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Volume 30, Issue 3
Recent federal science and technology initiatives are focusing public attention and funding on the need for innovative research in environmental quality, sustainability, medicine, and advanced materials.
Recent federal science and technology initiatives are focusing public attention and funding on the need for innovative research in environmental quality, sustainability, medicine, and advanced materials. Spectroscopy techniques will undoubtedly play a significant role in addressing these and other global challenges. In this social context, this article broadly surveys recent trends in spectroscopic techniques and instrumentation.
The United Nations (UN) has branded 2015 the "International Year of Light." UN agencies are sponsoring scientific and public awareness initiatives around the world to illuminate light's central role in society's response to issues such as resource sustainability, renewable energy, and global health. The global fanfare around the electromagnetic spectrum also provides a convenient framework for this article, which broadly summarizes emerging trends and future directions in spectroscopy. Accordingly, this overview emphasizes advances in optically based measurement techniques across the ultraviolet–infrared (UV–IR) spectral region or on other instrument types in which novel photonics technologies come into play.
History figures prominently into the International Year of Light programming, taking advantage of this year's landmark anniversaries of light-related breakthroughs: Fresnel's wave theory (1815), Maxwell's exploration of electromagnetism (1865), and Einstein's theory of general relativity (1915). As we examine the future of the field, it can be useful to look back on such milestones for a sense of how intertwined spectroscopy and society have always been. Spectroscopists harnessed the power of light to advance in the 20th century's most ambitious research programs, from the Manhattan Project to the Space Race to the Human Genome Project. Big-picture science initiatives like these returned the favor to today's spectroscopists with advances in electronics, optics, and computing tools that increased performance and simplified daily life at the laboratory bench.
"Science pushes technology and technology pushes science," said David W. Koppenaal, PhD, of Pacific Northwest National Laboratory (PNNL) (1). "It is a productive, yin-yang dynamic that, working together, accelerates scientific advancements." Koppenaal, PNNL's chief technology officer, received the American Chemical Society's 2014 Chemical Instrumentation Award for his decades of innovation in atomic spectroscopy. His award address credited this "necessary dynamic tension" for contributing to "the tremendous advance of chemical instrumentation and its role in advancing various areas of science" that he's witnessed during his career.
What's spinning that virtuous circle today? How will spectroscopic measurement figure into big 21st century efforts in science, technology, and engineering? How will advances in these fields change the rules of spectroscopic measurement in the future? With those questions in mind, this article scans the field of spectroscopy from a high altitude to identify some of the more noticeable shifts in the landscape of instruments and applications.
The field of spectroscopy connects the Year of Light to what PriceWaterhouse-Coopers calls megatrends - factual, data-driven macroeconomic forces that somehow impact global society and shape the behavior of corporations. In 2014, the global consulting firm identified five of them: a decline in the developed world's leadership in innovation; population aging and other demographic shifts; maldistribution of food, water, and other resources; increasing urbanization and megacities; and increasing "connectedness" through new technologies.
The same themes appear in a slew of ambitious science and technology-focused federal initiatives and grand challenges to stimulate manufacturing innovation, precision medicine, climate, materials research, renewable energy, and more. During its second term, the Obama administration has stepped up its efforts to rally universities, private industry, and government agencies around such projects.
Federal-level focus and funds for these multi-institutional, public–private efforts can boost the economy as well as science, but it's playing out against a backdrop of high anxiety among the academic and government scientists who would conduct this world-changing science. Trailblazing scientists struggling to maintain the momentum of their work in an era of sequestration and the persistent threat of government shutdowns are learning to circle the wagons. With flat budgets and more applicants than ever, agencies like the National Institutes of Health and National Science Foundation have tightened the criteria for awarding funds. Even established researchers with top-scoring grant applications are shut out, and it takes longer than ever for early-stage academic scientists to land their first major grant. The potential for a brain drain among the ranks of young investigators and graduate students is real. None of this bodes well for innovation over the long term.
Come what may, however, spectroscopists will continue to develop new and better ways of measuring matter - that's just what they do. Transferring intellectual property to the private sector, where it can solve real problems that affect real people, is all in a day's work for many academic and government scientists. It also helps pay the bills. The commercial market for spectrometers has its ups and downs, but it helps sustain forward motion. Innovation in spectroscopy has continued - possibly accelerated - during recent periods of challenge.
Richard Russo, PhD, a longtime atomic spectroscopy innovator at Lawrence Berkeley National Laboratory (LBNL), knows the drill. "My interest is seeing laser ablation [LA] solid sampling using laser-induced breakdown spectroscopy [LIBS] and inductively coupled plasma–mass spectrometric [ICP-MS] detection transitioned to industrial applications." Russo and two students launched Applied Spectra a decade ago to do just that. His commercial efforts align with LBNL's interests in promoting green technology and manufacturing innovation while also spinning off its technologies to the private sector. "Laser ablation sampling has been a workhorse of the geological community for many years," he said. "Changing paradigms in industry takes time, but we now see stronger growth from industrial applications because of the compelling advantages."
Yuri Ralchenko, PhD, leader of the atomic spectroscopy group at the National Institute of Standards and Technology (NIST), cited the growth of LIBS as evidence that innovation is going strong in atomic spectroscopy. "A century ago, atomic spectroscopy was the primary engine powering the steamship of scientific revolution in physics," he said, citing its fundamental role in quantum physics and Einstein's relativity theory. The role of elemental analysis has changed, but not its big-picture impact. "Today the flexibility, simplicity, and reliability of LIBS make it one of the most widely used field-portable spectroscopic methods for remote sensing, from geochemistry application to nuclear nonproliferation."
Both LIBS and LA-ICP-MS are prime examples of techniques that have blossomed as IR lasers have evolved during the past 30 years. Raman spectroscopy is another. In 1985, Raman was a well-established (2) experimental technique, but a tough sell for routine industrial applications. There were appealing advantages to the technique - no sample preparation, information-rich spectra - but the interference from sample fluorescence was a deal-breaker for many real-world measurements. The debut of Fourier transform (FT)-Raman in 1986 put the technique back on the table by adding the recently introduced continuous wave Nd:YAG laser to achieve Raman scattering without fluorescence interference.
In 2013, the Materials Research Society presented its Innovation in Materials Characterization Award to FT-Raman pioneers D. Bruce Chase and John F. Rabolt for their contributions made at DuPont and IBM Almaden Research Center, respectively (3,4). Now on faculty at the University of Delaware's Department of Materials Science and Engineering, they've recently teamed up on another new measurement approach with scientific and commercial promise. In 2010 they launched a company to develop their planar-array IR (PAIR) spectroscopy. The aptly named PAIR Technologies makes instruments combining dispersive elements like prisms and gratings with a standard globar and a two-dimensional (2D) IR focal plane array - a recently declassified military technology - to characterize dynamics in materials in real time. "The x-axis is the frequency domain and the y-axis provides spatial information on samples placed in the beam, either in transmission or using a specially developed hemispherical attenuated total reflectance accessory," Rabolt said. "It is a real double-beam instrument that takes sample and reference simultaneously using a very fast IR camera. One can get a spectrum in 100 μs."
Rabolt said he is excited about another emerging IR technique, a marriage of IR chemical analysis and atomic force microscopy (AFM) for nanoscale chemical analysis. IR microspectroscopy and AFM both took off about 30 years ago, but have only recently (5) joined forces. The AFM-IR technique produces the same molecular structure information produced in conventional IR spectroscopy, with the added benefit of extreme spatial resolution. According to Rabolt, the technique incorporates a tunable laser that allows researchers first to image a sample at AFM resolutions, and then scan it across the IR region. "The detector is actually the AFM tip in contact with the sample, which expands and contracts depending on whether the laser wavelength is absorbed or not. It allows us to obtain IR spectra at 50-nm spatial resolution." Rabolt said his lab acquired the instrument (made by Anasys Instruments) last May and has been exploring its use in polarized IR experiments. "We have two PhD students using the instrument full time and I have spent 150 hours learning the nuances of the instrument myself."
Anasys offers its commercial AFM-IR with a choice of tunable sources, including a quantum cascade laser (QCL). QCLs are tunable IR semiconductor lasers that, for some applications, compete with FT-IR on resolution and power performance - if not yet on price. First developed at Bell Laboratories in the mid-1990s, QCLs have benefited from recent advances in chip manufacturing and are now go-to IR sources for challenging absorption measurements in clinical, defense, environmental, and quality control applications. QCLs are constructed using standard semiconductor manufacturing techniques, in which GaAs and AlGaAs nanolayers are assembled to achieve specific wavelength and operational properties. In IR spectroscopy, QCLs are orders of magnitude "brighter" than a standard spectrometer globar, with an average power range from 10 to hundreds of milliwatts and 0.001 cm-1 resolution in continuous wave mode, said Don Kuehl, PhD, vice president of business development at Redshift Systems. QCLs are currently best suited to specialized applications that require higher resolution and power, or that are sited in energy-starved settings, Kuehl said. As it turns out, these are the types of measurements now in the cross-hairs of the public interest: methane emissions (hydraulic fracking), remote explosives detection and standoff management (counterterrorism), stable isotope measurements (climate change), and breath analysis (health care and disease control). But as technological advances reduce the cost of semiconductor materials and manufacturing, the cost and performance benefits of QCLs could make measurable waves (6).
"Even though the technology is 20 years old, QCLs are still in their infancy, residing primarily in the world of photonics," Kuehl said. "But as happened with FT-IR 40 years ago, we can expect major advances in technology to drive current markets and open new markets."
Having established that spectroscopic instruments have amazing new capabilities, the question now is what to do with all that new capacity. For starters, here's a short to-do list:
Spectroscopy and spectroscopists are getting it done. Here are a few ways it's taking shape today.
Health and Life Science
In his 2015 State of the Union address, President Obama proposed a massive push to make drug research faster, smarter, and genetically personalized. The Precision Medicine Initiative would, among other activities, launch national outreach efforts to recruit patient volunteers for whole-genome sequencing. When coupled with other patient-specific imaging and biomolecular structural data, scientists and physicians would have access to an enormous database offering a systems-level view of disease processes in individual patients. This information could dramatically accelerate the effort to develop new drugs engineered to stop the molecular underpinnings of a disease rather than its outward manifestations.
In cancer research, such information would add power to a growing effort to reinvent the technologies used for screening and early detection. Adapting existing spectroscopic and imaging modalities for routine clinical diagnostic use is considered a necessary step. As cancer biologists learn more about the complex molecular makeup of a tumor's microenvironment, they identify new targets for diagnostics that find traces of the disease while it is still relatively easy to treat. Spectroscopy can help differentiate between malignant or benign growths and help identify how abnormalities in molecular structure contribute to cancer's progression.
"The goal is not to find all cancers," said Sanjiv (Sam) Gambhir, MD, PhD, "but to find those that will follow a trajectory that will cause a person to die." Gambhir heads Stanford University's Multimodality Molecular Imaging Lab, where his range of tools includes fiber-optic photoacoustic imaging probes that couple with optical analyzers or ultrasound as less invasive alternatives to a surgical or endoscopic biopsy. Through Stanford's Molecular Imaging Program, Gambhir was part of the first team to obtain a clinical-grade imaging system (7) that incorporates magnetic resonance, photoacoustic, and Raman measurement capabilities in one device. The technology revolves around a specialized nanoparticle that, when injected in animal models, accumulates in tumors. The particle possesses properties accessible to all three imaging modes, which are used to achieve specific complementary measurements in brain tumor assessment and resection.
A collaborative effort between the University of Strathclyde and Renishaw Diagnostics is exploring surface-enhanced Raman scattering (SERS) in the detection and differentiation of different human papilloma virus (HPV) genotypes. This work makes use of specific probes and magnetic nanoparticles to capitalize on SERS's ability to simultaneously determine multiple targets in an assay, increasing throughput and turnaround times (8). Xiong Wan and colleagues (9) at Nanchang Hangkong University are developing an in-home LIBS technology designed to collect and send personal diagnostic indicators over the Internet of Things to remote clinics for interpretation. The device uses pulsed IR laser excitation to generate spectra of user-supplied tissues such as hair or fingernails.
Beyond the diagnostic and detection sphere, spectroscopy continues its yeoman's work in the basic life sciences lab - with some significant new applications on the horizon. As discussed above, vibrational spectroscopy and electron microscopy are increasingly used together to combine extreme resolution with powerful structural insights. One variant, tip-enhanced Raman spectroscopy (TERS) has been recently used in tandem with AFM in direct DNA sequencing (10). TERS has promise as a means to sequence cells gathered from specific phenotypes without the need for amplification. Stem cell scientists are looking for nondestructive ways to measure and stage the cell division process and other key phases in the cell cycle. Although the process can be observed in a microscope, researchers can't determine what phase of the cycle is taking place in a living cell without sample preparation methods that kill or damage it. Michael W. Blades and colleagues (11) at the University of British Columbia recently published a proof-of-concept study of Raman microspectroscopy in the in situ determination of cell cycle phase in single embryonic stem cells - in effect using molecular vibrations as a contrast agent instead of chemical stains.
Energy, Climate, and the Environment
"Nowadays there are several major trends in application of analysis of spectra of neutral and ionized atoms," said NIST's Ralchenko. "From the famous Hubble telescope snapshots of the most remote galaxies in the universe, to identification of extraterrestrial planets via Doppler-shifted spectral lines, to spectroscopic analysis of solar magneto-hydrodynamic structures, the measured spectra are the subject of exciting research that allows us to locate and explain new physical phenomena. This research has immediate implications for our planet."
Because the sun directly affects Earth's climate and the telecommunications network, he said, "it is not surprising that significant efforts are directed at spectroscopic analysis of processes in the upper atmosphere of Earth which are indicative of forthcoming global events due to the sun's activity."
Here on the ground, the North American shale oil and gas boom has put a complicated spin on the government's environmental science initiatives and the public's attitudes about the switch to green energy. Environmentalists are concerned that $2 per gallon gasoline and lower winter heating bills will sap momentum from the sustainable energy movement - with potential downstream impacts on climate change.
The widespread oil and gas industry practice of hydraulic fracturing, or fracking, is at the heart of the shale energy controversy. Horizontally directed drilling into coal beds and shale strata can extend the underground impacts of fracking to locations far removed from the well head, where concerns include risks to the quality and quantity of aquifers that supply drinking water. Fracking also creates surface impacts on surrounding air, water, and soil.
Fracking involves the pressurized injection of about 2 million gallons of water, sand, and chemical additives down the wellbore. The pressure creates fissures in the surrounding rocks, causing trapped oil and gas deposits to flow into the well casing and up to the surface. The fracking fluid permeates the surrounding rock and clay; some of it lingers there, and about a third of it gushes back to the surface as flowback. Operators aren't required to disclose the chemicals in their proprietary additive mixtures, but some estimates put the known number at over 100, including BTEX, the dreaded quartet of benzene, toluene, ethylbenzene, and xylenes linked to central nervous system impacts and other health problems. So-called produced water - the naturally occurring groundwater that flows up with the oil or gas production stream - also contains chemical remnants of fracking fluids and a range of naturally occurring substances including radioactive isotopes. This water, too, must be treated and discharged, permanently stored, or in growing instances recycled. Ensuring that it is safe for its assigned fate is job security for environmental spectroscopists in shale-intensive regions.
Environmental regulators are monitoring drinking water supplies for signs of radioactive materials from fracking wastes that treatment might have missed. The recommended Environmental Protection Agency (EPA) method for determining radium isotopes in drinking water is a venerable wet chemistry method that has been found to be ineffective for samples containing high ion concentrations. A recent study (12) of radium-rich wastewater samples from wells in the Marcellus Shale region compared the standard coprecipitation method (EPA Methods 903.0 and 904.0) to direct measurement using high-purity Ge gamma ray spectroscopy and a portable spectrometric radon gas detector. The spectroscopic techniques strongly outperformed the wet chemistry methods, suggesting these established procedures may only be detecting 1% of the radium present.
Methane gas emissions are another environmental hot spot in the fracking debate. Leaks in well casings and tanks, improperly constructed well beds, and the open ponds used to hold fracking water are monitored for atmospheric emissions. Well operators are some of the early adopters of the above mentioned tunable IR laser–based gas spectrometers optimized for remote "sniff tests."
On the exploration end of the fracking spectrum, oil and gas producers are using X-ray fluorescence (XRF) to scout out locations for new wells and predict their productivity. Drillers are adapting field-based XRF instruments to determine the presence of light elements like Al, Mg, P, S, and Si in rocks and clays, which reveal important insights about the permeability. Although XRF won't detect the oil or gas deposits themselves, they can characterize where it's most likely to be and help predict how much of it can be extracted.
Nanomaterials and Engineering
Engineered nanoparticles are used in medical diagnostics and drug delivery, electronics manufacture, solar energy, materials engineering, and environmental remediation.
Recent work at NIST has focused on establishing measurement criteria and standards for nanoparticles. NIST recently developed what it calls the world's smallest reference material (13), RM 8027 - a 1-mL quantity of silicon nanoparticles suspended in toluene. Each crystalline nanoparticle is certified to be approximately 2 nm in diameter, and was obtained by etching from a silicon wafer. The size and chemical composition of the particles is verified with dynamic light scattering, analytical centrifugation, electron microscopy, and ICP-MS.
For larger particles, a NIST team led by Michael Winchester (14) has been exploring the relatively new technique of single-particle ICP-MS, ideal for characterizing gold nanoparticles from 10 to 200 nm. They report that dwell times of 10 ms are optimal for producing data unimpaired by split particle events, particle coincidences, and false positives.
At Harvard Medical School, Ralph M. Weissleder, MD, PhD, seeks answers to questions like why cancer drugs stop working for some patients but not others. His laboratory has developed what it calls the world's smallest nuclear magnetic resonance (NMR) spectrometer, a palm-sized chip-based analyzer optimized to pick up signals from cancer-related cellular material suspended in blood or other specimens. His method introduces nanoparticles coated with a target-binding substance into the sample. The particles deposit these agents onto the desired targets, creating a measureable NMR signature. "Our chips are tiny," he said, "but they have a big magnetic bang."
Quantum dots, nanocrystalline semiconductor particles with unique quantum mechanical and electronic properties, are used in flat-screen televisions, medical imaging applications, and a wide range of electronic devices. A number of groups have applied ICP-MS to various measurement challenges in quantum dot engineering. At the University of Oviedo, scientists are assessing (15) ICP-MS and asymmetrical flow field-flow fractionation in the characterization of quantum dot bioconjugates and exploring the role of ICP-MS in bionano applications of phosphorescent metal-doped quantum dots biomedical applications.
If you happen to have access to a synchrotron in your laboratory, as they do at Lawrence Berkeley, connecting AFM and IR spectroscopy takes on a new twist. Berkeley scientists working with colleagues at the University of Colorado (16) reported orders-of-magnitude improvement in spatial resolution across the region with a technique they call synchrotron infrared nanospectroscopy (SINS). Berkeley's principal scientific engineer behind SINS, Hans Bechtel, stated that the method can obtain full broadband IR spectra of difficult samples at scales 100 to 1000 times smaller than conventional measurements. The team will use the technique to study complex molecular systems, such as those found in liquid batteries, living cells, novel electronic materials, and stardust. "This is not an incremental achievement," Bechtel said. "It's really revolutionary."
A recent collaborative study led by researchers at Arizona State University and Nion Company demonstrated improvements in electron energy loss spectroscopy with scanning tunneling electron microscopy (EELS-STEM). Their optimized instrument successfully produced high-resolution vibrational spectra of sample features in the 50–500 meV range, making it useful in a range characterizing nanotubes, quantum dots, and a variety of biological and polymer samples (17).
When the first issue of Spectroscopy was published in late 1985 (18), the field was entering a period of significant technological change. Whether by design or natural selection, many of these changes opened the job of spectroscopy to new types of users. The new PC-controlled instruments were lay-friendly. NMR morphed into a diagnostic imaging machine. Hyphenated techniques challenged chromatographers and spectroscopists to stretch their perspectives. Improved fiber-optics brought the analytical laboratory to the factory floor. This trend seems alive and well today, and it appears more and more people will be using spectrometers who do not regard themselves as "spectroscopists." However the profession's core culture and traditions as an academic discipline are durable enough to adapt to these and other changes as they always have. Spectroscopy will continue moving forward, as long as its best and brightest minds continue innovating with frequency and intensity.
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Michael MacRae writes about science, technology, and society. A former editor of Spectroscopy and its sister publication LCGC, he lives in Portland, Oregon. Direct correspondence to: email@example.com