DESIGN OF N-ELECTRODE LCEC FOR BIOCHEMICAL ANALYSIS

A NEED EXISTS FOR BETTER DEVICES AND NEW INSTRUMENTS TO ENHANCE DIAGNOSTICS AND FOR APPLICATION TO PHYSIOLOGY AND PHARMACOLOGY AS OUTLINED IN THE PROGRAM SPECIFICATIONS FOR NINCDS AND NIGMS. THE PROPOSED WORK WILL STUDY THE ENGINEERING VARIABLES AND APPLICATIONS OF COULOMETRIC ELECTRODES IN SERIES FOR LIQUID CHROMATOGRAPHY ELECTROCHEMICAL (LCEC) DETECTOR SYSTEMS (N-ELECTRODE LCEC). SERIES COULOMETRIC ELECTRODES ASSEMBLED FROM EXISTING COMMERCIAL SYSTEMS WHERE N IS 6-8' OFFER SUB-PICOGRAM SENSITIVITY, SELECTIVITIES OF UP TO 100,000 AND THE ABILITY TO DO COMPOUND IDENTIFICATION AND VERIFICATION BY PEAK RATIOS ON DIFFERENT ELECTRODES. SIX ELECTRODE ASSEMBLIES ALLOW THE DETERMINATION OF CATECHOLAMINES AND METABOLITES IN DIRECTLY INJECTED SERUM. THE ASSEMBLIES OF EXISTING EQUIPMENT ARE, HOWEVER, NOT OPTIMIZED AND ARE UNNECESSARILY EXPENSIVE. SPECIALIZED N-ELECTRODE CELLS OF TWO TYPES WILL BE CONSTRUCTED; FOUR ELECTRODE SAMPLE CONDITIONING OR "GATE" CELLS AND 6-10 ELECTRODE SIGNAL ANALYSIS OR "ARRAY" CELLS. THE CELLS WILL BE EVALUATED FOR PERFORMANCE VARIABLES, I.E., BAND SPREADING, BACK PRESSURE, SENSITIVITY, SELECTIVITY FOR THE FOUR-CELL "GATE" ELECTRODE, AND RESOLUTION FOR THE 6-10 CELL ARRAY ELECTRODE. PRELIMINARY APPLICATIONS FOR DIRECT INJECTION OF BIOLOGICAL SAMPLES FOR NEUROTRANSMITTERS WILL BE RUN AND COMPARED WITH EXISTING 6- AND 8-CELL SERIES DATA, PARTICULARLY FOR SAMPLES FROM PATIENTS WITH ALZHEIMER'S DISEASE. DETECTION OF BIOCHEMICAL LEVELS OF ENKEPHELINS WILL ALSO BE TESTED. A SECOND PROPOSAL COVERING APPLICATION OF THIS TECHNIQUE SPECIFICALLY TO ALZHEIMER'S DISEASE IS ALSO BEING SUBMITTED. IT IS EXPECTED THAT SENSOR ARRAYS WILL BE PRODUCED THAT HAVE BAND SPREADING COMPATIBLE WITH MICROBORE OR FAST LC COLUMNS, SENSITIVITY OF 200 FG OR BETTER FOR NEUROTRANSMITTERS AND RESOLUTION IN THE DETECTOR THAT WILL ALLOW SEPARATION OF COELUTING PEAKS WITH 60 MV DIFFERENCES IN THEIR CURRENT-VOLTAGE CURVES. THE PHASE I EFFORTS WILL BE DEVOTED PRIMARILY TO DEVELOPING THE SPECIFICATIONS FOR LATER PHASE II DEVELOPMENT. MARKETS EXIST FOR SUCH A PRODUCT IN THE GENERAL RESEARCH COMMUNITY, AND LARGER CLINICAL MARKETS EXIST IF THE UNIQUE SELECTIVITY OF THE PROPOSED SENSORS CAN BE SUCCESSFULLY APPLIED TO THE DIAGNOSIS OF PARTICULAR DISEASES.