Electric control of droplets in microfluidic devices.

The precision manipulation of streams of fluids with microfluidic devices is revolutionizing many fluid-based technologies and enabling the development of high-throughput reactors that use minute quantities of reagents. However, as the scale of these reactors shrinks, contamination effects due to surface adsorption and diffusion limit the smallest quantities that can be used. The confinement of reagents in droplets in an immiscible carrier fluid overcomes these limitations, but demands new fluid-handling technology. We present a platform technology based on charged droplets and electric fields that enables electrically addressable droplet generation, highly efficient droplet coalescence, precision droplet breaking and recharging, and controllable droplet sorting. This is an essential enabling technology for a high-throughput droplet microfluidic reactor. Networks of small channels are a flexible platform for the precision manipulation of small amounts of fluids. 2] The utility of such microfluidic devices depends critically on enabling technologies such as the microfluidic peristaltic pump, electrokinetic pumping, 5] and dielectrophoreticpump or electrowetting-driven flow; these technologies can form the essential building blocks for the assembly of fluidhandling modules. These modules can be used to perform a variety of key tasks including the measurement of precise aliquots of fluids, the combination of fluid streams, and the mixing of multiple fluid components. The assembly of such modules into complete systems provides a convenient and robust way to construct microfluidic devices. These have myriad uses; for example, high-throughput screening, the exploration of chemical phase diagrams, assays of biological molecules, single-cell analysis, and combinatorial approaches to protein crystallization can all be performed with only minimal consumption of reagents. However, virtually all microfluidic devices are based on flows of streams of fluids; this sets a limit on the smallest volume of reagent that can be used effectively because of the contaminating effects of diffusion and surface adsorption. As the dimensions of small volumes are decreased, diffusion becomes the dominant mechanism for mixing leading to dispersion of reactants. Moreover, surface adsorption of reactants, although small, can be highly detrimental at low concentrations and small volumes. As a result current microfluidic technologies cannot be reliably used for applications involving minute quantities of reagent—for example, bioassays at levels down to the single molecule are not easily performed. An approach that overcomes these limitations is the use of aqueous droplets in an immiscible carrier fluid; these droplets provide a well-defined, encapsulated microenvironment that eliminates cross-contamination or changes in concentration caused by diffusion or surface interactions. Droplets provide the ideal microcapsule that can isolate reactive materials, cells, or small particles for further manipulation and study. Moreover, by making droplets as small as one femtoliter, reactions of single biomolecules can be investigated. However, essentially all enabling technology for microfluidic systems developed thus far has focused on single-phase fluid flow, and there are few corresponding, active means to manipulate droplets. In particular, manipulating, mixing, and combining reagents in microfluidic geometries is much more difficult for droplets than for single streams, 20] especially when the droplets are stabilized with [*] Dr. D. R. Link, E. Grasland-Mongrain, A. Duri, F. Sarrazin, Prof. Z. Cheng, G. Cristobal, Prof. D. A. Weitz Department of Physics and DEAS Harvard University Cambridge, MA 02138 (USA) Fax: (+1)203-458-2514 E-mail: dlink@raindancetechnologies.com M. Marquez Los Alamos National Laboratory Chemistry Division Los Alamos, NM 87545 (USA) M. Marquez INEST Group Philip Morris USA Research Center Richmond, VA 23234 (USA) [**] This work was supported by Kraft Foods, Rhodia Corporation, and the NSF through the Harvard MRSEC (DMR-0213805 and DMR0243715). The authors thank H. A. Stone and M. P. Brenner for valuable discussions. Supporting information for this article is available on the WWW under http://www.angewandte. org or from the author. Communications