Continuous glucose sensor using novel genetically engineered binding polypeptides towards in vivo applications

As the importance of blood-glucose control for both diabetic and non-diabetic patients continues to increase, there is a need for more advanced glucose-sensing technologies. In particular, an in vivo glucose sensor is needed that exhibits high accuracy when operating in a continuous manner for a relatively long period of time (3-5 days). Development of such sensors has been hampered, as low accuracy and sensor drift become major problems with in vivo environments, especially for enzyme-based electrochemical glucose sensors. This paper reports on the use of a novel, binding polypeptide-based, fluorescent, glucose-sensing system that promises to overcome many drawbacks of an enzyme-based system while showing the potential for high accuracy, especially at hypoglycemic levels. Fluorescently labeled glucose recognition polypeptide elements were immobilized in a polyacrylamide hydrogel matrix placed on the tip of an optical fiber to realize a continuous glucose-sensing device towards in vivo applications. In vitro validation was performed in both buffered solutions and whole blood to characterize sensor parameters such as sensitivity and response time. Testing demonstrated that the reagentless polypeptide-based glucose-sensing system has extreme sensitivity in the hypoglycemic levels while providing high precision across the entire human physiologic glucose range. Additionally, the sensor was shown to function at physiologic temperature (viz., 37 °C) and displayed high selectivity for glucose without interference from other sugars (viz., fructose). This represents the first report of implementing immobilized glucose binding protein-like elements in a sensing device for continuous glucose monitoring, and establishes proof-of-concept as an excellent alternative to overcoming problems of current long-term, continuous glucose-sensing technologies.

Sensors and actuators. B, Chemical, 2010, 149, 51-58