Improving the Biocompatibility and In Vivo Analitical Performance of Intravascular Chemical Sensors

Department of Chemistry University of Michigan
ABSTRACT:
To date, the analytical performance of intravascular chemical sensors (both electrochemical and optical) capable of continuously monitoring blood gases and electrolytes for extended periods in critically ill patients has been limited by problems associated with initiation of thrombus formation on the sensor surfaces as well as localized arterial constriction that diminishes blood flow at the implant site. In this presentation, a new approach aimed at ultimately solving these fundamental biological response problems will be described. This method is based on fabricating intravascular chemical sensors with outer polymeric films that release low levels of nitric oxide (NO) locally, at the implant site. Such in-situ release of NO prevents platelet adhesion/activation on the surface of the sensors and, concomitantly, could provide a sustained release of NO or NO precursors that can serve to dilate the artery immediately surrounding the sensor, thereby maintaining blood flow. Polymer formulations/configurations have been developed that provide appropriate rates of NO release required to decrease platelet adhesion/activation (> 10-10 mol/cm2 min) yet do not interfere with the sensors' electrochemical response and analytical performance (e.g., selectivity, drift, etc.). In vivo evaluation of intravascular electrochemical blood gas sensors (oxygen) prepared with the NO release polymers has demonstrated that the analytical performance of the sensors prepared with the new NO release coatings are superior to control sensors (w/o NO release) placed into arteries of the same animals. SEMs of the sensors after such in vivo experiments confirms the dramatic reduction in platelet adhesion and activation on the surfaces of the sensors formulated with the new NO release coatings. It will be shown that the NO release chemistry is also compatible with preparing optical oxygen sensors based on a fluorescence quenching response mechanism.

BIO:
Mark E. Meyerhoff is Professor of Chemistry in the Department of Chemistry at the University of Michigan, Ann Arbor. He received his Ph.D. from the State University of New York at Buffalo in 1979. Following a short post-doctoral stint at the University of Delaware, he joined the faculty at Michigan as an Assistant Professor in the Fall of 1979. His research interests are in the field of analytical chemistry, particularly the development of new ion-, gas-, and bio-selective electrochemical sensors suitable for whole blood measurements of clinically important analytes. As a consultant, he was closely involved in the development of the first successful point-of-care blood-gas and electrolyte analyzers that were introduced to the clinical market in 1980s. Currently, he also has active research programs in the areas of novel non-separation immunoassay methods, immobilized metalloporphyrin phases for liquid chromatography, and the development and characterization of novel nitric oxide (NO) releasing polymeric materials for biomedical applications. He and his collaborators have authored more than 225 original research papers on these various topics over the past 23 years.
In addition to his new role on the Board of Editors for Clinical Chemistry, Professor Meyerhoff continues to serve on the editorial/advisory boards of Biosensors & Bioelectronics, Electroanalysis, Analytica Chimica Acta, Mikrochimica Acta, and Applied Biochemistry and Biotechnology. He is also active as a consultant and/or is on the Scientific Advisory Boards of several biomedical companies.