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The many facets of Raman spectroscopy for biomedical analysis.

Christoph Krafft1, Jürgen Popp1,2

Anal Bioanal Chem. 2015 Jan;407(3):699-717.

  1. Leibniz Institute of Photonic Technology, Albert Einstein Straße 9, D-07749 Jena, Germany.
  2. Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, D-07743 Jena. Germany.

 

Abstract 

A critical review presents applications of linear and nonlinear Raman microscopies in biomedical diagnostics of bacteria, cells and tissues and gives an overview of achievements of our research group. Linear Raman spectroscopy probes the full spectrum of Raman active vibrations providing a wealth of chemical and molecular information. Its routine use is challenging due to relatively weak signal intensities and confounding overlapping effects. Nonlinear variants such as coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) offer signal enhancement and rapid data acquisition. Raman, CARS and SRS images benefit from high contrast based on chemical composition and molecular structure in a label-free and non-destructive way. Using plasmonic nanoparticles and nanostructures as labels surface enhanced Raman scattering (SERS) is a complementary biomedical tool with sensitivities similar as fluorescence. The current state of the art is evaluated with the focus on papers that have been published within the last five years. Future developments are pointed out and illustrative examples are given in the context of identification of bacteria and cells, imaging of single cells, Raman activated cell sorting, diagnosis of tissue sections, fiber optic probes and progress in coherent Raman scattering microscopies. European networks such as RAMAN4CLINICS and CLIRSPEC are discussed to translate, disseminate and validate these innovate and powerful tools.

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Additional Information

Financial support of EU, Thüringer Kultusministerium, Thüringer Aufbaubank, Federal Minstry of Education and Research, Germany (BMBF), German Science Foundation (DFG), Fonds der Chemischen Industrie and Carl Zeiss Foundation are gratefully acknowledged.

 

Figure Legend: The figure shows examples of Raman images from single cells (a) and brain tumor tissue sections (b), and CARS image from brain metastases tissue section (c). The contrast in (a) displays lipid droplets (red) and cellular proteins in cytoplasm (green) and cell nucleus with nucleoli (blue). The multicolour code in (b) distinguishes cell nuclei (blue), lipids (green), proteins (red), cholesterol (yellow), cholesterol ester (magenta) and buffer (cyan). The molecular composition and number of cell nuclei change from normal (top), tumor (middle) and necrosis (bottom). The red scale in (c) visualizes the intensities of the vibrational band near 2850 cm-1 representing mainly lipids. The margin between tumor (top) and necrosis (bottom) is evident. The magnified inset demonstrate cellular details that correlate well with histopathology after staining.

The many facets of Raman spectroscopy for biomedical analysis. Global Medical Discovery