EP1444042A1 - Procede de deplacement d'un fluide d'interet dans un capillaire et microsysteme fluidique - Google Patents
Procede de deplacement d'un fluide d'interet dans un capillaire et microsysteme fluidiqueInfo
- Publication number
- EP1444042A1 EP1444042A1 EP02799424A EP02799424A EP1444042A1 EP 1444042 A1 EP1444042 A1 EP 1444042A1 EP 02799424 A EP02799424 A EP 02799424A EP 02799424 A EP02799424 A EP 02799424A EP 1444042 A1 EP1444042 A1 EP 1444042A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ferrofluid
- fluid
- capillary
- interest
- plug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
- B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
-
- 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
- B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
-
- 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
- B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
- H01F1/44—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of magnetic liquids, e.g. ferrofluids
- H01F1/447—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of magnetic liquids, e.g. ferrofluids characterised by magnetoviscosity, e.g. magnetorheological, magnetothixotropic, magnetodilatant liquids
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F21/00—Variable inductances or transformers of the signal type
- H01F21/02—Variable inductances or transformers of the signal type continuously variable, e.g. variometers
- H01F21/06—Variable inductances or transformers of the signal type continuously variable, e.g. variometers by movement of core or part of core relative to the windings as a whole
Definitions
- the present invention relates to a method of moving a fluid of interest in a capillary and to a fluid microsystem. It relates in particular to the field of microfluidics, and in particular fluidic microsystems. It allows high-throughput biological or chemical processes.
- the present invention can be combined with other functions to form a more complete and precise system of biological analysis.
- variable surface states to regulate flows, but nevertheless impose constraints on the physicochemical properties of the fluids to be transported and precise treatment of the surfaces. It is also possible to use the generation of bubbles to regulate the flow rates inside capillaries. Finally, mechanical systems for regulating the hydrostatic pressure also exist, installed upstream of the microcircuits or downstream, for example by fitting a wick made of an absorbent material.
- the purpose of the present invention is precisely to provide a solution to the aforementioned problems of the prior art by providing a method of moving a fluid of interest in a capillary comprising the following steps: - At least one ferrofluid train is placed in said capillary, said ferrofluid train comprising a ferrofluid plug and, placed at at least one of the two ends of the ferrofluid plug and integral with it, a plug of liquid immiscible with ferrofluid and the fluid of interest,
- said fluid of interest is placed in said capillary, in the vicinity of the ferrofluid train, and
- the present invention also provides a fluid microsystem for moving a fluid of interest comprising on the one hand a capillary in which is disposed at least one train of ferrofluid and on the other hand, outside of said capillary, a magnetic system making it possible to produce a magnetic field to control the movement of the ferrofluid train in the capillary, said ferrofluid train comprising a ferrofluid plug and, placed at and at one of the two ends of the ferrofluid plug and a plug liquid immiscible with ferrofluid and the fluid of interest.
- fluid of interest any liquid or gaseous fluid which it is necessary to move in a capillary, for example in microsystems of analysis.
- the fluid of interest can be for example a chemical reagent, a biological liquid, an aqueous solution, etc.
- the term “plug” is intended to mean a volume of fluid located in the capillary and forming by capillarity a “cylinder” conforming to the shape of the internal wall of the capillary. In other words, the fluid placed in the capillary forms a plug when it occupies, over a length which depends on the volume of this fluid, the entire section of the capillary.
- a train of ferrofluid also called “train” in the present description, comprises a plug of ferrofluid and at least one plug of liquid immiscible with the ferrofluid and with the fluid of interest integral therewith.
- the ferrofluid train moves in its entirety with the plug (s) of liquid immiscible with the ferrofluid and the fluid of interest.
- ferrofluids or magnetic fluids are fluids essentially comprising two constituents: (1) single-domain grains of ferromagnetic substance, of approximately 5 to 10 nm of magnetite or maghemite, (2) a carrier fluid.
- the ferrofluid When the carrier fluid is an organic compound, as is the case with most commercial ferrofluids, the ferrofluid is said to be "organic based” and the magnetic particles are dispersed in the carrier fluid by surfactants. When the carrier fluid is water, the ferrofluid is said to be “ion-based” and the particles are dispersed either by electrostatic forces or by bilayers of surfactant.
- the choice of ferrofluid corresponds to the choice of the inventors of a control, or piloting, by magnetic field to carry out the process of the present invention.
- the ferrofluids which can be used according to the invention preferably have a low viscosity and good physicochemical stability over time and as a function of temperature.
- the ferrofluid is preferably an ionic ferrofluid, for example a ferrofluid such as those described in the document GB-A-2244987.
- these ferrofluids have a high density of particles, a high magnetic susceptibility, and a great stability over time. They are obtained by fixing charged molecules on the surface of magnetic precursor particles which ensure colloidal stability without the use of surfactants.
- the fluid of interest is generally in the form of an aqueous solution.
- the a priori simplest solution for implementing ferrofluids according to the invention, in microchannels or microtubes of "lab-on a chip" is to work with ferrofluids with an organic base, because they are not miscible with l 'water.
- ferrofluids with an organic base, because they are not miscible with l 'water.
- there can then be the problem of contaminating and non-biocompatible deposits for example in the form of magnetic particles based on iron oxide, capable of interfering in the chemical reactions involved.
- the capillary is preferably a capillary whose internal wall is hydrophobic, that is to say whose internal wall has a contact angle greater than 90 °. This can be obtained for example by an adequate chemical treatment such as silanization, or by using hydrophobic materials such as those mentioned above.
- the material constituting the capillary can be chosen for example as a function of the fluid of interest and the physicochemical conditions of the chemical reactions carried out in the capillary.
- the capillary, or microtubes or microchannels can for example have an internal diameter of less than 1 mm, for example of 0.5 mm and less, which corresponds to the usual dimensions of fluid microsystems.
- the liquid immiscible with the ferrofluid and with the fluid of interest may for example be oil, in particular when the ferrofluid is an ionic ferrofluid and the fluid of interest an aqueous solution.
- the oil can be an organic oil, for example dodecane, or a mineral oil, for example oil M3516 sold by the company Sigma-Aldrich.
- a priori a thin film of oil can be created during the movement of the ferrofluid train on the internal wall of the capillary because the oil wets the hydrophobic surface better than water. But this is not detrimental if the oil is compatible with the fluid of interest.
- a biocompatible oil for example a mineral oil.
- a pre-wetting of the walls of the micro-channels can be carried out by first circulating an oil plug sufficient volume.
- a step of pre-wetting the internal wall of the capillary with the oil before placing in said capillary the ferrofluid train can be produced.
- oil plugs can also be placed in the capillary, alone, without ferrofluid plugs, for example to separate two plugs of fluid of identical or different interest located between two trains of ferrofluid, or before or after a single ferrofluid train.
- at least one plug of liquid immiscible with the ferrofluid and with the fluid of interest can be placed in the capillary between two plugs of fluid of interest.
- the ferrofluid train can consist of a ferrofluid plug and a liquid plug immiscible with the ferrofluid and the fluid of interest.
- This embodiment is for example useful for moving a fluid of interest placed on one side of the ferrofluid train, that is to say on the side of the immiscible liquid plug.
- a cap of liquid immiscible with ferrofluid and with the fluid of interest can be placed at each of the two ends of the ferrofluid cap.
- the ferrofluid train comprises a ferrofluid plug and two plugs of liquid immiscible with the ferrofluid and the fluid of interest. This embodiment is for example useful for moving a fluid of interest placed on either side of the ferrofluid train, or two liquids of different interest separated by the ferrofluid train.
- a plurality of ferrofluid trains can be arranged in the capillary, with ferrofluids identical or different from one train to another, and caps of liquid immiscible with the ferrofluid and the fluid of identical or different interest in the same train or from one train to another.
- This embodiment is for example useful for moving several plugs of one or more identical or different fluid (s) of interest, each plug of fluid of interest being separated from the next by a ferrofluid train according to the present invention or by a cap of liquid immiscible with ferrofluid and the fluid of interest.
- the magnetic system necessary to move the fluid of interest in the capillary can for example be constituted by permanent magnets or by electrical circuits, c 'ie electromagnets located for example in the immediate vicinity of the capillaries.
- This magnetic system can be fixed or mobile.
- the mobility of the magnetic field can be obtained, for example, by mechanically moving a permanent magnet or an electromagnet along the capillary, or by "activating" sequentially adjacent coils of electromagnets.
- the permanent magnet can be by example in the form of a magnetic bar, 1 electromagnet for example in the form of a coil or a solenoid.
- the sizes of the ferrofluid plugs and the magnets are adapted to the conditions of the desired application of the method of the present invention, that is to say for example to the speed of the fluid or to the radius of the capillary, so as to allow good coupling ferrofluid magnet / plug and therefore good flow control.
- the magnets can have a length of between 0.5 and 2 mm and the ferrofluid plugs approximately twice this length.
- the number of magnetic systems can be a function of the number of ferrofluid trains used.
- n fluid trains may require n magnetic systems.
- the control of the displacement of the fluid of interest in said capillary by action on said ferrofluid plug of a magnetic field generated by the magnetic system disposed outside of said capillary can be achieved in different ways .
- the flow or displacement of the fluid of interest in the microchannel can be obtained under the impulse of a pressure or a motor depression applied in the capillary.
- the control according to the present invention may consist in blocking, or in unblocking, the movement of the fluid in the capillary by blocking, respectively by unblocking, the movement of the train of ferrofluid by means of the magnetic system.
- a ferrofluid train consisting of a ferrofluid plug with two oil buffer plugs on each side and a single permanent or electromagnet.
- the withdrawal of the permanent magnet or the stopping of the electric current supplying the electromagnet allows the resumption of the flow of the fluid of interest.
- n ferrofluid plugs provided with 2xn oil buffer plugs and m magnets or electromagnets, with m ⁇ n. Additional oil plugs without ferrofluid plugs isolate the biological reagents from one plug to another.
- the microsystem may comprise one or n ferrofluid plugs respectively provided with one or 2xn oil buffer plugs and a sliding magnetic field obtained either by mechanically moving a permanent magnet along the capillary, or by "activating" sequentially adjacent coils of electromagnets.
- the movement of the magnetic field serves as a driving force to move the train of ferrofluid, and therefore the fluid of interest in the capillary.
- the present invention can be envisaged for obtaining the control, or piloting, of the flow of the fluid of interest inside the capillaries or microchannels.
- the present invention also has the advantage of implementing an external command or control of the movement of the fluid of interest in the capillary, of limiting or avoiding the deposits of ferrofluid in the form of a liquid film on the walls of the capillary, and to avoid the contamination problems associated with the devices of the prior art. It also provides a precise and easy-to-implement process for controlling the flow of fluids in microchannels.
- the present invention can advantageously be implemented for example in an automated in vitro diagnostic system, or a system for detecting biological contaminants in fields such as the food industry and / or industrial microbiological control.
- the device of the present invention can be the first element of a set comprising:
- a separation module for example by electrophoresis
- a detection module for example by electrophoresis
- FIG. 1 is a schematic representation of a fluid microsystem according to the present invention comprising a ferrofluid train
- - Figure 2 is a schematic representation of a fluid microsystem according to the present invention in which the magnetic system is a permanent magnet
- FIG. 3 is a schematic representation of a fluid microsystem according to the present invention in which the magnetic system is an electromagnet;
- FIGS. 5a and 5b are graphs of modeling as a function of time the flow speed in a capillary of 500 ⁇ m in diameter when passing through the magnetic field of a 2mm long ferrofluid plug.
- the static magnetic field is generated either by two permanent magnets in opposition (fig.5a) or by a solenoid (fig.5b); the origin of times is arbitrary;
- - Figures 6a and 6b are photographs showing the implementation of the process of the present invention, photographs taken on millimeter paper so as to highlight the size of the capillary and the plugs. Examples
- the ferrofluid train (3) comprises a ferrofluid plug (5) with two plugs (7) of liquid immiscible with the ferrofluid and the fluid of interest.
- the ferrofluid plug is an ionic ferrofluid plug containing 20% by mass of magnetic particles of maghemite covered with nitrate group and dispersed in water.
- the average particle diameter is 7.5 nm.
- the liquid immiscible with ferrofluid and the fluid of interest (7) consists of oil M3516 sold by the company Sigma-Aldrich
- the capillary (1) is made of glass, it has a diameter of 500 ⁇ m.
- the ferrofluid train has a length of 2mm.
- Figure 2 attached shows the same capillary with a magnetic system (11) which is a permanent magnet in the form of magnetic bars.
- Figure 3 attached shows the same capillary with a magnetic system (11) which is an electromagnet in the form of a solenoid.
- This configuration of the microsystem of the present invention makes it possible to block and unblock a flow having a speed V indicated by the arrow in the capillary or microchannel.
- the flow is created by an external driving pressure ⁇ p. Removal of magnets permanent or stopping the electric current allows the flow to resume.
- Example 2 Fluid microsystem "in n steps"
- the same train of ferrofluid as that used in example 1 is used in different applications shown diagrammatically in FIGS. 4a and 4b.
- FIG. 4a A first application is shown in Figure 4a.
- a single ferrofluid train (3) is used with several plugs (7) of mineral oil.
- Figure 4b A second application is shown in Figure 4b.
- several train of ferrofluids (3) are used alternately with several fluid plugs (L) of interest.
- a pressure ⁇ p causes the fluid plugs L to flow into the capillary.
- the magnetic system (11) allows, as in Example 1, to block or unblock this flow.
- FIGS. 5a and 5b annexed numerical simulations using the Matlab software (registered trademark) show for example the stopping of the flow in a capillary comprising a succession of trains of ferrofluid as in FIG. 4b and of water.
- the magnetic field is created either by two permanent magnets (fig.5a) in opposition or by a solenoid
- the magnetic field is 350 Gauss on the axis at the center of the capillary.
- the diameter of the solenoid is 1 mm and it has 10 turns and its length is that of a ferrofluid plug: 2 mm.
- the dimensions are 3 cm x l cm x l mm.
- FIGS. 6a and 6b are photographs showing the implementation of the process of the present invention in a capillary of 300 ⁇ m in diameter in teflon (registered trademark) and using mineral oil plugs (reference Sigma-Aldrich M3516 ), colorless, on either side of an ionic ferrofluid plug such as that described in Example 1, to avoid contamination with the plugs of aqueous phase (fluid of interest) colored with methylene blue.
- the application of a neodymium-iron-boron magnetic strip of 1 x 5 x 36 mm above the capillary allows piloting of the plugs from the outside with an accuracy of less than 200 ⁇ m and therefore of the flow at inside the capillary.
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0112192 | 2001-09-21 | ||
FR0112192A FR2829948B1 (fr) | 2001-09-21 | 2001-09-21 | Procede de deplacement d'un fluide d'interet dans un capillaire et microsysteme fluidique |
PCT/FR2002/003207 WO2003026798A1 (fr) | 2001-09-21 | 2002-09-19 | Procede de deplacement d'un fluide d'interet dans un capillaire et microsysteme fluidique |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1444042A1 true EP1444042A1 (fr) | 2004-08-11 |
EP1444042B1 EP1444042B1 (fr) | 2006-07-12 |
Family
ID=8867494
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02799424A Expired - Lifetime EP1444042B1 (fr) | 2001-09-21 | 2002-09-19 | Procede de deplacement d'un fluide d'interet dans un capillaire et microsysteme fluidique |
Country Status (7)
Country | Link |
---|---|
US (1) | US20040241693A1 (fr) |
EP (1) | EP1444042B1 (fr) |
JP (1) | JP4106328B2 (fr) |
AT (1) | ATE332748T1 (fr) |
DE (1) | DE60213120T2 (fr) |
FR (1) | FR2829948B1 (fr) |
WO (1) | WO2003026798A1 (fr) |
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2001
- 2001-09-21 FR FR0112192A patent/FR2829948B1/fr not_active Expired - Fee Related
-
2002
- 2002-09-19 AT AT02799424T patent/ATE332748T1/de not_active IP Right Cessation
- 2002-09-19 JP JP2003530425A patent/JP4106328B2/ja not_active Expired - Fee Related
- 2002-09-19 US US10/488,435 patent/US20040241693A1/en not_active Abandoned
- 2002-09-19 WO PCT/FR2002/003207 patent/WO2003026798A1/fr active IP Right Grant
- 2002-09-19 DE DE60213120T patent/DE60213120T2/de not_active Expired - Lifetime
- 2002-09-19 EP EP02799424A patent/EP1444042B1/fr not_active Expired - Lifetime
Non-Patent Citations (1)
Title |
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See references of WO03026798A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP1444042B1 (fr) | 2006-07-12 |
WO2003026798A1 (fr) | 2003-04-03 |
FR2829948B1 (fr) | 2004-07-09 |
DE60213120D1 (de) | 2006-08-24 |
JP2005503572A (ja) | 2005-02-03 |
FR2829948A1 (fr) | 2003-03-28 |
DE60213120T2 (de) | 2007-01-11 |
ATE332748T1 (de) | 2006-08-15 |
JP4106328B2 (ja) | 2008-06-25 |
US20040241693A1 (en) | 2004-12-02 |
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