Solubility is the primary physicochemical property determining the absorption and bioavailability of substances. Here, we present an optofluidic single-particle technique for microscale equilibrium solubility determination, based on on-chip hydrodynamic particle trapping and optical particle size monitoring. The method combines the rapidity, universality, and substance sparing nature of physical analysis, with the accuracy traditionally associated with chemical analysis. Applying the diffusion layer theory, we determined the equilibrium solubility from individual pure substance microparticles of as little as 14 μg in initial mass, in a matter of seconds to minutes. The reduction in time and substance consumption, when compared to the golden standard method, is above 2 orders of magnitude. With a simultaneous improvement above 3-fold in accuracy of the solubility data, the applicability of optofluidics based analytics for small-scale high-throughput quantitative solubility and biological activity screening is demonstrated.
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