product review
Raman f lexes its muscles Raman instruments are advancing to novel applications and markets. Rajendrani Mukhopadhyay
A
n “awakened giant” is how M. Bonner Denton at the University of Arizona likes to describe the current state of Raman spectroscopy. “I used to say Raman was the awakening giant of molecular spectroscopy,” he says. “Today, I say it’s the awakened giant of molecular spectroscopy. Raman is useful for everything from process control to routine analytical measurement, from measurement of exotic species to elucidation of structure.” Indeed, these days, the applications for Raman spectroscopy cover a mind-boggling range. The instruments—available as laboratory, industrial-process-control, and portable systems—are used for analyzing products in petrochemical and pharmaceutical plants; understanding properties of nanoscale materials; identification of mysterious materials by first responders; authentication of gems and minerals; clinical diagnostics; analysis of artworks and archeological objects; and even in forest science for studying variations in wood. The wide range of applications is reflected in the number of companies. Since previous Analytical Chemistry surveys of benchtop and portable Raman instruments were done (2002, 74, 433 A– 438 A; 2003, 75, 75 A–78 A), the number of companies offering Raman-based products has expanded. They include both small start-up companies and established manufacturers of analytical instrumentation. Some companies were formerly manufacturers for the telecommunications industry; when that sector went bust, they retooled their products to produce miniaturized Raman instruments. The tables list different types of Raman instruments. Table 1 lists examples of systems for lab-based analysis; Table 2 lists portable instruments that are made for customers outside of the scientific arena. Systems in Table 3 are geared for industrial process control. Note that the tables are meant to be representative, not comprehensive; vendors may offer similar products not included here.
He and his colleagues observed the phenomenon with filtered sunlight as a monochromatic source of photons, a colored filter as a monochromator, and the human eye as detector. But in its early life, Raman spectroscopy had a narrow appeal because of the need for specialized training. In the 1980s, the introduction of FT-Raman by D. Bruce Chase and Tomas Hirschfeld at DuPont piqued interest of some industrial laboratories because they could tweak their existing FTIR spectrometers to carry out the analysis. But in general, Raman’s applications remained limited by its relatively weak signal and lack of sensitivity. In the late 1980s, CCD detectors, small spectrographs, holographic filters, and diode lasers came along. These and other advances created instruments that were more sensitive, but from the late 1980s through the late 1990s, applications only spread to pure materials analysis, pharmaceuticals, plastics, and industrial process control. In the early 2000s, the attitude palpably changed. Now, Richard McCreery at the University of Alberta (Canada) observes, “There seems to be a bit of a renaissance.”
Beginning of Raman
Awake and reaching out
Sir C. V. Raman gave his name to the inelastic scattering of light and won the Nobel Prize in Physics in 1930 for the discovery. (The story goes that he declined alcohol for the Nobel Prize toast by saying, “Sir, you have seen the Raman effect on alcohol. Please do not try to see the alcohol effect on Raman.”)
The pace of the Raman market has picked up lately. Raman’s market size, currently ~$50 million worldwide, has always been smaller than IR spectroscopy’s ~$350 million market, but its growth is more rapid. According to the vendors, the market for Raman instruments has been growing by double
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Table 1. Selected laboratory Raman instruments.1 Product
Company
Cost (U.S.D.)
Applications
Senterra Raman Microscope
Bruker Optics, Inc. 978-439-9899 www.brukeroptics.com
r$80,000
Pharmaceutical, materials science, contamiIncorporates patented technology that makes nant identification, forensic science, biological analysis powerful, flexible, and easy to use; samples, and biomedical devices and products proprietary method for automatic calibration allows the user to easily and reliably collect Raman data; automatic fluorescence rejection eliminates fluorescence from many samples
Description of instrument
Multimodal Centice Corp. Multiplex 919-653-0424 Spectrometer www.centice.com
$19,995 (for fully Material identification for use in industries integrated system such as chemical, pharmaceutical, consumer with 785-nm laser) goods, food processing, and hazmat identification; also ideal for research laboratories and teaching environments
ExamineR Raman Microscope
Contact vendor for Life sciences, nanotechnology, semiconductor, Combines microscopy and Raman spectrosquote microbiology, geology, and forensic science copy to produce an affordable Raman microscope with outstanding imaging and spectral characteristics; the Raman module sits on top of the microscope, which reduces the laboratory footprint; changing excitation lasers is as simple as switching modules
DeltaNu 307-745-9148 www.deltanu.com
Delivers high sensitivity without compromising resolution by using a wide-area coded entrance aperture instead of a narrow slit; this feature also allows for low power density on the sample, preventing sample degradation and irreproducibility, by measuring a representative volume of a sample
FORAM 685-2 Foster & Freeman 888-445-5048 www.fosterfreeman.com
$56,000
Forensic applications such as the examination Compact benchtop Raman microscope with a of questionable documents, explosives, narcot- 680.4-nm laser, xyz manipulation stage, and ics, and trace evidence integral color FireWire camera for sample alignment; software includes spectral library tools, fluorescence correction algorithms, and forensic casework management; instrument is a class 3R laser product registered with the U.S. Food and Drug Administration
Aramis Confocal Raman Microscope
$120,000–350,000
Pharmaceuticals, clinical, polymers, product or contaminant identification, corrosion films, art and archaeology, semiconductors, carbon nanotubes, and ceramics and glasses
Comes with excitation wavelengths between 220 nm and 1.1 µm; up to four lasers and four gratings can be accommodated; benchtop system offers high spectral resolution that can be fully automated for selection of all functions; FTIR accessory with Same Spot Technology provides full synergism of Raman with FTIR
NRS-3000 JASCO Inc. Dispersive 800-333-5272 Raman www.jascoinc.com Spectroscopy Systems
$120,000–250,000
Pharmaceuticals, nanomaterials, chemical identification, semiconductors, polymers, ceramics and glasses, quality control and assurance, and education
Integrated Raman microscopy systems, with laser auto align, that range from single laser, single grating to advanced research-grade systems; up to three software-controlled, interchangeable gratings for enhanced lowwavenumber measurements; wavelength extension from deep UV through NIR; can add up to six lasers
RamanRxn1
r$70,000 (for academic system configurations)
R&D, process analytical measurements, chemical, pharmaceutical, nanotechnology, forensics, polymers, semiconductors, catalysts, geology, art and archaeology, gems, and bioprocessing
Laboratory model can be equipped with a variety of fiber-optic probes (for noncontact or reaction analysis with immersion sampling) or a microprobe (that can be used with a motorized stage); sample chambers for routine measurements are available; other microprobe options include confocal, heat/freezing stage, h and polarization; P AT technology can be used for representative sampling of solid materials in quality assurance and control
r$14,000
Research, education, forensic sciences, homeland security, materials research, pharmaceutical industry, polymers, process control, chemicals identification, and quality control
System provides rapid and reliable nondestructive analysis of liquids and solids; the QE65000 is designed for use at low light levels and configured for the required laser excitation wavelength; choice of 532- or 785-nm lasers and optical fiber probes; requires Spectrasuite system software
HORIBA Jobin Yvon 732-494-8660 www.jobinyvon.com
Kaiser Optical Systems 734-665-8083 www.kosi.com
Modular Ocean Optics Raman 727-733-2447 Spectroscopy www.oceanoptics.com Measurement Tools
1
Some companies may offer similar products not listed here. Contact the vendors for their full product lines.
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product review
Table 1. Selected laboratory Raman instruments (continued).1 Product
Cost (U.S.D.)
Applications
RamanStation PerkinElmer 400 800-762-4000 www.perkinelmer.com
Company
$60,000–150,000
Academic research, pharmaceutical research, High-performance, push-button dispersive process control, forensics, polymers, and ma- Raman spectrometer; incorporates a high-resoterials science lution CCD camera and 785-nm laser; provides full spectral range with high resolution and no moving parts; rapid acquisition, chemical imaging, and multisample analysis; remote sampling or reaction monitoring is possible using an optional fiber-optic probe
Description of instrument
TriVista and TriVista CRS
PI/Acton 978-263-3584 www.piacton.com
$89,750–200,000
Materials characterization, semiconductors, carbon nanotubes, biomaterials, and geology
Versatile systems that can be used in single or triple configurations; multiple experiments can be set up simultaneously; has the highest stray-light rejection and spectral resolution in a commercial instrument; upright and inverted microscopes and macro sampling accessories available; configurable for multiple excitation sources
Raman Microscope
Renishaw 847-286-9953 www.renishaw.com
$75,000– 500,000
Materials characterization, forensic analysis, and process analytical methods
Submicrometer spatial resolution with autoalignment; internal calibration and performance validation; configurable to include multiple excitation sources from UV through NIR with automated laser switching and alignment; interfaces for atomic force and scanning electron microscopes; global Raman imaging; 2D and 3D mapping and depth profiling
Model 3510 River Diagnostics Skin Compo- +31-10-408-9267 sition Anawww.riverd.com lyzer
Contact vendor for Skin science, cosmetics, transdermals/pharma- Meets the high standards required for practiquote ceuticals, nutraceuticals, and biologicals cal measurements of biological tissue in vivo, especially skin; in combination with dedicated software, obtains previously inaccessible information on the depth-resolved chemical composition of skin
STR series SEKI Technotron Laser Raman 408-986-9190 Spectrometer www.seki.com.sg
Contact vendor for Carbon-vapor deposited diamonds and nano- Highly compact and flexible system; high sensiquote diamonds, carbon nanotubes, surface science, tivity to measure weak Raman scattering; sysand polymer composition and structure tem comes with visible and NIR excitation laser sources that allow a wide variety of samples, including organic compounds, to be scanned
XR Series
Thermo Scientific (a part of $75,000–350,000 Thermo Fisher Scientific) 800-532-4752 www.thermo.com
Pharmaceuticals, forensics, polymers, specialty Complete line of FT and dispersive Raman chemicals, thin films and coatings, microelec- instrumentation designed to function as true tronics, food and beverages, semiconductors, analytical tools for quality control and research geology, art and archaeology, and gemology environments; users can quickly generate highquality, reliable data without having to become specialists
Synergy FT-Raman Accessory
Varian, Inc. 650-213-8000 www.varianinc.com
Pharmaceuticals, polymers, forensics, and materials
1
$80,000–90,000
Research-grade, external accessory for Varian Excalibur and FTS 7000 series FTIR spectrometers; includes a 2-W Nd:YAG laser operating at 1064 nm, selectable Rayleigh rejection filters, and liquid-nitrogen-cooled germanium detector; refractive collection optics and polarizer for accurate measurement of depolarization ratios are also available
Some companies may offer similar products not listed here. Contact the vendors for their full product lines.
digit percentages during the past 18 months. In comparison, the growth of the market for IR instruments has held steady at an ~3% annual rate. There are a couple of reasons for the dramatic growth. “Right now, the Raman market seems to be dividing itself into two parts,” says Richard Bormett of Renishaw. “The first part belongs to those who require research-grade instruments. The instruments can be customized or reconfigured by the user as their needs change.” Most laboratory and process-control systems fall into this category.
The second part, Bormett says, are the “static” instruments that are hardwired for a targeted application. A significant portion of the growth has been pushed by the introduction of these instruments, which tend to be handheld Raman spectrometers. They don’t require much technical expertise to operate, so the customer base has opened up beyond the industrial and academic R&D laboratories. Most portable instruments are designed such that the user just has to point to a sample and push a button. The instrument collects a spectrum, runs a comparison between the colM A Y 1 , 2 0 0 7 / A N A LY T I C A L C H E M I S T R Y
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lected spectrum and a library of known spectra, and comes up with hits in a matter of minutes or even seconds. Vendors are now talking about equipping police cars with miniaturized Raman spectrometers for analyzing mysterious white powders and installing instruments at loading docks so inspectors can check all the raw materials entering pharmaceutical plants. More people can now afford Raman instruments because their price has come down a bit, thanks to cheaper parts such as lasers. The less expensive instruments have helped spur the growth of the industry. Also, the development of Raman microscopy, in which the principles of Raman are coupled into a microscope format, has helped. With this technique, researchers can carry out Raman confocal measurements and imaging and get depth information about materials.
The allure of Raman One of the attractions of Raman spectroscopy is that “all material objects give a Raman spectrum,” says Richard Van Duyne of Northwestern University. “Nothing is Raman-silent except for monoatomic rare gases, which have no vibrations.” This means “you can apply it to just about anything, from gases to liquids to solids,” says Gerwin Puppels of Erasmus Medical Center (The Netherlands). The molecular specificity of the technique is another strong point. Van Duyne says it is absolutely unrivaled. “Raman has better specificity than IR spectroscopy. Only NMR spectroscopy beats Raman in terms of specificity.” The technique doesn’t require any sample preparation. “You can apply it in situ. You [can] take the technique to a sample of interest instead of having to do a lot of sample preparation for an instrument,” says Puppels. This combination—no sample preparation and applicability to all kinds of materials—means that analyses in forensics, homeland security, and clinical diagnostics have become of great interest. The nondestructive nature of Raman has caught the attention of gemologists and mineralogists. In gem and mineral identification, X-ray powder diffraction is the analytical gold standard, but it is a destructive method. Denton recounts an incident; “A gentleman brought us a pink sapphire crystal that had a blue inclusion in it. No one knew what the blue inclusion was, and no one had seen a sample like it before.” Because of the crystal’s uniqueness, the gentleman wanted to know what the blue inclusion was. But since the gem potentially was the only one of its kind in the world, he was understandably hesitant to crack it open for analysis. Denton and his colleagues used a confocal Raman microscope, which they focused into the blue section and obtained its spectra. Denton says, “We subsequently identified the material as hauyne,” a sodium calcium aluminum silicate with sulfate and chloride. Furthermore, the Raman effect can be observed through bottles, blister packs, and other types of packaging, making the technique attractive for authentication of pharmaceutical compounds and identification of potentially hazardous materials or illicit drugs. To illustrate the point, Eric Schmidt of Ahura Scientific says, “We often do a demo with Excedrin. We bring in a bottle of Excedrin from the drugstore and 3268
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shoot through the bottle to the tablets.” The resulting spectrum, he says, shows a mixture of the tablet ingredients like acetaminophen, aspirin, and caffeine. And even if the fingerprint of the plastic bottle ends up in the spectrum, Schmidt says it’s possible to recognize and take it into account. And Raman isn’t just for identification of molecules. “A lot of people aren’t widely aware of it, but experts in the field certainly are, that Raman is a quantitative technique,” points out Denton. “We’ve done sub-part-per-million analysis using dispersive Raman.” Raman analysis obtains information complementary to IR, and sometimes even NMR, spectra. “In Raman, the selection rules for which vibrations are Raman-active are different from the selection rules for IR. So a band that’s very strong in the IR may be weak or not even present in the Raman spectra and vice versa,” explains Dave Drapcho of Varian. “If you want to collect the entire vibrational spectrum of a molecule, you need both Raman and IR.” In some cases, Raman works when other types of spectroscopic analysis fail. For instance, IR spectroscopy is often stumped when water is involved because its fingerprint overwhelms the spectrum. Raman analysis is unaffected by water. In addition, experts point out that, unlike IR, Raman is better at recognizing whether a material is amorphous or crystalline. “You can get the same information from IR,” says Drapcho. “But the Raman spectrum is a bit more sensitive to those types of physical differences that you have in a compound.” Clinical applications of Raman spectroscopy are tantalizing because other techniques that give a comparable amount of detailed information, such as PCR and gel electrophoresis, are much more expensive and time-consuming and demand technical expertise from the user. “We’re convinced that Raman spectroscopy will become a very important clinical technology” with applications in oncology, atherosclerosis, and cell identification, says Puppels. In tissue and cellular analysis, Puppels explains, “The Raman spectrum is a representation of the overall molecular composition of a cell or of a tissue. As soon as tissue A is different from tissue B or cell A is different from cell B, it will be reflected, at one level or another, in differences in molecular composition. That will lead to differences in the Raman spectrum.” The differences in the spectra will be small—Puppels says they need to reproducibly measure differences on the order of 0.1%, but current instruments make this possible.
Problems and solutions But just as with every technique, Raman has its limitations. One is that it’s a relatively weak phenomenon because the effect is based on scattering of photons. “It is a technique where you have to be very careful to use all the photons that are available because there aren’t too many of them,” says Puppels. “The signal, if you compare with fluorescence, is weak.” But he and other experts say that the sensitivity of the instruments has improved significantly enough to compensate. Experts point to surface-enhanced Raman scattering (SERS) as a way to bypass the sensitivity problem (1). It’s a
product review
Table 2. Selected portable Raman systems.1 Product
Company
Cost (U.S.D.)
TruScan
Ahura Scientific, Inc. 978-657-5555 www.ahurascientific.com
~$50,000 including Incoming raw material verification, inspeclibraries and 24/7 tion of intermediate and final products; procustomer support cess troubleshooting; counterfeit identification for pharmaceuticals, fine chemicals; and petrochemical industries
Rugged, handheld system for rapid, accurate materials verification; designed for nontechnical operators so it’s easy to use; results obtained in 10,000 compounds from wellestablished databases; customers can build and manage their own libraries
InPhotote InPhotonics portable 781-440-0202 Raman spec- www.inphotonics.com trometer
r$45,000
On-site forensic analyses, homeland security, environmental analysis, quality control, and any application requiring high-quality data and portability
Provides lab-quality data in a portable pack–1 age; has 4-cm resolution, high sensitivity, and excellent stability for on-site chemical identification and quantitation; flexible sampling is achieved via the RamanProbe line of fiber-optic probes for through-package or in situ measurements
RSLPlus
$24,950
Petrochemicals, pharmaceuticals, foods, forensics, biologicals, hazardous materials, toxic applications, cosmetics; can be used for academic research
Battery-powered, handheld systems weigh
