Taking advantage of the reversible association-dissociation between glutathione (GSH) and glutathione S-transferase (GST), we have developed a novel method by surface-functionalizing GSH on silicon nanowire field-effect transistors (SiNW-FET) and then anchoring a particular GST-fused protein for the studies of protein-protein interactions. The reversible surface functionalization method has been proven by analytical techniques, fluorescence imaging, atomic force microscopic imaging, and electrical measurements. The reversible GSH-GST functionality on the SiNW-FET has made this sensorial device consecutively reusable and calibratable, allowing for quantitative analysis. In this work, we have demonstrated that the biologically modified SiNW-FET can be used as a screening sensor for the future studies of biomolecular associations, such as protein-protein interactions, protein-DNA interactions, protein-carbohydrate interactions, etc. (C) 2009 Elsevier Ltd. All rights reserved.