Affinity Sensor: A New Technique for Developing Implantable Sensors for Glucose and Other Metabolites

We describe affinity sensors for monitoring various metabolites in blood plasma by optical means. The principle of detection is similar to that used in radioimmunoassays and is based on the competitive binding of a particular metabolite and a fluorescein-labeled analogue with receptor sites specific for the metabolite and the labeled ligand. This concept has been directed toward the development of an affinity sensor for glucose. Concanavalin A, a protein with specific binding character for glucose, was immobilized on the inside surface of a hollow dialysis fiber. Fluorescein-labeled dextran was selected as the competitive labeled ligand. The molecular weight cutoff of the dialysis fiber is low enough to completely retain the 70,000 MW dextran within the fiber lumen while glucose can freely pass through the dialysis membrane. The sensor is completed by inserting a single optical fiber in the lumen of the dialysis fiber, thus allowing measurement of the unbound FITC-dextran. Preliminary tests of the sensor indicated the feasibility of the approach. Sensitivity to glucose in the physiologic range was obtained, but further work will be required to optimize the sensitivity and response time of the sensor.

[1]  J. Porath,et al.  Chemical Coupling of Peptides and Proteins to Polysaccharides by Means of Cyanogen Halides , 1967, Nature.

[2]  I. Goldstein,et al.  Protein-carbohydrate interaction. XX. On the number of combining sites on concanavalin A, the phytohemagglutinin of the jack bean. , 1968, Biochimica et biophysica acta.

[3]  R L Bowman,et al.  Fiber-optic colorimeter for submicroliter samples. , 1969, Analytical biochemistry.

[4]  C. Sanderson,et al.  A simple method for coupling proteins to insoluble polysaccharides. , 1971, Immunology.

[5]  Alan S. Michaels,et al.  ENZYMATIC CATALYSIS USING ASYMMETRIC HOLLOW FIBER MEMBRANES , 1975 .

[6]  I. Goldstein,et al.  Kinetic parameters for the binding of p-nitrophenyl α-d-mannopyranoside to concanavalin A , 1976 .

[7]  E. Klein,et al.  Transport and mechanical properties of hemodialysis hollow fibers , 1976 .

[8]  R. Korus,et al.  USE OF GLUCOSE ISOMERASE IN HOLLOW FIBER REACTORS , 1977 .

[9]  B. Breslau,et al.  Hollow Fiber Enzymatic Reactors: An Engineering Approach , 1978 .

[10]  A H Clemens,et al.  Closed-loop and Open-loop Devices for Blood Glucose Control in Normal and Diabetic Subjects , 1978, Diabetes.

[11]  J. Schultz,et al.  Affinity sensors for individual metabolites. , 1979, Biotechnology and bioengineering symposium.

[12]  J A Reynolds,et al.  Interaction of divalent antibody with cell surface antigens. , 1979, Biochemistry.

[13]  S R Goldstein,et al.  Fiber optic microfluorimetry for acute and chronic in-vivo animal studies. , 1980, Journal of biomechanical engineering.