BACKGROUND: Over 170 million people, more than 3% of the world's population, suffer from the hepatitis C virus (HCV) infection and the rate of death from liver-related mortality to HCV has increased. In respect of this, the development of assays for biological imaging should be urgently considered as an essential factor in diagnosis. RESULTS: A novel HCV-detecting technique using a nanoparticle-supported aptamer probe was demonstrated. With the aid of nanoparticle quantum dots (QDs) with carboxyl group as an imaging probe, and 5'-end-amine-modified RNA oligonucleotide as a capturing probe, target HCV NS3 was visually detected on chip. The QDs-based RNA aptamer for HCV NS3 showed high selectivity and specificity against other protein such as BSA. The detection limit of HCV N53 protein was 5 ng mL(-1) level. CONCLUSION: With a novel strategy for protein-aptamer interaction, the feasibility of applying QDs-based fluorescent detection technique to HCV viral protein assay for the development of a protein biochip was demonstrated. This scheme of QDs-mediated imaging with a target-oriented specific RNA aptamer for the detection of infectious HCV diseases provides an efficient strategy and a promising new platform for monitoring applications. (C) 2010 Society of Chemical Industry