Enhancing the sensitivity in optical biosensing by striped arrays and frequency-domain analysis

Abstract

Abstract An approach to enhance the sensitivity of optical biosensors is developed. It is based on patterning strips of biochemical probes and signal processing (frequency-domain analysis, FDA) to the resulting analytical data after a biorecognition assay. This paper introduces FDA, demonstrates for the first time its potential in real bioanalytical systems, describes its critical parameters, and discusses how to optimize them to efficiently exploit this approach for optical biosensing. The results show that FDA enables for the selective identification and removal of the undesired noise contributions from the analytical signal arising from a biorecognition event of interest, thus increasing signal-to-noise ratios and, therefore, enhancing the sensitivity of the analysis. In this study, we proof the concept with a model immunassay system for IgGs detection (BSA/anti-BSA) that achieves a sensitivity enhancement of up to 3 orders of magnitude, and then FDA is also demonstrated in a sandwich immunoassay to quantify casein that reaches a limit of detection of 4\u2009ng/mL (174\u2009pM). Beyond these particular assays, this work also addres to stablish the basis of this approach and to provide keys to stimulate future developments that expand the potential of FDA to other biorecognition assays, transduction systems, and applications.