Sensitive detection of small molecule-protein interactions on a metal-insulator-metal label-free biosensing platform.

The need to develop label-free biosensing devices that enable rapid analyses of interactions between small molecules/peptides and proteins for post-genomic studies has increased significantly. We report a simple metal-insulator-metal (MIM) geometry for fabricating a highly sensitive detection platform for biosensing. MIM substrates consisting of an Au-PMMA-Ag nanolayer were extensively studied using both theoretical and experimental approaches. By monitoring reflectivity changes at the normal incidence angle, we observed molecular interactions as the thickness of the biolayer increased on the substrate surface. These interactions included the adsorption of various proteins (Mw=6-150 kD) and interactions between small molecules (Mw≤2 kD) and the immobilized proteins. The interaction of designed monosaccharide-modified designed peptides with various lectins was also clearly detected. These interactions could not be detected by the conventional Au-only substrate. Thus, the MIM approach affords a powerful label-free biosensing device that will aid our understanding of protein interactions and recognition.