Silica-coated zinc oxide microspheres for single molecule force spectroscopy in aqueous and non-aqueous solvents

Optical tweezers have provided a revolutionary tool for single molecule biophysics, yet their application to problems in materials science and in organic solvent are still in their infancy. Here we report the synthesis of core/shell ZnO microspheres that can be used for both biological and chemical applications, due to their facile synthesis and trappability in different solvents. We show that addition of a 400 nm silica shell allows otherwise untrappable ZnO nanoparticles (r=255nm) to be stably trapped. Next, we demonstrate that these new beads allow for single molecule force-extension studies with optical tweezers utilizing either antibody/antigen complemention or strain-promoted azide/alkyne cycloaddition (SPAAC) to form linkages in situ. For the latter, we show how controlled UV ablation can be used to count the number of rupture steps to control for single molecule link formation in the presence of strong, all-covalent linkages. In addition to being trapped in many solvents, ZnO@SiO2 core/shell microspheres are tolerable of harsh synthetic conditions and can be synthesized without custom or oxygen-sensitive reagents.