GB2207064A

GB2207064A - Silicone membrane extraction

Info

Publication number: GB2207064A
Application number: GB08815590A
Authority: GB
Inventors: Francis Gregory Pius Mullins
Original assignee: Individual
Current assignee: Individual
Priority date: 1987-07-09
Filing date: 1988-06-30
Publication date: 1989-01-25
Anticipated expiration: 2008-06-30
Also published as: GB2207064B; GB8716140D0; GB8815590D0

Abstract

Selected species of organic molecule, e.g. phenol, amines, pharmacologically active substances, can be extracted from aqueous solution across a non-porous silicone rubber membrane (10), e.g. 1 to 300 mm thick. A test solution (from which the molecule is to be extracted) is treated with a substance which acts to lower the solubility of the selected species therein and is brought into contact with one side of the membrane (e.g. chamber 16), while a receptor solution is brought into contact with the other side of the membrane (e.g. chamber 18). The substance for treating the test solution may, for example, be acid or alkaline, to create a pH differential, or a salt or detergent to create an ionic strength differential. <IMAGE>

Description

SILICONE MEMBRANE EXTRACTION This invention relates to a method of and apparatus for extracting selected organic molecules from aqueous solution. At present it is envisaged that the invention will have two main spheres of usage, namely in analysis of water supplies and in extraction of pharmacologically active molecules from body fluids, such as whole blood, plasma, saliva, urine.

In the first aforesaid technical field public water supplies are continuousely monitored to ascertain levels of contaminating substances, such as phenol, whose presence, even at extremely low concentration, taints the water and gives rise to customer complaints of distastefulness. One of the most technically advanced monitoring method known hitherto involves computerised high pressure liquid chromatography as well as preliminary concentration of phenol on a "precolumn".

In addition to the equipment being expensive, cumbersome and complex, thewmaterial in the extraction columns has to be periodically replaced when it becomes too contaminated, and the sensitivity of the results is often impaired because in the resultant chromatographs (obtained by uv adsorption) the adsorption peak for phenol is extremely small compared to the closely adjacent peak. Another, even more recently developed method of monitoring water contaminants, such as phenol and pyridine, by optical absorbence using uv spectrophotometers and computer processing of the resultant data also suffers from lack of sensitivity at low concentrations.

In the second aforesaid technical field, an improved method of extraction of pharmacologically active compounds from body fluids, where they are present in extremely low concentrations, is sought.

This is important, for example, in enabling monitoring of levels of a therapeutic agent in blood or other body fluids.

It is an object of the present invention to provide a method of extracting selected organic molecules, such as phenol or amines or pharmacologically active molecules, from aqueous solution which is simpler, less expensive and yet more sensitive than hitherto known methods.

With this object in view, the invention proposes use of a non-porous silicone rubber membrane in an extraction cell.

More specifically the invention proposes a method of extracting a selected species of organic molecule from a solution comprising treating a test solution from which the molecule is to be extracted with a substance which acts to lower the solubility of the selected species therein, bringing the test solution into contact with one surface of a non-porous silicone rubber membrane and bringing a receptor solution into contact with the opposing surface of the membrane so that organic molecules of the selected species pass through the member from the test solution to the receptor solution.

The term "non-porous" is used herein to indicate that the relevant organic molecules being extracted or separated from the test solution do not pass through openings in the molecular structure of the membrane (which would enable all molecules below a certain size to pass therethrough by diffusion) but rather dissolve in the material of the membrane and move thereacross by diffusion.

In cases where the selcted species is an ionisable species the treatment of the test solution will serve to establish a pH difference between the test solution and the receptor solution. The selected molecules will then dissolve in the membrane and move thereacross under the influence of the pH gradient. However, in other cases, it may be some other differential, such as a difference in ionic strength between the test and receptor solutions, which causes the selected species to pass through the membrane.

When the method is applied to extraction of phenol from water the test solution should be acidified so as to have a pH less than 6 and preferably about 1.5, whilst the receptor solution should be made alkaline so as to have a pH greater than 8, preferably about 13.

When the method is applied to extraction of amines from water the pH gradient is reversed in that the test solution is alkaline and the receptor solution acidified. For pharmacologically active molecules which are ionisable the pH is chosen to suit the relevant species. In all such casts the receptor solution should be pH adjusted to act as an infinite sink for the relevant molecular species.

As mentioned, for species of organic molecules which are not ionisable, e.g. steroids, a pH gradient is not effective. Instead, a difference in ionic strength, provided for example, by addition of a salt, such as sodium chloride, can be used to drive the molecule into and across the membrane.

In the analysis of water supplies both the test and receptor solutions will advantageously be caused to flow continuously over the perspective membrane surfaces. In contrast, in the analysis of body fluids the receptor solution will preferably be static while the test solution is supplied in pulsed doses.

Incidentally, the terms test and receptor "solution" are used herein to mean any solvent or combination of solvents, with or without impurities or solutes therein. The receptor solution will usually be water, but could be methanol or any other suitable solvent system.

A further aspect of the present invention comprises an extraction cell suitable for carrying out the aforesaid method and consisting of a non-porous silicone rubber membrane retained within a casing such that respective chambers, for reception of the test and receptor solutions, overlie opposing surfaces of the membrane.

Preferably each chamber has a separate inflow and outflow duct to enable the respective solution to flow across the membrane.

The silicone rubber membrane material used for phenol extraction is conveniently- commercially available dimethylpolysiloxane. The preferred thickness thereof is in the range from 1 to 300}ism, more specifically5 pm to 50 pm. The receptor solution will usually be water, but could be methanol or any other suitable solvent solution the polarity pH of which is controllable.

It will be appreciated that by use of the method/cell of the invention it is possible in most cases to obtain an enhanced concentration of the relevant molecule. Whilst this is usually favourable in facilitating measurement it is not an essential result of the invention.

A further aspect of the invention is apparatus for measuring the concentration of a selected species of organic molecule in a solution comprising an extraction cell consisting of a non-porous silicone rubber membrane retained within a casing such that chambers, for reception, respectively, of a test solution from which the relevant molecule is to be extracted and a receptor solution, overlie opposing surfaces of the membrane, means for adding to the test solution an appropriate quality of a substance which acts to lower the solubility of the selected species therein, means for supplying the test and receptor solutions to the respective chambers and subsequently withdrawing same therefrom, and a measuring unit for determining the level of the relevant molecule in the receptor solution after it has been withdrawn from the cell.

The invention will be described further, by way of example, with reference to the accompanying drawings in which: Fig. 1 is a plan view of a silicone membrane extraction cell in accordance with the second aspect of the invention; Fig. 2 is a cross-section of the cell shown in Fig.

1; Fig. 3 is an enlarged fragmentary cross-section of the encircled part indicated in Fig. 2; and Figs. 4 and 5 are chromatograms obtained, respectively, by direct screening of river water spiked with phenol, and following extraction of same in accordance with the present invention and screening of the receptor solution under similar conditions.

As illustrated in Figs. 1 to 3, a practical example of an extraction cell in accordance with the second aspect of the invention comprises a non-porous silicone rubber membrane 10 clamped between two rectangular perspex blocks 12, 14 of substantially equal size. In this particular example the blocks 12, 14 are each about 150mm long, 50mm wide, and llmm thick. Centrally, on their mutually facing surfaces the blocks 12, 14 are formed with respective elongate shallow depressions 16, 18 which have rounded ends. These depressions 16, 18 are each about 90mm long, lOmm wide and 0.5mm in depth.

Leading into opposing ends of each depression 16, 18, each block 12, 14 has a respective inflow and outflow duct 20, 22; 24, 26. These ducts are all in the form of through-bores, the internal diameters of which decrease in successive steps from the surfaces of the blocks 12, 14 remote from the respective depressions 16, 18, to a duct region 25 of about 1.5mm diameter immediately adjoining the depressions 16, 18 (see Fig. 3).

Outwardly of the respective depressions 16, 18 each block 12,14 has an array of ten holes 27, 29 each of which is widened to provide circular recesses 28, 30 in the surface of the block 12, 14 remote from the respective depressions 16, 18. As shown in Fig. 1, there are two aligned rows of four holes 27, 29, each with a recess 28, 30 adjacent the opposing longitudinal sides of each block 12, 14, and one hole 27, 29, each with a recess 28, 30, at each end, all the holes 27, 29 being substantially equidistantly spaced from the next adjacent hole in the closed loop array.

The silicone rubber membrane 10 is commercially available dimethylpolysiloxane of a thickness of about 25 pm. It is generally of the same shape as the depressions 16, 18 in the blocks 12, 14, but somewhat larger so that in the assembled cell it overlies these depressions 16, 18 with a margin outwardly thereof of about lOmm in width all around. As indicated in Fig. 1, the outer edge of the membrane 10 is approximately in line with the centre of the respective holes 27, 29.

The blocks 12, 14 are secured to each other, with the membrane 10 held firmly therebetween, by bolts 32, which have their heads countersunk in the recesses 28, and respective nuts 34 accommodated in the corresponding recesses 30, washers 36 being provided in the base of each recess 28, 30 as indicated in Fig. 2.

The depressions 16, 18 in the facing surfaces of the blocks 12, 14 are completely separated by the membrane 10 and thus provide flow chambers at opposing sides of the mebrane 10. The respective inflow ducts 20, 22 and the respective outflow ducts 24, 26 of the two blocks 12, 14 are substantially in alignment.

When this cell is used for extraction of phenol a test solution is caused to flow through one of the chambers 16 or 18, and thus across one of the surfaces of the membrane 10, whilst a receptor solution is caused to flow in the same direction through the other chamber, 18 or 16 respectively, i.e. across the opposing surface of the membrane 10, as indicated by the arrows in Fig.

2. In this respect, a relatively large volume, such as 1 litre of test solution may be pumped through one chamber while a much smaller volume, such as 200 u9, of receptor solution is pumped through the other chamber so that the phenol is concentrated at the same time as being extracted. Alternatively, the receptor solution, which may be as little as 40 pull, for example, may be static in contact with its side of the membrane while the test solution flows over the opposing surface.

Various experiments have been carried out to check the effectiveness of the above-described cell in extraction of phenol from aqueous solution.

In this respect, Fig. 4 represents a chromatogram obtained by uv adsorption at > 270nm following direct injection of a river water sample spiked with 100 ppb (100 ugL-1) phenol into an analytical liquid chromatography column. This shows a large "solvent front" peak, with the phenol eluting as a partially separated peak.

Fig. 5 represents a chromatogram obtained under the same conditions, but with the sample having been passed through the above-described extraction cell and the receptor solution injected into the analytical column.

In this respect, the sample was acidified to pH 1.5, approximately to 0.1M hydrochloric acid, and the receptor solution was made basic to pH 13, approximately to 0.1M sodium hydoxide for passage through the cell. In this case, the resulting phenol peak is much larger and more clearly defined and the disturbance from the solvent front is negligible.

When used in the field to analyse test samples, the level of phenol in the original sample should, of course, be determinable by appropriate calibration.

In view of the effective phenol enrichment of the sample and the diminution of interference with the measurement of other substances, such as the solvent itself, when the method of the invention was put into practice as outlined above, an extraction cell in accordance with the invention could be used, without the need for an analytical column, to directly supply a detector, such as a uv spectrophotometer, photodiode array detector or mass spectrometer, in an automated procedure for sampling water for detecting trace substances, notably phenol The obvious advantage of this would be the much lower cost and the simplicity of the proposed method and extraction-cell compared to the known procedure and equipment.

The extraction cell of the invention is not limited to the particulars of the above-described example. It may be formed in a different manner and the dimensions, casing material and securing means used may all vary.

Also, in addition to suitable selection of pH values for the test and receptor solutions, the dimensions of the flow chambers and the flow rates used for the test and receptor solutions can be varied to optimise the partitioning behaviour of the molecular species of interest. In this respect, when the method and cell of the invention are applied to the extraction or separation of amines the pH gradient across the membrane is reversed with the test solution made alkaline and the receptor solution acidified. For other molecules, e.g.

chloronated hydrocarbons etc. suitable pH gradients can be selected.

For non-ionisable molecules (although these are unlikely to arise in the field of water analysis) a difference in ionic strength rather than pH can be established by treating the test solution with, for example, sodium chloride or a detergent.

It should also be noted that a test sample may be split into several portions, each portion then being passed through a respective extraction cell of a multicell arrangement. If the solutions applied to each cell are buffered so as to have different pka values, or different pH gradients across the membrane, a range of different molecular species can be extracted into the respective receptor solutions. For example, selective separation of several different phenols can be accomplished by such an arrangement.

Furthermore, the method of the invention is also of particular importance in another field, namely in extraction of pharmacologically active molecules from body fluids, since it can be adjusted as just mentioned to be highly selective for a particular molecular species. As such molecules are generally present in bodily fluids, such as blood, urine, or saliva, in extremely low concentrations, the concentration which is possible in conjunction with extraction by the method of the invention facilitates accurate measurement of drug levels. The sort of molecules which can be extracted in this way include steroids, barbiturates and opiates.

The cell used will obviously be much smaller than that described above, but the principles remain the same.

The test samples will also be much smaller and 1 ml samples may be successively injected into the chamber for the test solution by means of a peristaltic pump.

Similar qualities of receptor solution may be held in contact with the opposing surface of the membrane and then flushed through and into the detector instrument.

As previously mentioned, non-ionisable molecules like steroids will require a differential in ionic strength between test and receptor solutions to bring about effective positioning, as a pH differential will have no effect thereon.

Claims

1. A method of extracting a selected species of organic molecule from a solution comprising treating a test solution from which the molecule is to be extracted with a substance which acts to lower the solubility of the selected species therein, bringing the test solution into contact with one surface of a non-porous silicone rubber membrane and bringing a receptor solution into contact with the opposing surface of the membrane so that organic molecules of the selected species pass through the membrane from the test solution to the receptor solution.

2. A method as claimed in claim 1 wherein the test solution is treated in such a way as to establish a pH difference between the test solution and the receptor solution.

3. A method as claimed in claim 1 or 2 and applied to extraction of phenol from water wherein the pH of the test solution is less than 6 and the pH of the receptor solution is more than 8.

4. A method as claimed in claim 3 wherein the pH of the test solution is about 1.5 while the pH of the receptor solution is about 13.

5. A method as claimed in claim 1 wherein the test solution is treated in such a way as to establish a difference in ionic strength between the test solution and the receptor solution.

6. A method as claimed in any preceding claim wherein the test solution and/or the receptor solution are caused to flow across the respective surfaces of the membrane.

7. An extraction cell for carrying out the method as claimed in any of claims 1 to 6 and consisting of a nonporous silicone rubber membrane retained within a casing such that respective chambers, for reception of the test and receptor solutions, overlie opposing surfaces of the membrane.

8. An extraction cell as claimed in claim 7 wherein each chamber has a separate inflow and outflow duct.

9. An extraction cell as claimed in claim 7 or 8 wherein the membrane has a thickness of from lpm to 300 pm.

10. An extraction cell as claimed in claim 7, 8 or 9 wherein the membrane thickness is in the range from 5 to 50 )ism.

11. An extraction cell as claimed in any of claims 7 to 10 wherein the membrane material is dimethylpolysiloxane.

12. Apparatus for measuring the concentration of a selected species of organic molecule in a solution comprising an extraction cell consisting of a non-porous silicone rubber membrane retained within a casing such that chambers, for reception, respectively, of a test solution from which the relevant molecule is to be extracted and a receptor solution, overlie opposing surfaces of the membrane, means for adding to the test solutions an appropriate quantity of a substance which acts to lower the solubility of the selcted species therein, means for supplying the test and receptor solutions to the respective chambers and subsequently withdrawing same therefrom, and a measuring unit for determining the level of the relevant molecule in the receptor solution after it has been withdrawn from the cell.

13. Apparatus as claimed in claim 12 wherein the thickness of the membrane in the extraction cell is in the range 1 to 300 pm.

14. Apparatus as claimed in claim 12 or 13 wherein the means for supplying the test and receptor solutions to the respective chambers comprise respective inflow ducts and pumps.

15. Apparatus as claimed in claim 12, 13 or 14, wherein the measuring unit is connected to the chamber for the receptor solution so that receptor solution is supplied directly from the cell to the measuring unit.

16. Apparatus as claimed in any of claims 12 to 15 wherein the measuring unit is an ultra violet spectrophotometer, or an optical diode scanner, or a mass spectrometer.

17. A method of extracting a selected species of organic molecule from a solution substantially as hereinbefore described.

18. An extraction cell substantially as hereinbefore described and as illustrated in Figs. 1 to 3 of the accompanying drawings.

19. Apparatus for measuring the concentration of a selected species of organic molecule in a solution substantially as hereinbefore described with reference to the accompanying drawings.