Biomarkers are currently used for detection of diseases and monitoring therapeutic progresses in diagnostics. The accurate measurement of biomarkers in human patient samples is exceedingly important requirement for any analytical method. This project aims to develop an experimental demonstrator designed to provide pertinent solutions to three unmet medical needs in diagnostics: (1) high sensitivity; (2) high specificity and (3) label-free detection of disease biomarkers. Specifically, a novel biosensing nanotechnology will be implemented by coupling a new class of high affinity biorecognition elements called aptamers at the surface of plasmonic nanoplatforms recently developed in our laboratory. While the aptamers attached onto the metallic surface can specifically recognize the target molecules (biomarkers), the signal transduction will be based on ultrasensitive Surface Enhanced Raman Scattering (SERS). SERS has previously demonstrated its analytical performance toward “single-molecule sensitivity” and ability to identify and discern biomolecules by their spectral “Raman fingerprint” signature. By exploiting the complementary expertise of three research centers in SERS spectroscopy, chemistry and surface engineering, and fabrication and characterization of plasmonic nanoplatforms we expect to provide the feasibility of aptamer-modified SERS nanosensor for high sensitivity, high specificity and label-free detection of some relevant disease biomarkers. The as-fabricated “microchip” inserted in a Raman spectrometer to collect the SERS signal from the targeted biomarkers can offer unique characteristics, competitive advantages compared to other detection systems in the market and real potential for technology transfer.