MAY 18, 2007--Harvard University (Cambridge, MA, USA; www.techtransfer.harvard.edu) has licensed its coherent anti-Stokes Raman scattering (CARS) microscopy technology to Leica Microsystems (Wetzlar, Germany; www.leica-microsystems.com) for use in the company's confocal microscopes. The technology was developed in the lab of Xiaoliang Sunney Xie, professor of chemistry and chemical biology at Harvard. "This technology has far-reaching implications for helping advance important biomedical research," stated Isaac T. Kohlberg, chief technology development officer, Harvard University. "Our agreement with Leica Microsystems is aligned with our strategy to partner with the best and most expert companies, which, like us, are dedicated to excellence and quality."
CARS microscopy allows rapid and nonperturbative imaging of biological specimens with chemical selectivity. The contrast in CARS microscopy arises from the intrinsic vibrations of molecules. Every molecule has one or more chemical bonds, the bending or stretching of which have characteristic vibrational frequencies that depend on the bond length and strength. For example, lipids, a primary component of fat, contain carbon-hydrogen bonds, which vibrate at certain distinct frequencies. CARS microscopy "tunes" into these characteristic frequencies to build chemically selective images with extremely high sensitivity in living cells or organisms.
To image a specimen, such as tissues or cells, CARS microscopy utilizes two highly focused laser beams at different frequencies. By setting the difference between the two laser frequencies equal to the frequency of vibration of a particular chemical bond, molecules with that bond are made to vibrate coherently. This causes the sample to emit at a new frequency (called the "anti-Stokes" frequency) from the laser focus. An image is created by scanning the beams over the sample and detecting the intensity of the emitted anti-Stokes light at each position. In this way, one can map the concentration of the molecule of interest (for example, lipid) throughout the tissue, or within a cell with 300-nm lateral resolution.
The method offers much higher time resolution than other vibrational imaging techniques, allowing "movies" of biological activity and chemical processes to be taken within a living cell or organisms. By using excitation lasers at near-infrared wavelengths, which can penetrate deep into tissue, CARS microscopy can reach a depth of nearly 0.3 mm below the surface. Efforts are underway to extend CARS microscopy for not only cell biology applications, but also disease diagnostics and real-time surgical guidance.