Oxygen sensing membranes and methods of making same

• US 6,190,612 B1
• Filed: 01/21/1998
• Issued: 02/20/2001
• Est. Priority Date: 01/21/1998
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Bayer Corporation (Bayer AG), Novartis Ag
• Inventors: Collins, Thomas C., Berger, Joseph, Slovacek, Rudolf E.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US09/010,161
• Time in Patent Office: 1,126 Days
• Field of Search: 422/82.06, 422/82.07, 422/82.08, 436/68, 436/172, 436/136, 436/138
• US Class Current: 422/82.07
• CPC Class Codes: G01N 31/225 for oxygen, e.g. including dissolved oxygen

Abstract

Optical sensor formulations comprising polymeric sensing formulations and methods of predictably making optical sensor formulations, for, e.g., measuring O₂ levels in patient blood samples. These formulations may be, e.g., deposited as a membrane on light-transmissive substrates. In an embodiment, O₂-sensing formulations may be made by a process including selecting a first homopolymer comprised of first monomeric units, the first homopolymer having a first Perm_O2 value; selecting a second homopolymer comprised of second monomeric units, the second homopolymer having a second Perm_O2 value that is different from the first Perm_O2 value; and copolymerizing the first and second monomeric units to obtain a copolymer having an intermediate Perm_O2 value, i.e., between the two Perm_O2 values, the intermediate Perm_O2 providing the desired Perm_O2 for the desired oxygen sensing formulation. By adjusting the relative amounts of the first and second monomeric units, a series of polymers having a desired range of intermediate permeability values (and hence Stem-Volmer characteristic k_SV values) may be obtained.

Claims

1. A method of preparing a polymeric sensing composition containing a luminescent dye and a light transmissive, oxygen permeable matrix material, comprising the steps of:

a. selecting a luminescent dye of incorporation in said polymeric sensing composition;

b. determining a desired oxygen permeability (Perm_O2) range for said matrix material which will provide a Stem-Volmer constant in a desired range for said polymeric sensing composition; and

c. preparing said light-transmissive, oxygen permeable matrix material having a glass transition temperature of approximately −

40°

C. or approximately 110°

C. by

i. selecting a first homopolymer comprised of first monomeric units said first homopolymer having a first Perm_O2 value;

ii. selecting a second homopolymer having a second Perm_O2 value that is different than said first Perm_O2 value;

iii. copolymerizing said first and second monomeric units to obtain a copolymer having an intermediate Perm_O2 values, said intermediate Perm_O2 sufficient to provide a Stern-Volmer constant within said desired range of Stem-Volmer constants;

iv. incorporating said luminescent dye in said copolymer; and

v. incorporating a scattering filler material in said copolymer.

2. The method of claim 1, wherein said step of incorporating a luminescent dye further comprises incorporating a luminescent dye selected from the group consisting of pyrenes, pyrelenes, ligand metal complexes of ruthenium, Pt chlorin derivatives and Pt-porphyrin derivatives.

3. The method of claim 1, wherein said step of incorporating a luminescent dye further comprises incorporating octaethyl-Pt porphyrin or meso-tetraphenyl-tetrabenzo-Pt-porphyrin.

4. The method of claim 1, wherein said preparing said light-transmissive, oxygen-permeable matrix material step further comprises selecting said homopolymers from the group consisting of poly(amides), poly(acrylamides), poly(styrenes), poly(acrylates), poly(alkylacrylates), poly(nitriles), poly(vinyl chlorides), poly(vinyl alcohols), poly(dienes), poly(esters), poly(carbonates), poly(siloxanes), poly(urethanes), poly(olefins), poly(imides), and cellulosics.

5. The method of claim 1, wherein said preparing said light-transmissive, oxygen-permeable matrix material step further comprises selecting said monomeric units from the group consisting of ethylhexylmethacrylate and methylmethacrylate.

6. The method of claim 1, wherein said preparing said light-transmissive, oxygen-permeable matrix material step further comprises selecting said monomeric units from the group consisting of styrene and acrylonitrile.

7. The method of claim 1 wherein said copolymerization of said first and second amounts of monomeric units results in a light-transmissive, oxygen-permeable matrix having a Perm_O2 value providing a k_SV of at least 10×

10<sup>−

3</sup> at 37°

C.

8. The method of claim 1, wherein said scattering filler material is selected from the group consisting of TiO₂, zinc oxide, antimony trioxide, barium sulfate, magnesium oxide, blush polymers, and mixtures thereof.

9. The method of claim 8, wherein said scattering filler material is TiO₂ or a blush polymer.

10. A method of preparing a light-transmissive, oxygen-permeable matrix material for use in a polymeric sensing composition, comprising the steps of:

a. determining a desired oxygen permeability (Perm_O2) range for said matrix material which will provide a desired range of Stern-Volmer constants for said polymeric sensing composition;

b. selecting a first homopolymer comprised of first monomeric units, said first homopolymer having a first Perm_O2 value;

c. selecting a second homopolymer comprised of second monomeric units, said second homopolymer having a second Perm_O2 value that is different than said first Perm_O2 value; and

d. preparing a copolymer having an intermediate Perm_O2 value between said first and second Perm_O2 values by copolymerizing said first and second monomeric units in a ratio to obtain said copolymer, said intermediate Perm_O2 value providing a Stern-Volmer constant within said desired range of Stern-Volmer constants wherein said copolymer contains a scattering filler material to form the polymeric sensing composition having a glass transition temperature of approximately −

40°

C. or approximately 110°

C.

11. The method of claim 10, wherein a plurality of copolymers each having a separate intermediate Perm_O2 value between said first and second Perm_O2 values are prepared by copolymerizing said first and second monomeric units in a plurality of ratios to obtain said plurality of copolymers, said intermediate Perm_O2 values providing a plurality of Stern-Volmer constants within said desired range for said polymeric sensing compositions.

12. The method of claim 11, further comprising the step of selecting a light-transmissive, oxygen-permeable matrix material having a desired Perm_O2 value from said plurality of copolymers.

13. An oxygen sensor formulation comprising:

a. a luminescent dye; and

b. a light transmissive, oxygen permeable matrix material having a desired oxygen-permeability (Perm_O2) which provides a Stern-Volmer constant in a desired range for a polymeric sensing composition, made by the process of;

i. selecting a first homopolymer comprised of first monomeric units, said first homopolymer having a first Perm_O2 value;

ii. selecting a second homopolymer having a second Perm_O2 value that is different that said first Perm_O2 value;

iii. copolymerizing said first and second monomeric units to obtain a copolymer having a glass transition temperature of approximately −

40°

C. or approximately 110°

C. and having an intermediate Perm_O2 value between said first and second Perm_O2 values, said intermediate Perm_O2 providing said desired Stem-Volmer constant in said range; and

iv. including a scattering filler material in said copolymer.

14. The sensor formulation of claim 13 wherein said luminescent dye is selected from the group consisting of pyrenes, pyrelenes, ligand metal complexes of ruthenium, Pt-chlorin derivatives and Pt-porphyrin derivatives.

15. The sensor formulation of claim 14, wherein said luminescent dye is octaethyl-Pt porphyrin or meso-tetraphenyl-tetrabenzo-Pt-porphyrin.

16. The sensor formulation of claim 13 wherein said homopolymers are selected from the group consisting of poly(amides), poly(acrylamides), poly(styrenes), poly(acrylates), poly(alkylacrylates), poly(nitriles), poly(vinyl chlorides), poly(vinyl alcohols), poly(dienes), poly(esters), poly(carbonates), poly(siloxanes), poly(urethanes), poly(olefins), poly(imides), and cellulosics.

17. The sensor formulation of claim 16, wherein said monomeric units are selected from the group consisting of ethylhexylmethacrylate and methylmethacrylate.

18. The sensor formulation of claim 16, wherein said monomeric units are selected from the group consisting of styrene and acrylonitrile.

19. The sensor formulation of claim 13, wherein said scattering filler material is selected from the group consisting of TiO₂, zinc oxide, antimony trioxide, barium sulfate, magnesium oxide, and blush polymers, and mixtures thereof.

20. The sensor formulation of claim 19, wherein said scattering filler material is TiO₂ or a blush polymer.

21. The sensor formulation of claim 13, wherein said luminescent dye is octaethyl-Pt porphyrin and said monomeric units are ethylhexylmethacrylate in an amount of between about 5 to 15 mole percent of the total polymerizable monomer;

and methylmethacrylate.

22. The sensor formulation of claim 21, wherein said amount of ethylhexylmethacrylate is about 10 mole percent of the total polymerizable monomer.

23. The sensor formulation of claim 13, wherein said luminescent dye is meso-tetraphenyl-tetrabenzo-Pt-porphyrin and said monomeric units are ethylhexylmethacrylate, in an amount of between about 10 to 20 mole percent of the total polymerizable monomer;

and methylmethacrylate.

24. The sensor formulation of claim 23, wherein said amount of ethylhexylmethacrylate is about 15 mole percent of the total polymerizable monomer.

25. The sensor formulation of claim 13, wherein the luminescent dye is octaethyl-Pt porphyrin and said monomeric units are styrene, in an amount of between about 25 to 65 mole percent of the total composition of the copolymer;

and acrylonitrile.

26. The sensor formulation of claim 25, wherein said styrene content is about 55 mole percent.

27. The sensor formulation of claim 13, wherein the luminescent dye is meso-tetraphenyl-tetrabenzo-Pt-porphyrin and said monomeric units are styrene, in an amount of between about 35 to 75 mole percent of the total composition of the copolymer;

and acrylonitrile.

28. The sensor of claim 27, wherein said styrene content is 58 mole percent.