Quantitative Detection of Biological Nanoparticles in Solution via Their Mediation of Colocalization of Fluorescent Liposomes

Journal article, 2019

Detection of biomolecules and biological nanoparticles by means of induced aggregation of larger nanoparticles using light scattering as readout was first accomplished in the middle of the last century. Since then, technical advances together with novel nanomaterials have enabled more sophisticated readout schemes, paving the way for methods exploiting dual-probe hybridization for biomolecular or nonoparticle recognition that today can compete with established bioanalytical methods. Herein, we present a quantitative assay, with single-nanoparticle readout, utilizing receptor-containing cell-membrane mimics in the shape of approximately 100-nm lipid liposomes rather than conventional antibody-modified nanoparticles to enable detection of virus particles in solution. Specifically, the method is based on virus-mediated aggregation of differently fluorescent-labeled liposomes that contain the ganglioside GM1 receptor for the Simian Virus 40 (SV40). The aggregation kinetics of the differently colored liposomes is studied by monitoring the spatial colocalization level of the liposomes and a theoretical model that successfully represents aggregation kinetics versus virus concentration is proposed. The limits of detection are identified experimentally for our current setup and theoretically in a more general context. The consistency between theory and experiments suggests that the approach will be generically applicable for similar biosensing applications or for the study of related systems where natural interactions with cell-membrane components can be used to induce liposome aggregation.