WO2005033713A1 - 微量のサンプル又は試液の微小液滴を供給する装置 - Google Patents
微量のサンプル又は試液の微小液滴を供給する装置 Download PDFInfo
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- WO2005033713A1 WO2005033713A1 PCT/JP2004/014381 JP2004014381W WO2005033713A1 WO 2005033713 A1 WO2005033713 A1 WO 2005033713A1 JP 2004014381 W JP2004014381 W JP 2004014381W WO 2005033713 A1 WO2005033713 A1 WO 2005033713A1
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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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
-
- 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
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
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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"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1039—Micropipettes, e.g. microcapillary tubes
Definitions
- the present invention relates to a device for supplying a small amount of a sample or a test solution for performing a reaction in a fine groove (microchannel) having an inner diameter of several hundred nm to several hundred / zm.
- the reaction is usually performed with an inner diameter of the channel of several hundred nm to several hundred / zm and a channel length of several millimeters. Since it is at the cm level, it is possible to perform an analysis' reaction in a short period of time using a very small amount of test solution. This is the so-called fine total analysis system (—TAS). In this method, the sample volume actually required for the reaction and analysis is very small. pL—a few microliters)! / ⁇ .
- TAS fine total analysis system
- this reagent Since this reagent is difficult to sell and handle in a form held in a container with a volume of pL- ⁇ L due to stability problems, etc., it is usually relatively large at several hundreds of mL. The volume is distributed and sold in a form held in a container, and is provided for analysis. Also, since it is difficult to handle samples at the pL- ⁇ L level, a volume of several tens of L is usually collected from a container of several tens of ⁇ L and several mL, and added to the chip. Provided for analysis.
- the present invention is intended to solve such a problem, and efficiently uses a small amount of a test solution.
- Methods for dispensing a small amount of liquid include (1) a method using an inkjet nozzle using a piezoelectric electrostrictive element, (2) a method using a dispensing pin, and (3) a bubble formation due to heat generation.
- a method of using a bubble jet (registered trademark) There are known a method of using a bubble jet (registered trademark), and a method of (4) dispensing a small amount using a small syringe.
- these methods have been developed with the aim of dispensing a trace amount of liquid to the correct amount and position as accurately as possible.
- a droplet having a force of several liters and a small droplet of several tens of nL can be formed around an opening of a microchip without concentrating the droplet at a small "point" using an inkjet nozzle.
- a small amount of reagent solution is applied to the sample.
- the sample is applied as droplets (in a “dispersed state”), and pressure is applied.
- the applied sample solution is moved by the electric force.
- the present inventors have found that a target reagent solution or Z and a sample, which do not require a high positional accuracy, are introduced into a channel, and that it is possible to carry out an analysis' reaction, and arrived at the present invention.
- the present invention provides a micro mouth chip having a fine groove for performing an analysis reaction and an opening communicating with the groove.
- the apparatus is characterized in that a supply device and a sample or a sample solution are dispersed and applied as microdroplets to and around a microchip having a fine groove for performing analysis and reaction and an opening communicating with the groove.
- a sample or a reagent is supplied around a microchip opening (not a liquid stream).
- Any liquid can be applied as long as it can be applied as a droplet (Note: the result is a force that collects these droplets and a sample or sample solution is stored).
- a sample or reagent solution is microchip by ejecting droplets such as (1) a method using an ink jet nozzle using a piezoelectric element or (3) a method using a bubble jet using bubble formation by heat generation.
- the device for supplying the microdroplets is an ink jet device, and it is preferable to supply the microdroplets with the nozzle force of the ink jet device.
- a method based on the principle of a method using an ink jet nozzle using a piezoelectric electrostrictive element is preferable because a microdroplet can be formed without heating a sample or a test solution.
- the lower limit of the volume per microdroplet to be applied is usually 111 or more, preferably. More preferably, it is at least O.lpL, more preferably at least lpL, further preferably at least 2 pL, and the upper limit is usually at most 10 nL, preferably at most 5 nL, more preferably at most InL.
- volume per microdroplet The smaller the volume per microdroplet, the more uniform and reproducible the power to supply the sample and the test solution. If the volume per drop is too small, the time required for dispensing will be longer. (For example, O.lpL or more) is preferable.
- O.lpL O.lpL or more
- the optimum volume (capacity per droplet) and the total number of droplets are the viscosity of the sample or sample solution used, the surface characteristics around the opening of the microchip, the dropping speed of the droplet, and the required amount of the droplet. It should be decided appropriately in consideration of such factors!
- the lower limit is usually 10 or more, preferably 100 or more, more preferably 500 or more, and still more preferably 1000 or more
- the upper limit is 100,000 or less, preferably 10,000 or less, more preferably 5,000 or less, and even more preferably 2,000 or less.
- the supply device according to the present invention may be a single supply device (nozzle), a plurality of supply devices (nozzles), a single supply device (nozzle), or a plurality of supply devices (nozzles). It may be a combination of the principles.
- the microchip used in the present invention has at least a fine groove for performing an analysis reaction and an opening communicating with the groove.
- the fine groove is preferably formed in a plate, and the opening is preferably formed in the plate or a plate or a film covering the surface of the plate (Claim 2).
- the number of the fine grooves may be one or more than one, and may be appropriately selected according to a desired analysis reaction.
- the length of the groove is not particularly limited, and is appropriately selected according to the target analysis reaction.
- the lower limit is usually 0.1 ⁇ m or more, preferably 2 ⁇ m or more, more preferably 10 ⁇ m or more, and the upper limit is usually 500 ⁇ m or less, preferably Is 300 ⁇ m or less, more preferably 200 m or less (Claim 4).
- the shape of the opening is preferably a circle or a polygon.
- the microchip used in the present invention may have a liquid reservoir for holding a sample or a test solution, in addition to a fine groove for performing analysis and reaction and an opening communicating with the groove.
- the opening is usually formed on the bottom surface of the reservoir (claim 5).
- an intended amount of liquid is to be dispensed at a time using a technique other than the supply device according to the present invention, for example, a pit pin (using fine droplets).
- Pipette or pin must be accurately moved to the position of the opening.
- positional accuracy is not required, and the periphery of the opening is gradually wetted with the test solution and the sample, as shown in FIG. 1 (A).
- the sample Z can be supplied without air entering the opening.
- a sufficiently large droplet is supplied to the opening using a pipette, the liquid is supplied so as to cover the opening, as shown in FIG.
- air tends to be trapped in the channel, and the air bubbles that have accumulated in the channel impede the flow of the sample or sample solution or the current.
- the term “coating” is used to dispense the liquid as droplets only at the opening and its surroundings, instead of dispensing the liquid to the entire liquid reservoir, and gradually open the opening.
- Means that liquid is accumulated for example, a liquid ball.
- a single or a plurality of supply devices may be appropriately moved up, down, left and right.
- a method in which a plurality of supply devices (nozzles) are used to apply to the target application area without moving the nozzles (3) a supply device ( The droplet discharge port of the device is separated from the microchip opening by a certain distance so that the droplets supplied from the (nozzle) are dispersed by air resistance etc. while reaching the microchip opening.
- the range (area) for dispersing and applying the microdroplets may be any range (area) that covers the entire opening, for example, the lower limit is usually twice or more, preferably the area of the opening, preferably It is 4 times or more, more preferably 5 times or more, and the upper limit is usually 20 times or less, preferably 15 times or less, and more preferably 10 times or less. Disperse and apply the drops.
- the fine grooves (microchannels) for performing the analysis and reaction of the present invention may be formed by a known method.
- a chip having a microchannel can be manufactured as follows.
- a glass plate 1 When using glass as a base, first, as shown in FIG. 2, the surface of a glass plate 1 (not shown) is masked with a chrome-gold alloy, and further coated with a photoresist. Next, a photomask is created by designing the layout pattern of the microphone opening channel on the photosensitive film, and ultraviolet light is applied to the mask on the photomask. The exposed portion of the photoresist is dissolved away to expose the chrome Z gold alloy. The exposed metal is removed with aqua regia, and the exposed glass substrate surface is etched using hydrogen fluoride. Thus glass plate 1 After the channel 3 is formed, a flat channel 2 preferably made of the same material (glass in this example) as the substrate used is overlapped to form a closed channel.
- a through-hole is made using a drill or the like at the position of the flat plate 2 corresponding to the end portion of the channel 3 formed on the flat plate 1, and the through-hole is superimposed on the flat plate 1 so as to overlap the channel 3.
- An opening 4 is formed.
- the actual opening 4 is a force portion where the channel 3 of the flat plate 1 overlaps the flat plate 2.
- an opening 4 can be formed by making a hole with a drill or the like.
- a chip having microchannels can be manufactured without processing two flat plates. it can.
- the size of the channel 3 is generally several hundred nm / zm in force and several hundred nm in both width and depth.
- the length since it is possible to form a bent channel 3 in one chip, for example, provide a channel 3 with a length of about 15 cm on a substrate of lcmX 1 cm Talk about this.
- the test solution includes, for example, body fluids such as serum, plasma, cerebrospinal fluid, synovial fluid, and lymph fluid, excretions such as urine and feces, sputum, pus, skin-derived materials, various biological tissues, Biological samples such as cells, their extracts, etc., such as food, beverages, tap water, seawater, lake water, river water, factory drainage, washing water for semiconductors, washing liquid after washing medical equipment, etc.
- body fluids such as serum, plasma, cerebrospinal fluid, synovial fluid, and lymph fluid
- excretions such as urine and feces, sputum, pus, skin-derived materials
- various biological tissues such as cells, their extracts, etc., such as food, beverages, tap water, seawater, lake water, river water, factory drainage, washing water for semiconductors, washing liquid after washing medical equipment, etc.
- the target substance was contained at a predetermined concentration in the processed product obtained by dissolving or suspending appropriately in a buffer solution such as a Naal buffer solution, a borate buffer solution, a good buffer solution or the like, and reconstituting the water or the buffer solution. It contains a composition necessary to detect the measurement target contained in the sample such as a standard solution.
- the necessary composition examples include an antibody or nucleic acid for specifically recognizing the measurement target, Fluorescent dyes for labeling antibodies and nucleic acids, gels necessary to separate the complex in which the analyte or nucleic acid is bound to the analyte or nucleic acid from other components, and for maintaining these stably Required buffer components include, for example, enzymes and receptors that specifically react with the substance to be measured.
- the analysis accuracy is higher when a component that specifically reacts with the reagent is included, it does not matter if the subsequent separation analysis is specific, even if it does not include a specific component.
- a sample or reagent is introduced into channel 3, and then a certain amount of sample or reagent alone is separated and the sample or reagent is transferred to the analysis channel. Reagents can be introduced.
- the channels are crossed in a cross shape, and a sample ⁇ in one channel introduces a test solution or a mixture thereof, and pressure or pressure is applied to the other channel (analytical channel).
- the sample 6 at the intersection can be moved, for example, as shown in FIG. 3 (B).
- FIG. 4 for example, as shown in FIG. 4, the sample or the sample solution or the mixture 6 at the intersection can be moved to the analysis channel by pressure or electric power, as shown in FIG.
- FIG. 5 shows a sample as an example, and a force solution or a mixture of a sample and a solution may be similarly used.
- a gel used for separation of a target substance and a test solution containing a buffer solution component are distributed over the entire cross channel (a)-(d) V, Introduce using the pressure difference from one of the wells (priming). Then add sample to well (b) (sample reservoir, sample well, sample reservoir). Then, when the voltage of the cells of (a), (b), and (c) was set to zero and a voltage of 250 V was applied to (d), negative electric charges including components to be detected in the cell (b) were obtained. The component moves in the direction from (b) to (d) and the channel (b) — Satisfies (d).
- the test component does not move to the channels (a)-(c).
- Fig. 5 (B) for example, when the voltage of channel (a) is set to zero, 130V is applied to the cells (b) and (d), and 750 volts is applied to the channel (c), the channel becomes The components included in the intersection move in the directions from (a) to (c). For example, if channels (a)-(c) are filled with a gel polymer, the analytes are separated according to the size of the molecular weight and the magnitude of the electric charge while passing through the gel polymer.
- the upper plate (flat plate 2) can be made of a film, and in this case, there is no particular problem with the well. This is a very small (trace) world, where a necessary and sufficient amount of liquid droplets is formed at the opening due to surface tension and the like.
- the liquid overflows only by providing a groove in the lower plate (the flat plate 2), usually, the lower plate 1 in which the groove is dug is covered with the upper plate 2 to form a channel (a thin tube, a capillary), and the channel is formed therein.
- the liquid or the analyte in the liquid is moved by electrophoresis or other means.
- the upper plate 2 has an opening and is used only for introducing the sample solution • into the channel, a large-volume reservoir is not particularly necessary. However, for example, when the opening functions as a contact point between the electrode for electrophoresis and the electrophoresis buffer, a liquid reservoir for holding a sufficient amount of liquid for the electrode to come into contact with the liquid is required.
- a plurality of components may be applied to the opening 4 and reacted at the opening 4. Yes, but it can also be reacted in channel 3.
- the liquid is sent only by pressure, the linear velocity distribution of the liquid in the channel occurs, and the movement of the liquid in the peripheral part is smaller than in the central part, and a sharp separation image can be obtained. Not preferred. For this reason, it is preferable to form a uniform liquid flow by a method such as electrophoresis or electroosmotic flow, particularly in the detection part.
- quantification is performed using the channel structure (that is, the volume of the channel) (“constant volume”). "Send the sample into the analysis channel”), and if a sufficient amount of the sample solution and sample are allowed to flow, the entire channel will be filled with the target solution, so there is no problem in the analysis. Also, by changing the inner diameter of the channel from which the liquid is sent out, or by changing the applied pressure, the amount of the sample liquid or sample flowing through the channel can be changed. For example, in the Y-shaped channel in Fig. 7, if the cross-sectional area of the channel from reservoir A is 10 times that of reservoir B and the liquid is sent at the same pressure, the flow rate, that is, the mixing ratio of A and B is 10: It can be adjusted to 1 (continuous quantification).
- the liquid also remains in the opening. Normally, the volume inside the channel is so small that even if liquid remains in the opening, it can be used for the reaction.
- the present invention can be implemented by the following embodiments.
- the sample and the test solution containing the test substance are formed in the opening of the microchannel chip and its periphery. Disperse and apply one or more liquids as droplets of several tens of nL to several tens of nL. Part or all of the applied liquid Force, electrophoresis, electroosmotic flow It is introduced into the channel using any force and used for analysis, reaction, etc. Any device that has the ability to apply a certain amount of droplets in a predetermined range can achieve its purpose.
- the test substance is placed on one or more openings on the microchannel chip and its periphery. Disperse and apply the test solution containing the reacting substances as droplets of several fL to several tens of nL.
- the reagent solution is introduced into the channel using pressure or force such as electrophoresis or electroosmotic flow. Furthermore, a sample containing the test substance is dispersed and applied as droplets of several fL to several tens of nL in an opening different from the reagent.
- the area of the opening, the amount of droplets, and the number of droplets are set according to the purpose.
- the object can be easily achieved by dispensing a large number of droplets in a wide range if the dispensing time is not too long, rather than dispensing a large amount of droplets in a small amount.
- Reagents and samples are introduced into the channels using pressure or forces such as electrophoresis or electroosmotic flow. Then, a certain amount of the test solution and the sample are mixed by using the difference in the inner diameter in the channel, the volume of the intersection of the channels, and the like, and both components react.
- reaction product is introduced into the analysis channel by utilizing the volume of the channel intersection, etc., and the reaction product is sent to the detection area by pressure or force such as electrophoresis or electroosmotic flow.
- the reaction product is separated, analyzed, and quantified.
- the medium force of the opening on the microchannel chip is also selected, and one around it is selected. Then, apply a test solution containing a substance that reacts with the test substance and a sample containing the test substance alternately or simultaneously as droplets of several fL to tens of nL. The dispersed and applied liquids are mixed by contacting each other in the air or on the surface of the chip or in the opening, and the reaction is started.
- the amount of each of the liquids to be dispersed and applied is adjusted (for example, it is possible to determine the number of liquid droplets to be applied to each of the sample liquid and the sample in advance), thereby adjusting the mixing ratio between the two. be able to . Further, the number of droplets is adjusted to set the dispersion application range. After that, part or all of the reacted liquid is applied to the channel from the opening using pressure, electrophoresis, or electroosmotic flow. Will be introduced. A certain amount of the introduced reaction solution is measured using the volume of the channel and its intersection, and the reaction product is sent to the detection region of the analysis channel, where the reaction product is separated, analyzed, and quantified. Is
- test solution containing the substance that reacts with the test substance and the sample containing the test substance are applied alternately or simultaneously as droplets of several fL to several tens of nL.
- the liquid applied in a dispersed state is mixed in the air or on the surface of the chip or in the opening to start the reaction. Then, part or all of the reacted liquid is introduced into the channel from the opening A using pressure, electrophoresis, or electroosmotic flow.
- one or more openings (opening B, openings C,,,,,,) different from opening A and the surroundings are separated by another one or more of the above reaction product components.
- Reagent 2 is applied using an inkjet nozzle. All or part of the applied reagent solution 2 is introduced into the channel from the opening using pressure, electrophoresis, or electroosmotic flow.
- the introduced sample solution 2 and the reaction product are mixed in a fixed amount by utilizing the difference in the inner diameter in the channel, the volume of the intersection of the channels, and the like, and both components react.
- reaction product is introduced into the analysis channel using the volume of the channel intersection, etc., and the reaction product is sent to the detection area by pressure or force such as electrophoresis or electroosmotic flow.
- the reaction products are separated, analyzed and quantified. Further, it is also possible to sequentially send a reagent solution that further reacts with the above-described reaction product into the channel from a plurality of openings to perform a sequential reaction.
- the analysis / reaction apparatus of the present invention may be equipped with the following mechanism. That is, a sample containing one or more test substances or a reagent solution 1 containing a substance that specifically reacts with the test substance is applied to the opening of the microchannel chip and the surrounding area 1 using an inkjet nozzle. . After that, there is a sample using the inkjet nozzle Disperse droplets of a liquid that is not mixed with the test solution and that has a low specific gravity in the range 2 that is equal to or larger than the range 1. In this way, the previously applied reagent or sample is capped by a later applied liquid of low specific gravity, preventing evaporation of the reagent or sample and ensuring accurate reaction and analysis. Is improved.
- Micro-dispensing head (MD-K-130) shown in Fig. 11 [Microdrop
- the nozzle position accuracy can be controlled at 10 m ⁇ 2 m (catalog value) with respect to the MD-P-705-L body.
- the positional accuracy of the microchannel chip with respect to the liquid reservoir is determined by the positional accuracy of the method of holding the chip in the MD-P-705-L body.
- the relative position accuracy between the nozzle outlet and the reservoir is The accuracy is 510 ⁇ 102 m.
- 13 is a chip stage
- 14 is an XYZ axis driving part
- 16 is a reagent reservoir
- 17 is a microchip.
- the sample was a mixture of 2 nM Alexa-labeled 140 bp DNA and anti-AFP antibody Fa, a mixture of 500 pM AFP and Alexa-labeled 200 pM 70 bp DNA as internal standard (7.5 mM Hepes buffer pH 7.5). , 7.5 mM NaCl, 0.05% Tween 20, 0.1% BSA). Then, a pressure of 6.9 kPa is applied to the reservoir 7c, a pressure of + 0.345kPa is applied to the reservoir 7d and the reservoir 7h, and a pressure of-(minus) 7.59kPa is applied to the reservoir 7f. Is introduced into the channel.
- 7a to 7h are liquid reservoirs (the inner diameter of the liquid reservoir is usually 2 to 10mm and the volume is 5 to 50 / zL), and 8 and 9 are narrow grooves (channels) provided in the chip. ), And the inner diameter of the channel is usually 1 (500 / ⁇ .
- 8 is an analysis channel
- 9 is a sample introduction channel
- 10 is a detection site
- 11 is a chip caddy
- 12 is a chip body. It is.
- the spot size (discharge of droplets) of the discharge liquid on the surface of the microchip reservoir can be adjusted. Range) can be changed. In other words, when the ejection port is located sufficiently close to the opening of the microchannel, the ejected droplet lands on a very limited almost the same area. Can be landed (applied) in a wide range of spot sizes (eg, tens of forces to hundreds of ⁇ m diameter (range)).
- the scatter of the droplet landing area becomes too large, and it is necessary to introduce the liquid to be measured into the channel and obtain a sufficient amount of sample to perform the measurement. It is necessary to discharge a large amount of the test solution from the nozzle. Also, in some cases The discharged liquid leaks out of the liquid reservoir.
- the appropriate distance should be taken into consideration, including the performance of the microdroplet dispensing device used (e.g., discharge speed), the viscosity of the sample solution, and the environment in which the nozzle is installed (e.g., air circulation).
- FIG. 1 is a cross-sectional view showing a state in which a test solution Z sample is applied to an opening by (A) inkjet and (B) a pipette.
- FIG. 2 is a perspective view showing an example in which (A) a hole larger than the opening and (B) a hole having the same size as the opening are formed in the channel.
- FIG. 3 is an explanatory diagram showing (A) a state in which a sample is introduced into a cross-shaped channel, and (B) a state in which only a quantified sample is separated.
- FIG. 4 is an explanatory diagram showing a state in which (A) a sample is introduced into a double T-shaped channel and a state in which only (B) —quantitative sample is separated.
- FIG. 5 is an explanatory view showing (A) a state in which a sample is introduced into a cross-shaped channel, and (B) a state in which only a quantitative sample is separated.
- FIG. 6 is a diagram showing an example of a result of detecting fluorescence by the method of FIG. 5.
- FIG. 7 is an explanatory diagram of reaction in a channel.
- FIG. 8 is a perspective view showing one embodiment of the present invention.
- FIG. 9 is a plan view of FIG.
- FIG. 10 is a sectional view taken along the line mn of FIG. 9.
- FIG. 11 is a perspective view showing a dispensing device having an inkjet nozzle used in an example of the present invention.
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Abstract
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JP2005514447A JP4844124B2 (ja) | 2003-10-03 | 2004-09-30 | 微量のサンプル又は試液の微小液滴を供給する装置 |
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WO (1) | WO2005033713A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009013447A1 (en) * | 2007-07-20 | 2009-01-29 | Equine Healthcare Limited | Analyser and pump |
JP2010526294A (ja) * | 2007-05-02 | 2010-07-29 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | 試薬表面への診断液のピエゾ計量分配 |
JP2010526293A (ja) * | 2007-05-02 | 2010-07-29 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | 診断用液体のマイクロ流体装置内への圧電ディスペンシング |
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WO2001059440A2 (en) * | 2000-02-11 | 2001-08-16 | Aclara Biosciences Inc. | Microfluid device with sample injector and method of use |
WO2002082083A1 (fr) * | 2001-04-04 | 2002-10-17 | Wako Pure Chemical Industries, Ltd. | Electrophorese |
JP2003502656A (ja) * | 1999-06-22 | 2003-01-21 | テカン トレーディング アーゲー | 小型化されたインビトロ増幅アッセイを行うための装置および方法 |
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US7004184B2 (en) * | 2000-07-24 | 2006-02-28 | The Reagents Of The University Of Michigan | Compositions and methods for liquid metering in microchannels |
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Patent Citations (3)
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JP2003502656A (ja) * | 1999-06-22 | 2003-01-21 | テカン トレーディング アーゲー | 小型化されたインビトロ増幅アッセイを行うための装置および方法 |
WO2001059440A2 (en) * | 2000-02-11 | 2001-08-16 | Aclara Biosciences Inc. | Microfluid device with sample injector and method of use |
WO2002082083A1 (fr) * | 2001-04-04 | 2002-10-17 | Wako Pure Chemical Industries, Ltd. | Electrophorese |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010526294A (ja) * | 2007-05-02 | 2010-07-29 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | 試薬表面への診断液のピエゾ計量分配 |
JP2010526293A (ja) * | 2007-05-02 | 2010-07-29 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | 診断用液体のマイクロ流体装置内への圧電ディスペンシング |
US8304254B2 (en) | 2007-05-02 | 2012-11-06 | Siemens Healthcare Diagnostics Inc. | Piezo dispensing of a diagnostic liquid onto a reagent surface |
US8361782B2 (en) | 2007-05-02 | 2013-01-29 | Siemens Healthcare Diagnostics, Inc. | Piezo dispensing of a diagnostic liquid into microfluidic devices |
WO2009013447A1 (en) * | 2007-07-20 | 2009-01-29 | Equine Healthcare Limited | Analyser and pump |
Also Published As
Publication number | Publication date |
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JP4844124B2 (ja) | 2011-12-28 |
JPWO2005033713A1 (ja) | 2006-12-14 |
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