Raman spectroscopy limiting factor

Principles and Characteristics The prospects of Raman analysis for structural information depend upon many factors, including sample scattering strength, concentration, stability, fluorescence and background scattering/fluorescence from the TLC substrate. Conventional dispersive Raman spectroscopy has been considered as a tool for in situ analysis of TLC spots, since most adsorbents give weak Raman spectra and minimal interference with the spectra of the adsorbed species. Usually both silica and cellulose plates yield good-quality conventional Raman spectra, as opposed to polyamide plates. Detection limits for TLC fractions... 

Fortunately, in favorable cases enhancement mechanisms operate which increase the signal from the interface by a factor of 105 — 106, so that spectra of good quality can be observed - hence the name surface-enhanced Raman spectroscopy (SERS). However, these mechanisms seem to operate only on metals with broad free-electron-like bands, in particular on the sp metals copper, silver and gold. Furthermore, the electrodes must be roughened on a microscopic scale. These conditions severely limit the applicability of Raman spectroscopy to electrochemical interfaces. Nevertheless, SERS is a fascinating phenomenon, and though not universally applicable, it can yield valuable information on many interesting systems, and its usefulness is expected to increase as instrumentation and preparation techniques improve. 

Since most biomolecules normally exhibit medium or low Raman cross sections, an enhancement of the signal intensity for the ability to characterize even low concentrations would be preferable. Besides the application of resonance Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS) is a promising alternative. In doing so the vicinity of molecules to rough noble metal surfaces leads to Raman enhancement factors of 106-108 and even up to 1014 leading to a single molecule detection limit [9]. 

What is the state of process Raman spectroscopy right now Is it still slowly building Is it a niche market and unlikely to expand Is it thriving and flourishing Since almost all industrial applications will use a commercial instrument, the instrument vendors are the only ones who can really answer these questions but are likely to be bound by confidentiality agreements with their customers. In the absence of publications or other public disclosures, it is useful to examine the factors that may be limiting or appearing to limit the use of Raman spectroscopy for process control. 

A limiting factor in noninvasive optical technology is variations in the optical properties of samples under investigation that result in spectral distortions44 8 and sampling volume (effective optical path length) variability 49-54 These variations will impact a noninvasive optical technique not only in interpretation of spectral features, but also in the construction and application of a multivariate calibration model if such variations are not accounted for. As a result, correction methods need to be developed and applied before further quantitative analysis. For Raman spectroscopy, relatively few correction methods appear in the literature, and most of them are not readily applicable to biological tissue.55-59... 

We noted earlier that the detection limit is directly related to SNR and is often defined as an analyte concentration yielding a signal that is some factor, k, larger than the standard deviation of the blank, (Jbk- It is useful to define the detection limit for Raman spectroscopy as the minimum detectable value of the cross section-number density product, or ( SD)min- Of course, the concentration detection limit in terms of D or molarity will depend on the magnitude of p, but (PD)min is a more general definition that directly indicates spectrometer performance. In the vast majority of analytical Raman measurements at low values of PD, the SNR is background noise limited, so abk In... 

NIR-Raman spectroscopy has been used for a number of applications and is particularly useful for biological and biomedical uses. Fluorescence has been a limiting factor for much Raman analysis of biological samples, particularly whole-cell or whole-tissue samples. NIR excitation reduces interference from fluorescence and decreases photoinduced degradation of the sample, enabling researchers to obtain spectra for a variety of biomaterials and living cells. 

Surface-enhanced Raman spectroscopy (SERS) " involves obtaining Raman spectra in the usual way on samples that are adsorbed on the surface of colloidal metal particles (usually silver, gold, or copper) or on roughened surfaces of pieces of these metals. For reasons that are finally becoming understood, at least semiquantitatively, the Raman lines of the adsorbed molecule are often enhanced by a factor of 10 to lO. When surface enhancement is combined with the resonance enhancement technique discussed in the previous section, the net increase in signal intensity is roughly the product of the intensity produced by each of the techniques. Consequently, detection limits in the range of 10 to 10 " M have been observed. 

An alternative approach to improving the sensitivity of the Raman technique with potential for environmental applications arose in 1974 [11] with the discovery of surface-enhanced Raman spectroscopy (SERS) in which detection limits can typically be lowered by a factor of approximately 10 -10 relative to NRS, with SERS having the advantage of fluorescence suppression over the RRS. (Considerable research has been conducted for determining the sources of enhancement, and the reader is referred to the reviews of Vo-... 

Normal Raman spectroscopy has also been coupled to separation techniques such as CE [36,37,44] and TLC [42]. Morris and co-workers have shown CE-NRS to be an attractive analytical tool due to the short analysis times, relative ease in experiment setup, the high information content given by Raman, and, perhaps most importantly, the electrophoretic preconcentration enhancement factors that lower detection limits of normal Raman [44]. Two general classes of electrophoretic methods of concentration can be per-... 

SERS incorporates most of the advantages of Raman spectroscopy. The greatest benefits are enhanced sensitivity (10 M, ng level), selectivity and surface specificity. However, the great analytical potential for SERS is limited by several factors, amongst which the need for adsorbates on a limited number of metal surfaces [430]. Quantitative applications of SERS are difficult [431]. For SERS to... 

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