“We are now able to use microfluidics to study complex biochemical networks including blood coagulation (hemostasis) and protein crystallization.”

We recognized that standard single-phase microfluidic experiments were limited by two problems—slow mixing and the dispersion of solutes along the channel (which occurs even in the absence of flow). This manuscript describes our microfluidic system to overcome these limitations by localizing reagents within aqueous droplets, or "plugs," separated by water-immiscible carrier fluid, and utilizing chaotic advection to achieve rapid mixing within plugs.

Emulsions have been a focus of a broad range of work, including microfluidics, but this system described how droplet-based microfluidic systems may be used for performing chemical reactions and assays. For example, there is a simple method of forming plugs of multiple reagents at controlled concentrations—an essential component for performing reactions in plugs.

Dr. Rustem Ismagilov's most-cited paper with 218 cites to date: Kenis PJA, Ismagilov RF, Whitesides, GM, "Microfabrication inside capillaries using multiphase laminar flow patterning," Science 285(5424): 83-85, 1 July 1999. 218 cites. Dr. Rustem Ismagilov's paper(s) represented in the Research Front map with 100 cites to date: Song H, Tice JD, Ismagilov RF, "A microfluidic system for controlling reaction networks in time," Angew. Chem. Int. Ed. 42(7): 768-72, 2003. Source: Essential Science Indicators.

We also devised methods for splitting and merging these plugs to create complex microfluidic networks that can be used for high-throughput parallel analysis of samples. This system also enables the conversion of spatial evolution of chemical systems into temporal evolution (the conversion of distance into time).

This fundamental technology offers unprecedented control over chemical reaction networks on the nanoliter scale from milliseconds to years and paved the way for the use of microfluidics for many important chemical assays, including high-throughput screening and optimization of reaction conditions, organic reactions, kinetic assays, and protein crystallization, and even the synthesis of reaction networks on-chip.

My lab focuses on understanding complex biochemical systems at the organismal, network, and molecular levels. We developed droplet-based microfluidics to overcome the limitations of traditional microfluidics and extend the applicability of microfluidics to study these systems. We are now able to use microfluidics to study complex biochemical networks including blood coagulation (hemostasis) and protein crystallization.

Miniaturization and microfluidics are making a big impact across many fields, from engineering to biology. Technology is advancing at a rapid pace and tools are being developed to give us unprecedented abilities to control chemistry and biology on many time and length scales. We are working to take advantage of these advances and push the field in new directions.

We are particularly interested in the potential for microfluidics to bridge the gap between current and powerful analytical methods and the complex biological systems that are difficult to study because of size or time constraints. In addition, these systems are proving to be practically useful.

Microfluidic and other lab-on-a-chip technologies have innumerable practical applications in engineering, physics, biology, and chemistry. We and others have developed microfluidic technology to enable high-throughput crystallization of soluble and membrane proteins on the nanoliter scale for pennies per trial. In addition, there is a broad effort to develop high-throughput methods of performing reactions and assays in droplet-based systems.

Rustem F. Ismagilov
Department of Chemistry and Institute for Biophysical Dynamics
The University of Chicago
Chicago, IL, USA