Surface-Enhanced Raman Scattering-Based Bioimaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 318

typically an optical microscope [10]. With the introduction of commercial Raman
systems, this technique has emerged as a powerful and handy analytical tool for the
characterization of a wide variety of nanostructures over the last decade.
in this chapter, we present recent advances in the application of SERS in bioimag-
ing. We do not intend to provide a comprehensive literature review but instead
highlight several recent results as key examples that demonstrate the breadth of the
applications of SERS. following a brief introduction to Raman imaging using micro-
Raman spectroscopy (μRS), we present an overview of the instrumentation underlin-
ing the similarities and differences compared to conventional Raman spectroscopy
and recent development in deep noninvasive Raman spectroscopy for probing diffusely
scattering media, such as living tissue. in the following section, we mainly highlight
important considerations in the design and fabrication of bright SERS probes and
experimental approaches of SERS-based bioimaging with selected examples. We
conclude with a brief summary and outlook of the SERS-based bioimaging.

11.2 introduction

Spectral information obtained using conventional Raman spectroscopy is spatially
averaged over a large area (few millimeter square area), whereas micro-Raman spec-
troscopy (μRS) enables the collection of spectral information with submicron lateral
and vertical resolution. With the use of a high magnification objective, the laser beam
can be focused into a spot with an effective diameter (considering a gaussian footprint
of the beam) as small as approximately 200 nm, providing excellent resolution limited
only by the far-field diffraction limit. The unique combination of high chemical speci-
ficity, excellent lateral and vertical resolution, and nondestructive nature of μRS makes
it a powerful analytical tool for the characterization of nanostructured materials.
as mentioned earlier, surface-enhanced Raman scattering (SERS) involves the
dramatic enhancement (under ideal conditions more than 10 10 times) of Raman
scattering from molecules adsorbed on or in close proximity to a nanostructured
metal surface [11]. accidentally discovered nearly 35 years ago, SERS continues to
attract broad scientific and technological interest owing to its ever-expanding appli-
cation landscape. a nonexhaustive list of applications includes trace chemical and
biological detection, environmental monitoring, surface analysis, pharmaceutical
tracking, and molecular bioimaging [12-17].
optical bioimaging, which involves detection, localization, and monitoring of
molecular processes of cells and target tissues using inherent contrast offered by the
biological species or exogenous contrast agents, is a rapidly emerging field. SERS
offers numerous advantages for in vivo and ex vivo bioimaging:

1. on a per particle basis, SERS probes are significantly brighter compared to
near-infrared (niR)-emitting semiconducting quantum dots (QDs), which
have been extensively investigated for bioimaging applications. Even simple
designs involving individual gold nanoparticles tagged with resonant Raman
reporters are nearly 200 times brighter compared to QDs [18].