EP1771244A1 - Drop microreactor - Google Patents

Abstract

The invention relates to a drop microreactor, i.e. a microreactor comprised of a drop of a particular liquid, whereby this microreactor does not walls, and the interface of the particular liquid with the ambient medium and with the support onto which the drop is deposited define the boundaries of the microreactor. The microreactor is characterized in that it is comprised of a drop containing at least one ionic liquid. The invention also relates to methods for carrying out chemical or biochemical reactions and/or a mixture of the two while using said microreactor as well as to a lab-on-chip comprising a microreactor of the aforementioned type.

Description

 MICROREACTOR DROP

DESCRIPTION

TECHNICAL FIELD The present invention relates to a drop microreactor, that is to say to a microreactor consisting of a drop of a particular liquid, the microreactor being without a wall, the interface of the particular liquid with the ambient medium and with the support on which the drop is deposited defining the limits of the microreactor.

The present invention also relates to methods for carrying out chemical or biochemical reactions and / or mixtures using said drop microreactor, as well as to a lab on a chip comprising a microreactor according to the invention.

The particular liquid used in the present invention is an ionic liquid or a mixture of ionic liquids. The present invention finds many applications, particularly in lab-on-a-chip where very small volumes of reaction media are generally used. It makes it possible, for example, to synthesize on a soluble support, syntheses in parallel, convergent syntheses, immobilizations on the ionic liquids of chemical or biological molecules that can be detected (target molecules) or detect (probe molecules), enzymatic reactions, homogenization of catalysts and homogeneous catalysts, process optimization, dangerous reactions, combinatorial chemistry reactions, etc.

In the following description, references in square brackets [] refer to the attached list of references.

State of the art

Numerous microsystems or microreactors intended to carry out chemical or biochemical reactions at the level of the μl, see ni, are described in the literature, for example in documents [1] - [5].

Most of these devices involve a system of channels, as described in documents [1] - [3], included in a packaging, including glass, metal, silicon, organic polymer, ceramic, etc.

However, these microsystems generate a certain number of problems: the channels are easily clogged, they are subject to hydrodynamic pressure drops, for example when syringe pumps and pumps are used, and it is often difficult to avoid them. dead volumes and optimize a low-cost microsystem compatible with an aggressive chemical environment, including solvents used, working temperatures, pressures, etc.

Other microsystems use drops of liquids in which the authors perform reactions. These microsystems are described for example in documents [4] and [5]. These drops of liquids may be aqueous or organic solvents. the

However, in both cases, the authors are confronted with the evaporation of these solvents, which implies the need for a hood in the best case, or makes their use impossible in the worst case. In addition, in the case of water, few organic chemistry reactions are known. In the case of organic solvents, the users are confronted with the problems of toxicity, for example by inhalation, of safety, for example because of risks of ignition, as well as recycling.

On the other hand, to perform chemical reactions in these microsystems, it is often necessary to move the reagents to perform these reactions or mixtures. In the case of the channels, the displacement of the reagents is often imposed by means of pumps which make it possible to control pressures, or syringe pumps which make it possible to control flows.

The displacement can also be achieved by electro-osmosis which requires the control of surface charges.

In drop systems, electrowetting

(EWOD: for "electrowetting on dielectric") and acoustic waves are generally used, as described for example in document [5]. For aqueous solvents, this does not generally pose too many problems whereas for organic solvents, only a few are compatible with these techniques. Indeed, most solvents are insulators, but solvents must be conductive to be used in electrowetting. However, few chemical reactions are performed in aqueous medium although a number of authors work there, as illustrated in document [6]. Finally, several chemical applications, such as combinatorial chemistry, in situ syntheses, etc. require the use of soluble supports, for example polyethylene glycols, or insoluble, for example beads of Merrifield type resins, silica, etc., in the reaction medium, as illustrated by documents [7] and [8] ]. Existing approaches have several drawbacks: (i) On insoluble supports: the reactions in a heterogeneous medium have a slower kinetics in general than in solution; sometimes some reactions that are feasible in solution do not work on solid support; and - the reactions are difficult to follow,

(ii) On soluble polymeric supports: the purification of the reaction products is very delicate, the parallelization is difficult - low specific charge, and difficult recycling.

There is therefore a real need for a reactor that does not have the aforementioned drawbacks of channel microsystems, micro-systems with aqueous or organic solvent drops, and soluble or insoluble supports of the prior art. Presentation of the invention

The present invention precisely meets this need, and still others, explained below, by providing a microreactor characterized in that it consists of a drop comprising at least one ionic liquid.

The present invention still meets this need, and still others, explained below, by providing, according to a first embodiment, a method of implementing a chemical or biochemical reaction comprising the following steps: a drop of at least one ionic liquid on a surface; introducing into the at least one ionic liquid, before or after depositing it in the form of a drop, of at least one chemical or biochemical reagent, reacting chemically or biochemically, in said drop, the reagent with the ionic liquid or the reagents between them. The present invention still meets this need, and still others, explained below, by providing a method for mixing drops of ionic liquid comprising the following steps: depositing a first drop of at least a first ionic liquid on a surface; depositing a second drop of at least one second ionic liquid on said surface; optionally introducing into the first ionic liquid, before or after its deposition in the form of a drop on the surface, of at least a first chemical or biochemical reagent; optionally introducing into the second ionic liquid, before or after its dropwise deposit on the surface, at least one second chemical or biochemical reagent; - meeting the first drop and the second drop so as to form a single drop.

Thus, the drops of ionic liquids, identical or different in their volume and / or their content, each comprising or not, independently of one another, one or more reagent (s), and each including or not, independently l one of the other, a solvent, are mixed together, and therefore also their possible content, by combining said drops in a single drop. The step of joining the drops may be followed by a step of chemically or biochemically reacting, in the drop formed by their meeting, reagents when they are present in one and / or the other of the drops between them and / or with the first and / or the second ionic liquid (s), in particular when this (these) ionic liquid (s) is (are) functionalized.

The present invention therefore, for example, still meets the above-mentioned need, and still others, described below, by providing, according to a second embodiment, a method for implementing a chemical or biochemical reaction comprising the following steps: depositing a first drop of at least one first ionic liquid on a surface; depositing a second drop of at least one second ionic liquid on said surface; introducing into the first ionic liquid, before or after depositing in the form of a drop on the surface, at least one first chemical or biochemical reagent; introducing into the second ionic liquid, before or after its dropwise deposit on the surface, at least a second chemical or biochemical reagent; meeting, on said surface, the first drop and the second drop to form a single drop; and chemically or biochemically react in the drop formed by the first and second joined drops, said first reagent with said second reagent.

The present invention aims to provide a new use of ionic liquids as a microreactor, more particularly for applications in analytical techniques and chemical and biochemical reactions carried out on laboratories on a chip. It therefore also relates to a laboratory on a chip comprising at least one microreactor according to the invention.

In fact, the microreactor of the present invention is a reactor without wall: it is the interface of the ionic liquid with the ambient environment which defines the limits of the microreactor. Therefore, in the present description, it is also called "drop microreactor". the

The ionic liquids, on the basis of which the present invention is implemented, have a number of interesting physico-chemical properties described in document [9]. These properties include: their low volatilities and very low vapor pressures: ionic liquids have very low volatility and very low vapor pressures, unlike Volatile Organic Solvents (VOS) and solvents. aqueous so no evaporation problem when used in droplet format. They are especially less volatile than water and most organic solvents such as, for example, ether, tetrahydrofuran, dichloromethane, chloroform, ethanol, methanol, toluene, acetonitrile, solvents whose temperature boiling point is less than or equal to 110 ^° C. Above this temperature, they pass into the gaseous state, and are no longer usable as solvents in chemistry in conventional reactors. In contrast, ionic liquids do not present this problem. their high thermal stability: the ionic liquids are very thermally stable, some up to more than 400 ⁰ C, in contrast to their low flammability, their high solubilization of salts as well as neutral organic molecules and polymers, and various materials such as transition metal complexes, for example such as catalysts; their recycling is easy. they can be functionalized and can then serve as soluble supports with a high specific load and make it possible to carry out reactions with the same reactivity as in aqueous or organic solution. chemical and biochemical reactions can easily be followed by modern analysis techniques such as nuclear magnetic resonance (NMR) or high performance chromatography (HPLC) techniques; the purification of the reaction products is easy.

The following properties of ionic liquids can also be cited, particularly for their interest in laboratory-on-a-chip applications: these liquids can be used in electrochemistry and have a large electrochemical window; and they are compatible with biological molecules such as enzymes, proteins, nucleic acids (DNA and RNA), glycoproteins, lipids, etc.

According to the invention, the at least one ionic liquid may be chosen from any suitable ionic liquids and onium salts known to those skilled in the art, as well as from their mixtures. The documents [9] and [10] describe examples of ionic liquids, onium salts and their mixtures that can be used to implement the present invention, as well as their physicochemical properties and their manufacturing method (s). The usable liquid liquid is in liquid form at room temperature, it can be represented by the formula A _x ⁺ Xi ^" , in which A ₁ ⁺ represents a cation, functional or not, or a mixture of cations in which either of the cations is functional, at least one of the cations is functional, and in which Xi ^" is a functional anion or not, or a mixture of anions in which either none of the anions is functional or at least one anions is functional. The expression "ionic liquid" generally means a salt or a mixture of salts whose melting point is between -100 ^° C. and 250 ^° C.

The term "ionic liquid", without further specification, means a pure ionic liquid or a mixture of ionic liquids, functionalized or not, or a mixture of one or more ionic liquids, functionalized or not, with one or more reagents and / or solvents. By "non-functional ionic liquid" or

"Matrix ionic liquid" means an ionic liquid capable of solubilizing one or more chemical or biological species such as inorganic or organic salts, organic molecules, polymers of natural or synthetic origin. The expression "nonfunctional ionic liquid" therefore refers to a solvent consisting of an ionic liquid. These new "solvents" are non-volatile and have a very low vapor pressure. They are also polar and have the ability to dissolve functionalized onium salts that can then be used as supports soluble as described in [10]. They can be used pure or in mixture.

By "functionalized ionic liquid" or "task-specific ionic liquid" or "dedicated ionic liquid" is meant an ionic liquid of the formula indicated above, of which either the cation, the anion or both is ) carrier (s) of a function capable of reacting with a reagent present in the drop. They can be used pure or in mixture.

The term "functional cation" refers to a molecular group that has at least one chemical function, a portion of this group carrying a positive charge. The term "functional anion" refers to a molecular group that has at least one chemical function, a portion of this group carrying a negative charge. The term "non-functional cation" refers to a molecular group that does not have a chemical function, a portion of this group bearing a positive charge. The term "non-functional anion" refers to a molecular group that does not have a chemical function, a portion of this group carrying a negative charge.

When the ionic liquid A ₁ ⁺ Xi ^" does not contain any functional ion, it is called" non-functionalized ionic liquid. "It serves as an inert reaction medium or matrix with respect to the reactants but is capable of dissolving them.

When the ionic liquid A _x ⁺ Xi ^" has at least one functional ion, it is called" functionalized ionic liquid ". reaction medium and for another part of soluble support or matrix.

In the present invention, said at least one ionic liquid can therefore be a functionalized or non-functionalized ionic liquid, but also a mixture of functionalized ionic liquid (s) and ionic liquid (s). non-functionalized. The drop of ionic liquid forming the microreactor may therefore comprise, in addition to the functionalized ionic liquid, an unfunctionalized ionic liquid, or, in addition to the nonfunctionalized ionic liquid, a functionalized ionic liquid.

The choice of the or mixture of ionic liquid (s) depends on the mixture and / or the chemical or biochemical reaction that will be implemented in the

"Drop reactor" of the present invention.

The fact of having mixtures of ionic liquids is not a problem, in the case where all the constituents of the mixture are chemically inert under the conditions of use when this inertia is required in the practice of the present invention.

For example, a mixture of non-functional tetralkylammonium salts or phosphonium salts may be used.

On the other hand, the melting point of a mixture is lower than the melting point of the constituent of the mixture which melts at the lowest temperature. It may therefore be very important to use a mixture to have an ionic liquid with a reasonable melting point. Some functionalized salts, especially those with large anions such as NTf2 ^"PFε" / BF ₄ ^"or CF ₃ SO ₃ ^" , can be liquid at room temperature or melted at a low temperature, for example

Me ^: 3, N ^{N +} _. H.NTf _{2 is} liquid at room temperature. This ionic liquid is prepared by alkylation of Me ₃ N according to the following reaction:

Me, N ^" OH, NTf ₂

Tf representing CF ₃ SO ₂

In the present invention it is possible to use as Ai ⁺ a non-functional cation or a mixture of non-functional cations and as a

Xi ^" a non-functional anion or a mixture of non-functional anions.

In the present invention, it is also possible to use, as Al ^+, a functional cation or a cation mixture of which at least one is functional, and / or as X ₁ ^" a functional anion or a mixture of anions of which at least one is functional, said functional cations and functional anions corresponding to an ionic entity, namely respectively cationic or anionic, linked to at least one function Fi, Fi varying from F ₀ to F _n , n being a integer ranging from 1 to 10.

The term "ionic entity" refers to that portion of the cation or anion, which carries the charge, respectively positive or negative. The function Fi can be chosen in particular from the following functions: hydroxyl, carboxylic acid, amide, sulphone, primary amine, secondary amine, aldehyde, ketone, ethenyl, ethynyl, dienyl, ether, epoxide, phosphine (primary, secondary or tertiary), azide imine, ketene,

• Cumulene, heterocumulene, thiol, thioether, sulfoxide, phosphorus groups, heterocycles, sulphonic acid, silane, stannane or functional aryl, and any function resulting from a chemical, thermal, photochemical or microwave irradiation transformation of the above functions.

For example, the at least one ionic liquid may be chosen from an imidazolium salt, more generally an ammonium salt, a phosphonium salt, an onium salt or a mixture of these salts. As indicated above, these salts may be functionalized or non-functionalized.

As examples of matrix ionic liquids, that is to say unfunctionalized ionic liquids, there may be mentioned the following: 1-butyl-3-methylimidazolium tetrafluoroborate [bmim] [BF ₄ ]; 1-butyl-3-methylimidazolium hexafluorophosphate [bmim] [PF ₆ ];

1-butyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide [bmim] [NTf ₂ ]; (1-ethyl-3-methylimidazolium hexafluorophosphate [emim] [PF ₆ ] and -butyltrimethylammonium bis (trifluoromethylsulfonyl) imide [btma] [NTf ₂ ]. For the implementation of the present invention, it is possible to use, for example, an ionic liquid as defined above, in a stable composition containing in solution: at least one ionic liquid of formula Ai ⁺ Xi ^" , acting as the liquid matrix, and at least one functionalized ionic liquid ("task-specific"), for example a functionalized onium salt, of formula A ₂ ⁺ X ₂ ^" , as a reaction support, the functionalized onium salt, by for example, the functionalized ionic liquid, being dissolved in the unfunctionalized ionic liquid, to form a homogeneous phase,

Ai ⁺ representing a non-functional cation or a mixture of cations in which none of the cations is functional, and Xi ^" representing a non-functional anion or a mixture of anions in which none of the anions is functional,

A ₂ ⁺ representing a cation, functional or not, or a mixture of cations in which none of the cations is functional or in which at least one of the cations is functional, and X ₂ ^" representing an anion, functional or otherwise, or a mixture of anions in which none of the anions is functional or in which at least one of the anions is functional, with the proviso that A ₂ ⁺ and / or X ₂ ^" represent (s) or include (s), respectively a functional cation and / or a functional anion, said functional cations and functional anions corresponding to an ionic entity Y-, namely respectively cationic Y ⁺ - or anionic Y ^" -, optionally linked via an arm L, in particular an alkyl group comprising from 1 to 20 carbon atoms, to at least one Fi, Fi function ranging from F ₀ to F _n , n being an integer varying from 1 to 10, the functional cation can be represented in the form Y ⁺ -L-Fi, and the functional anion in the form Y ^"~

(Dk-F ₁ , k being equal to 0 or 1, and the functional anion may represent, when k is equal to 0, a simple anion, corresponding to Y ^~ Fi, in particular chosen from: OH ^" , F ^" , CN ^"RO", RS ^"RSOJ, RCOj, RBFJ, wherein R represents an alkyl group comprising from 1 to 20 carbon atoms or an aryl group comprising from 6 to 30 carbon atoms.

The expression "stable composition" designates a homogeneous mixture composed of the liquid matrix A ₁ ⁺ Xi ^" and of the salt (s) functionalized (s) A ₂ ⁺ X ₂ ^" . This composition is said to be stable insofar as it does not undergo spontaneous transformations over time. It can be verified that this composition is stable by spectroscopic analysis using nuclear magnetic resonance (NMR), infrared (IR), visible ultraviolet (UV), mass spectrometry or radiation methods. chromatography. The expression "functionalized ionic liquid" designates an entity of type A ₂ ⁺ X ₂ ^" in which the cation and / or the anion carries a function Fi as defined above.This function confers on said functionalized ionic liquid and on the stable composition , of which it forms part, chemical and / or physicochemical properties. The term "functionalized onium salt" refers to the ammonium, phosphonium and sulphonium salts, as well as all the salts resulting from the guaternization of an amine, a phosphine, a thioether or a heterocycle containing one or more of these heteroatoms, and bearing at least one function Fi. This expression also denotes an onium salt whose cation as defined above is not functionalized but whose anion carries a function Fi. This expression may also denote a salt whose anion and cation carry a function Fi. A preferred functionalized onium salt is especially chosen from the following:

Me ₃ N, CI ^" or NTf ₂ or PF ₆ ^" or BF ₄ ^"

Me, N ⁺ , CI ^" orNTf _{2 or} FP ₆ ^{" or} BB ₄ ^"

, CI ^" ouNTf ₂ ouPF ₆ ^" orBF ₄ ^"

m being an integer from 0 to 20.

A preferred non-functionalized onium salt is especially chosen from the following: imidazolium, pyridinium Me ₃ N ⁺ -Bu or Bu ₃ P ⁺ -Me, NTf ₂ ^" anions, PF ₆ ^" or BF ₄ ^" . In the present invention the ionic liquids can therefore be used pure or in a mixture, for example an ionic liquid with specific tasks at a certain concentration in another ionic liquid serving as the

matrix, for example to carry out supported reactions as described in document [10]. The functional salt dissolved in the matrix may be a liquid or a liquid. solid with high melting point, the important thing is that it is soluble in the matrix. It may also be an ionic liquid dissolved in a solvent or solvents, if appropriate chosen to be compatible with the techniques of displacement of the drop (s) when these techniques are implemented in the of the present invention. A liquid functionalized onium salt at a temperature below 100 ^° C. may be a specific-task ionic liquid or a solution of a salt functionalized in a non-functional ionic liquid matrix. According to the invention, when the ionic liquid forming the microreactor comprises at least one solvent, it can be any solvent useful for implementing the present invention, preferably compatible with the ionic liquid (s) used (s). ), preferably miscible or partially miscible. In the latter case, the solvent is sufficiently miscible to allow the implementation of the mixture or the chemical reaction according to the present invention.

The at least one solvent may be chosen for example from organic solvents such as dichloromethane, chloroform, trichlorethylene, dichloromethylene, toluene, acetonitrile, propionitrile, dioxane, N-methylpyrrolidone, tetrahydrofuran (THF ), dimethylformamide (DMF), ethyl acetate, ethanol, methanol, heptane, hexane, pentane, petroleum ether, the

cyclohexane acetone, isopropanol; or from aqueous solvents such as sulfuric acid, phosphoric acid, sodium hydroxide, etc. This list is of course not limiting, and any solvent compatible with the ionic liquids and with the mixture and / or the chemical reaction implemented can be used to implement the present invention.

Volatile solvents such as those mentioned above (VOS and above) that are miscible with ionic liquids can be used. These solvents evaporate, especially when heated.

According to the invention, the ionic liquid forming the microreactor may also comprise at least one reagent. This (these) reagent (s) may (for example) be that (those) used (s) to perform, in the microreactor drop of the present invention, the reagent mixture (s) and / or the reaction (s) ) or biochemical (s). It may also be one or more reagent (s) used (s) for detecting and / or analyzing the initial and / or final products resulting from the chemical or biochemical reactions carried out in the microreactor.

The at least one reagent can be introduced into the ionic liquid in powder form (solid), in liquid form or in solution. Whatever the mode of implementation of the present invention, the introduction of the reagent can be done by simple deposition of the liquid reagent, in or on the ionic liquid before or after the deposition of the drop or drops on the surface. Homogenization of the ionic liquid / reagent mixture can then be carried out by example by stirring, or when it is a drop, for example by vibration or simple brownian agitation.

According to the invention, when the reagent to be introduced into the ionic liquid is volatile, it is advantageously possible to fix it in the microreactor of the present invention by using a specially functionalized ionic liquid to fix said reagent. Thus, when the reagent is introduced into the ionic liquid, it is fixed by the latter and can no longer evaporate.

When the reagent is in solution, the solution is preferably carried out using a solvent chemically compatible with the ionic liquid, that is to say which does not react chemically with the ionic liquid, and preferably also, which does not interfere with the chemical or biochemical reaction that must be implemented in the drop. The solvent used must of course also be at least partially miscible with the ionic liquid. Examples of solvents usable for this purpose are given above. After introducing the reagent in solution into the ionic liquid, the solvent used may remain in the ionic liquid or be evaporated from the ionic liquid, for example by heating.

According to the invention, when the reagent is in liquid form or in solution, it is also possible to deposit a drop of this reagent solution on the surface near the drop of ionic liquid forming the microreactor of the present invention and to bring together these two drops in one drop in order to mix their contents. The combination of these two drops can be made for example by one of the displacement techniques described below, for example by electrowetting. Thus, the introduction of the reagent into the microreactor of the present invention may be by coalescing a drop of ionic liquid and a drop of reagent onto the surface.

In the process of the present invention, whatever the embodiment, the drop (s) can (s) be deposited on the surface, for example of a lab-on-a-chip, by any known technique of the person skilled in the art, for example by a technique chosen from the group comprising a manual deposition, a deposition by an automated or non-automated drop dispenser, for example from an ionic liquid reservoir, or a deposition by fractionation of a larger drop deposited on the surface.

According to the invention, each drop forming a microreactor has a volume such that it forms a drop.

If necessary, when the drop has to be moved, this drop must be displaceable by the chosen displacement technique. For example for use in a lab-on-a-chip, in general, the drop has a volume of 10 μl to a few microliters, for example. When a technique of displacement of the drop on the surface is used, preferably the drop has a volume of 10 μl to 10 μl. The present invention thus makes it possible to carry out chemical or biochemical reactions in reactors without a small volume wall. According to the invention, the surface on which the drop is deposited is preferably a surface allowing the formation of a drop of ionic liquid without it spreading too much, especially in order to prevent contiguous drops whose coalescence was not expected to touch (unwanted contamination between drops deposited on the surface). It may be, for example, a silica surface, a glass surface, a Teflon surface, etc. This is in fact the surface on which the chemical or biochemical reaction is carried out using the drop microreactor of the present invention. It may be any surface suitable for making a lab-on-a-chip, and preferably compatible with ionic liquids. The material of the surface is therefore preferably compatible with the drop format and, where appropriate, with the chosen technique of displacement of the drop (s). If a displacement technique is used, a preferred surface, for example a lab on a chip, is of course a surface having little adhesion with the ionic liquid (s) used, for example a hydrophobic or hydrophobic surface, for example a Teflon surface. .

The surface may have one or more cavities (recesses) provided to receive the drop or drops; one or more projections; it can also be a flat surface without relief; or else a combination of hollows and / or projections and / or planar surface. When an electrowetting displacement technique is used, the surface may be provided with a conductive wire (against electrode) allowing the

to polarize the drop to move it as described below.

This surface may be that of a lab-on-a-chip known to those skilled in the art, covered or not with a hood.

The presence of a cover covering the drop or drops and intended to prevent evaporation of the ionic liquid is advantageously not mandatory. However, it may be required if the chemical reaction carried out requires particular conditions, for example an inert atmosphere, an argon flow, or a suction of toxic volatile products.

According to the invention, a first drop of an ionic liquid and a second drop of an ionic liquid may be deposited on a surface, for example a lab on a chip. According to the invention, the expression "a first drop of an ionic liquid and a second drop of an ionic liquid" is understood to mean that at least two drops that are identical or different, either by the nature of the ionic liquid or by the nature of the reagent (s) introduced into the ionic liquid are deposited on said surface. The present description applies of course, independently, to each of the drops deposited on said surface.

In the process of the present invention, whatever the embodiment, it is possible to deposit, for example, 1, 2, 3, 4, 5, 1000 or more drops on the same surface, these drops being identical or different. , by their volume and / or by nature of the ionic liquid and / or by the nature of the reagents introduced into the ionic liquid. The present invention therefore has a particular advantage, particularly by its ease of implementation, to perform on the same laboratory on a chip chemical and / or biochemical reactions in parallel, for example multiparametric reactions, for example on a sample to be analyzed. In the implementation of the method of the invention, a first and a second drop can be combined. According to the invention, the expression "the first and second drops are combined" means that at least two drops deposited on the surface can be combined, in particular to mix them and / or to mix their contents, for example the first and second reagents. By "first and second reagents" means at least two reagents, each of the drops may comprise one or more reagents, each of the drops may consist of a functionalized or non-functionalized ionic liquid.

The combination of the two drops, or coalescence, can therefore trigger the chemical or biochemical reaction (s) or simply perform a mixture of reagents and / or ionic liquids. For example, if one of the drops comprises a specific task ionic liquid and the other a matrix ionic liquid and a reagent, the meeting, or bringing into contact, of these drops of ionic liquid makes it possible to performing the desired chemical reaction (s) between the reagent and the function carried by the ionic liquid.

The meeting of several drops can be done simultaneously or successively. Indeed, initially two or more drops can be combined in a single drop to chemically react their contents when they are mixed, then in a second time a third or more drop can be added to the mixing the two previous ones to perform a mixture or another chemical or biochemical reaction, and so on. Thus, a series of chemical and / or biochemical reactions can be carried out very easily, by simple combination of drops, thanks to the present invention, for example on a lab-on-a-chip basis.

The implementation of the present invention may consist, according to a first example in the succession of the following steps, as illustrated schematically in Figure 1 attached: -i- on a surface, for example in a reaction chamber of a laboratory on a chip depositing a first drop of ionic liquid (LI A) consisting of an ionic liquid, or of an onium salt, functionalized with a function A capable of reacting or not with a reagent B, and

on this surface, a second drop of a matrix ionic liquid containing a reagent B is deposited.

the first and second drops are combined, for example by a displacement technique such as those mentioned above, and after an adequate time of chemical reaction between the function A and the reagent B, a drop (LI C) is obtained, in which the ionic liquid is functionalized by the product (C) of the reaction A + B. "" Indicates a chemical bond between the ionic liquid and the function or molecule that functions the ionic liquid. It may be for example a covalent bond, etc.

It is possible to perform other chemical reactions after fusions with other drops of ionic liquid containing other reagents.

In a second example (not shown), the two drops of ionic liquid are matrix ionic liquids, each of the drops comprises one of the reagents A and B, and the bringing into contact (coalescence) of these two drops of LI makes it possible to perform a mixing reagents A and B in the LI drop formed from the two joined drops or a reaction between reagents A and B. In this example, the drops may not be functional ionic liquids, but only matrices. In the latter case, the reagents are simply in solution in these matrices which act as solvents.

The implementation of the method of the invention may also consist, according to a third example, in the succession of the following steps, in addition to the above-mentioned steps, as illustrated diagrammatically in the appended FIG. 2:

on this surface, depositing a third drop of an ionic liquid containing a reagent D (together with the deposition of both first in steps -i- and -ii- or after step -ii- or -iv-);

the drop of the preceding step -iv-is combined with the drop of ionic liquid, for example by a displacement technique such as those mentioned above, and

after an adequate time of chemical reaction between the product C and the reagent D, a droplet (LI E) is obtained, in which the ionic liquid is functionalized by the product (E) of the C + D reaction.

In a fourth example, in which the ionic liquids are all matrix ionic liquids, three drops of ionic liquids, each comprising one of the reactants X, Y and Z, are obtained by combining a single drop comprising an X + Y + Z mixture.

The present invention may also consist, according to a fifth example, in the implementation of a method for preparing a molecule M attached to an initial function F ₀ , bonded, in the drop of ionic liquid, optionally via an arm

L, in particular an alkyl group comprising from 1 to 20 carbon atoms, with an ionic entity Y ⁺ -, forming part of the cation A ₂ ⁺ of the functionalized salt used A ₂ ⁺ X ₂ ^" , and / or Y ^" -, forming part of of the anion X ₂ ^" of the functionalized salt used A ₂ ⁺ X ₂ ^" , the cation being in the form Y ⁺ -LF ₀ and / or the anion being in the form Y - (Dk-F ₀ , k being equal to 0 or 1, which process comprises the following steps, written from the definitions of the ionic liquids provided above: a first addition of a reagent B ₁ in a drop of ionic liquid of composition mentioned above and the reaction between said function F ₀ , and the reagent Bi, leading to a function F ₁ , linked to the ionic entity Y ⁺ -, forming part of the cation A ₂ ⁺ of the functionalized salt A ₂ ⁺ X ₂ ^" , and or at the ionic entity Y ^" -, forming part of the anion X ₂ ^" of the functionalized salt A ₂ ⁺ X ₂ ^" , according to one of the following reaction schemes:

or

n-1 successive additions of Bi reagents (optionally via a drop of ionic matrix liquid, solid reagents, liquid reagents, or a drop of aqueous Bi solution) in the ionic liquid drop of aforementioned composition, l <i <n, n ranging from 2 to 10, allowing, at each addition, the reaction between the reagent Bi and a function Fi _-1 , leading to obtaining a function F ₁ , la (nl ) ^th addition of the reagent B _n to the function F _{n _!} leading to obtaining the function F _n , the n-1 additions being able to be represented according to one of the following reaction schemes:

Y ⁺ -LF ₁₅ X "2 _{→ γ} + _ _L _ _F2jX - γ + _ _L _ _F ._ _i3 χ-

Y ⁺ -LF _n , X ^~ <- ^ - Y ⁺ -LE, X ^" * - ^Bl J or

B

A + Y- -CL ^ -F ₁ - → A ⁺ J- - (L) -F ₂ ... A +, Y- - ^ k- ^F ii

^B • _. Bi

A + Y ^" - (L), -Fn ^ - ^J - A ⁺ Y - (Lk-Fi <- ^ - J

cleavage of the function F _n , linked to the ionic entity Y ⁺ - or Y ^" - respectively of the cation A ₂ ⁺ and / or of the anion X ₂ ^" , making it possible to recover on the one hand the functionalized salt A ₂ ⁺ X ₂ ^' in the form Y ⁺ -LF ₀ , X ₂ ^" or A ₂ ⁺ , Y - (L) ^ - F ₀ , in solution in the ionic liquid Ai ⁺ Xi ^" , or in the form Y ⁺ -L -FO, X ₂ ^" or A ₂ ⁺ , Y ^" - (L) _k -FO, in which F ' _o represents a function different from F ₀ , and on the other hand the molecule M, according to one of the reaction schemes following:

γ + - _L - _Fn? χ- ^Cliva g ^e) M ₊ Y ⁺ -LF _0, X or

Y ⁺ -L - F ', XI ^Cleavage ) M + Y ⁺ - L-F' XI or

A ⁺ , Y ^" - (L) _k - F _n ^Cleavage ) M + A ⁺ , Y ^" - (L) _k - F ₀ or

^Cleavage )> MM + I

Reagents B ₀ to B _n can be introduced successively via a drop of matrix ionic liquid fused to the drop of functionalized ionic liquid. The molecule M is recovered at the end of the preparation process used. Document [10] describes this type of protocol that can be used in the present invention. In a sixth example, drops of ionic liquids containing supported reagents can be fused, ultimately resulting in a multisel in solution in a LI matrix. We can then go back to the previous example and react unsupported reactants through fusion with drops of matrix ionic liquids containing these reagents.

Thus, by successive coalescences of drops according to the process of the invention, it is possible successively to carry out mixtures and reactions, in ionic matrix liquids or with ionic liquids functionalized to carry out many types of chemical and biochemical reactions, the same way as in a conventional reactor.

The possibilities of sequences of steps according to the present invention are therefore infinite.

In these sequences, the matrix or functionalized ionic liquids used during the different reactions may be identical or different. Thus, according to the invention, said at least one first ionic liquid and said at least one second ionic liquid are independently selected from a functionalized or non-functionalized ionic liquid. The first ionic liquid may therefore comprise, in addition to the functionalized ionic liquid, an unfunctionalized ionic liquid, or else; in addition to the unfunctionalized ionic liquid, a liquid ionic functionalised. Similarly, and independently, the second ionic liquid may comprise in addition to the functionalized ionic liquid, an ionic liquid. no . functionalized, or else, in addition to the unfunctionalized ionic liquid, a functionalized ionic liquid. Of course, the first drop and the second drop may be the same or different and may have, independently, volumes as indicated above. The step of chemically or biochemically reacting the reagent or reagents with each other or with the function carried by an ionic liquid of a drop is carried out as any chemical or biochemical reaction step in a conventional reactor of the prior art, that is to say with walls, except that it is carried out in the microreactor drop of the present invention, that is to say in the drop of ionic liquid functionalized or not.

According to the invention, it can be any chemical or biochemical reaction. Examples of possible reactions in the microreactor of the present invention include the following:

Combinatorial chemistry reactions and syntheses on soluble support, such as those described in document [11].

Enzymatic reactions; for example, reactions using lipases such as those described in document [12]. Catalysis reactions; for example, metathesis of olefins such as that described in document [13].

Hazardous reactions ; examples that may be mentioned are reactions involving azides as described in document [14].

Electrochemical reactions; for example, the cathodic breaks of bonds as described in document [15]. - The heterogenization of catalysts and homogeneous catalysts.

Optimizations of chemical or biochemical reactions.

Syntheses in parallel. - Converging syntheses.

Fixed assets on ionic liquids of chemical or biological molecules that can be detected (target molecules) or detect (probe molecules), for example proteins, enzymes, nucleic acids (DNA and RNA), glycoproteins, lipids etc.

In this reaction step, the appropriate operating conditions for the implementation of the chemical or biochemical reaction in question in conventional reactor of the prior art are therefore implemented in the present invention in a drop of ionic liquid. For example, each of the drops forming a microreactor may be heated to allow conventional reactions of organic chemistry, for example up to 200 ⁰ C or more, because of the non-volatility of W

33

ionic liquids. The chemical reactions carried out in the ionic liquids can be carried out at ambient temperature but also at elevated temperatures.

The product (s) obtained during or after the chemical reaction (s) carried out in the drop of ionic liquid may (may) then be detected (s) or quantified (s). ) either directly within the lab-on-a-chip, for example by colorimetric or electrochemical detection or any other appropriate detection means known to those skilled in the art, or outside the lab-on-a-chip, for example by the high performance chromatography (HPLC), gas chromatography (GC) techniques, spectroscopic analysis, nuclear magnetic resonance techniques

(NMR), infrared (IR), visible ultraviolet (UV), mass spectrometry (MS), liquid chromatography-mass spectrometry (LC / MS), colorimetric, or any other technique appropriate analysis known to those skilled in the art to detect the molecules to be analyzed.

The analyzes may be carried out directly in the drop (for example by NMR, HPLC or another technique such as those mentioned above), or after release of the product of the reaction linked to the ionic liquid by cleavage (see Example 1), and / or extraction and / or purification of the product (s) resulting from the reaction carried out in the drop of ionic liquid. This extraction can be carried out for example by the technique described in document [10].

According to the invention, whatever the method used, it may further comprise a step of moving on the surface the ionic liquid or drops.

This displacement of the drop (s) may have different objectives, among these, there may be mentioned for example that of bringing together two or more drops of ionic liquid deposited on the surface in the mixing (s) and reaction applications (s) chemical or biochemical above between the drops and their contents; but also that of moving a drop of ionic liquid from a reaction zone of a lab-on-a-chip to another reaction zone of said laboratory, or of a reaction zone of a laboratory-on-a-chip up to a detection zone of said laboratory.

The displacement of the drip microreactors of the present invention can be achieved by any technique known to those skilled in the art to move a drop on a surface.

Advantageously, according to the invention, it is a displacement technique chosen from: - A mechanical displacement, for example by vibration, by capillarity, by means of a pusher or by transport on a mobile support. An example of transport on a mobile support that can be used in the present invention is a "treadmill" as described for example in document [16]. the

Electrostatic displacement, for example by electrowetting. The technique of displacement of drops of ionic liquid by electro-wetting has been discovered in the context of the present invention. Indeed, during their research, the inventors of the present were the first to demonstrate the property of ionic liquids can be moved on a surface in the form of drop, by electrowetting. This technique is particularly advantageous in the implementation of the method of the invention, particularly in "lab-on-a-chip" applications. For example, electrowetting on dielectric described in document [5] can be used in which the forces used are electrostatic forces. The drop is based on an electrode array, from which it is isolated by a dielectric layer and a hydrophobic layer. When the electrode near the drop is activated, the dielectric layer and the hydrophobic layer between the activated electrode and the drop permanently polarized by a counter electrode, acting as a capacitor, - the effects of electrostatic charge induce the displacement of drop on the activated electrode. The counter electrode is essential for the movement by electrowetting, it maintains an electrical contact with the drop during its movement. This counter electrode can be either a catenary (Ca) as described in [5], or a buried wire, or a planar electrode on the hood of confined systems. The electrodes can be made by depositing a metal layer, by the

example of a metal selected from Au, Al, ITO, Pt, Cr, Cu, or by photolithography. The substrate is then covered with a dielectric layer, for example Si ₃ N ₄ or SiO ₂ . Finally, a deposition of a hydrophobic layer is performed, such as, for example, a Teflon deposit made by spinning. By the electrowetting technique, gradually it is possible to move the drops of ionic liquids, and possibly to combine them to mix, to achieve complex protocols. Document [5] gives examples of implementations of adjacent electrode series for handling a drop in a plane usable in the present invention. This type of displacement can be used for example in biochemical, chemical or biological analysis devices in the medical field, environmental monitoring, quality control, etc.

Displacement by dielectric forces. This technique consists in manipulating an interface between two immiscible fluids. The document

[17] discloses, for example, a dielectric liquid displacement control device operable in the present invention. A drop of liquid is placed between two planes comprising pairs of electrodes. The drop of liquid has a permittivity greater than its environment defined by the space between the two planes comprising the electrodes. The displacement is electrically controlled by applying electrical voltages to the electrode pairs. A variant of this technique, usable in the present invention is described in document [18].

A displacement by thermal gradient or by electrocapillarity, for example by the technique described in document [19]. The technique involves dipping a drop of ionic liquid in a thermal gradient. This results in a fluid circulation at the interface of the drop effect Marangonie. This fluid circulation causes the movement of the drop.

Displacement by pressure waves or acoustic waves, for example by the technique described in document [20]. The technique consists of propagating acoustic waves on a hydrophobic surface. The wave disturbs the wetting of the drop, and causes its displacement.

The present invention allows the realization of chemical or biochemical reactions in small wallless reactors. In addition, the ionic liquids with specific tasks allow the realization of chemical reactions with the same reactivity as in solution. In addition, the reactions can be followed and the purification of the reaction products is easy, for example after cleavage. With the microreactor drop of the present invention, there is no clogging of channels, there is no loss of charge in hydrodynamic mode, for example when syringe pumps and pumps are used and it does not there are no dead volumes as with the microreactors of the prior art. In addition, unlike channels, with the present invention, there is no problem of diffusion. The reactions remain constant and individualized. In addition, the microsystem of the present invention is a microsystem at low manufacturing cost and compatible with an aggressive chemical environment, in particular by the solvents used, the working temperatures, the pressures, etc. Other features and advantages of the invention will become apparent on reading the examples which follow, given by way of illustration and not limitation with reference to the appended figures.

Brief description of the figures

Figure 1: schematic representation of a chemical reaction and / or biochemical manufacturing of a product C in a microreactor drop produced by the method of the present invention by combining a drop of ionic liquid functionalized with a function A (LI A ) and a drop of matrix ionic liquid comprising reagent B.

FIG. 2: schematic representation of a chemical and / or biochemical reaction for the production of a product E in a microreactor made by the method of the present invention by combining a drop of functionalized ionic liquid (LI A) and a drop of ionic matrix liquid comprising reagent B to form the product c immobilized on the ionic liquid (LI C), then by meeting LI C with a drop of ionic matrix liquid comprising the reagent D.

Figure 3: schematic representation of the displacement of a drop of ionic liquid by electrowetting to implement the method of the present invention.

FIG. 4: graph showing the trace of a chromatogram (A (absorbance) = f (time in minutes)) obtained on a drop of ionic liquid with a specific task before carrying out a chemical or biochemical reaction according to the method of present invention.

FIG. 5: graph showing the trace of a chromatogram (A = f (time in minutes)) obtained on the drop of specific task ionic liquid of FIG. 4, but after chemical or biochemical reaction and washing according to the method of the present invention invention.

Figure 6A-C: diagram of a device for moving drops of ionic liquid by electrowetting for the implementation of the method of the present invention when it comprises a step of moving.

FIG. 7: graph showing the trace of a chromatogram (A = f (time in minutes)) obtained on the drop of ionic liquid with a specific task during a stall reaction of a reaction product attached to an ionic liquid after implementation of a method of the invention. FIG. 8: spectrum of spectrometry obtained in example 4 (Intensity = f (m / z)). EXAMPLES

Example 1: Implementation of the process of the present invention with displacement of the drops to make a chain with several chemical reactions: case of the Grieco reaction

Three drops of ionic liquids, each of a volume of 0.5 .mu.l are deposited on a teflon surface of the reaction chamber described in document [16] and schematized in FIGS. 3 and 6 appended hereto.

The drops used in this example have the following composition: drop 1: drop of 4-aminobenzoic acid supported on ammonium salt 1 (see reaction scheme below) in 1M solution in [tmba] [NTf ₂ ] ; drop 2: drop of 2 equivalents of 4-nitrobenzaldehyde and 1.2 equivalents of TFA in 0.5 M solution in [tmba] [NTf ₂ ]; and drop 3: drop of 10 equivalents of indene in IM solution in [tmba] [NTf ₂ ].

The drop displacement technique used in this example is an electrowetting displacement technique whose operation is shown schematically in FIG. 6 (only one drop is shown in FIG. 6): the support (S) is structured so as to comprise a electrode network (E), a dielectric layer (D), a hydrophobic layer

(H) and connection means (Co) connected to an electric generator (V). The drops (G) are based on the array of electrodes (FIG. 6A), from which they are isolated by the dielectric layer and the hydrophobic layer.

When one of the electrodes, near the drop, is activated, the dielectric layer and the hydrophobic layer between the activated electrode and the drop under tension acts as a capacitance, the surface is charged and the drop polarized permanently by a counter electrode, acting as a capacitance, the effects of electrostatic charge induce the displacement of the drop on the activated electrode. The counter electrode is essential for the movement by electrowetting, it maintains an electrical contact with the drop during its movement. This counter electrode is here a catenary (Ca). The electrodes are made by depositing a gold layer, by photolithography. The substrate is then covered with a layer of SiO ₂ . Finally, a deposit of a teflon layer is made by spinning.

The drop is electrostatically attracted to the surface of this electrode (FIG. 6B). Thus, step by step it is possible to move the drops of ionic liquids and also to mix them by selectively activating one or the other of the electrodes of the electrode array. A catenary (Ca), arranged on the support, makes it possible to polarize the droplet. In this example, the aforementioned drops are moved to be successively joined. Figure 3 is a schematic representation of the protocol used: the the ^era drop (1) is moved to the ^2nd (2), the ^2nd to the ^era and, after assembly of these two drops, the drop (1 + 2) formed by a mixture thereof is moved to the 3 ^rd (3) drop to form a drop (4).

After melting the three drops, the resulting mixture is incubated at room temperature for 15 minutes. The reaction of Grieco is then total. After reaction in droplet, the droplet (1.5 .mu.l) is recovered in an eppendorf tube and washed several times with ether (3x20 .mu.l) in order to extract excess or secondary products from the ionic liquid. The ether solubilizes these products, but is not miscible with the chosen ionic liquid. The ionic liquid is then rid of excess or secondary products.

The chemical reaction carried out in this example is summarized by the reaction scheme below, in which [btma] [NTf ₂ ] represents the ionic matrix liquid used, and in which TFA represents trifluoroacetic acid.

The product 2 is cleaved from the support after overnight incubation at room temperature in the presence of a 7N solution of NH ₃ in methanol. Thus, in the reaction scheme above, the X treatment comprises the following successive steps:

1) Washing with ether;

2) NH3 / MeOH at room temperature (T ° A); and 3) Extraction with ether after evaporation of methanol.

HPLC analysis of the reverse phase reaction shows the appearance of the final product with a retention time different from that observed for the functionalized starting salt.

The HPLC analysis conditions used were as follows:

• Column: Nova-Pak (registered trademark) Ci ₈ , Column 3.9 x 150 mm, Part No. WAT 086344,

Waters (trademark)

• Conditions:

CH ₃ CN / H ₂ O: 2: 1

CH ₃ CN HPLC (Carlo Erba - (Trademark))

H ₂ O solution composed of 20 mmol of ammonium acetate and 1% of acetic acid λ = 254 ntn Flux = 1.5 ml / minute

Pressure: 9.58x10 ⁵ to 10.07 x 10 ⁵ Pa (1390-1,460 Psi) - Column Temperature: 30 ^° C

Figure 4 is the trace of the chromatogram obtained on the drop of ionic liquid (1) specific task before implementation of the chemical reaction. FIG. 5 is the trace of the chromatogram obtained on the drop of ionic liquid (4) after chemical reaction and washes.

FIG. 7 is the trace of the chromatogram allowing a follow-up of the cleavage carried out by means of the treatment X making it possible to release the product of the reaction. The disappearance of the product 2_ whose retention time is 3.65 min and the appearance of 3 to 3.06 min. In this figure, in solid lines, the pattern obtained after three hours of contact with NH3 / MeOH: mixture of starting product and trans-esterified product; in broken lines, the transesterification reaction completed (and thus unhooking of the ionic liquid) after a night of reaction (12 hours), the starting material is no longer detectable.

Example 2 Detimentation Reaction Implemented According to the Process of the Present Invention

Two drops of matrix ionic liquid ([btma] [NTF ₂ ]) of 0.5 μl each are deposited on the teflon surface of the reaction chamber described in document [16]. Each of the drops contains a reagent: drop No. 1 contains a tritylated thymidine base and drop No. 2 contains dichloroacetic acid.

The No. 1 drop is converged to the other drop using the electrowetting technique. The applied voltage is 45 V.

After merging the two drops, the mixture is incubated at room temperature for 5 minutes. An orange coloring of the drop highlights the formation of the desired product.

The chemical reaction implemented is as follows:

orange product

Wherein DCA is dichloroacetic acid, and EWOD represents electrowetting displacement.

Example 3: Implementation of an enzymatic reaction

A first reaction mixture is prepared as follows: 50 mM phosphate-citrate buffer pH 6.5 (10 ml), o-phenylene diamine (OPD, 20 mg) and hydrogen peroxide (4 μl). A drop of this mixture of a volume of 0.5 μl is dissolved in matrix ionic liquid ([btma] [NTF ₂ ]) (0.5 μl).

A second reaction mixture is prepared as follows: matrix ionic liquid ([btma] [NTF ₂ ]) (0.9 μl) and horse radish peroxidase (0.1 μl at 20 μM).

One drop (0.5 μl) of each of the mixtures is deposited on the teflon surface of the reaction chamber used in Examples 1 and 2 above.

The No. 2 drop is converged to the other drop using the electrowetting technique. The applied voltage is 45 V.

After melting the two drops, the mixture is incubated at room temperature for 20 minutes.

A brown coloration characteristic of the enzymatic reaction of formation of 2,3-diaminophenazine is observed.

Example 4: Implementation of the process of the present invention with displacement of drops to effect a reduction reaction

Two drops of ionic liquids each of a volume of 0.3 .mu.l are deposited on a teflon surface of the reaction chamber described in document [16] and schematized in FIGS. 3 and 6 appended hereto.

The drops used in this example have the following composition: the

drop 1: drop of aldehyde supported on an ammonium salt 4 (see reaction scheme below) in solution [0.5 M] in [bmim] [BF ₄ ];

drop 2: drop of BH ₃ .pyridine (10 equivalents) in [bmim] [BF ₄ ].

The drops are then converged to one another by electrowetting by applying a voltage of 55 V. After melting the drops, the mixture obtained is incubated at room temperature (18-25 ^° C.) for 2 hours.

After reaction in drop, the drop (0.6 .mu.l) is recovered in an Eppendorf tube (registered trademark) and washed several times with ether (3x20 .mu.l) in order to extract the excess or secondary products from the ionic liquid. The ether solubilizes these products but is not miscible with the ionic liquid chosen.

Then the mixture is then injected into mass spectrometry ("electrospray") and positive mode. The spectrum represented in the attached FIG. 8 is thus obtained showing at 252.2 μm the molecular ion corresponding to the alcohol derived from the reduction of the aldehyde. The peaks at 139.3, 365.5 and 478.5 respectively correspond to the ions bmim ^{+ -} , [2bmim, BF ₄ ^' ] ⁺ - and to the adduct [alcohol 5, bmim, BF ₄ ^~ ] ⁺ -. Reaction Scheme of Example 4

NTf ₂ . ^"NTf _2;

LIST OF REFERENCES

[I] P.D.I. Fletcher et al, Lab on a chip, 2003, 309-333.

[2] K. Jahnisch et al, Angew. Chem.Int. Ed., 2004, 43, 406-446.

[3] S.J.Haswell and P. Watts, GB-A-2,387,382.

[4] Tomohiro Taniguchi, Toru Torii, Toshiro Higuchi, Lab on a chip, 2002, 2, 19-23.

[5] M. G. Pollack et al, Microtas 2003, vol. 1, p.619.

[6] Linstrom, Chem rev, 2002, 102, 2751-2772.

[7] S. R. Wilson and A. Czarnik, "Combinatorial Chemistry: Synthesis and Aplication"; John Wiley and Sons New York, 1997;

[8] D.G. Gravet and K.D. Janda, Chem. Rev., 1997, 97, 489-510.

[9] T. Welton, Chemical Reviews, 1999, 99 (8), 2071-2083.

[10] S. Gmouth, M. Vaultier, FR-A-2,845,084 (WO 2004029004).

[II] Angew. Chem.Int. Ed. Engl. , 1996, 35, 2288-2337

(Balkenhohl et al., Review).

[12] "Journal of Molecular Catalysts A: Chemical, 2004, 214, 1, p113-119 (Vaultier et al) [13] JACS, 2003, 125, 9248-9249 (JC Guillemin et al). [14] "Advanced Organic Chemistry, Reactions,

Mechanisms and structures, Jerry March, Fourth edition, Wiley New York, 1992.

[15] "Chemical News, August-September 1998, p442

(J. Simonet). [16] Y. Fouillet, R. Charles, O. Constantine, H.

Jeanson, WO-A-02/061438 (FR-A-2 841 063).

[17] J. P. Pesant, M. Hareng, FR-A-2 548 431.

[18] J. A. Schwartz, J; V. Vykoukal and P. R. C. Gascoyne, "Droplet-based Chemistry on Programmable Microchips", Lab-on-a-chip, 2004, 4.

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[20] A.Wixforth, J.Scriba, C. Gauer; MST-NEWS, 5-2002.

Claims

1. Microreactor characterized in that it consists of a drop comprising at least one ionic liquid. The microreactor of claim 1, wherein the ionic liquid comprises a solvent. 3. Microreactor according to claim 1, wherein the ionic liquid comprises at least one reagent. 4. Microreactor according to any one of claims 1 to 3, wherein said at least one ionic liquid is a functionalized or non-functionalized ionic liquid. 5. Microreactor according to claim 4, comprising: in addition to the functionalized ionic liquid, an unfunctionalized ionic liquid, or in addition to the nonfunctionalized ionic liquid, a functionalized ionic liquid. 6. Microreactor according to claim 1, wherein the drop has a volume of 1 μl to 10 μl. The microreactor according to claim 1, wherein the at least one ionic liquid is selected from an ammonium salt, a phosphonium salt, a salt, imidazolium, an onium salt or a mixture of these salts. 8. A method of carrying out a chemical or biochemical reaction comprising the steps of: depositing a drop of at least one ionic liquid on a surface; introducing into the at least one ionic liquid, before or after its drop deposit, of at least one chemical or biochemical reagent, reacting chemically or biochemically, in said drop, the reagent with the ionic liquid and / or the reagents between them. The process of claim 8, wherein the drop of ionic liquid comprises a solvent. The method of claim 8 or 9, wherein said at least one ionic liquid comprises a functionalized or non-functionalized ionic liquid. 11. The method of claim 10, wherein the drop comprises: in addition to the functionalized ionic liquid, a nonfunctionalized ionic liquid, or in addition to the nonfunctionalized ionic liquid, a functionalized ionic liquid. The method of claim 8, wherein the drop has a volume of 1 μl to 10 μl. 13. The method of claim 8, wherein the ionic liquid is selected from an ammonium salt, a phosphonium salt, an imidazolium salt, an onium salt or a mixture of these salts. 14. The method of claim 8, wherein the drop is deposited on the surface by a technique selected from the group comprising a manual deposition, a deposition by an automated drop dispenser or not, a fractional deposition of a larger drop deposited on the surface. The method of claim 8, wherein the surface is a surface of a lab on a chip. The method of claim 8, wherein the surface is a teflon surface. The method of claim 8, further comprising a step of moving the drop of ionic liquid on the surface by a technique selected from mechanical displacement, electrostatic displacement, thermal displacement, or acoustic displacement. 18. A method of mixing drops of ionic liquid comprising the steps of: depositing a first drop of at least a first ionic liquid on a surface; depositing a second drop of at least one second ionic liquid on said surface; optionally introducing into the first ionic liquid, before or after its deposition in the form of a drop on the surface, of at least a first chemical or biochemical reagent; optionally introducing into the second ionic liquid, before or after its dropwise deposit on the surface, at least one second chemical or biochemical reagent; - meeting the first drop and the second drop so as to form a single drop. 19. A method of carrying out a chemical or biochemical reaction comprising the steps of: depositing a first drop of at least a first ionic liquid on a surface; depositing a second drop of at least one second ionic liquid on said surface; introduction into the first ionic liquid, before or after its dropwise deposit on the surface, of at least a first chemical or biochemical reagent; introduction into the second ionic liquid, before or after its deposit in the form of a drop on the surface, at least one second chemical or biochemical reagent; meeting, on said surface, the first drop and the second drop so as to form a single drop; and chemically or biochemically react in the drop formed by the first and second joined drops, said first reagent with said second reagent. The method of claim 18 or 19, wherein the drop of the first ionic liquid comprises a solvent. 21. The method of claim 18 or 19, wherein the first ionic liquid comprises at least one reagent. 22. Method according to one of claims 18 to 21, wherein said at least one first ionic liquid and said at least one second ionic liquid are independently selected from a functionalized or non-functionalized ionic liquid. 23. The method of claim 22, wherein the first ionic liquid comprises: in addition to the functionalized ionic liquid, an unfunctionalized ionic liquid, or in addition to the non-functionalized ionic liquid, a functionalized ionic liquid. 24. The method of claim 22 or 23, wherein the second ionic liquid comprises: in addition to the functionalized ionic liquid, a nonfunctionalized ionic liquid, or - in addition to the unfunctionalized ionic liquid, a functionalized ionic liquid. 25. The method of claim 18 or 19, wherein the first drop and the second drop are identical or different and each have a volume of 1 nl to 10 .mu.l. The process according to claim 18 or 19, wherein the first and second ionic liquids are each, independently of one another, selected from an ammonium salt, a phosphonium salt, an imidazolium salt, an onium salt or a mixture of these salts. 27. The method of claim 18 or 19, wherein the first and / or second drop is (are) deposited on the surface by a technique selected from the group comprising a manual deposition, a deposit by a drop dispenser automated or not, a fractional deposition of a larger drop deposited on the surface. 28. The method of claim 18 or 19, wherein the surface is a surface of a lab-on-a-chip. The method of claim 18 or 19, wherein the surface is a teflon surface. 30. The method of claim 18 or 19, further comprising a step of moving on the surface the first drop of ionic liquid and / or the second drop of ionic liquid by a technique selected from mechanical displacement, electrostatic displacement, thermal displacement or acoustic displacement. Use of a process according to claim 18 in a process for carrying out a chemical or biochemical reaction. 32. The method of claim 8, 19 or 31, wherein the chemical or biochemical reaction is a reaction selected from the group consisting of a synthesis reaction, an immobilization reaction of chemical or biological molecules on the surface, an enzymatic reaction, a catalyst heterogenization reaction, a catalysis reaction, and an electrochemical reaction. Use of a process according to claim 8, 19 or 31 in a process for optimizing a chemical or biochemical reaction. 34. On-chip laboratory comprising at least one microreactor according to any one of claims 1 to 7.