Research in genomics and proteomics is constantly identifying -- by qualitative screening -- thousands of new molecules of proteins, DNA and RNA critical to health or responsible for a disease. Detailed understanding of the structure and function of these molecules is of fundamental importance to biology and medicine, but it is difficult to achieve by traditional methods, which are labor intensive and consume large amounts of samples. Microfluidics allows manipulations and monitoring of minute volumes of solutions, and is attractive as the key technology for overcoming limitations of traditional methods. However, microfluidic devices have not yet found widespread applications as research tools. An intense research effort is directed towards solving three problems of microfluidics: i) large dispersion of solution along the channels increases consumption of reagents and also makes long (minutes to days) time scales difficult to access; ii) slow mixing of solutions makes very short (tens of milliseconds and below) time scales inaccessible; mixing approaches that rely on turbulence prohibitively increase the sample consumption; iii) chemistry of internal surfaces of devices is important and has to be controlled. This multi-disciplinary program will begin by developing a new microfluidic technology that is universal -- it will be useful for quantitative, high-throughput experiments on time scales ranging from tens of microseconds to days. Dispersion will be eliminated by localizing reagents inside aqueous droplets encapsulated by an immiscible fluid. Mixing inside the droplets will be accelerated by using chaotic advection, rather than turbulence. Surface chemistry to which solutions are exposed will be controlled by careful choice of surfactants. This program will then demonstrate the utility of this technology for biomolecular functional and structural studies. It will be used as the basis for unique kinetics systems suitable for measurements of dynamics on time scales from tens of microseconds to seconds. This kinetics system will be applied to measurements of fast enzyme kinetics and early events in RNA folding. This technology will also be used for protein crystallization to control both short time scale events such as nucleation, and to control long time scale events such as growth. Finally, the program will develop methods for making these technologies user-friendly and implement them in laboratories of our collaborators. This technology will improve health by enabling basic research. It will not only enable measurements and experiments that are impossible to do today; it will also make these measurements rapid, economical, and accessible to a wide community of researchers in biology, biophysics, and bioengineering.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BECM (01))
Program Officer
Korte, Brenda
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Schools of Arts and Sciences
United States
Zip Code
Sun, Bing; Rodriguez-Manzano, Jesus; Selck, David A et al. (2014) Measuring fate and rate of single-molecule competition of amplification and restriction digestion, and its use for rapid genotyping tested with hepatitis C viral RNA. Angew Chem Int Ed Engl 53:8088-8092
Kline, Timothy R; Runyon, Matthew K; Pothiawala, Mohammad et al. (2008) ABO, D blood typing and subtyping using plug-based microfluidics. Anal Chem 80:6190-7
Pompano, Rebecca R; Li, Hung-Wing; Ismagilov, Rustem F (2008) Rate of mixing controls rate and outcome of autocatalytic processes: theory and microfluidic experiments with chemical reactions and blood coagulation. Biophys J 95:1531-43
Li, Liang; Boedicker, James Q; Ismagilov, Rustem F (2007) Using a multijunction microfluidic device to inject substrate into an array of preformed plugs without cross-contamination: comparing theory and experiments. Anal Chem 79:2756-61
Ismagilov, Rustem F; Maharbiz, Michel M (2007) Can we build synthetic, multicellular systems by controlling developmental signaling in space and time? Curr Opin Chem Biol 11:604-11
Chen, Delai L; Ismagilov, Rustem F (2006) Microfluidic cartridges preloaded with nanoliter plugs of reagents: an alternative to 96-well plates for screening. Curr Opin Chem Biol 10:226-31
Hatakeyama, Takuji; Chen, Delai L; Ismagilov, Rustem F (2006) Microgram-scale testing of reaction conditions in solution using nanoliter plugs in microfluidics with detection by MALDI-MS. J Am Chem Soc 128:2518-9
Song, Helen; Chen, Delai L; Ismagilov, Rustem F (2006) Reactions in droplets in microfluidic channels. Angew Chem Int Ed Engl 45:7336-56
Song, Helen; Li, Hung-Wing; Munson, Matthew S et al. (2006) On-chip titration of an anticoagulant argatroban and determination of the clotting time within whole blood or plasma using a plug-based microfluidic system. Anal Chem 78:4839-49
Gerdts, Cory J; Tereshko, Valentina; Yadav, Maneesh K et al. (2006) Time-controlled microfluidic seeding in nL-volume droplets to separate nucleation and growth stages of protein crystallization. Angew Chem Int Ed Engl 45:8156-60

Showing the most recent 10 out of 22 publications