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Nanoparticle suspensions are used in numerous biomedical applications ranging from sensing and diagnostics to in vivo therapeutic agents and drug delivery mechanisms. One key challenge in developing these technologies is engineering particles that remain stable in the presence of physiological salt concentrations and different pH regimes encountered in applications. Here, we show an approach for high-throughput characterization of nanoparticle stability by directly measuring the interaction energy profiles between nanoparticles and surfaces. As nanoparticles are trapped and propelled along an optical waveguide, they scatter light. Our technique takes advantage of the confined Brownian motion exhibited by the particles as they fluctuate about the equilibrium position between the optical and particle-surface interaction forces. In this way, unlike colloidal probe atomic force microscopy, this technique is capable of making measurements that are not limited by thermal noise, and capable of mapping interaction energy profiles on the sub-kT scale, driven by sub-pN forces. We demonstrate direct measurement of the interactions between protein-coated gold nanoparticles with 50 nm diameters and surfaces in a variety of experimental conditions including changes in specific ions present, overall ionic strength and pH, giving insight into the dynamics of these biologically relevant systems at the nanoscale. These direct measurements on particles with sub-100 nm diameters offer new insights into suspension stability missed by indirect measurements such as absorbance spectroscopy, zeta-potential, and dynamic light scattering, and allow for the detailed study of sub-populations in a heterogeneous sample. Additionally, the sub-pN force resolution makes this a suitable platform for fundamental biophysical studies.
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