Detection Limit for Optically Sensing Specific Protein Interactions in Free-solution

TL;DR

This paper develops an analytical model to estimate the detection limits of optical sensing for specific protein interactions in free solution, considering refractive index changes and applicable to various experimental setups.

Contribution

It introduces a general framework based on Maxwell Garnett theory and chemical kinetics for estimating optical detection limits of protein interactions, including un-tethered scenarios.

Findings

Model reveals significant deviation from linear optical response in BSI.

Highlights the importance of unidentified factors affecting optical signals.

Provides a tool for predicting detection sensitivity in optical protein sensing.

Abstract

Optical molecular sensing techniques are often limited by the refractive index change associated with the probed interactions. In this work, we present a closed form analytical model to estimate the magnitude of optical refractive index change arising from protein-protein interactions. The model, based on the Maxwell Garnett effective medium theory and first order chemical kinetics serves as a general framework for estimating the detection limits of optical sensing of molecular interactions. The model is applicable to situations where one interacting species is immobilized to a surface, as commonly done, or to emerging techniques such as Back-Scattering Interferometry (BSI) where both interacting species are un-tethered. Our findings from this model point to the strong role of as yet unidentified factors in the origin of the BSI signal resulting in significant deviation from linear optical response.