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.

An X-ray transparent microfluidic platform for screening of the phase behavior of lipidic mesophases

“…13 We established that the discrepancy between on-chip and macroscopic sample behavior observed here did not result from potential inaccuracies in the ratio of volumes of chambers. At the same time, the value of 173 Å is at variance with previously reported lattice parameters of Pn3m cubic phases of MO mixed with detergent solutions, 13,14,33 which typically do not exceed 135–145 Å under conditions similar to ours.…”

“…Although microfluidic platforms for phase behavior studies have been demonstrated, 25–41 reported systems are only applicable to low-viscosity solutions and typically rely on phase transitions driven by composition changes due to diffusion of solutes, 25,26,33–36 evaporation of water, 28–32,40–42 and osmotic stress. 37,38 Such platforms are not suitable for the formulation of viscous mesophases with strict pre-set ratios of volume or weight of components.…”

“…23,24 Microuidics offers the potential to automate metering and parallelize preparation of multiple samples at nanoliter scales, which makes it very attractive for the studies of the phase behavior. Although microuidic platforms for phase behavior studies have been demonstrated, [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] reported systems are only applicable to low-viscosity solutions and typically rely on phase transitions driven by composition changes due to diffusion of solutes, 25,26,[33][34][35][36] evaporation of water, [28][29][30][31][32][40][41][42] and osmotic stress. 37,38 Such platforms are not suitable for the formulation of viscous mesophases with strict pre-set ratios of volume or weight of components.…”

Droplet Interfacial Tensions and Phase Transitions Measured in Microfluidic Channels

“…Microevaporationbased approaches with a single initial phase of liquid without a carrier phase by precise pumping to control the evaporation rate have also been used (48,49). Flow-through approaches are also common where either droplets (50) or slugs of liquid (51)(52)(53) change phase rapidly while moving in a channel due to the thermodynamic conditions of the system. Other studies have employed co-flow-based systems in which the position of the interface determines the phase equilibrium (54,55).…”

Fluid dynamics in crystal growth: The good, the bad, and the ugly

“…Such limitations may be overcome by the suitable application of fluid flows that promote mass transfer of the solute via convection. Much experimental work has been devoted to this topic [24][25][26][27][28][29][30][31][32][33], and we have carried out extensive modeling studies of solution crystal growth systems [34][35][36][37][38][39][40][41][42][43][44].…”