Sensor membrane, a method for the preparation thereof, a sensor and a layered membrane structure for such sensor

• US 20030070548A1
• Filed: 11/21/2002
• Published: 04/17/2003
• Est. Priority Date: 05/23/2000
• Status: Active Grant

• Current Assignee: Radiometer Medical ApS (Danaher Corporation)
• Original Assignee: Radiometer Medical ApS (Danaher Corporation)
• Inventors: Clausen, Lydia
• Granted Patent: US 7,195,697 B2
• Time in Patent Office: Days
• US Class Current: 96/4
• CPC Class Codes: C12Q 1/26 involving oxidoreductase
• CPC Class Codes: C12Q 1/58 involving urea or urease
• CPC Class Codes: C12Q 1/66 involving luciferase

Abstract

A membrane for a sensor, a method for the preparation thereof, a layered membrane structure and a sensor for analytical measurements which require controlled analyte permeability. The membrane, layered structure and sensor may be used for biological, physiological and chemical measurements, however, are especially applicable for electrochemical measurements of glucose, lactate, urea and creatinine. The membrane comprises at least one polymer material, at least one surfactant, and at least one hydrophilic compound in admixture to provide a membrane structure in which micelles of hydrophilic compound lined with thin layers of surfactant are randomly distributed in the bulk polymer of the membrane. Upon conditioning of the membrane a structure of a percolating network of pores lined with surfactant is formed which has excellent permeability properties. The membrane has the additional advantage of a proper adhesion to polymer encapsulant structures. The membrane is prepared from a mixture of at least one polymer material, at least one surfactant, at least one hydrophilic compound and at least one solvent.

Claims

1. A sensor membrane comprising at least one polymer material, at least one surfactant and at least one hydrophilic compound, which is not a polymer, in admixture.

2. A membrane according to claim 1 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol the solubility sphere of which has a common volume segment with a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from the solubility sphere of the at least one polymer.

3. A membrane according to claim 1 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol of which δ

_d-pol, δ

_p-pol, and δ

_h-pol are included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from the solubility sphere of the at least one polymer.

4. A membrane according to claim 1 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol the solubility sphere of which is included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from the solubility sphere of the at least one polymer.

5. A membrane according to claim 1 in which the at least one polymer is selected from polyvinyl chlorides, polyvinylidene chlorides, polyvinylidene-acrylonitrile copolymers and their mixtures with butadiene-acrylonitrile copolymers, polyesters and UV-curable acrylates thereof, polycarbonates, glycol modified polyethylene terephthalates, polyacrylates, polymethacrylates, polystyrenes, polyurethanes and UV-curable acrylates thereof as well as UV-curable epoxy acrylates, preferably polyvinyl chlorides, polyvinylidene chlorides, polyvinylidene-acrylonitrile copolymers and polyesters.

6. A membrane according to any of the preceding claims 1-5 in which the at least one polymer is present in an amount of between 70% and 99% by weight of the membrane.

7. A membrane according to any of the preceding claims 1 and 4-6 in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0.

8. A membrane according to any of the preceding claims 1-7 in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are included in a sphere of radius=9.2 and centered at δ

_d=16.6, δ

_p=12.0, δ

_h=20.7.

9. A membrane according to any of the preceding claims 1-7 in which the at least one hydrophilic compound is selected from the groups of alcohols, glycols and ethers:

C₂-C₄ alcohols ethanol, propanol, isopropanol, butanol, isobutanol and t-butanol;

C₂-C₄ di- and trialcohols ethylene glycol, propylene glycol, 1,3-propanediol, 1,2-, 1,3- and 1,4-butanediol and glycerol;

polyethylene (2-8) glycol and polypropylene (2-3) glycol;

mono- and polyethylene (2-8) glycol and mono- and polypropylene (2-3) glycol monomethyl and monoethyl ether;

polyethylene (2-8) glycol dimethyl, diethyl and methylethyl diether.

10. A membrane according to claim 9 in which the at least one hydrophilic compound is selected from diethylene glycol and triethylene glycol, preferably diethylene glycol.

11. A membrane according to any of the preceding claims 1-7 in which the at least one hydrophilic compound is selected from mono- and poly-(2-4) saccharides.

12. A membrane according to any of the preceding claims 1-11 in which the at least one hydrophilic compound is present in an amount of 1-20% by weight of the membrane.

13. A membrane according to any of the preceding claims 1-12 in which the at least one surfactant has a hydrophilic-lipophilic balance (HLB) value less than 12, preferably less than 10.

14. A membrane according to any of the preceding claims 1-10 and 12-13 in which the at least one surfactant is selected from the groups of:

polyethylene glycol fatty acid esters, preferably mono- and polyethylene (2-10) glycol laurates, myristates, palmitates, stearates and oleates;

polyethylene glycol ethers, preferably octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, octylphenyl, nonylphenyl, decylphenyl, dodecylphenyl, tetradecylphenyl and hexadecylphenyl ethers of polyethylene (2-10) glycol.

15. A membrane according to claim 14 in which the at least one surfactant is selected from polyethylene (3) glycol trimethylnonyl ether, polyethylene (4) glycol nonylphenyl ether and polyethylene (4) glycol lauryl ether.

16. A membrane according to any of the preceding claims 1-8 and 11-13 in which the at least one surfactant is selected from the groups of:

saccharide fatty acid esters, preferably mono-, di- and poly-glucoside, methylglucoside, glucopyranoside and maltoside laurates, myristates, palmitates, stearates and oleates;

saccharide fatty ethers, preferably octyl, nonyl, decyl, dodecyl and tetradecyl mono-, di- and poly-glucosides, methylglucosides, glucopyranosides and maltosides;

sorbitol fatty acid esters, preferably sorbitol and ethoxylated sorbitol laurates, myristates, palmitates, stearates and oleates.

17. A membrane according to any of the preceding claims 1-16 in which the at least one surfactant is present in an amount of 0.1-10% by weight of the membrane.

18. A membrane according to any of the preceding claims 1-17 in which the membrane has a thickness in the range 0.5-10 μ

m, preferably 1-5 μ

m.

19. A membrane according to any of the preceding claims 1-18 in which the membrane has a structure comprising micelles of hydrophilic compound lined with surfactant randomly distributed in the membrane bulk polymer.

20. A membrane according to any of the preceding claims 1-19 in which the membrane has a structure comprising a perculating network of pores lined with surfactant and isolated micelles of hydrophilic compound lined with surfactant.

47. A layered membrane structure for a sensor comprising a first membrane, an enzyme layer and a second membrane in which said first membrane is a membrane as described in any of the preceding claims 1-20 or in which the said first membrane is a membrane prepared by a method as described in any of the preceding claims 21-46.

48. A layered membrane structure according to claim 47 in which the enzyme layer comprises glucose oxidase, lactate oxidase, urease or enzymes for the oxidation of creatinine.

49. A layered membrane structure according to any of the preceding claims 47-48 in which said second membrane is selected from the groups of interference limiting membranes and ion selective membranes.

50. A sensor comprising a first membrane, an enzyme layer, optionally a second membrane and at least one electrode in which said first membrane is a membrane as described in any of the preceding claims 1-20 or in which the said first membrane is a membrane prepared by a method as described in any of the preceding claims 21-46 or in which said first membrane, said enzyme layer and said optional second membrane provide a layered membrane structure as described in any of the preceding claims 47-49.

51. A sensor according to claim 50 in which said first membrane is an outer membrane.

52. A sensor according to any of the preceding claims 50-51 in which the sensor is equilibrated at a relative humidity of at most 30% and has a water content corresponding hereto.

53. A sensor according to any of the preceding claims 50-52 in which the sensor is a planar sensor.

54. A sensor according to any of the preceding claims 51-53 in which the surface of the sensor facing the sample comprises the outer membrane and a polymer encapsulant structure.

55. A sensor according to claim 54 in which the outer membrane is bound to the polymer encapsulant structure.

21. A method for the preparation of a sensor membrane comprising the steps of:

mixing at least one polymer material, at least one surfactant, at least one hydrophilic compound, which is not a polymer, and at least one solvent in which the at least one polymer material is soluble

applying said mixture onto a substrate

evaporating the solvent, and

optionally conditioning the membrane.

22. A method according to claim 21 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol the solubility sphere of which has a common volume segment with a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from the solubility sphere of the at least one polymer.

23. A method according to claim 21 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol of which δ

_d-pol, δ

_p-pol, and δ

_h-pol are included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hdr, δ

_h-hydr of which are excluded from the solubility sphere of the at least one polymer.

24. A method according to claim 21 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol,δ

_h-pol the solubility sphere of which is included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from the solubility sphere of the at least one polymer.

25. A method according to claim 21 in which the at least one polymer is selected from polyvinyl chlorides, polyvinylidene chlorides, polyvinylidene-acrylonitrile copolymers and their mixtures with butadiene-acrylonitrile copolymers, polyesters and UV-curable acrylates thereof, polycarbonates, glycol modified polyethylene terephthalates, polyacrylates, polymethacrylates, polystyrenes, polyurethanes and UV-curable acrylates thereof as well as UV-curable epoxy acrylates, preferably polyvinyl chlorides, polyvinylidene chlorides, polyvinylidene-acrylonitrile copolymers and polyesters.

26. A method according to any of the preceding claims 21 and 24-25 in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are excluded from a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0.

27. A method according to any of the preceding claims 21-26 in which the at least one hydrophilic compound is selected from those hydrophilic compounds the Hansen solubility parameters δ

_d-hydr, δ

_p-hydr, δ

_h-hydr of which are included in a sphere of radius=9.2 and centered at δ

_d=16.6, δ

_p=12.0, δ

_h=20.7.

28. A method according to any of the preceding claims 21-26 in which the at least one hydrophilic compound is selected from the groups of alcohols, glycols and ethers:

C₂-C₄ alcohols ethanol, propanol, isopropanol, butanol, isobutanol and t-butanol;

C₂-C₄ di- and trialcohols ethylene glycol, propylene glycol, 1,3-propanediol, 1,2-, 1,3- and 1,4-butanediol and glycerol;

polyethylene (2-8) glycol and polypropylene (2-3) glycol;

mono- and polyethylene (2-8) glycol and mono- and polypropylene (2-3) glycol monomethyl and monoethyl ether;

polyethylene (2-8) glycol dimethyl, diethyl and methylethyl diether.

29. A method according to claim 28 in which the at least one hydrophilic compound is selected from diethylene glycol and triethylene glycol, preferably diethylene glycol.

30. A method according to any of the preceding claims 21-26 in which the at least one hydrophilic compound is selected from mono- and poly-(2-4) saccharides.

31. A method according to any of the preceding claims 21-30 in which the at least one surfactant has a hydrophilic-lipophilic balance (HLB) value less than 12, preferably less than 10.

32. A method according to any of the preceding claims 21-29 and 31 in which the at least one surfactant is selected from the groups of:

polyethylene glycol fatty acid esters, preferably mono- and polyethylene (2-10) glycol laurates, myristates, palmitates, stearates and oleates;

polyethylene glycol ethers, preferably octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, octylphenyl, nonylphenyl, decylphenyl, dodecylphenyl, tetradecylphenyl and hexadecylphenyl ethers of polyethylene (2-10) glycol.

33. A method according to claim 32 in which the at least one surfactant is selected from polyethylene (3) glycol trimethylnonyl ether, polyethylene (4) glycol nonylphenyl ether and polyethylene (4) glycol lauryl ether.

34. A method according to any of the preceding claims 21-27 and 30-31 in which the at least one surfactant is selected from the groups of:

saccharide fatty acid esters, preferably mono-, di- and poly-glucoside, methylglucoside, glucopyranoside and maltoside laurates, myristates, palmitates, stearates and oleates;

saccharide fatty ethers, preferably octyl, nonyl, decyl, dodecyl and tetradecyl mono-, di- and poly-glucosides, methylglucosides, glucopyranosides and maltosides;

sorbitol fatty acid esters, preferably sorbitol and ethoxylated sorbitol laurates, myristates, palmitates, stearates and oleates.

35. A method according to any of the preceding claims 21-34 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol the solubility sphere of which has a common volume segment with a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one solvent is selected from those solvents the Hansen solubility parameters δ

_d-sol, δ

_p-sol, δ

_h-sol of which are included in the solubility sphere of the at least one polymer.

36. A method according to any of the preceding claims 21-34 in which the at least one polymer is selected from those polymers of a solubility sphere of interaction radius=R_o-pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol of which δ

_d-pol, δ

_p-pol, and δ

_h-pol are included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one solvent is selected from those solvents the Hansen solubility parameters δ

_d-sol, δ

_p-sol, δ

_h-sol of which are included in the solubility sphere of the at least one polymer.

37. A method according to any of the preceding claims 21-34 in which the at least one polymer is selected from those, polymers of a solubility sphere of interaction radius=R_pol and centered at the Hansen solubility parameters δ

_d-pol, δ

_p-pol, δ

_h-pol the solubility sphere of which is included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0, and in which the at least one solvent is selected from those solvents the Hansen solubility parameters δ

_d-sol, δ

_p-sol, δ

_h-sol of which are included in the solubility sphere of the at least one polymer.

38. A method according to any of the preceding claims 21-37 in which the at least one solvent is selected from those solvents the Hansen solubility parameters δ

_d-sol, δ

_p-sol, δ

_h-sol of which are included in a sphere of radius=5.8 and centered at δ

_d=18.1, δ

_p=7.0, δ

_h=6.0.

39. A method according to any of preceding claims 21-34 in which the at least one solvent is selected from the groups of:

aliphatic C₅-C₈ alcohols pentanol, hexanol, heptanol and octanol;

alicyclic C₅-C₈ alcohols cyclopentanol, cyclohexanol, cycloheptanol and cyclooctanol;

aliphatic esters ethyl-, propyl-, isopropyl, butyl, isobutyl and t-butyl acetate, propionate and 2-hydroxy propionate;

alicyclic ethers tetrahydrofurane and 2-methyl tetrahydrofurane;

aliphatic ketones represented by the general formula R₁—

C(═

O)—

R₂ wherein R₁ and R₂ independently represent methyl, ethyl, propyl and isopropyl and butyl, isobutyl and t-butyl;

alicyclic C₅-C₈ ketones cyclopentanone, cyclohexanone, cycloheptanone and cyclooctanone.

40. A method according to claim 39 in which the at least one solvent is selected from tetrahydrofurane and cyclohexanone.

41. A method according to any of the preceding claims 21-40 in which the mixture comprises 70-99 parts per weight of polymer, 1-20 parts per weight of hydrophilic compound, 0.1-10 parts per weight of surfactant and 900-9900 parts per weight of solvent.

42. A method according to any of the preceding claims 21-41 in which the application of the mixture onto a substrate is performed using a solvent casting technique, preferably a dispensing technique.

43. A method according to any of the preceding claims 21-41 in which the application of the mixture onto a substrate is performed using a printing technique, preferably a serigraphic technique.

44. A method according to any of the preceding claims 21-43 in which the substrate for the application of the mixture is a polymer foil or a glass.

45. A method according to any of the preceding claims 21-43 in which the substrate for the application of the mixture is an enzyme layer of an sensor.

46. A method according to any of the preceding claims 21-45 in which the membrane conditioning step is a rinsing with an aqueous solution, preferably a rinsing with an aqueous solution of one or more salts and one or more surfactants.