Simple, robust storage of drops and fluids in a microfluidic device.

We describe a single microfluidic device and two methods for the passive storage of aqueous drops in a continuous stream of oil without any external control but hydrodynamic flow. Advantages of this device are that it is simple to manufacture, robust under operation, and drops never come into contact with each other, making it unnecessary to stabilize drops against coalescence. In one method the device can be used to store drops that are created upstream from the storage zone. In the second method the same device can be used to simultaneously create and store drops from a single large continuous fluid stream without resorting to the usual flow focusing or T-junction drop generation processes. Additionally, this device stores all the fluid introduced, including the first amount, with zero waste. Transport of drops in this device depends, however, on whether or not the aqueous drops wet the device walls. Analysis of drop transport in these two cases is presented. Finally, a method for extraction of the drops from the device is also presented, which works best when drops do not wet the walls of the chip.

On-line laser Raman spectroscopic probing of droplets engineered in microfluidic devices.

Sub-nanolitre droplets engineered in microfluidic devices constitute ideal microreactors to investigate the kinetics of chemical reactions on the millisecond time scale. Up to date, fluorescence detection has been extensively used in chemistry and biology to probe reactants and resultant products within such nanodroplets. However, although fluorescence is a very sensitive technique, it lacks intrinsic specificity as frequently fluorescent labels need to be attached to the species of interest. This weakness can be overcome by using vibrational spectroscopy analysis. As an illustrative example, we use confocal Raman microspectroscopy in order to probe the concentration profiles of two interdiffusing solutes within nanolitre droplets transported through a straight microchannel. We establish the feasibility of the experimental method and discuss various aspects related to the space-time resolution and the quantitativeness of the Raman measurements. Finally, we demonstrate that the droplet internal molecular mixing is strongly affected by the droplet internal flow.

X-ray microfocussing combined with microfluidics for on-chip X-ray scattering measurements.

This work describes the fabrication of thin microfluidic devices in Kapton (polyimide). These chips are well-suited to perform X-ray scattering experiments using intense microfocussed beams, as Kapton is both relatively resistant to the high intensities generated by a synchrotron, and almost transparent to X-rays. We show networks of microchannels obtained using laser ablation of Kapton films, and we also present a simple way to perform fusion bonding between two Kapton films. The possibilities offered using such devices are illustrated with X-ray scattering experiments. These experiments demonstrate that structural measurements in the 1 A-20 nm range can be obtained with spatial resolutions of a few microns in a microchannel.

Using Microfluidics to Decouple Nucleation and Growth of Protein Crystals.

A high throughput, low volume microfluidic device has been designed to decouple the physical processes of protein crystal nucleation and growth. This device, called the Phase Chip, is constructed out of poly(dimethylsiloxane) (PDMS) elastomer. One of the Phase Chip's innovations is to exploit surface tension forces to guide each drop to a storage chamber. We demonstrate that nanoliter water-in-oil drops of protein solutions can be rapidly stored in individual wells thereby allowing the screening of 1000 conditions while consuming a total of only 10 mug protein on a 20 cm(2) chip. Another significant advance over current microfluidic devices is that each well is in contact with a reservoir via a dialysis membrane through which only water and other low molecular weight organic solvents can pass, but not salt, polymer, or protein. This enables the concentration of all solutes in a solution to be reversibly, rapidly, and precisely varied in contrast to current methods, such as the free interface diffusion or sitting drop methods, which are irreversible. The Phase Chip operates by first optimizing conditions for nucleation by using dialysis to supersaturate the protein solution, which leads to nucleation of many small crystals. Next, conditions are optimized for crystal growth by using dialysis to reduce the protein and precipitant concentrations, which leads small crystals to dissolve while simultaneously causing only the largest ones to grow, ultimately resulting in the transformation of many small, unusable crystals into a few large ones.

Control and measurement of the phase behavior of aqueous solutions using microfluidics.

A microfluidic device denoted the Phase Chip has been designed to measure and manipulate the phase diagram of multicomponent 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.

Generation of polymerosomes from double-emulsions.

Diblock copolymers are known to spontaneously organize into polymer vesicles. Typically, this is achieved through the techniques of film rehydration or electroformation. We present a new method for generating polymer vesicles from double emulsions. We generate precision water-in-oil-in-water double emulsions from the breakup of concentric fluid streams; the hydrophobic fluid is a volatile mixture of organic solvent that contains dissolved diblock copolymers. We collect the double emulsions and slowly evaporate the organic solvent, which ultimately directs the self-assembly of the dissolved diblock copolymers into vesicular structures. Independent control over all three fluid streams enables precision assembly of polymer vesicles and provides for highly efficient encapsulation of active ingredients within the polymerosomes. We also use double emulsions with several internal drops to form new polymerosome structures.