Detection of biological molecules using chemical amplification and optical sensors

• US 6,319,540 B1
• Filed: 09/22/1999
• Issued: 11/20/2001
• Est. Priority Date: 11/22/1995
• Status: Expired due to Term

• Current Assignee: Minimed, Inc. (Medtronic Plc)
• Original Assignee: Minimed, Inc. (Medtronic Plc)
• Inventors: Mastrototaro, John Joseph, Van Antwerp, William Peter
• Primary Examiner(s): Moore, Margaret G.
• Application Number:
  US09/401,147
• Time in Patent Office: 790 Days
• Field of Search: 427/2.11, 427/2.12, 427/2.13, 427/384, 428/704
• US Class Current: 427/2.13
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence

Abstract

Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal. Specifically, the analyte transducer immobilized in a polymeric matrix can be a boronic acid moiety.

Claims

1. A method of immobilizing a boronic acid moiety in a solid support, the method comprising:

covalently attaching the boronic acid moiety to a solid support comprising a polymer matrix, wherein the boronic acid moiety comprises a compound of the formula;

 

wherein D¹ is a dye selected from the group consisting of fluorescent dyes, luminescent dyes and colorimetric dyes;

R¹, R³ and R⁴ are each independently substituents which can alter the electronic properties of the groups to which they are attached or are functional groups which can form covalent linkages to the polymer matrix;

each R² is a member independently selected from the group consisting of hydrogen and C₁-C₄ alkyl;

each L¹ and L² is a linking group having from zero to four contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus;

Z is a heteroatom selected from the group consisting of nitrogen, sulfur, oxygen and phosphorus;

x is an integer from zero to four; and

wherein the boronic acid moiety is attached to the polymer matrix by a covalent linkage to R¹.

2. The method according to claim 1, wherein said solid support is a biocompatible membrane.

3. The method according to claim 1, wherein said solid support is implantable within the body.

4. The method of claim 1, wherein the boronic acid moiety is attached to the polymer matrix using a covalent bonding technique selected from the group consisting of condensation, condensation-elimination and free radical polymerization.

5. A method of immobilizing a boronic acid moiety in a solid support, the method comprising:

covalently attaching the boronic acid moiety to a solid support comprising a polymer matrix, wherein the boronic acid moiety comprises a compound of the formula;

 

wherein D¹ is a dye selected from the group consisting of fluorescent dyes, luminescent dyes and colorimetric dyes;

R¹, R³ and R⁴ are each independently substituents which can alter the electronic properties of the groups to which they are attached or are functional groups which can form covalent linkages to the polymer matrix;

each R² is a member independently selected from the group consisting of hydrogen and C₁-C₄ alkyl;

each L¹ and L² is a linking group having from zero to four contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus;

Z is a heteroatom selected from the group consisting of nitrogen, sulfur, oxygen and phosphorus;

x is an integer from zero to four; and

wherein the boronic acid moiety is attached to the polymer matrix by a covalent linkage to R³.

6. The method of claim 5, wherein the boronic acid moiety is attached to the polymer matrix using a covalent bonding technique selected from the group consisting of condensation, condensation-elimination and free radical polymerization.

7. The method according to claim 5, wherein said solid support is a biocompatible membrane.

8. The method according to claim 5, wherein said solid support is implantable within the body.

9. A method of immobilizing a boronic acid moiety in a solid support, the method comprising:

covalently attaching the boronic acid moiety to a solid support comprising a polymer matrix, wherein the boronic acid moiety comprises a compound of the formula;

 

wherein D¹ is a dye selected from the group consisting of fluorescent dyes, luminescent dyes and colorimetric dyes;

R¹, R³ and R⁴ are each independently substituents which can alter the electronic properties of the groups to which they are attached or are functional groups which can form covalent linkages to the polymer matrix;

each R² is a member independently selected from the group consisting of hydrogen and C₁-C₄ alkyl;

each L¹ and L² is a linking group having from zero to four contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus;

Z is a heteroatom selected from the group consisting of nitrogen, sulfur, oxygen and phosphorus;

x is an integer from zero to four; and

wherein the boronic acid moiety is attached to the polymer matrix by a covalent linkage to R⁴.

10. The method of claim 9, wherein the boronic acid moiety is attached to the polymer matrix using a covalent bonding technique selected from the group consisting of condensation, condensation-elimination and free radical polymerization.

11. The method according to claim 9, wherein said solid support is a biocompatible membrane.

12. The method according to claim 9, wherein said solid support is implantable within the body.

13. A method of immobilizing a boronic acid moiety in a solid support, the method comprising:

entrapping the boronic acid moiety in a solid support comprising a polymer matrix, wherein the boronic acid moiety comprises a compound of the formula;

 

wherein D¹ is a dye selected from the group consisting of fluorescent dyes, luminescent dyes and colorimetric dyes;

R¹, R³ and R⁴ are each independently substituents which can alter the electronic properties of the groups to which they are attached or are functional groups which can form covalent linkages to the polymer matrix;

each R² is a member independently selected from the group consisting of hydrogen and C₁-C₄ alkyl;

each L¹ and L² is a linking group having from zero to four contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus;

Z is a heteroatom selected from the group consisting of nitrogen, sulfur, oxygen and phosphorus; and

x is an integer from zero to four.