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

This\nstudy explores the potential of seven ferrocenyl (Fc) compounds\nwith cross-linking groups as alternative redox labels to methylene\nblue (MB) for electrochemical aptamer-based (E-AB) sensors. The cross-linking\nefficiency, formal potential (<i>E</i><sup>0</sup>′),\nand electrochemical durability of these compounds were evaluated.\nCompound <b>Fc1a-X</b> exhibited superior performance, characterized\nby efficient cross-linking, a moderate and pH-insensitive <i>E</i><sup>0</sup>′, and enhanced durability during repeated\npotential scans. The attachment of <b>Fc1a-X</b>, which includes\na 3-carbon chain spacer and an <i>N</i>-hydroxysuccinimide-ester\ncross-linking group, to an amine-terminated monolayer on a Au electrode\ndemonstrated high cross-linking efficiency, which is critical for\nachieving high sensitivity. The <i>E</i><sup>0</sup>′\nof <b>Fc1a-X</b> attached to the aptamer monolayer was 0.14\nV, which is within the optimal range of −0.2 to 0.2 V vs Ag/AgCl.\nSquare wave voltammetry showed that the peak potential and current\nof <b>Fc1a-X</b> are pH-insensitive, which is critical for versatile\nuse. In serum, <b>Fc1a-X</b> maintained stable peak current\nlevels without a gradual decrease after an initial rapid decrease\nduring the first 2 h with considerably less reduction over 12 h compared\nto MB. Using <b>Fc1a-X</b> as the redox label, an E-AB sensor\neffectively detected doxorubicin in serum, covering the clinical range.\nThese findings suggest <b>Fc1a-X</b> as a promising candidate\nfor developing robust, versatile, and sensitive E-AB sensors.