Information at the speed of light
Raman spectroscopy is a technology that uses a laser to excite a molecule causing vibrations within the molecule's bonds. These vibrations change the wavelength of the excitation laser light causing a “Raman shift” that can be detected as a molecular fingerprint or spectrum particular to a specific chemical.
Most covalently bonded molecules have a Raman fingerprint. Raman fingerprints are particular to form and are unique for liquid, gas, or the various solid crystalline forms. For this reason Raman can be useful for observing state changes or understanding the polymorphic nature of solids.
Raman may also be used to both identify chemicals and quantify chemical compositions. For quantification the association between Raman intensity (number of scattered photons collected) and composition is mostly linear.
Raman has been around for more than 80 years, however, recent advances in detectors (CCDs used in common digital cameras), lasers (diode- based), and filters (wavelength- selective coatings) have enabled these systems to be made less expensively with greater performance and ruggedness. As a result they have been widely adopted as field based devices to check material purity, identify unknown chemicals as well as to increase digital bandwidth over optical lines in the telecommunications industry.
A Raman spectroscopy instrument has several key advantages now beginning to be exploited by the drug and chemical manufacturing industries:
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- Raman is a non-contact technology, requiring only an optical port to acquire a sample measurement.
- Raman is non-destructive avoiding sampling waste and modification of the substance being tested.
- Raman can couple with fiber-optics, allowing access to difficult to reach locations even with sometimes dangerous working conditions.
- Raman is largely heat insensitive, allowing measurements taken at very high temperatures to be compared to room temperature measurements.
- Raman is highly selective, meaning it can distinguish between very similar compounds easily.
- Raman is complimentary to other commonly used techniques like FTIR permitting better characterization of materials.
- Raman spectral fingerprint region is separate from the water band region permitting measurements to be interference free from moisture.
- Plastic and glass, although having unique Raman fingerprints, scatter at a rate much less than typical drug and chemical compounds allowing easy measurements through many common container materials.
Raman belongs to a class known as vibrational spectroscopy. Infra Red (IR) is the most popular of the other technologies in this class and is widely used to identify chemicals because of its fingerprint profiling. Along with being vibrational, Raman technology can also be grouped as a fundamental structural elucidation tool. In this class of instruments is IR, NMR and Mass Spectrometry which permit an analyst to get information about the basic structure and composition of the molecule under study.
These features make such a device ideal for use at pharmaceutical and chemical plants for measuring raw material quality, finished product potency, catalyst bed efficiency, reaction completion, chemical purity, and blend uniformity.
Limitations of Raman are:
- Dark colored solids are more challenging to measure as they absorb the few photons that are scattered
- Sensitivity of Raman has been improved but is still not at levels seen in mass spectroscopy or liquid chromatography yet
- Purely ionic materials, such as Sodium Hydroxide, NaCl, KBr, HCl, do not have a Raman spectrum
- Native fluorescent species can interfere with data collection in Raman
- Raman does not detect metal compounds
For pharmaceutical, industrial, chemical and biotechnology raw materials Raman is ideally suited as an ID tool. Of the approximately 10,000 most common materials used in the manufacturing industries Raman is suitable for measuring around 8500. Raman highlights:
- Hard to characterize cleaning agents such as chlorine bleach and peroxides can easily be measured and quantified
- Amino acids and vitamins are largely amenable
- Container, lid and liner materials can be identified quickly
- Buffers, solvents, and chromatography media are strong scatterers
- Solvated and anhydrous forms can be differentiated easily
- Polymorphs and Stereoisomers are quite simple
- Active pharmaceutical ingredients (API) exhibit quite strong spectra
- Excipients and inert materials can be identified and initial screening made on their purity
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Click here to learn more about the History of Raman Technology
