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Ultra high performance MALDI mass spectrometer for basic research use and clinical applications

Final Report Summary - EUROMALDI (Ultra high performance MALDI mass spectrometer for basic research use and clinical applications)

Mass Spectrometry (MS) is an instrumental method for identifying the chemical constitution of a substance by means of the separation of gaseous ions according to their differing mass and charge. MS is an analytical science covering the multiple fields of chemistry, physics and biology. Each world has its specific needs and ways of producing and analysing samples. Its application to clinical applications is complex since it involves a close interaction between doctors, hospital practitioners and analytical scientists. The challenge of obtaining a suitable instrument for biomarker discovery is a never ending story since instrument capabilities need to be improved continuously.

Matrix Assisted LASER Desorption-Ionization (MALDI) based MS shows several advantages for application in clinical routine, in terms of the specificity of the analysis, sensitivity and detection of molecules identified as significant biomarkers. MALDI Imaging is a label-free technique for visualization of the spatial distribution of molecules used for identification and localization of biomolecules, both small and large. It shows a wide variety of advantages when applied to biomarker characterization.

The present Euro MALDI project was focused at developing a new powerful proteomic solution for clinical applications. This has been a close and fruitful collaboration between Kratos Analytical Ltd., subsidiary of the Shimadzu Corporation, and the Aix-Marseille University, and is a part of a long term relationship between the two organisations that will result in wide social, societal and economic benefits.

Kratos has designed, developed and commercialize a mass spectrometer to enter the field of clinical research where high throughput methods are required. The main objective of the present project has been to optimize this prototype for use in a real clinical environment, making possible high resolution and high throughput analysis of lipids, proteins and carbohydrates compatible with clinical applications. The prototype has been validated through this project. Targeted applications for the outcome of the project were focused on glioblastoma and pancreatic cancer, which are two of the deadliest carcinomas. Forensic analysis was also performed on the new proteomic solution showing that the system is highly versatile.

The Aix-Marseille University is present in this project through the Academic Partner Proteomic Platform (PIT2), within the Centre de la recherche en oncologie et en oncopharmacologie (CRO2) which joins six research teams from the Schools of Pharmacy and Medicine, the Hôpital de Marseille and the Institut national de la santé et de la recherche médicale. This research unit are specialized in cancer research and hoist various facilities such as proteomics animal nursing imaging that render fundamental and translational research efficient.

Kratos Analytical Ltd is a wholly owned subsidiary of Shimadzu Corporation and has been manufacturing scientific instruments for many decades. Kratos Analytical was a pioneer and is a current world leader in the fields of x-ray photoelectron spectroscopy (XPS) and MALDI-MS. The history of MALDI at Shimadzu shows a large track of successes, as being the first company to launch a commercial MALDI-TOF system in 1987, the Nobel Prize awarded to Koichi Tanaka, a member of the Shimadzu staff, in 2002, or more recently the launch of the AXIMA Resonance instrument as the next generation of MALDI-QIT-TOF systems. Nowadays, Kratos has launched the MALDI-7090, its new ultra-high performance MALDI mass spectrometer for basic research and clinical applications, which has set a new dimension in MALDI-TOF-TOF design.

By the end of the project, both parties are very satisfied with the progress achieved and the targets fulfilled. The planned tasks have been already successfully finished, with minor adjustments from the initial idea. Secondments have been fully satisfied from both parties. Besides, the software suites initially planned are developed, including the development of brand new software for MS-Imaging that has been already used by both Kratos and CRO2 group for several publications and research projects. The software is highly compatible with clinical use. This software is going to be officially released in June 2016 at the 64th Annual Conference of the American Society for Mass Spectrometry.

The outcome of this project has already proved very satisfactory for the link between Shimadzu and Aix-Marseille University, and we believe that it will help as a founding stone upon which more results and achievements will be built in the future through other joint actions. Kratos/Shimadzu have obtained very positive commercial benefits, with the customer validation of its new instrument, the addition of crucial software solutions and the incorporation of key people to its staff. Aix-Marseille have obtained substantial investment benefits, access to a high-specifications instrument and its associated software solutions for its current and future research.

Besides, the project has had a strong impact on the employment and mobility of EU citizens. Post-doctorate students from Aix-Marseille that have participated in the project, as well as the recruited researcher, have been employed by Kratos. The scientific achievement and knowledge gathered by the PIT2 group at Aix-Marseille University will lead to the development of further research projects which will involve the recruitment of both pre-graduate students and post-docs. In addition to this, as a result of the experience gained in this project a new start-up company focused on development of software for clinical mass spectrometry has been founded in Spain (Clover Bioanalytical Software), and it is already creating further employment for highly skilled EU citizens (Ph.D. graduates).

Please refer to our website for more information at where the latest news and the main information about the project are shown.