Chris Petty, Thermo Electron Corp.
As recently as a few decades ago, most manufacturing industries worried only about those contaminants in their processes that were large enough to cause product failure or customer complaints. In contrast, troubleshooting labs today run on continual improvements in quality and process, and the obvious contaminants typically have been worked out of the system.
As customer expectations and required materials performance have increased, the contaminants now analyzed are smaller than ever. Analyzing greater numbers of the smallest particles and structures presents new challenges to spectroscopy, which is one of the principal techniques used to identify the chemical identity of a contaminant.
To get at these smaller problems, users tend to rely on a variety of spectroscopy tools, rather than on just one. Infrared microscopy, for example, has been available for a number of years and is extremely popular because the data gathered allows specific identification of the molecular compounds present. The theoretically smallest spot at which a user can look is approximately 10 μm (limited by the wavelength of the light). Modern instrumentation uses techniques such as redundant aperturing to push very close to that limit and to collect pure spectra, avoiding unwanted data from surrounding areas.
To drive an order of magnitude smaller, Raman spectroscopy is growing rapidly as a complementary technique. It provides similarly specific chemical information, which is critical for unique identification. It also is nondestructive and requires little or no sample preparation. Besides contaminant analysis, it is used increasingly in the development of pharmaceutical compounds and in elucidating physical structures.
Advances in Raman spectroscopy may be expected to continue to render the instrumentation simpler to use and the data easier to interpret. Further interfacing with automation will increase sample throughput, and software will be pushed to assist in the characterization and analysis of the huge volumes of data that are produced.
Early examples of this trend can be seen in the systems that are being developed with the pharmaceutical industry for the analysis of polymorphic forms of new drugs. Microtiter plates, typically comprising 96 or 384 wells that each hold a few microscopic crystals of a potential drug in different forms, can be analyzed automatically. The Raman system collects spectra from all the samples, and software categorizes the samples visually to highlight the few that are likely to warrant further study (Figure 1).
Figure 1. Raman spectroscopy gathers specific chemical information, showing which samples require further investigation.
Another class of analytical problems that increasingly is encountered asks not only “What is it?” but also “Where is it?” and “Is it in the location intended?” For this, the techniques of imaging and mapping are being applied with both Raman and Fourier transform IR spectroscopy. Both methods produce data akin to a digital “chemical photograph” of a sample on a microscopic scale. Using the same analogy, traditional microspectroscopy measurement offers information about only one “pixel,” or surface point.
With these techniques, a user can learn the relative position of the detected object and determine if it is where it is supposed to be. Chemical imaging is a different way of thinking about analysis and will be especially useful in manufacturing processes such as those involving polymer laminates in which more complex structures are being developed. A manufacturer can determine if what is seen is the right polymer, if it is where it is intended to be in the structure and if layers are bleeding into one another.
As new spectroscopy techniques develop, such as IR imaging, new applications emerge to take advantage of them. For example, many life sciences researchers have not traditionally used spectroscopy, yet now some are using spectroscopic imaging in areas such as cancer research to probe at a cellular level. They can take tissue samples and, in addition to viewing cell structures, can determine which chemicals are present in each area or where particular materials are concentrated.
Figure 2. Infrared imaging displays the chemical image next to the cell under investigation, offering a much more detailed representation of chemical concentration than traditional microscopy.
Spectroscopy has always been useful here, but it is a big leap from a single measurement to knowing where across the tissue section the relevant chemicals are located. Seeing a chemical image is much less of an imaginative leap than simply looking at a cell through a microscope because suddenly one has a chemical image next to it (Figure 2).
Meet the author
Chris Petty is the spectroscopy group director at Thermo Electron Corp. in Madison, Wis.; email: firstname.lastname@example.org.