow preventing means 70 of the second reagent flow path 56 is a flow path upstream and downstream of the junctions 57, 58 in the first reagent flow path 54.
- the channel resistance is set so that Rl> (R2 + R3 + R4).
- the channel resistance R1 upstream of the backflow prevention means 70 is set to the first reagent flow.
- the total channel resistance (R2 + R3 + R4) of the sum of the channel resistances upstream and downstream of the junctions 57 and 58 in the channel 54 (the other channel) is set to be larger.
- the channel resistance force of the backflow preventing means 70, the first reagent channel 54 is larger than the second reagent flow upstream of the backflow prevention means 70. It is possible to reliably prevent the liquid from flowing back into the passage 56.
- the liquid to be sent from the second reagent channel 56 is sent to the reagent supply channel 59, it is larger than the channel resistance R1 of the backflow preventing means 70 and at a pump pressure P2.
- the liquid to be fed can be fed from the second reagent channel 56 to the reagent supply channel 59 through the backflow preventing means 70.
- the pump pressure P2 of the liquid feed pump 55 to the second reagent flow path 56 is set to a pump pressure higher than the pump pressure P1 of the liquid feed pump 53 to the first reagent flow path 54.
- the first reagent flow path 54 and the second reagent flow path 56 are also surely sent to the reagent supply flow path 59 the liquid to be sent selectively.
- R1 is set to be 1 to: LOO times, preferably 5 to 30 times larger than (R2 + R3 + R4). ,.
- the first reagent channel 54 (the other channel) Let the first reagent push the mixed reagents further downstream.
- the liquid feed pump 55 to the second reagent channel 56 (one channel) is not driven, the first reagent flow having the channel resistance of the backflow preventing means 70 is provided.
- the liquid pressure in the channel 54 (the other channel) causes a slight back flow to the second reagent channel 56 (the one channel).
- the liquid supply pump 55 in the second reagent flow path 56 (the first flow path) is set to be more than the liquid supply pump 53 in the first reagent flow path 54 (the other flow path).
- a reagent, a specimen, a mixed solution thereof, a treatment liquid, or the like is sent from one flow path having a flow resistance of the backflow preventing means to the downstream flow path, and the liquid flows to the downstream flow path. After the liquid is accumulated, the liquid may be pushed further downstream by the liquid in the other channel.
- the liquid in the other channel may be a driving liquid for pushing out the reagent and the sample rather than the reagent.
- one flow path for preventing backflow is the second reagent flow path 56 and the other flow path is the first reagent flow path 54. Therefore, for example, in a test microchip, one flow path is used as a reagent flow path communicating with a reagent storage section in which a reagent is stored, and the other flow path is used to store a sample.
- the backflow prevention structure of the present invention can also be applied as a sample flow path communicating with the sample storage section.
- the pump pressure of the liquid feeding pump to the reagent flow path is set to a pump pressure larger than the liquid feeding pump pressure to the sample flow path, and these liquid feeding pumps are switched to thereby change the reagent.
- the reagent from the flow channel and the sample from the sample flow channel can be selectively sent to the merge flow channel reliably, and the back flow is prevented to prevent contamination of the reagent container. It is possible to reliably prevent the merged liquid from the merge channel from flowing backward.
- channel resistance corresponds to the coefficient of pressure loss when the fluid flows through the channel.
- the value of “channel resistance” can be obtained by measuring the flow rate when a fluid is flowed by applying pressure to the inlet of the flow channel and dividing the pressure by the flow rate.
- the flow path resistance R is
- the channel resistance can be increased by reducing the cross-sectional area S and increasing the channel length L.
- the backflow prevention means 70 is, for example, as shown in FIG. 8 (a), the backflow prevention means 70 having a flow passage cross-sectional area S2 smaller than the flow passage cross-sectional area S1 of the downstream flow passage 80.
- the channel length can be increased.
- the backflow prevention channel 82 having a channel cross-sectional area S2 smaller than the channel cross-sectional area S1 of the downstream channel 80 is curved, etc.
- the channel resistance can be increased by increasing the channel length of the backflow preventing channel 82.
- the flow passage cross-sectional area S2 is smaller than the flow passage cross-sectional area S1 of the downstream flow passage 80.
- a backflow prevention flow path 82 provided with a baffle plate member 84 may be used.
- the flow passage cross-sectional area S2 is smaller than the flow passage cross-sectional area S1 of the downstream flow passage 80.
- a backflow prevention flow path 82 provided with a bellows-like small-diameter portion 86 may be provided.
- the backflow prevention means 70 includes a backflow prevention flow channel cap which has a material force having a flow passage resistance larger than the flow passage resistance of the material forming the downstream flow passage in order to change the flow passage resistance. Make it up.
- the I CAN method has been described as a test microchip for genetic testing.
- the arrangement, shape, dimensions, size, etc. can be changed in various ways depending on the type of specimen, test item, etc., and various changes can be made within the scope without departing from the object of the present invention. is there.
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Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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EP06729130A EP1867385A1 (en) | 2005-03-31 | 2006-03-15 | Backflow prevention structure, and microchip for inspection and inspection device that use the same |
JP2007512422A JPWO2006109397A1 (ja) | 2005-03-31 | 2006-03-15 | 逆流防止構造、それを用いた検査用マイクロチップおよび検査装置 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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JP2005-103522 | 2005-03-31 | ||
JP2005103522 | 2005-03-31 |
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WO2006109397A1 true WO2006109397A1 (ja) | 2006-10-19 |
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PCT/JP2006/305109 WO2006109397A1 (ja) | 2005-03-31 | 2006-03-15 | 逆流防止構造、それを用いた検査用マイクロチップおよび検査装置 |
Country Status (5)
Country | Link |
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US (1) | US20060222572A1 (ja) |
EP (1) | EP1867385A1 (ja) |
JP (1) | JPWO2006109397A1 (ja) |
CN (1) | CN101146607A (ja) |
WO (1) | WO2006109397A1 (ja) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007058077A1 (ja) * | 2005-11-18 | 2007-05-24 | Konica Minolta Medical & Graphic, Inc. | 遺伝子検査方法、遺伝子検査用マイクロリアクタ、および遺伝子検査システム |
WO2014207857A1 (ja) * | 2013-06-26 | 2014-12-31 | 株式会社日立製作所 | 細胞毒性試験装置、及び細胞毒性試験方法 |
JP2017512645A (ja) * | 2013-12-30 | 2017-05-25 | ゼネラル・エレクトリック・カンパニイ | 試薬保存システム及び方法 |
JP2018057366A (ja) * | 2016-09-30 | 2018-04-12 | 積水化学工業株式会社 | マイクロ流体デバイス及び流体の送液方法 |
WO2022045241A1 (ja) * | 2020-08-27 | 2022-03-03 | 京セラ株式会社 | 流路デバイスおよび送液方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH02293393A (ja) * | 1989-05-08 | 1990-12-04 | Fujitsu Ltd | ホットウォールエピタキシャル成長装置 |
JPH03223674A (ja) * | 1989-11-30 | 1991-10-02 | Mochida Pharmaceut Co Ltd | 反応容器 |
JP2003181255A (ja) * | 2001-12-21 | 2003-07-02 | Minolta Co Ltd | マイクロチップ、該マイクロチップを用いた検査装置及び混合方法 |
JP2005021866A (ja) * | 2003-07-04 | 2005-01-27 | Yokogawa Electric Corp | 化学反応用カートリッジ |
JP2005326392A (ja) * | 2004-04-15 | 2005-11-24 | Tama Tlo Kk | 試料導入マイクロデバイス |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US20040053290A1 (en) * | 2000-01-11 | 2004-03-18 | Terbrueggen Robert Henry | Devices and methods for biochip multiplexing |
-
2006
- 2006-03-15 EP EP06729130A patent/EP1867385A1/en not_active Withdrawn
- 2006-03-15 WO PCT/JP2006/305109 patent/WO2006109397A1/ja not_active Application Discontinuation
- 2006-03-15 CN CNA2006800097956A patent/CN101146607A/zh active Pending
- 2006-03-15 JP JP2007512422A patent/JPWO2006109397A1/ja not_active Withdrawn
- 2006-03-28 US US11/390,286 patent/US20060222572A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02293393A (ja) * | 1989-05-08 | 1990-12-04 | Fujitsu Ltd | ホットウォールエピタキシャル成長装置 |
JPH03223674A (ja) * | 1989-11-30 | 1991-10-02 | Mochida Pharmaceut Co Ltd | 反応容器 |
JP2003181255A (ja) * | 2001-12-21 | 2003-07-02 | Minolta Co Ltd | マイクロチップ、該マイクロチップを用いた検査装置及び混合方法 |
JP2005021866A (ja) * | 2003-07-04 | 2005-01-27 | Yokogawa Electric Corp | 化学反応用カートリッジ |
JP2005326392A (ja) * | 2004-04-15 | 2005-11-24 | Tama Tlo Kk | 試料導入マイクロデバイス |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007058077A1 (ja) * | 2005-11-18 | 2007-05-24 | Konica Minolta Medical & Graphic, Inc. | 遺伝子検査方法、遺伝子検査用マイクロリアクタ、および遺伝子検査システム |
WO2014207857A1 (ja) * | 2013-06-26 | 2014-12-31 | 株式会社日立製作所 | 細胞毒性試験装置、及び細胞毒性試験方法 |
JP2017512645A (ja) * | 2013-12-30 | 2017-05-25 | ゼネラル・エレクトリック・カンパニイ | 試薬保存システム及び方法 |
JP2018057366A (ja) * | 2016-09-30 | 2018-04-12 | 積水化学工業株式会社 | マイクロ流体デバイス及び流体の送液方法 |
WO2022045241A1 (ja) * | 2020-08-27 | 2022-03-03 | 京セラ株式会社 | 流路デバイスおよび送液方法 |
Also Published As
Publication number | Publication date |
---|---|
EP1867385A1 (en) | 2007-12-19 |
JPWO2006109397A1 (ja) | 2008-10-09 |
CN101146607A (zh) | 2008-03-19 |
US20060222572A1 (en) | 2006-10-05 |
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