Zinc Oxide @ Silica Core/Shell Microspheres for Single-Molecule Force Microscopy in Aqueous and Nonaqueous Solvents

Abstract

Optical tweezers provide a platform for both manipulating and probing the chemistry of a single polymer molecule tethered between dielectric microspheres. It has been challenging to adapt this technology to organic solvents, in part due to the limited availability of optically trappable materials possessing the necessary diameter and refractive index contrast. Here we report on the development of broadly accessible optical trapping in aqueous and organic solvents that utilizes zinc oxide-silica core/shell microspheres (beads). The addition of a silica shell allows otherwise highly scattering zinc oxide nanoparticles to be stably trapped and readily functionalized. Trapping was observed in water, chloroform, tetrahydrofuran, and ethyl acetate. We demonstrate how these beads can be used to measure the force–extension curves of DNA and poly­(methyl methacrylate) respectively utilizing antibody/antigen complementation or strain-promoted azide/alkyne cycloaddition to form linkages in situ. In the latter, a strong, contiguous chain of covalent bonds is formed between the microspheres; therefore, UV bond photolysis was used to count the number of rupture steps and control for single-molecule link formation. In addition to being trappable in many solvents, ZnO@SiO2 core/shell beads can be used as solid support during harsh synthetic conditions and can be readily prepared in the presence of atmospheric oxygen.

Simultaneous Force and Darkfield Measurements Reveal Solvent-Dependent Axial Control of Optically Trapped Gold Nanoparticles

“…24 We note that Au NPs can remain dispersed in all solvents for days and even weeks without deteriorating, demonstrating true stability in both aqueous and organic conditions. 4 We can now compare trapping efficiency of Au NPs across varying solvent conditions. According to standard models, it is expected that trapping of noble metal nanoparticles should be more efficient in organic solvents, which have a higher RI than water.…”

“…Despite this demonstrated potential for studying single molecules and interactions, the OT technique has not been utilized in nonaqueous conditions to probe the structure, mechanics, and energetics of nonbiological polymers, molecular machines, and solution-based chemistry. This gap is a result of incompatibility of most existing OT probes with organic solvent environments. − A lack of appropriate probes has also prevented OT from being applied to the growing field of chemical imaging using force-detected absorption spectroscopy, which has so far been almost exclusively performed with AFM at lower force resolution. − Here, we demonstrate optical trapping in common organic solvents using gold nanoparticles (Au NPs). We leverage our instrument’s unique ability to trap, image, and detect force of noble metal NP simultaneously to characterize, for the first time, and explain solvent-dependent trapping effects and dynamics of Au NP.…”

“…In contrast, a commonly used higher index material, polystyrene (PS) ( n PS = 1.57), has a sufficient RI mismatch but breaks down in common organic solvents. Recent studies have used synthetic approaches to increase the effective RI of silica microspheres through the inclusion of a polystyrene or zinc oxide core. , However, these nonmetallic probes are still not appropriate for force-detected spectroscopy where high polarizability is necessary.…”

“…We observe that, for all solvents, the particle displacements are normally distributed as expected for a quadratic confining potential, which indicates stable trapping in all solvents . We note that Au NPs can remain dispersed in all solvents for days and even weeks without deteriorating, demonstrating true stability in both aqueous and organic conditions …”

“…Recent studies have used synthetic approaches to increase the effective RI of silica microspheres through the inclusion of a polystyrene or zinc oxide core. 3,4 However, these nonmetallic probes are still not appropriate for force-detected spectroscopy where high polarizability is necessary. An alternative trapping probe material for OT proposed here is a noble metal, such as gold or silver.…”