(420b) Microfluidic Platforms for Pharmaceutical Screening

Efficient screens for crystal formation and polymorph identification are an expensive and critical step in active pharmaceutical ingredient (API) development. Microfluidic applications have the potential to improve high throughput screens for crystallization and polymorph identification by reducing reaction volumes, improving control in both mixing and evaporation and drastically increasing the number of conditions that can be screened [1].

Presently, macroscale approaches use on the order of 5 µl of CD per condition tested [2]. Here we present a microfluidic platform that screens for crystallization of candidate drugs (CD) while using as little as 50 nl of solution per well with as many as 96 wells on one platform. This platform employs three modes of operation to control supersaturation and thereby induce nucleation and growth of CDs: evaporation, temperature control and free interface diffusion. These three methods were chosen because of their propensity for inducing nucleation and their wide use on the macroscale [3]. By utilizing these techniques for control of supersaturation in microfluidic networks, we generate large combinatorial combinations of different crystallization conditions with respect to CD concentration and precipitant concentration and composition, enabling improved efficiency in crystal screening and polymorph identification. Additionally, the platform has been modified such that analysis of the crystals can be obtained with raman spectroscopy without removing crystals from the wells (e.g. on-chip).

This presentation will cover the design, fabrication, and application of the microfluidic platform. The utility will be demonstrated with model compounds such as Acetaminophen, Naproxen, and Sulfathiazole.

References

[1] C. Hansen, E. Skordalakes, J. Berger, S. Quake, Proc. Nat'l Acad. Sci., 99, 2002, 16531-6. [2] S. Talreja, D.Y. Kim, A.Y. Mirarefi, C.F. Zukoski, P.J.A. Kenis, J. Appl. Crystallography, 2005, 38, 988-995. [3] C. Gardner, O. Almarsson, H. Chen, S. Morissette, Computers and Chemical Engineering, 28, 2004, 943?953; E. Ware and D. Lu, Pharmaceutical Research, 21, 2004, 177-184. [4] B. Schudel, C. Choi, B. Cunningham, P. J. A. Kenis, Lab on a Chip, 2009 9(12): 1676-1680.