Trends in Spectroscopy: A Snapshot of Notable Advances and Applications

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Spectroscopy, Spectroscopy-03-01-2019, Volume 34, Issue 3
Pages: 36-44

Spectroscopic measurement factors into every facet of modern life. Here, we survey noteworthy recent advances in and applications of atomic and molecular spectroscopy, touching on their uses in fields such as biomedicine, materials science, environmental monitoring, agriculture, pharmaceutical research, public safety, and more.

From the global climate, to national security, to individual healthcare, spectroscopic measurement factors into every facet of modern life. As always, spectroscopy and spectroscopists are providing the objective observations and measurements that help society make sense of a changing world. This article surveys noteworthy recent advances in and applications of atomic and molecular spectroscopy, touching on their uses in fields such as biomedicine, materials science, environmental monitoring, agriculture, pharmaceutical research, public safety, and more.

As it has for generations, spectroscopy remains a critical tool for answering the questions most relevant to society's health, prosperity, and quality of life. The core techniques under the spectroscopy umbrella are well established, but in a state of continual refinement and adaptation to meet changing demands. Although the appearance of a new blockbuster technique is a rarity these days, ongoing advances in optics, detection, and computing technology drive steady evolutionary progress in instrument performance, ease of use, and applicability to emerging analytical challenges.

To chronicle the evolution of the field, Spectroscopy has for many years published an annual overview of key trends in instrumentation and applications. As the latest installment in this series, this article attempts to identify current and emerging trends in the most widely used spectroscopic techniques among Spectroscopy's readership. It focuses on general trends in the scientific community as a whole, and the spectroscopy community in particular, before presenting separate sections dedicated to atomic and molecular techniques. This article is in no way a comprehensive review, but rather an individual take on the field based on a variety of sources, including proceedings of key spectroscopy-focused conferences, trend-focused articles in primary research journals, science articles in mainstream news media, individual researcher and institutional websites, and government information. Specific commercial products indicative of broad trends in commercial instrumentation are mentioned in a few places, but a more expansive review of new products will appear in Spectroscopy's post-Pittcon review coming up in the May issue.

Spectroscopy in Context

Whether mapping planet-wide climate shifts, detecting threats to food and water supplies, characterizing new nanomaterials, monitoring personal health indicators, or discovering a fundamental natural phenomenon, a spectrometer is never far from the action when it comes to society's emerging inflection points. Therefore, any survey of recent advances and trends in the field of spectroscopy must be presented in the context of the times.

During the preparation of this article, the federal government was just returning to work (at least for the time being) after the longest partial shutdown in its history. Regardless of its ultimate duration, this shutdown (like the 20 previous ones since 1976) will have will have both short- and long-term impacts on science and, by extension, spectroscopy. Most employees at science-focused federal agencies such as the U.S. Environmental Protection Agency, the National Oceanic and Atmospheric Administration, and NASA had been furloughed, and the National Science Foundation (NSF) had prepared to cancel dozens of grant proposal review meetings scheduled for January, according to the New York Times (1). Consequently, laboratories that depend on federal grant dollars from affected agencies were preparing to defer spending for equipment, new graduate students, and other research-related expenditures. The shutdown also cut into attendance at key scientific meetings, disrupted collection of data for long-term studies, and halted planning for future studies.

Overall, federal funding for research at academic and non-profit institutions has been declining since its peak in 2010–11, but has lately been holding relatively steady year-to-year, according to a report by the NSF (2). Federal research grants have traditionally been the primary funding source for science at U.S. universities. However, that began to change in 2014, when federal support dropped below 50% of academia's total research funding pie for the first time in decades. To keep up with rising costs of personnel, graduate education, equipment, and overhead, the NSF reports that institutions are increasingly reliant on funding from private philanthropy or corporate research contracts. Nevertheless, in a welcome trend for spectroscopy instrumentation manufacturers, the NSF reported that academic institutions spent $2.1 billion on capitalized research equipment in 2016 (the most recent year for which data is available), up 3% over the prior year. The majority of those expenditures (87%) were for instruments intended for life science, engineering, and physical science applications.

Against the backdrop of these broad trends, the diverse group of scientists who self-identify as spectroscopists are experiencing a mixed bag of good and not-so-good news. According to Spectroscopy's 2018 salary survey (3), spectroscopists are earning more than ever before. The average annual salary for spectroscopists in 2018 was $91,129, a 7.6% increase over the prior year and the first time in the survey's history that salaries surpassed the $90,000 mark. But the survey also found that spectroscopists may be working harder for that money, and deriving less satisfaction in the process. Stress levels and workloads were on the rise, and 13% of survey respondents said they were taking on extra work to augment their earnings.

The tools of the spectroscopy trade are as technologically diverse as the range of applications in which they are used. Regardless of technique, however, most of the major commercial spectrometer manufacturers are continuing their move toward smaller, more automated instruments (4). Often sold with preset analytical routines for common applications in specific industries, these instruments are designed for use by less experienced lab personnel, or to help skilled users perform more complex operations in less time. Handheld or portable devices for field measurements are increasingly common, as are purpose-built spectroscopy-based analyzers for point-of-care clinical or biological measurements. These types of instruments have been around for decades, of course, but manufacturers are increasingly successful at converting more complex laboratory techniques, such as Raman and nuclear magnetic resonance (NMR), into field-hardened analyzers. Another twist on the established benchtop spectrometer paradigm is the marriage of two or more different techniques into one instrument to reduce the time, expense, and complexity of obtaining a multimodal measurement. For example, instruments integrating UV/Vis absorbance with fluorescence and mid-IR with far-IR/terahertz measurements have been recognized as some of the most innovative introductions at recent Pittcons (5). The coupling of vibrational spectroscopy with various forms of imaging is bringing spectroscopy into the nanoscale range.

Trends in Atomic Spectroscopy

Atomic spectroscopy remains a workhorse of the analytical laboratory. The field encompasses several specialized techniques, ranging from the routine to the exotic, which are used in environments ranging from the ocean floor to the surface of Mars. According to market analysis firm Market Research Engine (Deerfield Beach, FL), the global market for commercial instruments for atomic techniques including atomic absorption (AA), inductively coupled plasma-optical emission spectroscopy (ICP-OES), inductively coupled plasma-mass spectrometry (ICP-MS), and x-ray fluorescence (XRF) analysis was expected to grow at 6% compounded annual growth rate to exceed $6.5 billion by 2024.

Trends and applications of atomic spectroscopy are largely driven by developments in key production industries, many of them highly regulated, such as pharmaceuticals, foods and beverages, petrochemicals, metals, and mining. Consequently, atomic spectroscopy is also fundamentally important in the monitoring of the downstream impacts of these industries on the ecosystem. The relentless drive to improve the accuracy and precision of elemental spectroscopic analysis has dramatically enhanced every step of the analytical process, from sample preparation to regulatory compliance. Advanced research in atomic spectroscopy focuses on the development of improved techniques for sample excitation and ionization, sample transport, interference elimination, and other fundamental areas.

Glow Discharges

Several groups (6–8) are concentrating on the further development of liquid-sampling or solution-cathode atmospheric-pressure glow discharge plasmas as versatile ionization sources for atomic and mass spectrometry. The approach is based on a process in which the surface of liquid passing through a glass capillary acts as the cathode of a direct-current glow discharge. The passing current vaporizes analyte-containing solutions to produce gas-phase solutes that are then ionized in the plasma. Developers believe the technique could eventually offer a cheaper, simpler alternative to the higher-powered plasma sources used in standard elemental mass spectrometers. Another area of heightened activity in the alternative ionization source domain is dielectric barrier discharge ionization. The technique has shown potential as a single ion source for both elemental quantification and molecular identification on a single instrument platform. It too offers reductions in operating cost, power consumption, and ease-of-use in a range of environmental sample matrices (9,10).

Laser Ablation and LIBS in the Spotlight


The hottest trend in the field is arguably the continuing rise of two laser-based methods: laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) and laser-induced breakdown spectroscopy (LIBS). LA-ICP-MS is enabling chemists to perform sensitive elemental and isotopic analysis directly on solid samples. A laser is focused on the sample, generating fine particles that are transported into a secondary excitation source of an ICP-MS spectrometer for digestion and ionization. In the plasma torch, excited ions are then transported into the MS detector. Many of the mechanisms of laser ablation also power LIBS. In this method, a short pulse from a high-power laser causes a high-temperature micro-plasma to form on the sample surface, exciting the electrons of the sample's component atoms and ions. As the plasma cools and the atoms and ions return to a ground state, the plasma emits light with discrete spectral peaks. LIBS can detect every element in the periodic table without requiring sample preparation, making it applicable to a wide range of sample matrices that include metals, semiconductors, glasses, biological tissues, insulators, plastics, soils, plants, soils, thin-paint coating, and electronic materials.

LIBS in particular is commanding new levels of attention, not only among the atomic spectroscopy world, but also across the analytical chemistry community. Its vibrancy is evidenced by a marked increase in LIBS-related presentations at major analytical science conferences such as Pittcon. In 2018, the Xth International LIBS Conference ran in conjunction with SciX, the annual meeting and exhibition of the Federation of Analytical Chemistry and Spectroscopy Societies (FACSS), significantly increasing the number of LIBS-related oral and poster presentations at the event. Speakers touched on a wide range of emerging LIBS applications at SciX, including underwater measurement of geologic carbon storage, determination of bitumen in oil sands, the use of AA spectroscopy to study ablated mass of samples in a laser-induced plasma, and the use of a femtosecond laser for tandem LA-ICP-MS/LIBS analysis, to list a few (11).

Atomic Absorption

Performance improvements in AA spectroscopy are helping to address increased demand for sensitive metals determinations with less sample pretreatment. In an effort to devise a faster, simpler approach to trace analysis of toxic metals in livestock, scientists at the Russian Academy of Sciences and Novosibirsk National Research State University developed a novel graphite furnace atomic absorption spectroscopy (GFAAS) method using two-stage probe atomization (12). GFAAS is not widely used for direct trace analysis of whole blood, because of strong interferences from the organic matrix. Bovine blood is especially problematic due to higher concentrations of proteins and lipids compared to human blood. The two-probe atomization process enabled determination of trace levels of cadmium (Cd)and lead (Pb) in bovine blood with minimal sample pretreatment, no matrix suppression, and lower non-selective absorption levels. Pharmaceutical manufacturers are exploring high-resolution continuous source GFAAS for the sequential determination of Cd and Pb impurities introduced by catalysts used in the drug synthesis process (13). For AA users who frequently need to switch among flame, graphite furnace and hydride atomization technologies, commercial systems that integrate multiple techniques are now available from most of the major AA manufacturers.

X-ray Analysis

X-ray fluorescence (XRF) spectroscopy is the other primary technique for elemental analysis among Spectroscopy's readership. Real-world applications of XRF abound because of its simplicity and nondestructive nature. XRF equipment has long been used in field work, at the production line, and in space exploration. Although general analytical chemistry and spectroscopy conferences typically offer workshops, short courses, and the occasional oral session on XRF and related techniques, the premier showcase of advances and new applications is the venerable Denver X-ray Conference, now gearing up for its 68th year. This event is an annual deep dive into all facets of x-ray analysis, including XRF for elemental composition, x-ray diffraction for structural characterization and phase identification structures, and a wide range of other advanced methods for materials characterization, microscopy, surface analysis, and beyond.

Last year's Denver X-ray Conference, held August 6-10 in Westminster, Colorado, presented a host of innovative applications of XRF in elemental analysis (14). Non-laboratory-based applications of XRF were prominent. Joel O'Dwyer and colleagues at CSIRO Mineral Resources (Kirrawee, NSW, Australia) described a novel XRF analyzer for both direct, on-stream elemental analysis and routine in-plant batch analysis of process stream slurries. The system was found to have potential as a more sensitive alternative to existing process analyzers, which are generally only able to measure concentrations above approximately 10 parts per million, and off-line or off-site analytical techniques, which can take hours or days to complete. A group from UHV Technologies (Lexington, KY) shared results of a study of an on-line XRF system as a lower-cost, in-line alternative to ICP-MS or AA for identifying metallic impurities introduced into pharmaceutical products during the manufacturing process. The performance of energy-dispersive (ED) XRF spectrometers (the kind most often used in field applications) has improved with the growing use of the silicon drift detector (SDD). As an alternative to the traditional silicon-lithium detector, SDDs offer better resolution and analytical performance at higher count rates. Maggi Loubser, a consulting scientist at GeoMag GeoChem (Meyerspark, Pretoria, South Africa) reported results from her tests comparing a handheld EDXRF analyzer with both a benchtop EDXRF system and a laboratory wavelength-dispersive XRF spectrometer. After calibrating all three systems with an identical set of reference materials, she found the handheld system's capabilities to be generally comparable to that of the more expensive off-line systems.

Total-reflection x-ray fluorescence (TXRF) remains an area of growth in x-ray analysis and a number of interesting applications were highlighted at the conference. For example, a multi-institutional team from California Institute of Technology, NASA, Arizona State University, and Loyola University used TXRF to assist in the cleaning of contaminated sample collectors used in the NASA Genesis mission. Upon returning to Earth after collecting pristine solar wind ions in space from 2001 to 2004, the spacecraft experienced a hard landing in which the solar wind collectors were damaged and contaminated. The surfaces of these collectors had to be thoroughly cleaned before the solar wind samples could be analyzed. TXRF was chosen to monitor the progress of contaminant removal because of its high surface sensitivity and non-destructive nature. TXRF has been explored as an alternative to ICP-OES and ICP-MS in liquid analysis, because it offers faster measurement times, and quantification can be performed by internal standard addition without the need to set up calibration curves. Atsushi Ohbuchi and co-workers described applications of TXRF in the trace element analysis of wastewater, finding its wide dynamic range and direct analysis capabilities to be well suited for screening analysis.

Notable Applications of Atomic Spectroscopy


Novel variations of ICP and ICP-MS have recently emerged across a range of key industries, including nanomaterials, biomedicine, agriculture/food, and environmental science.

Single-particle (sp) ICP-MS is becoming increasingly important in the characterization and sizing of metallic engineered nanoparticles (15) in soil, drinking water, wastewater, and other environmental matrices. The technique offers superior elemental specificity, sizing resolution, and sensitivity for metallic nanoparticles found in a wide range pharmaceuticals, foods, personal care products, and other consumer goods. Although certain nanoparticles are confirmed carcinogens, little is currently known about their environmental cycling and transport into humans, so the use of sp-ICP-MS for this work will likely continue to increase in the years ahead.

As the ability to sample and analyze individual human cells improves, single-cell (sc) ICP-MS is providing a fast and sensitive way to study elemental composition at the cellular level. Nanoparticles enter cells not only through environmental exposures, but also through certain pharmaceutical products, such as platinum-based chemotherapy drugs. Sc-ICP-MS is increasingly used to detect, measure, and determine bioavailability of key metal-containing species within the cell (16,17). The method allows detection of discrete pulses of positively charged ions in a time-resolved manner at microsecond data acquisition rates. It can monitor cells for intrinsic metal content and the uptake of ionic or nanoparticulate contaminates with minimal sample preparation. Used in conjunction with techniques such as flow cytometry, sc-ICP-MS opens the door to combined cell number counting and cellular metal mass quantification.

It's not often that a brand new multibillion-dollar industry materializes virtually overnight. But such is the case with the legal cannabis market. With a recent Pew survey showing the approval of 62% of Americans, 10 states and the District of Columbia have legalized the regulated sale of recreational cannabis, and 33 states permit the use of the plant for prescribed medical treatment. The worldwide market for legal cannabis sales in 2017 was valued at $9.5 billion (18), with the U.S. accounting for 90% of that amount. Customer demands for product quality and safety are requiring new applications for analytical technology beyond those originally developed for drug screening and law enforcement purposes, including tests for potency, residual solvents, pesticide contamination, and metals content. At minimum, most states require metals testing for the so-called Big Four toxic metals: arsenic, cadmium, lead, and mercury. AA, ICP-OES, and ICP-MS techniques are all suitable for metals analysis in cannabis samples, with each bringing its respective benefits and limitations to the table. For laboratories that don't require high sample throughput, AA offers high performance at the lowest cost. ICP with optical emission detection achieves comparable detection limits to AA with less sample processing, but at a higher operating cost. ICP-MS offers superior sensitivity and throughput, but is much more expensive to purchase and operate. As the industry matures and regulators requires the determination of more metals at lower concentrations, ICP-MS's role will likely increase (19,20).

Trends in Molecular Spectroscopy

This discussion will focus primarily on spectroscopic methods for molecular analysis and characterization that involve the measurement of dispersed/diffracted light across the ultraviolet (UV) through far-infrared (IR) spectral regions. The worldwide market for molecular spectroscopy instrumentation and related supplies was valued at $4.98 billion in 2018, and is projected to expand at a 6.6% compound annual growth rate to $6.85 billion by 2022, according to market research firm MarketsandMarkets (Northbrook, IL). Key drivers of new instrument sales are said to be an increased worldwide demand in the pharmaceutical and biotechnology industries, as well as new applications for emerging techniques such as terahertz spectroscopy in healthcare.

Terahertz (THz) Spectroscopy

THz spectroscopy appeared in the late 1980s, and has more recently benefitted from higher-intensity sources and more sensitive detectors. The THz wavelength region falls between the microwave and infrared spectral regions. Thus, THz spectrometers can measure vibrational activity occurring beyond the range of standard IR spectrometers while also enabling the observation of higher-energy phenomena than can be measured with microwave spectroscopy. This enables the evaluation of vibrational behavior within subunits of large molecules, especially proteins, DNA, lipids, and other biomolecules. THz systems can be configured for a range of real-world applications, including trace gas detection, layer thickness measurements, and high-speed contact-free material and quality testing in production or remote environments (21).

One traditional limitation of THz spectroscopy has been its inability to characterize single molecules, an area of increasing interest in biology and other fields. The long wavelengths of THz signals are tens of thousands of times larger than the size of typical molecules, making it impossible to focus on just one. However, a group at the University of Tokyo's Institute of Industrial Science is working to overcome that problem. The team recently reported (22) successful entry into the single-molecule regime with a novel THz spectrometer design. The system incorporates a single-molecule transistor, in which two adjacent metal electrodes serving as the transistor's source and drain are positioned on a thin silicon wafer in a shape resembling a bowtie. They isolated single molecules of fullerene, and placed them into the sub-nanometer gaps occurring between the source and drain. These electrodes help to focus the THz beam on the isolated molecule.

2-D IR Spectroscopy

Another area of increased recent interest in the molecular arena is 2-D IR spectroscopy, a powerful tool for gleaning structural and dynamic information from a wide range of systems of interest in biology and materials science. The technique subjects a sample to three excitation pulses to create nonlinear polarization. Measurement of the time delay between the first two pulses provides information on system dynamics. The third pulse probes the sample, creating emission data that reveals information on system evolution. By spreading IR spectra into a second dimension, the technique can reveal details about vibrational couplings and separate the effects of homo- and inhomogeneous dynamics. The technique's rich information content makes it an increasingly attractive alternative to linear mid-IR methods used in the study of molecular structures, environmental dynamics, and structural kinetics.

One of the most active groups in 2-D spectroscopy is led by Martin Zanni at the University of Wisconsin-Madison. His team recently (23) addressed two common technical challenges faced by spectroscopists studying reactions at surfaces and interfaces–low coverage of molecules at the surface and discerning between signals coming from the bulk and the surface. Their solution: a method called surface-enhanced attenuated total reflection 2-D infrared (SEAR 2-D IR) spectroscopy. This technique combines localized surface plasmons with a reflection pump-probe geometry to improve monolayer sensitivity.

Recently, a group at the University of Freiburg (24) reported what they believe to be the first use of 2-D spectroscopy on isolated molecular systems. Despite the technique's high information content and advantageous femtosecond-scale time resolution, it has not been useful for studying individual quantum-mechanical effects and thus been limited primarily to the study of bulk liquid or solid materials. In this work, the scientists first synthesized the target molecular compounds by adding individual components one by one onto a friction-free substrate made of nanometer-sized superfluid helium droplets. This approach enabled observation of the molecule's light-induced behavior in the helium environment, which the researchers expect to open new applications of 2-D spectroscopy in photovoltaic and optoelectronics research.

Raman Spectroscopy

Another of the most vibrant areas of molecular spectroscopy is one of the oldest. The Raman Effect was first described 90 years ago, but the vibrational spectroscopic technique harnessing that effect struggled for much of the 20th century to find real-world analytical application due to technical challenges such as interference from background fluorescence. By the mid-1980s, advances in laser and detection technologies caught up with the science behind Raman spectroscopy, and the faith of the technique's ardent proponents has been redeemed with a surge of new applications and commercial products. Today, a technique that not long ago was found only in more sophisticated spectroscopy labs is now packaged within handheld pushbutton analyzers used in the field by people with no scientific training whatsoever.

Surface-enhanced Raman spectroscopy (SERS) has grown in prominence across many application areas. Originally developed as a probe of electrochemical reactions and the adsorption of molecular species on metallic surfaces, SERS has been embraced by a broader community of analysts who value its inherent molecular specificity and single-molecule detection capability. SERS has proven useful as a chemical sensor in field-based applications, where it is used to measure drugs, explosives, heavy metals, toxic industrial chemicals, and more (25). In the life sciences, SERS provides an ultrasensitive biomolecular analytical technique for small molecules, macromolecular proteins, and living cells. SERS makes possible the direct, label-free detection of molecules through their intrinsic Raman fingerprints, making it especially suitable for characterizing dynamic 3-D structures like protein and lipid bilayers as well as for studying biomolecules near metallic surfaces (26).

Microscopy and Imaging

Significant advances continue to create new analytical possibilities through the coupling of vibrational spectroscopy with various modes of microscopy and imaging. A number of specialized techniques have emerged to perform IR and Raman spectroscopic imaging with nanometer-scale resolution, including tip-enhanced Raman scattering (TERS), IR scattering-type scanning near-field optical microscopy (IR s-SNOM), atomic force microscopy infrared (AFM-IR) analysis, and photo-induced force microscopy (PiFM). These techniques are achieving unprecedented spatial resolution and chemical contrast in a wide range of applications in materials science, biomedical research, polymer research, and beyond (27).


AFM-IR is increasingly used to explore the mid-IR spectral region with spatial resolution beyond the diffraction limit. Groups are using the technique for wide-ranging applications, such as subcellular-level imaging in fixed eukaryotic cells (28), the analysis of atmospheric aerosol particles (29), and the nonpolarimetric structural and anisotropic IR analysis of thin films and surfaces (30). Laser sources and detection methods have fueled the improvement of coherent Raman microscopy for biochemical analysis (31). Hyperspectral and multiplex imaging methods now achieve higher chemical sensitivity and image contrast, without sacrificing video-rate imaging speeds. Spectroscopy is also widely used for imaging on the macroscale. For example, laser-induced luminescence spectroscopy is being used as a remote sensing method in the exploration and discovery of new deposits of rare earth elements used in energy, transportation, computer, and telecommunications technologies (32).

Notable Applications of Molecular Spectroscopy

As is true with atomic spectroscopy, the most novel applications of molecular techniques in recent years have arisen in response to challenges or opportunities driven by current events. Instrument and application developers are exploring innovative uses of molecular spectroscopy to solve emerging questions in biology, healthcare, environmental management, advanced materials, energy production, and beyond.

The life science/healthcare sector remains the most robust area of innovation in molecular spectroscopy. Even the most mature techniques continue to evolve to meet the life science laboratory's growing demand for more information from smaller sample volumes and lower concentrations. A decade ago, for example, UV/Vis spectroscopy was at a disadvantage in certain applications, because it required large sample volumes, and was accurate only with relatively high sample concentrations. In contrast, emerging techniques based on microarrays were finding increasing use due to their ease of use and facility for extremely small sample volumes. Microvolume UV/Vis was a major breakthrough into the life science realm. Microvolume spectrophotometers eliminate the need to use traditional cuvettes. Instead, the user introduces a tiny drop of sample (often about 1 microliter) between two measurement surfaces within the instrument. Light passes directly through the sample over a pathlength determined by the distance between the two measurement surfaces–not by the dimensions of a cuvette. Eliminating the cuvette also sidesteps the need to dilute samples into larger buffer volumes, and, obviously, to clean the cuvette after use. The shorter pathlengths afforded by microvolume instruments allow measurement across a wider dynamic range, thereby improving measurement accuracy, reducing time, and minimizing sample consumption.

Often used as an extension of UV/Vis (or vice versa), near-IR spectroscopy is a well-established tool, not only in life science but also in the pharmaceutical and medical device arena. Near-IR's analytical range, sampling ease, operational simplicity, and compatibility with fiber-optic probes have given rise to a host of rugged spectrometers customized for in-, on-, at-, or near-line quality control of pharmaceutical and biopharmaceutical production processes. The technique's versatility is helping that industry explore new directions to meet changing needs. For example, manufacturers of flu vaccines are increasingly seeking cell-culture-based alternatives to poultry eggs as growth media for vaccine cultures. Cell-grown vaccines are of great interest in the industry, because they can be administered to patients with poultry allergies, are less prone to mutations, and are easier to scale up. However, infrastructural and regulatory issues must be overcome before cell-based methods can be more widely used in vaccine manufacturing. In a proof-of-concept study (33), a group at North Carolina State University tested a near-IR method to measure the concentration of influenza virus in cells grown in a bioreactor. They found that their probe provided near-real-time data on viral concentrations in multiple runs that rendered superior or comparable accuracy to the standard method, which can take an hour to produce results.

Another bioscience domain in which optical spectroscopy continues to hold great promise is the rapidly emerging field of wearable technologies. The potential of spectroscopy as a non-invasive (that is, "through-the-skin") monitor of blood glucose in diabetes management has been an active area of research for decades, and the wearables boom is sparking new ideas. Groups continue to explore various measurement modes such as near-IR (34) and Raman (35–37) in the quest to improve the quality of care for a disease that affects an estimated 425 million adults worldwide.

Beyond disease monitoring, wearable spectrometers are under study for a wide range of non-clinical applications. Recently a group at Drexel University developed a wearable headpiece to capture functional near-IR images of brain-to-brain coupling–a way of measuring and correlating brain responses among multiple subjects during natural verbal communication (38). The technique monitors oxygenated hemoglobin and deoxygenated hemoglobin in the cerebral cortex. Because conventional techniques such as functional magnetic resonance imaging (fMRI) require highly controlled laboratory environments that restrict the subjects' mobility, the near-IR method could provide advantages in neurolinguistics studies of natural human interactions. Other scientists have recently sought to extend near-IR's non-invasive capabilities for unobtrusive measurement of fitness indicators. A group of engineers at the University of British Columbia, for example, have recently teamed up with a sports physician to develop a health-monitoring smart garment using embedded near-IR sensors and software to measure local muscle metabolism. The idea is to help ensure an athlete trains at the appropriate level for their physical condition at any given point in time. For athletes recovering from an injury, metabolic data could help optimize a training regimen that promotes healing, without overtaxing the wearer. Conversely, the method could tell coaches when it is safe to push a healthy athlete harder when training for competition.

Society may be increasingly receptive to legalizing cannabis, but the opposite is true when it comes to the over-prescription and abuse of opioids such as Oxycontin and morphine. Prescription and non-prescription opioids are now responsible for 68% of U.S. drug overdose deaths, according to the National Institute on Drug Abuse (39). Relatively new on the scene is the synthetic opioid fentanyl, the highly potent painkiller famously linked to the accidental overdose death of rock musician Prince. Fentanyl-related deaths have increased by 540% in the U.S. since 2015 (40). A mere 2 mg of the drug is considered a lethal dose, and the danger is not confined to intentional users. Police officers, firefighters, and emergency medical personnel called to the scene of an overdose or criminal activity face heightened risk of accidental inhalation or exposure through the skin. As a result, instrument suppliers are developing specialized spectroscopy systems to help these non-scientist personnel protect themselves. Ion mobility spectrometry is effective in the collection and testing of invisible residues from areas suspected of contamination, while IR and Raman systems have been developed to identify unknown white powders or liquids (41).

The world reached an ominous environmental milestone last year with the first confirmed evidence that microplastics have entered the human food chain. A study (42) conducted by the Environment Agency Austria used FT-IR microspectroscopy to confirm the presence of polypropylene, polyethylene terephthalate, and other plastic particulates in fecal samples from eight participants from Europe, Japan, and Russia. Based on this study, the agency hypothesized that more than half the world population may have microplastics in their system. These <5 mm particles, fibers, and shards of degraded plastic have been found around the world in natural waters, beaches, Arctic sea ice, agricultural lands, and the air. They are small enough to be ingested by tiny marine lifeforms, but not necessarily to pass through without causing harm. They can harm organs and release chemicals that affect immunity, growth, and reproduction (43).

Just as atomic spectroscopy has found a new niche in measuring the impact of metallic particles on the environment and human health, FT-IR and Raman spectroscopy are the primary spectroscopic techniques for the identification of microplastics in the environment (44). However, human consumption of microplastics isn't always a result of environmental exposure. One recent study (45) used micro-Raman spectroscopy to determine the presence of microplastics in mineral water sold in bottles (plastic and glass) and beverage cartons. Scientists found small (50-500 micrometer) and very small (1-50 micrometer) fragments in every type of water, with nearly 80% of all particles ranging between 5 and 20 micrometers–a size not detectable by FT-IR microspectroscopy, which is generally limited to particles larger than 20 micrometers. Despite Raman's high profile in microplastics applications, its usefulness is still somewhat impaired by relatively slow analysis times, as well as the age-old problem of fluorescence interference. One group is working to speed up the process, with improved detectors, automated mapping and library matching methods, and nonlinear methods that enable real-time measurement (46).


In the more than 200 years since Joseph von Fraunhofer developed the first modern spectroscope, scientists have never stopped searching for new ways to make it better. Spectroscopy has returned the favor many times over, playing a critical role in the discovery and development of new materials, medicines, foods, chemicals, fuels, and other products intended to improve our standard of living. The introduction of innovations such as the microprocessor, laser, and advanced detectors dramatically sped up the pace of progress in the mid-to-late 20th century, launching the continuing trend toward commercial instruments combining high performance with a high degree of automation. Even as more lay-level users begin to wield spectrometer-based devices in their respective professions, the field will always be populated by spectroscopists with the training, insights, and tenacity required to extract high-quality data from complex samples and to translate that raw data into useful information. Thus, it is safe to assume that spectroscopic instrumentation and applications will continue to evolve and improve for the foreseeable future.


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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: