Nanoscale Sensor Has Potential Medical ApplicationsNanoscale Sensor Has Potential Medical Applications

Originally Published MDDI August 2003

R&D DIGEST

Physicists have created a first-of-its-kind nanoscale sensor using a single molecule less than 20 nm in length. Uses for the nano molecular sensor could encompass early diagnosis of genetic diseases. Other applications in medicine and biotechnology are also possible, says Giovanni Zocchi, assistant professor of physics at the University of California at Los Angeles (UCLA) and member of the California NanoSystems Institute. Zocchi is the leader of the research team developing the sensor. 

“This nanoscale single-molecule method could lead to significant improvements in early diagnosis of genetic diseases, including the growing number of cancer forms for which genetic markers are known,” Zocchi says. “The largest potential applications for this sensor may be in the drug discovery process, where the possibility of quickly gauging the gene expression response of cells to prospective drugs is crucial.” 

The nanoscale sensor uses a single molecule to detect the presence of a specific short sequence in a mixture of DNA or RNA molecules. According to Zocchi, “Traditional assays use an averaged procedure that detects a minimum amount of molecules, but our method can detect a single one. When a target molecule binds to the probe in the sensor, the probe molecule changes shape, and in its new conformation, pulls on the sensor. It is remarkable that a single molecule can actually move the sensor, because the relative sizes are comparable to one person trying to move a mountain, but mass is of no consequence at these minuscule scales.” 

The sensor motion is detected by an optical technique called evanescent wave scattering, which analyzes light that leaks out behind a reflecting mirror. This evanescent wave can be used to sense precisely the position of an object “beyond” the mirror. “Instead of detecting the presence of the target, we detect the changing conformation of the probe when the target binds to it,” Zocchi explains. 

The UCLA team is the first to report measurements of conformational changes in a single DNA molecule at the nanometer scale. “This single-molecule sensor could be an important component of a ‘lab on a chip' technology for doing chemical analysis on a chip,” Zocchi says. 
He adds that the team plans to use the nanoscale sensor for experimental leukemia research. The goal will be to determine whether the sensor's high sensitivity can detect a recurrence of cancer at an earlier stage than is now possible. “If we can increase the sensitivity of the detector, then it may be possible to detect genetic diseases at an earlier stage,” Zocchi adds. “It may become possible to diagnose the presence of an abnormality in DNA at an early stage, or the expression of a certain gene that should not be expressed.”

Zocchi explains that “a single-molecule sensor has, in principle, extraordinary sensitivity. Unlike previous single-molecule experiments, which were impractically complicated for large-scale applications, the simplicity of this design lends itself to many applications.”

The researcher speculates that having an efficient high-sensitivity method would be an important tool for testing how cells react to a new drug. He adds, “The nanosensor could also be a useful tool for stem cell research. A nanosensor based on this technology could potentially 
detect minute traces of biological weapons, based on a characteristic genetic signature. These are the first steps down a path toward devices that we expect will be really useful.” 

In addition to the proposed applications, Zocchi believes that the research could offer benefits in basic science. He also speculates that “the future will undoubtedly see nano-bio composite devices applied to perform molecular tasks. Ultimately these efforts will lay the groundwork for creating artificial systems with more and more of the characteristics that have been unique to living things.” Zocchi adds that “economy of scale allows nature to pack the most elaborate laboratory on Earth in the volume of a single bacterial cell; in the future, artificial systems may approach similar complexity.”

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