A novel DNA sensor based on a polypyrrole substrate and nanoparticle labeled ODN probes was prepared and characterized. In this sensor type the DNA sample to be analyzed was physically entrapped into the polypyrrole film during electropolymerization. The resulting sensor film was then exposed to ODN probes in solution. Sensitive electrical readout was achieved by electrochemical impedance spectroscopy. A further amplification in sensor response (as compared to using unlabeled ODN probes) was achieved by tagging ODN probes with US nanoparticles. We suggest that the sensor response is caused by an increase in charge transfer resistance upon binding of complementary CdS-ODN nanoparticle probes. The selectivity of the sensor was tested with various match and mismatch sequences. By appropriate choice of hybridization conditions the sensor was able to robustly discriminate between the exact match and a two-point mismatch sequence. (c) 2005 Elsevier B.V. All rights reserved.