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The Eastern Analytical Symposium (EAS) Award for Outstanding Achievements in Mass Spectrometry will be presented to Barbara Larsen on Thursday, November 19.

is a Nutrition and Biosciences fellow at the DuPont Experimental Station in Wilmington, Delaware. Her research focuses on the application of mass spectrometry to support the biotechnology business. She has a keen interest in ionization methods to ensure the continued relevance of mass spectrometry for biotechnology projects at DuPont. Larsen has a passion for 

—selecting the best measurement technology to provide the critical solution to a specific problem. For her work supporting biotechnology research, Larsen has developed a digestion protocol for bioproteins that provides coverage of the expressed protein sequence or deep proteomic coverage of the organism that produced the protein. In addition, these methods can be used to provide details on protein modifications that occur during host expression or during processing. Her research interests include using a systems biology approach including metabolomics, proteomics, and transcriptomics to improve enzyme production and probiotic organisms.

Larsen has been part of the DuPont Company for the past 35 years. She received her BS from the University of Santa Clara, California, and her PhD in Physical Chemistry at the University of Delaware, followed by a post-doctoral fellowship at Johns Hopkins School of Medicine. Larsen has received the Spectroscopy Society Award and the Delaware ACS Section Research Award. DuPont awarded her research with the Pederson Award, for significant scientific achievement that reflects technical excellence. 

She is currently a member of American Society of Mass Spectrometry—where she has served as the treasurer, vice president of programs, and president—and is on the advisory board for the society journal. As an active member of the American Chemical Society (ACS), she was made an ACS fellow for her service as the chair for the Delaware Valley Mass Spectrometry Discussion Group and as a counselor for the Delaware ACS section. She also serves on the editorial advisory board of 

Articles

Barbara Larsen Receives EAS Award for Outstanding Achievements in Mass Spectrometry

The New York Society for Applied Spectroscopy Gold Medal Award will be presented to Jerome Workman, Jr. and Howard Mark at the Eastern Analytical Symposium (EAS) on Wednesday, November 18. Workman is scheduled to deliver a talk on “The Present and Future of Chemometrics in the Analytical Sciences” while Mark is scheduled to deliver a talk on the “History of Calibration Transfer.” This year marks only the second time the committee has selected two winners for the Gold Medal Award since its inception in 1952. Mark and Workman were recognized for their contributions, individually and as a team, to the field of near-infrared (NIR) spectroscopy and chemometrics, leading to a wider adoption of the technology in the spectroscopy community.

Jerome Workman, Jr. is currently the Senior Technical Editor for 

. He is also a Certified Core Adjunct Professor at National University in San Diego, California, and a principal at Biotechnology Business Associates. He was formerly the Executive Vice President of Research and Engineering for Unity Scientific and Process Sensors Corporation. Workman has more than 75 U.S. and international patent applications since 1998 with 25 issued U.S. and international patents and multiple trade secrets. He has more than 500 technical publications, including 22 reference books on a broad range of spectroscopy, chemometrics, and data processing topics.he also has received many awards, including the 2002 Eastern Analytical Symposium Award for Achievements in NIR, the 2002 ASTM International Award of Merit, the 2009 Coblentz Society Williams-Wright Award, as well as awards from the Society for Applied Spectroscopy, National Institute of Standards and Technology (NIST), Frost and Sullivan, and other organizations. He is a fellow of the American Institute of Chemists, ASTM International, and the Royal Society of Chemistry.

Howard Mark serves on the Editorial Advisory Board of 

and runs a consulting service, Mark Electronics, in Suffern, New York. Mark has authored 243 papers including 75 installments of the "Statistics in Spectroscopy" column and 123 installments of "Chemometrics in Spectroscopy," four books, numerous book chapters, and seven patents. He was a Student Awardee to the 1964 Eastern Analytical Symposium, and has received the 2003 Eastern Analytical Symposium award for Outstanding Contributions in the Field of Near Infrared Spectroscopy, an Honorary Life Membership to the Council for Near Infrared Spectroscopy, awarded in 2010, and the 2011 Coblentz Society's Williams-Wright award for Outstanding Contributions to the Field of Industrial Vibrational Spectroscopy. Mark’s interests focus on application of electronics and especially, computers, to chemical Instrumentation and analysis, with emphasis on gas chromatography and spectroscopy, particularly mid- and near-infrared spectroscopy.

The New York Society for Applied Spectroscopy Gold Medal Award will be presented to Jerome Workman, Jr. and Howard Mark at the Eastern Analytical Symposium (EAS) on Wednesday, November 18.

Jerome Workman, Jr. and Howard Mark Receive the 2020 New York Society for Applied Spectroscopy Gold Medal Award 

The Eastern Analytical Symposium (EAS) Award for Outstanding Achievements in Magnetic Resonance will be presented to Arthur G. Palmer III on Monday, November 16.

received a BA in chemistry magna cum laude in 1980 from Haverford College. At Haverford, he conducted undergraduate research in the photochemistry of carbonyl carbene with Professor Colin F. Mackay. After two years working as an analytical chemist and two years teaching high school chemistry and physics, Palmer entered graduate school, first receiving his MS in Industrial Health from the University of Michigan in 1986 and then completing his PhD from the University of North Carolina at Chapel Hill in 1989. His doctoral research, conducted under the direction of Professor Nancy L. Thompson, developed the technique of high order autocorrelation in fluorescence correlation spectroscopy.

Palmer made the transition to nuclear magnetic resonance (NMR) spectroscopy during his work as a National Science Foundation Postdoctoral Fellow with Dr. Peter E. Wright at the Scripps Research Institute from 1989 to 1992. There, Palmer codeveloped, with Wright, Mark Rance, and John Cavanagh, sensitivity-enhanced heteronuclear single quantum coherence spectroscopy (HSQC) and began his first developments and applications of NMR spin relaxation to characterize macromolecular dynamics. Palmer moved to the Department of Biochemistry and Molecular Biophysics at Columbia University as an assistant professor in 1992 before being promoted to associate professor in 1998 and then to professor in 2001. Palmer currently holds the Robert Wood Johnson junior chair title and serves as interim Chair of the Department of Biochemistry and Molecular Biophysics and as Associate Dean for Graduate Affairs at Columbia University Medical Center. He is also the Director of NMR Spectroscopy at the New York Structural Biology Center.

Palmer is the author of 150 papers and the coauthor, with John Cavanagh, Wayne J. Fairbrother, Nicholas J. Skelton, and Mark Rance, of the book 

Protein NMR Spectroscopy: Principles and Practice

, now in its second edition. Palmer uses NMR spectroscopy and molecular dynamics simulations to elucidate the coupling between conformational dynamical properties and biological functions of proteins. His research interests include the development of novel methods in NMR spectroscopy, computational and theoretical analyses of protein dynamics, and applications to protein folding, molecular recognition, and catalysis. He has contributed in particular to the use of generalized order parameters for characterizing conformational entropic effects in molecular recognition, and the use of CPMG and R1r relaxation dispersion measurements for characterizing microsecond-millisecond time scale processes.

Palmer is interested in the conformational dynamic differences between mesophilic and thermophilic enzymes that contribute to differences in activity, using the ribonuclease H superfamily as a model system. Other recent applications include the mechanism of strand swapping in dimerization of cadherin cell adhesion proteins, the role of local dynamics in DNA recognition by the GCN4 bZip transcription factor, and dynamic control of the order of substrate addition in the DNA-repair enzyme AlkB.

Arthur Palmer Receives EAS Award for Outstanding Achievements in Magnetic Resonance

The Eastern Analytical Symposium (EAS) Award for Outstanding Achievements in Vibrational Spectroscopy will be presented to John A. Reffner on Tuesday, November 17. Reffner will also give a talk on “Advancing Our Knowledge Through Studies of Vibrational Spectra.”

Reffner’s scientific interests focus on uniting spectroscopy with microscopy and applying novel technologies to advance materials and forensic science. He pioneered the development of infrared micro-spectrometers, accessories, and innovative applications in infrared microprobe technology. Reffner’s scientific accomplishments are recognized by his receiving the 2016 American Society of Trace Evidence Examiners’ Edmond Locard Award, the 2015 Society of Applied Spectroscopy’s Gold Medal Award, the 2004 American Academy of Forensic Sciences award, the 2004 Paul L. Kirk Award, the 2002 New York Microscopical Society’s Abbe Memorial Award, the 2002 Georgia Microscopical Society’s Honorary Achievement Award, the 2000 Coblentz Society’s Williams-Wright Award, and the 1993 Illinois State Microscopical Society’s Emile M. Chamot Award. In 2011, Reffner was named a fellow of the Society of Applied Spectroscopy (SAS).

Reffner has authored 90 papers and four book chapters while inventing ten patents. He served as a consultant to the Connecticut State Police for over 25 years and has testified as an expert witness in criminal, civil, and intellectual property litigations. He is also on the advisory board of the Dr. Henry C. Lee Institute at the University of New Haven. His employment, since graduation from Akron University, includes B. F. Goodrich, Walter C, McCrone Associates, the University of Connecticut, American Cyanamid, Spectra-Tech, Nicolet, Thermo Scientific, SensIR, and Smiths Detection. Reffner is currently a professor of forensic science at John Jay College, which is part of the City University of New York (CUNY) in New York, New York.

The Eastern Analytical Symposium (EAS) Award for Outstanding Achievements in Vibrational Spectroscopy will be presented to John A. Reffner on Tuesday, November 17.

John Reffner Receives EAS Award for Outstanding Achievements in Vibrational Spectroscopy

Jerome Workman Jr. serves on the Editorial Advisory Board of Spectroscopy and is currently with Unity Scientific LLC. He is also an adjunct professor at Liberty University and U.S. National University. He can be reached at jworkman04@gsb.columbia.edu.

Recent collaborative research demonstrates the use of Kerr-gated Raman spectroscopy to study catalysts and catalytic reactions for investigating renewable energy sources. The approach overcomes fluorescence interference problems normally encountered using Raman spectroscopy of catalysts and can facilitate the development of renewable energy sources, such as producing gasoline from methanol.

 (1), was performed through a collaboration between the Central Laser Facility (CLF) of the Science and Technology Facilities Council (STFC), University College London, Ghent University, and the Catalysis Hub, The Catalysis Hub is a United Kingdom consortium aimed at leading the world in catalytic science.

Catalysis is an extremely important field of study in chemistry and involves the materials and processes of increasing the rate of a chemical reactions by the use of catalysts. Catalysts are the materials used to increase reaction rates, by lowering activation energies for reactions, and can be repeatedly used while not being consumed in the catalyzed reaction. Different classification types of catalysts include electrocatalysts, organocatalysts, photocatalysts, enzymes, and biocatalysts. Catalytic reactions occur in nature as well as in synthetic chemical reactions, such as in the production of petroleum products (alkylation, catalytic cracking, catalytic converters); bulk chemical production (catalytic oxidation, hydrogenation, and hydroformylation); fine chemical production (Heck reaction, and Friedel–Crafts reactions); and in food processing (hydrogenation and biocatalysis).

Natural and synthetic zeolite crystals (Figure 1) are essential catalysts, and represent the most-used catalysts by weight in the world. Zeolites are crystalline alumino-silicate, porous materials with regular molecule-sized nanopores—having a specific physical structure of channels and cavities, which affect their catalytic properties and efficiencies (their adsorption, diffusion, and reaction properties). Understanding zeolite structure and reaction properties is an important area of research in the field of catalysis.

Understanding the detailed structure and function of zeolites in chemical reactions has been an analytical challenge. The pores of zeolites may be contaminated with heavy hydrocarbons over time that get trapped within them—as contamination occurs over time the catalytic activity will decrease and eventually cease. When the zeolite is deactivated it must be replaced or reactivate using an expensive process. This entire activation and deactivation process is of keen interest to catalysis researchers.

One of the most common techniques used to investigate zeolite structure and catalysis is Raman spectroscopy. However, the fine structural information that might be available using the Raman technique is often obscured due to background fluorescence. CLF’s expertise in Kerr-gated Raman spectroscopy is providing the means for detailed spectra to be obtained without the fluorescence background problems.

Kerr-gated Raman spectroscopy uses the Kerr gate optical effect to remove most of the fluorescence background from the Raman signal when using Raman spectroscopy. The Kerr gate effect functions by plane polarizing the combined Raman scattered signal and fluorescence signal (resulting from a 1 ps laser pulse) by using a plane polarizer. Then by passing that combined signal through a 45o tilting CS2 containing cell of 2 mm pathlength (Kerr medium), the resulting signals are separated into a plane polarized fluorescence signal and a perpendicularly polarized Raman signal. By then passing the signals through a cross polarizer, the Raman scattering will pass (is transmitted) to the detector, while the fluorescence signal is blocked. Therefore the fine Raman spectral structure may be observed relatively free from the fluorescence background. The Kerr gate effect takes advantage of the time delay between the instantaneous Raman scattering signal and the delayed background fluorescence that occurs a few picoseconds or nanoseconds later.

“Kerr-gated Raman is remarkable because it makes it possible to detect tiny Raman signals from zeolite reactions that would otherwise be lost in a sea of fluorescence noise, said Professor Mike Towrie of CLF “The Ultra Laser Facility at the CLF allowed us to achieve a signal quality approximately 100 times better than if we’d used standard Raman. For me, this work has been exciting because it demonstrates the potential of Kerr-gated Raman to help answer many more questions in catalysis and in other areas such as battery science.”

Kerr-gated Raman spectroscopy is being applied to gain understanding of the potential for catalytic reaction chemistry to produce gasoline (mostly octane) from simple hydrocarbons, such as methanol. Better understanding of this reaction could result in producing gasoline from biomass fermentation as a renewable energy source—reducing both fuel production costs and environmental impact. Methanol is considered a clean energy option that can be produced from many renewable sources. A methanol molecule has only half the energy density of gasoline and, in the 1970s, the chemistry was developed to convert methanol into gasoline using a catalytic reaction involving zeolites. The size of the zeolite pores determines the type of hydrocarbon produced by the catalytic reaction—small pores produce light hydrocarbons—medium pores produce gasoline.

Using Kerr-gated Raman spectroscopy the CLF team were able to track all the stages of the reaction, in increments of three to four picoseconds, and observe a conversion of methanol to octane as longer chains of hydrocarbons were being formed. This allowed detailed observations of the entire reaction process. The Raman technique also provides information of the activation and deactivation of the zeolite catalysts. This rapid analysis technique has provided insight into the formation of polyenes as the cause of deactivation of the zeolite catalysts—a new and unexpected discovery. “I think that this will change the way people think about how these materials deactivate because, as soon as you know who the culprits are, you are able to design a strategy, said team leader Professor Andy Beale of University College London. He said, “There is a huge energy cost, as well as time cost, associated with reactivating catalysts frequently, so anything that can keep catalysts doing their job for longer will save money, energy and reduce the environmental impact resulting in greener fuels. The study could be significant for industry especially as methanol can be produced from biomass stocks meaning that gasoline may not have to come from fossil fuel stocks in the future.”

Reference
(1) I. Lezcano-Gonzalez, E. Campbell, A. E. J. Hoffman, M. Bocus, I. V. Sazanovich, M. Towrie, M. Agote-Aran, E. K. Gibson, A. Greenaway, K. De Wispelaere, V. Van Speybroeck, and A. M. Beale, “Insight into the effects of confined hydrocarbon species on the lifetime of methanol conversion catalysts,” Nature Materials 19, 1081–1087 (2020). (

https://doi.org/10.1038/s41563-020-0800-y

Recent collaborative research demonstrates the use of Kerr-gated Raman spectroscopy to study catalysts and catalytic reactions for investigating renewable energy sources.

Kerr-Gated Raman Spectroscopy is Being Used to Study Catalysis Reactions for Investigating Renewable Energy Sources 

In your paper (1), you state that single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) is an emerging methodology that holds promise to enable multielemental analysis of low-volume samples in the future. Can you explain why you believe this?

In my view, SC-ICP-MS has become a hot topic in the field of elemental analysis, and rightly so: Scientist working in the field of bioanalytics applied this approach to look into the smallest units of life. As a matter of fact, most biochemical processes take place in cells. Elemental bioanalysis in cells makes it possible to obtain deep insights into cellular processes and the biological status of specific cells. In comparison, the analysis of bioliquids mainly provides insights on a systemic level of the corresponding organism. Over the last decades, many scientists applied ICP-MS to study the elemental composition in all kinds of biofluids and tissues. Due to the latest technical developments it is now possible to achieve ever lower detection limits. Thus, it is now possible to examine individual cells and their elemental composition—at least partially. This may open a completely new field of application for ICP-MS and there are many scientists who are about to prove this.

Why is ICP-MS generally considered being the method of choice for multielemental analysis as compared to other ICP techniques (AES or OES) or more traditional atomic absorption (F-AAS or GF-AAS)?

ICP-MS is unarguably the gold standard for elemental and especially multielemental analysis. This is mainly due to the fact that this technique is extremely versatile compared to ICP-OES/AES and atomic absorption spectroscopy. Most AAS devices apply element-specific radiation sources (hollow cathode lamps) that enable the detection of a single element at the same time. Although there are some commercially available AAS instruments that allow the detection of 10-20 elements simultaneously, sensitivity limitations hamper the analysis of most trace and ultratrace elements. ICP-OES allows multielemental analysis, is relatively easy to setup, and well-suited for high-throughput analysis—however, spectral interferences can be challenging. ICP-MS allows high-throughput, multielemental analysis with the lowest-possible detection limits. It offers a linear detection range of up to 10 orders of magnitude, enables isotopic analysis (isotope dilution analysis for quantification, control of spectral interferences), and it is possible to analyze any type of sample material (gases, liquids, solids).Furthermore, high-resolution separation techniques such as HPLC, GC, CE etc. can be hyphenated to the ICP-MS. Overall, this makes ICP-MS the most powerful and versatile technique for elemental analysis.

What motivated you to focus on this specific application?

Several times, we have encountered situations, where limited sample volume was available. For example, limited volume of biofluids (blood serum or plasma) might be available in human sample cohorts for interdisciplinary clinical studies. In such cases, the principal investigator often selects the panel of analytical tests according to the required sample volume. Sample volume restrictions can also arise from the donor itself, even if there is no competing analysis. This is the case for animal models, especially for studies with mice where only a few µL of blood serum or plasma are available per animal. Since most of the published multielemental profiling methodologies require relatively large sample volumes, our aim was to provide a tool that overcomes this challenge. For this reason, in 2016 we have developed an ICP-MS based method, which allows the analysis of 29 elements in a 150 µL blood serum sample. However, we soon realized that there is a need for multielement analysis in even smaller sample volumes. This is for example the case when only small amounts of serum and sample are available (for example, in precious clinical cohorts or preclinical studies with rodents). We accepted the challenge and found that it is possible to detect 20 to 30 elements in 3–10 µL of biological fluids. These positive results have motivated us to optimize and validate the method. Finally, we have successfully applied the method in a preclinical model. The method turned out to be very easy to use, it does not require expensive or complicated changes in the experimental setup, and, above all, it has shown very good analytical performance. We then decided to publish the results of our study as well as the experimental setup in order to encourage other readers to perform multi-element analyses in the smallest sample volumes in a straightforward way.

What are some cancer-specific multielemental profiles that you have identified? What type of data analysis techniques were used to determine these profiles? Are there a few predominant elements that seem to be most often present in the mice cancer cells?

In the mouse cancer modes under evaluation, the presence of the tumor influences the serum concentration levels of various elements. Some elements, such as sulfur, calcium, manganese, zinc, strontium and molybdenum, were not affected significantly by the presence of the tumor. On the other hand, elements such as phosphorous and copper were increased in the serum samples of tumor bearing mice, independently of the tumor type. Iron, on the other hand, was depleted. These results seem to indicate that the presence of tumor systemically influences the concentration levels of some serum elements, independently from the tumor type. On the contrary, elements such as vanadium, chromium, bromine, rubidium, cesium and cobalt show trends for tumor-specific concentration changes. Furthermore, our results show that different immune T cells (CD4+ and CD8+) have specific mineral profiles reflecting their specific immune function. Moreover, the presence of a tumor seems to have an impact in the mineral contents of T cells. Indeed, we observed elemental modulations within CD8 cells that could be associated with presence of cancer, such as higher levels of magnesium and manganese and lower levels of iron, cobalt and rubidium. These findings might indicate an increased metabolic need of immune cells for Mn and Mg in the presence of a tumor.

What are the biggest challenges that you encounter in this analysis method? Are there any limitations to using this technique? What options or alternatives are available to overcome these challenges?

While the analysis of small amounts of biofluids is quite straightforward (centrifugation to remove particles and a simple dilution step), the analysis of cells is more challenging. In fact, one hurdle we faced during method development was to remove the cell sorting buffer (containing a high concentration of various elements of interest) from the cells. As large volumes of this buffer are required for a single cell-sorting experiment (roughly 10 liters in our case), it was not possible to prepare a buffer solution based on reagents which are suitable for trace elemental analysis. For a washing step, we applied filters or considered osmosis for buffer removal, but none of these sample preparation strategies proved to be suitable. Finally, applying a mild centrifugation step to form a cell pellet, followed by removing the supernatant with a pipette, provided satisfying results. However, the removal of a few microliters from an Eppendorf tube, and at the same time maintaining the integrity of a tiny cell pellet, remains the Achilles heel of the method and requires some finesse and experience.

With such small samples, is contamination an issue, and how have you overcome this potential problem?

Contamination is always a challenge in ultratrace elemental analysis. Acid-washing, working in a clean environment and under a fume hood are the minimum requirements to obtain high quality results. However, contamination is not more challenging in this method, as compared to most other ICP-MS based methods dealing with trace and ultratrace analysis. This is mainly due to the fact that a relatively moderate sample dilution of (1:10) and few sample preparation steps are applied. Contamination could arise, for example, from plastic materials. We mitigate this risk by applying an acid-washing step up front. Another, often underestimated source of contaminants are chemicals and reagents applied during sample preparation. They often contain elements (for example, iron) that enter the sample in this way and thus mix with the analytes. Due to the inherent properties of elemental mass spectrometry, it is then no longer possible to distinguish easily between endogenous and exogenous elements. This can lead to an overestimation of the element concentration. In our study we only apply buffer solutions and nitric acid during sample preparation. Thus, the overall contamination risk is relatively low.

Can you briefly summarize the results that you have achieved so far?

We have developed a quantitative analytical strategy that enables the analysis of 20 biologically relevant elements in low-volume samples (10 µL) of serum. By applying an optimized workflow, the method is also applicable for the quantification of 12 elements in a low number of sorted cells (250,000 cells). In our paper, we give detailed descriptions of the experimental setup. This enables scientist to apply the approach to study biological-relevant elements (major trace and ultratrace elements) in very small sample volumes. Applied to tumor cells, we could demonstrate that the presence of certain cancer types influences differentially the elemental composition of serum concentrations. Furthermore, we could show that different immune T cells (CD4+ and CD8+) have specific mineral profiles reflecting their specific immune function. Last but not least, the presence of a tumor effects the mineral composition of T cells.

Is there anything that you have done in your study that is different from what other researchers have done as they have examined the same problem?

Most of the ICP-MS-based approaches aiming to detect major trace and ultratrace elements in cells are challenged by the media or solvent in which the cells are transported into the plasma ionization source. If the cells are present in Milli-Q water, the “elemental background” is very low. This facilitates the detection of very small quantities of cellular elements. However, cells are prone to lyse in Milli-Q-water. This makes the cellular membranes permeable for ions and small molecules, which are eventually leaking out of the cell and changing the elemental composition of the cell. Fixation strategies, aiming to stabilize cellular membranes, can prevent lysis. Unfortunately, fixation methods tend to increase permeability of the cell membranes and consequently alter the endogenous elemental composition of the cell. Moreover, aggregation of cells is often seen after fixation and needs to be monitored. In fact, the presence of cells in the monodisperse state has to be confirmed by complementary analysis. Many of the reported SC-ICP-MS methods are overcoming this issue by using yeast cells. The use of yeast cells has two advantages: first, the cells are relatively big, meaning higher absolute quantity of elements per cell. Second, these cells are extremely robust compared to immune cells. Re-suspended in Milli-Q water, yeast cells can stay alive for a couple of hours without undergoing lysis. This timespan allows conducting SC-ICP-MS experiments with intact cells while maintaining an extremely low elemental background of the solvent. Suspensions of cells in buffer solutions, on the other hand, allow keeping the cells alive and preserve the integrity of the cell. However, such buffer solutions contain “contaminants”; for example, major or trace elements which are present in the raw materials. This makes it difficult to distinguish between “cellular” elements and elements from the buffer solution. We were able to overcome this limitation by using a sample preparation strategy that includes a washing step with a suitable buffer solution (containing a relatively low elemental background).

What are your next steps in this work? Do you know how well the discoveries of multielemental profiles in mice cancer cells may extrapolate to human cancer cells?

I am now working in a company which is rather focused on elemental analysis is food and pharmaceutical products. However, my former colleagues are continuing our research work and other scientist are working on different approaches to study trace- and ultratrace elements in cells. I am confident that rather sooner than later we will see new findings in this field, both in pre-clinical and clinical studies.

Tobias Konz is currently leading the Elemental Analysis group at UFAG Laboratorien (in Sursee, Switzerland), specializing in quantitative analysis of elements in food and pharmaceutical products (GMP and ISO environment). He studied biomedical chemistry at the Johannes-Gutenberg University (2000-2007), and completed his diploma thesis and PhD in Analytical Chemistry in the research group of Alfredo Sanz-Medel, under the supervision of Maria Montes-Bayón (University of Oviedo, Spain). In 2014, he started a professional career as ICP-MS specialist at the Nestlé Institute of Health Sciences (Lausanne, Switzerland) in the Nestlé Research organization. The main focus of his work has been to develop quantitative methods for multielemental analysis in low volume samples (biofluids) in a GLP and ISO regulated environment.

(1) T. Konz, C. Monnard, M. Rincon Restrepo, J. Laval, F. Sizzano, M. Girotra, G. Dammone, A. Palini, G. Coukos, S. Rezzi, J.-P. Godin, and N. Vannini, 

https://dx.doi.org/10.1021/acs.analchem.9b05643

Tobias Konz of Nestlé Research, Lausanne, Switzerland and various associates have developed and validated what they describe as a reliable, robust, and easy-to-implement quantitative method for multielemental analysis of low-volume samples. The ICP-MS-based method comprises the analysis of 20 elements (Mg, P, S, K, Ca, V, Cr, Mn, Fe, Co, Cu, Zn, Se, Br, Rb, Sr, Mo, I, Cs, and Ba) in 10 μL of serum and 12 elements (Mg, S, Mn, Fe, Co, Cu, Zn Se, Br, Rb, Mo, and Cs) in less than 250,000 cells, and involved the analysis of elemental profiles of serum and sorted immune T cells derived from naıv̈e and tumor-bearing mice. The results indicate a tumor systemic effect on the elemental profiles of both serum and T cells. Konz and his colleagues believe their approach highlights promising applications of multielemental analysis in precious samples such as rare cell populations or limited volumes of biofluids that could provide a deeper understanding of the essential role of elements as cofactors in biological and pathological processes. Konz spoke to us about this work.

Quantitative Methods for Multielemental Analysis in Low Volume Biofluids 

 Magazine is pleased to announce the addition of seven new members to its editorial advisory board: Karl S. Booksh, John Coates, Paul J. Gemperline, Barry K. Lavine, Igor K. Lednev, and Yukihiro “Yuki” Ozaki.

Karl S. Booksh is a professor in the Department of Chemistry and Biochemistry at the University of Delaware. He holds a BS in Chemistry from the University of Alaska and a PhD in Analytical Chemistry from the University of Washington. He is an American Chemical Society Fellow (2015) and a Society for Applied Spectroscopy (SAS) Fellow (2014), and is the president elect of SAS for 2021. His research group develops small chemical sensors capable of reliable measurements in the field or in the process chemical sensors for environmental, biomedical, and industrial process monitoring. His group also conducts chemometric analysis of collected data and multivariate sensor calibration. In terms of analytical techniques, Booksh is focusing largely on Raman, Laser-induced breakdown spectroscopy (LIBS), and fluorescence sensors with a bit of Raman imaging for fun. He is the author of over 100 peer-reviewed articles.

John Coates was educated and started his career in the United Kingdom. He first worked as an analytical chemist for Castrol Oil Company. He graduated from the Royal Society of Chemistry (RSC) and obtained his PhD in analytical chemistry at Brunel University. After moving to the United States as a senior staff scientist at Perkin Elmer Corporation, Coates accepted positions at Spectra-Tech (Stamford, Connecticut) and then at Nicolet Instruments (Madison, Wisconsin) before returning to a position at PerkinElmer’s Real-Time Systems Division (Wilton, Connecticut) a joint-venture with Dow Chemical Company (Midland, Michigan).

In 1996, Coates opted to leave the corporate world and formed his own company, Coates Consulting LLC, a consulting company focused on applied and industrial instrumentation, optical spectroscopy, and analytical instruments and sensors for dedicated applications, with a primary focus on instrument miniaturization and spectral sensors. Coates has been involved in the development of more than 100 different instrument and sensor products for dedicated applications and received the Williams-Wright Award for Industrial Spectroscopy, presented by the Coblentz Society, in 2013. Coates has 50 years of industrial experience.

Paul J. Gemperline has been the dean of the graduate school at East Carolina University (ECU) since 2009 and a faculty member in the department of chemistry since 1982. He earned his BS and PhD in chemistry from Cleveland State University. Gemperline’s area of research is chemometrics with more than 60 publications and $1.8 million in external grant funds from government and industrial sources. Gemperline's research focuses on the development of new computer algorithms and software tools for analysis of multivariate spectroscopic data. His work has led to advances in methods for monitoring, understanding, and controlling batch chemical and pharmaceutical processes. He has developed methods of cluster analysis and classification for rapid non-destructive testing of raw materials and finished products. His work with collaborators led to the development of a licensed patent for designing optical filters for chemical calibration.

Gemperline also served as the editor-in-chief of the 

Barry K. Lavine is a professor of chemistry at Oklahoma State University (OSU). Lavine’s research interests encompass many aspects of chemical analysis including optical sensors, vibrational spectroscopy, infrared and Raman imaging, and chemometrics. Lavine has published more than 115 research papers, 21 book chapters, and 16 review articles, along with being the editor for three ACS monographs. Lavine is on the editorial board of several journals including the 

. He has served as chair of the Northern New York (1997–2004) and Oklahoma (2006–2008) sections of the ACS. Lavine has also been the program chair for several meetings including SciX (1992), the Northeast Regional ACS Meeting (1999), and the Pentasectional Meeting of the local Oklahoma Sections of the ACS (2005). Lavine is the recipient of the 2015 Kowalski prize from the 

and the 2017 Chemometrics Award sponsored by the Eastern Analytical Symposium. He is also a SAS fellow.

Igor K. Lednev is a professor at the University of Albany, State University of New York. He received his PhD from the Moscow Institute of Physics and Technology and worked in several leading laboratories around the world in the United Kingdom, Canada, Germany, and Japan. Lednev accepted a faculty position at the University at Albany in 2002 and was promoted to full professor in 2013. His research focuses on the development and application of novel laser spectroscopy techniques for medical diagnostics and forensic purposes. Lednev is a cofounder of two startup companies commercializing his patented technology. He served as an advisory member on the White House Subcommittee for Forensic Science and is a fellow of SAS and the Royal Society of Chemistry. Lednev also launched a new annual National Institute of Justice (NIJ) Forensic Science Symposium at Pittcon in 2018.

He has co-authored about 240 publications in peer-reviewed journals and seven patents.

Yukihiro (Yuki) Ozaki received his PhD in 1978 from Osaka University. He joined Kwansei Gakuin University in 1989. From 1993 to March 2018, he was a professor in School of Science and Technology. Currently, Ozaki is a professor emeritus of the university. He has been a guest professor or scientist at Kobe University, Fukui University, and Riken and Toyota Physical and Chemical Research Institute. Ozaki is involved in studies of a wide range of molecular spectroscopy techniques, ranging from far-ultraviolet to far-infrared to Terahertz and Raman spectroscopy. His research focuses on both electronic and vibrational spectroscopy.

Ozaki has been a member of SAS for more than 30 years and fellow since 2013. He received several awards including the Bomem-Michelson Award (2014), Chemical Society of Japan Award (2017), The Medal with Purple Ribbon (2018), Pittsburg Spectroscopy Award (2019), and Charles Mann Award (2020).

Barry Wise received BS degrees in chemistry and chemical engineering from the University of Washington in 1982. After three years with Battelle Pacific Northwest National Laboratory, he returned to the University of Washington, where he received MS (1987) and PhD (1991) degrees in chemical engineering. Wise has authored more than 50 scientific publications, patents, and book chapters. He has also created a popular chemometrics software package, PLS_Toolbox, used by scientists and engineers worldwide. Wise is president and cofounder of Eigenvector Research Inc., which provides chemometrics software, training, and consulting. Thousands have attended Wise’s chemometrics short courses at conferences and at Eigenvector University.

Wise was named the winner of the Eastern Analytical Symposium Chemometrics Award for 2001 in recognition of his significant contributions to the field. He also received the Herman Wold Medal in Gold in 2019 for his deep commitment to the proliferation of chemometrics.

Spectroscopy Magazine is pleased to announce the addition of seven new members to its editorial advisory board.

Seven New Members Join Spectroscopy's Editorial Advisory Board

Of course, this year’s meeting is different because of our response to the presence of COVID-19. 

 There will be LIVE on-line sessions each day during the week of 

 Additionally, the EAS presents pre-recorded ON-DEMAND sessions available at any time through December 31 to those who register for the Symposium. And, be sure not to miss the on-line virtual exhibition for the latest innovations from the vendors you have come to rely on.

This year, the EAS Awards for achievements in spectroscopy recognize the outstanding contributions of Barbara S. Larsen (mass spectrometry), Arthur Palmer (magnetic resonance spectroscopy), and John Reffner (vibrational spectroscopy), and you can tune in to these award sessions, LIVE. Also live are the sponsor awards such as the SAS Gold Medal honoring Howard Mark and Jerome Workman, as well as the Ernst Abbe Award to Brian J. Ford. But there also are many pre-recorded on-demand sessions and posters on spectroscopic analysis of materials, forensic analysis, biological and pharmaceutical analysis, microscopy, Raman imaging, LIBS, and many more.

Two highlights of the EAS in years past have been the keynote lecture and the plenary lecture, and this year’s lectures should be exceptionally entertaining for attendees. The keynote lecture by Eric Green of the National Institutes of Health is titled “The Human Genome Project was just the Beginning: Research Opportunities at the Forefront of Genomics.” The plenary lecture, “The Fascinating Impact of Nanoscale Structure on Chromatography and Mass Spectral Ionization,” will be given by Susan Olesik, this year’s winner of the EAS Award for Outstanding Achievements in the Fields of Analytical Chemistry. Her lecture combines two themes that should interest a wide audience. In addition, this year there is a special lecture presented by Adam Lanzarotta of the USFDA on the “FDA’s Role in the 2019 Vaping Crisis.” These three lectures focus on important issues in science and how it affects the world around us.

The Eastern Analytical Symposium is known for its large suite of short courses tailored to the needs of analysts. This year we are proud to continue the tradition of short courses on a wide range of traditional and novel topics in analysis. Whether it’s gas or liquid chromatography, hyphenated methods, spectroscopic methods including imaging, NMR spectroscopy, FT-IR spectroscopy, or topics like communication or process analysis, there is a course at EAS for you!

These will be presented in a LIVE video format that allows interaction with the instructor, over several weeks, allowing interested persons to attend multiple short courses.

, for the latest news and registration info for this year’s virtual EAS. Be sure to take advantage of the discounted pricing we offer to those who register early!

Once again, the Eastern Analytical Symposium takes the spotlight November 16–19, providing analysts with the latest developments in areas ranging from biopharmaceutical analysis to materials characterization, from quality assessment to green analysis, and from environmental contaminant determination to antibody analysis, to name a few of the many areas covered.

The 59th Eastern Analytical Symposium

The Society for Applied Spectroscopy (SAS) Atomic Section is proud to honor four deserving students with the 2020 SAS Atomic Section Student Awards. These awards provide the winning students with the opportunity to present their work at the conference and normally include travel funding to attend the conference. This year, the winners will present during an on-demand access session as part of the SciX 2020 virtual conference. The awards also include a two-year membership to the society. The four winners are listed below.

who is a student at Rensselaer Polytechnic Institute under Prof. Jacob Shelley, will present his work on “solution-cathode glow discharge ionization sources for mass spectrometry.”

of the University of Natural Resources and Life Sciences Vienna (BOKU), who is studying under Prof. Thomas Prohaska, will present her work on “LA and MC-ICP-MS for isotope analysis of bone for biomedical applications.”

, a student at the University of Münster, under adviser Prof. Uwe Karst, will present his work on “LC–ICP-MS for Gd speciation in surface and drinking waters.”

 of the University at Buffalo, The State University of New York, whose adviser is Prof. Steven Ray, will present her work on “Exploration of microelectrochemical devices as temporal gating devices for LIBS and LAMIS.”

More information about the awards can be found on the SciX conference 

The 2020 SAS Atomic Section Student Awards

The qualitative and quantitative determination of trace elements is a stronghold of inductively coupled plasma–mass spectrometry (ICP-MS). Whereas in most cases the concentrations of a series of elements are determined in the bulk sample (often requiring a digestion upfront), the use of laser ablation (LA) in combination with ICP-MS allows further insight into an isotope of a given element within a sample, with the added benefit of avoiding labor intensive and contamination-prone digestion processes. LA-ICP-MS also allows the analysis of small samples with highly localized differences in trace elemental concentrations. Higher sensitivity and better interference removal using triple quadrupole instrumentation, as well as faster laser systems with specialized ablation cells enabling fast washout of material from individual laser pulses, has paved the way for new applications for LA-ICP-MS. The software supported recombination of data generated in a series of line scans covering the entire area of a sample. This was in conjunction with information on the laser position over time (using ablation rate, spot size, and stage movement velocity), allowing for the creation of a full image of elemental distributions in a sample. This is especially useful for biological samples, where the role of trace elements involved in biological processes is often unknown. This article will outline the principle of LA-ICP-MS for imaging applications, highlighting its potential to gain additional insights into the field of bioanalysis and metallomics. More specifically, the technique will be used to track the effect of environmental pollution on the distribution of heavy metals in the brain of a sentinel species in a highly urban area.

Metallomics takes an integrated approach to understanding the metallobiochemistry of cells and organisms in health and disease, utilizing analytical tools to elucidate the biological roles of metals in both space and time (1). In humans, every tenth protein depends on zinc for structure, catalysis, or regulation, and, together with other metal ions, every second protein contains a metal ion essential for its function. Most importantly, both the metal composition and the distribution in cells and tissues change during physiological and pathophysiological processes, with consequences in disease development, progression and treatment (2–4). Every cell utilizes a wide range of metal ions (such as sodium, potassium, magnesium, calcium, iron, molybdenum, manganese, zinc, and copper) and nonmetals (such as chloride, bromide, iodide, and selenium) in conjunction with the elemental building blocks of biological molecules (such as carbon, oxygen, nitrogen, hydrogen, sulfur, and phosphorus). Thus, depending on their specialized functions and activities, each type of cell has a unique metal ion composition or “metallome.” These attributes can be exploited to distinguish cells with altered characteristics (such as highly proliferative or malignant, diseased, or transitioning toward cell death through regulated or unregulated pathways), or senescent in a range of disease settings (such as dementia, diabetes, and cancer).

Prior to the development of elemental bioimaging achieved through coupling instrumentation, such as laser ablation to inductively coupled plasma–mass spectrometry (ICP-MS), metal analysis of biological samples largely consisted of bulk quantification and speciation approaches. However, it became clear that this bulk tissue concentration level information lacked the spatial resolution necessary to fully explore the roles of biological metals at the cellular and subcellular levels. Advancing our understanding of the role of biometals in fundamental biology and disease, therefore, required increased information on the spatial localization of metals in tissues, and this need has been met, to a large extent, through a number of elemental bioimaging techniques including, but not limited to, synchrotron X-ray spectroscopy, secondary ion mass spectrometry (SIMS), and LA-ICP-MS (5).

Elemental images or maps refer to an LA-ICP-MS analysis that provides information on the elemental distribution across a sample’s two-dimensional area. An example would be the surface of a biological tissue section. As the laser is fired at the sample surface, the sample is moved at a defined and constant rate. This process allows the time profile of a line scan to be translated into a distance profile. Gathering multiple profiles across the sample generates a 2D image of the elemental distribution in the sample (3D after the vertical reconstruction of sequential 2D image maps), where signal intensity is directly proportional to concentration. To avoid artifacts, the duty cycle of the ICP-MS instrument and the translation speed of the laser must be synchronized. Figure 1 highlights this process of image generation.

To image a given sample, a suitable area or region must be chosen through complementary imaging techniques such as classical histology or unstained microscopy images. Samples are typically provided for analysis as thin sections on microscopy slides. Depending on the sample type and level of structural preservation required, samples are either formalin-fixed paraffin-embedded (FFPE), or cryopreserved with or without embedding material. If an embedding medium is used, a material of suitable purity for trace elements must be selected to avoid unnecessarily high backgrounds.

To balance the analysis time versus image size, the spot size of the laser must be optimized. This parameter affects the spatial resolution of the image and the sensitivity and the speed of the analysis. Larger spot sizes ablate more material, and therefore allow a greater quantity of sample to reach the plasma while the image generation is achieved in a shorter time. Spot sizes of 10–25 µm can provide reasonable spatial resolution depending on tissue type and the biological questions posed. Smaller spot sizes (below 5 µm) provide superior cellular resolution, but require high sensitivity to obtain a signal-to-noise ratio (S/N) of 10, often used as a minimum for quantitative work. Subcellular resolution (below 1 µm) can be obtained through an approach called 

The correct choice of the laser wavelength and carrier gas is also important. A combination of a laser system in the deep ultraviolet (UV) range (such as 193 nm), in combination with helium as a carrier gas, often provides the best results. Several key comparative studies highlight the performance characteristics between 193, 213, and 266 nm laser systems (7–9).

To obtain high-quality images with enough contrast to differentiate detailed structures, it is important that the ICP-MS system used for analysis provide high signal-to-noise ratios for the elements under study. This includes not only detection sensitivity, but also the complete suppression of interferences. Particularly important elements in metallomics studies, such as iron, manganese, copper, or zinc, may be significantly biased by polyatomic and other interferences, such as 40Ar16O+ (on 56Fe), 54Fe+ and 56Fe+ (on 55Mn), 40Ar23Na+ (on 63Cu) or 32S2+, 32S16O2+ on 64Zn. There is also growing interest in understanding nutrient metabolism, and imaging additional elements such as Se, P, and S, is again biased by significant polyatomic interferences. Complete removal of these interferences in combination with high detection sensitivity is often only achieved using triple quadrupole–based ICP-MS instruments. Typical conditions for analysis often are similar to those summarized in Table I.

An increasing body of evidence has linked air pollution exposure to impacts on the brain, ranging from cognitive impairments in childhood (10) to increased incidence of dementia in the aged population (11). Metal dyshomeostasis has been implicated in a range of neurodegenerative disorders (12), and there is preliminary evidence linking these disorders to the accumulation of metals in the brains of dogs (13) and humans in highly polluted areas (14). Uncertainties remain, however, about how exogenous metals accumulate in the brain, with some evidence supporting the uptake of metal-rich nanoparticles by the olfactory neurons in the nose to the olfactory bulb region of the brain, and some speculation about particles that have reached the systemic circulation crossing the blood–brain barrier (13–14). Allowing for either uptake pathway, there is even less knowledge about how particles and particle-associated metals move through the parenchyma of the brain, or whether they accumulate. Studying these questions is challenging due to the requirement to address long-term accumulative processes and in the limited access to relevant material in the clinical setting.

To overcome this, the option of using animal sentinel species to determine metal concentrations and distributions within their brains was explored, focusing on urban populations with clear exposure contrasts to traffic-related air pollutants. This study focused on the use of the Eastern gray squirrel (

), because these are routinely culled as part of population control efforts in London and throughout the United Kingdom. Therefore, they provide a unique resource to explore the impact of environmental pollution on long-term metal accumulation in the brain. In this article, preliminary data exploiting LA-ICP-MS to explore elemental patterns within the brains of squirrels collected from inner London (high pollution) and outer London (low pollution) are presented. Following culling, whole brains were removed by pathology technicians at the Zoological Society of London before being snap frozen. The frozen samples were then cyrosectioned at 20 mm thickness before air drying on glass microscopy slides prior to LA-ICP-MS at 40 mm resolution for 63Cu, 57Fe, and 208Pb, using 31P as a morphology indicator.

The representative images are presented in Figure 2. This data are preliminary, but clear contrasts are apparent in the spatial distribution of the selected elements between the low- and high-pollution sites (clearest in panel C). The data show that Cu (often associated with brake dust) is elevated in the olfactory bulb region of animals living in inner London whereas Pb appeared elevated in this brain region in the animals from outer London. Additionally, Cu concentrations appeared to be higher throughout the brains of the squirrels collected from inner London. Overall, Fe appeared higher in the outer London sample with evidence of high concentrations in the mid-brain region and clear high-intensity foci scattered throughout the parenchyma.

As stated, these images at this time are simply indicative of the power of this technique to provide semiquantitative spatial data on metal concentrations within the brain, and it is planned to expand this work to a more comprehensive set of samples to complement our work using traditional ICP-MS analysis of digested samples from discrete brain regions. Ultimately, the power of these techniques requires that elemental maps be related to classical pathohistological examination of the tissues so that metal intensity can be correlated to markers of overt neurological disease, or, through the application of other multi-model analytical techniques, correlated to mechanistic pathways linking air pollutant exposure to disease initiation and progression.

LA-ICP-MS allows isotopic mapping of a range of elements in biological samples to be performed with high sensitivity and high resolution. One major caveat of LA-ICP-MS is its destructive nature, particularly when applied to biological samples. In contrast to its application in geology, where nanometer-thick layers can be removed from surfaces of hard materials, when applied to elemental bioimaging, it typically completely ablates and removes cells and tissues from their support substrates during the analysis.

The resolution that can now be achieved using LA-ICP-MS, particularly with oversampling approaches, is beginning to open up new applications in subcellular imaging (15), which is still highly dependent on cell size and the concentration of elements of interest. In the field of elemental bioimaging, rapid developments in laser hardware, affording smaller spot sizes and therefore higher-resolution mapping, now require the sensitivity to measure such small amounts of material. Depending on the type of ICP-MS (single quadrupole, triple quadrupole, sector field, time-of-flight), sensitivity may be a limiting factor to image endogenous metals at high resolution (such as 1 µm), especially when found in lower concentrations. However, particularly in metallomics, the power of this analytical technique lies in its incorporation into correlative multimodel imaging and molecular mass spectrometry workflows so that information relating to the chemical environment associated with specific elements is characterized and can be placed within the context of specific biological processes and their underlying mechanisms.

We would like to acknowledge Dr. Alexander Morrell and Maral Amrahli for their expertise and assistance in image processing at the London Metallomics Facility.

D. Riesop, A.V. Hirner, P. Rusch, and A. Bankfalvi, 

S.J.M. Van Malderen, JT van Elteren, and F. Vanhaecke, 

T. Van Acker, S. Van Malderen, L. Colina-Vegas, R. Ramachandran, and F. Vanhaecke, 

T. Van Acker, T. Buckle, S.J.M. Van Malderen, et al., 

43–53 (2019). doi:10.1016/j.aca.2019.04.064

 are with Thermo Fisher Scientific, in Bremen, Germany. 

 is with the RC Centre for Environment and Health, at King's College London and Imperial College London, in the United Kingdom. 

 are with the Institute of Zoology Zoological Society of London, in the United Kingdom. 

 are with the London Metallomics Facility of King’s College London and Imperial College London, in the United Kingdom. 

 is with King’s College London, in the United Kingdom. 

 is with the Department of Nutritional Sciences of King’s College London, in the United Kingdom. Direct correspondence to: 

Metallomics seeks to understand the metallobiochemistry of cells and organisms in health and disease. This ar ticle explains the principle of laser ablation–inductively coupled plasma–mass spectrometr y (LA-ICP-MS) for imaging applications and highlights its potential to provide additional insights in bioanalysis and metallomics.

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