From Macrofluidics to Microfluidics for the Crystallization of Biological Macromolecules

This review presents the goals and principles of microfluidic technologies applied to the crystallization of biological macromolecules. A comparison of the devices that are available commercially or described in the literature summarizes the current state-of-the-art in microfluidics. A novel chip based on the counter-diffusion of solute molecules playing the role of crystallization agents is described. Inside the microfluidic channels composing the chip mass transport essentially occurs by diffusion. The chip is made of a rigid polymer that is impermeable to gases and compatible with crystal examination and monitoring in polarized light. The selected material is also transparent to X-rays, and three-dimensional protein structures can be determined from crystals contained inside this device using X-ray diffraction data collected on a synchrotron source. The outstanding quality of the electron-density maps demonstrates that on-chip crystal analysis is feasible. The replacement of conventional crystallization setups by inexpensive microfluidic chips for screening best crystallization agents and automated crystal diffraction analysis is discussed.