Abstract

Raman spectroscopy has received increasing interest in biomedical applications because of its label‐free and in vivo detection capabilities. The main challenge for a wider application lies in its low detection sensitivity, especially for biomolecules. Various strategies have been employed to improve the detection sensitivity of Raman spectroscopy. In this work, we systematically compared two Raman techniques with improved sensitivity for the detection of microliter quantities of whole human tears: drop‐coating deposition Raman spectroscopy (DCDRS) and surface‐enhanced Raman spectroscopy (SERS). High‐quality and highly reproducible DCDR spectra of tears can be obtained in the ring zone of the dried coffee‐ring deposit. The major contribution is from the high‐abundant proteins, including lysozyme, lactoferrin, and albumin. Good SER spectra with excellent reproducibility can also be acquired in the deposit area and are contributed by uric acid and hypoxanthine in tears with a low abundance but strong interactions with the silver nanoparticles. The result demonstrates that DCDRS is advantageous for detection of some high‐abundant components and SERS for some low‐abundant components in the whole tears. A combination of both techniques is able to extract multiparameter information for a systematic analysis of clinical tears and can be further extended to the analysis of other body fluids. Copyright © 2014 John Wiley & Sons, Ltd.

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