Publications

Proceedings of SPIE - The International Society for Optical Engineering

Gourley, Paul L.; Cox, Jimmy D.; Hendricks, Judy K.; McDonald, Anthony E.; Copeland, G.C.; Sasaki, Darryl Y.; Curry, Mark S.; Skirboll, Steven K.

The speed of light through a bio fluid or biological cell is inversely related to the biomolecular concentration of proteins and other complex molecules comprising carbon-oxygen double bonds that modify the refractive index at wavelengths accessible to semiconductor lasers. By placing a fluid or cell into a semiconductor microcavity laser, these decreases in light speed can be sensitively recorded in picoseconds as frequency red-shifts in the laser output spectrum. This biocavity laser equipped with microfluidics for transporting cells at high speed through the laser microcavity has shown potential for rapid analysis of biomolecular mass of normal and malignant human cells in their physiologic condition without time-consuming fixing, staining, or tagging. We have used biocavity laser spectroscopy to measure the optical refraction of solutions of standard biomolecules (sugars and proteins) and human cells. The technique determines the frequency shift, relative to that of water, of spontaneous or stimulated emission from cavity filled with a biomolecular solution. The spectral shift was measured under conditions where the optical contrast between the cell and surrounding fluid was varied over wide limits. This was accomplished by decreasing the cell biomolecular concentration ∼10x by osmotic swelling and by increasing the protein content more than 100x in the fluid. The shift was also measured in human glioblastoma cells that had been sorted by conventional fluorescence-activated cell-sorting according to protein content. The results show that the wavelength shift increases in proportion to the protein concentration in the cell (mass per unit volume) relative to the concentration outside the cell. These results help to qualify the measurements of microcavity spectra in rapidly assessing biomolecular mass concentration (primarily protein) in human cancer cells.