Fluctuations of the number of adsorbed molecules in biosensors due to stochastic adsorption-desorption processes coupled with mass transfer

Abstract

We derived a simple theory of fluctuations of the equilibrium number of adsorbed molecules in biosensors, caused by the stochastic nature of adsorption-desorption (AD) processes coupled with mass transfer. The two-compartment model is used for approximation of the spatial dependence of analyte concentration in the reaction chamber, which is justified when a thin layer depleted of the analyte exists close to the surface on which the binding reaction occurs. By using the obtained analytical expression for the power spectral density of fluctuations we perform for the first time the quantitative analysis of the influence of the mass transfer on the fluctuations spectrum. For realistic parameter values, the influence of mass transfer proved to be significant, causing the increase in the fluctuations level of up to two orders of magnitude compared to the rapid mixing case. The dependences of the mass transfer influenced fluctuations spectrum on various parameters of the analyte-receptor binding process are also systematically investigated. The presented theoretical model of fluctuations enables good estimation of the AD noise, which affects the total noise and the minimal detectable signal of biosensors. It provides the guidelines for improvement of the limits of detection, and for optimization of detection methods. The theory is also proposed as a basis for development of highly sensitive methods for analyte detection and characterization of biomolecular binding processes, based on the measured fluctuations spectrum. It is applicable for various types of sensors whose operation principle relies on the adsorption process of analyte molecules.