Novel Microchip Enables Optical Observation of Single Molecules in Their Natural State


Research at Cornell University has created a microchip that isolates individual biological macromolecules such as enzymes and enables observation of their behavior as they interact with other molecules, one at a time. The nanostructured chip has holes that constrain laser illumination to just 2500 cubic nanometers of the solution, such that only about one small soluble molecule and one molecule of the enzyme of interest are contained in it. A laser beam interrogates each hole, producing a fluorescence signal only when the enzyme is interacting with a small soluble molecule. The rate of this reaction can be followed in real time for each enzyme molecule, which enables a clearer understanding of the reaction than when only data averaged over many hundreds or thousands of molecules are available. The research, which is funded in part by the Genome Program in the Office of Biological & Environmental Research, is highlighted on the cover of the January 31, 2003, issue of Science. The principal investigators of the project, professors of engineering and applied physics Watt W. Webb and Harold Craighead, note that the technique may enable rapid genome sequencing using just a single molecule of DNA, reading strands of DNA tens of thousands of base pairs long. This would overcome a significant limitation of the best current techniques which only can sequence up to about 1000 base pairs at a time.