EP2076781A1 - Fluid flow device, assembly for determining at least one characteristic of a physicochemical system comprising such a device, corresponding determination process and screening process - Google Patents

Fluid flow device, assembly for determining at least one characteristic of a physicochemical system comprising such a device, corresponding determination process and screening process

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Publication number
EP2076781A1
EP2076781A1 EP07858431A EP07858431A EP2076781A1 EP 2076781 A1 EP2076781 A1 EP 2076781A1 EP 07858431 A EP07858431 A EP 07858431A EP 07858431 A EP07858431 A EP 07858431A EP 2076781 A1 EP2076781 A1 EP 2076781A1
Authority
EP
European Patent Office
Prior art keywords
physicochemical
storage
channel
physico
flow device
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Withdrawn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
EP07858431A
Other languages
German (de)
French (fr)
Inventor
Mathieu Joanicot
Philippe Laval
Jean-Baptiste Salmon
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.)
Centre National de la Recherche Scientifique CNRS
Rhodia Operations SAS
Original Assignee
Centre National de la Recherche Scientifique CNRS
Rhodia Operations SAS
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 Centre National de la Recherche Scientifique CNRS, Rhodia Operations SAS filed Critical Centre National de la Recherche Scientifique CNRS
Publication of EP2076781A1 publication Critical patent/EP2076781A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G01N35/085Flow Injection Analysis
    • 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
    • B01L3/502738Containers 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 integrated valves
    • 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
    • B01L3/502769Containers 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
    • B01L3/502784Containers 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
    • 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
    • B01L2200/0673Handling of plugs of fluid surrounded by immiscible fluid
    • 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
    • B01L2300/0867Multiple inlets and one sample wells, e.g. mixing, dilution
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0633Valves, specific forms thereof with moving parts
    • B01L2400/0655Valves, specific forms thereof with moving parts pinch valves
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/54Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/117497Automated chemical analysis with a continuously flowing sample or carrier stream
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/117497Automated chemical analysis with a continuously flowing sample or carrier stream
    • Y10T436/118339Automated chemical analysis with a continuously flowing sample or carrier stream with formation of a segmented stream
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25625Dilution
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25875Gaseous sample or with change of physical state

Definitions

  • FLUID FLOW DEVICE ASSEMBLY FOR DETERMINING AT LEAST ONE CHARACTERISTIC OF A PHYSICO-CHEMICAL SYSTEM COMPRISING SUCH A DEVICE, METHOD OF
  • the present invention relates to a fluid flow device, a set of determination of at least one characteristic of a physico-chemical system comprising such a device, a determination method implementing this set, as well as a screening method. corresponding.
  • a physicochemical system which is intended to determine at least one characteristic, may be a pure body, but also a compound, such as for example one or more solute (s) dissolved in a solvent or a mixture of several pure bodies.
  • a characteristic of this physico-chemical system is in particular a characteristic curve of such a system, in particular a thermodynamic limit, in particular a phase diagram, such as a solubility curve, or even the miscibility limit for a mixture of two liquids.
  • the present invention aims more particularly, but not exclusively, the study of the solubility of such a physicochemical system. It is recalled that the solubility of a solute in a solvent is the maximum concentration of this solute that can be dissolved in this solvent at a given temperature. The solubility curve of this solute, which therefore forms a physicochemical system according to the invention, corresponds to the variation of this solubility as a function of temperature.
  • the methods conventionally used to determine this solubility curve are various. They involve different measures, during which at least one parameter is changed, especially the solute concentration and / or the temperature. In general, the methods used in the state of the art are of a systematic nature, so that they prove to be particularly lengthy to implement.
  • the invention proposes to remedy this drawback. It aims in particular to provide a solution for reliably determining at least one characteristic of a physicochemical system, which is accompanied by a significantly reduced handling time compared to the prior art.
  • the invention also relates to a set of determination of at least one characteristic of a physico-chemical system according to claim 13 attached.
  • the invention also relates to a method for determining at least one characteristic of a physico-chemical system according to claim 14 attached.
  • FIG. 1 is a front view, schematically illustrating a set of determination according to 1;
  • FIGS. 2A and 2B are side views, illustrating two positions of a valve fitted to the determination assembly of FIG. 1;
  • FIG. 3 is a graph illustrating a solubility curve that the invention proposes to determine
  • FIG. 5 is a view on a larger scale of FIG. 4.
  • FIG. 1 illustrates a determination assembly according to the invention, which firstly comprises a fluid flow device, designated as a whole by reference numeral 1.
  • a fluid flow device designated as a whole by reference numeral 1.
  • This latter comprises a wafer 2, which is produced in a known manner in FIG. for example PDMS (poly (dimethylsiloxane)).
  • PDMS poly (dimethylsiloxane)
  • it may be provided to form it in any other suitable material, such as glass, silicon, PMMA (polymethyl methacrylate), or a photoresist of SU-8 type MicroChem company, or NOA type from Nordland.
  • the invention also finds application in millifluidic flow channels, ie whose cross-section is greater than the values mentioned above.
  • the cross section of these millifluidic channels may reach a value close to 9 mm 2 , for example 3 mm by 3 mm, or even close to 25 mm 2 , for example 5 mm by 5 mm.
  • FIG. 1 illustrates more particularly the design of the microchannels, which are etched on the wafer 2.
  • microchannels 4 and 6 for supplying two first components, which are associated with two inputs 8 and 10. the latter is adapted to receive a first end of a nonrepresented tube, the other end is connected to a syringe also not shown.
  • the flow rate of the component administered by each syringe is controlled by means of a syringe pump, also not shown.
  • a microchannel 12 associated with an inlet 14 which cooperates with a tube, with a syringe, and with a not shown syringe driver.
  • This microchannel 12 is divided into two branches 16, affecting approximately a square shape, which meet at an intersection 18.
  • a microchannel 19 mixing in which open the downstream ends of the two microchannels 4 and 6, is put in communication with this intersection 18.
  • This connecting channel 20 is provided with an output 20 ', which will be noted that it is optional. It is put in communication with several so-called storage channels 22 ⁇ to 22 ⁇ .
  • the term "several" means "at least two".
  • these storage microchannels extend horizontally, namely that they are parallel to each other, while being perpendicular to the connecting channel 20.
  • these storage channels are not perpendicular to the link channel and are not parallel to each other.
  • the connecting channel 20 and the various storage channels 22i 22 6 define a comb, whose base is formed by the connecting channel and the teeth are formed by the storage channels.
  • this link channel and these storage channels define a quadrilateral, one side of which is formed by the link channel 20, two additional sides are defined by the end storage channels 22 ⁇ and 22 ⁇ , and one The last side is defined by a segment parallel to the link channel 20, which connects the downstream outputs of the different storage channels.
  • the aforementioned quadrilateral is a rectangle.
  • the storage microchannels 22i to 22 ⁇ are represented in number of six. However, in practice, a number of these channels is advantageously used which is between two and fifteen, preferably between five and ten. One can also consider using a single microchannel storage.
  • the storage microchannels cooperate with valves V 1 to V 6 , illustrated in a schematic manner, one of which V 1 is shown more precisely in FIGS. 2A and 2B.
  • the outlet 22 'x of the microchannel 22 ⁇ is placed in communication with a rigid tube 24, made for example of ethylene-propylene fluorinate (Teflon FEP) or Polyetheretherketone (PEEK ® ), namely that it does not deform substantially radially. during the flow of a fluid.
  • this rigid tube 24 opens into a flexible tube 26, made for example of PVC or silicone, which is associated with the valve Vi.
  • the latter is a tube-clamping solenoid valve of a type known per se.
  • the tubes 24 and 26 form a connecting member, connecting the outlet 22 'i of the microchannel 22i with the valve Vi.
  • This connecting member is independent of the wafer, namely that it can be reported, including removably, on the walls of the aforementioned outlet. This is advantageous, insofar as it is possible to make the wafer 2 of any material, regardless of the nature of the valve and its connecting member.
  • This solenoid valve Vi is conventionally provided with a piston 28 adapted to be actuated by a not shown coil, capable of crushing the tube 26 against a support 30. It should be noted that the length 1 of the flexible tube 26, between its connection with the rigid tube 24 and the pinching zone by the piston 28, is very small, for example close to 2 mm. This makes it possible to limit the parasitic displacements of the fluid in the different channels during the maneuvers of the valve.
  • valve shown in Figures 2A and 2B is advantageous. Indeed, this valve is physically isolated, thanks to the presence of the flexible tube 26, relative to the fluid present in the microchannel storage. Furthermore, this valve is reliable, while having a relatively low cost.
  • the invention provides for imposing two gradients according to the two dimensions x and y, respectively defined by the storage microchannels 22 and the connecting microchannel 20.
  • a gradient of operating condition including temperature, humidity, illumination, or concentration of another compound.
  • each of these modules 32 ⁇ and 32 2 may constitute a hot source or a cold source, .according to the steps of the method according to the invention.
  • the determination unit is provided with means capable of analyzing the contents of the different microchannels formed in the wafer 2.
  • these are means of visual analysis, namely a microscope 34 shown
  • the microscope 34 which is associated with an unrepresented camera, is connected in a conventional manner to a processing computer 36.
  • this solute A constitutes a physicochemical system that the invention proposes to study, which can be introduced into the microchannel 4. Furthermore, the abovementioned solvent B can be admitted via the microchannel 6, so that the mixture of the solute and the solvent forms a physicochemical set within the meaning of the invention. Finally, a carrier phase P, such as oil, which is not miscible with the solute mixture • and solvent, is admitted by the microchannel 12.
  • a succession of drops Gi which are directed towards the first storage channel 22i, is formed in a manner known per se.
  • Each drop is formed by the mixture of solute A and solvent B, namely the physicochemical set defined above.
  • these drops Gi are separated from each other by sections of oil, forming a carrier phase P immiscible with these drops. It will be noted that, during this step, a sufficiently high temperature is imposed so that the solute is entirely in liquid form in the drops Gi, that is, at the bottom and to the right of the curve CS of the figure 3.
  • the sum of the flow rates of the solute and the solvent is between 0.1 mL / hr and 5 mL / hr, in particular between 0.5 and 1 mL / hr.
  • the oil flow admitted by the microchannel 12 is between 0.5 and 10 mL / hr, especially between 1 and 5 mL / hr.
  • the filling of the various microchannels 22 has been performed at a high temperature, so that the different drops Gi to G 6 are in the fully liquid state. Then it is a question of lowering the temperature prevailing in these microchannels 22, so as to move towards the part situated at the top left of the curve C of FIG. 3, and so as to crystallize the solute present in all of these drops.
  • This change in temperature is obtained by modifying, as appropriate, the electric current supplied to the Peltier modules 32 2 and 32 2.
  • the left Peltier module 32 X is controlled so as to generate a relatively low temperature on its surface, for example around 10 0 C, while the right module 322 is controlled so as to generate a relatively high temperature for example of the order of 60 ° C.
  • the application of these different temperatures leads to a substantially linear gradient along each microchannel 22.
  • the temperature is close to that imposed by the module 32i while at the downstream end, the temperature is close to that imposed by the module 322-
  • this analysis is conducted visually through the microscope 34.
  • this microscope 34 has a wide field of view, to observe at the same time time the entire wafer. This is for example a binocular microscope.
  • an observation can be made through a crossed analyzer and polarizer to easily detect the presence of crystals that are birefringent. If the crystals are large enough, it is possible not to use birefringence.
  • Ti (Ti '+ T 1 ") / 2.
  • the computer 36 places, on the graph of FIG. 6, the different values Ti to T ⁇ thus obtained for the concentrations Ci to C 6 . From these different points, we thus obtain a solubility curve CS ', represented in FIG. 6, which is close to that CS of FIG.
  • the solubility curve a been plotted from six points, corresponding to six microchannels of storage. It will be understood that, if it is desired to improve the accuracy of the method of the invention, it is a question of increasing the number of microchannels of storage, which will make it possible to correspondingly increase the number of points from which performed the solubility curve. It is also possible to increase the number of drops present in the same storage channel, which contributes to reducing the distance between two adjacent drops. This improves the accuracy of the solubility temperature.
  • the concentration of impurities in the drops tends to vary.
  • the temperature was varied along the different storage channels, namely along the x axis.
  • another operating condition such as the hygrometric degree, the illumination or the concentration variation of another compound.
  • the analysis is of a visual type, thanks to the use of the microscope 34.
  • other types of analysis may be provided, especially of the Rar ⁇ an spectroscopy type, spectroscopy. infrared, UV or visible spectroscopy.
  • a succession of drops, forming plugs are directed in the different microchannels of storage.
  • the invention achieves the previously mentioned objectives.
  • the filling operations of the various storage channels, made according to the invention are reveal significantly faster than successive manipulations, which should be carried out in the state of the art. Furthermore, it is possible, thanks to the invention, to perform a direct reading of the desired characteristic, including a simple visual analysis.
  • drops of particularly small volume are advantageous .
  • these drops are real microreactors which, given their scale, are homogeneous and therefore do not require agitation, as might be the case for macroscopic systems.
  • This size of drops also ensures a rapid thermal equilibrium.
  • the use of this microscopic scale makes it possible to limit the inadvertent presence of impurities, which confers great precision on the determination thus made.
  • plugs is advantageous in terms of the accuracy of the determination of the desired characteristic.
  • the various plugs present in the storage channels are individual entities, likely to retain their original properties, especially their initial concentration.

Abstract

This device comprises: - a small plate (2), - at least one flow channel (20) cut into this small plate; - at least one storage channel (22<SUB>1</SUB>-22<SUB>6</SUB>) extending from this connection channel; and - a set of valves (V<SUB>1</SUB>-V<SUB>6</SUB>), each of which is suitable for allowing or stopping the flow of fluid in a corresponding storage channel.

Description

DISPOSITIF D'ECOULEMENT FLUIDIQUE, ENSEMBLE DE DETERMINATION D'AU MOINS UNE CARACTERISTIQUE D'UN SYSTEME PHYSICO-CHIMIQUE COMPRENANT UN TEL DISPOSITIF, PROCEDE DE FLUID FLOW DEVICE, ASSEMBLY FOR DETERMINING AT LEAST ONE CHARACTERISTIC OF A PHYSICO-CHEMICAL SYSTEM COMPRISING SUCH A DEVICE, METHOD OF
DETERMINATION ET PROCEDE DE CRIBLAGE CORRESPONDANTSDETERMINATION AND CORRESPONDING SCREENING METHOD
La présente invention concerne un dispositif d'écoulement fluidique, un ensemble de détermination d'au moins une caractéristique d'un système physico-chimique comprenant un tel dispositif, un procédé de détermination mettant en œuvre cet ensemble, ainsi qu'un procédé de criblage correspondant.The present invention relates to a fluid flow device, a set of determination of at least one characteristic of a physico-chemical system comprising such a device, a determination method implementing this set, as well as a screening method. corresponding.
Au sens de l'invention, un système physico-chimique, dont on se propose de déterminer au moins une caractéristique, peut être un corps pur, mais également un composé, tel que par exemple un ou plusieurs soluté (s) dissout dans un solvant, ou encore un mélange de plusieurs corps purs. Au sens de l'invention, une caractéristique de ce système physico-chimique est notamment une courbe caractéristique d'un tel système, en particulier une limite thermodynamique, notamment un diagramme de phases, tel qu'une courbe de solubilité, ou bien encore la limite de miscibilité pour un mélange de deux liquides.Within the meaning of the invention, a physicochemical system, which is intended to determine at least one characteristic, may be a pure body, but also a compound, such as for example one or more solute (s) dissolved in a solvent or a mixture of several pure bodies. Within the meaning of the invention, a characteristic of this physico-chemical system is in particular a characteristic curve of such a system, in particular a thermodynamic limit, in particular a phase diagram, such as a solubility curve, or even the miscibility limit for a mixture of two liquids.
La présente invention vise plus particulièrement, mais non exclusivement, l'étude de la solubilité d'un tel système physico-chimique. On rappelle que la solubilité d'un soluté dans un solvant est la concentration maximale de ce soluté que l'on peut dissoudre dans ce solvant, à une température donnée. La courbe de solubilité de ce soluté, qui forme par conséquent un système physico-chimique selon l'invention, correspond à la variation de cette solubilité en fonction de la température.The present invention aims more particularly, but not exclusively, the study of the solubility of such a physicochemical system. It is recalled that the solubility of a solute in a solvent is the maximum concentration of this solute that can be dissolved in this solvent at a given temperature. The solubility curve of this solute, which therefore forms a physicochemical system according to the invention, corresponds to the variation of this solubility as a function of temperature.
Les méthodes utilisées classiquement pour déterminer cette courbe de solubilité sont diverses. Elles font appel à différentes mesures, au cours desquelles au moins un paramètre est modifié, en particulier la concentration en soluté et/ou la température. De façon générale, les méthodes employées dans l'état de la technique sont de nature systématique, de sorte qu'elles se révèlent particulièrement longues à mettre en œuvre.The methods conventionally used to determine this solubility curve are various. They involve different measures, during which at least one parameter is changed, especially the solute concentration and / or the temperature. In general, the methods used in the state of the art are of a systematic nature, so that they prove to be particularly lengthy to implement.
Dans ces conditions, l'invention se propose de remédier à cet inconvénient. Elle vise en particulier à proposer une solution permettant de déterminer de manière fiable au moins une caractéristique d' un système physico- chimique, qui s'accompagne d'un temps de manipulation sensiblement réduit par rapport à l'art antérieur.Under these conditions, the invention proposes to remedy this drawback. It aims in particular to provide a solution for reliably determining at least one characteristic of a physicochemical system, which is accompanied by a significantly reduced handling time compared to the prior art.
A cet effet, elle a pour objet un dispositif d'écoulement fluidique, selon la revendication 1 annexée.For this purpose, it relates to a fluid flow device according to claim 1 attached.
D'autres caractéristiques avantageuses de ce dispositif font l'objet des revendications 2 à 12 annexées .Other advantageous features of this device are the subject of appended claims 2 to 12.
L'invention a également pour objet un ensemble de détermination d'au moins une caractéristique d'un système physico-chimique selon la revendication 13 annexée. L'invention a également pour objet un procédé de détermination d'au moins une caractéristique d'un système physico-chimique selon la revendication 14 annexée.The invention also relates to a set of determination of at least one characteristic of a physico-chemical system according to claim 13 attached. The invention also relates to a method for determining at least one characteristic of a physico-chemical system according to claim 14 attached.
D'autres caractéristiques avantageuses de ce procédé font l'objet des revendications 15 à 29 annexées. L'invention a enfin pour objet un procédé de criblage selon la revendication 30 annexée.Other advantageous features of this process are the subject of the appended claims 15 to 29. The invention finally relates to a screening method according to the appended claim 30.
L'invention va être décrite ci-après, en référence aux dessins annexés, donnés uniquement à titre d'exemple non limitatif, dans lesquels : - la figure 1 est une vue de face, illustrant de façon schématique un ensemble de détermination conforme à 1' invention, - les figures 2A et 2B sont des vues de côté, illustrant deux positions d'une vanne équipant l'ensemble de détermination de la figure 1 ;The invention will be described below, with reference to the accompanying drawings, given solely by way of non-limiting example, in which: - Figure 1 is a front view, schematically illustrating a set of determination according to 1; invention, FIGS. 2A and 2B are side views, illustrating two positions of a valve fitted to the determination assembly of FIG. 1;
- la figure 3 est un graphe, illustrant une courbe de solubilité que se propose de déterminer l'invention ;FIG. 3 is a graph illustrating a solubility curve that the invention proposes to determine;
- les figures 4A à 4C sont des vues de face, analogues à la figure 1, illustrant différentes étapes de mise en œuvre du procédé de détermination conforme à l'invention ;FIGS. 4A to 4C are front views, similar to FIG. 1, illustrating various steps of implementation of the determination method according to the invention;
- la figure 5 est une vue à plus grande échelle de la figure 4 ; etFIG. 5 is a view on a larger scale of FIG. 4; and
- la figure 6 est un graphe, analogue à la figure 3, sur laquelle est rapportée une courbe obtenue conformément à l'invention.- Figure 6 is a graph, similar to Figure 3, on which is reported a curve obtained according to the invention.
La figure 1 illustre un ensemble de détermination conforme à l'invention, qui comprend tout d'abord un dispositif d'écoulement fluidique, désigné dans son ensemble par la référence 1. Ce dernier comprend une plaquette 2, qui est réalisée de façon connue en soi par exemple en PDMS (poly- (diméthylsiloxane) ) . Cependant, à titre de variante, on peut prévoir de la former en tout autre matériau approprié, tel que du verre, du silicium, du PMMA (polyméthacrylate de méthyle) , ou encore une résine photosensible du type SU-8 de la société MicroChem, ou bien du type NOA de la société Nordland.FIG. 1 illustrates a determination assembly according to the invention, which firstly comprises a fluid flow device, designated as a whole by reference numeral 1. This latter comprises a wafer 2, which is produced in a known manner in FIG. for example PDMS (poly (dimethylsiloxane)). However, as an alternative, it may be provided to form it in any other suitable material, such as glass, silicon, PMMA (polymethyl methacrylate), or a photoresist of SU-8 type MicroChem company, or NOA type from Nordland.
Cette plaquette 2 possède une longueur et une largeur typique comprise entre 5 et 10 cm, ainsi qu'une épaisseur typique de 5 mm. Elle est gravée de différents microcanaux, selon les procédures classique de l'état de la technique, qui sont notamment décrites dans « D. C DUFFY, J. C .McDONALD, Olivier J.A. SCHUELLER, George M. WHITESIDES, ANAL. CHEN., 70, p.4974-4984, 1998 ». Dans l'exemple illustré, la section caractéristique de ces microcanaux est typiquement comprise entre 100 μm2 This wafer 2 has a length and a typical width of between 5 and 10 cm, and a typical thickness of 5 mm. It is etched with different microchannels, according to the conventional procedures of the state of the art, which are described in particular in "D. C DUFFY, J. C. McDONALD, Olivier J. SCHUELLER, George M. WHITESIDES, ANAL. CHEN, 70, p.4974-4984, 1998. " In the example illustrated, the characteristic section of these microchannels is typically between 100 μm 2
(par exemple 10 μm par 10 μm) et 1 mm2 (par exemple 1 mm par(for example 10 μm by 10 μm) and 1 mm 2 (for example 1 mm by
1 mm) . De manière typique, cette dimension provoque un écoulement laminaire au sein de ces microcanaux, avec un nombre de Reynolds inférieur à 10. A titre indicatif, en vue d' illustrer les propriétés de ces microcanaux, on citera l'ouvrage de Stéphane COLIN, microfluidique (traitée1 mm). Typically, this dimension causes a laminar flow within these microchannels, with a Reynolds number of less than 10. As an indication, in order to illustrate the properties of these microchannels, mention will be made of the work of Stéphane COLIN, microfluidic (treated
EGEM série microsystèmes, aux Editions HERMES SCIENCES PUBLICATION) .EGEM microsystems series, published by HERMES SCIENCES PUBLICATION).
On notera cependant que, à titre de variante, l'invention trouve également son application à des canaux d'écoulement de type millifluidique, à savoir dont la section transversale est supérieure aux valeurs mentionnées ci-dessus. Ainsi, la section transversale de ces canaux millifluidiques peut atteindre une valeur voisine de 9 mm2, soit par exemple 3 mm par 3 mm, voire voisine de 25 mm2, soit par exemple 5 mm par 5 mm.However, it will be noted that, by way of an alternative, the invention also finds application in millifluidic flow channels, ie whose cross-section is greater than the values mentioned above. Thus, the cross section of these millifluidic channels may reach a value close to 9 mm 2 , for example 3 mm by 3 mm, or even close to 25 mm 2 , for example 5 mm by 5 mm.
La figure 1 illustre plus particulièrement le dessin des microcanaux, qui sont gravés sur la plaquette 2. On retrouve tout d' abord deux microcanaux 4 et 6 d' amenée de deux premiers composants, qui sont associés à deux entrées 8 et 10. Chacune de ces dernières est propre à recevoir une première extrémité d'un tube non .représenté, dont l'autre extrémité est reliée à une seringue également non représentée. De façon classique, le débit du composant administré par chaque seringue est contrôlé par l'intermédiaire d'un pousse-seringue, également non représenté. II est par ailleurs prévu un microcanal 12, associé à une entrée 14 qui coopère avec un tube, avec une seringue, ainsi qu'avec un pousse-seringue non représentés. Ce microcanal 12 se divise en deux dérivations 16, affectant à peu près la forme d'un carré, qui se rejoignent en une intersection 18. Un microcanal de mélange 19, dans lequel débouchent les extrémités aval des deux microcanaux 4 et 6, est mis en communication avec cette intersection 18. En aval de l'intersection 18, à savoir au-dessous de celle-ci sur la figure 1, un canal dit de liaison 20 s'étend de façon longitudinale, en l'occurrence verticalement. Ce canal de liaison 20 est pourvu d'une sortie 20', dont on notera qu'elle est optionnelle. Il est mis en communication avec plusieurs canaux dits de stockage 22χ à 22β. Au sens de l'invention, le terme « plusieurs » signifie « au moins deux ».FIG. 1 illustrates more particularly the design of the microchannels, which are etched on the wafer 2. There are firstly two microchannels 4 and 6 for supplying two first components, which are associated with two inputs 8 and 10. the latter is adapted to receive a first end of a nonrepresented tube, the other end is connected to a syringe also not shown. In a conventional manner, the flow rate of the component administered by each syringe is controlled by means of a syringe pump, also not shown. There is further provided a microchannel 12, associated with an inlet 14 which cooperates with a tube, with a syringe, and with a not shown syringe driver. This microchannel 12 is divided into two branches 16, affecting approximately a square shape, which meet at an intersection 18. A microchannel 19 mixing, in which open the downstream ends of the two microchannels 4 and 6, is put in communication with this intersection 18. Downstream of the intersection 18, namely below this in Figure 1, a so-called connecting channel 20 extends longitudinally, in this case vertically. This connecting channel 20 is provided with an output 20 ', which will be noted that it is optional. It is put in communication with several so-called storage channels 22χ to 22β. For the purposes of the invention, the term "several" means "at least two".
Dans l'exemple illustré, ces microcanaux de stockage s'étendent horizontalement, à savoir qu'ils sont parallèles entre eux, tout en étant perpendiculaires au canal de liaison 20. Cependant, on peut prévoir que ces canaux de stockage ne sont pas perpendiculaires au canal de liaison et ne sont pas parallèles entre eux. Ainsi, il est possible de les disposer autour d'un cercle. Comme le montre la figure 1, le canal de liaison 20 et les différents canaux de stockage 22i à 226 définissent un peigne, dont l'embase est formée par le canal de liaison et dont les dents sont formées par les canaux de stockage. Par analogie avec l'électricité, les différents canaux de stockage s'étendent ainsi en parallèle à partir de ce canal de liaison.In the illustrated example, these storage microchannels extend horizontally, namely that they are parallel to each other, while being perpendicular to the connecting channel 20. However, it can be expected that these storage channels are not perpendicular to the link channel and are not parallel to each other. Thus, it is possible to arrange them around a circle. As shown in Figure 1, the connecting channel 20 and the various storage channels 22i 22 6 define a comb, whose base is formed by the connecting channel and the teeth are formed by the storage channels. By analogy with electricity, the different storage channels thus extend in parallel from this link channel.
On peut en outre noter que ce canal de liaison et ces canaux de stockage définissent un quadrilatère, dont un côté est formé par le canal de liaison 20, deux côtés supplémentaires sont définis par les canaux de stockage d'extrémité 22χ et 22ε, et un dernier côté est défini par un segment parallèle au canal de liaison 20, qui relie les sorties aval des différents canaux de stockage. Dans l'exemple illustré, le quadrilatère précité est un rectangle .It may further be noted that this link channel and these storage channels define a quadrilateral, one side of which is formed by the link channel 20, two additional sides are defined by the end storage channels 22χ and 22ε, and one The last side is defined by a segment parallel to the link channel 20, which connects the downstream outputs of the different storage channels. In the illustrated example, the aforementioned quadrilateral is a rectangle.
Dans l'exemple illustré, les microcanaux de stockage 22i à 22ε sont représentés au nombre de six. Cependant, en pratique, on utilise avantageusement un nombre de ces canaux qui est compris entre deux et quinze, de préférence entre cinq et dix. On peut également envisager d'utiliser un unique microcanal de stockage.In the illustrated example, the storage microchannels 22i to 22ε are represented in number of six. However, in practice, a number of these channels is advantageously used which is between two and fifteen, preferably between five and ten. One can also consider using a single microchannel storage.
A leur extrémité aval, située à droite sur la figure 1, les microcanaux de stockage coopèrent avec des vannes V1 à V6, illustrées de façon schématique, dont l'une Vi est représentée de façon plus précise sur les figures 2A et 2B. Le débouché 22' x du microcanal 22χ est mis en communication avec un tube rigide 24, réalisé par exemple en fluorinate d' ethylene-propylene (Teflon FEP) ou Polyetheretherketone (PEEK®) , à savoir qu'il ne se déforme sensiblement pas radialement lors de l'écoulement d'un fluide. Puis, ce tube rigide 24 débouche dans un tube souple 26, réalisé par exemple en PVC ou silicone, qui est associé à la vanne Vi. Cette dernière est une électrovanne à pincement de tube, de type connu en soi.At their downstream end, situated on the right in FIG. 1, the storage microchannels cooperate with valves V 1 to V 6 , illustrated in a schematic manner, one of which V 1 is shown more precisely in FIGS. 2A and 2B. The outlet 22 'x of the microchannel 22χ is placed in communication with a rigid tube 24, made for example of ethylene-propylene fluorinate (Teflon FEP) or Polyetheretherketone (PEEK ® ), namely that it does not deform substantially radially. during the flow of a fluid. Then, this rigid tube 24 opens into a flexible tube 26, made for example of PVC or silicone, which is associated with the valve Vi. The latter is a tube-clamping solenoid valve of a type known per se.
Il est à souligner que les tubes 24 et 26 forment un organe de liaison, reliant le débouché 22' i du microcanal 22i avec la vanne Vi. Cet organe de liaison est indépendant de la plaquette, à savoir qu'il peut être rapporté, notamment de façon amovible, sur les parois du débouché précité. Ceci est avantageux, dans la mesure où il est possible de réaliser la plaquette 2 en tout matériau, indépendamment de la nature de la vanne et de son organe de liaison.It should be noted that the tubes 24 and 26 form a connecting member, connecting the outlet 22 'i of the microchannel 22i with the valve Vi. This connecting member is independent of the wafer, namely that it can be reported, including removably, on the walls of the aforementioned outlet. This is advantageous, insofar as it is possible to make the wafer 2 of any material, regardless of the nature of the valve and its connecting member.
Cette électrovanne Vi est pourvue de manière classique d'un piston 28 propre à être actionné par une bobine non représentée, susceptible d'écraser le tube 26 contre un support 30. Il est à noter que la longueur 1 du tube souple 26, comprise entre son raccordement avec le tube rigide 24 et la zone de pincement par le piston 28, est très faible, par exemple voisine de 2 mm. Ceci permet de limiter les déplacements parasites du fluide dans les différents canaux, lors des manœuvres de la vanne.This solenoid valve Vi is conventionally provided with a piston 28 adapted to be actuated by a not shown coil, capable of crushing the tube 26 against a support 30. It should be noted that the length 1 of the flexible tube 26, between its connection with the rigid tube 24 and the pinching zone by the piston 28, is very small, for example close to 2 mm. This makes it possible to limit the parasitic displacements of the fluid in the different channels during the maneuvers of the valve.
La structure de la vanne représentée aux figures 2A et 2B est avantageuse. En effet, cette vanne est isolée physiquement, grâce à la présence du tube souple 26, par rapport au fluide présent dans les microcanaux de stockage. Par ailleurs, cette vanne est fiable, tout en présentant un prix de revient relativement peu élevé.The structure of the valve shown in Figures 2A and 2B is advantageous. Indeed, this valve is physically isolated, thanks to the presence of the flexible tube 26, relative to the fluid present in the microchannel storage. Furthermore, this valve is reliable, while having a relatively low cost.
Comme cela ressortira plus clairement de ce qui va suivre, l'invention prévoit d'imposer deux gradients selon les deux dimensions x et y, définies respectivement par les microcanaux de stockage 22 et le microcanal de liaison 20. En l'occurrence, selon la direction x, il s'agit en particulier d'imposer un gradient de condition opératoire, notamment de température, d'humidité, d' éclairement, ou encore de concentration d'un autre composé.As will become more clearly apparent from the following, the invention provides for imposing two gradients according to the two dimensions x and y, respectively defined by the storage microchannels 22 and the connecting microchannel 20. In this case, according to FIG. direction x, it is in particular to impose a gradient of operating condition, including temperature, humidity, illumination, or concentration of another compound.
Dans ces conditions, l'ensemble de détermination conforme à l'invention comprend des moyens permettant d'imposer un tel gradient le long des canaux 22. Dans l'exemple illustré, ces moyens comprennent deux modules à effet Peltier 32i et 322 permettant d'imposer un gradient de température. De façon connue en soi, un module à effet Peltier est susceptible de provoquer des variations de température en fonction d'un courant électrique qui lui est imposé. A titre purement non limitatif, on peut utiliser des modules conformes à ceux commercialisés par la société Melcor sous la référence CPI 4-71-06L.Under these conditions, the entire determination according to the invention comprises means for imposing such a gradient along the channels 22. In the example illustrated, these means comprise two Peltier modules 32i and 32 2 for d impose a temperature gradient. In a manner known per se, a Peltier effect module is capable of causing temperature variations as a function of an electric current imposed on it. For purely non-limiting reasons, it is possible to use modules conforming to those marketed by Melcor under the reference CPI 4-71-06L.
Le premier 32i de ces modules est placé au voisinage de l'extrémité amont des microcanaux de stockage 22, illustrée à gauche de la figure 1. Par ailleurs, le second 322 de ces modules est prévu au voisinage de l'extrémité aval de ces mêmes canaux, à savoir celle placée à droite de cette figure, où ces deux modules sont représentés en traits mixtes . Comme on le verra plus précisément dans ce qui suit, chacun de ces modules 32χ et 322 est susceptible de constituer une source chaude ou une source froide, .en fonction des étapes du procédé conforme à l'invention.The first 32i of these modules is placed in the vicinity of the upstream end of the storage microchannels 22, illustrated on the left of FIG. 1. Moreover, the second 32 2 of these modules is provided near the downstream end of these same channels, namely that to the right of this figure, where these two modules are shown in phantom. As will be seen more precisely in what follows, each of these modules 32χ and 32 2 may constitute a hot source or a cold source, .according to the steps of the method according to the invention.
Enfin, l'ensemble de détermination est pourvu de moyens propres à analyser le contenu des différents microcanaux ménagés dans la plaquette 2. Dans l'exemple illustré, il s'agit de moyens d'analyse visuelle, à savoir un microscope 34 représenté de façon schématique, dont le faisceau est dirigé vers les différents microcanaux de stockage 22. Le microscope 34, qui est associé à un appareil de prise de vues non représenté, est relié de façon classique à un ordinateur de traitement 36.Finally, the determination unit is provided with means capable of analyzing the contents of the different microchannels formed in the wafer 2. In the example illustrated, these are means of visual analysis, namely a microscope 34 shown The microscope 34, which is associated with an unrepresented camera, is connected in a conventional manner to a processing computer 36.
La mise en œuvre de l'ensemble de détermination conforme à l'invention, décrit ci-dessus, va maintenant être explicitée dans ce qui suit. Dans l'exemple, on souhaite déterminer la courbe de solubilité d'un soluté dans un solvant, telle que celle représentée à la figure 3. Sur cette dernière, les ordonnées correspondent à la concentration C en soluté dans le solvant, alors que la température T est reportée en abscisses. Ainsi, au-dessous et à droite de cette courbe de solubilité CS, le soluté est entièrement liquide alors que, en haut à gauche de cette même courbe, des cristaux de ce soluté peuvent se former dans la solution.The implementation of the determination set according to the invention, described above, will now be explained in the following. In the example, it is desired to determine the solubility curve of a solute in a solvent, such as that shown in FIG. 3. On the latter, the ordinates correspond to the solute concentration C in the solvent, whereas the temperature T is plotted on the abscissa. Thus, below and to the right of this solubility curve CS, the solute is entirely liquid whereas, at the top left of this same curve, crystals of this solute can form in the solution.
Au sens de l'invention, ce soluté A constitue un système physico-chimique que l'invention se propose d'étudier, qui peut être introduit dans le microcanal 4. Par ailleurs, le solvant précité B peut être admis par le microcanal 6, de sorte que le mélange du soluté et du solvant forme un ensemble physico-chimique au sens de l'invention. Enfin une phase porteuse P, telle que de l'huile, qui n'est pas miscible avec le mélange du soluté et du solvant, est admise par le microcanal 12.For the purposes of the invention, this solute A constitutes a physicochemical system that the invention proposes to study, which can be introduced into the microchannel 4. Furthermore, the abovementioned solvent B can be admitted via the microchannel 6, so that the mixture of the solute and the solvent forms a physicochemical set within the meaning of the invention. Finally, a carrier phase P, such as oil, which is not miscible with the solute mixture and solvent, is admitted by the microchannel 12.
Dans une étape préliminaire, il s'agit de remplir les différents microcanaux 20 et 22, ainsi que les tubes 24 et 26, au moyen d'huile ou bien de tout liquide approprié, ce qui permet de s'affranchir des problèmes dus à la compressibilité de l'air. Les différentes vannes Vi à V6 sont par ailleurs fermées. Puis, on ouvre uniquement la première vanne V1 (figure 4A), tout en admettant le soluté A et le solvant B par les microcanaux 4 et 6, ainsi que de l'huile par le microcanal 12.In a preliminary step, it is a question of filling the various microchannels 20 and 22, as well as the tubes 24 and 26, by means of oil or of any appropriate liquid, which makes it possible to overcome the problems due to the compressibility of the air. The different valves Vi to V 6 are also closed. Then, only the first valve V 1 (FIG. 4A) is opened, while admitting solute A and solvent B via microchannels 4 and 6, as well as oil via microchannel 12.
Comme le montre cette figure 4A, en aval de l'intersection 18, il se forme de manière connue en soi une succession de gouttes Gi, qui sont dirigées vers le premier canal de stockage 22i. Chaque goutte est formée par le mélange du soluté A et du solvant B, à savoir l'ensemble physico-chimique défini ci-dessus. De façon habituelle, ces gouttes Gi sont séparées les unes des autres par des tronçons d'huiles, formant une phase porteuse P non miscible avec ces gouttes. On notera que, lors de cette étape, on impose une température suffisamment élevée pour que le soluté se trouve entièrement sous forme liquide au sein des gouttes Gi, à savoir que l'on se situe en bas et à droite de la courbe CS de la figure 3.As shown in FIG. 4A, downstream of the intersection 18, a succession of drops Gi, which are directed towards the first storage channel 22i, is formed in a manner known per se. Each drop is formed by the mixture of solute A and solvent B, namely the physicochemical set defined above. In the usual way, these drops Gi are separated from each other by sections of oil, forming a carrier phase P immiscible with these drops. It will be noted that, during this step, a sufficiently high temperature is imposed so that the solute is entirely in liquid form in the drops Gi, that is, at the bottom and to the right of the curve CS of the figure 3.
Les valeurs des débits respectifs de soluté et de solvant, admis par les canaux 4 et 6, permettent de connaître la concentration Ci de soluté dans les différentes gouttes Gi. A cet égard, la somme des débits du soluté et du solvant est comprise entre 0,1 mL/hr et 5 mL/hr, notamment entre 0,5 et 1 mL/hr. Le débit d'huile, admise par le microcanal 12, est compris entre 0,5 et 10 mL/hr, notamment entre 1 et 5 mL/hr. Une fois que le premier microcanal 22i est rempli de premières gouttes Gi, on ferme la première vanne Vi, selon la procédure explicitée à la figure 2B, tout en ouvrant la seconde vanne V2 (figure 4B) , selon la procédure de la figure 2A. Par ailleurs, on modifie les débits respectifs de soluté et de solvant, de manière à former des gouttes G2 dans lesquelles la concentration C2 en soluté est différente de celle Ci évoquée précédemment.The values of the respective flow rates of solute and solvent, admitted via channels 4 and 6, make it possible to know the concentration Ci of solute in the different drops Gi. In this respect, the sum of the flow rates of the solute and the solvent is between 0.1 mL / hr and 5 mL / hr, in particular between 0.5 and 1 mL / hr. The oil flow admitted by the microchannel 12 is between 0.5 and 10 mL / hr, especially between 1 and 5 mL / hr. Once the first microchannel 22i is filled with first drops Gi, it closes the first valve Vi, according to the procedure explained in Figure 2B, while opening the second valve V 2 (Figure 4B), according to the procedure of Figure 2A . Moreover, the respective flow rates of solute and solvent are modified so as to form drops G 2 in which the solute concentration C2 is different from that mentioned above.
Ceci permet alors de remplir le second microcanal de stockage 222, .au moyen d'un second type de gouttes G2, comme l'illustre la figure 4B. De manière itérative, on remplit les différents microcanaux 22i à 22e au moyen de gouttes différentes Gi à Ge, pour lesquelles les concentrations en soluté varient de Ci à Ce- II est avantageux que cette concentration varie selon l'axe y, dans les différents microcanaux 22. Cette concentration peut ainsi varier de manière déterminable avec les ordonnées des microcanaux, notamment de façon monotone, par exemple de manière linéaire, exponentielle, ou encore logarithmique.This then makes it possible to fill the second storage microchannel 22 2 . by means of a second type of drops G 2 , as shown in Figure 4B. Iteratively, the different microchannels 22i to 22e are filled by means of different drops Gi to Ge, for which the solute concentrations vary from Ci to Ce. It is advantageous for this concentration to vary along the y axis in the various microchannels. 22. This concentration can thus vary determinably with the ordinates of the microchannels, especially monotonically, for example linearly, exponentially, or logarithmically.
Au terme de ces différentes étapes (voir figure 4C) , on a rempli l'ensemble des microcanaux de stockage 22±, où i = 1 à 6, au moyen de gouttes G±. Par ailleurs, pour un même microcanal 22i, la concentration C^ de soluté dans l'ensemble des gouttes Gi est identique alors que, dans les différents canaux 22i à 226, les concentrations Ci à C6 sont différentes .At the end of these different steps (see FIG. 4C), all the storage microchannels 22 ±, where i = 1 to 6, were filled by means of drops G 1. Moreover, for the same microchannel 22i, the concentration C 1 of solute in the set of drops G 1 is identical while, in the different channels 22 1 to 22 6 , the concentrations C 1 to C 6 are different.
Comme évoqué précédemment, le remplissage des différents microcanaux 22 a été réalisé à une température élevée, de sorte que les différentes gouttes Gi à G6 se trouvent à l'état entièrement liquide. Puis il s'agit d'abaisser la température régnant dans ces microcanaux 22, de façon à se déplacer vers la partie située en haut et à gauche de la courbe C de la figure 3, et de manière à cristalliser le soluté présent dans l'ensemble de ces gouttes. Cette modification de température est obtenue en modifiant, de- façon appropriée, le courant électrique fourni aux modules Peltier 32χ et 322- Ensuite, il s'agit d'imposer un gradient de température le long des différents canaux de stockage 22i à 226. A cet effet, le module Peltier de gauche 32X est commandé de manière à générer une température relativement basse à sa surface, voisine par exemple de 100C, alors que le module de droite 322 est commandé de manière à générer une température relativement élevée, par exemple de l'ordre de 600C. Etant donné la nature de la plaquette 2, l'application de ces températures différentes conduit à un gradient sensiblement linéaire le long de chaque microcanal 22. Ainsi, à l'extrémité amont, la température est proche de celle imposée par le module 32i alors que, à l'extrémité aval, la température est proche de celle imposée par le module 322-As mentioned above, the filling of the various microchannels 22 has been performed at a high temperature, so that the different drops Gi to G 6 are in the fully liquid state. Then it is a question of lowering the temperature prevailing in these microchannels 22, so as to move towards the part situated at the top left of the curve C of FIG. 3, and so as to crystallize the solute present in all of these drops. This change in temperature is obtained by modifying, as appropriate, the electric current supplied to the Peltier modules 32 2 and 32 2. Next, it is a matter of imposing a temperature gradient along the various storage channels 22 1 to 22. . For this purpose, the left Peltier module 32 X is controlled so as to generate a relatively low temperature on its surface, for example around 10 0 C, while the right module 322 is controlled so as to generate a relatively high temperature for example of the order of 60 ° C. Given the nature of the wafer 2, the application of these different temperatures leads to a substantially linear gradient along each microchannel 22. Thus, at the upstream end, the temperature is close to that imposed by the module 32i while at the downstream end, the temperature is close to that imposed by the module 322-
Le fait de remplir les différents microcanaux 22i à 226 avec des ensembles physico-chimiques différents permet de faire varier la concentration en soluté, selon l'axe y. Par ailleurs, la mise en œuvre des modules Peltier 32χ, 322 permet de faire varier continûment la température selon l'axe x. Conformément à l'invention, on a donc recréé un repère orthogonal analogue à celui du graphe représenté en figure 3, comme cela est illustré sur la figure 5, où les valeurs de concentrations Ci à Cç, sont portées sur l'axe des y.The fact of filling the various microchannels 22 1 to 22 6 with different physicochemical assemblies makes it possible to vary the concentration of solute along the y axis. Furthermore, the implementation of Peltier 32χ, 32 2 modules makes it possible to continuously vary the temperature along the x axis. In accordance with the invention, an orthogonal reference mark similar to that of the graph represented in FIG. 3 has thus been recreated, as illustrated in FIG. 5, where the concentration values Ci to Cc are plotted on the y-axis.
Il s'agit ensuite de procéder à une étape d'analyse, de manière à identifier les gouttes des microcanaux de stockage 22 où sont présents des cristaux. Cette analyse est menée de manière visuelle par l'intermédiaire du microscope 34. De façon avantageuse, ce microscope 34 présente un large champ de vision, afin d'observer en même temps l'ensemble de la plaquette. Il s'agit par exemple d'un microscope binoculaire.It is then necessary to carry out an analysis step, so as to identify the drops of storage microchannels 22 where crystals are present. This analysis is conducted visually through the microscope 34. Advantageously, this microscope 34 has a wide field of view, to observe at the same time time the entire wafer. This is for example a binocular microscope.
A titre d'exemple, on peut réaliser une observation à travers un analyseur et un polariseur croisés pour détecter aisément la présence de cristaux qui sont biréfringents . Si les cristaux sont suffisamment gros, il est possible de ne pas faire appel à la biréfringence.By way of example, an observation can be made through a crossed analyzer and polarizer to easily detect the presence of crystals that are birefringent. If the crystals are large enough, it is possible not to use birefringence.
Pour chaque microcanal de stockage, à savoir pour i = 1 à 6, on note sur la figure 5 Gi' les gouttes dans lesquelles sont présents des cristaux et Gi' ' les gouttes qui en sont dépourvus. Pour un même canal de stockage, les gouttes présentant des cristaux sont situées à gauche, à savoir du côté de la plus basse température.For each microchannel of storage, namely for i = 1 to 6, we note in Figure 5 Gi 'the drops in which are present crystals and Gi' 'drops that are lacking. For the same storage channel, the drops with crystals are located on the left, namely on the side of the lowest temperature.
Pour chaque i de 1 à 6, on note respectivement Gi' (1) et Gi'' (1) les deux gouttes adjacentes présentant des états différents, dont l'une est cristallisée et l'autre non cristallisée. En d'autres termes, la goutte Gi' (1) est la goutte présentant la température la plus haute parmi toutes celles cristallisées, alors que la goutte Gi'' (1) est la goutte présentant la température la plus basse parmi toutes celles non cristallisées. On en déduit alors deux températures, respectivement notées T1' et Ti' ' , qui correspondent aux gouttes ainsi identifiées .For each i of 1 to 6, Gi (1) and Gi (1) respectively denote the two adjacent drops having different states, one of which is crystallized and the other of which is not crystallized. In other words, the drop Gi '(1) is the drop having the highest temperature among all those crystallized, while the drop Gi''(1) is the drop with the lowest temperature among all those not crystallized. We then deduce two temperatures, respectively noted T 1 'and Ti'', which correspond to the drops thus identified.
On en déduit alors la température de solubilité Ti, pour chaque concentration Ci, où i = 1 à 6 :We then deduce the solubility temperature Ti, for each concentration Ci, where i = 1 to 6:
Ti = (Ti' + T1" ) /2.Ti = (Ti '+ T 1 ") / 2.
L'ordinateur 36 place alors, sur le graphe de la figure 6, les différentes valeurs Ti à Tβ ainsi obtenues pour les concentrations Ci à C6. On obtient donc, à partir de ces différents points, une courbe de solubilité CS' , représentée sur la figure 6, qui est proche de celle CS de la figure 3.The computer 36 then places, on the graph of FIG. 6, the different values Ti to Tβ thus obtained for the concentrations Ci to C 6 . From these different points, we thus obtain a solubility curve CS ', represented in FIG. 6, which is close to that CS of FIG.
Dans l'exemple décrit précédemment, la courbe de solubilité a . été tracée à partir de six points, correspondant à six microcanaux de stockage. On conçoit que, si l'on désire améliorer la précision du procédé de l'invention, il s'agit d'augmenter le nombre de microcanaux de stockage, ce qui permettra d'augmenter de façon correspondante le nombre de points à partir desquels est réalisée la courbe de solubilité. Il est également possible d' augmenter le nombre de gouttes présentes dans un même canal de stockage, ce qui contribue à diminuer la distance entre deux gouttes adjacentes. Ceci permet d'améliorer la précision sur la température de solubilité.In the example described above, the solubility curve a. been plotted from six points, corresponding to six microchannels of storage. It will be understood that, if it is desired to improve the accuracy of the method of the invention, it is a question of increasing the number of microchannels of storage, which will make it possible to correspondingly increase the number of points from which performed the solubility curve. It is also possible to increase the number of drops present in the same storage channel, which contributes to reducing the distance between two adjacent drops. This improves the accuracy of the solubility temperature.
Au terme de la mise en œuvre des étapes décrites ci- dessus, on a pu déterminer une caractéristique du système physico-chimique à étudier, à savoir sa courbe de solubilité. Il est alors possible de recommencer cette suite d'étapes avec un autre système physico-chimique, tout en l'associant au même solvant et en conservant les mêmes concentrations et le même gradient de température. De manière itérative, on réalise ces étapes pour toute une gamme de systèmes physico-chimiques de sorte que, au terme du procédé de criblage ainsi mis en œuvre, on peut alors identifier au moins un système physico-chimique intéressant en fonction de l'application visée.At the end of the implementation of the steps described above, it was possible to determine a characteristic of the physico-chemical system to be studied, namely its solubility curve. It is then possible to repeat this sequence of steps with another physico-chemical system, while associating it with the same solvent and keeping the same concentrations and the same temperature gradient. Iteratively, these steps are carried out for a whole range of physico-chemical systems so that, at the end of the screening method thus implemented, one can then identify at least one physicochemical system of interest depending on the application. referred.
L'invention n'est pas limitée à l'exemple décrit et représenté . Ainsi, dans cet exemple, la concentration du soluté varie selon l'axe y, à savoir pour des canaux différents. Cependant, on peut faire varier un autre paramètre du système physico-chimique que se propose d'étudier l' invention. Ainsi, il est possible d'admettre par le microcanal 4 un premier fluide comprenant un soluté et un premier type de solvant et, par le microcanal 6, un deuxième fluide formé de ce même soluté et d'un second solvant miscible avec le premier solvant. En ajustant les débits injectés dans ces microcanaux, on remplit les canaux de stockage au moyen d'un ensemble physico-chimique, pour lequel la concentration en soluté est constante mais la proportion des deux solvants précités est variable. A titre de variante supplémentaire, il est également possible de faire varier, selon l'axe y, le pourcentage d'impuretés présentes dans l'ensemble physico-chimique constitué du soluté et du solvant. Dans ce cas, on injecte une solution à une concentration donnée en soluté dans le canal 4. Par ailleurs, dans le canal 6, on injecte cette même solution qui comprend en plus une concentration donnée en impuretés, telles que des nanoparticules ou des molécules. Ainsi, suivant le rapport des débits, la concentration en impuretés dans les gouttes a tendance à varier.The invention is not limited to the example described and shown. Thus, in this example, the concentration of the solute varies along the y-axis, ie for different channels. However, another parameter of the physico-chemical system that the invention proposes to study can be varied. Thus, it is possible to admit, via the microchannel 4, a first fluid comprising a solute and a first type of solvent and, via the microchannel 6, a second fluid formed from this same solute and a second solvent miscible with the first solvent. . By adjusting injected flow rates in these microchannels, the storage channels are filled by means of a physicochemical unit, for which the concentration of solute is constant but the proportion of the two aforementioned solvents is variable. As a further variant, it is also possible to vary, along the y axis, the percentage of impurities present in the physicochemical assembly consisting of the solute and the solvent. In this case, a solution is injected at a given concentration of solute in the channel 4. Moreover, in the channel 6, the same solution is injected, which additionally comprises a given concentration of impurities, such as nanoparticles or molecules. Thus, according to the ratio of flow rates, the concentration of impurities in the drops tends to vary.
A titre d'exemple supplémentaire, on peut prévoir d' étudier des diagrammes de phases d' équilibre liquide- liquide, par exemple éthanol-hexadécane. Selon l'axe y, on fait varier la proportion d'un liquide par rapport à l'autre et on impose un gradient de température suivant l'axe x. On observe alors une limite entre des gouttes homogènes et des gouttes constituées de deux liquides non miscibles .As a further example, it is possible to study diagrams of liquid-liquid equilibrium phases, for example ethanol-hexadecane. According to the y axis, the proportion of one liquid is varied with respect to the other and a temperature gradient is imposed along the x axis. A limit is then observed between homogeneous drops and drops consisting of two immiscible liquids.
Dans l'exemple reprit et représenté, on a fait varier la température le long des différents canaux de stockage, à savoir selon l'axe x. Cependant, on peut faire varier une autre condition opératoire, telle que le degré hygrométrique, l' éclairement ou la variation de concentration d'un autre composé. Dans l'exemple décrit et représenté, l'analyse est de type visuel, grâce à l'utilisation du microscope 34. Cependant, à titre de variante, on peut prévoir d'autres types d'analyses, notamment de type spectroscopie Rarαan, spectroscopie infra-rouge, spectroscopie UV ou visible. A titre de variante supplémentaire, il est possible de sonder chaque goutte au moyen d'un appareil d'analyse, par exemple de type spectroscope RAMAN. Cela peut être fait de façon automatique, en plaçant la plaquette sur une table (x,y) motorisée et programmable, de type connu, de façon à placer successivement chaque goutte en regard de l'appareil d' analyse.In the example taken and shown, the temperature was varied along the different storage channels, namely along the x axis. However, it is possible to vary another operating condition, such as the hygrometric degree, the illumination or the concentration variation of another compound. In the example described and shown, the analysis is of a visual type, thanks to the use of the microscope 34. However, as a variant, other types of analysis may be provided, especially of the Rarαan spectroscopy type, spectroscopy. infrared, UV or visible spectroscopy. As a further variant, it is possible to probe each drop by means of an analysis apparatus, for example of the RAMAN spectroscope type. This can be done automatically, by placing the wafer on a table (x, y) motorized and programmable, known type, so as to successively place each drop next to the analysis apparatus.
Dans l'exemple décrit et représenté, on identifie des gouttes présentant deux états différents, à savoir un état cristallisé et un état non cristallisé. Cependant, ces états différents, identifiés conformément à l' invention, peuvent être d'un autre type, à savoir par exemple un état liquide simple d'une part, ainsi que la présence de deux liquides non miscibles d'autre part. On peut ainsi accéder à une courbe caractéristique différente d'une courbe de solubilité, à savoir la limite de miscibilité dans le cas d'équilibres liquide-liquide.In the example described and shown, there are identified drops having two different states, namely a crystallized state and a non-crystallized state. However, these different states, identified according to the invention, may be of another type, namely for example a simple liquid state on the one hand, and the presence of two immiscible liquids on the other hand. It is thus possible to access a characteristic curve different from a solubility curve, namely the miscibility limit in the case of liquid-liquid equilibria.
A titre de variante supplémentaire, il est également possible de réaliser une cartographie en deux dimensions d'une réaction chimique. On introduit des réactifs à des concentrations différentes dans les microcanaux de stockage, alors qu'on fait varier la température ou l' éclairement suivant l'axe x. On observe alors, par exemple par spectroscopie Raman, le produit de la réaction correspondante.As a further alternative, it is also possible to perform a two-dimensional mapping of a chemical reaction. Reagents at different concentrations are introduced into the microchannels of storage, while the temperature or illumination is varied along the x axis. The product of the corresponding reaction is then observed, for example by Raman spectroscopy.
Dans l'exemple décrit et représenté, on dirige une succession de gouttes, formant des bouchons, dans les différents microcanaux de stockage. Cependant, il est possible d'injecter directement un mélange de soluté et de solvant, sans faire appel à une phase porteuse.In the example described and shown, a succession of drops, forming plugs, are directed in the different microchannels of storage. However, it is possible to directly inject a mixture of solute and solvent, without using a carrier phase.
L'invention permet d'atteindre les objectifs précédemment mentionnés.The invention achieves the previously mentioned objectives.
En effet, les opérations de remplissage des différents canaux de stockage, réalisées selon l'invention, se révèlent nettement plus rapides que les manipulations successives, auxquelles il convient de procéder dans l'état de la technique. Par ailleurs, il est possible, grâce à l'invention, de réaliser une lecture directe de la caractéristique recherchée, moyennant notamment une simple analyse visuelle.Indeed, the filling operations of the various storage channels, made according to the invention, are reveal significantly faster than successive manipulations, which should be carried out in the state of the art. Furthermore, it is possible, thanks to the invention, to perform a direct reading of the desired characteristic, including a simple visual analysis.
De plus, la possibilité de former, grâce à l'invention, des gouttes de volume particulièrement réduit, est avantageuse.. En effet ces gouttes sont de véritables microréacteurs qui, étant donné leur échelle, sont homogènes et ne nécessitent par conséquent pas d'agitation, comme cela pourrait être le cas pour des systèmes macroscopiques. Cette taille de gouttes assure également une mise en équilibre thermique rapide. Par ailleurs, l'utilisation de cette échelle microscopique permet de limiter la présence intempestive d'impuretés, ce qui confère une grande précision à la détermination ainsi réalisée.In addition, the possibility of forming, thanks to the invention, drops of particularly small volume, is advantageous .. Indeed these drops are real microreactors which, given their scale, are homogeneous and therefore do not require agitation, as might be the case for macroscopic systems. This size of drops also ensures a rapid thermal equilibrium. Moreover, the use of this microscopic scale makes it possible to limit the inadvertent presence of impurities, which confers great precision on the determination thus made.
Enfin, on notera que l'utilisation de bouchons est avantageuse, en termes de précision de la détermination de la caractéristique recherchée. En effet, les différents bouchons présents dans les canaux de stockage constituent des entités individuelles, susceptibles de conserver ainsi leurs propriétés originelles, en particulier leur concentration initiale. Finally, it will be noted that the use of plugs is advantageous in terms of the accuracy of the determination of the desired characteristic. Indeed, the various plugs present in the storage channels are individual entities, likely to retain their original properties, especially their initial concentration.

Claims

REVENDICATIONS
1. Dispositif d'écoulement fluidique, comprenant :Fluidic Flow Device, comprising:
- une plaquette (2) , - au moins un canal de liaison (20) ménagé dans cette plaquette ; plusieurs canaux de stockage (22i~226) s' étendant à partir de ce canal de liaison ; plusieurs vannes (Vi-V6) , dont chacune est propre à autoriser ou à arrêter l'écoulement de fluide dans un canal de stockage correspondant ; et des moyens (32χ, 322) propres à imposer un gradient d' au moins une condition le long de chaque canal de stockage (22x-226) . - a wafer (2), - at least one connecting channel (20) formed in this wafer; a plurality of storage channels (22i ~ 22 6) extending from this connecting channel; a plurality of valves (Vi-V 6 ), each of which is adapted to allow or stop the flow of fluid in a corresponding storage channel; and means (32χ, 32 2 ) for imposing a gradient of at least one condition along each storage channel (22 x -22 6 ).
2. Dispositif d'écoulement fluidique selon la revendication 1, caractérisé en ce que ce dispositif comprend en outre des moyens (4, 6, 12, 18) de formation d'une succession de bouchons (Gi-Ge) dans une phase porteuse (P), dans le canal de liaison (20) et chaque canal de stockage (22) .2. Fluidic flow device according to claim 1, characterized in that this device further comprises means (4, 6, 12, 18) for forming a succession of plugs (Gi-Ge) in a carrier phase ( P), in the connecting channel (20) and each storage channel (22).
3. Dispositif d' écoulement fluidique selon la revendication 2, caractérisé en ce que les moyens de formation de bouchons comprennent au moins un premier canal d'amenée (4, 6) du (des) composant (s) desdits bouchons, ainsi qu'un second canal d'amenée (12) de la phase porteuse, formant une intersection avec le ou chaque premier canal d'amenée.3. fluid flow device according to claim 2, characterized in that the plug forming means comprise at least a first supply channel (4, 6) of the component (s) of said plugs, and a second supply channel (12) of the carrier phase, forming an intersection with the or each first supply channel.
4. Dispositif d'écoulement fluidique selon l'une quelconque des revendications précédentes, caractérisé en ce que la section transversale du canal de liaison (20) et de chaque canal de stockage (22x-226) est comprise entre 100 μm2 et 25 mm2.4. Fluid flow device according to any one of the preceding claims, characterized in that the cross section of the connecting channel (20) and each storage channel (22 x -22 6 ) is between 100 microns and 2 25 mm 2 .
5. Dispositif d'écoulement fluidique selon la revendication 4, caractérisé en ce que le canal de liaison et chaque canal de stockage sont des microcanaux (20, 22χ- 226) , dont la section transversale est comprise entre 100 μm2 et 1 mm2.Fluidic flow device according to claim 4, characterized in that the connecting channel and each storage channel are microchannels (20, 22 22χ- 6), whose cross section is between 100 microns 2 and 1 mm 2.
6. Dispositif d'écoulement fluidique selon l'une quelconque des revendications précédentes, caractérisé en ce que chaque vanne (V1-V6) est du type à pincement de tube.6. Fluid flow device according to any one of the preceding claims, characterized in that each valve (V 1 -V 6 ) is of the tube clamp type.
7. Dispositif d'écoulement fluidique selon l'une quelconque des revendications précédentes, caractérisé en ce que le débouché (22' i) de chaque canal de stockage (22X- 226) est mis en communication avec une vanne correspondante (Vi-V6) par l'intermédiaire d'un organe de liaison (24, 26) indépendant de la plaquette (2).7. Fluidic flow device according to any one of the preceding claims, characterized in that the outlet (22 'i) of each storage channel (22 X - 22 6 ) is placed in communication with a corresponding valve (Vi- V 6 ) via a connecting member (24, 26) independent of the wafer (2).
8. Dispositif d'écoulement fluidique selon la revendication 6 et 7, caractérisé en ce que l'extrémité de chaque canal de stockage (22i-226) opposée au canal de liaison -(20) est mise en communication avec un tube rigide (24), qui débouche dans un tube souple (26) propre à coopérer avec une vanne correspondante (Vi-Vβ) à pincement de tube . 8. Fluidic flow device according to claim 6 and 7, characterized in that the end of each storage channel (22i-22 6 ) opposite the connecting channel - (20) is placed in communication with a rigid tube ( 24), which opens into a flexible tube (26) adapted to cooperate with a corresponding valve (Vi-Vβ) pinching tube.
9. Dispositif d'écoulement fluidique selon l'une des revendications précédentes, caractérisé en ce que les canaux de stockage (22!-226) sont parallèles les uns aux autres .9. fluid flow device according to one of the preceding claims, characterized in that the storage channels (22 ! -22 6 ) are parallel to each other.
10. Dispositif d'écoulement fluidique selon la revendication 9, caractérisé en ce que les canaux de stockage parallèles (22i-22s) sont perpendiculaires au canal de liaison (20) .10. Fluidic flow device according to claim 9, characterized in that the parallel storage channels (22i-22s) are perpendicular to the connecting channel (20).
11. Dispositif d'écoulement fluidique selon l'une quelconque des revendications précédentes, caractérisé en ce qu'il est prévu entre deux et quinze, de préférence entre cinq et dix canaux de stockage (22!-226) .11. Fluid flow device according to any one of the preceding claims, characterized in that it is provided between two and fifteen, preferably between five and ten storage channels (22! -22 6 ).
12. Dispositif d'écoulement fluidique selon la revendication précédente, caractérisé en ce que les moyens permettant d' imposer un gradient comprennent une première source (32χ), placée au voisinage d'une première extrémité de chaque canal de stockage, ainsi qu'une deuxième source12. Fluidic flow device according to the preceding claim, characterized in that the means for imposing a gradient comprise a first source (32χ), placed in the vicinity of a first end of each storage channel, and a second source
(322), placée au voisinage d'une deuxième extrémité de chaque canal de stockage, les première et deuxième sources étant propres à imposer des conditions différentes, en particulier des températures différentes .(322), placed in the vicinity of a second end of each storage channel, the first and second sources being adapted to impose different conditions, in particular different temperatures.
13. Ensemble de détermination d'au moins une caractéristique d'un système physico-chimique, comprenant un dispositif d'écoulement fluidique conforme à l'une quelconque des revendications précédentes, des moyens d'analyse (34), propres à identifier au moins deux états différents du système physico-chimique, ou d'un ensemble physico-chimique comprenant ledit système physico-chimique, dans chaque canal de stockage, ainsi que des moyens de traitement (36) mis en relation avec les moyens d'analyse (34).13. An assembly for determining at least one characteristic of a physicochemical system, comprising a fluid flow device according to any one of the preceding claims, means of analysis (34) suitable for identifying at least one two different states of the physicochemical system, or a physico-chemical unit comprising said physico-chemical system, in each storage channel, as well as processing means (36) related to the analysis means (34). ).
14. Procédé de détermination d'au moins une caractéristique d'un système physico-chimique, mettant en œuvre un ensemble de détermination selon la revendication 13, procédé dans lequel :A method for determining at least one characteristic of a physico-chemical system, implementing a determination set according to claim 13, wherein
- on injecte différentes fractions dudit système physico-chimique (A) dans les différents canaux de stockagedifferent fractions of said physicochemical system (A) are injected into the different storage channels
(22χ-226) , en faisant varier au moins un paramètre de ce système physico-chimique (A) ou d'un ensemble physico- chimique (Gi-Gβ) comprenant ce système physico-chimique, dans les différents canaux, tout en maintenant ce paramètre invariant dans un même canal de stockage ;(22χ-22 6 ), by varying at least one parameter of this physico-chemical system (A) or of a physico-chemical unit (Gi-Gβ) comprising this physicochemical system, in the different channels, while now this invariant parameter in the same storage channel;
- on immobilise lesdites fractions du système physico-chimique ; - on impose un gradient d' au moins une condition le long des différents canaux de stockage (22i-226) ;said fractions of the physicochemical system are immobilized; - we impose a gradient of at least one condition along the different storage channels (22i-22 6);
- on identifie au moins deux états différents du système physico-chimique, ou dudit ensemble physicochimique (Gx-Gβ) , dans les canaux de stockage ; et - on en déduit la ou chaque caractéristique de ce système physico-chimique.at least two different states of the physico-chemical system, or of said physicochemical set (Gx-Gβ), are identified in the storage channels; and - We deduce the or each characteristic of this physico-chemical system.
15. Procédé de détermination selon la revendication15. Determination method according to claim
14, caractérisé en ce que le paramètre que l'on fait varier est la composition du système physico-chimique ou de l'ensemble physico-chimique comprenant ce système.14, characterized in that the parameter that is varied is the composition of the physico-chemical system or the physico-chemical complex comprising this system.
16. Procédé de détermination selon la revendication16. Determination method according to the claim
15, caractérisé en ce que le paramètre que l'on fait varier est la concentration du système physico-chimique dans l'ensemble physico-chimique.15, characterized in that the parameter that is varied is the concentration of the physico-chemical system in the physico-chemical complex.
17. Procédé de détermination selon la revendication 14, caractérisé en ce que l'ensemble physico-chimique est formé par le mélange du système physico-chimique, qui est notamment un soluté, et d'un adjuvant, notamment un solvant, et le paramètre que l'on fait varier est la nature de l'adjuvant, tout en conservant la même concentration en système physico-chimique dans l'ensemble physico-chimique.17. Determination method according to claim 14, characterized in that the physico-chemical unit is formed by the mixture of the physicochemical system, which is in particular a solute, and an adjuvant, in particular a solvent, and the parameter that one varies is the nature of the adjuvant, while maintaining the same concentration in physicochemical system in the physicochemical set.
18. Procédé de détermination selon l'une quelconque des revendications 14 à 17, caractérisé en ce qu'on fait varier le paramètre du système ou de l'ensemble physicochimique de manière proportionnelle, notamment linéaire, par rapport à la distance séparant les différents canaux de stockage (22χ-226) .18. Determination method according to any one of claims 14 to 17, characterized in that the parameter of the system or of the physicochemical unit is varied proportionally, in particular linear, with respect to the distance separating the different channels. storage (22χ-22 6 ).
19. Procédé de détermination selon l'une des revendications 14 à 18, caractérisé en ce que la condition dont on impose un gradient est une condition opératoire, notamment la température, le degré hygrométrique ou l'intensité d' éclairement .19. Determination method according to one of claims 14 to 18, characterized in that the condition which is imposed a gradient is an operating condition, including the temperature, the hygrometric degree or the intensity of illumination.
20. Procédé de détermination selon l'une des revendications 14 à 19, caractérisé en ce que les deux états différents correspondent à des phases différentes du système et/ou de l'ensemble physico-chimique.20. Determination method according to one of claims 14 to 19, characterized in that the two different states correspond to different phases of the system and / or the physicochemical set.
21. Procédé de détermination selon la revendication 20, caractérisé en ce que les phases différentes correspondent respectivement à la présence et à l'absence, dans l'ensemble physico-chimique, de cristaux formés par le système physico-chimique.21. Determination method according to claim 20, characterized in that the different phases correspond respectively to the presence and absence, in the physicochemical set, of crystals formed by the physicochemical system.
22. Procédé de détermination selon l'une des revendications 14 à 21, caractérisé en ce qu'on injecte le système et/ou l'ensemble physico-chimique sous forme de bouchons, en particulier de gouttes (Gi-G6) , dans une phase porteuse (P) non miscible avec ces bouchons.22. Determination method according to one of claims 14 to 21, characterized in that the system and / or the physicochemical set is injected in the form of plugs, in particular drops (Gi-G 6 ), into a carrier phase (P) immiscible with these plugs.
23. Procédé de détermination selon l'une des revendications 14 à 22, caractérisé en ce qu'on injecte le système physico-chimique avec une première valeur du paramètre dans un premier canal de stockage (22i) , tout en maintenant ouverte une première vanne (Vi) associée à ce canal et en maintenant fermées les autres vannes (V2-V5) , puis on ferme ladite première vanne tout en ouvrant une seconde vanne (V2), et on injecte le système physicochimique avec une seconde valeur du paramètre dans le second canal de stockage (222) , puis on injecte de manière itérative le système physico-chimique avec d'autres valeurs dudit paramètre dans les autres canaux de stockage.23. Determination method according to one of claims 14 to 22, characterized in that injects the physico-chemical system with a first value of the parameter in a first storage channel (22i), while keeping open a first valve (Vi) associated with this channel and keeping the other valves closed (V 2 -V 5 ), then closing said first valve while opening a second valve (V 2 ), and injecting the physicochemical system with a second value of parameter in the second storage channel (22 2 ), then iteratively injects the physicochemical system with other values of said parameter in the other storage channels.
24. Procédé de détermination selon l'une des revendications 14 à 23, caractérisé en ce qu'on remplit les différents canaux de stockage (22i~226) avec un système physico-chimique et/ou un ensemble physico-chimique dans un premier état, notamment liquide, on amène ce système et/ou cet ensemble dans un second état, notamment cristallisé, et on applique ledit gradient de condition, de façon à amener à nouveau dans le premier état initial seulement une partie du système et/ou de l'ensemble. 24. Determination method according to one of claims 14 to 23, characterized in that fills the various storage channels (22i ~ 22 6 ) with a physicochemical system and / or a physicochemical set in a first state, in particular liquid, this system and / or this set is brought into a second state, in particular crystallized, and said condition gradient is applied, so as to bring back to the first initial state only a part of the system and / or all.
25. Procédé de détermination selon l'une des revendications 14 à 24, caractérisé en ce qu'on identifie lesdits au moins deux états différents par analyse des différentes fractions du système physico-chimique injectées dans les canaux de stockage. 25. Determination method according to one of claims 14 to 24, characterized in that said at least two different states are identified by analysis of the different fractions of the physico-chemical system injected into the storage channels.
26. Procédé de détermination selon la revendication 25, caractérisé en ce qu'on réalise une analyse visuelle, notamment grâce à un microscope (34) associé à un appareil de prise de vues. 26. A method of determination according to claim 25, characterized in that a visual analysis is carried out, in particular by means of a microscope (34) associated with a camera.
27. Procédé de détermination selon la revendication 25, caractérisé en ce qu'on réalise une analyse de type spectroscopie, en particulier RAMAN ou infra rouge.27. Determination method according to claim 25, characterized in that a spectroscopy-type analysis is carried out, in particular RAMAN or infrared.
28. Procédé de détermination selon l'une quelconque des revendications 22 à 27, caractérisé en ce que, pour chaque canal de stockage (22i-22g) , on identifie deux valeurs adjacentes (T'i(l), T''i(l)) du paramètre qui correspondent à deux états différents des bouchons (G1-G6) et on réalise une moyenne de ces deux valeurs pour accéder à une valeur caractéristique (Ti) de ce paramètre, pour chaque canal de stockage.28. A method of determination according to any one of claims 22 to 27, characterized in that, for each storage channel (22i-22g), two adjacent values are identified (T'i (1), T''i ( l)) of the parameter which correspond to two different states of the plugs (G 1 -G 6 ) and an average of these two values is obtained to access a characteristic value (Ti) of this parameter, for each storage channel.
29. Procédé de détermination selon la revendication 28, caractérisé en ce que la caractéristique du système physico-chimique est une courbe caractéristique de ce système, et on déduit cette courbe caractéristique à partir des différentes valeurs caractéristiques (Ti-Tg) .29. Determination method according to claim 28, characterized in that the characteristic of the physicochemical system is a characteristic curve of this system, and this characteristic curve is deduced from the different characteristic values (Ti-Tg).
30. Procédé de criblage de plusieurs systèmes physicochimiques, dans lequel on prépare plusieurs systèmes physico-chimiques, on détermine au moins une caractéristique de chaque système physico-chimique selon l'une quelconque des revendications 14 à 29 et on identifie au moins un système physico-chimique préféré présentant au moins une caractéristique préférée. 30. A method for screening several physicochemical systems, in which several physico-chemical systems are prepared, determining at least one characteristic of each physicochemical system according to any one of claims 14 to 29 and identifying at least one physicochemical system. preferred chemistry having at least one preferred characteristic.
EP07858431A 2006-10-13 2007-10-12 Fluid flow device, assembly for determining at least one characteristic of a physicochemical system comprising such a device, corresponding determination process and screening process Withdrawn EP2076781A1 (en)

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FR0608995A FR2907228B1 (en) 2006-10-13 2006-10-13 FLUID FLOW DEVICE, ASSEMBLY FOR DETERMINING AT LEAST ONE CHARACTERISTIC OF A PHYSICO-CHEMICAL SYSTEM COMPRISING SUCH A DEVICE, DETERMINING METHOD AND CORRESPONDING SCREENING METHOD
PCT/FR2007/001667 WO2008046989A1 (en) 2006-10-13 2007-10-12 Fluid flow device, assembly for determining at least one characteristic of a physicochemical system comprising such a device, corresponding determination process and screening process

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Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5148635B2 (en) * 2007-03-05 2013-02-20 ロディア オペレーションズ Method for tracking crystallization of substances and corresponding microfluidic device and screening method
WO2009157863A1 (en) * 2008-06-26 2009-12-30 Wigstroem Joakim Microfluidic device
US9126127B2 (en) * 2011-05-24 2015-09-08 Bucknell University Apparatus and method for separating hydrophilic and hydrophobic components
GB201115895D0 (en) 2011-09-14 2011-10-26 Embl Microfluidic device
US20150174549A1 (en) * 2013-10-25 2015-06-25 The Brigham And Women's Hospital Corporation High-throughput synthesis of nanoparticles
WO2015116978A1 (en) * 2014-01-31 2015-08-06 Carnegie Mellon University Device and method for clinical data sampling and specimen banking
US11971377B2 (en) * 2018-03-12 2024-04-30 The Penn State Research Foundation Method and apparatus for temperature gradient microfluidics
JP2023063027A (en) * 2021-10-22 2023-05-09 株式会社エンプラス Fluid handling device and fluid handling system including the same

Family Cites Families (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3449938A (en) * 1967-08-03 1969-06-17 Univ Utah Method for separating and detecting fluid materials
US3799742A (en) * 1971-12-20 1974-03-26 C Coleman Miniaturized integrated analytical test container
US4231990A (en) * 1977-08-31 1980-11-04 S.A. Anarec Apparatus for the treatment of fluids
US4479762A (en) * 1982-12-28 1984-10-30 Baxter Travenol Laboratories, Inc. Prepackaged fluid processing module having pump and valve elements operable in response to applied pressures
US4601881A (en) * 1984-11-01 1986-07-22 Allied Corporation Liquid handling system
US5077017A (en) * 1987-11-05 1991-12-31 Biotrack, Inc. Integrated serial dilution and mixing cartridge
JPH0754285B2 (en) * 1989-02-04 1995-06-07 動力炉・核燃料開発事業団 Sampling method and apparatus for precipitated impurities in liquid sodium
US5213967A (en) * 1992-02-25 1993-05-25 Merck & Co., Inc. Automated sterility testing system with concurrent sample dissolving, diluting and mixing
US5716852A (en) * 1996-03-29 1998-02-10 University Of Washington Microfabricated diffusion-based chemical sensor
US6130098A (en) * 1995-09-15 2000-10-10 The Regents Of The University Of Michigan Moving microdroplets
US5863502A (en) * 1996-01-24 1999-01-26 Sarnoff Corporation Parallel reaction cassette and associated devices
US5948684A (en) * 1997-03-31 1999-09-07 University Of Washington Simultaneous analyte determination and reference balancing in reference T-sensor devices
CA2259395C (en) * 1996-07-15 2002-03-05 Sumitomo Metal Industries, Ltd. Equipment for crystal growth and crystal-growing method using the same
DE19648695C2 (en) * 1996-11-25 1999-07-22 Abb Patent Gmbh Device for the automatic and continuous analysis of liquid samples
US6045755A (en) * 1997-03-10 2000-04-04 Trega Biosciences,, Inc. Apparatus and method for combinatorial chemistry synthesis
SE512875C2 (en) * 1997-03-24 2000-05-29 Rolf Skoeld Method and apparatus for characterizing the physical and / or chemical properties of a fluid
US6004822A (en) * 1997-04-04 1999-12-21 Alfred LaGreca Device and method for measuring solubility and for performing titration studies of submilliliter quantities
US5869004A (en) * 1997-06-09 1999-02-09 Caliper Technologies Corp. Methods and apparatus for in situ concentration and/or dilution of materials in microfluidic systems
US6637463B1 (en) * 1998-10-13 2003-10-28 Biomicro Systems, Inc. Multi-channel microfluidic system design with balanced fluid flow distribution
DE19907448A1 (en) * 1999-02-22 2000-08-31 Uwe Spohn Flowing system for carrying out e.g. analysis reactions comprises variable speed positive displacement pumps preceding a mixing point and set flow resistance, enabling variable and steady state conditions to be set up
US7150994B2 (en) * 1999-03-03 2006-12-19 Symyx Technologies, Inc. Parallel flow process optimization reactor
US7052545B2 (en) * 2001-04-06 2006-05-30 California Institute Of Technology High throughput screening of crystallization of materials
US7244402B2 (en) * 2001-04-06 2007-07-17 California Institute Of Technology Microfluidic protein crystallography
WO2001062887A1 (en) * 2000-02-23 2001-08-30 Zyomyx, Inc. Chips having elevated sample surfaces
DE60108482T2 (en) * 2000-03-07 2006-02-16 Symyx Technologies, Inc., Santa Clara PROCESS OPTIMIZING REACTOR WITH PARALLEL FLOW
US8071051B2 (en) * 2004-05-14 2011-12-06 Honeywell International Inc. Portable sample analyzer cartridge
US6615856B2 (en) * 2000-08-04 2003-09-09 Biomicro Systems, Inc. Remote valving for microfluidic flow control
US7378280B2 (en) * 2000-11-16 2008-05-27 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US7010391B2 (en) * 2001-03-28 2006-03-07 Handylab, Inc. Methods and systems for control of microfluidic devices
US6418968B1 (en) * 2001-04-20 2002-07-16 Nanostream, Inc. Porous microfluidic valves
US6919046B2 (en) * 2001-06-07 2005-07-19 Nanostream, Inc. Microfluidic analytical devices and methods
US7077152B2 (en) * 2001-07-07 2006-07-18 Nanostream, Inc. Microfluidic metering systems and methods
FR2831081B1 (en) * 2001-10-24 2004-09-03 Commissariat Energie Atomique PARALLELISED AND SYNCHRONIZED INJECTION DEVICE FOR SEQUENTIAL INJECTIONS OF DIFFERENT REAGENTS
US7094379B2 (en) * 2001-10-24 2006-08-22 Commissariat A L'energie Atomique Device for parallel and synchronous injection for sequential injection of different reagents
US20040005720A1 (en) * 2001-10-30 2004-01-08 Cremer Paul S. Method and apparatus for temperature gradient microfluidics
DE10204414A1 (en) * 2002-02-04 2003-09-04 Siemens Ag Microfluidic system
US7459127B2 (en) * 2002-02-26 2008-12-02 Siemens Healthcare Diagnostics Inc. Method and apparatus for precise transfer and manipulation of fluids by centrifugal and/or capillary forces
US7112444B2 (en) * 2002-04-24 2006-09-26 Wisconsin Alumni Research Foundation Method of performing gradient-based assays in a microfluidic device
US6883957B2 (en) * 2002-05-08 2005-04-26 Cytonome, Inc. On chip dilution system
US7901939B2 (en) * 2002-05-09 2011-03-08 University Of Chicago Method for performing crystallization and reactions in pressure-driven fluid plugs
US20050266582A1 (en) * 2002-12-16 2005-12-01 Modlin Douglas N Microfluidic system with integrated permeable membrane
US7125711B2 (en) * 2002-12-19 2006-10-24 Bayer Healthcare Llc Method and apparatus for splitting of specimens into multiple channels of a microfluidic device
DE10302721A1 (en) * 2003-01-23 2004-08-05 Steag Microparts Gmbh Microfluidic arrangement for dosing liquids
SE0301639D0 (en) * 2003-06-06 2003-06-06 Biacore Ab Method and apparatus for characterization of intercations
US7655470B2 (en) * 2004-10-29 2010-02-02 University Of Chicago Method for manipulating a plurality of plugs and performing reactions therein in microfluidic systems
US9477233B2 (en) * 2004-07-02 2016-10-25 The University Of Chicago Microfluidic system with a plurality of sequential T-junctions for performing reactions in microdroplets
US7731910B2 (en) * 2005-08-05 2010-06-08 Hewlett-Packard Development Company, L.P. Microfluidic mixing assembly
WO2008147382A1 (en) * 2006-09-27 2008-12-04 Micronics, Inc. Integrated microfluidic assay devices and methods
FR2907227B1 (en) * 2006-10-13 2009-04-10 Rhodia Recherches & Tech METHOD AND FACILITY FOR DETERMINING AT LEAST ONE PARAMETER OF A PHYSICAL AND / OR CHEMICAL TRANSFORMATION AND CORRESPONDING SCREENING METHOD

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2008046989A1 *

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