A DEVICE AND METHOD FOR CONVERTING AND SEPARATING AT LEAST ONE REACTANT AND A REACTION PRODUCT THEREOF

Abstract

The invention relates to a method and a device device for converting at least one reactant(5) into a reaction product and separating the at least one reactant from the reaction product, wherein the device comprises a vessel(10) with a vessel inner volume (11) and a confinement (20) submerged in the vessel inner volume (11), the confinement (20) providing a confinement inner (21) volume which is in fluid connection with the vessel inner volume (11), wherein the vessel inner volume (11) contains a first fluid (1) with a first density p1 and a second fluid with a second density p2, with p1 > p2, so that the first fluid (1) forms a lower phase and the second fluid (2) forms an upper phase in the vessel inner volume (11), wherein the confinement contains a third fluid (3) with a third density p3 with p3 > p2 so that the second fluid forms an upper layer and the third fluid forms a lower layer in the confinement inner volume (21), wherein the third fluid may be the same as or different from and is physically separated from the first fluid (1), wherein at least one of the first, second fluid and third fluid is at most partly with the other two, but preferably immiscible, wherein the at least one reactant (5) and the reaction product (6) have a different affinity for at least two of the first, second (2) and third fluid, wherein at least one of the first (1) and third fluid (3) contain a fourth phase (4) which is a solid or semi solid and is selected from the group of materials capable of promoting the conversion of the at least one reactant into the reaction product.

Claims

1. A device for converting at least one reactant into a reaction product and separating the at least one reactant from the reaction product, wherein the device comprises a vessel with a vessel inner volume and a confinement submerged in the vessel inner volume, the confinement providing a confinement inner volume which is in fluid connection with the vessel inner volume, wherein the vessel inner volume contains a first fluid with a first density ρ1 and a second fluid with a second density ρ2, with ρ1 > ρ2, so that the first fluid forms a lower phase and the second fluid forms an upper phase in the vessel inner volume, wherein the confinement contains a third fluid with a third density ρ3 with ρ3 > ρ2 so that the second fluid forms an upper layer and the third fluid forms a lower layer in the confinement inner volume, wherein the third fluid may be the same as or different from and is physically separated from the first fluid, wherein at least one of the first, second fluid and third fluid is at most partly miscible with the other two, wherein the at least one reactant and the reaction product have a different affinity for at least two of the first, second and third fluid, wherein at least one of the first and third fluid contain a fourth phase which is a solid or semi solid and is selected from the group of materials capable of promoting the conversion of the at least one reactant into the reaction product.

2. The device according to claim 1, wherein the first and third fluid are at most partly miscible.

3. The device according to claim 1, wherein the fourth phase is positioned on a bottom of the vessel or a bottom of the confinement.

4. The device according to claim 3, wherein the confinement further comprises a liquid impermeable confinement wall.

5. The device according to claim 1, wherein the fourth phase is a biologically active material or a catalytically active material capable of promoting a chemical reaction or a combination hereof.

6. AThe device according to claim 1, wherein the fourth phase further comprises one or more materials selected from the group of a stationary phase that can carry out separations according to the principles of chromatography, a sorbent that can effectuate selective trapping of one or more agents transported by the fluidic flow, a porous or non-porous solid reagent carrier, wherein the reagent carrier may contain covalently or non-covalently bonded reagent(s), trapped liquid(s) or gas(es), an immobilized chemical reagent, scavenger, reaction support, trapping sorbent or a combination or two or more hereof.

7. AThe device according to claim 1, wherein the at least one reactant is contained in the first fluid, and one or more of the second and third fluid contain a compatibilizer for improving the compatibility of the reaction product with the second and/or third fluid.

8. AThe device according to claim 1, wherein the at least one reactant is contained in the third fluid, and the first or the second fluid contain a compatibilizer for improving the compatibility of the reaction product with the first or the second fluid.

9. The device according to claim 1, wherein the device comprises an agitator configured for agitating at least one of the first, second and third fluid.

10. AThe device according to claim 9, wherein the agitator is further configured for agitating the confinement.

11. AThe device according to claim 10, wherein the agitator comprises a first set of rotatable impellers at a position outside of the confinement and proximal to the bottom of the confinement.

12. The device according to claim 10, wherein the agitator further comprises a second set of rotatable impellers at a position proximal to an open top face of the confinement and below an upper surface of the second fluid.

13. AThe device according to claim 11 , wherein the impellers may be agitated at the same speed as the confinement or at a different speed.

14. AThe device according to claim 9, wherein an agitation speed of the agitator is variable.

15. AThe device according to claim 1, wherein a position of the confinement (20) in an upright direction of the reaction vessel is variable.

16. AThe device according to claim 1, wherein the one or more of the first, second and third fluid contain a material capable of selective trapping the at least one reactant or the reaction product, and combinations of two or more of such materials.

17. The device according to claim 1, wherein the confinement comprises a bottom and a peripheral wall which are liquid impermeable, and a top face which is at least partly open and capable of communicating with the vessel inner volume.

18. A method for converting at least one reactant into at least one reaction product and separating the at least one reactant from the at least one reaction product, wherein the method comprises the steps of feeding the at least one reactant to one or more of a first, second or third fluid contained in a vessel with a vessel inner volume into which a confinement is submerged, the confinement providing a confinement inner volume in fluid connection with the vessel inner volume, wherein the first fluid has a first density ρ1 and the second fluid has a second density ρ2, with ρ1 > ρ2, wherein the first fluid is at most partly miscible with the second fluid so that the first fluid forms a lower phase and the second fluid forms an upper phase in the vessel inner volume, wherein the vessel inner volume is at most partly filled with the second fluid in fluid connection with the confinement inner volume, wherein the confinement contains the third fluid with a third density ρ3, wherein ρ3 > ρ2 so that the second fluid forms an upper layer and the third fluid forms a lower layer in the confinement inner volume, wherein the third fluid may be the same as or different from the first fluid, wherein at least one of the first, second fluid and third fluid is immiscible with the other two, wherein at least one of the first and third fluid contain a fourth phase which is a solid or semi solid and is selected from the group of materials capable of promoting the conversion of the at least one reactant into the reaction product, wherein the at least one reactant and the at least one reaction product have a different affinity for at least two of the first, second and third fluid.

19. The method according to claim 18, wherein at least one of the first, second or third fluid is subjected to agitation.

20. The method according to claim 19, wherein agitation is carried out in such a way that mass transfer between the first, second and third fluid is promoted, while mixing of the first, second and third fluid is reduced to a minimum.

21. AThe method according to claim 18, wherein the fourth phase is a catalyst, a catalyst comprising a catalytically active material supported on a carrier material or an immobilized biological entity capable of transforming reactants into a desired reaction product.

22. AThe method according to claim 18, wherein the at least one reactant is supplied to the second fluid, wherein the reactant has a compatibility with the first fluid that is higher than with the second fluid, wherein the at least one reactant is subjected to a reaction in the first fluid to form at least one reaction product, wherein the at least one reaction product has a compatibility with the third fluid that is higher than with the first and second fluid and wherein the reaction product is recovered from the third fluid.

23. AThe method according to claim 18, wherein the at least one reactant is supplied to the second fluid, wherein the at least one reactant has a compatibility with the third fluid that is higher than with the second fluid, wherein the at least one reactant is subjected to a reaction in the third fluid to form the at least one reaction product, wherein the at least one reaction product has a compatibility with the first fluid that is higher than with the second and third fluid and wherein the at least one reaction product is recovered from the first fluid.

24. AThe method according to claim 18, wherein the at least one reactant is supplied in excess.

25. The device according to claim 1, wherein at least one of the first, second fluid and third fluid is immiscible with the other two.

26. The device according to claim 2, wherein the first and third fluid are immiscible.

27. The device according to claim 5, wherein the fourth phase is a biologically active material comprising cells or fragments thereof.

28. The device according to claim 10, wherein the agitator is configured for agitating the confinement by rotating, rocking, wagging, or oscillating the confinement.

Description

[0052] The present invention is further illustrated in the detailed description below, in the appending figures and description thereof.

[0053] FIG. 1 shows a schematic representation of a preferred embodiment of a device of the present invention.

[0054] FIG. 2 shows a schematic representation of the reactions occurring in example 4.

[0055] FIG. 3 shows in example 1, the evolution of the concentration of reactant BA and reaction product MPPA in the reactant mixture, and in the extracting buffer.

[0056] FIG. 4 shows in example 2, the evolution of the concentration of reactant BA and reaction product MPPA in the extracting buffer as the conversion of BA into MPPA proceeds.

[0057] FIG. 5 shows in example 2, the evolution of the reaction product yield (MPPA yield), and the loss of reactant BA into the extracting buffer as a function of reaction time.

[0058] As can be seen from FIGS. 1 and 2, the device of the present invention comprises a vessel 10 with a vessel inner volume 11. In the vessel inner volume 11 a confinement 20 is positioned, which in turn comprises an inner confinement volume 21 surrounded by a confinement peripheral wall 28. The inner confinement further comprises a bottom 27, and an upper face 26 which is at least partly open, but which in a preferred embodiment may be fully open. As a result, the confinement inner volume 21 is in fluid connection with the vessel inner volume 11 along its upper face 26 only. The vessel inner volume 11 is at least partly filled with fluid 1, 2, 3, the confinement 20 is submerged therein. Vessel 10 may contain one single confinement 20. The confinement may take any position in the vessel inner volume 11, but preferably it is positioned centrally in the vessel inner volume 11 in crosswise direction of the vessel inner volume. Alternatively, two or more confinements 20 may be provided, which may be positioned adjacently in the vessel inner volume 11 at a distance from each other, either according to a geometrically regular pattern or not. In the case where two or more confinements 20 are present, the two or more confinements may be shifted with respect to each other in height direction of the vessel 10 or they may be positioned at the same height.

[0059] In the vessel inner volume, means 30 may be provided for imparting motion to at least one of the first, second and third fluid contained in the vessel inner volume. Motion is understood to comprise many ways known to the skilled person of subjecting one or more of the first, second and third fluid phase to motion, for example to rotation, vibration, shaking, flow, wagging, rocking, oscillating or any other type of motion considered suitable by the skilled person, or combinations hereof. The means for imparting motion may be arranged to impart motion to one of the first, second or third fluid only, or to two or more hereof.

[0060] The means for imparting motion are preferably designed in such a way that mass transfer between adjacent fluids 1, 2 in the vessel inner volume 11 is promoted and diffusion of chemical compounds between the first and second fluid 1, 2 is promoted. Motion may cause the first and second fluid to be mixed to a certain degree, but motion is preferably done in such a way that mass transfer of one or more chemical compounds from one fluid to another is promoted while the mixing of adjacent fluids is limited. Similarly, the means for imparting motion are preferably designed in such a way that mass transfer between adjacent fluids 2, 3 in the confinement inner volume 21 and mass transfer between the second fluid 2 and third phase 3 is promoted. Motion may cause the third and second fluid to be mixed to a certain degree, but preferably the mixing is limited. This way for example, mass transfer or diffusion of a reactant supplied to the second fluid 2 towards the third phase 3 which contains a catalyst for catalysing the conversion of the reactant to a desired reaction product, may be promoted. Additionally, transfer or diffusion of the desired reaction product from the third phase into the second fluid towards the first fluid may be promoted as well, so that isolation of the desired reaction product is facilitated.

[0061] According to a preferred embodiment of this invention, the means for imparting motion comprise an upright extending axis 35 of the vessel 10, which may be subjected to a.o. rotation, vibration, rocking, etc. According to a further preferred embodiment of the invention as shown in FIGS. 1 and 2, the confinement 20 may be mounted to the upright axis 35. In a preferred embodiment, motion is understood to comprise rotation of the confinement 10, by rotating the axis 35. Thereby the angular velocity may vary or may be set at a constant value. Means for imparting rotation are well known from the prior art, and may for example comprise a direct mechanical connection of the axis to an external actuator, or an indirect coupling to an external force field, for example a ferromagnetic element present in the device which is actuated by a fluctuating external magnetic field.

[0062] Separation performance of the at least one reactant and at least one reaction product can be controlled by various parameters, and may for example be controlled by varying the motion speed of the at least one confinement, the position the confinement in the vessel inner volume, the size of the confinement or a combination of two or more hereof. Therefore, the position of the confinement 20 in the vessel inner volume 11 may either be fixed or be variable, in particular in height direction of the vessel inner volume and axis 35. Varying the position of the confinement 20 will in particular permit changing the working volume of the third fluid contained in the confinement inner volume 21, but it will also permit changing the working volume of the first and second fluid. Separation performance may further be improved by the presence of one or more materials capable of selective trapping the at least one reactant or the at least one reaction product, and combinations of two or more of such materials.

[0063] The motion shaft 35 or axis may be provided with additional motion imparting members, such as one or more impellers 31, 32 or any equivalent means known to the skilled person. The motion shaft 35 may comprise a first set of impellers 31, at a position outside of the confinement 20 and proximal to the bottom 27 of the confinement. The motion shaft 35 may be provided with a further second set of impellers 32 at a position proximal to an open top face 26 of the confinement and below an upper surface 15 of the second fluid. If so desired, additional impellers may be provided at a position considered suitable by the skilled person. Separation performance can be controlled by varying the rotation speed, and the position, size and numbers of the impellers. Moreover, the position of the confinement inside the vessel inner volume can be easily changed depending on the envisaged working volumes of each phase.

[0064] The vessel inner volume 11 contains a first fluid 1 with a first density p1, and a second fluid 2 with a second density p2, wherein p1 > p2. The first and second fluid are selected such that the first fluid 1 is at most partly miscible with the second fluid 2 so that the first fluid 1 forms a lower phase and the second fluid 2 forms an upper phase in the vessel inner volume 11. Preferably however, the first and second fluid 1, 2 are immiscible.

[0065] The confinement is submerged in the vessel inner volume in such a way that the second fluid 2 contained in the confinement inner volume 21 is in fluid connection with the second fluid 2 in the vessel inner volume 11, along the at least partly open upper face of the confinement 20. The confinement may be positioned such that its inner volume 21 is partly filled with the second fluid 2 and partly with a third fluid 3, or fully filled with third fluid 3. In the confinement inner volume, a third fluid is contained with a third density p3, wherein p3 > p2 so that the second fluid 2 forms an upper layer on top of the third fluid 3, which forms a lower layer in the confinement inner volume 21. The position of the confinement in the vessel inner volume 11, and the amount of first and second fluid in the vessel inner volume will determine the amount of third fluid 3 and second fluid 2 contained in the confinement inner volume 21.

[0066] The third fluid 3 may contain a third fluid 3, which is selected such that it is at most partly miscible with, preferably immiscible with the second fluid 2. The third fluid may be the same as or may be different from the first fluid 1. The first fluid 1 may be a liquid, or a mixture of two or more liquids, or it may have one or more solids or one or more reactants dissolved or dispersed therein. The second fluid 2 may also be a liquid, or a mixture of two or more liquids, or it may have one or more solids or one or more reactants dissolved or dispersed therein. The third fluid 3 may be a third liquid, or a mixture of two or more liquids, or it may have one or more solids or one or more reactants dissolved or dispersed therein. With miscible is meant that the two fluids may be mixed in all proportions that is, to fully dissolve in each other at any concentration, and form a homogeneous solution in all proportions. With two fluids being immiscible is meant that there are certain proportions in which the mixture of the two fluids does not form a solution.

[0067] In a preferred embodiment, the third fluid 3 contains a fourth phase 4, in particular a fourth solid member. The solid member 4 can comprise a wide variety of types of materials, for example immobilized biologically active materials such as cells or fragments thereof, a catalyst capable of promoting a chemical reaction, a stationary phase that can carry out separations according to the principles of chromatography, a sorbent that can effectuate selective trapping of one or more agents transported by the fluidic flow, a porous or non-porous solid reagent carrier, or a porous or non-porous solid reaction support, where the reagent carrier or reaction support may contain covalently or non-covalently bonded reagent(s), trapped liquid(s) or gas(es), an immobilized chemical reagent, catalyst, scavenger, reaction support, or trapping sorbent, or immobilized biological materials such as cells or fragments thereof or any other material that is capable of reacting with at least one reactant comprised in the first fluid.

[0068] The confinement 20 may house within its inner confinement volume 21, fourth phase or solid or semi solid member 4. The third fluid 3 will usually serve to protect or isolate the fourth phase 4 from the second fluid 2. In an embodiment it is however also possible that the solid member 4 is housed in inner vessel volume 11.

[0069] The confinement can further be equipped with means for providing exchange of energy, heating, cooling, introduction of acoustic energy, or application of electromagnetic radiation or microwave radiation, designed to be connected with one or more reaction confinement(s).

[0070] Either the vessel 10 or the confinement 20 or both can further be equipped with means for exchanging matter such as supplying or feeding of one or more reactants and/or removal of products or by-products. This will permit to provide the conditions for carrying out a specific desired biological or chemical reaction, or to control, accelerate, or delay a biological or chemical reaction. In an example, means may be provided for supplying a reactant to the confinement inner volume 21, and for removing first fluid 1 containing one or more reaction products from the vessel inner volume 22. Means may also be provided to replenish first fluid 1 and to remove second fluid 2 or third fluid 3.

[0071] In a preferred embodiment, a supply member may be provided for supplying the mixture containing two or more compounds to be separated from each other either to the first, the second or the third fluid 1, 2, 3. Preferably however, the supply member is arranged for supplying the mixture containing two or more compounds to be separated from each other to the second fluid 2. According to a further preferred embodiment a withdrawer 50 may be provided for withdrawing a desired reaction product 55 from the first fluid 1 or from the third fluid 3, but preferably from the first fluid 1. Batchwise withdrawal or withdrawal in the continuous mode may be provided.

[0072] The device and method of this invention may be exploited either in continuous mode or batchwise.

[0073] According to a preferred embodiment, the supply member is provided for supplying the at least one reactants to the second fluid 2. According to a further preferred embodiment a withdrawer 50 may be provided for withdrawing a desired reaction product obtained from the conversion of the at least one reactant in the confinement from the first fluid 1, or from the third fluid in case the reaction proceeds in the third fluid 3.

[0074] According to a still further preferred embodiment, at least one compound is at least one reactant and is contained in the third fluid, for example in the third fluid 3, converted into a reaction product and the reaction product may be recovered from the first fluid.

[0075] As conversion of the at least one reactant is carried out in one of the fluids, and since at least one of the fluids is selected such that a reaction product obtained by the conversion of the at least one reactant shows a higher affinity for another one of the fluids, simultaneous conversion of the at least one reactant and recovery of the reaction product may take place. This is of particular importance where the reaction product acts as an inhibitor of the reaction, as continuous removal of the reaction product may be carried out, which will drive the equilibrium of the reaction towards the reaction product. Similarly, this may be of particular importance where a co-product or side product of the reaction acts as an inhibitor of the reaction, and continuous removal of the coproduct or side product may be carried out. An example hereof is the conversion of a fatty acid and an alcohol to an ester, wherein water produced as a byproduct acts as an inhibitor for the esterification reaction and water removal may shift the thermodynamic equilibrium towards desired end product.

[0076] As can be understood from the above, the confinement 20 is suitable for carrying out a wide variety of reactions or separations, for example biological or chemical reactions, or physical or chemical trapping.

[0077] The device of the present invention is particularly suitable for use with heterogeneous processes in chemistry and biotechnology wherein a solid member contacts a fluidic medium which contains reactants or other agents, sample solutes, and/or reaction products resulting from the interactive processing of the agents contained in the fluidic medium with the solid member(s). The convective flow provided by the device of this invention ensures the mass transfer between the first and second fluid, necessary to accomplish the reaction.

[0078] A method of this invention comprises the steps of feeding a mixture comprising one or more reactants to a vessel 10 with a vessel inner volume 11 and a confinement 20 submerged in the vessel inner volume 11, the confinement 20 providing a confinement inner 21 volume as described above, with a bottom 27 and a peripheral wall 28 which are liquid impermeable and with an upper face 26 which is at least partly open so that the confinement inner volume 21 is in fluid connection with the vessel inner volume 11. The vessel inner volume 11 contains a first fluid 1 with a first density p1, and a second fluid with a second density p2, wherein p1 > p2 and the first and second fluid 1, 2 are at most partly miscible but are preferably so that the first fluid 1 forms a lower phase and the second fluid 2 forms an upper phase in the vessel inner volume 11. The confinement inner volume 21 is partly filled with the second fluid 2 which is in fluid connection with the second fluid 2 in the vessel inner volume 11. The confinement further contains a third fluid 3 with a third density p3, wherein p3 > p2 so that the second fluid forms an upper layer and the third fluid forms a lower layer in the confinement inner volume 21. The second and third fluid 2, 3 are at most partly miscible but are preferably immiscible.

[0079] In a first preferred embodiment of this method where isolation of one or more compounds from a complex mixture containing several dissolved compounds is envisaged, the first and second fluid 1, 2 and the third fluid 3 are selected such that a first compound 5 to be recovered has an affinity for the second fluid 2 which is lower than an affinity for the first fluid 1, whereas the affinity of the remainder of the complex solution for the third fluid 3 is higher than for the second fluid 2. After the complex solution has been supplied to the second fluid 2, and motion has been imparted to the content of the vessel, compound 5 will tend to move into fluid 1 from which it can be recovered. If needed or desired, fluid 1 may comprise a compatibilizer for improving the compatibility of the compound and the first fluid. Because of the affinity differences, the method of this invention permits isolating one or more compounds from a complex mixture while simultaneously limiting the risk to entraining of other compounds and/or solvent from the complex mixture.

[0080] In an alternative to this first preferred embodiment, the first and second fluid and the third fluid are selected such that the compound 5 has an affinity for the second fluid 2 which is lower than an affinity for the third fluid 3, and the remainder of the mixture has a higher affinity for the first fluid. After having been supplied to the second fluid, and having imparted motion to the content of the vessel, compound 5 will tend to diffuse into third fluid 3 from which it can be recovered. If needed or desired, third fluid 3 may comprise a compatibilizer for improving the compatibility of the compound and third fluid 3.

[0081] According to a still further alternative, a first compound 5 to be recovered has an affinity for the second fluid 2 which is lower than an affinity for the first fluid 1, a second compound may have an affinity for the third fluid 3 which is higher than for the second fluid 2 and the first fluid 1 whereas the affinity of the remainder of the complex solution for the second fluid 2 is higher than for the first and third fluid. This will permit separation of a first and second compound from the complex mixture, thereby limiting the risk to entraining of further compounds from the mixture.

[0082] It shall be clear that many permutations of the above are possible.

[0083] In a second embodiment where conversion of a compound 5 contained in the mixture is envisaged, for example conversion of a reactant into one or more reaction products, the second fluid 2 and third fluid 3 may be selected such that compound 5 has an affinity for the second fluid 2 which is lower than an affinity for the third fluid 3. Third fluid 3 comprises a fourth phase 4, for example a catalyst or an enzyme or similar, for catalyzing the conversion of compound 5 into one or more desired reaction products. After having been supplied to the second fluid, and having imparted motion to the content of the vessel, compound 5 will tend to diffuse into third fluid 3, where it contacts the catalyst or enzyme and is converted into a desired reaction product. Third fluid 3 will in this case be selected such that the affinity of the one or more reaction products for third fluid 3 is lower than that for second fluid 2, which in turn will be lower than the affinity for fluid 1. Motion imparted to the system, will support mass transfer from the third fluid, through the second fluid and towards the first fluid. The one or more reaction products may then be recovered from first fluid 1. In order to control reaction product affinity, first fluid 1 may contain a compatibilizer, or a compatibilizer may be supplied to first fluid 1.

[0084] According to an alternative embodiment, the third fluid contains the reactant 5 that is to be converted into a desired reaction product. Motion imparted to the content of the vessel 10, will support contact between reactant 5 and catalyst or biocatalyst 4, and cause the reaction product to diffuse into second fluid 2 after which it may then be recovered from first fluid1, because of a better compatibility with fluid 1. In order to control reaction product affinity, first fluid 1 may contain a compatibilizer, or a compatibilizer may be supplied to first fluid 1.

[0085] It shall be clear that many permutations of the above are possible.

[0086] Compatibilizers are generally known to the skilled person and may for example comprise a solvent with a certain polarity, hydrophilicity or a pH buffer.

[0087] The invention is further elucidated in the examples below.

Example 1 Extraction of 1-Methyl 3-Phenyl Propyl Chiral Amine (MPPA)

[0088] The apparatus of the present invention was applied to investigate the behavior of benzyl acetone (BA) and MPPA chiral amine in the three liquid phase system composed by O,O′-Bis(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol (PEG-C), n-heptane and citric acid buffer solution. The hydrophobic organic solvent heptane (683 kg/m3), which has a smaller density than both the aqueous citric acid and the PEG-C hydrophilic solutions, is immiscible and stays above the PEG and the citric acid buffer solutions. The experiment was conducted filling the inner tubular confinement (20), which is fixed to the agitator shaft with a solution of PEG-C. The volume of the PEG solution (third solution) amounted to 28 mL. The bottom of the vessel was first filled with 220 mL of acidic buffer (first solution) and then with 920 mL of heptane (containing 5 g of BA and 5 g of MPPA). The heptane solution was therefore in fluid contact with both PEG and citric acid buffer solutions but the miscible latter mentioned phases were physically separated by the inner tubular confinement (20).During the extraction, the content of BA and MPPA and PEG were analyzed and determined in both heptane and buffer phases. As shown in FIG. 3, MPPA progressively accumulated into the buffer extracting phase. After 5 hours of operation, the buffer resulted enriched with an MPPA extraction rate of 71% while the content of PEG was very low (9.7%). BA was not detected in the acid buffer phase. The heptane middle phases resulted BA enriched (20%) (FIG. 3). The remaining BA was found in the PEG solution, in the inner tubular confinement volume.

Example 2 Transamination Reaction for Chiral Amine Synthesis With Simultaneous in Situ Product Recovery (ISPR).

[0089] The apparatus of the present invention can be applied to perform the synthesis and ISPR of MPPA chiral amine (one step process) in the three liquid phase system composed by PEG-C, n-heptane and citric acid buffer solution. The hydrophobic organic solvent heptane (683 kg/m3), which has a smaller density than both the aqueous citric acid and the PEG-C hydrophilic solutions, is immiscible and stays above the PEG and the citric acid buffer solutions. The enzymatic takes place in the confinement inner volume. Here the enzyme, placed at the bottom, is surrounded by PEG C (polyethylene glycol high molecular weight amine donor). Being heavier and insoluble in heptane, PEG-C would preferentially form a layer on the top of the enzyme thus restricting the enzyme to the bottom of the inner tubular cylinder of the spinning reactor. Enzyme is therefore covered and ‘protected’ by the PEG layer. The ketone substrate BA (originally dissolved in n-heptane) binds or diffuses from heptane into the PEG C layer. The enzymatic reaction either occurs at the PEG C layer or at the enzyme- PEG C interphase. As soon as the product amine MPPA is formed, it is extracted into the citric acid buffer (aqueous solution) via travelling through n-heptane due to partitioning. In 17 days, 0.8 g of MPPA was formed, extracted and therefore isolated into the citric acid buffer (FIG. 4). This corresponds to a MPPA product yield value of 15% (FIG. 5). A very low amount of unreacted BA substrate was co-extracted in the citric acid buffer during the entire test (FIG. 4 and FIG. 5).

Example 3 Extraction of Boric Acid Derivatives From Suzuki Reaction

[0090] In another example, related to a transition metal catalyzed reaction, the first fluid comprises an aqueous phase, the third fluid comprises a low polarity solvent, e.g. ethyl acetate, that captures the catalyst and the second fluid comprises a conventional solvent e.g. n-heptane for the product/reagents. Because the solubility of reagents/products is likely to be low in a low polarity solvent such as ethyl acetate, then concentration of reagents/products will be low in this phase so maybe it could be used for macro-cyclisations even perhaps semi continuous.

[0091] In such reaction, the chemical catalyst will be positioned inside the confinement and be covered by PEG. The idea is that the catalyst has ligands so that it forms hydrogen with the PEG layer. Above PEG layer there will be the non-PEG miscible solvent (not n-heptane but another) and the extraction layer at the bottom is aqueous (first fluid). This type of set-up can be used to extract boric acid derivatives from Suzuki reaction .

Example 4 Synthesis and Separation of Both (R)- and (S)- Amine or Alcohol Enantiomers

[0092] The use of our device would allow to combine enzymatic kinetic resolution reactions with the subsequent de-acylation and separation steps required for the synthesis and separation of (R)- and (S)- amine and alcohol enantiomers. Depending upon the affinity of the substrates, the enzymatic kinetic resolution of one enantiomer could occur in the first fluid or in the third fluid. Assuming that the reaction occurs in the first fluid, also called source phase, such fluid could be water or an organic solvent such as methanol or toluene. A lipase could be used as biocatalyst. Being in fluid contact with the second fluid, and being more hydrophobic than the unreacted enantiomer, the formed chiral ester would preferentially migrate from the source phase (which can be either the fluid one or the fluid three) to the hydrophobic second fluid. Heptane could be selected as second fluid. The contact of the second fluid with the receiving phase, which is an aqueous acidic solution, would further enhance the recovery and enrichment of the reacted enantiomer in the receiving phase while the acylating agent would partition into the second fluid.