High-throughput, cell-based assays require small sample volumes to reduce assay costs and to allow for rapid sample manipulation. However, further miniaturization of conventional microtiter plate technology is problematic due to evaporation and capillary action. To overcome these limitations, we describe droplet-based microfluidic platforms in which cells are grown in aqueous microcompartments separated by an inert perfluorocarbon carrier oil. Synthesis of biocompatible surfactants and identification of gas-permeable storage systems allowed human cells, and even a multicellular organism (C. elegans), to survive and proliferate within the microcompartments for several days. Microcompartments containing single cells could be reinjected into a microfluidic device after incubation to measure expression of a reporter gene. This should open the way for high-throughput, cell-based screening that can use >1000-fold smaller assay volumes and has approximately 500x higher throughput than conventional microtiter plate assays.

Drops of water-in-fluorocarbon emulsions have great potential for compartmentalizing both in vitro and in vivo biological systems; however, surfactants to stabilize such emulsions are scarce. Here we present a novel class of fluorosurfactants that we synthesize by coupling oligomeric perfluorinated polyethers (PFPE) with polyethyleneglycol (PEG). We demonstrate that these block copolymer surfactants stabilize water-in-fluorocarbon oil emulsions during all necessary steps of a drop-based experiment including drop formation, incubation, and reinjection into a second microfluidic device. Furthermore, we show that aqueous drops stabilized with these surfactants can be used for in vitro translation (IVT), as well as encapsulation and incubation of single cells. The compatability of this emulsion system with both biological systems and polydimethylsiloxane (PDMS) microfluidic devices makes these surfactants ideal for a broad range of high-throughput, drop-based applications.

Soft lithography using polydimethylsiloxane (PDMS) allows one to fabricate complex microfluidic devices easily and at low cost. However, PDMS swells in the presence of many organic solvents significantly degrading the performance of the device. We present a method to coat PDMS channels with a glass-like layer using sol-gel chemistry. This coating greatly increases chemical resistance of the channels; moreover, it can be functionalized with a wide range of chemicals to precisely control interfacial properties. This method combines the ease of fabrication afforded by soft-lithography with the precision control and chemical robustness afforded by glass.

Double emulsions are useful templates for microcapsules and complex particles, but no method yet exists for making double emulsions with both high uniformity and high throughput. We present a parallel numbering-up design for microfluidic double emulsion devices, which combines the excellent control of microfluidics with throughput suitable for mass production. We demonstrate the design with devices incorporating up to 15 dropmaker units in a two-dimensional or three-dimensional array, producing single-core double emulsion drops at rates over 1 kg day(-1) and with diameter variation less than 6%. This design provides a route to integrating hundreds of dropmakers or more in a single chip, facilitating industrial-scale production rates of many tons per year.

The following article is based on the Symposium X presentation given by David A. Weitz (Harvard University) on April 11, 2007, at the Materials Research Society Spring Meeting in San Francisco. The article describes how simple microfluidic devices can be used to control fluid flow and produce a variety of new materials. Based on the concepts of coaxial flow and hydrodynamically focused flow, used alone or in various combinations, the devices can produce precisely controlled double emulsions (droplets within droplets) and even triple emulsions (double emulsions suspended in a third droplet). These structures, which can be created in a single microfluidic device, have various applications such as encapsulants for drugs, cosmetics, or food additives.

A microfluidic melt emulsification method for encapsulation and release of actives is presented. Using a water-in-oil-inwater (W-O-W) double emulsion template, solid capsules can be formed by freezing the middle shell phase. Actives encapsulated inside the solid shell can be controllably and rapidly released by applying a temperature trigger to melt the shell. The choice of the shell materials can be chosen to accommodate the storage and release temperatures specific to the applications. In addition, we have also demonstrated the same concept to encapsulate multiple actives in multicompartment capsules, which are promising as multifunctional capsules and microreactors.

For many applications in microfluidics, the wettability of the devices must be spatially controlled. We introduce a photoreactive sol-gel coating that enables high-contrast spatial patterning of microfluidic device wettability.

Amorphous nanoparticles (a-NPs) have physicochemical properties distinctly different from those of the corresponding bulk crystals; for example, their solubility is much higher. However, many materials have a high propensity to crystallize and are difficult to formulate in an amorphous structure without stabilizers. We fabricated a microfluidic nebulator that can produce amorphous NPs from a wide range of materials, even including pure table salt (NaCl). By using supersonic air flow, the nebulator produces drops that are so small that they dry before crystal nuclei can form. The small size of the resulting spray-dried a-NPs limits the probability of crystal nucleation in any given particle during storage. The kinetic stability of the a-NPs—on the order of months—is advantageous for hydrophobic drug molecules.