EP1843833A1 - Method and device for dosing and mixing small amounts of liquid - Google Patents
Method and device for dosing and mixing small amounts of liquidInfo
- Publication number
- EP1843833A1 EP1843833A1 EP05820542A EP05820542A EP1843833A1 EP 1843833 A1 EP1843833 A1 EP 1843833A1 EP 05820542 A EP05820542 A EP 05820542A EP 05820542 A EP05820542 A EP 05820542A EP 1843833 A1 EP1843833 A1 EP 1843833A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- liquid
- reservoir
- channel structure
- reservoirs
- mixing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
- B01F31/86—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations with vibration of the receptacle or part of it
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
- B01F31/87—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations transmitting the vibratory energy by means of a fluid, e.g. by means of air shock waves
-
- 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
-
- 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
- B01L2300/089—Virtual walls for guiding liquids
-
- 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
- B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
- B01L2400/0436—Moving fluids with specific forces or mechanical means specific forces vibrational forces acoustic forces, e.g. surface acoustic waves [SAW]
-
- 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
- B01L2400/0493—Specific techniques used
- B01L2400/0496—Travelling waves, e.g. in combination with electrical or acoustic forces
-
- 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
- B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
-
- 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
- B01L3/502769—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 multiphase flow arrangements
- B01L3/502776—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 multiphase flow arrangements specially adapted for focusing or laminating flows
Definitions
- the invention relates to a method for integrated metering and mixing of small amounts of liquid, a device and an apparatus for carrying out this method and a use.
- Diagnostic assays are now largely automated.
- defined volumes of sample liquid and reagents are pipetted into a cuvette or into the well of a microtiter plate and mixed.
- a first reference measurement is carried out in which, for example, the optical transmission through the cuvette is determined.
- a second measurement of the same parameter is made. By comparing the two measured values results in the concentration of the sample with respect to a particular ingredient or even the presence of the ingredient.
- Typical volumes are in the sum of a few hundred microliters, whereby necessary mixing ratios of sample to reagent between 1: 100 and 100: 1 can occur.
- reagents may be provided for mixing with a sample.
- high throughput instruments which are typically found in specialized laboratories, there are also efforts to make assays decentralized and without much instrumental effort. It would be desirable if the recently introduced "lab-on-a-chip" technology could be used, where the Processing of liquids can be performed on or integrated into a chip. Assay times of less than one hour are desirable.
- microfluidic systems are used, for example, in which liquid is moved by electro-osmotic potentials, see, for example, Anne Y. Fu, et al. "A micro-fab- ricated fluorescence-activated cell sorter", Nature Biotechnology Vol. 17, November 1999, p. 1109 ff.
- a method for mixing liquids in the microliter range is described in DE 103 25 307 B3, in which small volumes of liquid are mixed in microtiter plates with the aid of sound-induced flow.
- Another method for generating movement in small amounts of liquid on a solid surface is described in DE 101 42 789 C 1.
- a liquid is mixed with the aid of surface sound waves or mixed several liquids together.
- an amount of liquid is brought to a region of a substantially planar surface whose wetting properties differ from the surrounding surface in such a way that the liquid preferably remains on it, being held together by its surface tension , Movement of the amount of liquid can be generated by the momentum transfer of a surface acoustic wave to the liquid.
- the wetting properties of the surface can determine a volume, as described in DE 100 55 318 A1.
- the volumes are defined by hydrophilic and hydrophobic regions over the wetting angle on a substantially smooth surface. If several volumes have been defined in this way which are to be reacted, the volumes are moved toward one another in order to achieve this.
- liquid residues or liquid molecules of the analyte or the reagent can adhere to the surface, so that the movement of a volume loss or a concentration reduction of unknown level can not be excluded.
- channels of defined cross-section which are filled with liquid capillary. If the liquid is an aqueous solution, then at the end of the channel a hydrophobic barrier is attached, which can not be filled capillary. Furthermore, there is a lateral branch on this channel with a likewise hydrophobic surface, which can not be capillary filled.
- the cross-section and length of the channel between the hydrophobic barrier and the hydrophobic branch now define a volume which can be separated and moved by pneumatic pressure through the branch (Bums et al., An integrated nanoliter DNA analysis device, Science 282, 484 (1998) )). This type of volume definition results in high costs due to the necessary wetting structure of the surface (hydrophilic to fill the channel itself and hydrophobic for the barrier and the branch).
- liquid in the present text includes i.a. pure liquids, mixtures, dispersions and suspensions; and liquids containing solid particles, for example, biological material.
- dosing and mixing liquids may also be two or more similar solutions that differ in ingredients dissolved therein that are to be reacted.
- the object of the present invention is to specify a method and a device with the aid of which a precise metering of liquid quantities on or in an integrated chip is possible and which enables precise mixing of the liquids.
- a first liquid is produced placed in or on a first reservoir.
- a second liquid is brought into or onto a second reservoir in such a way that it is completely filled.
- the first and the second liquid are brought into contact via at least one first connecting channel structure which comprises at least one region which, in the direction of the connection line of the two reservoirs, has a smaller cross section than the reservoirs themselves.
- Liquid exchange is effected by laminar flow in the connection channel structure and the liquids are mixed in and on the second reservoir.
- the liquids come into contact via the connecting channel structure. At the interface between the two liquids, only negligible diffusion occurs because the cross-section of the connection channel structure is comparatively small.
- a laminar flow is generated along the connection channel structure in the direction of the second reservoir, the first liquid is moved through the connection channel structure in the direction of the second reservoir. For example, by accurately selecting the period of time over which the laminar flow is generated in the connection channel structure, or the flow rate, a precise definition of the volume of the first liquid to be metered to the second liquid is made.
- the amount of the second liquid is precisely determined by the size of the reservoir. In or on the second reservoir then optionally takes place the reaction between the liquids.
- the second reservoir thus constitutes a reaction chamber.
- the method according to the invention enables the metering and mixing of liquids in a large dynamic range.
- the mixing ratio of reagents to sample liquid z. B. from 1: 100 to 100: 1 can be set.
- pipettes and / or corresponding filling structures can be used. The precision requirements of these elements are low, since the definition of the volumes of liquid participating in the reaction are determined by the method according to the invention or the device itself, in particular by the duration or the velocity of the laminar flow in the connection channel structure and the volume of the second reservoir.
- the laminar flow is preferably caused by the irradiation of sound waves towards at least a part of the connection channel structure.
- the reservoirs and the connecting channel structure can be designed in three dimensions or two-dimensionally.
- the reservoirs and interconnect channel structures may be correspondingly shaped depressions in a surface.
- Other configurations are correspondingly shaped cavities.
- the reservoirs and connection channel structures are formed by correspondingly shaped regions of a surface, which are wetted by the liquids more preferably than the surrounding regions of the surface.
- wetting-modulated surfaces are described, for example, in DE 100 55 318 A1. The liquids are held by their surface tension on the preferably wetted areas.
- the amount of the second liquid participating in the reaction is determined by the dimensions of the second reservoir. If the second reservoir, for example via corresponding filling structures, for. As filling channels and / or filling, filled, any existing supernatants of liquid in these Be Shell Modellen outside the reservoir for geometric reasons do not participate in the mixing, especially when the mixing is effected by laminar flow pattern.
- the laminar flow is generated in or on the connecting channel structure with the aid of sound waves.
- surface acoustic waves are used, which can be generated, for example, with one or more interdigital transducers.
- Surface sound waves transmit their impulse to the liquid or substances contained in it in order to put it in motion.
- the momentum transfer of surface acoustic waves generated with the aid of interdigital transducers to liquids on surfaces is described in DE 100 55 318 A1.
- the latter has an emission direction in the direction of the extension of at least one part of the connection channel structure.
- the first and second liquids may be contacted via the connection channel structure using, for example, capillary forces.
- the connecting channel structure is chosen so small in its lateral dimensions, that at least one of the liquids is pulled by the capillary forces along the channel. So z.
- a first liquid can be brought onto or into the first reservoir, which propagates through the capillary forces in or on the connection channel structure.
- the liquid stops its movement, since only relatively small capillary forces act through the larger cross section of the reservoir in comparison to the connecting channel structure.
- the second liquid is applied, which comes into contact with the first liquid at the entry point of the connecting channel structure in the second reservoir.
- connection between the two liquids is made via a small "bridge drop" which is placed between the two liquids and creates a liquid bridge.
- the bridge drop has a much smaller volume than either of the two liquid quantities.
- pipettes and / or corresponding filling structures can be used.
- the requirements for the precision of these elements are low, since the definition of the volumes of liquid participating in the reaction by the method according to the invention or the erf ⁇ ndungswashe Device itself, in particular by the duration or the speed of the laminar flow in the connection channel structure and the volume of the second reservoir.
- the filling structures may also comprise filling channel structures with small cross-sections compared to the reservoirs.
- the production of a corresponding structure is very simple, since the same process steps are used, which are also used in the production of the reservoir or in the connecting channel structure.
- the comparatively small cross-sections effectively prevent any supernatants present after filling in the filling channel structures from taking part in the mixing. In this way it is prevented that possibly existing in the filling channel structures supernatants the determination of the at the
- Such filling channel structures may have a small cross-section which ensures that the liquid moves through the filling channel structures or on the filling channel structures due to capillary action in the direction of the reservoirs. For a precise filling is easy to carry out.
- the method according to the invention can be carried out with a single connection channel structure between the two reservoirs.
- This is the first reservoir at least partially emptied by the laminar outflow of the first liquid.
- Another embodiment according to the invention comprises at least two connecting channel structures between the two reservoirs.
- a laminar flow is generated by means of surface acoustic waves, which serves for moving the first liquid from the first reservoir in the direction of the second reservoir.
- the first fluid in the first reservoir is thus becoming less and less due to the laminar outflow.
- second liquid flows into the first reservoir from the second reservoir via the second connection channel structure.
- the liquids are mixed. It is particularly favorable if this mixing process is effected by generating substantially laminar flow patterns. This ensures that any supernatants on the filling structures take part in the mixing as little as possible or not at all.
- Sound waves that are radiated into the second reservoir You can z. B. be generated using surface acoustic waves. These can be used directly to generate flow in the liquid by their momentum transfer. In other implementations, the surface acoustic waves can be used to radiate sound waves through a solid, such as a reservoir bottom, into the liquid. For the generation of surface acoustic waves known per se interdigital transducers can be used, which can be easily produced by lithographic techniques. It is preferred if separate devices are used to produce the laminar flow and the mixing. However, the invention also includes embodiments in which the laminar flow and the mixing are produced with the same device.
- the method according to the invention is not limited to the metering and mixing of only two quantities of liquid.
- additional reservoirs may be connected to the second reservoir in addition via further connecting channel structures, from which further fluids are metered into the second reservoir.
- the addition can be done simultaneously or sequentially.
- a device for metering small quantities of liquid has a first reservoir for a first liquid, a second reservoir for a quantity of a second liquid and at least one connecting channel structure which connects the two reservoirs and at least in one region has a cross section in the direction of the line of connection of the reservoirs which is smaller than the cross sections of the reservoirs.
- the reservoirs and the at least one connecting channel structure can be formed as depressions or cavities in a solid body.
- the reservoirs and the at least one connecting channel structure are formed by surface areas which are more preferably wetted by the liquids.
- the device according to the invention furthermore has at least one device for generating laminar flow along the at least one connecting channel structure.
- a preferred embodiment comprises a device for generating sound waves, preferably surface acoustic waves. It is particularly easy to use of an interdigital transducer for generating the surface acoustic waves, which can be easily prepared by lithographic techniques.
- the device according to the invention has at least one device for mixing the quantities of liquid in or on the second reservoir.
- a second sound wave generating device is provided for generating sound waves entering the second reservoir.
- the device according to the invention can be designed as a cost-effective and practical A wegteil.
- a device according to the invention which is to be used for metering and mixing more than two quantities of liquid, has a corresponding number of reservoirs with a corresponding number of connecting channel structures for integrated metering and mixing of more than two quantities of liquid.
- the method according to the invention and the device according to the invention can be used particularly effectively for the metering and mixing of biological fluids, in which a precise metering of very small amounts of fluid is necessary.
- the devices according to the invention can be operated automatically with a correspondingly designed automatic machine.
- FIG. 2 shows a section through an inventive device of FIG. 1 along the line A-B
- FIG. 3 shows a section through an inventive device of FIG. 1 along the line C-D
- FIG. 4 shows the section of FIG. 2 when carrying out a step of the method according to the invention
- FIG. 5 shows a modification of the device according to the invention of FIG. 1 in a horizontal cross-section
- FIG. 6 shows the section of a surface of a further embodiment of the device according to the invention with wetting-modulated surface
- FIG. 7 is a partial side view of the embodiment of FIG.
- 8 is a partial view of a surface of a modification of the embodiment of Fig. 6,
- FIGS. 10a-10c show horizontal cross sections through an embodiment according to the invention during three different states.
- FIGS. 1 to 4 comprises a disposable part made of plastic, for example. While Fig. 1 shows the horizontal cross section to illustrate the arrangement of the individual elements, Fig. 2 shows a section along the line A-B and Fig. 3 shows a section along the line C-D.
- the individual elements are, as clearly shown in FIGS. 2 to 4, cavities in the plastic part. In the lateral sectional figures, only the cavities are shown.
- the structures can be formed for example by pressing metallic counterparts of the molds and subsequently with a film - here from below - be completed.
- the plastic part can be produced as an injection molded part.
- Reservoirs 1 and 3 are connected to each other via a capillary channel 5.
- the reservoir 1 is connected via two further channels 7 with upwardly open filling nozzle 17.
- the channels 7 also have such a small cross-section that capillary forces act on a liquid therein.
- the reservoir 3 is connected via a capillary channel 11 with the filling nozzle 19.
- the dimensions and the process control are chosen so that the Reynolds number of the considered liquids is in the range of the laminar flow.
- the necessary parameters can be determined in preliminary tests. Typical viscosities of liquids used are in the range of 1 mPa-s to several 100 mPa s at speeds of 1 mm per second to 1 cm per second. Suitable system cross sections are then in the range of a few 100 microns with a total length of a few cm.
- acoustic chip 13 denotes an acoustic chip. This is, for example, a piezoelectric solid-state chip on which an interdigital transducer for generating surface acoustic waves is applied in a manner known per se.
- the interdigital transducer on the acoustic chip 13 is a unidirectional radiating transducer which generates surface acoustic waves only in the direction of the reservoir 1.
- acoustic chip 15 designates a further acoustic chip, which likewise carries an interdigital transducer in a manner known per se.
- This interdigital transducer is configured in such a way that the surface sound waves generated with it enable sound wave radiation into the reservoir 1.
- the emission of sound waves into a liquid volume, the is removed from the surface acoustic wave generating interdigital transducer by a solid, is described in DE 103 25 307 B3.
- the acoustic chip 15 may, for. B. also be provided on the other side of the reservoir 1.
- the acoustic chips 13, 15 are connected via electrical connections (not shown) to an AC voltage source with which an AC voltage of a frequency of a few 10 MHz can be generated in order to produce surface acoustic waves with the interdigital transducers.
- Such a device is used as follows for carrying out the method according to the invention.
- the reservoir 3 is filled with a small amount of liquid. Due to capillary forces, this liquid enters the channel 5. However, the liquid does not enter the reservoir 1, because there the cross-section is considerably larger and so the capillary force is abruptly weaker.
- the reservoir 1 is pressurized, for. B. completely filled by a pipette with a larger amount of another liquid. It is harmless if 17 supernatants remain in liquid in the filling channels 7 for the reservoir 1 or the filling nozzle. These do not participate in the mixing process to be carried out later by generating laminar flow patterns in the reservoir 1 for geometrical reasons and are therefore not relevant for the determination of the liquid volume participating in the mixing process.
- a laminar flow is generated by the momentum transfer of the surface acoustic waves to the liquid in the channel 5.
- the time duration over which the interdigital transducer is operated, or the pumping power the amount of liquid which flows laminarly via the capillary channel 5 into the reservoir 1 can be precisely determined.
- the determination of the necessary time duration or the pumping power can be determined for example on the basis of preliminary tests.
- the laminar flow thus ensures a defined supply of liquid.
- Fig. 5 shows a modification of the embodiment of Figs. 1 to 4.
- the capillary channel 6 between the reservoir 3 and the reservoir 1 is not rectilinear.
- An acoustic chip 14 with an interdigital transducer is used, which does not have to radiate unidirectionally here. It is sufficient if the acoustic chip 14 is arranged such that one of its emission directions points in the direction of the capillary channel 6.
- a surface acoustic wave is radiated in the indicated direction, the momentum transfer of which leads to the liquid in the capillary channel 6 to a laminar flow.
- Figs. 6 and 7 show an embodiment which can be realized on the surface of a solid-state chip.
- the reservoirs 101 and 103 include surface regions whose wetting properties are selected such that they are preferably wetted by a liquid.
- the reservoirs 101, 103 are hydrophilic compared to the surrounding solid surface. This is z. B. by
- the reservoirs 101 and 103 are connected by a flat interconnect channel structure 105 whose wetting properties are also chosen.
- an interdigital transducer On the surface is located in a manner not shown, an interdigital transducer whose emission direction along the channel 105 goes to produce laminar flow in the channel 105.
- the channel 105 is selected so narrow that capillary forces act on liquid thereon.
- Such a device is used as follows. A liquid drop 123 of a first liquid is applied to the reservoir 103 and, due to the described wetting properties of the surface, does not move outwardly from the reservoir 103 and is held together by its surface tension. Due to capillary forces, this liquid moves along the channel structure 105.
- Liquid droplet 121 is applied to the reservoir surface 101. Also, this liquid drop 121 is held together by the selected wetting properties of the surface and its surface tension. Its size is selected so that the reservoir surface 101 is completely filled. By selecting the size of the surface 101 so that the volume is determined. At the junction between the channel structure 105 and the reservoir surface 101, only negligible diffusion of the two liquids occurs due to the small cross section of the channel structure 105.
- the emission direction of which proceeds along the channel structure 105 laminar flow is created along the channel structure 105, which, as in the three-dimensional embodiments of FIGS. 1-5, leads to liquid transport along the channel structure 105.
- interdigital transducer In the area of the reservoir surface 101 there is an interdigital transducer, with the aid of which a laminar flow pattern for mixing the liquids is produced.
- the interdigital transducer is likewise not shown in FIGS. 6 and 7 for the sake of clarity.
- the operation of the two-dimensional structure of FIGS. 6 and 7 corresponds to the operation of the three-dimensional structures of FIGS. 1 to 5.
- FIGS. 6 and 7 show a modification of the embodiment of FIGS. 6 and 7.
- the reservoir surfaces 101 and 103 are not interconnected by a channel structure 105 here.
- a connection of the amounts of liquid 121 and 123 is done here by targeted introduction of a "bridge drop" 127 small volume, which provides a liquid bridge between the two liquid quantities, via the with the aid of the as in the embodiment of Figs. 6 and 7 generated laminar flow in the manner described a liquid transport can take place.
- FIG. 10 is a schematic representation of another Aidssom- tion.
- Reservoirs 201 and 203 are interconnected via two capillary structures 223, 227.
- An interdigital transducer 213, which is indicated only schematically, has at least one emission direction along the channel structure 227.
- Below the reservoir 201 there is a surface acoustic wave generation device 215, eg, a surface acoustic wave generator 215.
- B. also an interdigital transducer, which similar to the surface acoustic wave generating device 15 already described can emit a sound wave in the liquid in the overlying reservoir.
- a first liquid is introduced in the reservoir 203.
- the liquid enters the capillaries 223, 227 due to the capillary force.
- a second liquid is introduced into the reservoir 201 for its complete filling.
- the operation of the interdigital transducer 213 generates a surface acoustic wave at least in the direction indicated.
- the momentum transfer of the surface acoustic wave to the liquid in the channel 227 produces a laminar flow there.
- the liquid from the channel 227 enters the reservoir 201 and is replenished from the reservoir 203.
- the liquid boundaries 229, 231 move accordingly. Since it is a laminar and not a turbulent flow, apart from the diffusion at the liquid boundaries 229, 231 no mixing takes place. The result is a state as shown in Fig. 10b.
- the respective proportion of the liquids in the reservoir 201 can be determined.
- a surface acoustic wave is generated, which leads to the emission of a sound wave into the liquid in the reservoir 201 and there causes corresponding flow patterns for thorough mixing of the two liquids.
- the result is a mixture 233, as indicated in Fig. 10c.
- connection channel structures between the reservoirs can also be designed two-dimensionally with corresponding wetting structures as well as three-dimensionally with corresponding recesses or cavities.
- the figures are not to scale.
- the ratio of VoIu mina of the channel structures to the volume of the reservoirs z. B. between 1/10 to 1/100.
- the method according to the invention and the devices according to the invention make it possible to precisely meter in a quantity of liquid to a quantity of liquid defined by the volume of the second reservoir, for example by selecting the time during which a laminar flow is generated along the connection channel structure of the devices according to the invention.
- the method is easy to carry out and the device can be made small, compact and possibly disposable.
- the embodiments according to the invention can be operated in an automaton.
- a machine has z.
- B. a receptacle for a device according to the invention, which makes electrical contact with the Interdigitaltransducern.
- Automatically operated pipetting heads and / or dispensers are provided, which are arranged in such a way that they are arranged above the reservoirs or the filling structures when the device is inserted in the receptacle.
- a control preferably provided with a microprocessor unit, which serves for timing the pipetting heads / dispensers and the interdigital transducer in order to process a desired metering and mixing protocol.
- the evaluation instruments such. B. optical measuring devices, etc., to detect the possibly triggered by the mixing process reaction.
- reaction chamber 101 Reservoir surface, reaction chamber
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Processing And Handling Of Plastics And Other Materials For Molding In General (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102005000835A DE102005000835B3 (en) | 2005-01-05 | 2005-01-05 | Method and device for dosing small quantities of liquid |
PCT/EP2005/013598 WO2006072384A1 (en) | 2005-01-05 | 2005-12-16 | Method and device for dosing and mixing small amounts of liquid |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1843833A1 true EP1843833A1 (en) | 2007-10-17 |
EP1843833B1 EP1843833B1 (en) | 2009-04-15 |
Family
ID=35911180
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP05820542A Not-in-force EP1843833B1 (en) | 2005-01-05 | 2005-12-16 | Method and device for dosing and mixing small amounts of liquid, apparatus and use |
Country Status (6)
Country | Link |
---|---|
US (1) | US8186869B2 (en) |
EP (1) | EP1843833B1 (en) |
JP (1) | JP4956439B2 (en) |
AT (1) | ATE428492T1 (en) |
DE (2) | DE102005000835B3 (en) |
WO (1) | WO2006072384A1 (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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EP1833598B1 (en) * | 2005-01-05 | 2008-10-08 | Olympus Life Science Research Europa GmbH | Method and device for dosing and mixing small amounts of liquid |
JP2008100182A (en) * | 2006-10-20 | 2008-05-01 | Hitachi Plant Technologies Ltd | Emulsification apparatus and apparatus for manufacturing particulate |
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- 2005-12-16 JP JP2007549812A patent/JP4956439B2/en not_active Expired - Fee Related
- 2005-12-16 WO PCT/EP2005/013598 patent/WO2006072384A1/en active Application Filing
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WO2006072384A1 (en) | 2006-07-13 |
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DE502005007112D1 (en) | 2009-05-28 |
EP1843833B1 (en) | 2009-04-15 |
DE102005000835B3 (en) | 2006-09-07 |
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