Microfluidic platforms for the screening of solid forms of candidate drugs

This paper reports a microfluidic platform to screen for crystallization conditions of candidate drugs (CD). Identification of solid forms of CDs on a microfluidic platform provides critical information regarding a given CD's physiological properties, which is crucial in the selection of the most promising CDs. On-chip screening for crystallization conditions is carried out through three different methods: free interface diffusion, temperature control, and/or directed evaporation. The microfluidic chips are comprised of 8 × 12 arrays of wells, with the whole chip consuming a total volume of only 5 μl. Key features of the chips include combinatorial mixing to generate different conditions, improved solvent compatibility, minimized solvent absorption and evaporation, and solvent containment through the incorporation of a combination of traditional pneumatic valves that are open in rest, as well as new, passively closed valves. These microfluidic chips allow for many more crystallization conditions to be screened with the same, limited, amount of a CD available in the initial drug development activities. Here we validate these chips through the screening of solid forms of acetaminophen.