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EP1833608A1 - Microreacteur - Google Patents

Microreacteur

Info

Publication number
EP1833608A1
EP1833608A1 EP05850267A EP05850267A EP1833608A1 EP 1833608 A1 EP1833608 A1 EP 1833608A1 EP 05850267 A EP05850267 A EP 05850267A EP 05850267 A EP05850267 A EP 05850267A EP 1833608 A1 EP1833608 A1 EP 1833608A1
Authority
EP
European Patent Office
Prior art keywords
fluid
magnetic
microfluidic
beads
magnetic particle
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.)
Withdrawn
Application number
EP05850267A
Other languages
German (de)
English (en)
Inventor
Matthias Franzreb
Tilmann Rogge
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.)
Karlsruher Institut fuer Technologie KIT
Original Assignee
Forschungszentrum Karlsruhe GmbH
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 Forschungszentrum Karlsruhe GmbH filed Critical Forschungszentrum Karlsruhe GmbH
Publication of EP1833608A1 publication Critical patent/EP1833608A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502761Containers 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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00457Dispensing or evacuation of the solid phase support
    • B01J2219/00459Beads
    • B01J2219/00466Beads in a slurry
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00457Dispensing or evacuation of the solid phase support
    • B01J2219/00459Beads
    • B01J2219/00468Beads by manipulation of individual beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/005Beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614Delimitation of the attachment areas
    • B01J2219/00621Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00722Nucleotides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00725Peptides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00731Saccharides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668Trapping microscopic beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877Flow chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples

Definitions

  • the invention relates to a device for transporting at least one magnetic particle fraction through a microfluidic system according to the preamble of the first claim.
  • Microfluidic systems are central handling systems for fluids, such as liquids or gases, with or without solids in micro- and nanotechnology, and are found particularly in the field of life sciences or biomedicine, where nano-objects in the form of large biomolecules, e.g. Peptides or proteins, must be handled [I]. Since direct handling of such small objects is seldom possible, so-called beads are often used in the field of life sciences. Beads are polymer bodies, usually spheres, on the functionalized surface of which e.g. DNA or proteins bound and so become manageable for synthesis or analysis. In this growing market, commercial devices are already being offered today, with which analyzes are carried out with the aid of individual beads [2].
  • Magnetic beads are commonly used in biochemistry today and are distributed by several commercial vendors (eg http://www.magneticmicrosphere.com/supply.htm). Such beads are usually superparamagnetic and monodisperse with diameters from 1 micron to 10 microns available and are used for analysis and synthesis purposes.
  • the handling of magnetic microbeads can be done on a larger scale with the help of so-called high-gradient magnetic separators [7].
  • a separation or fixation of magnetic microbeads usually takes place by simple permanent magnets based on rare earths.
  • this approach is quite inflexible and requires to release the fixation always moving components that allow a spatial separation between the reaction vessel with Magnetbeads and permanent magnet.
  • the object of the invention is therefore to provide a microfluidic system in which particle fractions (beads) are guided serially and directionally through channels and reaction chambers without a net movement of the fluid taking place.
  • Mass transfer in fluidic systems usually takes place via the movement of the fluid, with which the substances contained therein are moved to different locations.
  • the mass transfer within the device according to the invention is not carried out as usual by the flowing fluid, but by the Transport of the beads on the principle of a "fluidic ratchet".
  • the beads By generating a blocking force during the movement of the fluid, the beads can be fixed.
  • Ratchet is the name for a device z. B. tool in which a locking device allows only one direction of movement (freewheel), in the opposite direction it locks and moves an object z. B. screw or belt.
  • the directions of movement can be reversible.
  • the device according to the invention involves the provision of a microfluidic system in which particle fractions (beads) can be guided serially and directionally through channels and reaction chambers without a larger-scale fluid movement taking place.
  • a small-scale fluid movement which causes a movement of the particles, combined with a switchable force (blocking force), which at least fixed but at least significantly reduces the speed of movement of the particles.
  • the fluid movement may be generated mechanically or electrically (e.g., electro-osmosis).
  • the blocking force can be generated by magnetic fields acting on magnetic beads, by electrochemical induced electro fields induced by electrostatic fields due to dielectric constant differences of fluid and particles (dielectrophoresis, electrostatics) by optical fields generating forces due to refractive effects according to laser tweezers Surface forces that attach to the bead surfaces.
  • An actuator generates a periodic, small-scale forward and backward movement (freewheeling) of the fluid in the channel system.
  • an inhomogeneous magnetic field blocking device
  • the beads can be fixed during the return movement. Due to the fixation during the return movement of the fluid and the solution of the fixation during the forward movement, a directed movement of the beads through the channel system results without a net movement of the fluid. The directions of movement can be reversed.
  • Superparamagnetic particles are introduced into a fluidic channel system. As long as no other forces act on these particles, These particles are carried along with every movement of the fluid in the channel system. If a movement direction of the particles is blocked during a periodic fluid movement, the particles are transported in one direction. The surrounding fluid is moved by this periodic movement only by the volume amount of the particles in the reverse direction. The periodic movement of the fluid otherwise leads to no significant mixing, since in the smallest channel systems, a turbulent mixture is extremely difficult to achieve. The volume of the reaction chambers is extremely low, whereby the required amount of reactants is very low. Channel dimensions of a few micrometers and volumes of the reaction chambers in the nanoliter range are achieved.
  • the magnetic blocking force on the superparamagnetic particles should preferably be in the range of 10-100 pN.
  • the magnetic force on the particles results from the volume and the susceptibility of the particles as well as from the product of field strength times the gradient of the magnetic field. While the achievable field strengths are limited to a few teslas, very soft field micrographs can generate very high field gradients over short distances.
  • the magnetic holding force is achieved by soft magnetic microstructures immediately adjacent to the fluid region, which distort an externally generated magnetic field.
  • the smallest, lateral dimensions of these structures should correspond approximately to the diameter of the beads used, while the vertical dimensions should be three to ten times.
  • the production takes place after resist structuring with mask technique by electroplating. Subsequently, the structures are cast with plastic.
  • the plastic fulfills two functions. On the one hand, this creates a flat surface, which does not affect the bead movement. adversely. On the other hand, the plastic serves as a bonding partner for the
  • Housing part with the fluidic channel structures Housing part with the fluidic channel structures.
  • the particle motion depends on the flow velocity of the fluid, and can be well realized with spheres [12] as well as biological entities such as cells [13]. If no turbulences are formed during the periodic fluid movement, it is expected that the mass transfer within the fluid will not be significantly greater than the diffusion rate. As the extensive literature in the field of micromixers shows [14], [8] the intended induction of turbulence in microfluidic systems is difficult to achieve.
  • the device according to the invention fulfills various requirements for this purpose.
  • the fluid movement must be large enough to move particles through the fluid. These are in the channel system flow rates of about 1 - 10 mm / s necessary. The speed of the
  • Particles in the fluid channels from the ratio of channel size to particle size, the fluid velocity, the adhesion of the particles to the channel walls and the shape of the particles from.
  • the fluid channels must be designed so that a periodic fluid movement within the fluidic structures can spread well. It is important that the system is sufficiently incompressible and does not store the fluid movement elastically. Since the flow rate and thus also the movement of the beads depends on the channel cross-section, the flow rate can also be varied within the system. Thus broadening of the channel cross-section in the region of the reaction chambers can extend the residence time. The filling of the reaction chambers and the continuous supply of reactants are ensured by a slow flow through the reaction chambers perpendicular to the direction of movement of the beads. This also allows the complete replacement of the ingredients of individual reaction chambers.
  • the fluidic channels should have a cross-section that approximately corresponds to the bead size. For example, with a bead size of 4 ⁇ m, the channel width and height should not exceed 10 ⁇ m. Structures with these dimensions can be produced both by photolithography and X-ray lithography. Which method is most suitable depends on the required structural quality and the suitable plastics.
  • microstructures are carried out in many ways: with optical lithography (SU8, polyimide), by hot stamping (mold insert production by LIGA method or machining technique) or by X-ray deep lithography.
  • optical lithography SU8, polyimide
  • hot stamping molding insert production by LIGA method or machining technique
  • X-ray deep lithography X-ray deep lithography
  • microfluidic actuators is necessary at least at one point.
  • a periodic fluid movements must be generated, and / or requires the work with minimal amounts of material, for example, a metering devices with fast switching times.
  • Piezo actuators are suitable for both tasks, for example.
  • actuators lies in the short switching times (typically one millisecond) and the large force generated thereby.
  • the coupling of the mechanical movement into the system can take place either directly or via a translation system.
  • actuators can be represented via pressure spring systems or by shafts to electrically operated motors.
  • the functional principle of the device according to the invention requires a periodic fluid movement, which can only be used efficiently if the system is incompressible and the fluid has only a freely movable interface at the exit (eg gas bubble). This requires Rigid fluid supply or high flow resistance in the fluid supply area. Furthermore, a simple Bead-removal is possible at any time. For this purpose, the beads are collected in at least one chamber and flushed out as needed.
  • the AMS to the desired peptide length.
  • the beads are guided through the individual reaction areas of the device.
  • the device according to the invention allows for purposes in which only small amounts of material are needed, a fast and material-saving synthesis of complex molecules, for example peptides, proteins, oligonucleotides, DNA, oligosaccharides or RNA, whose synthesis is carried out by successive individual reactions. Small quantities of substances, but with a wide range of variations, are needed, for example, in the context of drug discovery and development in pharmaceutics and biomedicine.
  • the quantities of substances and times required for sequencing proteins or DNA sections can be further reduced.
  • the proteins or DNA sections are bound to beads and analyzed stepwise during the passage of various reaction chambers.
  • the device according to the invention can by additional components be extended for detection, such as magnetoelectric [16], by (integrated) optical systems [2] or electrochemical [17].
  • a combination of synthesis, reaction and analysis can also be carried out with the device according to the invention. For example, molecules can be synthesized in a first area, exposed to various substances in a subsequent area, and then directly analyzed.
  • sensors can be introduced into the reaction chambers or the fluid channels to more precisely control the reactions.
  • FIG. 1 System elements and principle for magnetic ratchet Fig. 2 Exemplary microstructure for generating an inhomogeneous magnetic field
  • FIG. 4 Exemplary Production of a Fluid Structure
  • FIG. 5 Exemplary Production of a Bond Connection
  • FIG. 6 Exemplary Construction of a Device According to the Invention
  • Fig. 1 shows a schematic sectional view of the essential elements and the principle of a fluidic ratchet.
  • an actuator 1 for generating a fluid flow 8 in the fluid channels 6.
  • the fluid flow 8 moves the beads 4. Equipped with a mixing chamber volume 3 and a microstructured soft iron magnetic core 2 for generating a magnetic blocking force.
  • the device is completed with a housing 5.
  • the fluid moves 8 and with him the beads 7. If the blocking force is turned on, the beads are fixed in the direction of magnetic structure. 9
  • FIG. 2 shows a schematic sectional view with the field lines 10 of an inhomogeneous magnetic field which has been switched on, produced by an NEN soft iron magnetic core 2 in microstructure is embedded in plastic 11.
  • the magnetic beads 4 are fixed from the fluid-filled channel 6 direction 9 magnetic core 12.
  • FIG. 3 shows, by way of example, the schematic illustration of the production of the soft-magnetic microstructure in which an electroplating start layer 16 is deposited on substrate 13 (for example silicon or glass), then resist 15 is applied by spin coating and patterned, followed by electroplating with, for example Permalloy (NiFe in the ratio (80/20) and the spin coating of the sealing layer 14.
  • substrate 13 for example silicon or glass
  • resist 15 is applied by spin coating and patterned, followed by electroplating with, for example Permalloy (NiFe in the ratio (80/20) and the spin coating of the sealing layer 14.
  • FIG. 4 shows, by way of example, the schematic production of a microfluidic channel structure " .8 Openings 19, which serve to supply fluid, are introduced into the substrate 13. These holes can be introduced mechanically (for example drilling, lasing), wet-chemically or by reactive ion etching.
  • the trench structures are formed by structuring (stripping) the resist spun onto the substrate (for example SU8, PMMA, polyimide).
  • FIG. 5 shows the bonding of the structures produced in FIG. 3 and FIG. 4 by pressure 20 and heat 20, thereby creating the microfluidic channel structures 21.
  • FIG. 6 shows an exemplary embodiment of a device according to the invention consists of a microstructured magnet, a microfluidic channel structure, an actuator and fluidic connections.
  • the supervision of this system shows the fluidic structures.
  • the time required for bead transport 8 periodic fluid movement 7 is generated by an actuator 1, which is located at the beginning of the fluid system.
  • an actuator 1 located at the beginning of the fluid system.
  • the beads are introduced into the system and after the fluidic ratchet principle [Fig. 1] moves through the microfluidic channel.
  • a compensation chamber 24 at the end of the fluid structure with a free liquid level allows the periodic movement.
  • the residence time of the beads 4 can be regulated by the geometric shape, where column structures lead the beads 4 there.
  • the beads are collected and rinsed out if necessary.
  • the reaction substances are fed perpendicularly to the direction of movement via the microfluidic fluid guide.
  • introduction 26 and branch 22 the filling of the chambers is facilitated and also allows a continuous regulation of the substance concentration.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'objet de la présente invention est la mise au point d'un dispositif permettant la production d'un système microfluidique dans lequel des fractions particulaires (billes) peuvent être guidées de manière sérielle et dirigée dans des canaux et des chambres de réaction sans qu'il en résulte un mouvement net de fluide. A cet effet, un mouvement de fluide à petite échelle qui provoque un mouvement des particules est combiné avec une force commutable (force de blocage) qui fixe les particules. Ledit dispositif est approprié pour être utilisé dans la bioanalyse ou la synthèse chimique.
EP05850267A 2004-12-24 2005-12-14 Microreacteur Withdrawn EP1833608A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200410062534 DE102004062534B4 (de) 2004-12-24 2004-12-24 Mikroreaktor
PCT/EP2005/013425 WO2006069627A1 (fr) 2004-12-24 2005-12-14 Microreacteur

Publications (1)

Publication Number Publication Date
EP1833608A1 true EP1833608A1 (fr) 2007-09-19

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP05850267A Withdrawn EP1833608A1 (fr) 2004-12-24 2005-12-14 Microreacteur

Country Status (3)

Country Link
EP (1) EP1833608A1 (fr)
DE (1) DE102004062534B4 (fr)
WO (1) WO2006069627A1 (fr)

Families Citing this family (4)

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Publication number Priority date Publication date Assignee Title
ATE542136T1 (de) * 2010-03-15 2012-02-15 Boehringer Ingelheim Int Vorrichtung und verfahren zur manipulation oder untersuchung einer flüssigen probe
DE102011076051A1 (de) 2011-05-18 2012-11-22 Siemens Aktiengesellschaft Magnetophoretische Analytselektion und -anreicherung
DE102011077905A1 (de) * 2011-06-21 2012-12-27 Siemens Aktiengesellschaft Hintergrundfreie magnetische Durchflusszytometrie
DE102012211626A1 (de) * 2012-07-04 2014-01-09 Siemens Aktiengesellschaft Anordnung zur Quantifizierung von Zellen einer Zellsuspension

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DE19949912C2 (de) * 1999-10-16 2003-02-27 Karlsruhe Forschzent Vorrichtung für eine Kraftübersetzung, Verfahren zu deren Herstellung und deren Verwendung
AU2000274922A1 (en) * 2000-08-08 2002-02-18 Aviva Biosciences Corporation Methods for manipulating moieties in microfluidic systems
ATE303863T1 (de) * 2000-10-17 2005-09-15 Febit Ag Verfahren und vorrichtung zur integrierten synthese und analytbestimmung an einem träger
DE10057396C1 (de) * 2000-11-18 2002-04-04 Karlsruhe Forschzent Verfahren zum Abtrennen eines dispergierten oder gelösten Stoffes und Magnetseparator
US20030073110A1 (en) * 2001-07-03 2003-04-17 Masaharu Aritomi Method for isolating nucleic acid and a cartridge for chemical reaction and for nucleic acid isolation
JP2005511066A (ja) * 2001-12-07 2005-04-28 ダイアックス、コープ 磁気応答性粒子を洗浄する方法及び装置
DE10231925A1 (de) * 2002-07-10 2004-01-22 Horst Dr. Ahlers Reaktorsystem zur Durchführung chemischer und biochemischer Prozesse
DE10320869A1 (de) * 2003-05-09 2004-12-16 Evotec Technologies Gmbh Verfahren und Vorrichtungen zur Flüssigkeitsbehandlung suspendierter Partikel

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Title
See references of WO2006069627A1 *

Also Published As

Publication number Publication date
DE102004062534A1 (de) 2006-07-06
WO2006069627A1 (fr) 2006-07-06
DE102004062534B4 (de) 2007-05-10

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