Raman Spectroscopy

The combination of confocal Raman and atomic force microscopes allows chemical and surface topography imaging of large samples without any ongoing process control by an operator. This article describes the relevant measurement principles and presents examples of automated measurements on nanostructured materials.

The continuing pace of technological advancements in scientific instruments has recently led to a wide range of commercially viable portable and handheld instruments, and the Raman spectroscopy market is no exception. While security applications have received much of the early attention in relation to handheld instruments, other applications are beginning to replace demand from the security markets.

Chemical analysts who use spectroscopy to extract molecular information from samples have been following the developments in Raman instrumentation. Vibrational spectroscopy provides detailed molecular information, but Fourier-transform IR has been much easier to use than Raman. Now that Raman equipment is smaller, cheaper, faster, and easier, analysts are interested. Columnist Fran Adar will discuss why.

A new method for the early detection of gastric cancer uses a combination of feature extraction based upon continuous wavelets for Fourier transform-infrared spectroscopy (FT-IR) and classification using an artificial neural network trained with a back-propagation algorithm.

Raman microscopy was developed as a tool for microanalysis complementary to the electron microscope, which enabled identification of the elements in a microspot. The first realization for Raman imaging was implemented using a nonconfocal optical method. Subsequently, a confocal scheme was developed, which provided better contrast in the Raman image. A number of successful examples from pathology, pharmaceutical analysis, and geology will be shown.

Raman microspectroscopy is a powerful tool for noninvasive chemical analysis of tissues, cells, and cellular structures. To achieve the highest signal-to-noise ratio and fidelity of Raman spectra, the background must be minimized. The difference in temporal dependence of Raman and fluorescence signals can be used for very effective discrimination. A careful system design, based upon the employment of very efficient Kerr-gating materials, makes confocal Raman microscopy possible with significantly shorter acquisition times. The new instrument is tested for a variety of biomedical systems. The possible applications are outlined together with the routes for further improvement.

Columnist Fran Adar discusses the evolution of Raman spectroscopy instrumentation and new applications for this more sensitive, easy-to-use technology.

Lambda Solutions, Inc.

WITec GmbH

In this investigation the authors assess the potential of Raman spectroscopy as a tool for probing conformational changes in membrane-spanning proteins - in this case, the sodium potassium adenosine triphosphatase (Na+,K+-ATPase).

November 2006. Raman spectroscopy is a promising new tool for noninvasive, real-time diagnosis of tissue abnormalities. Here, we show evidence of its application for cancer diagnosis in four distinct tissue types: skin, breast, gastrointestinal tract, and cervix. Multivariate statistical analysis and discrimination algorithms allow for automated classification of the spectra into clinically relevant pathological categories using histology as a gold standard. Although limitations exist, the technique shows every indication of being an exciting prospect in the management of cancer in a clinical setting.

September 2006. The authors rapidly acquire complete vibrational spectra in the fingerprint region using a single femtosecond laser for broadband coherent anti-Stokes Raman scattering (CARS) microscopy to image spatially variant compositions of condensed-phase samples.

Recent progress in photonic crystal design is transforming surface-enhanced Raman spectroscopy (SERS) from a research tool into a powerful new analytical technique. High sensitivity can be achieved due to the enormous amplification of the Raman signal of molecules in contact with nanostructured metal surfaces. This article highlights the performance of SERS substrates for a range of applications, illustrating the versatility of the technology, as well as future directions.

Outstanding stray light rejection performance of a triple-spectrometer system is demonstrated. Low-frequency Raman spectra of solid powder samples, including Stokes-AntiStokes Raman data, as low as 5 cm-? from the excitation line are presented.

Chemical images of polystyrene beads on silicon acquired using Raman mapping and image processing are reviewed. The effects of the objective on the quality of the final image, particularly its magnification and numerical aperture, and the step size of the map, are discussed as well.

Advances in Raman spectroscopy and imaging generate large amounts of information pertaining to the chemical and physical composition of materials. The distillation of meaningful and useful information from such quantities of data can be challenging. New image analysis software combined with powerful chemometric techniques permit an analyst to perform rapid calibrationless and quantitative analysis and discover features easily overlooked using less rigorous methods. This article describes mapping and analysis of a painkiller tablet using a dispersive Raman microscope and accompanying software.

In conventional designs for dispersive Raman spectrometers, there is a tradeoff between spectral resolution and light throughput. A new design approach using Multimodal Multiplex (MMS) technology provides approximately 12x the throughput of a conventional slit-based system with no compromise in spectral resolution. This translates into a signal-to-noise advantage of greater than 3.5x for equivalent measurement times. In addition, the wide area aperture is ideally suited to large sample spot illumination, which yields measurements that are more representative of the bulk of the sample being analyzed.

Carbon nanotubes are unique nanostructures with remarkable mechanical and electrical properties. Due to their tremendous potential for future innovations, great efforts are made to characterize these structures. In the following study, carbon nanotubes were investigated with Confocal Raman Microscopy and Atomic Force Microscopy using only one single instrument.

Surface-enhanced Raman spectroscopy (SERS) is a widely studied technique capable of adding single-molecule detection capability to the rich information provided by Raman spectroscopy. in this aricle, the authors show an additional system gain of more than two orders of magnitude to SERS by using a dielectric microsphere resonator to capture and excite the target system.

Guest author John Coates describes a new, compact handheld Raman instrument.

The authors review the operating principles of a silicon Raman laser and show that by introducing a longitudinal variation of the waveguide width in the cavity, the lasing efficiency can be increased significantly.

The authors review the operating principles of a silicon Raman laser and show that by introducing a longitudinal variation of the waveguide width in the cavity, the lasing efficiency can be increased significantly.

Confocal Raman microscopy can be useful when applied to all samples that are heterogeneous on the micrometer to millimeter scale and that generally can be investigated by Raman spectroscopy. This article presents examples of confocal Raman microscopy from various fields of application including pharmaceutical analysis and stress measurements in semiconductors.

A new system for multitechnique spectral searching is described that utilizes analysis of several hit lists resulting from spectral similarity searches performed simultaneously in reference databases for multiple complementary analytical techniques. This paper demonstrates the benefits of this multitechnique approach using the complementary techniques of IR and Raman spectroscopy.

Compounds of magnesium and calcium are common components of pharmaceutical formulations. Spectroscopic imaging can provide a complete understanding of a formulation. This paper compares two spectral imaging techniques — energy dispersive X-ray fluorescence (EDXRF) microscopy and Raman microscopy.

The authors present a novel technique for obtaining very high stability and reproducibility of a Raman spectrum, using grating corrected laser stabilization. An externally stabilized laser with a grating spectrometer provides exceptional quantum efficiency in the entire dynamic range. These components then are used to build a library of pharmaceutical raw materials and tested on samples of unknown material.

Due to its high information, vibrational content, the Raman spectrum provides important and specific molecular information. In this article, Raman microanalysis and instrumentation is discussed with specific application to the forensic science laboratory, where evidence integrity is of the utmost importance.

The acquisition of Raman spectra can be eased greatly through the use of surface-enhanced Raman spectroscopy (SERS). In this article, the authors discuss a new substrate technology that delivers reliable and consistent surface enhancement.