Plasmonic nanomaterials reveal noble optical properties for next-generation biosensors. Nanoplasmonic biosensors have become simple, sensitive, smart, and consistent with advanced healthcare programs requirements. Notably, an individual nanoparticle analysis can yield unique target information, based on which the next-generation biosensor is revolutionary for end-point detection (single or multiplex), and can be functionally extended to biological phenomena monitoring. Here, we present a single nanoplasmonic sensing technology based on localized surface plasmon resonance for label-free and real-time detection of highly reliable cancer markers (mutant gene and telomerase) in clinical samples. The sensor specifically detects mutant DNA, and can detect telomerase from as few as 10 HeLa cells. This approach can be easily translated to detect other pathological targets with high sensitivity and specificity, and monitor key interactions between biomolecules such as nucleic acids and proteins during disease development in real time. This system has great potential to be further developed for on-chip and simultaneous analysis of multiple targets and interactions. (C) 2014 Elsevier B.V. All rights reserved.