The University Record, November 2, 1992

Sub-microscopic sensor monitors chemical changes inside living cells

By Sally Pobojewski
News and Information Services

A U-M chemist has developed the first ultrasmall fiber-optic sensor capable of monitoring chemical properties within a living cell.

With a tip visible only under magnification, the new sensor is 1,000 times smaller than existing fiber-optic sensors and responds in milliseconds, or 100 times faster than current optical sensing devices.

In preliminary tests, the U-M sensor accurately measured pH or acidity levels in animal cells without damaging the cells in any way. According to Raoul Kopelman, professor of chemistry, the fiber-optic sensor has the potential to monitor many other cellular chemical properties, including levels of calcium, potassium and carbon dioxide.

A description of the sensor fabrication process and results of pH measurements in aqueous solutions, mouse and rat embryos are reported in the Oct. 30 issue of Science.

“This shows the potential of nanotechnology [the fabrication of ultrasmall devices] for use in optical microscopy and cellular biology,” Kopelman said. “It demonstrates that you can use ordinary light to analyze biological samples with volumes at least a million times smaller than is possible with current optical microscopy techniques.”

Potential biological applications for the probe in research and medicine are extensive, according to Kopelman. They include testing the effects of new drugs on single cells—which could reduce the need for animal tests—monitoring embryos for birth defects, gene sequence identification, and detection of individual cells or even single molecules within a sample.

“Not only can this sensor measure the chemical properties of cells, it can monitor chemical changes that take place within cells as they respond to external changes in their environment and to internal changes that occur in embryonic cells as an organism develops,” Kopelman said.

The probes are produced with a new technique called near field photopolymerization, which was developed by Kopelman and his associates. The process begins when researchers shine a beam of light into one end of a nanofabricated optical fiber probe that is coated with aluminum to prevent light from escaping through the sides. Light emerges from a very small opening in the far end of the probe, which rests in a solution of simple molecules called monomers. The light induces a chemical reaction between monomers in solution and molecules on the end of the probe, which produces or “grows” a polymer tip.

“The polymer tips will only grow in the presence of light,” said Weihong Tan, a graduate student who helped develop the probe fabrication process. “By varying the diameter of the light beam, we control the size of the polymer sensing tips on the end of the probe.

“By varying the monomer solution, we can change the type of polymer tip we produce,” Tan added. “The nature of the polymer tip determines what the sensor is sensitive to or what chemical properties it can measure.”

According to Kopelman, his research team has already produced optical probes just 200 angstroms across or about 20 times the size of an average molecule.

“The most difficult part of the process is controlling the size of the polymer tip,” Tan said. “Our ultimate goal is to produce a sensing tip just one molecule or about 10 angstroms across.”

Other members of the research team, in addition to Kopelman and Tan, include Craig Harris, assistant professor of toxicology; Zhong-You Shi and Duane Birnbaum, research associates, and Steve Smith and Bjorn A. Thorsrud, graduate students. The research is funded by the U.S. Department of Energy. The U-M has filed a patent application for the sensing probe.