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

The Science

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 2,500 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 principal investigators of the project 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 1,000 base pairs at a time.

Principal Investigator

Watt W. Webb
Cornell University

Co-Principal Investigator

Harold Craighead
Cornell University

BER Program Manager

Dawn Adin

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]


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.


Levene, M. J., J. Korlach, S. W. Turner, M. Foquet, H. G. Craighead, W. W. Webb. 2003. “Zero-Mode Waveguides for Single-Molecule Analysis at High Concentrations,” Science 299. DOI:10.1126/science.1079700.