High Resolution High Throughput Mass Spectrometry to Characterise Materials, Chemicals, and BioCatalysts

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

This proposal will equip UoM new equipment that will enable high throughput high resolution ion mobility mass spectrometry analysis. This bid will increase capacity for analysis and extend our capacity to measure a wide range of analytes. Specialist equipment will be used to measure the mass and the shape of a large number of newly synthesised chemicals. In the simplest terms possible, mass spectrometry measures the movement of ions in a vacuum to give mass and ion mobility mass spectrometry measures the movement of ions in a gas to give shape. If we measure mass very accurately we can work out what atoms a molecule is made of and if we measure the shape very accurately we can work out how the atoms are arranged. So for a large range of different molecules we will be able to tell what we have made and how much we have made.

The PI has been making ion mobility mass spectrometers and using ion mobility mass spectrometry for over 20 years. She has pioneered its use in many areas of chemistry and in this proposal we plan to do it even faster and with more accuracy.

This equipment will be located with the Manchester Institute for Biotechnology in the Michael Barber Centre for Collaborative Mass Spectrometry. It will be used by research teams at the University of Manchester as well as by external users from both academia and instrument. We will use this state of the art instrumentation to underpin investments by EPRSC in the Future Biomanufacturing Research hub and the Prosperity Partnership with AstraZeneca as well as other programs in materials and catalysis. This new capability will consist of two mass spectrometers coupled to novel ionisation sources. A State-of-the-art Cyclic IMS QTof MS instrument will provide unique enhanced analytical capabilities for molecular identification and structural characterisation of complex mixtures complete with full ion mobility data. A second "work-horse" DESI interfaced Synapt XS instrument will provide broader research access and wider application, and act as an initial screening platform prior to Cyclic Structural work for rapid mass spectrometry analysis. The ionisation sources will enable analysis with minimal sample preparation both directly from surfaces via Desorption Electrospray ionisation and with microfluidic droplet dispensing to provide a unique ultra-high-throughput (uHTP) screening capability. This will provide mass and structural data for a range of chemical analytes from small molecules to polymers, supramolecular compounds to biopharmaceuticals.

Planned Impact

The high resolution high throughput mass spectrometry (HRHTP-MS) instruments and the development of unique screening capabilities will innovate HTP IM-MS research applications that will accelerate the ability to screen and accurately measure metabolites, targeted small molecule and proteins, their interactions and modifications, and hence transform our understanding of biological processes. It will accelerate the identification and understanding of bottlenecks in biocatalyst and strain engineering workflows with the benefit of rapid, accurate and direct identification of chemicals targets, and will transform screening capabilities in research areas across chemistry, advanced materials, bio manufacturing and bio catalysis, and healthcare diagnostics. The IM-MS platforms will build on existing analytical and interdisciplinary expertise to provide unparalleled access to state-of-the-art equipment infrastructure and support alongside recent EPSRC investments.
Whilst aligned closely to the UoM research strategy and Industrial Biotechnology Research Beacon, the proposed facility is also strategically aligned with the EPSRC MS roadmap (2016, https://epsrc.ukri.org/files/research/massspectrometryroadmap/) and with the future EPSRC strategy for Mass Spectrometry in the UK which demands connected national Centres with advanced analytical capabilities. It also recognizes that in order to deliver high-impact studies and set the research agenda the UK mass spectrometry community needs to be amongst the early adopters of new technologies that significantly enhance performance to provide quick contributions to the field, setting new standards pushing the research fields rapidly forwards. The HRHTP-MS platforms will provide the UK with unique innovation in HTP IM-MS, facilitating high resolution mass and structural analysis without which analytical screening will remain a major bottleneck in many key EPSRC research themes.

The HRHTP-MS platforms will provide an open and shared facility in the interdisciplinary MIB (Faculty of Science and Engineering at UoM) and will benefit from being part of the MBCCMS, which is a national flagship research hub of MS with a well-established network of academic and industrial collaborations. The facility also will benefit from UoM strategic industrial partnerships including Waters Corp and AZ, and major new EPSRC funded initiatives including the Future Biomanufacturing Research Hub, Catalysis Hub and Prosperity Partnership with academic and industrial partners. The specialist instruments will be housed close to biological research laboratories (bacterial/mammalian cell growth and automation) and supported and managed by expert technical and data analysis/management support. This will allow the delivery of novel capabilities to a broad range of cross-disciplinary expert and non-expert users. The expert technical support will ensure that the full breadth of research applications are provided and novel methods developed in collaboration with both academic and industrial users. Forming part of a wider core facility infrastructure within the MIB (including NMR, EPR, In silico computational modelling and synthetic biology and directed evolution pipelines) and connected across UoM, the instruments will be managed as fully open access resources with full training and technical support provided. The instrumentation will support a very strong research portfolio of national and international research grants led by MIB PIs that will ensure early delivery of research impact.

Central to the growth of this facility and to National importance will be the involvement of external users. The Future BRH has 20 core industrial partners (Allergan, Almac, Arcinova, Biocatalysts, Biopropane consortium, BP, Britest, Calysta, CoEBio3 consortium (8 companies), Croda, GSK, Ingenza, Johnson Matthey, Prozomix, Quorn, Shell, Singer, Sphere Fluidics, Unilever, Victrex) as well as 9 associate partners who will have access to this.

Publications

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