Ferrocenyl Compounds as Alternative Redox Labels for Robust and Versatile Electrochemical Aptamer-Based Sensors

Abstract

This study explores the potential of seven ferrocenyl (Fc) compounds with cross-linking groups as alternative redox labels to methylene blue (MB) for electrochemical aptamer-based (E-AB) sensors. The cross-linking efficiency, formal potential (E⁰′), and electrochemical durability of these compounds were evaluated. Compound Fc1a-X exhibited superior performance, characterized by efficient cross-linking, a moderate and pH-insensitive E⁰′, and enhanced durability during repeated potential scans. The attachment of Fc1a-X, which includes a 3-carbon chain spacer and an N-hydroxysuccinimide-ester cross-linking group, to an amine-terminated monolayer on a Au electrode demonstrated high cross-linking efficiency, which is critical for achieving high sensitivity. The E⁰′ of Fc1a-X attached to the aptamer monolayer was 0.14 V, which is within the optimal range of −0.2 to 0.2 V vs Ag/AgCl. Square wave voltammetry showed that the peak potential and current of Fc1a-X are pH-insensitive, which is critical for versatile use. In serum, Fc1a-X maintained stable peak current levels without a gradual decrease after an initial rapid decrease during the first 2 h with considerably less reduction over 12 h compared to MB. Using Fc1a-X as the redox label, an E-AB sensor effectively detected doxorubicin in serum, covering the clinical range. These findings suggest Fc1a-X as a promising candidate for developing robust, versatile, and sensitive E-AB sensors.