When Less Gold is More: Selective Attomolar Biosensing at the Nanoscale

Abstract

The development of biosensors has become increasingly important to tackle the spread of potentially pandemic pathogens and for the decentralization of healthcare services. Despite progress, achieving selective detection of ultralow concentrations of biomarkers in complex fluids with point-of-care devices is a standing challenge. Here, an efficient material platform for the sensing of biomarkers down to attomolar concentrations with excellent selectivity and a tuneable linear response range is reported. It is demonstrated that by decreasing the Au nanoislands on an elsewhere passivated surface, it is possible to more than double their electrochemical response to low biomarker concentrations via a gate-type mechanism. As an exemplary application, the first sensing of glycated albumin, a key biomarker for diabetes management, in clinically relevant levels by conjugation of a selective DNA aptamer to the Au nanoisland surface is showcased. With a limit of detection of 0.55 × 10−18 m, the excellent selectivity of this platform against nonspecific biomolecules is validated. This platform shows exceptional sensitivity and selectivity in mouse serum, further highlighting its potential for clinical utility. The versatility of this platform to detect other biomarkers, like miRNAs, is also showcased. These findings provide a flexible material platform for the scalable and low-cost engineering of future point-of-care biosensors.