@article { , title = {Systematic investigation of protein phase behavior with a microfluidic formulator}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {101}, number = {40}, year = {2004}, note = {Times Cited: 9}, pages = {14431-14436}, abstract = {We demonstrated a microfluidic device for rapidly generating complex mixtures of 32 stock reagents in a 5-nl reactor. This "formulation chip" is fully automated and allows thousands of experiments to be performed in a single day with minimal reagent consumption. It was applied to systematically study the phase behavior of the protein xylanase over a large and complex chemical space. For each chemical formulation that demonstrated a pronounced effect on solubility, the protein phase behavior was completely mapped in the chip, generating a set of empirical phase diagrams. This ab initio phase information was used to devise a rational crystallization screen that resulted in 72-fold improvement in successful crystallization hits compared with conventional sparse matrix screens. This formulations tool allows a physics-based approach to protein crystallization that may prove useful in structural genomics efforts.}, keywords = {egg-white lysozyme, crystal-growth, trichoderma-reesei, crystallization, solubility, diagram, nucleation, assay}, URL = {://000224369600024}, author = {Hansen, C. L. and Sommer, M. O. A. and Quake, S. R.} }