Theory of Selectivity of label-free nanobiosensors: A geometro-physical perspective

Modern label-free biosensors are generally far more sensitive and require orders of magnitude less incubation time compared to their classical counterparts. However, a more important characteristic regarding the viability of this technology for applications in genomics/proteomics is defined by the Selectivity, i.e., the ability to concurrently and uniquely detect multiple target biomolecules in the presence of interfering species. Currently, there is no theory of Selectivity that allows optimization of competing factors and there are few experiments to probe this problem systematically. In this article, we use the elementary considerations of surface exclusion, diffusion limited transport, and void distribution function to provide guidance for optimum incubation time required for effective surface functionalization, and to identify the dominant components of unspecific adsorption. We conclude that optimally designed label-free schemes can compete favorably with other assay techniques, both in sensitivity as well as in selectivity.