Control and Measurement of the Phase Behavior of Aqueous Solutions Using Microfluidics

Abstract

A microfluidic device denoted the Phase Chip has been designed to measure and manipulate the phase diagram of multi-component fluid mixtures. The Phase Chip exploits the permeation of water through poly(dimethylsiloxane) (PDMS) in order to controllably vary the concentration of solutes in aqueous nanoliter volume microdrops stored in wells. The permeation of water in the Phase Chip is modeled using the diffusion equation and good agreement between experiment and theory is obtained. The Phase Chip operates by first creating drops of the water/solute mixture whose composition varies sequentially. Next, drops are transported down channels and guided into storage wells using surface tension forces. Finally, the solute concentration of each stored drop is simultaneously varied and measured. Two applications of the Phase Chip are presented. First, the phase diagram of a polymer/salt mixture is measured on-chip and validated off-chip and second, protein crystallization rates are enhanced through the manipulation of the kinetics of nucleation and growth. Keywords microfluidics; PDMS; water permeation; high throughput protein crystallization; phase diagram; nucleation; growth; Ostwald ripening Microfluidic instruments are capable of precisely manipulating sub-nanoliter quantities of fluids. Their purpose is to vastly reduce the amount of fluids used in chemical processing and provide accurate delivery of fluids in a defined geometry on the micron length scale with a temporal accuracy of milliseconds. A microfluidic device can include channels for transporting fluids, valves for controlling flow, nozzles to create drops, pumps to propel fluids, storage chambers, and mixers to homogenize multiple fluid streams and drops 1-4 . To this panoply of components we add the abilities to store drops and to controllably vary the water content of stored drops. Each of these primitive functions can be combined in numerous ways to create complex devices optimized for specific tasks. Other powerful features of microfluidics are the ease and rapidity of their construction and the low cost of materials. This paper reports the development of a microfluidic device, the Phase Chip shown in Figure 1a, which is designed to determine the phase diagram of multi-component fluid mixtures. The

Droplet confinement and leakage: Causes, underlying effects, and amelioration strategies

“…The bottom of the device also has less capacity for the absorption of water and hence reaches saturation faster than the walls, causing wetting to occur on this surface preferentially. 61 Generalised substrate-driven droplet deformation tends to occur in regions of high shear stress, i.e., in channels rather than chambers and in the centre of channels rather than at their edges. This suggests that either the surface treatment at this differential surface is worse in channels or it erodes faster in channels due to higher flow rates.…”

“…This is caused either by Ostwald Ripening 8 of the droplet population or by the partitioning of water from the droplets into the PDMS device (see supplementary material 28 for further information). 61 Information on variables that affect droplet shrinkage are discussed as amelioration strategies in Sec. II E. When droplet shrinkage occurs due to partitioning of water into the PDMS device, it is analogous in mechanism to the substrate-driven droplet spreading failure mode, where the wetting of the droplet on the device surface is followed by partitioning of the aqueous droplet contents into the PDMS elastomer, causing fission of the droplet in the z-axis.…”

“…Conversely, the loss of droplet content due to shrinkage in unsaturated PDMS devices can be leveraged to allow control of the droplet volume. 61 However, when using non-fluorinated oils for droplet creation, the device can instead be stored in mineral oil or silicone oil, though the later is hard to remove from the PDMS surface to enable visualisation. As can be seen in Table S1 in the supplementary material, 28 storage of droplets in mineral oil-soaked devices, for example, removes significant droplet failure modes when compared to systems where droplets were stored in water-soaked devices, such as localised substrate-driven droplet deformation, satellite droplet formation, and substrate-driven droplet spreading.…”

Enhanced transcription rates in membrane-free protocells formed by coacervation of cell lysate

“…We and others have previously shown how droplet-based microfluidic devices can be used to study the kinetics of in vitro expression of a reporter protein using commercial in vitro transcription and translation kits (21-23). The volume of droplets can be controlled via osmotic transport of water to and from reservoir channels filled with concentrated salt solutions (24,25) and separated from the droplet traps (25) by a thin (15-μm) polydimethylsiloxane (PDMS) membrane (Fig. S1F).…”

Design and application of a microfluidic device for protein crystallization using an evaporation-based crystallization technique

“…The use of a microdialysis-based microfluidic device was another important technique for protein crystallization Shim, Cristobal, Link, Thorsen, Jia et al, 2007), which used dialysis to supersaturate the protein solution. The protein crystals grown in polydimethylsiloxane (PDMS) (Hansen et al, 2006) and polymethylmethacrylate (Sauter et al, 2007) devices can be analyzed directly on-chip by X-ray diffraction.…”