Integrated potentiostat for electrochemical sensing of urinary 3-hydroxyanthranilic acid with molecularly imprinted poly(ethylene-co-vinyl alcohol).

Abstract

Changing demographics, the rise of personalized medicine and increased identification of biomarkers for diagnosis and management of chronic disease have increased the demand for portable bioanalytical instrumentation and point-of-care. The recent development of molecularly imprinted polymers enables production of low cost and highly stable sensing chips; however, the commercially available and full functional instruments employed for electrochemical analysis have shortcomings in actual homecare applications. In this work, integrated circuits (ICs) for monolithic implementation of voltammeter potentiostat with a large dynamic current range (5 nA to 1.2 mA) and short conversion time (10 ms) were fabricated in a 0.35 μm complementary metal-oxide-semiconductor (CMOS) process. The new instrumentation was tested with molecular imprinted sensors for 3-hydroxyanthranilic acid (3HAA) in urine. The sensor consisted of molecular imprinted of poly(ethylene-co-vinyl alcohol)s (abbreviated as EVALs) for implementation in a flow injection analysis system. The EVAL containing 32 ethylene mol% had the highest imprinting effectiveness for the target molecules. Fit-for-purpose figures of merit were achieved with a limit-of-detection (LOD) of 3.06 pg/mL. The measurements obtained in real undiluted urine samples fell within the reference concentration range of 50-550 ng/mL.