<title>Surface-enhanced Raman scattering (SERS): nanoimaging probes for biological analysis</title>

Abstract

We have developed a surface enhanced Raman scattering (SERS) based nanoimaging probe capable of chemical imaging with nanometer scale spatial resolution. Using this SERS-nanoimaging probe it is possible to image individual chemical components within sub-cellular environments. The probe consists of a tapered coherent fiber optic imaging bundle that has been coated with a roughened layer of metal, providing a SERS active substrate. The fiber optic bundle is tapered using a specially programmed micropipette puller, allowing precise control over the probe tip's diameter, and thus the resolution of images. Tapered bundles having individual fiber elements ranging from 100-800 nanometers on the tapered end and 4 micrometers in diameter on the proximal end have been investigated. Through modification of the fibers' tapered tips, generation of nanoscale imaging with inherent image magnification and short pass filtering effects is possible. Following tapering of the fiber optic bundles, the fiber probes are spin-coated with alumina particles and coated with silver to provide a reproducible SERS active surface. Characterization of the response of these SERS nanoimaging probes has been evaluated using common SERS active chemical species (e.g., benzoic acid, brilliant cresyl blue, etc.) and application of these nanoimaging sensors to biological systems is discussed.

A nanoscale probe for dynamic-chemical imaging

“…Following tapering, the bundles are etched with hydrofluoric acid to produce a uniform array of spikes, six around each fiber element: see Figure 1(C). 4 These cladding spikes then have a SERS-active metal deposited onto them by vacuum evaporation. This process results in fibers with enhancement factors of 10 9 to 10 11 , with less than 2% variation in enhancement at any location across the bundle 5 (see Figure 2).…”

Army relevant Biological Hazards Detection with Commercial SERS substrates

“…(77,78) Significant research efforts have also been concentrated on better directing the optimization of the substrate surface from which the SERS enhancement occurs. (75,(79)(80)(81)(82) Based in part on experimental and as well as theoretical efforts, the directed fabrication of SERS platforms has focused on modifying the feature size (83)(84)(85) , spacing between objects, geometry and shape of structures (86)(87)(88) , identity and incorporation of metals on the surface (89) , feature height, and the character of the foundation layer (66,(90)(91)(92) on which the architecture is fabricated. (78,93,94) There are numerous examples in the literature detailing how variation in some of these parameters in some cases can result in very dramatic changes to the overall SERS enhancing capabilities of the substrate surface.…”

Surface-Enhanced Raman Scattering as an Emerging Characterization and Detection Technique

“…In proof-of-principle studies, such probes have been used for chemical differentiation of various samples with <100 nm spatial resolution [68,[101][102][103][104]. In one such study, gelatin was homogenously mixed with brilliant cresyl blue (BCB), while benzoic acid was spotted at various locations around the edge.…”

“…To provide a nanosensor/nanoprobe capable of obtaining dynamic images, a novel nanoimaging probe has been developed whereby coherent fiber optic imaging bundles were coupled with SERS for real-time subdiffraction-limited chemical imaging [68,[101][102][103][104]. This SERS nanoimaging probe has an advantage of providing both temporal and spatial resolution, thereby allowing the monitoring of the movement of macromolecules across membranes.…”