Imagine how a single eyelash might move in an Olympic-sized swimming pool. Viscous forces exerted by water would prevent the lash from moving very far through the liquid in which it sits. Now imagine a structure only one millionth the size of the eyelash, something on the scale of nanometers. Overcoming these forces is a problem researchers face when attempting to manipulate gold nanowires, small rods that can be used to construct tiny devices or to deliver drugs to cells. At such a small scale, the viscous force water exerts on the wire becomes extremely problematic, akin to a swimmer moving through molasses. Controlling movement with any precision or accuracy has eluded researchers for decades, stifling potential applications of nanowire technology. Recently, Johns Hopkins University researchers in Physics and Astronomy in the Krieger School of Arts and Sciences, and Biomedical Engineering at Johns Hopkins School of Medicine have developed a way to manipulate these thin rods using a technique called electric tweezers. The tweezers use electric fields to rotate and position wires with high accuracy. “Many experts in fluid mechanics said moving such small particles in liquid would be fruitless,” said Chia-ling Chien, a principle investigator on the study. Chien is the Jacob L. Hain Professor of Physics and director of Johns Hopkins Materials Research Science and Engineering Center. “We wanted to see how difficult it would be and if we can precisely control and manipulate their rotation and movement,” he said. Donglei Fan, a PhD graduate and postdoctoral fellow in the Whiting School of Engineering Department of Materials Science and Engineering, developed the electric tweezers technology. Fan, Chien and professor of materials science and engineering Robert Cammarata joined forces with Zhizhong Yin, a former postdoctoral fellow in Biomedical Engineering and his adviser, Andre Levechenko, an associate professor of biomedical engineering at Hopkins. The latter two were spearheading use of micro/nanotechnology for biomedical applications, and this collaboration helped realize the great potential of using this technology for precise drug delivery. They published a paper on this technology in the July 2010 Nature Nanotechnology, along with doctoral candidate in biomedical engineering, Raymond Cheong and former postdoctoral fellow in physics and astronomy, Frank Q. Zhu. A soon-to-be-published review article written by Fan, Zhu, Cammarata and Chien illustrates the electric tweezers technique and its application to deliver a dose of a potent anti-cancer molecule to a single cell. The
tweezers work by positioning two electrodes and applying a voltage, which creates an electric field. Nanowires can be made to carry a charge, and can be held, translated and rotated by controlling the direction of the field, and generating the appropriate force. “Previous work has tested optical or magnetic techniques to similarly manipulate smaller entities, however, these techniques are limited in that they can only capture particles in their field, but cannot move them. The electric technique is also relatively simple to set up and does not require extensive instru-mentation as required by optical and magnetic systems,” Chien said. Although tissues and cells are susceptible to damage by strong electric fields, Chien stresses the electric fields are well within range of biological tolerance. Another advantage of using electric tweezers is its extreme precision, where it’s possible to specifically target one cell in a plate of hundreds of thousands—roughly equivalent to a cargo plane guiding a parachute to one person in a crowd. One can also target different locations of the cell, such as the cytoplasm or nucleus for site-specific drug delivery, Chien explains. This can be guided by light microscopy. Before the advent of electric tweezers and nanowire technology, guiding small molecules to individual cells would have been virtually impossible. “We can observe how a single cell might communicate with its neighboring cells, and how it might respond to a very low dose of a drug,” Chien said. Researchers predict this will improve our understanding of cell biology, and cell targeting. For example, some drugs are difficult to get across the cellular membrane, but delivery can be improved by attachment to gold nanowires. Beyond biological applications, Chien said electric tweezers could be used in other materials-based applications, such as constructing circuits. Carbonbased structures, such as carbon nanotubes, have unique electrical properties, and can similarly be controlled using electric tweezers. “Using electric tweezers, it is now possible to assemble structures piece-by-piece,” Chien said, which was previously difficult to do with physics at the nanoscale. Electric forces can rotate small wires to create nanomotors that can mimic small protein motors in cells. Although potential in vivo applications are far off, the technique will undoubtedly improve our understanding of cell-to-cell communication, and the tools researchers have to study drug responses. Jacob Koskimaki is a pre-doctoral fellow in Biomedical Engineering at Johns Hopkins University.
Spring 2011
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