Theoretical and Experimental Investigation of Ligand-Induced Particle–Particle Interactions

Studying particle–particle interactions is important in understanding the performance and limits of nanoparticle-based biosensors. Gold nanoparticles (AuNPs) are among the most popular nanomaterials in biosensing due to their unique optical and chemical properties. When AuNPs are functionalized with a ligand of interest, the AuNPs aggregate upon binding to the target. This results in a localized surface plasmon resonance frequency change, which can be visualized with a dark-field microscope. This target-mediated aggregation is used in sensing various biomolecules. Due to the complex nature of functionalized AuNPs, to date, most studies have been focused on explaining the AuNP behavior in a case-specific manner. We present a general theoretical model for target-mediated aggregation in biosensing. This simple theory is solely based on statistics and thermodynamic equilibrium. DNA functionalized AuNPs were used as the experimental model to verify the theory. The theoretical model was used in predicting the dose–response curve for different conditions: changing probe DNA density, dissociation constant, and particle concentration with an excellent agreement to experimental results. This validated theory improves our understanding of particle–particle interactions and can omit the need for time-consuming parameter optimization in particle-based biosensor development.