Protein−Salt−Water Solution Phase Diagram Determination by a Combined Experimental−Computational Scheme

Abstract

A continuously fed microfluidic chamber has been developed for determination of solution phase diagrams for protein−precipitant systems. Laminar flow and diffusion in the chamber create significant gradients in concentration, so crystals form in only part of the chamber. By combining observation of the location of the crystal-rich regions with a computer simulation of flow and transport in the chamber, a solution phase diagram is generated. The device was tested successfully on the well-studied lysozyme−NaCl−water system, and it was then used to determine a phase diagram for the lysozyme−NaNO3−water system, which has been shown to produce triclinic rather than tetragonal crystals but was not as well characterized.