Molecular imaging technology leads to breakthroughs in drug testing and fingerprinting
Studies into specialist imaging technologies at the University have led to improved biomedical analysis techniques, such as the study of drugs for the pharmaceutical industry. This research is led by Professor Malcolm Clench and the University’s Bioanalysis Research Group. Dr Simona Francese has also had significant success in applying the technique to analysis of latent fingermarks for forensic applications, benefiting Home Office scientists and crime scene investigation units.
The research
Clench’s research initially investigated how to adapt Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging (MALDI-MSI) to study the distribution of pharmaceuticals in biological tissues. In 2004, Clench’s group published the first European paper on MALDI-MSI of pharmaceuticals in Europe, and only the second in the world. Co-authored with a Pfizer scientist, this publication detailed a method for studying the distribution of an anti-fungal compound in skin. Further work with Syngenta identified agrochemicals in plants and led to the application of MALDI-MSI in the horticultural sector. Distribution of a bioreductive drug in solid tumours was reported in 2007 in association with researchers at the Institute of Cancer Therapeutics, University of Bradford.
Following these successes, Clench received research council funding to develop instrumentation for MALDI-MSI and to expand the range of applications. One key development was the adaptation of a commercial mass spectrometer to incorporate a laser to produce higher quality images. Clench improved the specificity of MALDI-MSI analysis for small molecules and proteins in collaboration with Syngenta and GlaxoSmithKline (GSK). Clench also has an ongoing collaboration with Waters Corporation in co-development of instrumentation and software for Matrix Assisted Laser Desorption Ionisation Ion Mobility Separation Mass Spectrometry Imaging (MALDI-IMS-MSI).
Image of Drug Distribution (Red) in a 3D Living Skin Equivalent Model acquired by Mass Spectrometry Imaging. This image shows clearly that the drug treatment is located in its intended site: the epidermal layer of the skin.
In 2008, Clench received funding from Cancer Research UK, together with Professors Tozer and Paley at the University of Sheffield to investigate protein signatures in tumours following vascular-targeted therapies. This led to five high impact papers. Funding was also obtained from the European Cosmetic Agency to use MALDI-MSI to analyse ex vivo human skin for the identification of irritants and sensitisers.
Francese collaborated with Clench on a number of aspects of MALDI-MSI before going on to adapt the technique of MALDI-MSI for examination of latent fingermarks, which combined identification of an individual with information on the chemical content of fingermarks. This research led to two patented technologies. Eleven peer reviewed papers on the developments of this technique for fingermark analysis have been published and funding has been obtained from the Home Office to determine the feasibility of incorporating MALDI-MSI into routine fingermark analysis.
The impact that the MALDI-MSI research can have in fingerprint and forensic science include increased detections, adding contextual evidence to cases and providing higher specificity in substance identification than existing processes.
2014 manual of fingerprint development techniques, edited by the Home Office
The impact
Four technologies have been patented regarding mass spectrometry techniques and applications, in the UK, EU, USA and China, two of which are licensed to commercial partners. By developing new techniques for pharmaceutical companies, Clench’s Bioanalysis group has changed practice within the industry. Specifically, a sustained professional relationship with GSK since 2006, with a succession of CASE studentships, has speeded up the drug discovery pipeline. More recent work by Francese with the Home Office to embed MALDI mass spectrometry analysis of fingerprints into routine forensics is gaining impact. Francese is working with West Yorkshire Police to provide information on fingerprint and non-fingerprint forensic evidence, which is feeding into their crime scene investigations.
Clench’s work with the pharmaceutical industry has led to gains for University partners including Pfizer Global R&D, GSK, Syngenta, Quotient Bioresearch Ltd and instrument manufacturers Waters Corporation. For example, Clench has collaborated with Waters Corporation since 2006 and the company has invested about £350K per year in MALDI imaging since then. The company sells £5-10m of MALDI systems each year of which 30% are for MALDI imaging. The University’s help in the development of this business for the company has been described as vital.
Since Francese’s initial paper on fingermark analysis in 2009, she has further developed the methodology to aid in the identification of sexual assault victims and to analyse fingermarks recovered from crime scenes by standard forensic techniques. She has been funded by the Home Office to convert this research into a validated method. Francese co-developed a powder discharge device (patent pending), which has been licensed to Consolite Forensics for further development. The initial work was funded through the EPSRC.
The work of both researchers has attracted attention from the media in recent years. Francese’s fingerprint analysis findings have been featured on The One Show, BBC1 (viewing figures 4,170,000) and Science in Action, BBC Radio World Service. It has also been covered in national, local and specialist press, including The Daily Mail, Yorkshire Post, Science Daily, Police Oracle and The Engineer. Clench's investigations of agrochemical distribution in plants using MALDI-MSI resulted in his participation in a BBC 4’s 'Afterlife - The Strange Science of Decay', assessing uptake of decayed plant material in new plant growth by MALDI-MSI (overall viewing figures of over 800,000).
Clench and Francese provide expert advice and consultancy to industry for MALDI-MSI, with clients including: Unilever, Procter and Gamble, Croda Chemicals, and Alk-Albello (Denmark). The scale of impact of MALDI-MSI work at the University was evidenced by three Mass Spectrometry open days held annually (2010-13), attracting over 250 delegates, including over 100 from industry. The third of these open days was organised in conjunction with the British Mass Spectrometry Society.
Finally, two important appointments also recognise Clench’s expertise in MALDI-MS at a national and international level: he was appointed the British Mass Spectrometry Society (BMSS) Lecturer, currently leading the Imaging Group; and as the UK member of the Management Committee of EU COST Action BM1104 'Mass Spectrometry Imaging: New Tools for Healthcare Research' (2011-2015).