SBIR-STTR Award

The basic characteristics of fritt type coulometric sensors make them uniquely suited for high sensitivity liquid chromatography electrochemical detection in microbore systems specifically engineered to optimize their properties. The proposed work is based on optimizing a conceptually simple design in which the first sensor in a multiple sensor array is the retaining fritt of a microbore column. Preliminary studies have indicated the desirability of developing the concept as an integrated system - pump, column, sensor, detector - to minimize bandspreading and noise. Specific primary design goals of 10 fg sensitivity for catecholamines and metabolites have been established based on feasibility and the requirements of the specific applications studies proposed in microdialysis and microtissue assays. secondary design goals of optimizing resolution by utilizing multiple series sensors ar-e also proposed. The proposal is directed towards the development of a modular series of devices for the research market as either complete stand alone packages or retrofits to existing pumps and detectors.

The long-term objectives are to:(1) develop a low cost, high sensitivity, high speed modular integrated column/multi-electrochemical system that is adaptable to most existing liquid chromatography pumps and electrochemical detectors; and(2) utilize the speed and sensitivity of the system to develop more detailed understanding of endogenous biochemical processes and pharmacological mechanisms.Phase II studies will be directed at:(1) improving the 10 fg sensitivities and resolution of compounds in 30 sec to 3 min intervals of the Phase I prototype systems;(2) developing the manufacturing designs and protocols to implement a low cost production system with equivalent or better performance;(3) extending the Phase I biologial microdialysis work to demonstrate the utility of better time resolution in basic research in the exitotoxic model of neuronal data and the pharmacology of the dopaminergic and serotonergic systems;(4) extending the application field to different compound groups (e. g. amino acids and carbohydrates) and different markets (e. g. the Japanese clinical market for homovanillic acid and vanilyl mandelic acid assay in neonate neuroblastoma screening); and(5) initiating a theory and application publication sequence to lay the groundwork for market penetration in Phase III.Awardee's statement of the potential commercial applications of the research:The initial commercial application for the system is as an accessory for the approximate 400 groups performing microdialysis work. Secondary, potentially larger applications are in specific high volume clinial tests, e. g. neuroblastoma sreening in Japan, urinary and plasma catecholamines, where speed and throughput are major factors.National Institute of Mental Health (NIMH)