Wavelength Tech Forum: Raman

June 13, 2008

This month's Technology Forum looks at the topic of Raman and the trends and issues surrounding it. Joining us for this discussion are Dr. Troy Alexander, Teamleader of the Radiometric Sensor Development and Applications Team at the U. S. Army Research Laboratory-Sensors and Electron Devices Directorate; Joe Hodkiewicz, Director of Raman, with Thermo Fisher Scientific; and Dr. Jorge Macho, Director, Total Technical Service, with Ocean Optics, Inc.

This month's Technology Forum looks at the topic of Raman and the trends and issues surrounding it. Joining us for this discussion are Dr. Troy Alexander, Teamleader of the Radiometric Sensor Development and Applications Team at the U. S. Army Research Laboratory-Sensors and Electron Devices Directorate; Joe Hodkiewicz, Director of Raman, with Thermo Fisher Scientific; and Dr. Jorge Macho, Director, Total Technical Service, with Ocean Optics, Inc.

How can Raman be used in detecting biological weapons and/or hazards?

(Alexander) Recently, there has been significant interest in utilization of various Raman spectroscopic techniques for rapid and accurate determination of phenotypically diverse biological threat agents ranging from toxins to bacterial cells. Of particular interest is surface-enhanced Raman spectroscopy (SERS). SERS has experienced a substantial growth in interest due to its high sensitivity coupled to significant chemical information content. Noteworthy, several different research groups have demonstrated that SERS can be used to unambiguously identify small amounts of toxins, viruses, bacterial endospores and bacterial cells. In at least one case, detection sensitivity has been demonstrated to be sufficient enough to detect a single micron-sized bacterial endospore. No doubt the resurgence in interest for SERS has been driven by the relatively recent maturation of techniques to reliably fabricate nano-scale roughened/patterned plasmonic surfaces. Ready availability of nano-scale plasmonic (i.e., SERS-active) surfaces has made application of SERS to biological threat agent detection a much more attractive endeavor than in past decades.

(Macho) Today the main interest in biochemical hazards is to be able to identify threats on the field. The best solution will be a portable SERS system with adequate libraries and fingerprinting software.

In what ways is Raman being used in biomedical diagnostic procedures?

(Alexander) Vigorous research has been underway to develop novel Raman-based methods and instrumentation focused on biomedical diagnostics. While still largely at the research phase, many of these approaches illustrate high potential for success and may vastly increase or improve diagnostic tools available to both medical and veterinary practitioners. Notable among recent developments are methods to a) monitor the onset of very early tooth decay; b) perform ex-vivo tissue analysis (i.e., biopsy); c) perform transcutaneous blood analysis; and d) urine analysis. In addition to substantially reducing diagnosis time, such Raman spectroscopic approaches have the potential to greatly improve flexibility provided to medical professionals.

(Hodkiewicz) A great deal of experimental work is currently being done using Raman spectroscopy as a diagnostic aid. Raman is being investigated as a means of identifying cancerous cells, bacteria, viruses, and even plaques within arteries. Most of this work is still at the early stages and being done in the laboratory, but Raman shows a great deal of promise for many of the applications and will undoubtedly play a greater role in medical diagnostics in the future.

(Macho) Another common trend and potential market expansion is in the biomedical field. There is a lot of research and available instrumentation and applications that utilize miniature portable, fiber optic-based, Raman spectrometers. Some applications include: cancer detection, non-intrusive metabolites analysis, dialysis control, and diabetes among others that are published every day.

What impact has Raman had on the field of nanotechnology in recent years?

(Alexander) Raman has had a tremendous impact on nanotechnology over the past decade. More specifically, it is arguable that the resurgence of surface-enhanced Raman spectroscopy (SERS) has been driven by the maturation of nanotechnology and micromachining techniques. For example, within the past five years SERS-active nanopatterned surfaces have been developed and marketed which are sensitive and quantifiably homogenous. Additionally, the Surface Enhanced Raman Scattering Science and Technology Fundamentals program (recently initiated by the Defense Advanced Research Projects Agency (DARPA), has been formulated to focus on development of fabrication methodologies which can be leveraged to produce high sensitivity and reproducible SERS-active metallic surfaces. Fruits of this program are expected to exert a significant impact on the broader acceptance of SERS for applications beyond routine spectrochemical analysis.

(Hodkiewicz) Raman spectroscopy has proven to be extremely useful for basic research in nanotechnology. In particular, Raman can provide a great deal of information on the structure of carbon nanotubes. Raman spectroscopy has contributed to the work of many researchers working on means of synthesizing carbon nanotubes. Now the push is to functionalize and apply carbon nanotubes and again Raman is providing useful insights into these processes which is almost certainly speeding the development.

(Macho) Raman is one of the main techniques used for characterization of carbon nanotubes, diamond thin films, and other nanotechnology-related materials. At the same time, nanotechnology has generated new and easy applications for SERS analysis.

What applications do you see for Raman exploring in the future?

(Alexander) In the near-term, I expect Raman to have a significant impact on applications such as routine medical diagnosis, homeland security, and defense applications. I expect that more long-term applications will likely include spectral sensing applications which must be conducted at locations remote to the event of interest. As for example, forensic remote detection of individuals, selective harvests of food crops, and practical quantum computers.

(Hodkiewicz) The range of possibilities is immense. Raman has a number of attributes which make it very attractive to a wide range of applications. Raman is generally non-destructive, non-contact, information rich, and suitable for use in just about any environment ranging from vacuum to air to aqueous. Raman microscopy is also routinely used to discriminate areas smaller than a micron. This makes the range of potential applications quite large.

(Macho) Technology is moving towards the elimination of fluorescence interference in small systems. Using UV excitation is one of the main technologies aimed to achieve this. Non-fluorescent samples will launch a revolution for on line applications for all kinds of processes since the required chemometric models will be simpler and analysis time will be shorter.

What's new and exciting in the Raman field?

(Alexander) Perhaps one of the most exciting developments in the Raman field in recent years has been the production of compact, battery-driven Raman spectrometers. This development has been well accepted and has gone a long way towards bringing Raman out of the laboratory into real-world applications. Several companies now market hand-held Raman spectrometers which produce high signal-to-noise (S/N) spectra with relatively short acquisition time and powerful onboard computers. However, one area which may benefit from further development is extension of the spectral tuning range provided by these spectrometers. For example, most available hand-held spectrometers are only tunable up to ~ 2400 cm-1; several applications may gain an advantage by extending this range to include Raman shift frequencies up to ~ 4000 cm-1.

(Hodkiewicz) There is development in Raman along a number of fronts right now. A lot of work is being done with surface-enhanced Raman spectroscopy (SERS) to increase detection limits using Raman, new Raman microscopes are pushing well below the one micron barrier, and portable instruments are taking Raman instruments into the field. Personally, I am most excited about the new developments which make Raman into a routine analysis technique that anyone can use and apply. It is these developments that are making Raman accessible to today's busy scientist. Today's scientist needs to be able to effectively utilize a wide array of tools. They need something that they can just walk up to and get meaningful results out of quickly. They do not have the time or the desire to become experts on the technology. Developments that make the technology more accessible are going to expand the community of Raman far beyond what it is today and this is really exciting.

(Macho) Secondary techniques derived from the Raman effect are taking advantage of instrumentation's cost and size reduction as well as systems modularity and flexibility. Surface enhanced Raman spectroscopy is the first technique that is "revitalizing" from these facts; other techniques are following the same steps. Combining SERS techniques with Raman imaging will open a brand new field on chemical and biochemical sensors in the near future.

What do you think?

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