Advancing Trace Elemental and Speciation Analysis with a Focus on Metrology

For more than 20 years, Heidi Goenaga-Infante, a science fellow and the leader of the inorganic analysis team at LGC, has been working on elemental and speciation analysis. Two recent areas of investigation include the analysis of trace metals in biological samples, and the study of nanomaterials. In these studies, Goenaga-Infante puts particular emphasis on metrology-advancing this work by developing validated reference methodologies. Goenaga-Infante is the 2020 recipient of the Lester W. Strock Award from Society of Applied Spectroscopy (SAS) and the SAS New England Regional Section, in recognition of her contributions to the field of analytical atomic spectrometry, and she recently spoke to us about her work. This interview is part of an ongoing series of interviews with the winners of awards that are presented at the SciX conference.

What led you to study trace elemental and speciation analysis?

My PhD supervisor, Professor Alfredo Sanz-Medel at the University of Oviedo, inspired me with a fascinating lecture on the speciation work by his group in the 1990s. This was at a very early stages of my university journey, and my heart and head fell in love with the topic. Professor Sanz-Medel supervised my PhD on the “Speciation Analysis of Cadmium in Biological Samples,” and this was followed by postdoctoral research on trace elemental and speciation analysis at the University of Antwerp under the supervision of Professor C. Freddy Adams. I was then fortunate to be offered a permanent position at LGC Ltd. in Teddington, UK, and asked to lead a small group developing metrological applications of speciation analysis.

Your research covers a range of areas-from metallomics research to the characterization of nanoparticles. How do you choose your projects, and what are your biggest challenges in these areas?

The UK National Measurement Laboratory (NML) at LGC is one of the top three institutes worldwide for chemical and bioanalytical measurements. Our world-leading science and method development helps solve measurement challenges across areas such as healthcare and food safety, both in the United Kingdom and globally. As such, our project areas are underpinned by a range of stakeholder and customer needs, prioritized and reviewed by an expert group involving academia, industry, clinical experts, and government representatives. LGC’s presence in the atomic spectrometry community is invaluable in identifying emerging areas of high impact in which metrological principles can play an important role to improve the quality of measurements. Moreover, within the organization as a whole there are many opportunities to work with different disciplines that benefit the output of our work. One important thing to highlight is the importance of recruiting high-caliber scientists and having access to state-of-the art instrumentation. Without that, we would not be able to deliver high-quality science in such a broad portfolio of measurement areas. My biggest overall challenge has been coaching emerging scientists to deliver first-class measurement solutions to key problems as well as helping develop them to develop their careers within LGC.

You co-authored a study on quantitated iron spatial distribution in biological tissues using online double isotope dilution analysis with laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) (1). Can you explain the significance of this work and how it can advance disease model development and detection of neurodegenerative diseases?

I wish I could say that our work directly impacts the treatment and cure of these chronic diseases affecting many of our friends and families, but our contribution is rather modest, although important. The role of metals, including iron (Fe) in the diagnosis  or treatment of neurodegenerative diseases, has been studied by many groups. Having reliable methods to image key disease biomarkers and monitor targeted treatments or drugs is essential to the development of improved therapies. LA-ICP-MS is a powerful tool for determining the spatial distribution of elements, both endogenous and externally tagged to biological samples, such as preclinical or post-mortem brain tissue. However, the relationship between the intensity of the element and the concentration at which it is present is often biased by matrix effects. Therefore, absolute concentrations obtained by reliable calibration strategies in the absence of reference materials are urgently needed to help validate measurements by non-destructive techniques. With this in mind, our work has described a reference methodology based on the use of LA-ICP-MS with isotope dilution analysis for the accurate quantification of the spatial distribution of Fe in a model-tissue sample. A comprehensive estimation of the associated measurement uncertainty for the analyte spatial distribution was also achieved. Our high-level approach is invaluable to validate existing higher throughput methods used for medical research as carried out by our collaborators and stakeholders across the United Kingdom.

You developed a systematic approach to accurately quantitate plasma selenoprotein P (SEPP1)-a biomarker for human nutrition and disease-at clinical levels using species-specific double isotope dilution MS (2). What is the impact of this work?

The output of this work was a validated reference methodology for SEPP1. This is the major selenoprotein in plasma responsible for transport and distribution of selenium (Se), which is a key essential element to human health. SEPP1 has been associated with neurodegenerative diseases such as Alzheimer’s disease and type 2 diabetes. Considering that SEPP1 is a biological active form of Se and most of the plasma Se is associated with this protein, it represents one of the most accurate selenium-status biomarkers for human nutrition. For clinical purposes, SEPP1 has usually been characterized and quantified using antibody-based enzyme immunoassays such as ELISA. However, those assays often suffer from a lack in selectivity and results are usually associated with high standard deviation values. Hence, there are some inconsistencies and lack of data comparability in the results obtained for SEPP1 in humans. Since developed, our methodology has been actively used to estimate the bias of ELISA results for SEPP1 in clinical research led by collaborators from hospitals in the United Kingdom and from overseas. It is planned to use such a valuable measurement tool for the production of new speciated reference materials that the community can use to validate their measurements and also to provide reference values to clinical trials involving Se and its species as mediating agents.

In a recent study, you developed and validated a methodology for the accurate determination of number concentration of inorganic nanoparticles using single-particle ICP-MS (spICP-MS) without a nanoparticle reference material (3). Why did you undertake this project? What challenges did you face in this work?

Nanomaterials are increasingly being used in innovative products manufactured by advanced industries and provide enhanced, unique properties of great commercial and societal value. Measuring the number concentration of nanoparticles in colloidal suspension is a major interest for a large range of industries, including the pharmaceutical, personal care, cosmetics, and food packaging industries. Such methods are invaluable to underpin industry measurements. They also help industry to ensure the quality and efficacy of products and compliance with legislation. A number of methods capable of measuring particle number concentration in colloidal suspensions have been proposed, but neither SI-traceable approaches nor reference materials certified for nanoparticle number concentration were available when we did the work. Therefore, in our role as a National Measurement Laboratory, we undertook the challenge of developing and validating a methodology traceable to the SI, enabling the determination of analyte transport efficiency (TE) on the basis of weight measurements only, without the need for a reference material for calibration. Because the approach is based on direct and continuous measurements of the weight of sample uptake and the weight of sample reaching the plasma on-line over time (sample mass flow) while the ICP-MS system is in equilibrium, we named it the “dynamic mass flow” method. We faced great challenge. In particular, elucidating whether there was agreement between the mass-based TE of the sample–solution and the nanoparticle-based TE was the most critical. It is important to note that in this work, a conventional nebulizer with a cooled spray chamber (2 °C) was used. This helped to reduce the amount of water vapor (produced from evaporation of water from the aerosol in the spray chamber) entering the plasma, thus minimizing the contribution of this source of error to the uncertainty of the mass-based TE. Therefore, investigation of the feasibility of the dynamic mass flow (DMF) approach to obtain accurate nanoparticle number concentration data when using interfaces operated at ambient temperature or other types of nebulizers (such as high transport efficiency nebulizers) is still ongoing. Having said that, the DMF method shows promise for the validation of other laboratory techniques for particle number concentration. It has also been demonstrated to be useful for the characterization of quality control nano-objects (such as LGCQC5050) that can be used with the particle frequency or size methods in a more targeted manner for a range of applications.

What does the Lester W. Strock award mean to you?

Receiving such a prestigious award made me feel very honored, and to be honest, it took me by surprise. It increases my motivation to achieve my best and to keep seeking new opportunities. I wish to express my thanks those that have helped me and mentored me during my career, to my wonderful team at LGC, and last but not least, to those who nominated me, and to the Society for Applied Spectroscopy (SAS) for the award.

Where is the future of your work headed?

Our mission is to maintain our capability on core areas of metrology (high accuracy elemental, isotope ratio, and speciation and metallomic analysis) as well as continue bringing our metrology impact to emerging areas of research such as the characterization of nanomaterials. This work will focus on application areas driven by legislation and with a keen interest in nanomedicine. Also, more effort will be put into establishing a multidisciplinary platform for biomarker quantification and imaging of tissue down to single cells. This work will support medical research into the diagnosis and treatment of chronic diseases like cancer, neurogenerative diseases, and Wilson’s disease. A significant amount of our time and effort will continue to be dedicated to providing calibration services for reference material certification and for proficiency testing and clinical trials.

References

• D.N. Douglas, J. O'Reilly, C. O'Connor, B.L. Sharp, and H. Goenaga-Infante, “Quantitation of the Fe spatial distribution in biological tissue by online double isotope dilution analysis with LA-ICP-MS: a strategy for estimating measurement uncertainty.” J. Anal. At. Spectrom.31, 270–279 (2016). DOI: 10.1039/c5ja00351b

• C.L. Deitrich, S. Cuello-Nuñez, D. Kmiotek, F.A.Torma, M.-E. Del Castillo Busto, P. Fisicaro, and H. Goenaga-Infante. “Accurate quantification of Selenoprotein P (SEPP1) in plasma using isotopically enriched seleno-peptides and species-specific isotope dilution with HPLC coupled to ICP-MS/MS” Anal Chem. 88(12), 6357–6365 (2016).

• S. Cuello-Nuñez, I. Abad-Alvaro, D. Bartczak, M.E. del Castillo Busto, D.A. Ramsay,  F. Pellegrino, and H. Goenaga-Infante, “The accurate determination of number concentration of inorganic nanoparticles using spICP-MS with the dynamic mass flow approach.” J. Anal. At. Spectrom., Advance Article (2020). DOI: 10.1039/c9ja00415g

Heidi Goenaga-Infante has more than 20 years of experience in elemental and speciation analysis, starting with her PhD at Oviedo University, Spain. She joined LGC in 2003 as a senior researcher in speciation analysis, and is currently a science fellow. She is also the principal scientist and team leader of the Inorganic Analysis team, leading 14 PhD and postgraduate scientists. Her group currently focuses on trace element speciation analysis, metallomics research, the characterisation of nanomaterials, high-accuracy isotope ratio analysis, quantitative elemental bio-imaging, and the characterization of “speciated” reference materials and standards.

Goenaga-Infante is the UK representative at the Inorganic Analysis Working Group of the international Consultative Committee for Metrology in Chemistry (CCQM). She is also a member of the international advisory boards of Analytical and Bioanalytical Chemistry and the RSC journal Metallomics and of the Editorial Board of the Journal of Analytical Atomic Spectrometry, and a member of IUPAC. She is the Government Chemist representative on the Nanomaterials Environment and Health Government Group chaired by the UK Department of Environment, Food, and Rural Affairs (DEFRA) and the LGC representative to ISO TC 24 (Particle characterization). She is the EURAMET representative for inorganic analysis at the CCQM Key Comparison Working Group. She has acted as the coordinator of the EU EUROPEAN Metrology Research Proposal (EMRP) NanoChop “Chemical, Optical and Biological characterisation of Nanomaterials in Biological Samples.” She is the lead author of more than 106 scientific research papers and 5 book chapters.