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Raman spectroscopy has become an increasingly common analytical method for real-time, on-line, in-line, and off-line in situ monitoring of product quality in a variety of pharmaceutical, chemical, and biological manufacturing environments, including wastewater quality [1]. The major shortcomings of Raman spectroscopy conducted in the near UV, visible, and IR are that: 1) highly efficient fluorescence emissions from targeted and surrounding materials within the excitation volume of a complex sample often obscures or alters the Raman signature of the materials of interest [2,3,4]; 2) essential and informative fluorescence features of many organic and biological materials are not excited when excitation occurs at wavelengths longer than 250 nm [5]; and 3) Raman signal strength is diminished due to Rayleigh Law and lack of resonance effects. This is especially true of simple organic compounds and biological materials such as amino acids, proteins, peptides, and whole microbial organisms as well as a wide range of active pharmaceutical ingredients as well as their presence in other manufacturing environments and environmentally in wastewater. Unless excitation occurs at wavelength less than about 250 nm, there is significant overlap between Raman and native fluorescence spectral regions from a wide array of organic and biological materials including active pharmaceutical ingredients (APIs) and excipients. This overlap obscures weak Raman emissions and alters the emission spectra of fluorescence emissions due to strong CH and OH Raman bands, both of which reduce the fidelity of spectral classification. This overlap is considerably worse for excitation above 260 nm. Raman emissions provide information about the chemical bonds within the mixtures present in the excitation volume of detection. Fluorescence emissions provide complementary information about the overall electronic configuration of the targeted material. Together, Raman and fluorescence information more fully describe the chemical compounds of interest. Simultaneous acquisition of both forms of emissions coupled with chemometric analysis enables detection and characterization of a wide range of organic and biological material not possible when excitation occurs in the near UV, visible, or IR. We will describe two, new, compact, low cost, instruments employing deep UV excitation to address these growing applications: the DUV Raman PL 200, and the TraC-X. The DUV Raman PL 200 is a portable, 7”x 8”x 25”, 22 lb instrument, which is fully self-contained including a 248 nm laser and controller, a spectrometer with two, computer controlled, holographic gratings, and a multi-stage thermo-electrically cooled 2048x122 element, back thinned, back illuminated, high quantum efficiency detector. And we will also describe the TraC-X sensor, a 3”x 3.5”x 7.5”, < 2 lb, fully self-contained, deep UV excited autofluorescence-only instrument, with built-in deep UV source, low spectral resolution spectrometer, detectors, and microprocessor for analyzing spectral results and providing processed information. As examples, we will discuss applications for real-time in situ monitoring of APIs during continuous liquid and powder manufacturing in the pharmaceutical industry and measurement of nitrates and nitrites in wastewater treatment plants.
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