A Nanoelectronic Enzyme-Linked Immunosorbent Assay for Detection of Proteins in Physiological Solutions

Semiconducting nanowires are promising ultrasensitive, label-free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field-effect transistors (FETs) function by sensing the charge of a bound molecule. However, solutions of physiological ionic strength compromise the detection of specific binding events due to ionic (Debye) screening. A general solution to this limitation with the development of a hybrid nanoelectronic enzyme-linked immunosorbent assay (ne-ELISA) that combines the power of enzymatic conversion of a bound substrate with electronic detection is demonstrated. This novel configuration produces a local enzyme-mediated pH change proportional to the bound ligand concentration. It is shown that nanowire FETs configured as pH sensors can be used for the quantitative detection of interleukin-2 in physiologically buffered solution at concentrations as low as 1.6 pg mL(-1). By successfully bypassing the Debye screening inherent in physiological fluids, the ne-ELISA promises wide applicability for ligand detection in a range of relevant solutions.