Highly sensitive thermal detection of thrombin using aptamer-functionalized phase change nanoparticles

Abstract

This paper describes a novel thermal biosensing technique for the highly sensitive and selective detection of thrombin using RNA aptamer-functionalized phase change nanoparticles as thermal probes. The presence of thrombin in solution leads to attachment of nanoparticles onto a substrate modified with the same aptamer by forming sandwiched complexes. The phase changes of nanoparticles from solid to liquid adsorb heat energy and generate sharp melting peaks during linear temperature scans, where the positions and areas of the melting peaks reflect the presence and the amount of thrombin, respectively. A detection sensitivity of 22 nM is achieved on flat aluminum surfaces, and the sensitivity can be enhanced by four times using silicon nanopillar substrates that have higher surface area. The thermal detection is immune to colored species in solution and has been used directly to detect thrombin in serum samples. By combining the high specificity of aptamers and the large surface area of silicon nanostructures, the thermal signals obtained during phase change of nanoparticles provide a highly sensitive, selective and low-cost method for thrombin detection.