Objective: The overarching goal of this project is to develop a copolymer membrane in which a blend of conducting and biocompatible polymers create a anti-fouling sensing matrix for long term in vivo sensing.
The ability to detect physiologically relevant targets in real-time, in vivo has the ability to revolutionize modern healthcare. Whether it is monitoring therapeutics with narrow windows of efficacy, glucose levels for tight glycemic control, or inflammatory markers to monitor heart disease, the ability to perform real-time, continuous monitoring gives the healthcare provider and patient the necessary information to make decisions on courses of treatment and the subsequent efficacy of that treatment for the individual patient. Current technology for detection of small molecules and other biologically-relevant targets, however, has not met these demanding need as they remain cumbersome, laboratory bound techniques such as immunoassays and chromatography. Thus, development of implantable devices capable of such detection is of great interest to the global health community.
In this project, we are coupling the electrochemical aptamer-based sensor platform, which, unlike the vast majority of reported biosensor platforms, achieve exceptional selectivity in complex samples matrices, with a conducting/biocompatible copolymer permselective membrane creating a class of biosensors capable of performing long term in vivo continuous monitoring as implantable devices. Coupling the promising E-AB sensor platform with biocompatible membrane materials will support the selective detection afforded by the sensor platform on a scaffold that is resistant to biofouling species allowing long-term use in vivo. The sensors comprise a gold electrode that is coated with a mixed polymer membrane containing both biocompatible and conducting polymers. By covalently linking respective redox-tagged RNA (with careful modification of the sugar backbone) or DNA aptamers to the conducting membrane a three-dimensional porous sensing matrix will be created. This project will involves the synthesis and characterization of the conducting polymer coupled with the sensing oligonucleotide, the synthesis and characterization of the biocompatible polymer and evaluation of biofouling, and the demonstration of long-term, in vivo sensing capabilities of the copolymer modified sensor using representative anti-aminoglycoside antibiotic aptamers and an anti-cocaine aptamer as model systems both in vitro and in vivo.