Because of the weakness of the Raman signal and the relative high intensity of the laser line, traditional Raman instruments (before 1990) were made with large double monochromators (with a single-channel detector) or large triple monochromators (with a multichannel detector). Many technological innovations starting in about 1990 made it easier to build instruments with higher sensitivity and lower utility requirements (1). Because of this, the percentage of Raman users who do analysis rather than study the light-scattering phenomenon itself has grown, as has the number of publications illustrating solutions to real-world problems. Raman is now known to be a beneficial, easy-to-use technique. While hard numbers are not readily available on the market size (especially taking into account that there were always people who "built" their own systems with monochromators not sold as Raman instruments), we can assume that 20 years ago, before the rapid evolution started, there were probably not more than 150–200 instruments sold per year. On the other hand, according to the 2006 SDI report (2), no less than 860 instruments were shipped in 2005. Their assessment is that the market is far from mature. In this article we will try to indicate why people are using Raman spectroscopy.  

Raman spectroscopy is a light-scattering phenomenon in which a laser photon of well-defined energy (<0.5 cm

  in width) is scattered by a molecule or crystal. Usually this scattering is mediated by vibrational transitions. To have something vibrate, there must be at least two atoms to beat against each other. The more atoms in a molecule or crystal, the more "degrees of freedom," and therefore the greater the number of bands that will appear in the spectrum. So the first thing that we learn is that we are detecting bonded species — single atoms or elemental ions will not have a vibrational spectrum (not rocket science). 

The next question is how to derive analytical information from the spectra. This is where things become interesting. As the number of atoms that vibrate gets bigger, the interpretation gets more challenging. One would like to associate a given band with a particular vibration. Those of you who use IR spectroscopy know that there are bands that are easy to identify (CH, SH, >C=C<, >C=O functional groups), but the spectrum below 1500 cm

  becomes quite complicated. This is because the vibrations of the various atoms are coupled together strongly. Who remembers the coupled pendulum experiment in elementary physics? Two balls of similar mass are hanging from a support. The balls are weakly coupled together with a weak spring. When you start one ball in motion, you will find that the remaining ball will slowly start to move. One mass cannot move independently of anything to which it is coupled. The same thing happens in molecules or crystals. Everything is coupled together, so if you try to imagine isolating the motion of one atom, it will start to pull on atoms of similar masses that have similar bonds (that is, force constants) that are close to it. The result is that if you imagine everything wiggling together, the wiggling will relax into "normal modes," which is a name for the natural vibrations of the system. Each vibration, which defines a natural state, is independent of other vibrations, and each one will have its own characteristics that include frequency, intensity, and polarization properties. If you change the molecule slightly, such as by adding a methyl side group to a linear hydrocarbon, the spectrum will probably change dramatically. The reason that some functional groups do have bands that can be recognized and can be easily identified is that the criteria for similar mass or force constant are not met. So, for CH and SH modes, the proton, which has a very small mass, beats against the C or S. If you calculate the reduced mass for the two groups, you will see that they are quite different, so the frequencies are quite different (2800–3100 cm

  for SH). The reason the CH band can have such a range is that there are often multiple protons on each carbon that couple together, and as a second order effect, the hydrogen motion is affected by what is attached to the carbon. As a rule of thumb, aliphatic CH groups appear below 3000 cm

, ethylenic CH groups appear near 3015 cm

, and aromatic CH groups appear near 3060 cm

. You might wonder why I do not list OH and NH groups. The answer is that when they are isolated from interactions, they have sharp bands at 3334 cm

O, gas phase), but H-bonding has profound effects on the spectra (3). Because the H-bonding in hydroxyl is much stronger than in NH groups, these effects are potentially stronger. The stronger the H-bonding, the more the bands will be downshifted. And when the environment of the NH or OH group is not homogeneous, there can be very large effects on the widths. In liquid H

  wide. But in some aluminum-containing minerals, the OH band splits and is quite sharp. Because of these effects, it often is not easy to spectrally differentiate OH from NH.  

 For anyone interested in using Raman spectroscopy for interpretation of spectra of organic materials, in conjunction with or without IR spectroscopy, it is strongly recommended that a few good references be acquired (4,5). 

The situation for inorganic materials is in some ways more complicated, and in some ways less complicated. For those materials that have identifiable molecular groups (carbonates, nitrates, phosphates, sulfates, silicates, and others in a form of MO

), the number of atoms in the molecules is much more limited than that of organic materials. In these cases the frequency of the symmetric stretch of each of these groups tends to be fairly robust; it can shift somewhat with anion. In the solid form, however, there can be more than one crystal phase, which can cause shifts, crystal field splittings, and correlation field splittings when there is more than one molecular unit in the unit cell. Unfortunately, there is no textbook (of which we are aware) that covers these materials adequately, but we can point you to some literature articles that can get you started (6–8). In addition, you will need to be prepared to learn the geological nomenclature; for instance, the two forms of CaCO

 are called calcite and aragonite. Geologists can tell you the differences in their structures.  

The situation becomes even murkier when you look at inorganic materials in which there really is no molecular functional group in the unit cell. In this case, when there is more than one crystallographic phase, the spectra do not even indicate that the chemistry is identical. The most prominent example is that of carbon. There is graphite, other black carbons in various states of disorder, fullerenes (buckyballs and nanotubes, single-walled and multiwalled), and diamond. All of these structures are pure carbon, but they all have different spectra. Another class of materials with this behavior is some metal oxides. TiO

 both occur in three crystal phases, whose spectra appear totally different. Even SiO

 occurs in many phases, due in part to the ability of silicon to be coordinated tetrahedrally and octahedrally. 

An area of particular importance is that of metal oxides. The Raman spectrum does not directly tell you the oxidation state nor the stoichiometry, but it does provide a "fingerprint" that gives unequivocal identification as a secondary standard. Consider the oxides involved in corrosion of common metals. Fe

, also known as hematite, is orange, and it has a distinctly different spectrum from Fe

), known as magnetite (the mineral that is magnetic and is sometimes used in a compass). Then there are two forms of iron oxy hydroxide, FeOOH; goethite and lepodocrocite have different spectra. Metallic iron is rarely used in its unalloyed form. The oxides of alloys often are composed of more than one metallic element, and the composition is also reflected in the spectra. The best source of information for these systems is the scientific literature, but some information is available in a text by Ross (9). 

The Raman spectra of semiconductors also should be mentioned here. The most common ones are either formed from one element (Si, Ge, diamond) or two elements (III-V and II-VI materials). Si, Ge, and diamond have two atoms in the unit cell, which is why they are Raman active (refer to the discussion at the beginning). The lattices are cubic, so the vibrations of the group IV semiconductors associated with each of the directions in space are degenerate (that means equivalent), so one line appears in the spectrum. The III-V and II-VI semiconductors occur either in the cubic form (analogous to silicon) or the wurtzite form. Remember my comment about geological names? Wurtzite is the geologists' name for ZnS. It is a hexagonal structure closely related to the diamond–silicon structure by rotating every other set of planes in the (111) direction. If one of these semiconductors occurs in the cubic form, there are two possible bands observed in the Raman spectrum. This is a result of the fact that the two atomic types allow for polarity. When the phonon (vibration) is composed of atomic motion parallel to the phonon wavevector (scattering direction), the energy of the field separation adds to the vibrational energy, producing a longitudinal phonon with higher frequency than the transverse phonon. In case you are not confused enough, if there are free carriers, they will shield this effect and the longitudinal optical (LO) phonon (which can be identified by its polarization properties) will appear at the frequency of the transverse optical (TO) phonon. And there is more. There can be electric field effects at the surface due to something called "surface states." And by using different excitation wavelengths, you can control the depth of penetration of the light to separate these various effects. In the wurtzite lattice, there are two functional groups in the unit cell, which is hexagonal. So there are more phonons possible, some of which will also exhibit field effects.  

Then there is bandgap engineering, in which different semiconductors are layered, sometimes with near atomic layer thicknesses. Sometimes layers are repeated to make synthetic crystals called superlattices. The spectra will show effects of boundaries, superlattices, fields, and confinement. Fortunately, there are some textbooks available to help with all this (10,11).  

Before we go on, let me just add that the Raman effect can be mediated by transitions other than vibrations (10). These include electronic transitions (for instance, rare earth ions in crystals or "free electrons" in semiconductors, or plasmons) and magnetic transitions. But usually these are phenomena that are studied by physicists, and not of interest to most analysts.  

Applications in Materials Development, Characterization, and Analysis

So now that we know what we can measure, let's see where it can be useful.  

The polymer molecule can be identified, and its "morphology" characterized. The morphology refers to the physical state of the polymer. In processing, has it been oriented or crystallized? These parameters will affect the performance of the polymer and are engineered into manufactured parts. For example, polyethylene terephthalate (PET) fibers used in tire cords must be strong (high orientation, maybe not so crystalline), and PET films used for drug delivery must be amorphous so that there is a means for the active pharmaceutical ingredient (API) to diffuse. Raman spectra enable differentiation between the amorphous and crystalline phases, and determination of the degree of orientation. Very often, metal oxides such as TiO

 are added to control the optical properties, and these are easily detected and identified.  

Virtually all of the components of the tablets are detectable by Raman spectroscopy. Manufacturers need to know if their final products are consistent with their formulations. How well have the components been mixed? Has the active pharmaceutical ingredient (API) changed polymorph or pseudomorph (acquired or lost water) during the tablet production or during its shelf life? Even though Raman spatial resolution has been considered overkill for this application (laser spot size about 1 μm vs. particle size 20 μm or larger), new techniques are showing how high-sensitivity Raman maps can be acquired over the entire range of the tablets.  

There is a great deal of excitement in this area among researchers who understand the potential that Raman can have in characterizing biological tissue. Not only can lipids, proteins, nucleic acids, and carbohydrates be differentiated, but members of each class have different spectra. This area, however, is far from mature, offering fantastic opportunity for anyone looking to explore new ways to characterize disease processes. 

The ability to record Raman spectra and maps of metal oxides covers the broadest range of scientific disciplines — corrosion, art conservation, paint pigments, and catalysis, to name a few. The end products of corrosion enable one to model the corrosion mechanism, and consequently to figure out how to prevent it. The identification of metal oxides in art pieces enables the conservator to improve their condition, preserving cultural heritage. Identification of oxides enables analysis and quality control of manufactured paints. The systematic analysis of the catalytic surface, under well-defined chemical–physical conditions, provides a detailed understanding of the catalytic mechanism for a given system; subsequent engineering of the catalytic substrate can provide billions of dollars in fuel and product savings. 

Figure 1 shows a Raman image of an iron alloy that had been corroded. The sample had been embedded in epoxy and cross-sectioned. Video images showed areas of varying shades of white and grey. The white areas tended to be nonoxidized metal, whereas the grey regions reflected spectra of a mixture of hematite (Fe

). The Raman image was reconstructed from the hyperspectral cube produced by mapping the sample. Pure spectra were extracted from the cube and used to model the map.  

Figure 1: Micrograph of a corroded metal surface. The piece had been embedded in epoxy, cross-sectioned, and polished. 

Raman spectroscopy has been found to be the method of choice for characterizing carbon nanotubes, and because of the intense enhancement, there is sensitivity to single tubes.  

Figure 2: Model spectra used to fit the hyperspectral cube. The red spectrum represents hematite, and the green spectrum represents magnetite. 

The current state of the art in the engineering of electronic circuits on semiconductors makes use of the fact that engineering strain into the substrate can improve the electronic mobility, and therefore the overall performance. Because of this, strain is being engineered into silicon by several methods, and the strain is being measured with 0.2-μm spatial resolution by the Raman microscope. In addition, Raman has been used to identify contaminating defects on semiconductors as well as many other commercial products.  

Figure 3: (a) Raman images of hematite and magnetite; (b) same as (a) but with two images overlaid. 

In considering any of these applications, keep in mind that Raman spectroscopy might not be a primary measurement. That means that if, for example, you want to determine the crystalline phase of ZrO

, the spectrum doesn't tell you the phase directly (as X-ray diffraction [XRD] would). But once someone has measured the XRD and Raman spectrum of the different phases, you know which spectrum corresponds to which phase. So you can use the Raman spectra to identify the phase under conditions where XRD would not work; that is, at higher spatial resolution.  

Figure 4: Raman image and video overlaid. 

Analysis of engineered and manufactured materials can now benefit from Raman spectroscopy. This follows from the instrumental evolution of the last 20 years. This note surveys what kind of information is available from Raman spectroscopy and what applications can benefit from their measurement. 

 is the Worldwide Raman Applications manager for Horiba Jobin Yvon (Edison, NJ). She can be reached by email at: 

(1) F. Adar, M. Delhaye, and E. DaSilva, 

, July 2006 (Strategic Directions International, Inc., Los Angeles). 

Infrared and Raman Spectro of Polyatomic Molecules

 (D. Van Nostrand, Co., Princeton, New Jersey, 1945). 

Infrared and Raman Characteristic Group Frequencies, Tables and Charts 

(John Wiley and Sons, Ltd., Chichester, UK, 2001). 

(5) D.W. Mayo, A. Miller, and R.W. Hannah, 

Course Notes on the Interpretation of Infrared and Raman Spectra

 (Wiley-Interscience, Hoboken, New Jersey, 2004). 

(7) A. Wang, J. Han, L. Guo, J. Yu, and P. Zeng, 

(8) R. Frost, T. Klopogge, and J. Schmidt, Non-destructive Identification of Minerals by Raman Microscopy, 2003, 

www.sci.qut.edu.au/minerals/ijvs%20Raman%20paper/IJVS%20Raman%20paper.htm

Articles

Molecular Spectroscopy Workbench

Chemical analysts who use spectroscopy to extract molecular information from samples have been following the developments in Raman instrumentation. Vibrational spectroscopy provides detailed molecular information, but Fourier-transform IR has been much easier to use than Raman. Now that Raman equipment is smaller, cheaper, faster, and easier, analysts are interested. Columnist Fran Adar will discuss why.

Raman Applications That Are Driving a Rapidly Expanding Market

Nippon Instruments' PE-1000 Mercury Analyzer is a fully automated mercury analyzer that offers simplicity of operation, high-throughput to increase laboratory efficiency, and detection limits as low as 0.01 ppb in hydrocarbon samples. According to the company, the product utilizes sealed sample vials, a liquid injection autosampler, and a revolutionary design, complete with their new atomic fluorescence detection system. 

ABB's new Horizon MB FT-IR software (used with the MB3000 lab analyzer) reportedly handles a number of spectral formats in native form and also has a large number of import and export options. According to the company, sampling accessories designed for performance, reliability, and ergonomics are offered for both MB3000 (Mid-IR) and MB3600 (Near-IR) Analysis. 

Inorganic Ventures introduces its 2008–2009 catalog of stocked certified reference materials, featuring standards for ICP, ICP-MS, IC, AA, wet chemistry, and the latest EPA methods. According to the company, products are color-coded by application and indexed by both catalog number and subject. 

PIKE Technologies' grazing angle option for its VeeMAX II ATR accessory is designed to aid in the analysis of monomolecular layers on silicon to obtain FT-IR spectra. The accessory reportedly provides high throughput to cut down on sampling time and facilitate detection of the monomolecular layers of silicon without utilizing a liquid nitrogen-cooled detector. Crystal options for the accessory include ZnSe, ZnS, and Si. 

HORIBA Jobin Yvon introduces the XploRA Raman microscope, designed to combine microscopy and chemical analysis. The system retains the full functionality of the user's microscope coupled with high-performance Raman spectroscopy. According to the company, the product has a minimal footprint and includes the GO!™ Guided Operation wizard for ease of use. 

The new Apollo XV SDD from EDAX utilizes the latest generation SDD chip technology for high performance specifications, including energy resolutions of <128eV @ Mn K and <52eV @ C K. According to the company, the new detector expands the EDAX portfolio of silicon drift detectors for all X-ray microanalysis applications. 

Thermo Fisher Scientific introduces air-cooled Peltier accessories for use with the company's UV-vis spectrophotometers. The accessories are designed to deliver precise temperature control in a compact air-cooled design. According to the company, by using air instead of water to regulate the temperature, the accessories eliminate the procedure of monitoring recirculating water levels. 

Retsch's new Mixer Mill MM 400 is designed for fast and efficient homogenization of small sample volumes in the laboratory. According to the company, the product processes a great variety of materials dry, wet, or cryogenically, and is suitable for the mixing of powder with wax prior to pelletizing. 

The In-Spec Nano-Kit from GFS Chemicals is designed specifically for the short pathlength/small sample spectrophotometers that can be used for DNA/RNA quantification tests. According to the company, the kit comes with two standards that allow users to verify the photometric accuracy of their instrument at 260 nm, 280 nm, and 320 nm. 

CVI Melles Griot introduces Universal Controllers that reportedly run DPSS or diode lasers from 405 nm to 660 nm in cw or modulation mode where appropriate. According to the company, a common format and command set simplifies integration, and CDRH/CE turn key and OEM versions are available. 

The XR-100SDD Silicon Drift Detector (SDD) from Amptek reportedly enables extremely high count rate applications with high energy resolution. According to the company, the product is designed for XRF applications from OEM handheld instruments to benchtop analyzers. 

The Thermo Scientific Antaris MX FT-NIR analyzer is designed for QC testing and remote process monitoring using fiber optic technology. According to the company, the system provides data integration with existing PLC or OPC-based protocols plus ERP systems for real-time feedback. 

Bruker Optics' VERTEX 80v vacuum FT-IR spectrometer is designed to provide high rejection of the interference from atmospheric gases, such as water vapor and carbon dioxide. Data acquisition is based on dual-channel 24-bit analog-to-digital converters integrated with the detector, which reportedly yield a high signal-to-noise ratio. According to the company, the instrument's linear air bearing interferometer allows a resolution < 0.07 cm

Hamamatsu Corporation's InGaAs devices for LD monitoring include front-illuminated and back-illuminated InGaAs PIN photodiodes. The company's G8941 series (G8941-01/-02/-03) is a sub-mount and front-illuminated type InGaAs PIN photodiode with active areas ranging from 0.3 mm to 1 mm in diameter, and a back-illuminated InGaAs PIN photo-diode, the G9230-01, is eutectic-bonded to a ceramic substrate, eliminating the need for wire bonding. 

PIKE Technologies introduces the GladiATR diamond ATR accessory for FTIR analysis. The ATR accessory has a monolithic diamond crystal design and is compatible with pressure applications up to 30,000 psi. According to the company, the product provides a full mid-IR spectral range (4000–400 cm

) and extended far-IR spectral range (400–2 cm

-Trometer series CCD array spectrometers from B&W Tek reportedly use a high UV-NIR response wide dynamic range back-thinned CCD array with a low stray light optical bench and are designed for meeting challenging spectroscopic requirements with wide dynamic range, high QE, and high signal-to-noise ratio. 

JASCO's IRT-5000 and IRT-7000 FT-IR microscope accessories are designed with a "Smart Mapping" function that reportedly enables mapping analyses of a limited area without the use of an automated sample stage. According to the company, the products also feature a "Smart Monitoring" function, which allows simultaneous viewing of the full sample image on the software display using an integrated high-resolution CCD camera. 

Hitachi introduces two new UV-Vis models: the U-3900 (single monochromator) and U-3900H (double monochromator). The products are designed to offer high-performance specifications and functionality for a wide range of applications in the environmental, food, biotech, pharma, and chemical industries, as well as material sciences, for liquid and solid sample measurements. 

SPEX CertiPrep's Tinted Indicator surrogate standards enable users to verify that surrogate standards have been added. According to the company, the surrogate standards will change to an orange tint in the presence of neutral or basic solutions and a red tint for acidic solutions. 

The DSi dual SiGNUM interface encoder from Renishaw combines two SiGNUM SR readheads for high accuracy with an angularly repeatable and customer located propoZ reference position, which is unaffected by bearing wander or switch-off. According to the company, the encoder combined with the REXM ring offers better than +/–1 arc second total installed accuracy. The encoder reportedly can operate at speeds as high as 4500 rpm and temperatures as high as 85 °C. 

Departments

Featured products from the spectroscopy marketplace.

Products

 (IBO), a publication of Strategic Directions International, Inc. (SDi), a consulting and market intelligence firm specializing in this market, the total worldwide market for analytical and life science instrumentation and related aftermarket and service revenues was estimated to have exceeded $35 billion in 2007. This represented an overall increase in industry revenues of about 7.0% from 2006, which was somewhat of a surprise given the outlook at the beginning of 2007. The specter of a recession in the United States and a more modest economic slowdown in Europe is a pause for concern, but continued growth in developing countries, especially China and India, should be a countervailing force, particularly if domestic demand in those countries can compensate for reduced export growth. 

Of course, we still must endure the burden of high petroleum prices, Middle East turmoil, and the distraction and future consequences of political change in America and other countries. Nevertheless, opportunities related to continuing demand for commodities such as copper, aluminum, steel, and oil, as well as some renewed strength in the pharmaceutical sector for technology expenditures, should help to offset some global negatives. With all this in mind, SDi projects a slightly lower overall industry revenue increase in 2008 of 6.4%, which is still within the narrow range of growth experienced during the last two years. 

In 2007 it became clear just how important Asia is to the industry. The market in China expanded dramatically, and for some companies it is now their single largest market after the U.S., and growing two to three times as fast. Japan was a disappointment last year, and difficulties in that economy suggest that 2008 will be no better. The European market generally was more robust than North America, although currency exchange rates added uncertainty to economic prospects while affecting supplier financial reports both positively and negatively based on manufacturing locations.  

Figure 1: 2007 spectroscopy market by sector ($7.8 billion). 

Major events of 2007 included the acquisition of Strategene (La Jolla, California) (polymerase chain reaction) and Velocity11 (Menlo Park, California) (laboratory automation) by Agilent Technologies (Wilmington, Delaware) (mass spectrometry [MS], high performance liquid chromatography [HPLC], gas chromatography [GC]), which was a reaffirmation of Agilent's desire to be more deeply involved in the life science market; MDS Sciex's (Concord, Ontario, Canada) (MS) purchase of Molecular Devices (Sunnyvale, California) (microplate readers) for similar reasons; and the final formation of a publicly traded Bruker family of companies with the merger of Bruker Biosciences (optics, X-ray, and MS) and Bruker Biospin (both in Billerica, Massachusetts) (nuclear magnetic resonance [NMR]). We also saw much more focus by industry participants on the applied markets of food safety, forensics, and environmental testing. These companies also benefited from their involvement in the petroleum processing and petrochemical markets. 

There is also a growing interest in the aftermarket aspect of the industry revenue mix, which includes such areas as consumables, software updates, and accessories. This is in recognition of the growing importance of those areas as the market expands and matures. In fact, in some market segments, the aftermarket is growing faster than instrument system revenues and is often more profitable. So it should be noted that all the revenue projections in this article include the total mix of revenue sources: instrument system sales, aftermarket, and service.  

Figure 2: 2007 molecular spectroscopy market by technique. 

The spectroscopy market can be segmented into three distinct sectors: molecular spectroscopy, atomic spectroscopy, and MS. The applications of the techniques included in each sector and their prospects differ significantly, even within each sector. Worldwide revenues for all spectroscopy segments is estimated at $7.8 billion for 2007, or about 22% of the entire laboratory analytical and life science instrument market. The overall spectroscopy market is estimated to have grown 7.6% in 2007, slightly more than what we forecasted last year. SDi projects 2008 spectroscopy market growth to be moderately lower than for 2007, increasing at about 6.7%. This is a function of some of the hotter markets cooling down and a projected global economic slowdown. Still, the spectroscopy market is projected to grow faster than the remainder of the laboratory instrument market, which is a continuation of the pattern for the last three years. 

Molecular spectroscopy techniques account for about 39% of the spectroscopy market, although many diverse techniques are represented that address a wide range of applications in almost every industry category. Atomic spectroscopy is the second largest sector at almost 33%, while MS represents slightly more than 28% of spectroscopy revenues. Please note that LC and GC front-ends to mass spectrometers, and their associated aftermarket and service revenues, are not included in this analysis.  

Figure 3: 2007 atomic spectroscopy market by technique. 

The market for molecular spectroscopy is estimated to have reached $3.1 billion for 2007. Overall, the total revenues for all categories of molecular spectroscopy grew 6.3% last year. However, growth rates differ measurably for the various instrumental techniques, led by the continuing success of the NMR segment, while fluorescence spectroscopy is expected to experience the slowest growth. No single technique dominates this market, although the NMR and UV–vis product segments account for over 50% of the overall molecular spectroscopy market. 

Molecular spectroscopy instruments are especially focused on the important life science industries, including pharmaceutical, biotechnology, and the agriculture, food, and beverage industries, which now account for about 35% of the market. Organic chemicals, academia, and government sectors account for an additional 30% of revenues, much of which is also life science–oriented. But molecular spectroscopy techniques have an enormous range of applications, so they can be found in every industry segment, including environmental testing and polymer manufacturing.  

Figure 4: 2007 mass spectrometry market by technique. 

NMR is one of the highest performance analytical methods commercially available to scientists, and it rivals high-end MS in many respects. The demand for such high-end capabilities seems to have no end, which will help to continue the nearly 10% growth in NMR expected once again in 2008, despite the fact that this segment of the market will account for nearly $1 billion on its own. The ever-increasing strength of the superconducting magnets used in NMR, which correlate strongly with cost, is one of the key drivers in the rampant growth of this market. But so too is demand for NMR probes, which can significantly improve the performance of older NMR systems, of which there is a fairly large installed base. 

The NMR market is comprised of a number of related instrument types, including high-field NMR, hyphenated NMR, low-field (fixed magnet) NMR, imaging NMR, and electron paramagnetic resonance (EPR). High-field NMR and hyphenated NMR (mostly LC–NMR) are pharmaceutical and biotech oriented with a focus on structural analysis. Low field instruments are designed for quality control applications, especially for moisture and fat content analysis in foodstuffs. NMR imaging systems are applicable in clinical and biotech settings for combined imaging and spectral analysis of samples and organisms. There is also renewed interest in the development of mid-range instruments as lower cost alternatives to expensive ultra-high performance instruments, but with significantly better resolution than existing conventional 300 MHz instruments. EPR is a useful technique for the analysis of free radicals, transition metals, and material defects. High-field NMR is by far the largest segment of the market.  

Figure 5: Spectroscopy market by product segment ($ billion). 

Demand for conventional fluorescence spectroscopy, and to a lesser extent UV–vis spectroscopy, continues to be siphoned off by microplate readers that can perform either, or in some cases both, of these analyses on a single platform. Unlike the remainder of the fluorescence market, which consists significantly of niche products, a very large portion of the UV–vis market is made up of photometric colorimeters that are used very heavily in water and environmental monitoring applications. There has been a significant surge in activity in these industries, which is contributing most significantly to the expected growth in the UV–vis market, somewhat offsetting weaker areas of the market. 

The market for color measurement is similar to but quite different from conventional UV and visible spectrophotometers. It is almost entirely disconnected from other molecular spectroscopy markets based on the suppliers participating in the market, and the end-users and their applications. Color matching of paints, textiles, and automotive body finishes is a major application, so portability is an important feature of these instruments. Growing applications include digital imaging, printing, and graphics, and even instruments that aid in tuning high-definition television sets. The color measurement market has seen significant consolidation and is now dominated by X-Rite (Grand Rapids, Michigan), with well over 50% market share. The top three competitors now account for over 80% of global sales. Despite the expected economic slowdown and likely weaker sales of color measurement products to consumers, the laboratory and industrial side of the market should be largely insulated from a downturn.  

Figure 6: Estimated growth by spectroscopy sector for 2008. 

The near infrared (NIR), IR, and Raman spectroscopy markets are all experiencing significant shifts toward alternative design configurations that diverge markedly from conventional laboratory benchtop systems. While some microplate readers can now perform these spectrometric measurements, these instrumental techniques will be largely unaffected. Another important trend is the movement toward on-line applications using remote sensors, especially fiber optics, especially for NIR and Raman, since these techniques are quite adaptable to these applications. A third trend is the focus on handheld Raman and NIR instruments for security applications and on-site polymer analysis. 

The market for atomic spectroscopy instruments is experiencing steady growth and is predicted to expand about 4.7% in 2008, only a slightly lower pace than experienced during the last few years. However, within this $2.5 billion market, growth varies widely for the techniques included. Market demand for atomic spectroscopy instrumentation has especially benefited from the increased global demand for minerals and metals and their concomitant high prices, as well as by recently enacted environmental regulations. These positive market forces do exhibit different influences based on the capabilities and usefulness of individual spectroscopic methods. In addition to application-based market forces, the expanding markets in China, India, and other emerging market countries are shifting the regional demand that suppliers wish to emphasize.  

Table I: Spectroscopy product growth prospects for 2008 

X-ray spectroscopy has been a major growth segment for the last two years, especially X-ray fluorescence (XRF) and X-ray diffraction (XRD). Combined, these two techniques represented more than $1 billion in 2007 revenues. XRF continues to benefit from hazardous substance regulations and related types of analysis. This regulatory climate has stimulated the meteoric rise of handheld XRF instruments, which have moved far beyond the traditional XRF applications in metals analysis into the broader area of consumer product testing, driven by concerns about, for example, lead in Chinese-made toys. However, we are now seeing a leveling off in demand for these handheld instruments and accelerated growth in higher-performance benchtop systems as the application requirements evolve. 

In contrast with XRF, XRD remains largely a laboratory technique. Here the growth has come mainly from product innovation combined with a shift in applications from primarily materials science to life science. XRD is crucial to life science research because of its use in studying protein structures as well as crystalline forms of drugs and other biological molecules of interest. Through the introduction of advanced X-ray sources and detectors, the capabilities of XRD instruments are expanding: they can perform more sophisticated analyses in a shorter amount of time. This increase in productivity naturally comes with an increased price tag, fostering the fastest growth among the atomic spectroscopy techniques.  

Apart from the X-ray techniques, the greatest growth will be experienced by inductively coupled plasma–mass spectrometry (ICP-MS), with growth in the 6–7% range for 2008. Environmental concerns are the main driver. ICP-MS is the most sensitive atomic spectroscopy technique, allowing analyses at the part-per-billion and even part-per-trillion level. Changes in environmental regulations typically have been increasingly restrictive of allowable levels of particular elements such as arsenic. Many countries' regulations are now so stringent for particular elements that ICP-MS is the only practical method of analysis. Similarly, elemental analyzers, those instruments that quantify a small number of specific elements, are also benefiting from environmental regulation. Furthermore, because these instruments are highly specialized, they cater to a wide variety of very particular applications in many industries. Total organic carbon (TOC) analysis is one of the most important of these techniques and has wide application in pharmaceutical and semiconductor laboratories and facilities, as well as for drinking water analysis. 

The market for atomic absorption (AA) instruments is expected to remain flat this year. This actually represents an improvement over last year, which saw a modest decline in the market. China, India, and other industrializing nations continue to be a source of growth for the AA market, while the traditional regional markets continue to be problematic. Lower cost AA instruments are particularly well suited to these emerging markets. The situation is slightly better for other varieties of optical emissions spectroscopy: arc-spark and ICP. Both of these techniques should experience low single-digit growth for the year. Arc-spark's primary application is metals analysis but for primary metals production and recycling. Demand for these instruments has shifted markedly from North America and Western Europe to emerging markets, especially China.  

Elemental analyzers are specific-purpose instruments for the analysis of a limited number of elements. These instruments fall into two broad categories: organic analyzers and inorganic analyzers. Organic analyzers include TOC, CHN and protein, and sum parameters analyzers (total and bound nitrogen and extractable organic halogens). Inorganic analyzers are used for carbon–sulfur determinations and for mercury, arsenic, boron, and cyanide analysis. Organic analyzers, especially TOC analyzers, continue to exhibit much higher growth potential than inorganic analyzers. Pharmaceutical and semiconductor water analysis, as well as food-related applications, drive this market, while metals composition and trace metals analysis are key application areas for inorganic analyzers. While organic analyzers have enjoyed good growth for a number of years, recent interest in metals analysis has given new life to this mature technique. 

With historically strong positions and broad product offerings, Thermo Fisher (Madison, Wisconsin) and PerkinElmer (Shelton, Connecticut) remain safely in the top two positions in overall market share. However, the increasing importance of the X-ray techniques has elevated companies primarily involved in XRF and XRD, namely PANalytical (Natick, Massachusetts), Bruker, and Rigaku (The Woodlands, Texas). Varian (Palo Alto, California) is also an important supplier of AA, ICP, and ICP-MS instrumentation. Spectro Analytical (a division of Ametek, Mahwah, New Jersey) is the leading supplier in arc-spark, while in the variegated world of elemental analyzers, LECO (St. Joseph, Missouri) remains the top company, with Shimadzu (Columbia, Maryland) and Horiba (Edison, New Jersey) as its main competitors. 

For many years now, the MS market has been the growth leader in spectroscopy as the technical performance of various MS products keeps pace with the progressively more challenging analytical applications in the laboratory. The worldwide market for MS neared the $2.2 billion mark in 2007 as revenue growth exceeded 11%. This rapid expansion is expected to continue in 2008. The popularity of MS is clearly a function of its utility. Scientists also are taken by the plethora of exciting new product introductions that promise greater sensitivity, speed, and throughput, and for some products lower prices are hard to resist. 

Most areas of the market will continue to see very strong growth in popularity. The continued investment in research and development by both the private and the public sector for analytical technologies is helping to continue the fairly steady trend in performance improvements in MS. While it is not certain which MS techniques will become the future leaders as a result of technological breakthroughs yet to come to fruition, it is fairly certain that the overall category will remain one of the premier analytical groups for years to come. 

While the pharmaceutical industry will remain the bread and butter of demand for most MS techniques, biotechnology demand will continue to significantly outpace that of the traditional pharmaceutical segment. Demand from secondary industries for MS, including agriculture and food, environmental testing, and petrochemicals, has surged as of late, and that trend is expected to continue into 2008. While this demand surge in the food, environmental, and petrochemical sectors will, to some extent, benefit all segments of the MS market, it will clearly have the most impact on the GC–MS market, which should see very strong growth as it has for the last two years. 

As expected, Agilent Technologies' 2006 entry into the triple-quadrupole and quadrupole time-of-flight (Q-TOF) segments of the market has had a major impact on much of the landscape of the MS market. This was especially evident in the triple quadrupole marketplace, where Agilent quickly surfaced as a formidable competitor, capturing market share and attracting new customers for this important technology, while adding fuel to the fire for the tandem LC–MS market. Agilent's involvement, coupled with strong responses from other suppliers, will contribute to achieving double-digit growth for the tandem LC–MS and LC–TOF market. 

Within the tandem LC–MS market, the triple-quadrupole segment will dominate in 2008, in terms of both size and growth. However, demand for ion trap–based spectrometers also will see nearly double-digit growth, and will be characterized by a shift from conventional three-dimensional mass analyzers to the more innovative two-dimensional and three-dimensional designs that provide more efficient ion trapping capabilities and improved performance. 

Single-quadrupole LC–MS instruments are growing in popularity because they carry lower price tags than tandem LC–MS units and can address routine applications for quality control and environmental analysis very efficiently. Improved mass detectors, as well as the coupling of new generation fast LC systems, increase sensitivity and speed of analysis. Although the matrix-assisted laser desorption ionization (MALDI)-TOF market has settled into a lower level of steady growth, it continues to find favor among various customer groups, especially in the biotech and clinical fields. Magnetic sector is the exception in the MS market, exhibiting minimal to flat growth in demand, but it is still the preferred technique for specialized applications such as isotope ratio analysis for drug scanning and geological applications. GC–MS should benefit from increased opportunities in the petroleum and petrochemical industries as well as from environmental initiatives. 

The Fourier transform (FT)–MS market is trending toward mainstream status, and this should continue in 2008 thanks to the efforts of Thermo Fisher Scientific and its very successful LTQ-FT, first introduced in 2002, and the even more wildly popular LTQ-Orbitrap, which hit the market in 2005. These systems have not only spurred the development of tandem FT-MS systems with ion trap or quadrupole front-ends, and now account for most of the segment's sales, but they have also brought far more attention to the category. This excitement has also benefited other suppliers, including Varian (which now owns the IonSpec) and Bruker Daltonics.  

Although the development of FT-MS has rendered the method far more accessible to a broad swath of scientists, pitting it more directly against Q-TOF MS, demand for Q-TOF continues to experience robust growth, due in part to continued technological advancements, such as Waters' (Milford, Massachusetts) ion mobility enhanced instrument, the HDMS Synapt. The combined growth of the FT-MS and Q-TOF markets demonstrates that there is still an enormous appetite for high performance MS. 

Spectroscopy Continues to Be the Preferred Solution to Analytical Challenges

Every day, a new challenge pops up in laboratories around the world, and more often than not, spectroscopy comes to the rescue. Handheld and benchtop XRF instruments have been helping to reduce lead contamination of waste disposal sites and nearby groundwater for the last two years, and now the presence of lead in toys looks to this technology as a readymade solution. Atomic absorption spectroscopy has been declining in recent years as other techniques such as ICP, ICP-MS, and XRF have offered advantages such as higher sensitivity and faster analysis, albeit at a price. But now the burgeoning applications in emerging markets in Asia and Eastern Europe have given new life to this reliable technology. 

Likewise, the race between HPLC and mass spectrometry as to which is the fastest has led to LC–MS instruments that offer both speed and sensitivity not dreamed of just a few years ago. Such performance can now provide drug development scientists with information in a more timely manner and at a resolution level that engenders confidence. And we must not forget the important structural information that new generations of NMR, X-ray, and MS systems offer to these same challenged developers. 

China and India have now become markets of major interest to mass spectrometer manufacturers as demand soars in those two robust economies. In China, the rapidly expanding petrochemicals industry, coupled with a genuine interest in improving environmental quality, has been a boon to the GC–MS instrument market. China is now one of the top markets for this technology. India, on the other hand, represents an outstanding opportunity for LC–MS instruments in support of its growing pharmaceutical and biotech industries. India was once a market known only for generic drug production, but now it is becoming a location for new drug development as well. China also has made progress in these activities. 

Portable mass spectrometers, handheld UV–vis, and NIR instruments are also providing emergency response personnel, military forces, environmental engineers, and industrial QC inspectors with the technologies to take the analysis to the location instead of taking the sample to the laboratory, saving time, expense, and perhaps lives as well. Miniaturization, clever packaging, and attention to customer needs have enabled spectroscopy manufacturers to deliver solutions that are making big differences in today's dynamic business, social, and political community. 

So the saga continues. New techniques, new markets, and expanding applications all drive innovation, resulting in a growing use of spectroscopy-based technology worldwide and year-round, and perhaps for decades to come. 

 or other instrumentation research, contact Strategic Directions International, Inc. 6242 West-chester Parkway, Suite 100, Los Angeles, CA 90045, (310) 641-4982, fax; (310) 641-8851, E-mail: 

 is President and Chief Executive Officer of Strategic Directions International, Inc., Los Angeles, California. 

Spectroscopy techniques are an important facet of the laboratory analytical and life science instrument industry, which continues to expand as its analytical requirements migrate across industries and geographic regions. Overall industry growth has been in the 6-8% range for the last few years, which is a sign of both its maturity and its stability. The demands of the life science marketplace, environmental concerns, and the search for new materials are important driving forces. Likewise, the shifting market focus from North America and Europe to Asia is changing the face of the industry. It is expected that 2008 will be a good year for the industry despite the likely economic slowdown in North America and Europe.

Spectroscopy: A Technology for All Seasons

It's true, the average spectroscopist's salary actually went down in the past year, a surprising development after many years of steady climbing. For the 772 respondents from all walks of the spectroscopy community who took part in this year's salary survey, change hasn't been good.  

Before we break down salaries, the following are a few statistics regarding this year's survey:  

The average age of all respondents is 46.7 years. The average age of male respondents is 47.9 years, and females is 41.6 years.

On average, respondents have 19.9 years of experience in their profession, and 8.3 years of experience in their current position.

90% of respondents are employed full-time; 4% are postdoctoral researcher/graduate students; 2% are employed part-time; and 1% are unemployed.

17% of respondents are senior scientists/researchers/research fellows; 15% are chemists/spectroscopists; and 15% are laboratory directors/managers.

2% of respondents hold associate's degrees; 32% hold bachelor's degrees; 23% hold master's degrees; and 40% hold doctoral degrees.

57% of respondents have their highest degree in chemistry and 8% in biology.

24% of respondents specialize in applied research/development; 14% in general testing and analysis; and 11% in quality control/assurance validation.

59% of respondents' companies offer in-house training.

Common benefits offered by respondents' companies include 401(k) (75%), retirement plan (62%), and child care (12%).

According to this year's survey, the mean salary for all respondents is $77,634, which is down from $79,605 — a decline of $1,971, and even lower than the 2006 average of $77,980 (see Table I). This represents the first downturn in salary we've seen in our annual survey, but some demographic differences might help explain the decrease. One major difference between this year's salary survey and the last is that the percentage of respondents aged under 39 years was up 6% — it was 21% in 2007 and 27% in 2008. This increased number of respondents with less experience and lower salaries definitely did its part to drag the mean salary of the entire respondent group down this year. Along the same lines, there was a 7% increase in respondents who have under 15 years of professional experience in the spectroscopy field — from 32% in 2007 to 39% in 2008. 

Table I: 2001â2008 Average salaries 

That being said, salaries are still down across the board, as the majority of respondents for this year's survey are reporting lower earnings than last year. In the 2007 salary survey article, it was reported that spectroscopists aged 60 to 64 had a mean salary of $98,319. For 2008, that number went down to $85,953, while respondents over age 65 reported an annual income of $68,681, much less than the $85,733 average income reported last year. However, 27.5% of respondents in the age group of 60 to 64 reported an annual base salary of $100,000 and over. Meanwhile, the average age of survey respondents was 46.7 years, and in that age group, the mean annual base salary for 2008 is $89,873, which is a big improvement over last year's $85,236. So, depending on how you look at it, salaries are down, but it's not as dire as it seems on the surface. 

Rounding out the salaries for the different age groups, respondents ages 20 to 24 earn an annual base salary of $33,600; ages 25 to 29 earn $41,344; ages 30 to 34 earn $64,610; ages 35 to 39 earn $71,395; ages 40 to 44 earn $75,955; ages 45 to 49 earn $89,873; ages 50 to 54 earn $81,999; and ages 55 to 59 earn $90,113 (Figure 1). 

Once again, the gender earnings gap is significantly wide. According to the survey, composed of 75% males and 25% females, males are making $81,481, while females are making significantly less at $65,381, a gap of $16,100, up from $14,218 last year. 

A startling finding in our survey was that males earn more than females at all levels of education. At the associate's degree level, males out-earn females $64,000 to $43,000, the largest difference in the study by a startling margin of $21,000. For respondents with bachelor's degrees, males earn $67,479 to $53,446 for females, a difference of $14,033. The gap grows wider again at the master's degree level, with males earning $78,372 and females reporting an income of $60,473, a margin of $17,899. The smallest difference in salary comes at the doctorate level, but males ($94,927) are still far ahead of females ($87,067), a gap of $7,860. 

The gender salary gap is also present in each level of professional experience. For respondents with less than 5 years of experience, males out-earned females $47,317 to $42,608 — a difference of $4,709. For those with 5 to 9 years of experience, the gap more than doubles, with males earning $67,689 to $57,390 for females — a rift of $10,299. The subsequent years of experience don't get any better for the gender earnings gap. With 10 to 15 years of experience, it's males $80,001 versus females $70,596 (difference: $9,405); with 16 to 20 years of experience, it's males $89,753 versus females $71,756 (difference: $17,997); with 21 to 35 years of experience, it's males $87,028 versus females $77,169 (difference: $9,859); and with 36 to 40 years of experience, it's males $95,158 versus females $82,750 (difference: $15,408). In other words, it takes females between 36 and 40 years to earn slightly more than males are earning within 10 to 15 years (Figure 2). 

Figure 2: Salary gap between males and females at different levels of experience, 2008. 

The gap is just as wide when levels of education are taken into account. Of the respondents who are working with an associate's degree, males earn $64,000 while females earn just $43,000. The gap closes a bit with a bachelor's degree, with males earning $67,479 compared to $53,446 for females — but still a large difference of $14,033. Males leap way ahead with a master's degree, raking in $78,372 versus $60,473 for females, giving them an edge of $17,899. When it comes to doctoral degrees, the gap is narrower, but still significant, with males earning $94,927 compared to $87,067 for females — a margin of $7,860 (Figure 3). 

Figure 3: Salary gap between males and females at different levels of education, 2008. 

Why does such a gap still exist in today's world, where equality is supposed to be the norm? Will this gap ever close, or will it continue to grow? According to David W. Ball, professor of chemistry at Cleveland State University in Ohio, "I certainly hope that the gap closes. The question that this gap brings up is whether it is characteristic of the field of spectroscopy, or whether other technical fields demonstrate the same inequity." 

Respondents in the private sector, the largest employer of scientists again this year (60% of respondents) reported an income of $84,173 in 2008, virtually the same as last year's number of $84,831. Scientists working in acedemia (21% of respondents) are making $60,284 this year, down slightly from $61,189 in 2007. Meanwhile, those working in government/national labs (15% of respondents) have an annual base salary of $76,612, up from $74,853 last year (Figure 4). 

Figure 4: Salary summary by job sector, 2006â2008. 

CEOs received a big raise this year, as respondents with the title of CEO/president reported a mean income of $158,833, up from $144,900 in 2007. Technical directors also recieved a boost of over $10,000, reporting a salary of $103,615, up from $93,000 last year. Another increase occurred for those respondents who fall under the category of senior scientist/researcher/research fellow, with a mean income of $97,321, up from $91,041 in 2007. As for job specialties, the highest earners are those in corporate management, with an income of $179,250. Following that are those in production/manufacturing ($84,077), project management ($82,677), and applied research/development ($82,001). 

Satisfaction, stress, and salary have proven once again that they are closely tied together in the professional lives of our respondents. This year's survey revealed that 44% of respondents are extremely or very satisfied with their current position (up from 33.1% last year), 42% are satisfied (up from 36.7% last year), and 14% are not satisfied or not at all satisfied (up from 4.2% last year) (Figure 5). Respondents who claim to be extremely or very satisfied earn a mean of $85,658 in annual base salary, while those who are satisfied earn $73,866, and those who are not satisfied or not at all satisfied earn $64,800. 

Figure 5: Job satisfaction levels, 2008. 

As satisfaction goes up, it appears that stress goes down. For 2008, 48% of respondents say their stress level at work has increased over the past year (down from 52.4% last year), 45% say it is the same (up from 40.7% last year), and 6% say that their stress level has decreased over the past year (up from 4.6% last year). Interestingly, of those respondents who said their stress has increased, 54.1% were women. Among respondents whose stress level has increased, the most common reasons for the increase are staff management uncertainty (45%), business uncertainty (42%), and negative workplace attitudes (40%). For respondents whose stress level has decreased, the most common reasons for the decrease are improved workplace attitudes (48%), more automation through new equipment (21%), and new technology having increased productivity/quality (21%). 

As for workload, 62% of respondents say their workload has increased over the past year, 31% say it has decreased, and 6% say it is the same. Among respondents whose workload has increased, the most common reasons for the increase are increased business (56%), staffing cuts (44%), and new equipment added to the lab (38%). 

According to our survey, 20% of respondents are considering making a job change in the next year, virtually the same number as last year. For those who are considering a job change, the top reasons for considering a job change are professional advancement (57%), income (53%), and intellectual challenge (38%). 

Once again, education is key when it comes to higher earnings. For 2008, spectroscopists who have obtained doctorates (40% of respondents) have a mean salary of $93,525, which is up from $92,600 last year. Respondents at the associate's degree level (2%) also see an increase in annual base salary with $57,000, up from $50,875 in 2007. 

Figure 6: Stress levels, 2007â2008. 

However, after touting sharp increases in pay last year, this year respondents who hold bachelor's and master's degrees saw a steep decline in their base salaries. Scientists with bachelor's degrees (32%) experienced a drop from $68,292 in 2007 to $63,670 in 2008, a plunge of $4,622 and the first decrease since 2005. Respondent's with master's degrees (23%) experienced a similar plummet, earning $73,341 in 2008, down $4,342 from the 2007 salary of $74,639.  

For the second year in a row, the Southwest (where 16% of respondents live) is the region with the highest average salary, earning an annual income of $89,049, slightly down from $89,735 last year. This year, the Midwest (29% of respondents) earned the least, with $70,040, down from $71,820 in the previous survey. Last year's lowest salary region, the Northwest (5% of respondents), earned $73,135, which is up from $67,306 in 2007. 

Narrowly above the Northwest is the Southeast (16% of respondents), with $73,993 in annual base salary, a big decline from $79,700 last year. The Northeast (26% of respondents) earns second-place honors again this year, with $82,926, slightly up from $82,040 in 2007 (Figure 7). 

Figure 7: Salary summary by geographical location, 2008. 

The data presented in this article are a small sampling of the spectroscopy community as a whole. If you would like to share your thoughts on this article and its data, and how it relates to your career, please e-mail us at: 

 Salary Survey was designed by the corporate research department with the assistance of 

. A link for the online survey was sent to the entire circulation list of 

. The invitation was successfully sent to 20,481 subscribers. A total of 772 individuals responded, for a response rate of 3.8%. The field time of the survey was January 9, 2008, through January 23, 2008. To encourage participation, all subscribers who responded to the survey were entered into a drawing to win one of five $100 gift cards. Maximum Statistical Error @ 95% Confidence Level: +/– 3.6%. 

Spectroscopy staff editor Brian Johnson discusses this year's salaries and trends in employment for spectroscopists.

2008 Salary Survey: Salaries and Stress Shrink

While the overall laboratory UV and Visible spectroscopy market was worth well over $700 million in 2007, the UV/Vis/NIR segment represented less than 10% of it. UV/Vis/NIR instruments utilize multiple detectors to cover a broader spectrum of analysis, and typically are among the highest-end systems in the UV-Vis market. 

More basic and more common UV-Vis spectrophotometers typically make use of a photomultiplier (PMT) detector, which covers the UV and visible spectrum, as well as a portion of the very near infrared (NIR) spectrum up to about 1100 nm. In order to cover the complete NIR spectrum, UV/Vis/NIR systems typically combine a PbS (lead sulfide) detector with the PMT detector, expanding the range to cover the entire NIR spectrum up to 2500 nm, and often well into the mid-infrared, up to 3300 nm.  Other, higher performance systems might utilize an InGaAs (indium gallium arsenide) detector instead, which is only capable of up to about 1800 nm, but provides better resolution and eliminates some of the gap in performance that can exist between PMT and PbS detection ranges. Some of the newer UV/Vis/NIR systems on the market actually combine all three, making for a more expensive but higher performance instrument.  

Conventional UV/Vis/NIR instruments are utilized most heavily in applications related to semiconductor, electronics, fiber optics, and other materials used in photonics. Although there is some use in the pharmaceutical and biotechnology industry, microplate readers generally handle such applications, which typically involve the analysis of liquids, rather than solids. 

The worldwide market for UV/Vis/NIR spectrophotometers was nearly $50 million in 2007, about two-thirds of which was related to initial systems. Average longer-term annual growth should be in the mid-single digits, although 2008 looks to be somewhat of a down year thanks to a likely downturn in the semiconductor and electronics industry. 

The foregoing data were based on SDi's market analysis and perspectives report entitled 

Edition Global Assessment Report, 9th Edition: The Laboratory Life Science and Analytical Instrument Industry, September 2006

. For more information, contact Stuart Press, Senior Consultant, Strategic Directions International, Inc., 6242 Westchester Parkway, Suite 100, Los Angeles, CA 90045, (310) 641-4982, fax: (310) 641-8851, 

While the overall laboratory UV and Visible spectroscopy market was worth well over $700 million in 2007, the UV/Vis/NIR segment represented less than 10% of it. UV/Vis/NIR instruments utilize multiple detectors to cover a broader spectrum of analysis, and typically are among the highest-end systems in the UV-Vis market.

Market Profile: UV/Vis/NIR

In the last column, a simplified figure portrayed the expected distribution of measurements for one selected calibration point. Any one point can be used to establish the proportionality factor between measured response and analyte amount; the range of expected measurement values means there will be a concomitant range of proportionality constants. In part to establish a useable dynamic range for our actual measurements, we typically use several calibration points, and each will produce a range of proportionality constants. Figure 1 represents the results of a linear regression analysis line fit to a number of calibration points. The dependent variable 

 is measured as a function of the independent variable 

. This is one of the simplest forms of regression analysis, and it predicts the value of one variable from another when the relationship between them is assumed to be linear. The geometrical description of the line is of the form 

 is the dependent variable. The slope of the line is 

 (representing the best-fit proportionality constant), and 

 = 0). Simplistically, the goal of a regression analysis is to find those values of 

 that describe a line closest to the data. The equation given above that describes the line is a restatement of the more common form of a line equation 

. This author prefers the given form because it emphasizes that some instrumental response should be observed even in the absence of analyte; this measured value previews a determination of noise in the analytical system. The restated form of the equation also emphasizes that both 

 are variables with a range related to the confidence limits required. Thus, the values of 

 given in Figure 1 reflect the range of values.  

The well-behaved linear regression is a focus of the calibration section of undergraduate analytical chemistry textbooks, and the elusive goal of some of our laboratory work in quantitative analysis. Because the amount of analyte is assumed known to a high degree of accuracy (or without any error at all), this value on the 

 axis is considered to be an independent variable. The random errors in the measured values for the "known and fixed" amount are distributed along the vertical 

 axis. We begin with an overview of the term "expected." We prefer an analytical world to be simpler rather than more complex, and linear as contrasted with multivariate. In constructing analytical protocols, usually we choose to measure a dependent value directly and simply proportional to the analyte (or value) of interest, and we will modify the testing protocol to provide this linear proportionality across the range of interest. Within the constrained testing and development phase of the protocol, the simplicity and linearity of the model for the distribution of results can be confirmed. As the protocol is put into place in the real world, and experience accrues — or as the analytical milieu changes, as requisite analytical tolerances grow tighter, or even as instruments or analysts change — a previously sufficient linear model might need to be reworked and revalidated. 

Figure 1: Generic appearance of a linear regression line that links observed response (y axis) to known analyte amount (x axis). The figure originally appears in reference 2. 

A more sophisticated regression analysis might continue to provide useful results, but the need to invoke such a "fix" should also trigger a re-evaluation of the underlying "expected" assumptions. 

What do we measure in MS that provides a response directly proportional to the amount of sample? Mass spectra plot the relative abundances of ions of various masses, and (to a pretty good approximation) the amount of sample present does not change the appearance of the mass spectrum. In a gas chromatography (GC)–MS instrument, as in the use of other detectors for GC, we could use the single-channel detector response (tabulated as the total ion current) as a measured value proportional to the amount of sample. In this approach, the "area-under-the-curve" is derived from the absolute magnitude of the total ion current. Of course, the magnitude of the total ion current is a function of the mass range scanned, and this would be kept constant in preparation of a calibration curve and analysis of samples. Because mass spectra are additive, the mass range usually scanned for organic GC–MS does not include the masses of low mass background ions such as air, argon, or carbon dioxide. Including any background ions in the total ion current summation will increase the variance of the measured results. Alternatively, we can choose as a measured response the absolute intensities of several ions of specific masses that appear in the mass spectrum of the targeted analyte. These summed intensities represent a subset of total ion current, with a value proportional to the amount of sample. The accuracy of such a quantitative determination might be enhanced because variance contributions from ions of background masses are removed from the proportionality equations. It is not necessary to include all the ions in the analyte's mass spectrum within such a summation of absolute ion current; any representative subset should provide a calibration curve of similar quality. However, it is important to include several such ions, especially at low values of the measured absolute ion current.  

As described, in quantitative MS, the measured value traditionally has been the absolute intensity of an ion or group of ions. Many other measurements — both kinetic and thermodynamic in basic nature — can be completed, but these measurements are topics for future columns. In deference to the simple traditional question of how much analyte there is, the analyst almost always will be constructing a proportionality curve for calibration based upon absolute ion intensities. The analyst might select a mass range, or, as described earlier, include only ions of masses specific to the sample, or, to increase specificity and increase accuracy, include only ions specified within a narrow mass window. With use of higher resolution, sensitivity usually is traded in a balance against mass resolution. But a lower sensitivity under the usual conditions might be compensated by the use of a higher gain in the detection system, or an offsetting advantage of lower noise in the signal, such that the requisite sensitivity and desired accuracy can still be achieved. The analyst should be aware that at very low levels of analyte, the certainty with which a "standard"calibration amount is known decreases. In such a situation, the errors on the independent 

 axis can no longer be ignored in the quantitative analysis. 

After deciding just what to measure, quantitative MS becomes an exercise in statistics. Motulsky's 1995 book is titled 

 (3); analysts trained in MS should also develop an intuitive feel as to the quality of their measured values. They should be aware of the sources of error in an instrumental measurement such as GC–MS, including not only the inherent uncertainties associated with ion statistics, but also those more usually relegated to chromatographic separations. 

In addition, the analyst must be aware of the potential errors and variances in sample preparation. Analytical chemists spend as much (if not more) time in preparing samples as in analyzing them. Increasingly, the sources of errors are to be found in the aspects of sample preparation variation rather than in the instrumental analysis. There certainly will be times when things are "just not right"; the intuitive analyst tracks down the uncertainties, and only then can he or she testify to the validity of reported results with confidence. 

Columnist Ken Busch presents the third of a five-part series on quantitative mass spectrometry. In this installment, he focuses on an overview of regression analysis for calibration lines and curves in mass spectrometry.

Spectroscopy-03-01-2008

Raman Applications That Are Driving a Rapidly Expanding Market

Products

Spectroscopy: A Technology for All Seasons

2008 Salary Survey: Salaries and Stress Shrink

Market Profile: UV/Vis/NIR

Quantitative Mass Spectrometry Part III: An Overview of Regression Analysis