Correlation of Capture Efficiency with the Geometry, Transport, and Reaction Parameters in Heterogeneous Immunosensors.

Abstract

Higher capture efficiency of biomarkers in heterogeneous immunosensors would enable early detection of diseases. Several strategies are used to improve the capture efficiency of these immunosensors including the geometry of the system along with the transport and reaction parameters. Having a prior knowledge of the behavior of the above parameters would facilitate the design of an efficient immunosensor. While the contributions of the transport and reaction parameters toward understanding of the mechanism involved in capture have been well studied in the literature, their effect in combination with the geometry of the sensors has not been explored until now. In this work, we have experimentally demonstrated that the capture efficiency of the antigen-antibody systems is inversely related to the size of the sensor patch. The experimental system was simulated in order to get an in-depth understanding of the mechanism behind the experimental observation. Further, the extent of heterogeneity in the system was analyzed using the Sips isotherm to obtain the heterogeneity index (α) and the reaction rate constant (K(D)) as fitted parameters for a sensor patch of 1.5 mm radius. The experimental kinetic data obtained for the same sensor patch matched reasonably with the simulation results by considering K(D) as the global affinity constant, which indicated that our system can be considered to be homogeneous. Our simulation results associated with the size dependency of the capture efficiency were in agreement with the trends obtained in our experimental observations where an inverse relation was observed owing to the fact that the mass-transfer limitation decreases with the decrease in the size of the sensor patch. The possible underlying mechanism associated with size dependency of capture efficiency was discussed based on the time-dependent radial variation of captured antigens obtained from our simulation results. A study on the parametric variation was further conducted for the nonmixed and mixed systems on the transport (Deff), reaction (K(D)), and geometric parameters (R). Two different correlations were established for the nonmixed and mixed systems between the capture efficiency (f) and a nondimensional number (t(D)/t(R)) consisting of the above-mentioned parameters. Such unified relations will be useful in designing heterogeneous immunosensors and can be extended to microfluidic immunosensors.