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Science Translational Medicine  19 Jun 2013:
Vol. 5, Issue 190, pp. 190ec101
DOI: 10.1126/scitranslmed.3006749

Early identification of a tumor increases the odds of positive outcomes. To this end, the Holy Grail of cancer detection has been the ability to capture a biomolecular image of a suspicious tissue that exposes its benign and malignant elements. Zavaleta et al. took a major step toward attaining this goal by coupling the surface-enhanced Raman scattering (SERS) phenomenon with an endoscopy system to identify individual optically different nanoparticles in a mixture applied to colon tissue samples.

SERS results from the interaction of photons with the surface of metallic nanoparticles and produces distinct spectral fingerprints in the presence of different surface-bound molecules. This creates a library of nanoparticles with precisely tuned emission “flavors,” which are essential for keeping track of nanoparticle identity in a mixture, allowing for multiplexed detection of several biomarkers at once. In order to capture this rich spectral information near tissue (such as the colon), the authors used a conventional endoscopy conduit, through which they threaded a bundle of optical fibers in order to illuminate the tissue and relay the identifying emissions to a specialized image analysis system. To test the device, the authors first applied nanoparticle mixtures of 10 different flavors on glass slides and on human colon samples. The device was able to quantify concentrations of each individual nanoparticle in the mixtures, even on colon samples with a considerable background signal. As a further challenge, researchers recruited three inexperienced users to test the device by analyzing various mixtures of the nanoparticles spread on the surface of a pig colon. The users showed almost perfect selectivity and accuracy in identifying the correct nanoparticle type and concentration. Last, researchers conducted a pilot clinical study to endoscopically acquire the characteristic background signal from the colons of three patients. The actual SERS nanoparticles could not be used in patients yet because of pending regulatory approval, but the SERS signal intensity from the particles on excised colon tissue proved to be much stronger than the colon background signal.

Provided that the SERS nanoparticles are approved for clinical use and conjugated with tumor marker–specific probes, this system has the potential to greatly improve early detection of malignancies. Another remaining technical challenge is to expand the viewing field of the Raman instrument because the millimeter-scale spot size of its illumination fiber currently limits the interrogation area.

C. L. Zavaleta, et al., A Raman-based endoscopic strategy for multiplexed molecular imaging. Proc. Natl. Acad. Sci. U.S.A., 23 May 2013 (10.1073/pnas.1211309110). [Full Text]

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