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Abstract

Droplet-based microfluidics offers tremendous capabilities for high-throughput-screening systems, but so far, the dearth of appropriate analytical assays has limited its widespread application. Here, we present a novel, label-free sensor method for the detection of biochemical reactions inside of micron-sized droplets. The method exploits the osmotically driven change in droplet size as a quantitative marker of the total osmolarity. Changes in osmolarity, which originate, for example, from the metabolic activity of cells, can be detected down to a few mOsm/l. We characterize the sensor system by investigating mixtures of two types of monodisperse aqueous droplets in oil, containing various, fixed amounts of solute. Differing concentrations of solute induce water flow between the droplets through the oil, compensating for the osmotic pressure until equilibrium is reached. The flux is mediated by the diffusion of reverse micelles and increases with increasing differences in solute concentration. We apply the method to monitor and quantify the metabolic activity of encapsulated yeast at the single cell level and demonstrate its use for live/dead assays. Due to its simple and broadly applicable principle, our novel sensor method provides a powerful analytical tool for screening applications, and advances the evolution of high-throughput-screening systems with droplet-microfluidics.