Optimization of capacitive affinity sensors: drift suppression and signal amplification

The detection limit of capacitive affinity sensors based on the gold-alkanethiol system can be improved by optimization of sensor preparation and by signal amplification. The dissociation of the gold-sulfur binding is often a critical point leading to operative errors of such sensors. The stability of self-assembled monolayers prepared with different thiols on gold electrodes in aqueous and organic solvents was studied by the capacitive technique. The results show that monolayers made of 16-mercaptohexadecanoic acid are stable in aqueous solution and can be hardly extracted from a gold surface by ethanol, methanol, or dioxane, while a considerable damage of self-assembled monolayers was observed due to incubation in chloroform or dimethylformamide. In contrast, self-assembled monolayers made from short-chain disulfides or thiols (such as 3,3'-dithio-bis(propionic acid N-hydroxysuccinimide ester) or 11-mercaptoundecanoic acid) displayed a poor stability in aqueous phase. Capacitive affinity sensors based on these short-chain thiols showed a considerable drift of the signal. The use of long-chain thiols resulted in a stable signal; it was applied to compare capacitive effects due to immobilization of different biological molecules and for preparation of different biosensors. The response of capacitive biosensors can be amplified by formation of a sandwich structure. This principle was illustrated by subsequent adsorption of polyclonal anti-HSA after binding of HSA with a sensor for HSA based on monoclonal antibodies, (C) 1999 Elsevier Science B.V. All rights reserved.