Trapping single small molecules in solution

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Professor Adam E. Cohen of Harvard University is supported by an award from the Experimental Physical Chemistry Program to develop a trap capable of suppressing the Brownian motion of single small molecules in solution, with molecular diameters as small as 1 nm. The trap combines photon-by-photon tracking and real-time electrokinetic feedback to induce an electrokinetic motion that cancels the Brownian motion of one molecule. The Cohen Lab will study the random Brownian jumps of a molecule struggling to escape from the trap, as well as the responses of a molecule to electrokinetic and optical perturbations. The researchers' goal is to develop a platform via which nearly any fluorescent or fluorescently labeled molecule can be studied at the single-molecule level, without relying on chemical immobilization on a surface. The trap will be used to study the bending dynamics of single small molecules of DNA.Many biomolecules show strikingly more complex behavior at the single-molecule level than is observable in bulk, ensemble-averaged experiments. This complexity arises from dynamic heterogeneity corresponding to distinct configurations of the atoms. Often sparsely populated molecular sub-states are important for the biological function. The task of studying biomolecules one-by-one is complicated by the fact that the molecules do not hold still in free solution, a consequence of Brownian motion, while surface immobilization may disrupt the molecular function. The present research promises to increase the range of molecules that can be studied at the single-molecule level. This research combines nanofabrication, optics, microfluidics, electronics, computer programming, and biochemistry. The student and postdoc working on the project will gain experience in all of these diverse areas. In addition, high school students will spend summers working on the trap. Results of the research will be widely disseminated in public lectures and videos available on the Internet, as well as conventional scientific publications.