EP1397483B1 - Systeme microfluidique - Google Patents

Systeme microfluidique Download PDF

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Publication number
EP1397483B1
EP1397483B1 EP03718772A EP03718772A EP1397483B1 EP 1397483 B1 EP1397483 B1 EP 1397483B1 EP 03718772 A EP03718772 A EP 03718772A EP 03718772 A EP03718772 A EP 03718772A EP 1397483 B1 EP1397483 B1 EP 1397483B1
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EP
European Patent Office
Prior art keywords
reservoir
micro
reservoirs
fluid system
channel
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.)
Expired - Lifetime
Application number
EP03718772A
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German (de)
English (en)
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EP1397483A1 (fr
Inventor
Johan-Valentin Kahl
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.)
Ibidi GmbH
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Ibidi GmbH
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Filing date
Publication date
Priority claimed from EP02008966A external-priority patent/EP1357178A1/fr
Priority claimed from DE2002124725 external-priority patent/DE10224725A1/de
Application filed by Ibidi GmbH filed Critical Ibidi GmbH
Priority to EP03718772A priority Critical patent/EP1397483B1/fr
Publication of EP1397483A1 publication Critical patent/EP1397483A1/fr
Application granted granted Critical
Publication of EP1397483B1 publication Critical patent/EP1397483B1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2400/0457—Moving fluids with specific forces or mechanical means specific forces passive flow or gravitation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0605—Valves, specific forms thereof check valves

Definitions

  • the invention relates to a microfluid system with a substrate, at least two reservoirs and at least one channel integrated into the substrate, the two reservoirs combines.
  • the pumps may be mounted in or on the microfluidic system. pump however, have many disadvantages. Thus, the microfluidic system can only be used in conjunction with an external power source and must be connected to this permanently become. (For an integrated pump, a power cable is required with one external pump, the system must be connected to hoses).
  • Another application is the detection of certain substances in a channel system, where it is necessary to pass certain liquids through one after the other to run the same channel. Again, these are flow rates and reaction times observed. Pumps would have to work extremely accurately and have a special Electronics are controlled.
  • the object of the invention is to provide a microfluid system with which in a simple Way liquids can be transported and without the microfluid system requires an external connection.
  • microfluidic system acts it is a microfluid system with a substrate, at least two reservoirs and at least one channel integrated in the substrate, which connects two reservoirs, the mouth of at least one channel above the base of a Reservoirs is arranged.
  • liquids can be transported in a simple manner be tilted by the microfluidic system to one side, which a liquid from a reservoir (a higher reservoir) through a associated channel in a arranged at the other end of the channel reservoir flows.
  • a liquid enters this mouth through Reservoir flows, thereby preventing the liquid from flowing back into the channel can.
  • the fluid in a reservoir into which a channel with a arranged above the base mouth opens so the flows Liquid only from the reservoir, if sufficient inclination of the Micro fluid system is reached so that the liquid can penetrate into the channel. In this way it can also be achieved that only a predetermined amount of liquid flows from a filled reservoir into a canal.
  • the microfluidic system according to the invention can have a plurality of channels and / or Reservoirs include.
  • Several channels can lead into a reservoir. advantageously, various channels at different heights open into a reservoir.
  • Several reservoirs can be filled with different liquids.
  • the channels may preferably intersect and / or divide. That way you can from different reservoirs, possibly according to inclination, different liquids flow into the same channel.
  • the reservoirs and channels can be advantageously also be arranged such that thereby a closed fluid circuit is formed.
  • the footprint of at least one reservoir relative to a reservoir sidewall be inclined. This means that the angle between the base and the side wall is not equal to ⁇ / 2. With such a suitably chosen reservoir geometry can be further adjusted at which angle of inclination of the microfluidic system a liquid from a reservoir flows into a channel.
  • the microfluid system can be completed be and include a pressure equalization device that each reservoir with at least connects to another reservoir. This can in particular an airtight To be completed.
  • the pressure compensation device may be in the form of integrated into the substrate Can be formed channels that open into the reservoirs so that no Liquid can penetrate and thus serve only the gas or pressure equalization.
  • the device may preferably also be in the form of lines which connect the reservoirs, but are not integrated into the substrate.
  • the reservoirs may be gas permeable Lids are completed so that the pressure is equalized with the environment.
  • At least one reservoir may be closed with a lid, the lid has a filter.
  • a filter Through such a filter, a gas exchange with the environment or with another, associated reservoir, without that pollutants enter the reservoir or escape from the reservoir can.
  • At least one channel has a charged surface, colloids, microfilters and / or a Have device for reflux prevention.
  • the electrostatic force increases with the charge of the organelle or the Molecule.
  • the salt concentration in the channel is increased, the Debye length decreases and the zeta potential (Gouy-Chapmann theory).
  • the less strong charged organelles / molecules dissolve and may be e.g. transported away by river become.
  • the highly charged organelles / molecules remain attached. So can Organelles / molecules are separated according to their charge.
  • DNA molecules be purified when these form the most highly charged molecule and therefore stick the longest (with increasing ionic strength).
  • the DNA can then be analyzed by known methods.
  • colloids of different sizes can be introduced. These can perform various tasks: the purification of liquids; the filtering out certain substances from liquids; the introduction of certain substances in liquids; the introduction of certain substances in the presence of specific Substances in the liquid. It can be exploited that liquids from different directions through the colloid barrier. Especially Colloids with a functionalized surface can be used.
  • Microfilters can be used to filter out certain substances.
  • the colloids can be used in conjunction with microfilters.
  • the colloids can also be fixed by rejuvenating a canal in it; the channel can be formed, for example, conical.
  • the colloids may e.g. by Membranes are fixed with a defined pore size or microfilter in the channel. It is also possible to arrange different sized colloids one behind the other.
  • the device for preventing backflow allows corresponding Channels may be used only for liquid transport in a channel direction.
  • the device for reflux prevention can preferably as a check valve be educated.
  • At least one channel and / or reservoir may contain at least one analysis substance exhibit.
  • an analysis substance already in the production of the Microfluidic system are introduced into a channel, so that a later preparation the microfluidic system is simplified.
  • the channel and / or the reservoir having an analysis substance in a shell, which only after a predetermined time or at predetermined environmental parameters dissolves.
  • microfluidic system at least one further channel having a charged surface, solids, in particular colloids, microfilters and / or a device to prevent backflow.
  • a further channel having a charged surface, solids, in particular colloids, microfilters and / or a device to prevent backflow.
  • microfluidic systems can be optically highly transparent areas and or integrated into the substrate have optical components. This allows cells and / or cell compartments be visually examined in the channels.
  • the optically highly transparent areas or the integrated optical components have a protective film. Such a film may scratch the areas or Prevent components. Before using the microfluidic system, the protective film may be removed.
  • Another task is a system to provide for transporting liquids, in which easily liquids can be transported and without the microfluidic system an external Connection required.
  • a system for transporting liquids in a microfluidic system comprising a microfluidic system having a substrate, at least two reservoirs and at least one integrated into the substrate channel, the connects two reservoirs, and a device for pivoting the microfluidic system around at least one axis in at least two directions.
  • a microfluidic system it may advantageously be one of the microfluidic systems described above act.
  • Panning is understood to mean the rotation through an angle between 0 and 2 ⁇ .
  • the microfluidic system may be one axis in two directions and / or multiple Axes are pivoted in one direction.
  • the microfluidic system can be periodically swung back and forth about an axis.
  • the device for pivoting is such designed so that the microfluidic system are pivoted about several axes can. These pivoting movements about different axes can in particular overlay; this can be a kind of tumbling motion of the microfluidic system arise.
  • a pivoting movement by an angle smaller than 2 ⁇ about a first axis with a complete circular rotation about a second axis be superimposed.
  • a pivoting movement in particular in a complete Circular rotation, can also be the centrifugal force applied to the fluids be used for liquid transport.
  • the device for pivoting can comprise, for example, hydraulic devices, with which the device is moved.
  • the device for pivoting means for fixing of the microfluidic system Preferably, the device for pivoting means for fixing of the microfluidic system.
  • microfluidic systems are always at the same Position of the device arranged.
  • Accuracy Accuracy can be repeated.
  • the invention also provides a system for transporting liquids in one A microfluidic system provided comprising a microfluidic system having a substrate, at least two reservoirs and at least one integrated into the substrate A channel connecting two reservoirs, wherein a first reservoir has a volume, and a device disposed on the first reservoir, around the volume to apply pressure.
  • the microfluidic system is to one of the previously described microfluidic systems.
  • the device for pressurizing as an elastic membrane be formed, which is arranged in the form of a lid on the reservoir.
  • Mechanical pressure on the diaphragm will increase the volume of the reservoir with pressure applied.
  • the pressure can be, for example, by hand or by means of a microphone be exercised.
  • the device for pressurizing a print cartridge or print cartridge include.
  • the device for pressurizing have a device for heating and / or cooling the volume.
  • a device for heating or cooling of a gas in the volume expands This turns out or contracts, leaving the volume with a positive or negative pressure is applied.
  • the microfluidic systems may have a plurality of channels and / or have reservoirs. It can have multiple channels in a reservoir lead.
  • the channels may also intersect and / or divide.
  • the invention also provides a method for growing and / or analyzing Providing cells with the steps of providing a microfluidic system with a substrate, at least two reservoirs and at least one integrated into the substrate Channel connecting two reservoirs, introducing at least one line in at least a channel, filling at least one reservoir with a liquid, and Transporting the fluid through one connected to the filled reservoir Channel by pivoting the microfluidic system by at least one axis in at least two directions.
  • the microfluidic system can move around an axis in two directions and / or pivoted about several axes in one direction.
  • the microfluidic system provided may be one of those previously described Act microfluidic systems.
  • cells can be grown in a microfluidic system be, with the Nährmediummakers and the product disposal in the Microfluid system are integrated.
  • a periodic swinging back and forth of the Microfluidic system for example, liquid from one each higher Reservoir flow into a lower reservoir through the canal. It can the geometries of the channel and the reservoir are coordinated so that There is much more fluid in the reservoirs than in the channel (typically a factor of 10-200).
  • Concentration of the gas dissolved in the liquid in the channel this liquid can by tilting the carrier into one of the reservoirs. Because of the high Amount of fluid in the reservoir in relation to the channel will find a corresponding Dilution instead. With repeated rockers, the accumulation becomes more toxic Ensures substances and the supply of nutrient media in the channel.
  • cells can be kept alive in a canal system over a long period of time become.
  • a method for growing and / or analyzing cells provided with the steps of: providing a microfluidic system with a substrate, at least two reservoirs and at least one integrated into the substrate Channel connecting two reservoirs, introducing at least one cell into at least a channel, filling at least one reservoir with a liquid, and Transporting the fluid through one connected to the filled reservoir Channel by pressurizing the liquid.
  • a microfluidic system with a substrate, at least two reservoirs and at least one integrated into the substrate Channel connecting two reservoirs, introducing at least one cell into at least a channel, filling at least one reservoir with a liquid, and Transporting the fluid through one connected to the filled reservoir Channel by pressurizing the liquid.
  • it may be the provided microfluidic system with one of the previously described microfluidic systems act.
  • the filling of the reservoir further filling with a gas.
  • concentration of the gas in the Liquid can be determined by the residence time of the liquid in the reservoir become.
  • a constant supply of dissolved gases in the liquid can through a connection of the reservoirs are ensured with the appropriate gas.
  • a Reservoir with solids, especially with colloids, and another reservoir with a liquid filled to functionalize the solids By targeted filling different reservoirs and subsequent pivoting of the chamber can filled reservoirs are filled with liquid. Those in the reservoirs Solids or parts of the solids can thus dissolve in the liquid. By pivoting again, the liquid with the dissolved substances in one selected channel. This can e.g. serve cells in one supply chronologically defined sequence with nutrient medium. Also, so can the effect various substances are detected on cells.
  • An advantageous method of detecting molecules may include the steps of: Molecules in a first liquid can functionalize the surface of a colloid. Molecules of a second fluid bind to the functional groups of the Colloid surface. A third fluid contains molecules, which are special components the connected and / or functional group with attached molecule replaces. In each of these sub-steps certain reactions can be detected.
  • the methods can be used to prepare cell organelles (e.g. Zellkem or mitochondria) or cell molecules (DNA, proteins) to separate and / or identify. These are the cells located in the substrate / channel destroyed. This can e.g. by osmotic pressure, shear forces, compressed air, or special solvents take place.
  • the application of these methods is in one Microfluidic system particularly easy to implement.
  • the released cell compartments can be filtered out, chemically bound, separated in the gel, electrophoretically moved and / or separated, immobilized or fixed to charged surfaces become.
  • the necessary components can be introduced into the microfluid system be or can be filled in the canal.
  • the methods can be used in particular for the following analysis methods In situ hybridization, FISH (fluorescence in situ hybridization) and CGH (comparative genomic hybridization).
  • organelles and / or molecules in a microfluidic system completely automated with channels, reservoirs and the described components be separated from cells and analyzed.
  • all of the methods described above can be carried out in such a way that the microfluid system represents a self-sufficient system due to the pivoting movements.
  • This can be realized by using the embodiments shown above. This ensures a long-term care of the cells.
  • the carrier is first completed by a Abziehdeckel. This is opened in use so that the test can be carried out. This allows a storable test with living cells.
  • Fig. 1 shows a microfluidic system with a substrate 1, two reservoirs 2 and 3 and an integrated into the substrate 1 channel 4.
  • the mouths 5 and 6 of the channel 4th are each arranged above base surfaces 7 and 8 of the reservoirs 2 and 3.
  • Within the reservoirs 2 and 3 are standing on the base 7 and 8 hollow cylinder 9 and 10 are formed, through which the channel 4 is guided.
  • the hollow cylinder 9 and 10 are located directly along the reservoir side walls 13 and 14 and go in these over.
  • the mouths 5 and 6 are at different heights, from the Base 7 and 8 seen, arranged so that, depending on the reservoir a different Tilt angle of the microfluidic system is required to allow a liquid flows into the channel 4.
  • the mouth-side surfaces 11 and 12 of the hollow cylinder 9 and 10 are chamfered so that the liquid as it flows out of the Mouth does not splash up but flows to the side.
  • Fig. 2a shows a microfluidic system, wherein in the channel 4 cells 15 are arranged.
  • the liquid reservoirs 2 and 3 each comprise liquid volumes 16 and 17 and - arranged above it - gas volumes 18 and 19.
  • the liquid is a nutrient medium.
  • Reservoirs 2 and 3 are airtight through lids 20 and 21 completed.
  • Reservoirs 2 and 3 are through the lids over a gas channel 22 interconnected, whereby a gas exchange and thus a pressure equalization is possible.
  • toxic Substances 23 During the cultivation of the cells 15 arise toxic Substances 23.
  • the microfluidic system is pivoted to one side. Such a tilted microfluid system can be seen in Fig. 2b.
  • the Slope flows liquid from the reservoir 2 into the lower reservoir 3.
  • the toxic substances 23 are removed from the cells 15 and in the reservoir 3 diluted;
  • the cells are supplied with fresh nutrient medium from the reservoir 2.
  • the gas from the reduced gas volume 19 flows through the gas channel 22 in the reservoir 2, whereby a pressure equalization is created.
  • the channel system with a movable membrane be completed.
  • This membrane can e.g. placed in a lid be.
  • the Pressure can be applied both by hand, as well as transmitted via a microphone.
  • certain vibration frequencies or superpositions of vibration frequencies of the pressure difference in the Channel are created. This can serve to adhere forces of particles, such as e.g. Cells to determine on the inner walls of the canal system. Also, by doing so the mixture of two substances accelerates or the targeted transport be carried out by liquids. This is good especially in small channels realize.
  • the microphone is directly above the carrier appropriate. Thus, a targeted movement of the liquid in the carrier without a connection system respectively.
  • the liquid can also by applying an overpressure be transported on at least one side of the channel through the channel.
  • the channel system with individual plugs and / or a Plug connector provided. These connectors may e.g. via a hose system with z. B. pressure cartridges connected.
  • a valve By opening the valve becomes an overpressure Generated in the duct system
  • the valve is an automatic one controllable valve, e.g. around a piezo valve.
  • a liquid from a reservoir or channel also transported simultaneously into several channels connected thereto by pressurizing the reservoir or channel.
  • FIG. 3 shows various colloid arrangements in a channel 4.
  • Fig. 3a includes the channel colloids 24, which are fixed by a microfilter 25.
  • Fig. 3b the channel 4 tapers in the direction of flow.
  • large colloids are stored 24 on.
  • smaller colloids 26 are arranged, creating a colloid barrier is formed from different sized colloids.
  • the colloid barrier in Fig. 3c comprises only large colloids 24 which are fixed in front of a constriction.
  • the analysis substances can also be included in cases, which only after a certain time or at certain parameters (e.g., pH, pks value) (as with certain Drugs). So can run in a specific time sequence Analysis processes without external control, such as a solvent exchange, expire.
  • the carriers or microfluidic systems can be used with the already integrated substances be delivered.
  • FIG. 4 a shows a cross section of a microfluid system with a substrate 1, in which two reservoirs 27 and 28 are arranged one above the other.
  • the reservoirs can be accessible from the side by each laterally another channel (not shown) in each reservoir.
  • the base areas of the reservoirs are relative to Side surface inclined, the inclination angle is different Will the microfluidic system pivoted about a first, smaller angle ( Figure 4b), so only reaches you Liquid in the lower reservoir 27, the channel mouth and flows into the channel.
  • Figure 4c the liquid reaches from the second reservoir 28, the channel mouth and can this channel flow through.

Claims (15)

  1. Système microfluidique comprenant un substrat, au moins deux réservoirs et au moins un canal qui est intégré dans le substrat et qui relie deux réservoirs, étant précisé qu'au moins un canal débouche au-dessus de la surface du fond d'un réservoir.
  2. Système microfluidique selon la revendication 1, ce système étant fermé et comprenant un dispositif d'équilibrage de pression qui relie chaque réservoir à au moins un autre réservoir.
  3. Système microfluidique selon la revendication 1 ou 2, dans lequel au moins un canal présente une surface chargée, des matières solides, en particulier des colloïdes, des microfiltres et/ou un dispositif pour empêcher un reflux.
  4. Système microfluidique selon l'une des revendications précédentes, dans lequel il est prévu au moins un autre canal qui comporte une surface chargée, des matières solides, en particulier des colloïdes, des microfiltres et/ou un dispositif pour empêcher le reflux.
  5. Système microfluidique selon l'une des revendications précédentes, dans lequel au moins un canal et/ou un réservoir présentent au moins une substance à analyser.
  6. Système microfluidique selon l'une des revendications précédentes, dans lequel le substrat comporte au moins une zone très transparente optiquement et/ou au moins un composant optique intégré.
  7. Système microfluidique selon la revendication 6, dans lequel chaque zone très transparente optiquement et/ou chaque composant optique intégré présente un film protecteur.
  8. Système pour transporter des liquides dans un système microfluidique, comprenant
    un système microfluidique selon l'une des revendications précédentes, avec un substrat, au moins deux réservoirs et au moins un canal qui est intégré dans le substrat et qui relie deux réservoirs, et
    un dispositif pour faire pivoter le système microfluidique sur au moins un axe dans au moins deux directions.
  9. Système pour transporter des liquides dans un système microfluidique, comprenant
    un système microfluidique selon l'une des revendications 1 à 7, avec un substrat, au moins deux réservoirs et au moins un canal qui est intégré dans le substrat et qui relie deux réservoirs, un premier réservoir présentant un volume,
    et un dispositif disposé sur le premier réservoir pour mettre ledit volume sous pression.
  10. Procédé pour la culture et/ou l'analyse de cellules, comprenant les étapes suivantes :
    mise en place d'un système microfluidique selon l'une des revendications 1 à 7 comprenant un substrat, au moins deux réservoirs et au moins un canal qui est intégré dans le substrat et qui relie deux réservoirs,
    introduction d'au moins une cellule dans au moins un canal,
    remplissage d'au moins un réservoir avec un liquide, et
    transport du liquide à travers un canal relié au réservoir rempli, grâce au pivotement du système microfluidique sur au moins un axe dans au moins deux directions.
  11. Procédé pour la culture et l'analyse de cellules, comprenant les étapes suivantes :
    mise en place d'un système microfluidique selon l'une des revendications 1 à 7 comprenant un substrat, au moins deux réservoirs et au moins un canal qui est intégré dans le substrat et qui relie deux réservoirs,
    introduction d'au moins une cellule dans au moins un canal,
    remplissage d'au moins un réservoir avec un liquide, et
    transport du liquide à travers un canal relié au réservoir rempli, grâce à la mise sous pression du liquide.
  12. Procédé selon la revendication 10 ou 11, selon lequel le remplissage du réservoir comprend aussi un remplissage avec un gaz.
  13. Procédé selon l'une des revendications 10 à 12, selon lequel un réservoir est rempli avec un solvant destiné à détruire des cellules et/ou un réservoir est rempli avec un liquide destiné à purifier des molécules.
  14. Procédé selon l'une des revendications 10 à 13, selon lequel un réservoir est rempli avec des matières solides, en particulier des colloïdes, et un autre réservoir est rempli avec un liquide destiné à fonctionnaliser les matières solides.
  15. Procédé selon l'une des revendications 10 à 14, comprenant l'étape supplémentaire suivante :
    analyse par fluorescence des cellules et/ou de compartiments de cellules.
EP03718772A 2002-04-22 2003-04-17 Systeme microfluidique Expired - Lifetime EP1397483B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP03718772A EP1397483B1 (fr) 2002-04-22 2003-04-17 Systeme microfluidique

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP02008966A EP1357178A1 (fr) 2002-04-22 2002-04-22 Sytème microfluide
EP02008966 2002-04-22
DE10224725 2002-06-04
DE2002124725 DE10224725A1 (de) 2002-06-04 2002-06-04 Mikrofluidsystem
PCT/EP2003/004033 WO2003089565A1 (fr) 2002-04-22 2003-04-17 Systeme microfluidique
EP03718772A EP1397483B1 (fr) 2002-04-22 2003-04-17 Systeme microfluidique

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EP1397483A1 EP1397483A1 (fr) 2004-03-17
EP1397483B1 true EP1397483B1 (fr) 2005-05-25

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EP03718772A Expired - Lifetime EP1397483B1 (fr) 2002-04-22 2003-04-17 Systeme microfluidique

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EP (1) EP1397483B1 (fr)
AT (1) ATE296347T1 (fr)
AU (1) AU2003222824A1 (fr)
DE (1) DE50300574D1 (fr)
WO (1) WO2003089565A1 (fr)

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CN109991035B (zh) * 2017-12-29 2021-12-24 台达电子工业股份有限公司 微量取样装置
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EP4310571A1 (fr) 2022-07-22 2024-01-24 ibidi GmbH Dispositif d'inclinaison destiné à la microscopie

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GB2314343B (en) * 1996-06-18 2000-08-23 Liau Ming Yi Method and apparatus for cultivating anchorage dependent monolayer cells
DE19917848C2 (de) * 1999-04-15 2002-11-14 Inst Molekulare Biotechnologie Nanoaktorische Vorrichtung und deren Verwendung
TWI233449B (en) * 1999-07-01 2005-06-01 Ind Tech Res Inst High efficient cell-cultivating device

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AU2003222824A1 (en) 2003-11-03
ATE296347T1 (de) 2005-06-15
EP1397483A1 (fr) 2004-03-17
DE50300574D1 (de) 2005-06-30

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