This project, supported in the Analytical and Surface Chemistry Program, is directed towards the development of enzyme immunoassay type sensors for the selective quantification of biomacromolecules. During the tenure of this three-year standard grant, Professor Meyerhoff and his students at the University of Michigan will investigate the fundamentals of operation of thioctic acid self-assembled monolayer bound enzyme-antibody electrodes capable of assaying protein antigens in untreated whole blood. Novel sensors are introduced having the capability of assaying human chorionic gonadotropin (hCG) and prostate specific antigen (PSA) at the part-per-trillion level in undiluted whole blood. Future efforts will be geared towards the miniaturization of sensor devices which are capable of automated, multi-component analyses of protein analyte over a wide dynamic concentration range. In addition, Professor Meyerhoff is also continuing his efforts in developing enzyme- linked binding assays (ELBAs) whereby the complexation and binding sites of charged biological macromolecules that interact specifically with glycosaminoglycans can be characterized. The latter techniques are used in the assessment of carbohydrate structure and content of intact glycoproteins. Few analytical probes can rival the sensitivity and selectivity for biological macromolecules as exhibited by enzyme-antibody type sensors. These devices are capable of sub-part-per-trillion detection of protein analyte present in complex matrices such as whole blood and waste water. Professor Meyerhoff and his students at the University of Michigan are advancing new generations of these devices which are capable of assaying mixtures of protein analytes over wide concentration ranges with minimal sample pretreatment. This analytical technology will be broadly applicable to biotechnology, clinical chemistry, and pharmaceutical research and manufacture.