Spectroscopy of Scattered Light for the Characterization of Micro and Nanoscale Objects in Biology and Medicine

Abstract

The biomedical uses for the spectroscopy of scattered light by micro and nanoscale objects can broadly be classified into two areas. The first, often called light scattering spectroscopy (LSS), deals with light scattered by dielectric particles, such as cellular and sub-cellular organelles, and is employed to measure their size or other physical characteristics. Examples include the use of LSS to measure the size distributions of nuclei or mitochondria. The native contrast that is achieved with LSS can serve as a non-invasive diagnostic and scientific tool. The other area for the use of the spectroscopy of scattered light in biology and medicine involves using conducting metal nanoparticles to obtain either contrast or electric field enhancement through the effect of the surface plasmon resonance (SPR). Gold and silver metal nanoparticles are non-toxic, they do not photobleach, are relatively inexpensive, are wavelength-tunable, and can be labeled with antibodies. This makes them very promising candidates for spectrally encoded molecular imaging. Metal nanoparticles can also serve as electric field enhancers of Raman signals. Surface enhanced Raman spectroscopy (SERS) is a powerful method for detecting and identifying molecules down to single molecule concentrations. In this review, we will concentrate on the common physical principles, which allow one to understand these apparently different areas using similar physical and mathematical approaches. We will also describe the major advancements in each of these areas, as well as some of the exciting recent developments.Index headings: Light scattering; Spectroscopy; Nanoparticle; Surface plasmon; Surface enhanced Raman; SERS. INTRODUCTIONT he spectroscopy of scattered light has played an increasingly important role in biology and medicine because it can provide information about subcellular and extracellular biological structures using native contrast, as well as information about nanoparticles that are employed as the exogenous imaging markers or vehicles for the delivery of therapeutic agents. Light scattering by these microscopic objects is governed by the very basic principles of electromagnetic wave propagation and interaction with matter developed many decades ago. The impressive advances in biomedical instrumentation that have recently been achieved are examples of the successful applications of these fundamental principles. An analogy can be made between the development of biomedical light scattering and the development of other medical imaging modalities, for example the discovery of the very basic physics of X-rays led to the development of computed tomography decades later, while the initial understanding of another basic physical effect, nuclear magnetic resonance, eventually led to magnetic resonance imaging. Thus it can be argued that the field of biomedical optics is primarily concerned with the technological development of new medical applications of electromagnetic wave interactions, described by Maxwell's equations, with exogenous and endogenous...

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