Raman spectroscopy has undergone a revolution during the last seven to 10 years, largely as a result of massive investment in the telecommunications industry. What were previously very large benchtop instruments requiring a Ph.D. operator, liquid nitrogen cooling, and price tags approaching $500,000 have evolved into portable and even handheld instruments suitable for both laboratory and field operations.
“The catchphrase here is ‘out of the lab,’” says Eric Bergles, VP of sales and marketing at Bayspec (San Jose, CA). “And that has been the key to applying Raman to new markets and applications, which are cropping up everywhere.”
Raman is effective for noncontact, nondestructive chemical analysis. Its attraction has been its applicability to many sample types with no preparation required.
One knock against Raman, however, is that many materials exhibit light-induced fluorescence when common Raman excitation wavelengths of 532 nm or 785 nm excitation wavelengths are used. Fluorescence interference may be tens or hundreds of times higher than the useful Raman signal.
But at longer-wavelength 1064 nm excitation, Raman overcomes interfering fluorescence, enabling the practical application of Raman in situations where it could not previously be used.
Over the next decade, Mr. Bergles sees Raman moving into food inspection applications, among others. With up to 40 percent of our produce coming from overseas, monitoring fruits and vegetables for pesticide residues through traditional testing could hold up shipments for days or weeks. “With Raman, you can do spot checks and know instantly if the produce is contaminated.”
Perhaps no industry has been as slow to take analysis “out of the lab” as highly protocol- and regulationdriven pharmaceutical manufacturing. Seven years into the U.S. Food and Drug Administration’s PAT (Process Analytic Technology) initiative, samples from production suites are still walked over to a wet lab, where their analysis can take hours, sometimes days.
For small-molecule drug making, Raman is used to image the distribution of ingredients in pills and to confirm the identity of raw materials at loading docks, but its application is nowhere as diverse as in broader industry. And despite having several applications where Raman would be ideal, biotech manufacturing is still farther behind than small-molecule drug manufacturing.
A 2011 report from VTT Technical Research Centre of Finland notes that Raman has not been applied to bioprocessing despite being standard in other process industries.
One downside of Raman as an atline or in-line bioprocess “laboratory,” says Lee Smith, Ph.D., president of Process Instruments (Salt Lake City, UT), is the presence of highly colored or fluorescent materials. “When present, they will swamp the weak Raman signal,” he says. A corollary is that Raman is not particularly sensitive below part-permillion concentrations.
In a bioreactor, Raman is capable of detecting analytes currently measured by sensors or off-line analysis (e.g., HPLC and LC-MS). Examples are glucose, lactate, glutamine, glutamate, cell density, osmolality, ammonium, and dissolved gases. Unlike off-line measurements, Raman provides numbers in real time.
A group at Biogen Idec (Weston, MA) recently reported the use of real-time Raman spectroscopy for measuring growth and metabolic profiles of mammalian cell cultures, as well as levels of cell metabolites.
- Provides great laser stabilization and narrow linewidth with CleanLaze® technology
- Features a spectral resolution as fine as 3cm-1, wide Raman shift coverage up to 4000cm-1, and a TE cooled 2048 pixel CCD array
- Now offers an 830nm excitation wavelength option in addition to the current 785nm and 532nm configurations
B&W Tek, Inc.
Elixir™ Multi-functional Analytical Tool
- Designed to be a cost effective, multi-functional tool for the forensic laboratory
- Combines the ability to measure the refractive index of glass with high resolution microscope imaging and microspectroscopy by transmission, reflectance, fluorescence and polarization
- Features the ability to measure Raman spectra of microscopic samples
- Combines a scientific-grade, back-thinned CCD array detector, high-throughput optical bench and advanced electronics to create a remarkably sensitive system for demanding low-light level Raman applications from 150-2100 cm-1
- Designed for use with 785 nm lasers and can accommodate both probe- and cuvette-based analysis of aqueous solutions, powders and surface media
TruScan RM Handheld
- Features highly selective Raman spectroscopy
- Provides fast, point of need raw material identification (10-15 seconds)
- Portable, handheld and weighs less than 2 lbs (0.9kg)
- Clear PASS or FAIL results enable user independence and require no secondary interpretation
Thermo Fisher Scientific