MassMatters

Smokin’! Laser Focused on Ambient Ionization

Special Feature: Jim Scrivens... p16

Reflections: Manuela Pacciarini... p21

Welcome to the latest edition of Mass Matters!

This time we look back at the Ambient Ionisation SIG Meeting that took place in February, which was well attended and featured a really nice mix of presentations .. some not for the faint of heart!

We also welcome the new BMSS Chair Neil Oldham to his latest role with the society, and of course we extend our gratitude to Jackie Mosely who stepped down in October and becomes Chair of the Advisory Board.

Associate Editor, Mervyn Lewis continues his series of ‘Reflections’ articles, shining the spotlight on our industry to encourage others to consider MS as a career. In this issue, Mervyn speaks with Manuela Pacciarini from Swansea University.

We hope you enjoy the issue .. happy reading!

Best, Jon.

Jonathan Jones, BMSS Publicity Secretary

Chair’s Report

Welcome to the latest edition of Mass Matters. As ever, a big thanks goes to Jon Jones and Krisztina Radi for all their hard work in bringing it together. As this is my first and Chair of BMSS, let me start by introducing myself. My name is Neil Oldham, and I am Professor of Biomolecular Mass Spectrometry at the University of Nottingham. I have been at Nottingham since 2006 and prior to that I was at the University of Oxford (first at the Dyson Perrins, then the Chemistry Research Laboratory). I joined the BMSS committee in 2014 as a co-opted member, and then served subsequently as an elected general member, Papers Secretary, Vice Chair and now Chair. I am really looking forward to serving as the Society’s Chair for the next two years, and hope to see BMSS continue to go from strength to strength.

I would like to thank those members who stood down from the Committee last October: Jackie Mosely, my predecessor as Chair, who has been a very active member over the years, and who continues in the role of Immediate Past Chair, with the important task of providing a link between the Executive Committee and Advisory Board; Pete O’Connor, another stalwart of the Committee, who was Papers Secretary and, most recently, Treasurer of the Society; Zoltan Takats, who fulfilled the very valuable post of Special Interest Group Coordinator; and Chris Hopley, who as Digital Communications Officer was instrumental in the development and roll-out of BMSS’s new website and society management tool.

I’d also like to thank current members of the committee who are continuing to serve in their existing or new roles. Amongst the changes from October 2022 are: Andy Ray to Vice Chair, Mark Barrow to General Secretary, Mark McDowall to Treasurer, Hannah Britt to Education Officer, Chris Titman to SIG Coordinator and Andrea LopezClavijo to Digital Comms Officer. Rian Griffiths continues as Papers Secretary, Jon Jones as Publicity Officer, and Liam Heaney as general

member. Krisztina Radi and Angela Taylor agreed to serve another year as Co-opted Members, as they started a little late in the cycle last year.

Finally, on the topic of committee membership, I’d like to welcome the new members of the committee who joined us last October: Aneika Leney, Mike Morris and Rhodri Owen as elected members (Rhodri previously served as a co-optee); Patrick Sears as a Casual Member; and Oliver Hale as a new Co-opted Member. Last but by no means least, a big thanks to Lisa Sage, the Society’s indispensable Administrator, who makes so much happen behind the scenes.

I hope you will agree with me that last year’s BMSS Annual Meeting at the Royal Northern College of Music (RNCM) was a great success, with an excellent scientific programme, as well as plenty of social activities and networking opportunities. It’s really great to see that we can hold meetings with three parallel sessions full of high-quality science. You might be surprised to see that we are going back to the RNCM again this year. BMSS prides itself on being a national society, and the Committee tries, as much as is practically possible, to hold its annual meetings in a variety of locations. So, understandably, you might be wondering why we have opted for Manchester again. The answer is that, under the circumstances of high demand for conference venues, it was the only site we saw that could offer the facilities we require, at the right time of year and at a reasonable cost. It seems that as things start returning to normal, post-Covid, there is renewed demand for conference venues, which greatly reduced our options this year. I hope it will reassure members to hear that we are aware sensitive to the issue of returning to the same venue multiple times and that we are already scoping new locations for the 2024 meeting.

I’m sure many of you will have seen the sad news of the passing of Jim Scrivens. Jim was an active supporter

of BMSS for many years and was well known to many members of the UK and international mass spectrometry community. He will be greatly missed, as will Brian Cooper, a very popular and skilful electronics technician who supported mass spectrometry at Swansea University over a long period. Please see the In Memoriam section for reflections on both of these very valued members of the mass spectrometry family.

Finally, I’d just like to remind everyone that BMSS is your society, and that if you have any thoughts or suggestions on its activities, you are very welcome to pass them on to members of the Committee, and I promise that they will be discussed.

With very Best Wishes,

Prof. Neil Oldham BMSS Chair

Neil Oldham, BMSS Chair

2023 BMSS membership subscription

Renew your BMSS membership subscription for 2023!

You can renew quickly and easily on-line by visiting the BMSS Website: www.bmss.org.uk.

Encourage your colleagues to join the BMSS! As a member of the BMSS they will:

• Be part of a community of people with similar interests

• Have the opportunity to keep up to date with recent technological developments, learn more about MS and share knowledge and experience e.g. by joining Special Interest Groups (SIG’s)

• Be eligible to apply for grants towards small items of equipment, summer studentships and conference travel

• Be entitled to discounts for BMSS meetings

• Benefit from reduced subscription fees to the European Journal of Mass Spectrometry

• Receive copies of Mass Matters, the official benefit from 20% off relevant book titles when purchased via Wiley Publishing (discount code required) publication of the BMSS, published three times a year

Students: education programme by applying for travel grants, presenting research at meetings and by taking part in the Barber oral prize and Bordoli poster prize competitions. All student members also receive a general mass spectrometry text book upon joining.

New & Established spectrometrists: Can benefit from courses, careers events, links with

other societies (such as ChromSoc. & RSC) and networking via the BMSS Annual Conference and Special Interest Group Meetings. Any membership

admin@bmss.org.uk

Recent publications by BMSS members...

Native Ambient Mass Spectrometry of an Intact Membrane Protein Assembly and Soluble Protein Assemblies Directly from Lens

Tissue

O. J. Hale, H. J. Cooper, Angew. Chem. Int. Ed. 2022, 61, e202201458; Angew. Chem. 2022, 134, e202201458.DOI: 10.1002/ anie.202201458

Intact protein assemblies with molecular weight 90-113 kDa were analysed directly from eye lens tissue by nanospray-desorption electrospray ionization (nanoDESI). Detergent micelles in the solvent solubilised and preserved the assemblies of the tetrameric membrane protein Aquaporin-0 (113 kDa). Mass spectrometry imaging under non-denaturing conditions revealed the spatial distribution of these protein assemblies, and in situ top-down analysis identified their constituents.

The increasing role of structural proteomics in cyanobacteria

Jaspreet K. Sound; Jeddidiah Bellamy-Carter; Aneika C. Leney. The increasing role of structural proteomics in cyanobacteria. Essays Biochem (2022) EBC20220095. https://doi.org/10.1042/ EBC20220095

Proteomics has applications in many biological areas. In this review, we cover the exciting recent developments happening within the cyanobacterial field and how mass spectrometry is help driving forward are knowledge in particular on circadian systems and mechanisms behind photosynthesis. The assay applied in both healthy and diseased populations.

Rapid identification of mosquito species and age by mass spectrometric analysis

A team at the University of Liverpool, led by Rob Beynon and Hilary Ranson, a vector biologist at the Liverpool School of Tropical Medicine, have used REIMS (Rapid Evaporative Ionisation Mass Spectrometry) as a tool for profiling of mosquito populations . The methodology was proven using laboratory reared mosquitoes, but validated in the field by analysis of mosquitoes on Deeside in the Northwest. It was possible to use REIMS to identify the mosquito species and sex and to build an age profile of a mosquito population –importance because the older the female, the more oviviparous (egg laying) cycles, the more blood meals she will take, increasing the risk of mosquito borne infections.

Iris Wagner, Linda Grigoraki, Peter Enevoldson Michael Clarkson, Sam Jones, Jane L Hurst, Robert J Beynon and Hilary RansonBMC Biology 2023, 21(1):10. https://doi. org/10.1186/s12915-022-01508-8

Non-invasive screening of breast cancer from fingertip smears - a proof of concept study

Russo, C., Wyld, L., Da Costa Aubreu, M. et al. Non-invasive screening of breast cancer from fingertip smears—a proof of concept study. Sci Rep 13, 1868 (2023). https://doi. org/10.1038/s41598-023-29036-7

Breast cancer is a global health issue affecting 2.3 million women per year, causing death in over 600,000. Mammography (and biopsy) is the gold standard for screening and diagnosis. Whilst effective, this test exposes individuals to radiation,

has limitations to its sensitivity and specificity and may cause moderate to severe discomfort. Some women may also find this test culturally unacceptable. This proof-of-concept study, combining bottom-up proteomics with Matrix Assisted Laser Desorption Ionisation Mass Spectrometry (MALDI MS) detection, explores the potential for a non-invasive technique for the early detection of breast cancer from fingertip smears. A cohort of 15 women with either benign breast disease (n = 5), early breast cancer (n = 5) or metastatic breast cancer (n = 5) were recruited from a single UK breast unit. Fingertips smears were taken from each patient and from each of the ten digits, either at the time of diagnosis or, for metastatic patients, during active treatment. A number of statistical analyses and machine learning approaches were investigated and applied to the resulting mass spectral dataset. The highest performing predictive method, a 3-class Multilayer Perceptron neural network, yielded an accuracy score of 97.8% when categorising unseen MALDI MS spectra as either the benign, early or metastatic cancer classes. These findings support the need for further research into the use of sweat deposits (in the form of fingertip smears or fingerprints) for non-invasive screening of breast cancer.

Probing Interkingdom Signaling Molecules via Liquid Extraction Surface Analysis–Mass Spectrometry

Shaun N. Robertson, Fadi Soukarieh, Thomas M. White, Miguel Camara, Manuel Romero*, and Rian L. Griffiths. Anal. Chem, 2023. https://doi.org/10.1021/acs. analchem.2c05703

Previously, metabolites diffused or secreted from microbial samples have been analyzed via liquid chromatography–mass spectrometry (LC–MS) approaches following lengthy extraction protocols. Here, we present a model system for growing biofilms on discs before utilizing rapid and direct surface sampling MS, namely, liquid extraction surface analysis, to study the microbial exometabolome.

Mass spectrometry in the clinical laboratory. A short journey through the contribution to the scientific literature by CCLM.

Rankin-Turner S, Heaney LM. Clinical Chemistry and Laboratory Medicine 2022; Clin Chem Lab Med. 2022 Oct 26;61(5):873-879. https://www.degruyter.com/ document/doi/10.1515/cclm-20220984/html

This mini-review has been produced as part of a special issue for the 60th anniversary of Clinical Chemistry and Laboratory Medicine (CCLM). In this paper, we discuss the research published in CCLM relating to the use of mass spectrometry for clinical analyses, featuring some of the most interesting additions to the literature released by the journal. This brief overview highlights the excellent research done by collaboration between the clinical and analytical communities, including the publication of a two-part CCLM special issue in 2020 on the use of MS for clinical applications.

4th - 8th

18th - 22nd June

12th - 14th September 2023

17th - 20th July

17th - 23rd August

Are you looking for an alternative service and support supplier for your ThermoFisher, Sciex or Waters LC-MS instruments? As the only independent service provider with own hardware R&D, MS Vision has the knowledge to provide high quality service for your instruments

• Flexible, cost effective and transparent service solutions

• Instrument qualifications

• Relocations

• Trainings

• Instrument upgrades (High mass, ECD, Omnitrap

• Refurbished LC-MS instruments installed with warranty

AI SIG Meeting - Macclesfield

By Andrew Ray AstraZeneca, Macclesfield, UK & Vice Chair, British Mass Spectrometry Society

The 8th Ambient Ionisation Special interest Group meeting took place on the 1st February at AstraZeneca, Macclesfield; with over 90 delegates, 7 exhibitors, 10 oral presenters and 17 poser presenters it promised to be a great day of science. We kicked off with a different sort of Keynote speaker, Jim Higginson a head and neck cancer surgeon who has taken time out of frontline clinical practice to complete a PhD with Prof. Zoltan Takats at Imperial College studying the application of ambient mass spectrometry to head and neck cancer. His talk highlighted the potential advantages of ambient mass spectrometry to the clinician but also how important it is to ask the right questions of scientists, clinicians and patients. The potential use of REIMS in trans-Oral Robotic surgery was highlighted, potentially meaning that the patient doesn’t need to have a tooth removed, jaw broken and tongue cut!

Olivia Jackson from the University of Manchester stepped in at short notice and presented on her work on the use of chemical ionisation mass spectrometry (CIMS) to study the dispersal of pesticides using the FIGAERO-CIMS which allows the simultaneous analysis of gaseous samples but also particles in aerosols. This is important as how pesticides get into the atmosphere is not well understood and also how they may be transformed as there is the potential for degradation products to be toxic

Irene Sham from the University of Liverpool agreed to fill in for her colleague who was unable to attend. She described the development of a paper-chromatography-spray ionisation technique for the

analysis of paracetamol in saliva, this is important as overdose of paracetamol is the leading cause of acute liver failure in developed countries. Other ambient techniques have been attempted for this analysis but suffer from strong matrix effects suppressing the ionisation. By effectively doing paper chromatography before applying a voltage and spraying into the mass spectrometry, many of these matrix effects can be alleviated. The method was developed and validated, this was shown to be applicable across the clinical targeted range with LODs very similar to that achieved by UPLC/MS

SIFT/MS is a technique capable of quantitation of volatiles without standards, however the applicability of the technique has been limited due to the requirement to only use water as a diluent for the headspace analysis. Mark Perkins from element updated us on some recent work looking at extending the applicability through mixed aqueous/organic solvents. Although some reduction in response is observed the technique still works

well with the caveat for some analytes where there is overlap between the ion monitored for the analyte and those formed from the solvent.

Unfortunately, Rian Griffiths from the University of Nottingham wasn’t able to be present in person but she was able to present her work via Teams. Rian presented her research, a collaboration with the Veterinary School, analysing differences in lipid profiles between healthy sheep feet and ovine footrot diseased (OFD) sheep feet using liquid extraction surface analysis (LESA) mass spectrometry. Footrot is a polymicrobial infection that has a high economic burden and impacts on animal welfare. This study aims to determine whether a scientific approach could aid early determination of OFD and therefore facilitate early intervention with treatments. Lipids common to each sample were shown to have significant differences in abundance between samples. Structural characterisation of lipids of interest were described, with assignments made.

Katia Capuccini from Imperial College presented on the analysis of vaginal swabs by DESI for Preterm Birth Risk Stratification In Patients With Cervical Shortening. Preterm birth is still the primary cause of death for children under 5, however this is difficult to detect and to treat as there are multiple pathological processes involved. What is known is that Preterm birth risk is associated with vaginal microbiota composition – when there is high diversity microbiota (compared to a normal state of Lactobacillus species dominance) there is an increased risk of preterm birth. Analysis of vaginal swabs by DESI was used to distinguish between Lactobacillus dominant and depleted groups. Further work investigated if was a metabolic signature that could help predict cervical shortening and the consequent need for a preventative intervention.

There is a very large trade in counterfeit medicines, which can put patients life at risk as they may not receive the correct medicine or any at all. Stephen Holman from AstraZeneca discussed some initial work looking at detection of genuine and counterfeit tablets by ASAP/MS. This involves building a model, although initial work indicated that the tablets had to be milled first to produce more reproducible spectra than simply wiping the capillary across the tablet. The model was successfully applied and able to distinguish between genuine and counterfeit tablets. Further work is required to understand why the model needs to be rebuilt and to potentially identify what drug may have been added in a counterfeit medicine.

In a follow-on from Katia Capuccini’s work, Eftychios Manoli described his work on a point-of-care solution for the swab analysis by DESI/

Keynote speaker Jim Higginson of Imperial College

FEATURE: AI SIG MEETING

MS. This involved transitioning to a much smaller instrument with less resolution and development of a new DESI platform that enabled simultaneous rotation & linear motion with an adjustable swab grip for all swab types. As all functions are controlled by software it becomes a more flexible platform. The swab protocol was developed to incorporate DESI spray profile and instrument performance for quality control. Comparable m/z features were observed on the new instrument set-up vs the original instrument, although further development is required recruitment has started to have a large number of samples to compare against clinical microscopy.

Vanshni Vekereya from LGC presented on the development of meat speciation by deployable ASAP that had been shown at a previous meeting. An expanded model was used to demonstrate the separation between seven different meats, this model was very robust having been acquired over two years by four different analysts and produced a very high correctness score (99.37%). Some very interesting work was shown in the area of meat adulteration where 5% contamination could be identified as adulterated. Processed meat was also studied and interestingly when the original homogenisation

approach was used the meat could be identified (in this instance beef from a burger) but this could not be identified by dipping the capillary in the meat. It was also shown that the ability to discriminate between processed meats was not affected by the presence of additional ingredients.

Our final speaker was Jim Reynolds from Loughborough University talking on the application of sheath flow probe electrospray ionisation (sfPESI) for the analysis of drug metabolites in dried blood spots (DBS). The analysis of DBS can be simplified by ambient ionisation but previous work has suffered from ion suppression effects. This work described the analysis of cocaine metabolites using sfPESI, this uses a GELoader tip with an acupuncture needle through it and filled with an extraction solvent, the analytes are extracted by touching the surface and then a voltage applied to facilitate an electrospray. This can be used to analysis wet and dried samples, as only a very small amount of material is removed it is minimally destructive. This approach was updated to make a continuous flow interface, initially significant variation was observed between samples but addition of sodium acetate reduced this. Interestingly some surface activity based separation is observed between the cocaine metabolites and the sodium

formate clusters. Some quantitative performance was demonstrated but lower detection limits are required for zero tolerance level drug monitoring.

We then wrapped up the meeting by awarding the Peter Ryan award to Kei Wong from the University of Nottingham for his poster ‘Coupling an in vivo D.melanogaster tumour model with mass spectrometry imaging to study the efficacy of anticancer drug agents’ – thanks to Stephen Holman for the judging. The only remaining act was to handover the SIG to Patrick Sears, after launching the Ambient ionisation SIG at BMSS in Cardiff in 2011, there

has been so much fantastic science and it is amazing to see how we’ve grown from an initial meeting of 30people to the near 100 we had recently. However, I feel its now time to move on and hand over the reins to Patrick – I’m sure he’ll do a fantastic job of leading the SIG going forward. If anyone would like to join the organising committee for the AI SIG then I’m sure Patrick would be delighted to welcome you!

Kei Wong, recipient of the The Peter Ryan Award

REIMS – Current Perspectives

By Mike Morris & Steve Pringle Waters Corporation, Wilmslow, UK

One of the perpetual challenges for analysis by mass spectrometry (MS) is the sample preparation that needs to be undertaken on raw samples prior to ionization and MS analysis. Early MS sources required the samples to be in the vapour phase in order to be ionized by electron or chemical ionization. The ability to analyse solid samples with field desorption or fast atom bombardment opened up MS to many previously intractable sample types. The introduction of electrospray (and atmospheric pressure chemical ionization) in the late 1980s brought MS techniques to a much wider audience, with simple dissolution often being sufficient for analysis. However, the simplest form of sample preparation is no pre-treatment at all, and the advent of direct ionization techniques has opened up MS analysis to an even wider audience. They bring the ability to directly probe samples, generating sample-related aerosols (REIMS) or droplets with desorbed sample surface molecules (DESI) that can be introduced directly into the ion source of the instrument.

REIMS (Rapid Evaporative Ionisation Mass Spectrometry) is a technique invented in 2009 by Zoltan Takats primarily to provide real-time feedback during the surgical resection of tumors by electro-cautery. The electro-cautery generates an aerosol from the specimen due to rapid introduction of energy. The aerosol is directed onto a collision surface within the MS and the resulting lipidomic fingerprint is used to classify the target tissue using machine learning techniques (Balog 2013). Early target surgeries were breast (St John

2017), colorectal (Mason 2019), gynecology (Phelps 2018) and liver (Vaysse 2021). More recently Takats group has published data from endometrial (Marcus 2022) and gynecology (Tazafetas 2020) target cancers and included other energy sources such as harmonic scalpels (Manoli 2021) and mid-

in burns injuries. They found that REIMS spectra showed detectable molecular differences between non-viable and healthy control skin samples. Demonstrating the diagnostic potential of reliably distinguishing healthy from damaged tissue in situ.

IR lasers (Ogrinc 2019). Interest in this area has prompted other groups to extend the investigation of laser assisted REIREIMSMS to the diagnosis of skin conditions with an ongoing clinical trial (SpiderMass NCT04472546 clinicaltrials. gov), and Mohs surgery (Janssen 2020) for the removal of skin tumours. PIRL (picosecond infrared laser) REIMS has been shown to distinguish between different Medullobalstoma subgroups inducing little damage to the tissue (Woolman,2017). The noncontact nature of LA-REIMS has the advantage of targeting specific visual features of the sample, or just a testing the overall bulk material.

A recent article Yau et al (2022) investigated the possibility of using REIMS and LC/MS to guide the debridement of non-viable tissue

In another example of point-ofcare testing Davies et al (2021) investigated the potential that REIMS could be used to assist with surgical decision making during aortic surgery by differentiating between normal and aneurysmal tissue. Many current intraoperative decisions are subjective and based on the appearance of the vessel perceived surgical risks and likelihood of early recurrent disease. An intraoperative point-of-care test, to help guide surgical decisions, would positively affect surgical choices which ultimately may impact patient outcomes.

Insects

Mosquitos are a vector in the spread of many diseases. Malaria remains a leading cause of mortality and morbidity in Africa, killing over 600,000 people. Recently Morgan

et al (2022) showed identification of insecticide resistance among mosquito larvae suggesting the possibility to profile wild mosquito populations in the field, particularly where they are key vectors of disease.

Food

There are a number of potential applications of direct ionization approaches in food analysis including the investigation of olive oil (Mangraviti 2021) and cocoa/ chocolate (Chang 2022) among others. For example, recent papers have shown REIMS has potential to assist with the prevention of food fraud, differentiating the duration that tuna have been wet-aged (Shen et al 2022) and detecting the substitution of lower cost catfish for premium sole (Shen et al 2022a). In the adulteration of high value milks Cui et al (2022) profiled, and successfully differentiated, four common commercial varieties of milk.

REIMS has also been applied to the prediction the palatability of beef, measured by customer preference (Zhai et al 2022). Correct correlations of acceptance of beefy flavor (86.25%), juiciness (83.75%), overall (81.25%), overall flavor (81.25%), grilled flavor (78.75%), and tenderness (75%) were achieved using various machine learning techniques.

Boar taint is a contemporary off-odour present in meat of uncastrated male pigs. As European Member States intended to abandon surgical castration of pigs by 2018, the detection of the chemicals giving rise to this smell was of significant interest to the pork industry. REIMS was used for the rapid (<10s) and accurate detection of boar taint in neck fat where untargeted screening of samples enabled discrimination between sow, tainted and untainted

Figure 1 An OPO laser hitting a liquid sample in a well generating an aerosol

FEATURE

boars in an abattoir environment (Verplanken 2017).

Beer

The beer industry plays an important role in the economy since this is the third most consumed beverage worldwide. Cardoso et al (2022) analysed 32 different beers were by REIMS. They produced a predictive model (PLS-DA) discriminating the beers by both their brands and type (Premium and Standard American lagers). They showed that REIMS provided a rich fingerprint of beers, discriminated the different brands and types with 96.9% and 97.9% accuracy, respectively.

Summary

REIMS has the potential to be used for rapid analysis in a wide variety of applications where speed of measurement is a critical attribute, and the sensitivity and specificity of the direct ionization approach is fit-for-purpose in the defined application space.

References

Balog et al. 2013, Sci.Trans.Med. 5, 194ra93. https://doi.org/10.1126/ scitranslmed.3005623

Cardoso et al. 2022, Anal.Methods 14, 1540. https://DOI.org/10.1039/ d2ay00063f

Chang et al. 2022, Food Control 133, 108617. https://doi.org/10.1016/j. foodcont.2021.108617

Cui et al. 2022, J.Agric.Food Chem. 70, 7786. https://doi.org/10.1021/ acs.jafc.2c01447

Davies et al. 2021, Eur.J. CardioThoracic Surgery 60, 562. https:// doi.org/10.1093/ejcts/ezab166

Janssen et al. 2020, Int.J.Comp. Assisted Rad. and Surg. 15, 1665. https://doi.org/10.1007/s11548020-02200-4

Mangraviti et al. 2021, LWT 110715. https://doi.org/10.1016/j. lwt.2020.110715

2 REIMS iKnife system with

Manoli et al., 2021, Anal.Chem. 93, 5906. https://doi.org/10.1021/acs. analchem.1c00270

Marcus et al. 2022, Cancers 14, 5892. https://doi.org/10.3390/ cancers14235892

Mason et al. 2019, Surg.Endoscopy 34, 3618. https://doi.org/10.1007/ s00464-019-07140-y

Morgan et al. 2022, J.Insect Sci. 22, 1. https://doi.org/10.1093/jisesa/ ieac052

Ogrinc et al. 2019, Nature Protocols 14, 3162. https://doi.org/10.1038/ s41596-019-0217-8

Phelps et al. 2018, Brit.J.Cancer 118, 1349. https://dx.doi.org/10.1038/ s41416-018-0048-3

Shen et al. 2022, Food Res.Int. 156, 111307. https://doi.org/10.1016/j. foodres.2022.111307

Shen et al. 2022a, Food Control 142, 109248. https://doi.org/10.1016/j. foodcont.2022.109248

St.John et al. 2017, Breast Cancer Res. 19, 59. https://dx.doi.

org/10.1186/s13058-017-0845-2

Tazafetas et al. 2020, PNAS 117, 7338. https://dx.doi.org/10.1073/ pnas.1916960117

Figure

MassLynx and Benchtop Xevo Q ToF applied to the speciation of fish.

FEATURE: SUMMER STUDENTSHIP REPORT

The investigation of sulfluramid’s transformations, and their behaviour in soil and plants

By Sophie Singer Supervisor: Dr Joanne Roberts, Glasgow Caledonian University

Introduction

Per- and polyfluoroalkyl substances (PFAS), refer to a complex group of (>9000) (1) related organofluorine chemicals that were fabricated in the 1940s (2) and have been extensively used since. Their extreme durability and physicochemical properties have resulted in their ubiquitous use in industry and consumerismspanning from fire-fighting foams, and non-stick pans, to the perhaps lesser known- textiles, electronic devices, dental floss to all forms of cosmetics such as lip balms, and in some cases being an undisclosed ingredient (3–5). They bioaccumulate and biomagnify through protein binding (rather than lipid partitioning) including to those found in the blood and liver of animals (6). Hence our inescapable exposure, from food and drinking water consumption, and even inhalation of the dust and air indoors (7,8). PFAS exposure is unavoidable, they are transported over long-range distances, and are capable of migration through the 5 environmental spheres (9,10), consequently, they are found at significant levels in places far from anthropogenic sources such as in polar bears in the arctic regions, to penguin eggs in antarctica (11,12). They are referred to as ‘Forever chemicals’- as only the nonfluorinated functional moieties of the chain are unstable and prone to biodegradation and transformation

to other active PFAS, that remain highly persistent in the environment and the food chain, for an extremely long and still yet to be determined length of time (13).

Sulfluramid (Table 1), a commonly used name for a commercial insect bait, with the active ingredient N-ethyl perfluorooctane sulphonamide (EtFOSA) is classified by the WHO as a Class II pesticide - moderately hazardous (14). However, it is known to transform to various PFAS, a subject area poorly understood, and of great scientific focus recently. Amongst the sulfluramid transformation products, two of the most studied PFAS has been found. Namely: perfluorooctane sulphonic acid (PFOS) which is a priority hazardous substance under the Water Framework Directive (15); and perfluorooctanoic acid (PFOA). They are subject to restrictions according to The Stockholm Convention of Persistent Organic Pollutants (POPs) 2009. PFOS, its salts and perfluorooctanesulphonyl fluoride (PFOSF) – a precursor to many PFOS based compounds – are pursuant to Annex B of the convention (Restriction of production and use). PFOA and its related substances, are pursuant to Annex A (Elimination). They comply with the Stockholm Conventions toxicity criteria for bioaccumulation, mutagenicity, and endocrine disruption. Despite the well documented health and environmental hazards, and restrictions of PFAS, specific exemptions for the production and

uses are still in place (16). Brazil was granted a licence for ongoing use of sulfluramid as it is used extensively for the control of leaf cutting ants of the genera Atta.spp and Acromymex, where their mutualistic symbiotic relationship with fungus is necessary for their survival. Their management is necessary to protect the economy as one of the most important contributors to the global market for a variety of crops.

Using only the declared data it has been estimated that 76-616 tonnes of PFOS could have been emitted from the use of sulfluramid alone in Brazil between 20102018 (18,19). The estimations were derived from the yields of PFOS determined from a study by Zabaleta, et al. Where PFOS yields using technical sulfluramid were 34 % and commercial 277 %. Significant amounts of PFOS and related compounds are found with uncertain sources due to the transformation of precursors and undeclared uses. Studies have demonstrated that metabolite transformation products in various plants differs to that by soil and microbes and the transformation pathways are species specific (19,20). The study outlined in this report aimed to investigate the sulfluramid transformation and uptake behaviour in soil and two widely used leafy greens.

Materials and Methods

The reagents were purchased from Sigma Aldrich (≥ 98 % purity, Darmstadt, Germany)- technical

sulfluramid, perfluorooctane sulphonamide (FOSA) and perfluorooctane sulphonic acid (PFOS). Acetonitrile (ACN) & formic acid (≥ 98%, Optima LCMS grade, Fisher Scientific, Loughborough, UK). Sodium Chloride (≥ 99 % Sigma Aldrich). Deionised (DI) water (Purelab, Elga, UK) with a resistance of 18 MΩ

Experimental

Plant pots (10) were filled with store bought compost. 10 mL of solution of sulfluramid ((0.5 mg.mL-1) in methanol/DI water 50/50) was spiked into 3 lettuce plants & 2 basil plants, leaving 5 controls (3 lettuce and 2 basil). All experiments were performed in lab environments and watered from below. Samples were cropped after 35 days and 41 days for the basil and lettuce respectively. The plants were placed into 10 mL centrifuge tubes (Eppendorf, polypropylene). Soil samples (10) collected from each pot were stored in a 10 mL centrifuge tube and placed in the freezer. The plant material was homogenised in a food processor prior to extraction.

QuEChERS Extraction

A wet weight (~5 g) of each sample was transferred to a clean polypropylene centrifuge tube, topped with DI water (1 mL) and sodium chloride (1 g) shaken vigorously for ~30 seconds then vortexed for 5 minutes. ACN (~5 mL) (accurate sample to ACN 1:1 ratio) added then centrifuged @ 3000 rpm for 10 minutes. The supernatant was collected using a

pipette and transferred to a glass test tube and fully evaporated at 40oC in an electric heater. The samples were reconstituted with (1 mL) ACN / DI water (20/80 v/v) and passed through a 0.2 µm nylon syringe filter into polypropylene LCMS screw top vials.

Systems Parameters

The LCMS/MS system consisted of an Ultimate 3000 RS pump, Ultimate 3000 RS autosampler and Ultimate 3000 RS column oven all from Dionex) attached to a Q-exactive Orbitrap mass spectrometer detector (Thermo Scientific) with Electrospray ionisation (ESI) source. The column oven was set at 30˚C and the autosampler at 10˚C.

A reversed phase C18 column (Thermo Scientific, Accucore, 2.6 µm chromatography column (100 × 2.1 mm)) and C18 guard cartridge and a delay column was used to separate the analytes with a gradient elution method. A constant flow rate of 0.2 mL.min-1 was set. Acetonitrile (A) was used as the organic solvent, and the aqueous (B) 10 mmol ammonium formate in DI water (18 MΩ), adjusted to pH 3.5 with formic acid. Starting with 2 % of (B) over 1 min and maintained there for 10 mins, then increased to 35 % (B) and held for 5 mins, then decreased back to 2 % (B) and equilibrated there for 6 minutes. The full ms scan range was set at 80-900 m/z with a mass resolution of 17,500. Trace finder and Chromeleon software was used for the LC-MS data acquisition and peak processing.

Results and Discussion

High resolution mass spectrometry (HRMS) has the potential to provide elemental composition of organic molecules. This is measured by the mass accuracy which is a calculation used in HRMS to determine how close the experimental mass (accurate mass) is to the theoretical mas (exact mass). The calculation is shown in Equation.1. The mass accuracy acceptance criteria for an ion is (± 5 ppm) .

FEATURE: SUMMER STUDENTSHIP

A summary of sulfluramid and its suspected and detected transformation products is listed and can be seen in Table 1. A [M-H]-

either FOSAA or N-MeFOSE. Their respective mass accuracies are ~1.5 ppm, and -63.9 (see Table 1.). FOSAA can be assigned

rather than low resolution. Similarly, the ion at m/z 583.9 has several possibilities and the correct ion determined structures are proposed

precursor ion was found at m/z 555.9 which has potential to be

with certainty by calculating and comparing the mass errors, which can only be distinguished on a high-resolution mass spectrometer

and shown on Table 1 at Novel** (a & b). On examination of the product ion spectrum, there was no ion consistent with the loss of a methyl

group, therefore it is less likely to be the N-methyl version Novel (b). There was a product ion with m/z 497.9469 consistent with the loss of C(OH)CHCOOH group in Novel structure (a), therefore this is more likely.

Multiple transformation products were determined across all matrices. N-EtFOSE, N-MeFOSAA, and N-MeFOSA were not detected in any of the samples. FOSAA and PFOS were by far the most abundant products. FOSA and PFOS have only one mass unit difference which would be problematic if they co-eluted given their structure similarity. However, a chromatographic separation was afforded between the two, and this can be seen in 2 (c & d).

Table 2. Displays the mass (µg) and mole (nmol) balance data of the detected transformation products in the total plant and soil. The values shown in the table have been corrected for concentration factors, and an assumed 20 % moisture content in the soil samples accounted for. The results present an incomplete material balance. The sum of the compounds detected in both the soil and lettuce samples

equates to ~1 % of the mass of spiked sulfluramid, and for soil + basil ~ 0.3 %. These discrepancies could arise from several factors and more work is required. Measures to prevent volatilisation from surface of soil and testing the water in the tray underneath the plant pots is worth consideration for future work.

Figure 1 displays a graph of the mass distribution of the detected analytes (data in Table 2). All the columns show that a larger mass of compounds was detected in both the soil and plant material of the lettuce than the basil and soil. This could be for a number of reasons, including: water content; lipid and protein content; and growth time (lettuce was grown for 6 days longer). However, it can be seen that the novel transformation product was detected only in the leaves of the basil plants, this presents an interesting result that would need further investigation. There could be a species dependant transformation that is present in basil but not lettuce. Interestingly, a significant one-sided soil to plant ratio for FOSAA has been observed. FOSAA could be taken up by the plant more slowly or formed in the roots of the plants. It may be that FOSAA and PFOS (the most abundant lettuce

and basil transformation products) could be end stage transformations, suggesting that the FOSAA product may remain longer prior to PFOS transformation. More PFOA is detected for the lettuce soil system than basils, but more work is required. Future work to develop a concentration vs time curve for transformation products could provide deeper insight into the transformation behaviour.

It can be seen in Figure 2 (a-f) the retention times are fairly close. Now that some of the transformation products are known, the chromatography can be developed further to improve the chromatographic resolution. The product ions for sulfluramid and transformation products FOSA and PFOS are shown in Figure 2.

Conclusion

In this work, the transformations and behaviour of sulfluramid was investigated in soil, lettuce and basil. A high-resolution mass spectrometry instrumental method was used to detect and quantify the transformation products and precursor sulfluramid. The lettuce was harvested after 41 days, and basil after 35 days, those detected in all three matrices were: Sulfluramid;

PFOA; FOSA; PFOS; and FOSAAdetected in only the basil plant was a novel transformation product. Two proposed structures can be seen for this in Table 1 and the structure (b) has been determined as most likely based on product ion patterns. The presence in basil leaves alone suggest a species-specific interaction worth future investigation. The results present an incomplete mass balance, and repeated tests need to be carried out on the samples to gain better representation of the distribution of sulfluramid and transformation products in the matrices. Also, worth consideration would be to test the water underneath pots for analytes, and to apply measures to avoid any potential volatilisation. As well as spiking standards (where available) of the individual metabolites into pots to study their uptake/ transformation behaviour and comparing it with the sulfluramid transformations. More results would be needed for insight into the transformation mechanisms. For example, plotting a concentration vs time curve for metabolites could provide insight into the order and location of transformations, aiding in the investigation of whether sulfluramid is breaking down in the soil or the plant material, or both, and the proportions.

References

1.PFAS | NIOSH | CDC [Internet]. [cited 2022 Sep 30]. Available from: https://www.cdc.gov/niosh/topics/ pfas/default.html#print

2.Buck RC, Korzeniowski SH, Laganis E, Adamsky F. Identification and classification of commercially relevant per- and poly-fluoroalkyl substances (PFAS). Integr Environ Assess Manag [Internet]. 2021 Sep 1 [cited 2022 Sep 30];17(5):1045–55. Available from: https://onlinelibrary. wiley.com/doi/full/10.1002/ ieam.4450

3. Here are some important takeaways about testing and contamination - EHN [Internet]. [cited 2022 Sep 30]. Available from: https://www.ehn.org/pfassummary-2657611806/here-aresome-important-takeaways-about-

testing-and-contamination

4. Boronow KE, Brody JG, Schaider LA, Peaslee GF, Havas L, Cohn BA. Serum concentrations of PFASs and exposure-related behaviors in African American and nonHispanic white women. Journal of Exposure Science & Environmental Epidemiology 2019 29:2 [Internet]. 2019 Jan 8 [cited 2022 Oct 7];29(2):206–17. Available from: https://www.nature.com/articles/ s41370-018-0109-y

5. Buck RC, Franklin J, Berger U, Conder JM, Cousins IT, Voogt P de, et al. Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins. Integr Environ Assess Manag [Internet]. 2011 Oct 1 [cited 2022 Oct 7];7(4):513–41. Available from: https://onlinelibrary.wiley.com/doi/ full/10.1002/ieam.258

6. SAY NO TO SULFLURAMID -IPEN. org [Internet]. [cited 2022 Sep 30]. Available from: https://ipen. org/sites/default/files/documents/ en_ipen-sulfuramide-factsheetv1_10a-en.pdf

7. Winkens K, Giovanoulis G, Koponen J, Vestergren R, Berger U, Karvonen AM, et al. Perfluoroalkyl acids and their precursors in floor dust of children’s bedrooms –Implications for indoor exposure. Environ Int. 2018 Oct 1;119:493–502.

8. EPA Announces New Drinking Water Health Advisories for PFAS Chemicals, $1 Billion in Bipartisan Infrastructure Law Funding to Strengthen Health Protections | US EPA [Internet]. [cited 2022 Oct 7]. Available from: https://www.epa. gov/newsreleases/epa-announcesnew-drinking-water-healthadvisories-pfas-chemicals-1-billionbipartisan

9. Environmental Fate and Transport Processes – PFAS — Perand Polyfluoroalkyl Substances [Internet]. [cited 2022 Oct 6]. Available from: https://pfas-1. itrcweb.org/5-environmental-fateand-transport-processes/

10. PFAS, what is it, why is it in our environment and why is it a problem? [Internet]. [cited 2022

Oct 6]. Available from: https://www. pfasfree.org.uk/about-pfas

11. Xie Z, Zhang P, Wu Z, Zhang S, Wei L, Mi L, et al. Legacy and emerging organic contaminants in the polar regions. Science of The Total Environment. 2022 Aug 20;835:155376.

12. Fenton SE, Ducatman A, Boobis A, DeWitt JC, Lau C, Ng C, et al. Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research. Environ Toxicol Chem [Internet]. 2021 Mar 1 [cited 2022 Sep 30];40(3):606. Available from: / pmc/articles/PMC7906952/

13. National Academies of Sciences E and MD on E and LSEHMI, Mantus E, Shelton-Davenport M, Johnson A. Understanding, Controlling, and Preventing Exposure to PFAS. Understanding, Controlling, and Preventing Exposure to PFAS [Internet]. 2020 Aug 10 [cited 2022 Sep 30]; Available from: https:// www.ncbi.nlm.nih.gov/books/ NBK560951/

14. The WHO. Recommended

Classi¬fication of Pesticides by Hazard and Guidelines to Classi¬fication 2019. Available at: https://apps.who.int/iris/bitstream/ handle/10665/332193/9789240 005662- eng.pdf

15. Perfluorooctane sulfonate (PFOS) and related substances: sources, pathways and environmental data. 2019 [cited 2022 Oct 6]; Available from: www. gov.uk/environment-agency 16. Listing of POPs in the Stockholm Convention [Internet]. [cited 2022 Oct 6]. Available from: http://chm. pops.int/TheConvention/ThePOPs/ ListingofPOPs/tabid/2509/Default. aspx

17. Barbosa Machado Torres F, Guida Y, Weber R, Machado Torres JP. Brazilian overview of per- and polyfluoroalkyl substances listed as persistent organic pollutants in the stockholm convention. Chemosphere. 2022 Mar 1;291:132674.

18. Zabaleta I, Bizkarguenaga E, Nunoo DBO, Schultes L, Leonel J, Prieto A, et al. Biodegradation and

Uptake of the Pesticide Sulfluramid in a Soil-Carrot Mesocosm. Environ Sci Technol [Internet]. 2018 Mar 6 [cited 2022 Oct 6];52(5):2603–11. Available from: https://pubs.acs.org/ doi/abs/10.1021/acs.est.7b03876

19. Zhao S, Zhou T, Zhu L, Wang B, Li Z, Yang L, et al. Uptake, translocation and biotransformation of N-ethyl perfluorooctanesulfonamide (N-EtFOSA) by hydroponically grown plants. Environmental Pollution. 2018 Apr 1;235:404–10.

20. Zhang H, Wen B, Hu X, Wu Y, Pan Y, Huang H, et al. Uptake, translocation, and metabolism of 8:2 fluorotelomer alcohol in soybean (Glycine max L. Merrill). Environ Sci Technol [Internet]. 2016 Dec 20 [cited 2022 Oct 7];50(24):13309–17. Available from: https://pubs. acs.org/doi/abs/10.1021/acs. est.6b03734

Co-funded by the Chromatographic Society

In Memoriam: Memories of Jim Scrivens

The Mass Spectrometry community was deeply saddened by the passing of Prof. Jim Scrivens in January 2023. Several if Jim’s friends wished to pay tribute with the recollections of their dear colleague.

Remembrance words courtesy of Jon Williams

It was very sad news to hear our Mass Spectrometry family and Scientific Community lost Professor Jim Scrivens. I had only recently found out the full extent of his illness and battle. I always had scientific support off Jim and he helped me many times during my career. I will always be truly grateful and thankful for the opportunities and help he offered me.

In the 1990’s during my PhD research, I spent one year working with him and his Group in ICI Wilton, Teesside. It was a steep learning curve. The MS group at ICI included Mike Taylor, Tony Jackson, Richard Jennings and George a team of incredibly good mass spectrometrists, who certainly helped me get a better understanding of MS during that time. The ICI laboratory was full of interesting instrumentation ranging from a massive sector-type instruments, quadrupole, TOF, etc coupled with a range of interfaces such as GC and LC. Maldi, ESI, EI, FD, FI were just some of the ionization techniques being employed daily to solve problems in the lab. During my period at ICI, Jim acquired an LCT from Micromass and had access to an Autospec-oaToF. Jim had close links with Micromass and he would often remind me of how much he respected their excellent

instrumentation and scientists. So, thanks to Jim this is where my journey with TOF instrumentation began. Following my research, I worked as a Demonstration Chemist of the LCT for a number of years in Wythenshawe. The number of units our ToF team sold during that period was incredible.

In 2004 Jim offered me a position at Warwick University. The project was to look into the ‘shape’ of biomolecules using an Ion Mobility-

MS in collaboration with Micromass/ Waters Corp. I will be forever grateful that Jim asked me to join him on this project. I spent a significant amount of time driving up and down the M6 but it was a rewarding experience working with Kevin Giles and Bob Bateman. After a number of years working on applications on the prototype instrument, the first commercial Ion Mobility-Mass Spectrometer was launched. Jim was so excited. I remember him saying that the instrument will truly be a

‘game-changer’! He was not wrong! Jim was a good character and you could always hear his laughter in any building before you could precisely locate him. He was a good man and so passionate about ion mobility-mass spectrometry, mass spectrometry and all interfaces associated with it.

Whilst using the cyclic-Ion Mobility ToF Mass Spectrometer and Multiple Reflecting ToF technology in my latter years at Waters Corp. myself

Jim with the Cyclic IMS device on which he spent his latter years researching with Waters

and colleagues would frequently have visits from Jim and we would once again collaborate on interesting problems. Here is the last picture I had with Jim on one of his visits. It’s easy to see which instrument he was going to use and that smile tells the story really of somebody who was very passionate about mass spectrometry-based techniques and Micromass/Waters Corp. instrumentation. I will be forever grateful. RIP Jim.

Remembrance words courtesy of Mark McDowall

I first met Jim Scrivens at the IMSC conference in Swansea (1985). I was a freshly minted PhD presenting a poster, of no significance, and Jim walked past and diligently scrutinized my work. He kindly assisted me by pointing out some of my dyslexic faux pas. Jim ‘under full sail with all guns blazing’ was a magnificent and somewhat intimidating vessel to behold.

Over the following 35+ years I got to know Jim firstly as a discriminating & catalytic customer of the MS company that I had the privilege to work for at that time. In later years we became firm friends collaborating on educational projects in India.

Jim was acutely aware of the upward trajectory of his life and the privileges that flowed from that. Jim was committed to nurturing future generations of scientists, wafting them onto the escalator of a career in Mass Spectrometry, …and it was that strand of his personality that I knew best and admired.

In the 2010’s we collaborated to deliver several one-week practical training courses in proteomics at Bangalore. Jim and members of the ‘Scrivens Group’ (Warwick University) traveled to India to deliver the course pro bono. Those events were always packed to capacity, dynamic, and greatly appreciated. At the end of each day

we would fight our way through chaotic traffic to get back to our hotel. After a quick freshen-up the

and took me for lunch at the Bear Inn in Berkswell, a pub that would later become a cherished

earned a BSc, MSc, and PhD degree in Chemistry. He never forgot where he came from and was great

team would convene on the terrace with a bottle of something cold & crisp to decompress.

Jim and I had coherent views on building a better more inclusive society but divergent opinions on the political strategies for making our respective visions a reality. Naturally that divergence of thought lead to entertaining discussions that lasted long into those balmy Indian nights.

I shall miss my old friend, …and our conversations on the terrace!

Remembrance words courtesy of Kostas Thalassinos

I had the privilege of knowing Jim, who was not only my PhD and postdoctoral supervisor, but also my mentor and friend.

I first met Jim in 2002, where I visited him at Warwick to find out about a PhD project position in his lab. Jim picked me up from the station with two other professors

place for Jim's group for its many happy memories. During lunch we discussed my degree and research project, hobbies, and even my experience at a Joe Satriani concert the night before, over two pints of beer might I add. After lunch, I toured the lab and had further discussions with Jim about the PhD project. I was impressed with both the lab and Jim, and when I asked about applying, Jim responded by saying, "That was the interview, you were able to talk science even after two pints and all three of us bombarding you with questions. Take the weekend to think about it and let me know on Monday." It turned out that the other two joining us for lunch were Prof. Sir Howard Dalton who was then head of Defra and Keith Jennings Jim’s close friend and mentor and the person who developed collision induced dissociation, a major development in mass spectrometry.

Jim grew up in a coal-mining valley in South Wales and later attended Manchester University where he

at giving opportunities to others, regardless of their background, which I could relate to coming from a small farming village.

After his PhD Jim joined ICI’s research centre in Wilton initially using NMR to characterise molecules adsorbed on chemical catalysts. He soon, however, became interested in mass spectrometry, and successfully introduced it as an analytical technique in several production and pilot processes. Jim always wanted to know everything there is about what he found interesting so he took over heading the mass spectrometry division but on the condition that ICI would pay for him to visit world experts in the field in order to learn from them.

In 1990, he was granted his wish and a sabbatical from ICI to visit experts in the US, where he spent time with some of the leading figures in the field. These included Mike Gross in Nebraska, Simon Gaskell in Baylor, Charlie Wilkins in Riverside and Klaus Bieman in MIT.

Jim, Kostas and Keith Jennings at their favorite pub!

SPECIAL FEATURE: MEMORIES OF JIM SCRIVENS

For his encounter with Bieman Jim used to say, “He was the cleverest person I ever met, it felt like he took my brain out washed it all over then put it back in…”

Upon his return, he commissioned the first industrial four-sector tandem mass spectrometer, the ZAB-T, which was used to obtain field desorption MS and MS/MS to characterize complex formulations. Soon after the new ionisation method of MALDI was introduced, Jim pioneered its approach for the study of polymer microstructure and published numerous papers on the topic. The work on cation attachment led to a collaboration with Professor Mike Bowers and, together with Mike’s group at UCSB Jim utilized IMMS to study shape-selective features in polymer systems. It also started a longlife collaboration and friendship between the two.

Jim was appointed as a Visiting Professor in the Chemistry Department of the University of Warwick in 1994 and as a Professorial Fellow in Biological Sciences in 2001. After a period (2001-2005) where he had joint appointments at ICI and Warwick, Jim retired from ICI and took up a full time Chair in the Department of Biological Sciences in 2006.

During his period with ICI Jim had also served on many Research Council committees and also served as Chairman of Governors of Ings Farm School (1996-2005).

One of Jim’s great skills was the understanding of the close ecosystem that exists between industry, instrument manufacturers and academia and the need to bring everyone together to develop new solutions to solve challenging problems in science, something he was extremely good at and ahead of his time.

Over the years he developed a very close working relationship with mass spectrometry instrument manufacturers initially from VG in Manchester and then later, as they evolved, from Micromass and Waters. He was very proud of this and had many good friends there. It allowed him to be at the forefront of exciting new developments in our field and be the first to develop new and novel methods using these instruments.

His time at Warwick marked some major developments in our field. After his appointment in Warwick Jim, with funding from DEFRA, commissioned Waters to build a commercial mass spectrometer incorporating mobility separation, initially to study the misfolding of prion proteins. This became the successful SYNAPT range of instruments. For the first time people could have access to ion mobility analyses and nowadays all major manufacturers offer some form of ion mobility in their instruments. Having access to this new technology was for Jim and all of us there at the time like being kids in a candy shop. The group started exploring its use for a wide variety of applications; protein structure, proteomics, mass spectrometry imaging, ambient ionization, you name it.

He left Warwick in 2015 and after a small break he became Professor at Teesside University. There he established the Waters Centre of Innovation, He was also the academic lead on a Teesside and Centre for Process Innovation collaboration on the application of mass spectrometry approaches to support the design, manufacture, and characterisation of biotherapeutics.

As a supervisor, Jim was always generous with his time, advice, and resources. He would never say no to an experiment, he would argue with you about it but would never say no. He always paid for us to attend conferences, introducing us to other major players in the field. I learned a great deal just by sitting quietly in his office while the leading figures from universities and industry would come to visit him. He had a ton of energy, was always in high spirits, had a great sense of humour and the most distinctive laughter which could be heard from a great distance. He had two soft green leather sofas in his office and one of these industrial coffee machines with coffee always being available. The group would all pass by his office in the morning for a cup of coffee and a catch up. We developed some lifelong friendships with each other and are still in touch over the years. We would spend time discussing everything from the housing and benefits situation in the UK, to arts, science, Elaine and the boys and everything in between.

What I would not give to enter that office in Warwick one more time, pour two cups of coffee, sit in those comfortable green sofas, have a chat with Jim and hear him laugh. God knows there is a lot going on in world at the moment to talk about.

Goodbye Jim, thank you for you love, kindness and support.

Call for Nominations for

The British Mass Spectrometry Society may bestow two prestigious awards in any one year. We invite your nominations for candidates eligible for the Aston Medal and/or the BMSS Medal in 2023+.

THE ASTON MEDAL

The Aston Medal is the Society's most prestigious scientific award, given to individuals deserving special recognition by reason of their outstanding contributions to knowledge in the biological, chemical, engineering, mathematical, medical, or physical sciences relating directly to mass spectrometry.

THE BMSS MEDAL

This occasional award recognises sustained contributions by individual members of the BMSS to the development and delivery of MS, primarily within the UK, enabling education and increasing awareness of MS and its utility .

THE NOMINATION PROCESS

The nomination procedure is open to all BMSS Members and all submissions will be warmly welcomed. To nominate a candidate for either the Aston Medal or the BMSS Medal you should reach out to the BMSS General Secretary for a nomination form and guidance on submitting a cogent nomination

www.bmss.org.uk

In Memoriam: Brian Cooper

Remembrance words courtesy of Gareth Brenton

Friends and colleagues of Brian Cooper were saddened by his passing in Dec 2022. A loved Swansea University electronics technician, he passed away peacefully at the age of 80. Brian was kind and generous, and his extraordinary talents as a technician in the mass spectrometry team of Swansea university were greatly valued by staff and postgraduate students alike. He will be deeply missed by all who knew him.

Brian graduated in electronics and electrical engineering from University College London (1960’s). His first employment was for a transformer winding company in Hirwaun, south Wales. The long trips from home each day encouraged Brian to seek employment closer to his Swansea home and he signed up as a technician in the local university chemistry department (ca. 1977). Brian’s skills and endeavour were

research unit. Brian was based in mass spectrometry for the rest of his career. He helped my research and I, as well as others, came to rely on his outstanding ability. Colleagues and students alike admired him and his unwavering commitment to fix that problem.

Brian would tackle any electronics ‘problem’ for you but prized fixing analogue circuitry most (those were the days when electronics was fathomable, with circuits composed of single component technologies). He built the electronics of at least six home-built mass spectrometers in the Swansea research group between 1983 and 2007, i.e., a quadrupole-electric sector istrument; modified ZAB and MS9; a laser dissociation MS; two highresolution energy spectrometers; two orthogonal ToFs. These were the days before widespread service contracts; circuit diagrams of instruments were shipped with an order making a repair possible. Additionally, he repaired and maintained numerous commercial

quickly recognised and the mass spectrometry unit led by Professor John Beynon FRS took up moreand-more of his time. It didn’t take long before Beynon poached Brian to work exclusively for his

and other glorious challenges presented by hapless PhD students and staff. Luckily Brian didn’t do software which saved him from the tedium of dealing with all that office paraphernalia, giving us his undivided attention.

Brian was an avid sportsman who enjoyed playing tennis, squash, and football, some to an international standard. He maintained an active and healthy lifestyle throughout his life. His athletic prowess was the envy of many, inspiring others in the mass spec unit to stay fit and active. For a brief period, we even had a ‘running club’, where the oldest generally returned before the youngest recruits. In his latter years he held a season ticket with Swansea City Football Club.Despite being a bachelor, Brian had a warm and generous personality, and always willing to lend an ear to those in need. There are many former PhD students who know what he meant to them. He was a true friend to many and had a positive impact on

the lives of those around him.

Brian's passing has left a deep void in the hearts of all who knew him. His unwavering dedication to his work, his love for sports, and his kind and gentle nature will always be remembered. His memory will live on in the hearts of his colleagues and friends at the university, as well as all those whose lives he touched throughout his long and fulfilling life. Brian, you will be missed.

MS (too long to list, from MS9 to Orbitraps and ToFs) inter alia - gas chromatographs, liquid chromatographs, super-critical fluid systems, capillary electrophoresis, counter current chromatography,

Brian in his neat and tidy electronics workshop, c.2006.

Brian (squatting) at play with the mass spec group on Caswell bay, early 1990s.

Reflections: Mass Spectrometry as a Career Choice

Manuela Pacciarini Research Assistant, Swansea University, UK

Interviewed by Mervyn Lewis, Associate Editor

What was your impression of Mass Spectrometry when you were first introduced to it?

In 2013, during my master’s degree, I attended a module called “analytical methods for organic chemistry”, where I firstly heard of Mass Spectrometry. Despite the incredible range of analytical techniques developed and available, I fell in love with mass spec because of its huge versatility. Almost every molecule present in the world have the potential of being identified through a Mass Spectrometry analysis. At that time, I wasn’t aware that by simply exciting a molecule you could gain such a vast amount of information about its chemical nature. It was unbelievable to me! My love for chemistry and physics, alongside my curiosity, pushed me to deep dive into this technique. Moreover, after some time working with the Mass Spectrometry, I found out that, what seemed to be quite straightforward and simple, was often difficult and time consuming. This increased my interest in the subject and my willingness to undercover all its aspects.

What persuaded you that Mass Spectrometry could be a good career option for you? Were you attracted by an application of Mass Spectrometry or excited by the prospect of developing it as an instrumental technique?

Since my first years as a young scientist, I always appreciated the

vastness of Mass Spectrometry applications: from molecule identification and chemical structure elucidation to complete metabolomic studies, toxicology application, biomarker discovery (which is the focus of my current project) and many more. Indeed, the ma uses that Mass Spectrometry has, is what persuaded me that it could be a great career option. The potential of Mass Spectrometry is incomparable to other analytical techniques. Personally, I am more attracted by the clinical application of this technique, especially its use as a potent diagnostic tool. However, mass spectrometers were built to be useful R&D tools, so a re-design of the instrument, along with automation and software developments might be required for high throughput screenings.

How did you go about finding your first opportunity in Mass Spectrometry?

My first working experience with Mass Spectrometry has been during my PhD. I am currently pursuing my PhD degree in one of the most experienced Mass Spectrometry Lab in the UK, the Griffiths Wang lab in Swansea, Wales. The Griffiths Wang lab especially focuses on the analysis of a particular class of fats, the sterols, present in human cells through Liquid Chromatography-Mass Spectrometry analysis. Thanks to the experience with sterols that I gained during my master’s degree, I was a good candidate for the PhD position that Professors Wang and Griffiths opened in October 2019, that was focusing on Mass Spectrometry method development for the identification of sterol biomarker in human neurodegenerative diseases.

I am currently in the process of finishing my PhD and writing-up my thesis. And yes, if you were wondering, I have loved the Mass Spec. experience!

In what application fields do you see new opportunities in Mass Spectrometry?

Personally, I can’t think of a field where Mass Spectrometry can’t find a place or a reason to be. However, if I should choose, I believe that human health is the most promising field of application for such analytical technique. The precision, the reproducibility, the sensitivity of Mass Spectrometry makes it a perfect tool for both

diagnosis and disease progression monitoring, as well as for human health screenings and health checks. A good, well written and designed protocol for Mass Spectrometry can be easily followed and give reproducible results. Moreover, Mass Spectrometry run times are typically between 5 minutes and one hour. This means that in one day multiple analyses can be performed, making it suitable for clinical/diagnostic purposes. I won’t be surprised to see in the nearest future clinical laboratories well equipped with a mass spectrometer!

What is your opinion about the impact that automation and informatics will have on Mass Spectrometry?

I think that to implement the Mass Spectrometry technology we need automation and informatic support. Indeed, with these tools, possible errors that can interfere with the reproducibility, such as observational errors and cross contaminations can be avoided. For instance, the substitution of the human operator with an automated machine able to perform the same action an innumerable number of times could eliminate those risks. Moreover, a good automated system must have a solid software implementation and an upgraded informatic technology. Data interpretation and quantification also require new software. However, currently this is probably the most difficult implementation to achieve. The mathematical algorithms are very specific, and sometimes they struggle to adapt to universal purposes. For example, some software for lipid data interpretation is very good for the identification of the phospholipid family but not so much for steroids. Automation and informatic support are

definitely needed to implement Mass Spectrometry technology, but we still need good scientists to do the hard jobs (luckily!), especially compound identification and method development.

Could you describe your views on career prospects in Mass Spectrometry for young people?

When I was in University, I didn’t know the numerous job positions that a Mass Spectrometry scientist could apply for. I thought it was merely an analytical type of job: prepare samples, inject the samples, read the results, individuate the target. I couldn’t be more wrong! If you type on google “Mass Spectrometry jobs” you will be surprised about the vast number of jobs, you might find! From product specialist, helping other people to develop their projects based on the use of a specific instrument, to analytical scientist, developing methods for the separation and identification of new molecules. But you can also help the engineers developing a new instrument, or

becoming a sales expert, selling instruments around the world. And finally, you can also work in university, researching your own projects and teaching the students the beauty of Mass Spectrometry. In conclusion, my message is: if you really like Mass Spec go for it! Don’t be scared by the complicated theoretical principles under this technology, as soon as you start working on it everything will be clearer and clearer, it’s a promise. The variety of working experiences and job opportunities is immense and you will find the place or the role that best fits you!

Acknowledgements

Manuela would like to thank Prof. Yuqin Wang and Prof. William J. Griffiths (University of Swansea) for their mentoring and support throughout her Research Assistant job and PhD, as well as all the funding bodies and collaborators.