IBA-DAPNe: a new system for sub-micron scale molecular speciation and quantification

Lead Research Organisation: University of Surrey
Department Name: Chemistry

Abstract

Our vision is to develop a unique resource for molecular imaging and profiling that will be truly internationally leading. Molecular imaging is widely used for the characterisation of materials, and there are numerous methods available for generating and liberating ions from a surface and hence generating a chemical concentration map including those using mass spectrometry (MS). Since 2004, there has been an explosion of new MS methods in which a sample is analysed under ambient conditions. This has enabled the high throughput analysis of samples that are not vacuum compatible and has significantly speeded up the sample handling, which is often the time-limiting factor of vacuum-based techniques. Quantification, chemical speciation and spatial resolution are three key drivers for a multitude of applications, and there is currently not a single technique that can provide all these attributes at the sub-micron scale.

Direct Analyte Probed Nano Extraction Mass Spectrometry (DAPNe-MS) is a method of selecting and removing a small quantity of material from a surface, using a capillary tip attached to a nanomanipulator. The extracted material is then introduced into a mass spectrometer via nanoelectrospray ionisation. The technique has achieved sensitivity at the attogram level and is particularly suited to picking up trace materials from surfaces. Unlike imaging mass spectrometry techniques, the process of sample removal and ionisation are decoupled and there is minimal fragmentation. This provides better selectivity and opportunities for superior quantification compared with other ambient MS methods.

Due to its recent inception, no DAPNe facility exists in the UK. Surrey houses in its Ion Beam Centre (IBC) the only ambient pressure imaging MeV-Secondary Ion Mass Spectrometry (SIMS) system in the world which offers sub-micron molecular imaging (EP/I036516/1). SIMS, an Ion Beam Analysis (IBA) technique, is known for its excellent spatial resolution but a drawback is the fragmentation that occurs during the sputtering process. Currently available techniques at Surrey and NPL have imaging capability with high spatial resolution, can distinguish between molecular species and even provide molecular concentration maps. Techniques which provide trace element information at the ppb level in ambient conditions (Particle Induced X-ray Emission - PIXE, also an IBA technique) are also readily available. The missing component is trace molecular information, which DAPNe will provide. We will use current techniques to highlight specific regions which require a more detailed analysis with very high sensitivity using this new unique probe. Complementary use of IBA and DAPNe (IBA-DAPNe) is unique internationally and would provide unprecedented level of characterisation of samples at the sub-micron scale in full ambient conditions.

The proposed IBA-DAPNe system will provide missing information for researchers from any discipline and research projects will be prioritised on the basis of scientific excellence. Access will be provided free of charge for the first two years. We see particular benefits for those working across 6 key EPSRC themes: Energy, Manufacturing for the Future, Healthcare Technologies, Global Uncertainties, ICT and Engineering.

Planned Impact

This proposal supports research in applications ranging from energy and electronics through to the aerospace and automotive industries. It also underpins developments in national security and healthcare technologies. The fields of energy and biotechnology are estimated to contribute nearly £30 billion per annum to the UK, while the national security industry is worth £30 billion. The manufacturing industry is worth 10% of UK output. Establishing a new DAPNe system at Surrey will enable academia and industry to work together on new technologies in the above-mentioned areas.

In 2013 David Willets together with the department for Business Innovation and Skills laid down the 'Eight Great Technologies', which will propel the UK to future growth. Through the applications conceived in the case for support, IBA-DAPNe will contribute to the knowledge base of 5 of these areas: Satellites (PV materials), Advanced Materials (carbon fibre composites, adhesion), Synthetic biology (interaction of endogenous compounds with NC3Rs), Energy (fuel cells, batteries, smart fibres) and Regenerative Medicine (proteins in fibres).

It is envisaged that society will be beneficially impacted by research carried out on materials for energy, which are central to electric vehicles. Electric vehicles offer promise in terms of sustainability and lowering of the carbon footprint. The associated positive environmental impact will be of both economic and societal benefit. The societal impact associated with smart phone technology and proposed health benefits of wearable technologies for health, have all been enabled by research into materials for electronics. Advanced electronic materials provide faster and smaller computing and
communications systems are transforming how society lives and works.

Materials for energy are central to the technologies responsible for electric vehicles, which will be at the heart of a future economy associated with sustainability and lowering the carbon footprint The associated positive environmental impact will be of both economic and societal benefit. Energy materials will also impact society by reducing energy bills at the domestic level through smart electricity storage in the home. Storage capacity of the national grid is far short of current demands. Research into materials for energy can address this, benefitting society and industry alike.

Materials for electronics have societal impact in terms of advantages associated with smart phone technology and proposed benefits of wearable technologies for heath. Advanced electronic materials provide faster, smaller and more portable systems in computing and communications, which are transforming how society lives and works.

As part of the 5 year National Security Strategy and Strategic Defence and Security Review, the Prime Minister announced an £178 billion investment over the next decade, including provision for knowledge transfer with universities. This highlights both the importance of security to society, and end-user/academic partnerships. Investment in security assures continued trade and foreign investment in the UK, which contributes to the economic wealth of society at large.

The skills and facilities will be made open for use by other academics and industrial researchers, helping to ensure that the UK stays at the forefront of Analytical Science, which maintains the health of all the other disciplines above. The associated facilities will be seen and recognised as a valuable resource. Public interaction is key to realising the full impact of the research proposed here; it will increase awareness of the challenges and progress in the applications of Ion Beam Analysis and Raman Spectroscopy as well as the wider materials field.
 
Description We have been working with users from the University of Surrey and UK academia, industry and internationally using our EPSRC funded strategic equipment. At Surrey, ongoing research with bioscientists is giving new information about drug distribution in and between cells (experiments with Dany Beste); it has allowed our Natural Products Group in Chemistry (Dulcie Mulholland and Moses Langat) to discover novel compounds in African plants that could be used medicinally (see publication); it has allowed the group of Prof McFadden et al to discover more about cell feeding patterns through isopoptomer analysis. In immunology, the tool has been used to extract lipid profiles from macrophages for the first time. Using the strategic equipment we have also been able to demonstrate for the first time the significance of detecting cocaine and heroin in a fingerprint by comparing the fingerprints of drug users to the background population. This work has been accepted for publication by the journal Clinical Chemistry and will be published on 22 March. Through working with Josef Stefan Institute and iThemba labs (South Africa), we have demonstrated the viability of using the technique to detect drugs in medulla of hair samples. We have also worked with BP to show that the technique can be used to detect oil residues on rocks. We have worked with AstraZeneca to show that the technique can detect drugs in tissue. Through working with the University of Birmingham we have found that it is possible to detect proteins using DAPNe. This has opened up some new possibilities for future research and has led to successful award of an EPSRC fellowship. We are also working with NPL to develop the reliability of measurements using DAPNe and have published a paper in Analytical Chemistry. In particular, we have been investigating the factors influencing precision and reproducibility of analysis, and have established the optimum parameters for internal standard incorporation, sample extraction and data processing. We hope this will be of use to our growing base of users in the following years of our grant.
Exploitation Route We have been publicising the technology and some preliminary applications. This has helped to increase awareness of the technique and we now have a good user base. The technique appears to have particular relevance in the analysis of biological samples. We are hoping to gain research funding from EPSRC to develop the DAPNe method further - in particular to provide spatially resolved proteomics on a microscale. We have gained interest from bio scientists at key institutes across the UK - Oxford, Southampton, Warwick, Imperial - to name a few - and we aim to deliver high quality research for these users in the next year of the grant. The equipment is also being advertised through the National Ion Beam Centre and now the EU project Radiate, from which we can deliver transnational access
Sectors Energy,Environment,Healthcare,Government, Democracy and Justice,Culture, Heritage, Museums and Collections,Pharmaceuticals and Medical Biotechnology

 
Description We have been using the strategic equipment in collaboration with a number of new collaborators (see relevant section on Partnerships) to develop new medical testing methods, based on a single fingerprint. Using the strategic equipment, we have developed methodology to determine from a fingerprint deposited by a patient WHAT drugs they have taken, WHO the patient is (from the fingerprint ridge details) and WHEN the fingerprint was deposited. This gives a new possibility for testing patients for compliance with their treatment regimes from their own homes. We have started working with hospitals and have successfully detected antibiotics in fingerprints. This will be useful in tackling antimicrobial resistance internationally, where drug compliance for (e.g. Tuberculosis) is poor. We are now applying for continuation funding to develop the method further, both from MRC and from Intelligent Fingerprinting Limited
First Year Of Impact 2016
Sector Healthcare
Impact Types Societal

 
Description Lecture at Kings College London
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Toxicologists at Kings College hospital now aware of a new potential tool for hair analysis or fingerprint analysis
 
Description Lecture at Wexham Park Hospital
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact We presented on a potential new way to monitor antibiotic use from a fingerprint to clinicians and patients at Wexham Park Hospital
 
Description Participation in the Particle Induced X Ray Emission International Commitee
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Improved awareness internationally of the ability to use mass spectrometry in conjunction with ion beams
URL http://pixe2017.irb.hr/Committees
 
Description SBRI IRC Showcase
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact The project has provided proof of concept data for rapid screening for explosive compounds at high sensitivity using mass spectrometry.
 
Description Biometric Identity
Amount £28,794 (GBP)
Funding ID 86202375 
Organisation Defence Science & Technology Laboratory (DSTL) 
Sector Public
Country United Kingdom
Start 09/2017 
End 03/2018
 
Description Debbie Charlton PhD Award Bio Metric Identity
Amount £39,000 (GBP)
Organisation Defence Science & Technology Laboratory (DSTL) 
Sector Public
Country United Kingdom
Start 10/2018 
End 09/2024
 
Description EPSRC Impact Accleration Account
Amount £13,232 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 03/2018
 
Description EPSRC Impact Accleration Account - Surrey
Amount £19,475 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 09/2017
 
Description EPSRC Summer Studentships
Amount £2,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 08/2017
 
Description Innovate UK IRC Call on Weapons Detection
Amount £60,000 (GBP)
Funding ID IRC 2016 - 850235372792016 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 04/2017 
End 09/2017
 
Description Ion Beam Analysis for the 2020's and beyond: an integration of elemental mapping and omics
Amount £1,025,483 (GBP)
Funding ID EP/R031118/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2018 
End 04/2023
 
Description NPL Surrey Studentships
Amount £60,000 (GBP)
Organisation Intelligent Fingerprinting Limited 
Start 10/2017 
End 09/2020
 
Description Research Infrastructures
Amount £10,000,000 (GBP)
Funding ID 824096 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 01/2018 
End 12/2021
 
Description iCURe
Amount £30,000 (GBP)
Funding ID 11-03 / 517236144 
Organisation SETsquared Partnership 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 01/2018
 
Description AstraZeneca 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We have been developing a mass spectrometry method using DAPNe for the spatially resolved detection of drugs in tissue
Collaborator Contribution AZ have provided tissue mimetic samples, dosed with olanzapine, ternafenadine and other drugs as a model sample to explore the capabilities of DAPNe for tissue imaging
Impact Abstracts submitted to ASMS; presented at PIXE 2016 in Croatia; IBA 2017 in Shanghai.
Start Year 2016
 
Description Dstl 
Organisation Defence Science & Technology Laboratory (DSTL)
Country United Kingdom 
Sector Public 
PI Contribution We have been developing new mass spectrometry methods for the rapid screening of explosive residues
Collaborator Contribution Dstl have allowed Patrick Sears (Principal Scientist) to work in our laboratory with us to advise on best practise for explosive detection (common adduct signals, solvent systems etc)
Impact Innovate UK funding from the IRC ; 2 manuscripts in preparation
Start Year 2016
 
Description Francesco Romolo 
Organisation Sapienza University of Rome
Department Faculty of Medicine and Psychology
Country Italy 
Sector Academic/University 
PI Contribution We have been developing methodology to detect cocaine and its metabolites in the hair of prisoners
Collaborator Contribution La Sapienza have provided hair samples collected from the pubic region of prisoners
Impact Project is in progress
Start Year 2017
 
Description HMPPS 
Organisation HM Prison Service
Country United Kingdom 
Sector Public 
PI Contribution In our facility we are testing fingerprint samples for novel psychoactive substances
Collaborator Contribution partners at HMPPS are carrying out urine drug tests to go alongside fingerprint testing as well as commissioning a third party to carry out data analysis
Impact training of prison officers in fingerprint collection and mass spectrometry
Start Year 2018
 
Description Home Office Centre for Applied Science and Technology 
Organisation Home Office
Department Centre for Applied Science and Technology
Country United Kingdom 
Sector Public 
PI Contribution We have been training Dr Steve Bleay, Acting Head of Department to use high resolution mass spectrometry. Dr Bleay is interested in the adoption of mass spectrometry imaging for future forensic casework
Collaborator Contribution Dr Bleay in return has provided lectures on our forensic course (>15 hours) and co-supervision of project students. He has also provided access to the CAST laboratory for fingerprint development prior to mass spectrometry
Impact Greater awareness at CAST of mass spectrometry imaging methods.
Start Year 2016
 
Description Intrepid Forensics 
Organisation University of Leicester
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution We trained Annelies Voohaar to use mass spectrometry for use in her project to understand the effect of molecularly imprinted polymers for the enhancement of fingerprints
Collaborator Contribution Annelies was working in our laboratory for 3 months
Impact physics, chemistry and forensic science. results reported to fingerprint specialists in the UK and in the Netherlands
Start Year 2017
 
Description Josef Stefan Institute 
Organisation Institute Josef Stefan
Country Slovenia 
Sector Academic/University 
PI Contribution We have been developing a new method for drug detection in hair using DAPNe, together with Primoz Pelicon from JSI
Collaborator Contribution Primoz has provided hair samples and imaging of these samples using MEV SIMS
Impact Reported at CAARI 2017 and IBA 2017 (Shanghai)
Start Year 2016
 
Description Kings College 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We hosted a summer student from Kings College London to work on paper spray mass spectrometry
Collaborator Contribution Collection of clinical samples
Impact We are writing a publication and we have detected mephedrone in fingerprints for the first time
Start Year 2018
 
Description Multiforesee EU COST Action 
Organisation Sheffield Hallam University
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a project aimed at linking researchers in the area of imaging in forensics. Our team's contribution has been to participate in a Round Robin study and show the potential for Mass Spec imaging in forensics
Collaborator Contribution Imaging of fingerprint samples using mass spectrometry
Impact links the forensic community with analytical scientists working on new tools
Start Year 2016
 
Description National Physical Laboratory 
Organisation NPL Ltd
PI Contribution We are exploring different methods for normalising drug signals in tissue.
Collaborator Contribution NPL have helped with provision of samples, spraying of internal standards, and mass spectrometry imaging. they have also provided us with a desorption electrospray ionisation source to borrow
Impact Paper in analytical chemistry and others being drafted. training of phd students and ongoing collaboration with AstraZeneca
Start Year 2017
 
Description National Physical Laboratory 
Organisation National Physical Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution We are exploring the dual use of elemental imaging (use ion beams) and molecular imaging (using mass spectrometry). Surrey is providing funding for studentships, access to IBA and access to mass spectrometry
Collaborator Contribution NPL has provided access to mass spectrometry (complementary imaging methods), sample preparation, data processing facilities, student supervision and has funded student travel.
Impact ESPRC fellowship application made and rated highly by referees; >10 conference presentations; 3 papers in preparation; training of 4 PhD students; follow-on funding from Innovate UK and Dstl
Start Year 2016
 
Description Netherlands Forensic Institute 
Organisation Netherlands Forensic Institute
PI Contribution Development of antibody labelling approaches using ion beam analysis and mass spectrometry
Collaborator Contribution Development of antibody labelling approaches
Impact work is ongoing
Start Year 2016
 
Description Public Health England 
Organisation Public Health England
Department Public Health England Porton Down
Country United Kingdom 
Sector Public 
PI Contribution We are using ion beam techniques and mass spectrometry imaging to locate Au labelled drugs relative to other markers in tissue samples
Collaborator Contribution partners are providing sectioned tissues
Impact Studying au labelled drugs in marmoset tissues.
Start Year 2019
 
Description RBI 
Organisation Ruder Boskovic Institute
Country Croatia 
Sector Public 
PI Contribution We are seeking to explore the relation between drugs and their metabolites in fingerprints for drug testing and toxicology purposes and have been using DAPNe for this
Collaborator Contribution RBI have given beam time to understand more about how chemical imaging of drugs and metabolites
Impact student trained in Croatia in imaging analysis
Start Year 2018
 
Description Surrey and Border NHS Trust 
Organisation Surrey and Borders Partnership NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution We are searching for antipsychotic drugs in fingeprrints using LC-MS
Collaborator Contribution Partners are helping with recruitment of patients and collection of samples
Impact we have detected antipsychotic drugs and their metabolites in fingerprints for the first time
Start Year 2018
 
Description Surrey and Borders NHS Trust 
Organisation Surrey and Borders Partnership NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution we are developing novel methods for the detection of drugs of abuse from a fingerprint, using mass spectrometry
Collaborator Contribution collection of patient samples
Impact Funding from iCURe (see funding section) funding from intelligent fingerprinting (see funding section)
Start Year 2016
 
Description University of Birmingham 
Organisation University of Birmingham
Department School of Biosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Use of FAIMS -MS for explosive detection and use of DAPNe for spatially resolved proteomics
Collaborator Contribution training on FAIMS MS at Bristol ; provision of samples and expertise of RA at Surrey
Impact postdoc has applied for follow on funding to explore this work further. this is a multidisciplinary project, requiring the collaboration of physicists, engineers, chemists and bioscientists
Start Year 2017
 
Description University of Bristol 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution Analysis of nano composite samples using direct analyte probed nano extraction
Collaborator Contribution Provision of nano composite samples
Impact training of staff
Start Year 2016
 
Description University of Liverpool 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Development of paper spray metrology
Collaborator Contribution Liverpool have provided laser cut and wax channel substrates for paper spray mass spectrometry
Impact Data under review
Start Year 2017
 
Description Wexham Park Hospital 
Organisation Wexham Park Hospital
PI Contribution We have been developing a new method using mass spectrometry to screen for antibiotic drug use
Collaborator Contribution Wexham park have provided clinical staff time (clinicians and research nurses) to assist with the collection of patient fingerprint samples
Impact 2 UK patent applications submitted; 2 grant applications currently under review by MRC; new collaboration with TB clinicians working in Vietnam; 1 manuscript in preparation;
Start Year 2016
 
Description ithemba labs SA 
Organisation iThemba LABs
Department Nuclear Physics
Country South Africa 
Sector Public 
PI Contribution Analysis of hair samples for pharmaceutical compounds using DAPNe
Collaborator Contribution Collection and preparation of hair samples including longitudinal sectioning
Impact Data under review
Start Year 2016
 
Title Fingerprint Test for Antibiotics 
Description We have developed a test for antibiotic use that uses a fingerprints. We have tested the fingerprints of patients from Wexham Park Hospital, undergoing treatment for Tuberculosis and have found that we can detect the drugs that they are taking using mass spectrometry. We are now applying for follow-on funding from MRC 
Type Management of Diseases and Conditions
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2017
Development Status Actively seeking support
Clinical Trial? Yes
Impact Submission of a patent application (Dec 2017) 
 
Description Appearance in Japanese Documentary on Forensic Science 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact We appeared in a documentary about fingerprint development techniques. I was interviewed and we gave a demonstration of DAPNe to show what information (drugs etc) would be obtained from a fingerprint
Year(s) Of Engagement Activity 2017
 
Description Hampshire Science Group and Three Counties Science Group talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk to general public at Hampshire Science Group and another talk at 3 Counties Science Group. Increased knowledge of these groups on ion beam analysis and mass spectrometry. have been asked to give further talks
Year(s) Of Engagement Activity 2018
 
Description Interviews for national and international news 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Various media articles including https://www.telegraph.co.uk/news/2017/09/22/fingerprint-test-can-detect-cocaine-30-seconds/ ; http://www.independent.co.uk/news/science/fingerprint-test-cocaine-use-detect-washed-hands-illegal-drugs-sweat-surrey-university-a7961821.html; https://www.cnbc.com/2017/09/22/new-drug-test-can-detect-cocaine-in-a-fingerprint-in-seconds.html; https://www.sciencedaily.com/releases/2017/09/170922193142.htm
Year(s) Of Engagement Activity 2017
 
Description Media reports in 2018 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Widespread news coverage (>200 articles) of our finding that cocaine resides on fingerprints of non-drug users, but that we can set a threshold to distinguish drug use from environmental exposure
Year(s) Of Engagement Activity 2018
URL https://www.independent.co.uk/news/science/drugs-cocaine-heroin-fingerprints-traces-people-class-a-s...
 
Description Portsmouth physical society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 20 pupils attended the talk and this sparked questions and a discussion afterwards. I was also asked to give a lecture in November to the University of Third Age from one of the audience members.
Year(s) Of Engagement Activity 2018
 
Description Training event at international Atomic Energy Agency 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This will take place in June in Italy and we will train forensic experts to use ion beam analysis techniques
Year(s) Of Engagement Activity 2019
 
Description school visit boxgrove school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact workshop for children at Boxgrove primary school (100 children in year 2). School reported that students were inspired by the work we are doing
Year(s) Of Engagement Activity 2018