Core-shell nanostructures for ultrasensitive detection of α-thrombin

We have synthesized a stable, sensitive and specific surface-enhanced Raman tag, and demonstrated its application in human α-thrombin detection. The tag consists of aptamer-modified core-shell nanoparticles with hydrophobic Au@Ag as core and silica as shell encapsulating Raman active molecules. By taking advantage of the Raman signal enhancement effect by metallic nanostructures, high stability and robustness of glass-coated core-shell nanostructures and the recognition capabilities of aptamers, we designed a sandwich detection for protein identification with high selectivity and sensitivity. In this way, we realized the ultrasensitive detection of α-thrombin. GDNs (glass-coated, dye-tagged nanoparticles), which were conjugated with oligonucleotides or antibodies, were extremely soluble in water, and had mechanical and chemical stability, easily controllable-size distribution and friendly biocompatibility. Specifically, the glass coating renders the particles amenable to use in many solvents without altering the Raman spectral response and makes agglomeration a nonfactor. All these merits open the door of the real applications in diagnostics or medical investigations in complex biofluids, such as human plasma and serum. Using the aptamer-modified GDNs as Raman tags, we successfully performed the detection of α-thrombin in human plasma. Furthermore, the overall method have been proved effective and selective, and may be implemented for multiplex target analysis simultaneously.