Abstract: A nanostructural sensing substrate includes indium tin oxide (ITO) film coated upstanding silicon nanowires (ITO/USNWs). The ITO/USNWs are fabricated by coating an ITO film on USNWs, the density of which has been reduced using a facile Ag-assisted chemical etching method. Furthermore, the bioreceptor modified ITO/USNWs are developed to serve as the sensing substrate of the EGFETs device for label-free diagnosis of biomarker related diseases, such as Alzheimer's disease (AD), acute myocardial infarction, coronary artery disease (CAD), hepatic encephalopathy, lung fibrosis, Cushing's syndrome and cancers. The ITO-coated-USNWs are also used in nano-featured cell based biosensors (CBB) for electrically quantitative evaluation of drug release.