EP1082594A2 - Procede et dispositif pour traiter des quantites infimes de substances - Google Patents

Procede et dispositif pour traiter des quantites infimes de substances

Info

Publication number
EP1082594A2
EP1082594A2 EP99926440A EP99926440A EP1082594A2 EP 1082594 A2 EP1082594 A2 EP 1082594A2 EP 99926440 A EP99926440 A EP 99926440A EP 99926440 A EP99926440 A EP 99926440A EP 1082594 A2 EP1082594 A2 EP 1082594A2
Authority
EP
European Patent Office
Prior art keywords
reservoir
carrier material
substance
carrier
magnetic
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.)
Ceased
Application number
EP99926440A
Other languages
German (de)
English (en)
Inventor
Markus Kalkum
Martin Müller
Eckhard Nordhoff
Richard Reinhardt
Holger Eickhoff
Holger Rauth
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Original Assignee
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Max Planck Gesellschaft zur Foerderung der Wissenschaften eV filed Critical Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Publication of EP1082594A2 publication Critical patent/EP1082594A2/fr
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
    • 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
    • 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
    • G01N2035/1041—Ink-jet like dispensers
    • 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
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1053—General features of the devices using the transfer device for another function for separating part of the liquid, e.g. filters, extraction phase
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • the invention relates to methods for processing very small amounts of substance in the reservoir of a fluid metering device, in particular to a method for collecting, cleaning and / or concentrating substance samples in capillary-shaped containers, e.g. in micropipettes or microdispensers, and devices for implementing the methods.
  • a magnetic separation device for separating magnetic particles from a non-magnetic test medium.
  • the magnetic particles are small particles on the surfaces of which the substances of interest are bound, or, for example, biological cells in which magnetic substances are incorporated. With a large number of magnets, a magnetic field gradient is built up in the test medium in such a way that the magnetic particles are moved to the vessel wall and collected there.
  • the magnetic separator known from US-A-5 186 872 has the following disadvantages.
  • the separator has a complex structure. To form the field gradients, at least four magnets must be present, which are arranged in a predetermined manner and require the use of certain containers for the test medium.
  • the for characteristic container dimensions in the cm range designed conventional separation device allows, especially when using electromagnets, no miniaturization. This prevents use at the above-mentioned interface between macroscopic containers and miniature carriers for the tools used.
  • the conventional separation device is limited to the pure separation process. The loading of magnetic particles with the substances of interest in the separating device is not provided.
  • a sample collector is known from US Pat. No. 5,498,550 in which complexes of protein samples and magnetically labeled antibodies are manipulated in a reactor under the action of an external magnetic field.
  • this sample collector is not suitable for handling substance quantities with volumes in the nl to ⁇ l range.
  • Another disadvantage is the restriction to certain substances that enter into the respective antigen-antibody reaction for complex formation.
  • a system for controlling magnetic particles in pipetting arrangements is also known from WO 97/44671 and JP 08/062224 (in: Patent Abstracts of Japan, 1996). The magnetic particles are suspended in a pipette-shaped cuvette and can be pulled to the edge of the cuvette with an external permanent magnet. When the permanent magnet is removed, the particles are released and can sink to the open end of the cuvette.
  • This system is also limited to the manipulation of larger sample volumes in the ml range. Furthermore, there is a disadvantage in that the particle control only comprises the binding or release, but not a specific movement of the particles in the cuvette.
  • a magnetic separation device is described in WO 96/09550 (or US Pat. No. 5,567,326), in which magnetizable particles are extracted from a non-magnetic test medium. The test medium is housed in a cuvette arrangement in which each cuvette is diving a pin-shaped permanent magnet is set up. The disadvantage of this technique is that the cuvettes do not allow the test medium to be dispersed, and thus that
  • Test medium is difficult to handle.
  • the method should be easy to integrate into the usual methods for sample handling, sample detection and sample processing from biochemistry, genetic engineering and medicine.
  • the object of the invention is also to provide a device for implementing such a method.
  • the object of the invention is achieved by a method or devices according to claims 1 and 11, respectively. Preferred embodiments of the invention result from the dependent claims.
  • the method according to the invention for collecting substance samples is based on the arrangement and movement of a solid phase (carrier material) directly in the reservoir of a microdosing device, the substance of interest being bound on the surface of the carrier material and being held in the reservoir for a predetermined sequence of work steps.
  • the reservoir has a characteristic volume that is generally less than 500 ⁇ l and preferably less than 10 ⁇ l, in particular less than 2 ⁇ l, up to 1 nl.
  • the dosing device is designed for microdrop delivery in the sub nl range.
  • the carrier material can be formed by magnetic particles which are moved by an external magnetic field force or by a porous carrier ball which is moved by an external mechanical actuation.
  • the carrier material consists of an inherently incompressible and hard material. This means that the carrier material does not undergo a change in shape when the metering device is actuated, for example by applying a pressure pulse.
  • the bond between the substance or substances of interest and the surface of the carrier material takes place via the formation of van der Vaals forces due to hydrophobic interactions. This means that the binding takes place with a relatively low specificity with regard to the individual substance and the invention can thus be implemented with entire substance classes in mixtures of substances (e.g. mixtures of peptides, proteins, DNA or oligonucleotides).
  • the term “reservoir” of the dosing device here denotes the active dosing volume or stroke volume or - when implemented with appropriate devices - the pipette volume or the dispenser volume.
  • the metering device can be formed by any suitable pumping or metering device which is set up to deliver predetermined amounts of fluid from the reservoir to a target substrate.
  • the invention is preferably implemented with dosing devices for the smallest amounts of substance (nanoliter and sub-nanoliter). These include, for example, micropipettes or microdispensers or micropumps (in particular with a pneumatic or electric drive) or other microdroplet devices which function analogously to the inkjet techniques.
  • the carrier material is preferably arranged or moved in the immediate vicinity of an outlet opening of the reservoir of the metering device.
  • a particular advantage of the invention is its compatibility with any conventional metering device. It was found for the first time that a sample collection according to the principle of the known solid phase purification in metering devices is possible without impairing their function. This applies in particular to the implementation of the invention in microdosing devices with nl volumes.
  • a device according to the invention is characterized in that a carrier as a solid phase with a binding-active surface is arranged in the reservoir of a fluid metering device and can be manipulated with an external drive device.
  • a plurality of fluid metering devices are preferably operated in parallel, only one common drive device being provided for manipulating the solid phases.
  • the invention has the advantage that the problem of miniaturized sample purification or collection is solved for the first time.
  • the invention is simple with available micropipettes or microdispensers, especially with their single or serial use, can be implemented without disrupting conventional processes.
  • For the first time it has been possible to bind sample substances to a carrier material in microdispensers and to move them in the microdispenser without restricting the function of the microdispenser. This is an unexpected and significant success, since normally, for example, piezoelectric microdispensers show a functional failure if there is a compressible component inside, for example based on particles, suspended liquids or gas inclusions.
  • a particular advantage of the invention relates to use with micropipettes or microdispensers.
  • the geometric properties of the dispenser tip and the electrical piezo parameters must be optimally coordinated.
  • the invention makes it possible that the solid carrier material required for a temporary attachment of the molecules does not interfere with the dispersion process, ie neither the vessel dimensions nor the pressure wave running through the liquid are effectively influenced. Further advantages and details of the invention are described below with reference to the accompanying drawings:
  • FIG. 1 a schematic illustration of a first embodiment of the invention, in which a magnetic carrier material is used in a metering device
  • FIG. 2 a schematic illustration of a second embodiment of the invention in which a porous carrier bale is used in a metering device
  • FIG. 3 shows a schematic top view of a device according to the invention with a number of microdispensers, each of which is set up to implement the method according to the invention
  • FIG. 4 a schematic side view of the device according to FIG. 3.
  • the invention is preferably implemented with metering devices which are set up for dispensing liquid quantities in the nl to pl range.
  • the dosing device each has a dosing reservoir in the 1/10 nl to ⁇ l range, from which droplets or portions with volumes below 100 pl can be dispensed, preferably when actuated by pressure.
  • An example of such a metering device is a microdispenser, as described below with reference to FIGS. 1 and 2 will be explained.
  • the piezoelectric dispenser 1 shows an example of the end of a piezoelectric microdispenser that was used to implement the method according to the invention in accordance with a first embodiment of the invention (magnetic manipulation of the solid carrier material). is aimed.
  • the piezoelectric dispenser 1 comprises an electrical converter 2 and a dosing reservoir 3, which is formed by a capillary.
  • the converter 2 is set up to reduce the volume of the metering reservoir 3 in the form of a pulse. When the converter 2 is actuated for a pulse time
  • a pressure wave runs through the liquid 4 in the dosing reservoir 3. This causes a liquid to be ejected at the outlet 5 (diameter around 50 ⁇ m) of the dosing reservoir 3, which is formed here by the end of the capillary ( Dispenser tip).
  • the liquid 4 comprises, for example, a solution or suspension of sample molecules which, in biochemical applications, comprise peptides, proteins, nucleic acids or DNA molecules, fats or carbohydrates.
  • sample molecules which, in biochemical applications, comprise peptides, proteins, nucleic acids or DNA molecules, fats or carbohydrates.
  • a large number of magnetic particles 7 are arranged in the dosing reservoir 3, preferably in the vicinity of the outlet 5, which are provided with a drive device for holding and / or moving the magnetic Particles 7 in the form of a magnetic device 8 can be manipulated.
  • the magnet device 8 comprises two permanent magnets 81, 82, each with a variable distance with respect to the dosing reservoir 3 with the magnetic particles. Both permanent magnets 81, 82 point toward the reservoir 3 with the same pole. Further details of the magnet device 8 and an associated drive device (not shown here) are explained below with reference to FIGS. 3 and 4.
  • the magnetic particles 7 have a diameter which is approximately one to two powers of ten smaller than the diameter of the dispenser nozzle (outlet 5) and preferably in the region from 0.25 to 2 ⁇ m. This ensures that the particles
  • the deposited particles 7, i.e. the particles adhering to the inner wall of the dispenser under the magnetic field force do not impede the piezoelectric dispensing process due to their small spatial expansion.
  • the particles 7 have an affinity for the sample molecules, so that they are bound to the particles from the liquid 4 inside the dispenser tip.
  • the magnetic particles 7 can be moved in a predetermined manner in the metering reservoir 3 by changing the magnetic field forces.
  • the magnetic field forces are changed by moving the microdispenser 1 and the magnet device 8 relative to one another, the permanent magnets 81, 82 preferably being moved with respect to the stationary dispenser tip.
  • the particles 7, which form the solid carrier material (solid phase) are moved through the liquid 4, flowed around by it and mixed with it, so that further sample molecules are bound while other solution components remain in the liquid 4.
  • the sample molecules of interest can be collected in sufficient quantities (enrichment).
  • the targeted movement of the particles with the bound sample substances through the liquid represents an essential advantage of the invention that cannot be achieved by conventional dispensing systems with large liquid volumes. According to the invention, not only statically bound or released states are decisive for the particles, but also dynamically bound states, in which are deliberately moved through the liquid. Further processing steps are explained below.
  • the permanent magnets 81, 82 are preferably NdFeB magnets with an application-specific remanence. When used with microdispensers, the remanence is preferably approx. 1 Tesla to 1.5 Tesla.
  • Fig. 2 shows a second embodiment of the invention, again using the example of a microdispenser 1 with a piezoelectric transducer 2 and a dosing reservoir 3, from the outlet 5 of which a microdrop 6 can be dispensed when the transducer 2 is actuated.
  • a carrier bale 9 is provided as the carrier material, which has a drive device for holding and / or moving the bale 9 in the form of a thread-like or rod-shaped actuating element 91, which is movable through the metering reservoir 3 of the dispenser 1 (arrow direction).
  • the carrier bale 9 is a coherent, sponge-like solid phase which has the largest possible active surface.
  • the preferably porous, but incompressible material of the carrier bale 9 consists, for example, of nitrocellulose or a column filling material such as is used in HPLC separations (for example material "Porous" (registered trademark)).
  • a mechanical operating principle is implemented in the second embodiment.
  • the carrier bale 9 is moved with the actuating element 91 through the interior of the dosing reservoir 3 in order to collect sample molecules.
  • the carrier bale 9 can be flowed through by the liquid 4 in the microdispenser 4, so that an undesired dispensing of liquid is avoided.
  • the carrier bale 9 is pulled upward through the dispenser tip through the transducer 2.
  • a dosing device is prepared by taking up the solid carrier material in the reservoir of the dosing device.
  • the magnetic particles are taken up and deposited in the reservoir (for example in the metering reservoir of the microdispenser), in which a particle suspension is filled into the reservoir either through the outlet of the reservoir or through an additional supply line with the simultaneous action of the magnetic field forces . Under the action of the magnetic field forces, the particles are immediately drawn to a reservoir wall and held there (landfill).
  • the preparation step comprises feeding the carrier bale into the reservoir of the metering device and fixing the actuating element used for this purpose in such a way that the carrier bale is positioned in the reservoir near its outlet.
  • a solution is added or the substance samples of interest are dispensed. This recording is carried out accordingly through an outlet of the metering device or through an additional supply line.
  • the forces acting on the respective carrier material are changed in such a way that the carrier material moves through the absorbed solution or suspension and is thereby washed around by it, so that the substance binds to the carrier material.
  • the magnetic field forces are changed such that the magnetic particles move from the original deposit site to another part of the reservoir wall (e.g. opposite wall).
  • the drive element (for example in FIG. 2, reference number 91) is moved in such a way that the carrier material is flushed around by the solution or suspension.
  • the movement of the carrier material through the liquid is preferably carried out periodically with a large number of movements.
  • the speed and The duration of the carrier material movement and thus of the binding step are chosen depending on the application.
  • the liquid is discharged from the reservoir of the metering device through the outlet or through a line leading away from the opposite (upper) end.
  • a further solution or suspension with the substance of interest or without a sample substance can now be added.
  • the substance is enriched in the reservoir.
  • Concentration is initially carried out in the bound state on the carrier materials.
  • the bound substance is then released into the liquid or suspension again by taking up a suitable elution solution in the reservoir.
  • the elution solution has a higher concentration than the originally supplied solution.
  • the second In this case it can be provided to supply a cleaning solution with which a predetermined type of substances which were unintentionally bound to the carrier materials in the previous binding step can be detached again. This corresponds to cleaning or another selective choice of substances. The substance is then detached again from the carrier materials using a suitable elution solution.
  • micro-preparative and microsynthetic purposes can also be pursued with suitable repetition with selected substances. It is thus possible, for example, to first collect and / or clean a first reaction partner in the reservoir, in order then to react it with a correspondingly collected and / or cleaned second reaction partner. This reaction can take place in the bound state on the carrier material or in the dissolved or suspended state in the reservoir or after dispensing on a substrate.
  • the intended dosing with the dosing device is carried out by dispensing the concentrated or purified solution onto a target substrate.
  • this is done by dropping drops through the outlet as intended.
  • peptides from a volume of the order of 1 .mu.l to 2 .mu.l are bound to the surface of magnetic particles, then with approx. 10 ⁇ l of rinsing liquid are cleaned and then eluted in a few 100 nl to 10 nl.
  • Several analyzes of each eluate are made with application-specific amounts of substance. For this purpose, approx. 0.1 nl to 1.0 nl per analysis dispensed onto a sample carrier.
  • FIGS. 3 and 4 schematically show a processing station for the parallel processing of a large number of substances in top and side views.
  • the processing station comprises a dispenser unit 10 with a multiplicity of microdispensers 1 (for example piezoelectric dispenser according to FIG. 1), a magnet unit 20 with a multiplicity of magnet devices 8 and a drive unit 30 which is used to adjust the position or to move the magnet unit 20 is set up in relation to the dispenser unit 10.
  • a dispenser unit 10 with a multiplicity of microdispensers 1 (for example piezoelectric dispenser according to FIG. 1)
  • a magnet unit 20 with a multiplicity of magnet devices 8
  • a drive unit 30 which is used to adjust the position or to move the magnet unit 20 is set up in relation to the dispenser unit 10.
  • the microdispensers 1 of the dispenser unit 10 are arranged as a straight row.
  • the number and spacing of the microdispensers are selected depending on the application and the shape of the respective macroscopic container from which samples are to be taken.
  • the arrangement of the microdispensers is preferably adapted to the shape of a microtiter plate. In the embodiment shown, for example sixteen microdispensers 1 are provided corresponding to a microtiter plate with sixteen volumes arranged in rows.
  • the microdispensers 1 are attached to a holding and adjusting device (not shown).
  • the magnet unit 20 comprises a plurality of magnet devices 8, the number of which is at least equal to the number of microdispensers 1. Preferably, however, at the ends of the Row of microdispensers 1 each to create an additional magnetic unit to create uniform field conditions in the microdispensers at the ends of the row.
  • Each magnet device 8 consists of two spaced apart permanent magnets 81, 82, between each of which a microdispenser is arranged for substance processing.
  • the permanent magnets 81, 82 are fastened to the longitudinal sides of a frame 21 which surrounds the row of microdispensers and which extends in a manner corresponding to the row of dispensers.
  • the frame 21 can be moved with the drive unit 30 in a direction parallel to the longitudinal extent of the microdispensers 1 (up / down movement) and in a reference plane oriented perpendicular to the microdispensers 1 (forward / backward movement).
  • the long sides of the frame 21 are spaced such that a microdispenser in a position immediately adjacent to one of the permanent magnets 81, 82 is exposed essentially exclusively to the field forces of this permanent magnet and negligibly low field forces of the opposite permanent magnet.
  • the distance is chosen so that when the microdispensers change position from one to the opposite permanent manganese (forward / backward movement), the particles cannot sink so far towards the outlet under the effect of gravity that they affect the force action range of the respective permanent magnet. This ensures that the particles do not reach the outlet and cannot cause any disturbances due to clogging or the like.
  • the distance of the permanent magnet rows along the long side of the frame 21 is less than 1 cm when combined with microdispensers and is preferably approx. 6 mm to 7.5 mm.
  • the drive unit 30 comprises two servomotors 31, which
  • Pivot levers 32 are connected to the ends of the frame 21. By simultaneously actuating the servo motors 31, the frame 21 with the swivel levers 32 can be pivoted from a first position in which the dispenser row is arranged near one permanent magnet row (permanent magnets 81) to a second position in which the dispenser row is close to the respective other permanent magnet row ( Permanent magnet 82) is arranged. All dispensers and all permanent magnets are advantageously moved simultaneously relative to one another.
  • the servomotors are preferably set up to provide different swiveling speeds. For example, three swivel speeds are provided, at which different particle speeds are achieved in the reservoir of each microdispenser. With the three swiveling speeds, the change of position from the first to the second position requires, for example, approx. a quarter of a second, a half a second or a second and a half.
  • the drive unit 30 further comprises two adjusting devices 33, with which the height position of the magnet devices 8 with respect to the longitudinal direction of the microdispensers can be adjusted.
  • the actuating devices 33 are preferably spring suspensions with predetermined setting positions. There is preferably a first position in which the processing takes place in the microdispensers and a second position in which the dispenser ends protrude below the level of the frame 21, for example in order to be filled into a vessel (for example into the volumes of a microtiter plate) to become.
  • the servomotors 31 with the frame 21 for releasing the dispenser tips are pressed upwards against return springs of the actuating device 33 and anchored in the filling position.
  • the drive unit 30 also has a motor suspension 34, the actuation of which is in turn synchronized with the mounting and actuating device of the row of dispensers.
  • the processing station according to FIGS. 3 and 4 must be adapted accordingly. Accordingly, the carrier bales are to be fastened in rows to a common carrier and to be actuated with adapted actuating elements in a direction corresponding to the longitudinal direction of the microdispenser (up / down movement).
  • the actuating elements in particular have a wire or thread suspension for each carrier bale, with which the carrier bale can be pulled up from the outlet (or the nozzle) of the microdispenser to an upper dispenser area.
  • the suspension Above the piezoelectric transducer, the suspension can be moved magnetically or mechanically.
  • the processing according to the invention of the smallest amounts of substances in microdispensers has the advantage that only small amounts of the eluent are required in order to elute the bound sample substances in the dispenser tip from the solid phase.
  • 100 to 300 nl of a mixture of acetonitrile (80% by volume) with trifluoroacetic acid (0.1% by volume) are used as eluents.
  • the elution agent is taken up through the microdispenser outlet (nozzle) by creating a negative pressure (for example about 10 mbar) on the microdispenser via a supply line.
  • the eluent is sucked into the microdispenser by adjusting the surface forces or the capillary forces.
  • the implementation of the invention is not limited to the embodiments described above. In particular, the following modifications are possible.
  • the use of magnetically and mechanically actuated carrier materials is possible simultaneously.
  • two permanent magnets it is possible to provide only one permanent magnet, the position of which in relation to the respective microdispenser is changed with an adjusting device so that the magnetic particles remain constantly under the influence of the field.
  • More than two permanent magnets can also be provided per dispenser.
  • the microdispensers or micropipettes described other metering devices can also be used. Additional means for shaping the magnetic field in the area of the reservoirs of the microdispensers can be provided.
  • electromagnets or magnets based on micro superconductors can be used if there is enough space for their positioning.
  • the steps of the method according to the invention described above can be repeated and modified in order to achieve certain processings.

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  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Devices And Processes Conducted In The Presence Of Fluids And Solid Particles (AREA)

Abstract

Pour traiter des substances dans un réservoir (3) d'une unité de dosage de microgouttelettes (1), un matériau support solide dont la surface présente une activité de liaison est déplacé dans le réservoir, et la substance est liée à la surface du matériau support qui comprend des particules magnétiques (7) ou une balle support.
EP99926440A 1998-05-27 1999-05-27 Procede et dispositif pour traiter des quantites infimes de substances Ceased EP1082594A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19823719 1998-05-27
DE19823719A DE19823719B4 (de) 1998-05-27 1998-05-27 Verfahren zum Aufkonzentrieren von Substanzen
PCT/EP1999/003667 WO1999061881A2 (fr) 1998-05-27 1999-05-27 Procede et dispositif pour traiter des quantites infimes de substances

Publications (1)

Publication Number Publication Date
EP1082594A2 true EP1082594A2 (fr) 2001-03-14

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP99926440A Ceased EP1082594A2 (fr) 1998-05-27 1999-05-27 Procede et dispositif pour traiter des quantites infimes de substances

Country Status (4)

Country Link
US (1) US7105357B1 (fr)
EP (1) EP1082594A2 (fr)
DE (1) DE19823719B4 (fr)
WO (1) WO1999061881A2 (fr)

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US7105357B1 (en) 2006-09-12

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