WO1994010557A1

WO1994010557A1 - Membrane manufacturing method

Info

Publication number: WO1994010557A1
Application number: PCT/US1993/010618
Authority: WO
Inventors: Iqbal Husain; Patrick Ranft; David Nichols; Neil Plotkin
Original assignee: Porton Diagnostics, Inc.
Priority date: 1992-11-05
Filing date: 1993-11-05
Publication date: 1994-05-11
Also published as: AU5458094A

Abstract

A method for forming a membrane comprising the steps of suspending a droplet of membrane solution inside the walls of an aperture formed in a body, and then drying the suspended droplet.

Description

Membrane Manufacturing Method

FIELD OF THE INVENTION:

The present invention relates to a method for manufacturing ion selective 5 membranes.

BACKGROUND:

Ion sensitive electrodes are generally utilized in the medical field to detect ion levels in fluids. Typically, these electrodes detect ion levels by measuring the electrical potential 10 (EMF - electromotive force) generated across a membrane separating two solutions with different concentrations of ions. This type of membrane is generally referred to as an ion selective electrode membrane.

When placed in contact with a solution, ion selective electrodes provide an electrical output which is a function of the concentration of a particular ion in the solution. In 15 general, an output potential is measured between a sensing electrode responsive to the concentration of the particular ion and a reference electrode held at a constant potential. Ion selective electrodes obey the Nernst Equation:

where, E = the sensing electrode potential 20 Eo = the reference electrode potential

R = the gas constant T = the absolute temperature n = the valence of the ion f F= Faraday's constant, and i 25 a; = the ion activity in the solution.

Any change in the activity of the measured species in solution causes a change in the measured potential which can be related to the concentration of the unknown specimen by proper calibration. Ion-selective electrodes are generally available for anions, e.g. F-, C1-, Br-, etc. and for cations, e.g. H+, Na+, K+ etc. They are also available from certain divalent ions, for example Ca++.

Ion selective electrode membranes, and their use in analysis equipment, are generally described in the commonly assigned U.S. patent applications serial numbers 07/763,696 and 07/750,534, the disclosure of each being hereby incorporated by reference. Ion selective electrode membranes and their use are also described in U.S. Patent No. 5,098,545, the disclosure of which is also incorporated by reference.

Ion selective electrodes include liquid membrane electrodes which are generally the subject of the present application. Liquid membranes for use in ion selective electrodes have been solvent-cast in a variety of configurations. Typically, the membrane constituents are dissolved in a volatile solvent such as tetrahydrofuran (THF) and then spread upon a surface and allowed to dry. This process yields a thin membrane with a conformation determined by the shape of the surface. Generally, a surface formed as a cup or a flat plate is utilized.

The membrane may be bound to a non-conductive casing material such that the peripheral edge of the membrane forms a solvent bond with the casing. For example, membranes may be formed in the side of plastic tubes, glass tubes or plastic-coated metal tubes. Alternatively, the surface on which the membrane is formed may be electroactive, for example the gate of a field effect transistor, a glassy carbon electrode, or a conductive wire. In the cases of a glassy carbon electrode surface, or a conductive wire surface, the membrane may be utilized without being separated from the surface. In the case of a field effect transistor the membrane is separated from the surface and cut into a desired shape before use. Ion selective electrode membranes formed by the techniques generally described herein as typical of the prior art are disclosed in U.S. Patent Nos. 4,600,495 to Fogt, 5,013,421 to Rao et al. and 4,314,895 to Spaziani et al.

A problem with the prior art techniques for forming ion selective electrode membranes occurs when large numbers of inexpensive ion selective electrodes are to be manufactured in a configuration wherein the membrane must be free to contact an aqueous electrolyte on both of its surfaces. In these circumstances, prior art techniques requiring the use of a pre-fσrming surface to solvent cast the membrane may only be utilized if the surface can be left in place as part of the device utilizing the membrane, or if the surface is removed after membrane drying. If the pre-forming surface is to be left in place, the surface must either be porous to the electrolyte utilized in the device and electro-inert, or must be manufactured from an electro-conductive material. If the pre-forming surface is porous and electro-inert, the pores can allow the membrane solution to penetrate the porous material to form a thick layer within the porous material. If the pre-forming surface is manufactured from an electro-conductive material, junction potentials will occur between the membrane and the material. In either case membrane performance will be degraded. The prior art technique wherein the pre-forming surface is removed also presents problems during manufacture of the ion selective electrode. If the pre-forming surface is to be removed, the surface must be provided either as a part of a disposable component, to be discarded after the manufacture of a single membrane, or as part of a re-usable manufacturing tool. The former situation, wherein the surface is part of a disposable component, disadvantageously increases manufacturing costs due to the need to manufacture and replace the disposable component. The latter situation, wherein the surface is part of a re-usable tool, disadvantageously increases manufacturing costs due to the need to clean the tool after the formation of each electrode.

The use of a pre-forming surface may also be disadvantageous due to the membrane taking on the features of the surface, including any machining imperfections or surface irregularities. The membrane may also pick up any debris from the surface. A further disadvantage is that in the case where the membrane is to be formed with a peripheral solvent bond to a non-conductive casing, mechanical limitations may constrain the application of a shear force by relative movement of the membrane and the forming surface. This may lead to membrane damage if the forming surface is moved away from the membrane in a perpendicular direction.

We have developed a method for forming membranes for use in ion-selective electrodes that overcomes the disadvantages associated with prior art techniques.

SUMMARY OF THE INVENTION: According to the method of the present invention, a droplet of membrane solution is suspended inside the walls of an aperture in a body and dried in-situ without direct mechanical support. Surface tension forces hold the drop in a symmetrical shape that changes as the drop dries. Provided that the diameter of the aperture, the volume of the membrane solution and the solids content of the membrane solution are properly controlled and matched, the drying droplet will continue to span the aperture until all solvent in the membrane solution has evaporated, leaving a thin membrane across the aperture. The present invention is applicable to the formation of all types of thin polymer membranes across apertures in components wherein both the polymer and the material of the component are at least partially soluble in a given solvent The process of the present invention overcomes the aforementioned disadvantages of prior art processes and advantageously allows the high-speed manufacture of large numbers of inexpensive ion selective membranes, minimizing use of additional disposable tools or tool re-cleaning operations. The process of the present invention is also advantageously amenable to automation by automating the fluid delivery tool.

A further advantage of the process of the present invention is that a good seal is formed between the membrane and the casing. A still further advantage of the process of the present invention is that the membrane is smooth and symmetrical since it has not been in contact with any surfaces except along its periphery.

BRIEF DESCRIPTION OF THE DRAWINGS: FIG. 1 is a cross-sectional view of a portion of a body suitable for use in the method of the present invention.

DETAILED DESCRIPTION OF THE INVENTION:

The method of the present invention comprises the steps of suspending a droplet of membrane solution within the walls of an aperture formed in a body, and then drying the suspended droplet. Figure 1 depicts a portion of an apparatus suitable for use in the method of the present invention.

With reference to Figure 1 , in an embodiment of the method of the present invention, a membrane is formed by dispensing a droplet of membrane solution, 6, into an aperture, 2, of a suitable body, 4, to suspend the droplet in the aperture. The aperture has the cross sectional shape desired in the final membrane. Suitable cross sectional shapes include, but are not limited to, circular and polygonal, for example hexagonal or octagonal.

Preferably the aperture is a cylindrical hole thereby having a circular cross sectional shape.

The aperture depicted in Figure 1 is such a cylindrical hole and has a diameter, D and length, L. Membranes may be formed in any suitable body such as plastic bodies, glass tubes, or plastic-coated metal tubes.

The membrane solution may be dispensed into the aperture using a variety of fluid delivery tools known in the art, for example through a hypodermic needle or through a pipette. The volume of the droplet of membrane solution will depend on the diameter of the aperture, however the volume of the droplet should be sufficient to contact the walls of the aperture and allow the droplet to become suspended in the cavity.

The volatile solvent of the membrane solution is allowed to evaporate at ambient temperatures for several minutes, or evaporated by heat or vacuum drying, at which time the membrane has assumed a stable and uniform double concave shape completely spanning the cross sectional area of the aperture. The membrane thus formed, 10, has a greater thickness at the interface, 8, of the membrane and the body and tapers in a radially inward direction towards the center of the aperture, 2 forming a thin film with uniform double concave surfaces, 12.

The thickness of the membrane at its thinnest point is shown as T. Preferably the membrane is as thin as possible while remaining sufficiently strong to span, and assume a self supporting double concave shape in, the aperture. The membrane solution is comprised of a volatile solvent, any suitable organic plastic matrix material that is at least partially soluble in the solvent, an ion exchange material, and a non-volatile plasticizer that is a solvent for the ion exchange material. The ion exchange material can be any of the suitable ion exchange material already known in the art such as valinomycin, monensin, crown ethers, etc. The suitable solvents include, but are not limited to, volatile solvents selected from the group consisting of tetrahydrofuran (THF), methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), acetone, toluene and benzene. A suitable plastic matrix material is ion selective electrode (ISE) grade PVC. Other suitable plastic matrix materials include polyurethane and silicone rubber. Suitable . plasticizers include, but are not limited to, bis (1 butylpentyl) decane-1, 10 diyl diglutarate, dioctyl adipate, diocytl sebacate, and 2-nitro-p-cymene. Generally, the membrane solution has a solids content ranging from 10-20% (w/w) (percent, weight for weight), and a viscosity ranging from 5-25 cps (centipoise). The size of the droplet generally ranges from 5-30 μl (microliters, liters x 10⁶). As will be recognized by those of ordinary skill in the art the relationship between the size (volume) of the droplet and the viscosity of the membrane solution will affect the ability of the droplet to span the aperture and form the membrane. Accordingly, when the size (volume) of the drop is towards the small end of the specified range, the viscosity of the membrane solution must be correspondingly larger in order for the membrane to be able to span the aperture. Conversely, when the size of the drop is high, the viscosity of the membrane should not be so high that the drop is not self supporting in the aperture.

In a preferred embodiment of the present invention, the membrane solution comprises: 8% by weight Dioctyl Adipate, 7%, by weight ISE Grade PVC; 1%, by weight Valinomycin and 84%, by weight, Tetrahydrofuran (THF) and has a total solids content of 16 % (w/w) and a Brookfield Viscosity (25°C) of 18 cps. In an alternate preferred embodiment of the present invention, the membrane solution comprises: 12.68% by weight, Bis (1 -butylpentyl) decane-1, 10-diyl diglutarate (ETH 469); 4.90%, by weight ISE Grade PVC; 0.55%, by weight Valinomycin, 0.09%, by weight Potassium Tetrakis (4-chlorophenyl) borate and 81.78%, by weight, Tetrahydrofuran (THF) and has a total solids content of 18.2% (w/w) and a Brookfield Viscosity (25°C) of 29.5 cps.

The body can be any suitable non-reactive material that is at least partially soluble in the solvent of the membrane solution, such as rigid polyvinylchloride (PVC), thermoplastic resins made from acrylonitrile, butadiene, and styrene (ABS copolymers), styrene, polycarbonates, acrylic, glass tubes or plastic-coated metal tubes. The diameter of the aperture in the body varies depending on the desired diameter of the membrane being produced. The height of the aperture cavity is sufficient to contain the entire volume of the membrane solution. Preferably, in the case where the aperture is a cylindrical hole, the diameter of the cylindrical hole ranges from 1.5 mm to 2.0 mm, and the height of the cylindrical hole ranges from 0.8 mm to 2.5 mm.

The membrane formed by the process of the present invention may be readily incorporated into sensors or other instruments by incorporating the body into the instrument Preferably, the body utilized in the method of the present invention has dimensions advantageously suited for incorporation of the membrane containing body into the instrument that will utilize the membrane.

The process of the present invention will be further illustrated by the following examples.

EXAMPLE 1

This example illustrates the formation of a membrane selective for potassium ions according to the method of the present invention. The membrane formulation utilized was as follows: Membrane Formulation

Dioctyl Adipate 8 % (w/w)

ISE Grade PVC 7 % (w/w)

Valinomycin 1 % (w/w)

Tetrahydrofuran (THF) £4 % (w/w) 100 % (w/w)

Total Solids: 16 % (w/w) Brookfield Viscosity (25°C): 18 cps The membrane was formed in a cylindrical hole in a plastic body having the following properties:

Cylindrical Hole Properties

Material: Rigid PVC (BF Goodrich, Geon Vinyl Div.) Diameter: 2.0 mm (D, in Figure 1) Length: 2.3 mm (L, in Figure 1) In order to form the membrane, a 7 μl aliquot of membrane solution was dispensed into the above cylindrical hole through a 48 gauge needle. The THF solvent was allowed to evaporate for 5 minutes at ambient conditions at which time the membrane had assumed a stable and uniform double concave shape completely spanning the cross-sectional area of the hole.

Microscopic analysis indicated that the membrane was radially symmetrical and was approximately 178 μm thick (T in Figure 1) near the center and approximately twice as thick near the wall. The membrane exhibited a nernstian slope, response time, and electrical resistance comparable to those prepared by methods described in the prior art

EXAMPLE 2

This example illustrates the effects of using too small a volume of a membrane solution having too low a viscosity. The procedure in Example 1 was repeated using a 5 μl aliquot sample of the membrane solution. The volume viscosity ratio of the membrane solution was insufficient to enable the membrane to completely span the cross-sectional area of the hole.

EXAMPLE 3 This example illustrates the effects of using too large a volume of a membrane solution. The procedure of Example 1 was repeated using a 20 μl aliquot sample of the membrane solution. The volume/viscosity ratio of the membrane solution was too great to enable the droplet to remain suspended in the whole. In effect the droplet weighed too much. As a result the droplet passed down the length of the cylindrical hole without forming a membrane spanning the cross section of the hole. Since no occlusive, uniformly ■ shaped membrane was created, this construction could not be used in an ion selective electrode.

Claims

WHAT IS CLAIMED:

1. A method for forming a membrane comprising the steps of: suspending a droplet of a membrane solution inside the walls of an aperture formed in a body, and drying the suspended droplet.

2. The method of claim 1 in which said body is a plastic body.

3. The method of claim 1 in which said body is a glass tube.

4. The method of claim 1 in which said body is a plastic-coated metal tube.

5. The method of claim 1 in which said suspended droplet is evaporated at ambient temperature.

6. The method of claim 1 in which said suspended droplet is evaporated by heating said membrane with hot air.

7. The method of claim 1 in which said suspended droplet is evaporated by vacuum drying said membrane.

8. The method of claim 1 in which said aperture is a cylindrical hole.

9. The method of claim 8 in which the said cylindrical hole has a diameter ranging from 1.5mm to 2.0mm.

10. The method of claim 8 in which the said cylindrical hole has a length ranging from 0.8mm to 2.5mm.

11. The method of claim 1 in which the said droplet ranges in size from 5-30μl.

12. The method of claim 1 in which said membrane solution is comprised of an organic plastic matrix material, a volatile solvent a non- volatile plasticizer and an ion exchange material being soluble in said plasticizer, and in which said body is partially soluble in said volatile solvent.

13. The method of claim 12 in which said plastic matrix material is selected from the group consisting of ion selective electrode (ISE) grade PVC, polyurethane and silicone rubber.

14. The method of claim 12 in which said volatile solvent is selected from the group consisting of tetrahydrofuran (THF), methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), acetone, toluene and benzene.

15. The method of claim 12 in which said plasticizer is selected from the group consisting of dioctyl adipate, diocytl sebacate, Bis (1-butylpentyl) decane-1, 10-diyl diglutarate and 2-nitro-p-cymene.

16. The method of claim 12 in which said ion exchange material is selected from the group consisting of valinomycin, monensin, and crown ethers.

17. The method of claim 12 specifically adapted for the analysis of potassium ions in which said matrix material is polyvinylchloride, said ion exchange material is valinomycin and said plasticizer is dioctyl adipate.

18. The method of claim 12 in which said membrane solution is prepared from a mixture comprising 8% by weight dioctyl adipate, 7% by weight polyvinylchloride, 1% by weight valinomycin, and 84% by weight tetrahydrofuran.