Method for producing an ionic sensor

• US 5,591,400 A
• Filed: 10/31/1994
• Issued: 01/07/1997
• Est. Priority Date: 10/31/1994
• Status: Expired due to Term

• Current Assignee: Terumo Cardiovascular Systems Corporation (Terumo Corporation)
• Original Assignee: Minnesota Mining and Manufacturing Co (3M Company)
• Inventors: Patil, Sanjay L., Dektar, John L.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US08/332,244
• Time in Patent Office: 799 Days
• Field of Search: 422/82.05, 422/82.06, 422/82.07, 422/82.08, 422/55, 422/57, 436/172, 427/162, 427/163.2
• US Class Current: 427/163.2
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/75 Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73

Abstract

The present invention provides processes for the preparation of ionic sensors that include a matrix material, such as ion-permeable cellulose, having a sensing component included therein, such as a fluorescent dye, and an opaque overcoat material. For example, the present invention provides a method of making an ionic sensor comprising: contacting a water-swellable ion-permeable matrix material with an aqueous-based bath of a sensing component, or precursor thereof, under conditions effective to covalently attach the sensing component, or precursor thereof, to the water-swellable ion-permeable matrix material; wherein the aqueous-based bath comprises water and an organic solvent in an amount effective to solubilize the sensing component, or precursor thereof; contacting the water-swellable ion-permeable matrix material having covalently attached sensing component, or precursor thereof, with an aqueous solution having a pH of at least about 10 and an ionic strength of at least about that of a 5% aqueous sodium chloride solution to form a sensing element; and covering the sensing element with an opaque overcoat material. Also provided is a method of making a precursor to a preferred sensing component, i.e., acetoxypyrenetris(sulfonyl)chloride, which is made using a thionyl chloride method. If the sensing component is attached to the matrix material using amine groups, any unreacted amine groups can be capped by contacting them with a solution comprising an acetylating agent, an organic amine, and an ethereal solvent.

Claims

1. A method of making an ionic sensor comprising:

(a) contacting a water-swellable ion-permeable matrix material with an aqueous-based bath of a sensing component, or precursor thereof, under conditions effective to covalently attach the sensing component, or precursor thereof, to the water-swellable ion-permeable matrix material;

wherein the aqueous-based bath comprises water and an organic solvent in an amount effective to solubilize the sensing component, or precursor thereof;

(b) contacting the water-swellable ion-permeable matrix material having covalently attached sensing component, or precursor thereof, with an aqueous solution having a pH of at least about 10 and an ionic strength of at least about that of a 5% aqueous sodium chloride solution to form a sensing element; and

(c) coveting the sensing element with an opaque overcoat material.

2. The method of claim 1 wherein the aqueous solution used in step (b) comprises:

(a) a base selected from the group consisting of sodium carbonate, sodium hydroxide, and mixtures thereof; and

(b) a salt selected from the group consisting of sodium chloride, sodium acetate, sodium sulfate, and mixtures thereof.

3. The method of claim 1 wherein the sensing component precursor is acetoxypyrenetris(sulfonyl)chloride, which is made by a method comprising:

(a) converting hydroxypyrenetrisulfonate to acetoxypyrenetrisulfonate; and

(b) reacting acetoxypyrenetrisulfonate with thionyl chloride and a catalytic amount of disubstituted formamide to form acetoxypyrenetris(sulfonyl)chloride.

4. The method of claim 1 wherein the aqueous-based bath is buffered.

5. The method of claim 4 wherein the aqueous-based bath is buffered with a salt selected from the group consisting of sodium carbonate, sodium bicarbonate, sodium monobasic phosphate, sodium dibasic phosphate, sodium borate, and mixtures thereof.

6. The method of claim 1, prior to the step of covalently attaching the sensing component, or precursor thereof, to the matrix, further including:

(a) reacting the water-swellable ion-permeable matrix material with an epoxide having at least two epoxy groups per molecule to form an epoxy-modified matrix material; and

(b) reacting the epoxy-modified matrix material with an organic amine having at least two amine groups per molecule to form an amine-modified matrix material.

7. The method of claim 6 further including a step of capping any unreacted amine groups on the matrix material having the sensing component, or precursor thereof, covalently attached thereto, by contacting the unreacted amine groups with a solution comprising an acetylating agent, an organic amine, and an ethereal solvent.

8. The method of claim 7 wherein the organic amine is a tertiary amine and the solution further includes a catalyst.

9. The method of claim 8 wherein the catalyst is a substituted pyridine.

10. A method of making an ionic sensor comprising:

(a) reacting acetoxypyrenetris(sulfonyl)chloride with an amine-modified polymeric ion-permeable matrix material to form bound acetoxypyrenesulfonamide;

wherein the acetoxypyrenetris(sulfonyl)chloride is made by a method comprising;

(i) converting hydroxypyrenetrisulfonate to acetoxypyrenetrisulfonate; and

(ii) reacting acetoxypyrenetrisulfonate with thionyl chloride and a catalytic amount of disubstituted formamide to form acetoxypyrenetris(sulfonyl) chloride;

(b) converting the bound acetoxypyrenesulfonamide to the hydroxy form to form a sensing element; and

(c) covering the sensing element with an opaque overcoat material.

11. The method of claim 10 wherein the polymeric ion-permeable matrix material is cellulose.

12. The method of claim 10 wherein the step of reacting acetoxypyrenetris(sulfonyl)chloride with the amine-modified polymeric ion-permeable matrix material comprises reacting them in an aqueous-based bath comprising water, an organic solvent in an amount effective to solubilize the acetoxypyrenetris(sulfonyl)chloride, and buffer salts.

13. The method of claim 10 further including a step of capping any unreacted amine groups on the matrix material having the sensing component, or precursor thereof, covalently attached thereto, by contacting the unreacted amine groups with a solution comprising an acetylating agent, an organic amine, and an ethereal solvent.

14. The method of claim 10 wherein the step of converting the bound acetoxypyrenesulfonamide to the bound hydroxy form comprises combining the bound acetoxypyrenesulfonamide with an aqueous solution having a pH of at least about 10 and an ionic strength of at least about that of a 5% aqueous sodium chloride solution.

15. The method of claim 14 wherein the aqueous solution comprises:

(a) a base selected from the group consisting of sodium carbonate, sodium hydroxide, and mixtures thereof; and

(b) a salt selected from the group consisting of sodium chloride, sodium acetate, sodium sulfate, and mixtures thereof.

16. A method of making an ionic sensor comprising:

(a) applying to a surface of a first polymeric ion-permeable matrix material, a second polymeric ion-permeable matrix material having mixed therein an opaque agent;

(b) reacting both matrix materials with an epoxide having at least two epoxy groups per molecule to covalently bond the two matrix materials together and form pendant epoxy groups;

(c) reacting the epoxy groups with an organic amine having at least two amine groups per molecule to form pendant amine groups;

(d) reacting acetoxypyrenetris(sulfonyl)chloride with the pendant amine groups in an aqueous-based bath comprising water, an organic solvent in an amount effective to solubilize the acetoxypyrenetris(sulfonyl)chloride, and buffer salts, to form bound acetoxypyrenesulfonamide;

wherein the acetoxypyrenetris(sulfonyl)chloride is made by a method comprising;

(i) converting hydroxypyrenetrisulfonate to acetoxypyrenetrisulfonate; and

(ii) reacting acetoxypyrenetrisulfonate with thionyl chloride and a catalytic amount of a disubstituted formamide to form acetoxypyrenetris(sulfonyl) chloride;

(e) converting the bound acetoxypyrenesulfonamide to the bound hydroxy form; and

(f) capping any unreacted amine groups on the matrix material by contacting them with a solution comprising an acetylating agent, an organic amine, and an ethereal solvent.

17. The method of claim 16 wherein the first polymeric ion-permeable matrix material is cellulose, the second polymeric ion-permeable matrix material is dextran, and the opaque agent is carbon black.