(606b) Octanol-Water Partitioning Coefficient Measurements in Picoliter Drops Using a Segmented Flow Microfluidic Device

Partitioning of pollutants between water and organic phases is critical in determining their fate in the environment, bioavailability and toxicity. The spatial and temporal mobility of a substance is largely determined by its solubility in water. Currently, the EPA uses partition coefficients to predict the environmental fate, aquatic toxicity and bioaccumulation instead of measurements like molecular weight, conformation, hydration states, ionic charge, etc. Partitioning into an organic phase (typically octanol) is often used as a measure of bioavailability for herbicides, pesticides, pharmaceuticals, and potentially toxic chemicals. The octanol-water partition coefficient is a prerequisite for testing biological degradation and bioaccumulation in water for which the EPA Office of Prevention, Pesticides, Toxic Substances (OPPTS) publishes Harmonized Test Guidelines. Currently, octanol?water partitioning is an important physiochemical property of pharmaceutical drugs and agrochemicals and is required measurement by legislation as part of the profile for high volume production chemicals. The partition coefficient is measured by a variety of methods, with the most common being some variant of the shake-flask method. The shake-flask method typically requires several days to complete and liters of solution.

In this presentation, a novel microfluidic method for measuring octanol-water partitioning coefficients in single picoliter drops is described. Picoliter water droplets are generated in octanol carrier fluid within a T-shaped segmented flow device fabricated in Poly(dimethylsiloxane). The partition coefficient of the fluorescent dyes are measured as a function of pH using epifluorescence microscopy. The results agree well with published measurements based on the batch shake-flask method. The microfluidic partitioning measurements are conducted in minutes across thousands of picoliter droplets. The methods presented here are rapid, provide detailed statistics, and can be run in parallel enabling the simultaneous partitioning of thousands of compounds for combinatorial chemistry applications.