Ultrafast laser illuminates intracellular features

March 28, 2005
March 28, 2005, Albuquerque, NM--An ultrafast laser technique, developed by Sandia National Laboratories researcher Paul Gourley and colleagues, has provided laboratory demonstrations of accurate, real-time, high-throughput identification of liver tumor cells at their earliest stages, without chemical reagents.

March 28, 2005, Albuquerque, NM--An ultrafast laser technique, developed by Sandia National Laboratories researcher Paul Gourley and colleagues, has provided laboratory demonstrations of accurate, real-time, high-throughput identification of liver tumor cells at their earliest stages, without chemical reagents.

The technique generates a laser beam in single human cells pumped from a flask through tiny microchannels. The beam is altered by what it encounters. These changes, registered by an imaging spectrometer, instantly identify cancer-modified mitochondria in cells gone wrong. The technique could be critical to advancing early detection, diagnosis, and treatment of disease.

"To rapidly assess the health of a single mammalian cell, the key discovery was the elucidation of biophotonic differences in normal and cancer cells by using intracellular mitochondria as biomarkers for disease," Gourley said. "This technique holds promise for detecting cancer at a very early stage and could nearly eliminate delays in diagnosis and treatment."

The technique is effective because it measures changes in the cell architecture, especially those arising from alterations in protein density, cytoskeleton shape, and distribution of mitochondria � changes that occur when a cell becomes cancerous, according to Gourley.

In Gourley's device, a nano-thin layering of gallium aluminum arsenide combinations sends up numerous tiny beams from a small cross-sectional generating area. These beams are reinforced or thwarted by the position and density of the mitochondria.

"The pictures we get from normal and cancer cells are very different," Gourley said. "Mitochondria conspire to cluster around the nucleus and work together to supply energy to the healthy, functioning cell. In contrast, the mitochondria in the cancer cell sit all over, isolated and balled up in a quiescent, non-functioning state. Apparently, the rapidly growing cancer cells derive energy from an alternative source such as free glucose in the cell."

Fortunately, the mitochondrion is nearly the same size as the light wavelength (800 nm), which makes the laser extremely sensitive to subtle changes in the mitochondria size and effects of clustering. To date, the research team has found that 90%-95% of the light scatter generated is from optical properties of mitochondria.

According to Bob Naviaux, professor at the School of Medicine at the University of California at San Diego and co-director of its Mitochondrial and Metabolic Disease Center, what's attractive about this method for identifying cancer cells is that is is a very rapid and general method that potentially can be applied to cancer cells from solid tumors as well as hematological malignancies like leukemia. Naviaux looks forward to examining a wider population of cancer cells to validate the method, combining the resources of his Center with Sandia's laser expertise.

In addition, the biocavity laser may be applied not only to identifying the spectra associated with cancer cells but also those associated with stem cells, and how these optical signals change as they differentiate into nerve, muscle, and other tissues. According to Naviaux, at present there is no rapid method for identifying the transitional states of a stem cell with the functional cell type it eventually becomes.

A difficulty still ahead is viewing cancer cells in fluids taken directly from the body, rather than isolated by type in a flask. According to the researchers, this problem will be solved by winnowing out unlikely particles through size and frequency.

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