Heparin-selective polymeric membrane electrode

• US 5,236,570 A
• Filed: 03/10/1992
• Issued: 08/17/1993
• Est. Priority Date: 03/10/1992
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: University of Michigan
• Inventors: Ma, Shu-Ching, Yang, Victor C., Meyerhoff, Mark E.
• Primary Examiner(s): Niebling, John
• Assistant Examiner(s): Bell, Bruce F.
• Application Number:
  US07/849,218
• Time in Patent Office: 525 Days
• Field of Search: 204/403, 204/415, 204/416, 204/418, 204/153.12, 435/817
• US Class Current: 204/403.06
• CPC Class Codes: G01N 27/3335 the membrane containing at least one organic component G01N27/3271 takes precedence; aspects concerning the enzyme reagent in enzyme electrodes C12Q1/001
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

An anion exchange membrane for ionic macromolecules, specifically heparin, which is formed of a polymeric matrix material, an anion exchange material suitable for heparin detection, and a plasticizer can be employed in an electrochemical sensor arrangement to directly measure the concentration of heparin ions in blood or blood fluid. Potentiometric response to heparin has been observed with membranes comprising 30-70 wt. % polymeric matrix material, such as polyvinyl chloride, 0.1-12 wt. % quaternary ammonium salt, such as tridodecyl methyl ammonium chloride, and 30-70 wt. % of a plasticizer, such as dioctyl sebacate.

Claims

1. An ion-selective electrode membrane comprising, in admixture, a polymeric matrix material, an anion exchange material, and a plasticizer, the electrode membrane admixture being selective to heparin.

2. The electrode membrane of claim 1 wherein the anion exchange material is selected from the group consisting of a quaternary ammonium salts, quaternary phosphonium salts, and quaternary arsonium salts.

3. The electrode membrane of claim 2 wherein the anion exchange material is a quaternary ammonium salt.

4. The electrode membrane of claim 3 wherein the quaternary ammonium salt is selected from the group consisting of triethyl phenyl ammonium iodide, tetrapentyl ammonium bromide, trimethyl phenyl ammonium, dimethyl dioctadecyl ammonium bromide, tetraoctylammonium bromide chloride, hexadecyl trimethyl ammonium bromide, tetraethyl ammonium perchlorate, tetramethyl ammonium bromide, tetrabutyl ammonium iodide, tridodecyl methyl ammonium chloride, polybrene, and trioctyl methyl ammonium chloride.

5. The electrode membrane of claim 4 wherein the quaternary ammonium salt is tridodecyl methyl ammonium chloride.

6. The electrode membrane of claim 1 wherein the polymeric matrix material is selected from the group consisting of polyvinyl, polyurethane, cellulose triacetate, and poly(vinyl alcohol)/poly(vinylchloride) copolymer.

7. The electrode membrane of claim 6 wherein the polymeric matrix material is polyvinylchloride.

8. The electrode membrane of claim 1 wherein the plasticizer is selected from the group consisting of dicapryl adipate, di-n-hexyl azelate, dipropylene glycol dibenzoate, tri-n-butyl citrate, 2-ethyl hexyl epoxytallate, di(2-ethylhexyl maleate)dioctyl maleate, tri-(n-octyl,n-decyl)trimallitate, methyl oleate, isopropyl palmitate, t-butyl phenyl diphenyl phosphate, butyl octyl phthalate, diisooctyl phthalate, glyceryl triacetyl ricinoleate, dibutyl sebacate, isopropyl isostearate, dioctyl sebacate, dioctyl phthalate, dibutyl phthalate, and o-nitrophenyl octyl ether.

9. The electrode membrane of claim 8 wherein the plasticizer is dioctyl sebacate.

10. An electrode membrane comprising:

30-70 weight percent polymeric matrix material;

30-70 weight percent plasticizer; and

0.1-12 weight percent anion exchange material, the membrane being selective for heparin.

11. The electrode membrane of claim 10 wherein the anion exchange material is a quaternary ammonium salt selected from the group consisting of triethyl phenyl ammonium iodide, tetrapentyl ammonium bromide, trimethyl phenyl ammonium, dimethyl dioctadecyl ammonium bromide, tetraoctylammonium bromide chloride, hexadecyl trimethylammonium bromide, tetraethyl ammonium perchlorate, tetramethyl ammonium bromide, tetrabutyl ammonium iodide, tridodecyl methyl ammonium chloride, polybrene, and trioctyl methyl ammonium chloride.

12. The electrode membrane of claim 11 wherein the quaternary ammonium salt is tridodecyl methyl ammonium chloride.

13. The electrode membrane of claim 10 wherein the polymeric matrix material is selected from the group consisting of polyvinyl, polyurethane, cellulose triacetate, and poly(vinyl alcohol)/poly(vinylchloride) copolymer.

14. The electrode membrane of claim 13 wherein the polymeric matrix material is polyvinyl chloride.

15. The electrode membrane of claim 10 wherein the plasticizer is selected from the group consisting of dicapryl adipate, di-n-hexyl azelate, dipropylene glycol dibenzoate, tri-n-butyl citrate, 2-ethyl hexyl epoxytallate, di(2-ethylhexyl maleate)dioctyl maleate, tri-(n-octyl,n-decyl)trimallitate, methyl oleate, isopropyl palmitate, t-butyl phenyl diphenyl phosphate, butyl octyl phthalate, diisooctyl phthalate, glyceryl triacetyl ricinoleate, dibutyl sebacate, isopropyl isostearate, dioctyl sebacate, dioctyl phthalate, dibutyl phthalate, and o-nitrophenyl octyl ether.

16. The electrode membrane of claim 15 wherein the plasticizer is dioctyl sebacate.

17. A electrode membrane having selectivity for heparin comprising:

about 1.4 to 2.0 weight percent tridodecyl methyl ammonium chloride;

about 65 weight percent polyvinyl chloride; and

about 33 weight percent dioctyl sebacate.

18. An ion-selective membrane electrode comprising:

(a) a housing containing a reference solution;

(b) an electrode arranged in the housing so that it is disposed in the reference solution; and

(b) an ion-selective membrane of a polymeric matrix material which is non-reactive with the liquid medium, an anion exchange material, and a plasticizer, the ion-selective membrane being selective to heparin, the ion-selective membrane being disposed on one end of the housing so as to seal the reference solution inside the housing and to contact a sample solution external to the housing.

19. A solid state membrane electrode for measuring the concentration of heparin in a liquid medium as a function of potentiometric response comprising a conductive substrate and a membrane material arranged to be in adherence with said conductive substrate, said membrane material comprising a polymeric matrix material which is non-reactive with the liquid medium, an anion exchange material, and a plasticizer, said membrane material being selective to heparin.