Using Microfluidics to Observe the Effect of Mixing on Nucleation of Protein Crystals

• Published in: Journal of the American Chemical Society Vol. 127; no. 27; pp. 9672 - 9673
• Main Authors: Chen, Delai L, Gerdts, Cory J, Ismagilov, Rustem F
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 13.07.2005
• Subjects: Biological and medical sciences; Crystallization - methods; Fundamental and applied biological sciences. Psychology; General aspects; Microfluidics - instrumentation; Microfluidics - methods; Molecular biophysics; Proteins - chemistry; Crystal growth; Mixing quality; Fluidic devices; Crystal nucleation; Flow velocity; Biological macromolecule; Microminiaturization
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja052279v

This paper analyzes the effect of mixing on nucleation of protein crystals. The mixing of protein and precipitant was controlled by changing the flow rate in a plug-based microfluidic system. The nucleation rate inversely depended on the flow rate, and flow rate could be used to control nucleation. For example, at higher supersaturations, precipitation happened at low flow rates while large crystals grew at high flow rates. Mixing at low flow velocities in a winding channel induces nucleation more effectively than mixing in straight channels. A qualitative scaling argument that relies on a number of assumptions is presented to understand the experimental results. In addition to helping fundamental understanding, this result may be used to control nucleation, using rapid chaotic mixing to eliminate formation of precipitates at high supersaturation and using slow chaotic mixing to induce nucleation at lower supersaturation.