A versatile proton transfer reaction-mass spectrometry platform for online monitoring of VOCs.

Proton-transfer-reaction mass spectrometry (PTR-MS) is a specialized branch of mass spectrometry that is used for online monitoring of volatile organic compounds (VOCs). Commercially available PTR-MS instruments have a response time of about 100 ms and reach a detection limit in the single digit pptv region. It uses gas phase hydronium ions as ion source reagents. This makes PTR-MS spectrometers ideally suited for rapid and sensitive analysis of VOCs in a wide range of bioscience research programmes enabled by the online, simultaneous real-time detection, monitoring and quantification of VOCs.

PTR-MS uses the 'soft' ionisation technique of proton transfer from protonated water (H3O+), which is produced as an ion beam by an ion source. During this interaction a proton transfers from the hydronium to the trace gas molecule of interest that leads to a protonated and hence ionised molecule. This reaction is energetically possible for all VOCs with a proton affinity higher than that of water and is thus amenable to alkanes, alkenes, alkynes, aromatics and other organic molecules; PTR-MS therefore provides good coverage of the volatilome. This coverage can be further enhanced with the use of different reagent gases; this is available via fast switching and includes O2+, NO+, Kr+ and Xe+. Furthermore, combining the unique PTR ionisation with Time-of-Flight MS permits for high-sensitivity and high-resolution detection. PTR-MS thus offers major advantages over current analysis methods and it meets many of the demands of contemporary bioscience programmes such as rapid continuous monitoring.

The ability to monitor chemical diversity of the volatilome in situ and in real-time provided by the requested PTR-MS platform will provide major new insights towards our understanding of the underpinning mechanisms of biological systems. This aligns with BBSRC strategic priorities by underpinning research programmes that tackle major challenges in synthetic biology, bioenergy, food nutrition and health, integrative microbiome research and strategic approaches to industrial biotechnology (IB).

We propose a unique, multi-purpose proton transfer reaction (PTR) mass spectrometer platform (PTR-MS) for continuous online monitoring of volatile organic compounds (VOCs) with applications in many areas of bioscience research. The PTR-MS instrument will provide a powerful alternative analysis approach to routine GC-MS, which is offline, and often time consuming and thus limiting for many of the real time high-throughput measurement demands in current and future research programmes. The instrumental configuration will be truly unique to the UK bioscience community and will provide significant infrastructure and technology for many research groups at the Manchester institute of Biotechnology (MIB) and the wider University of Manchester (UoM), including academic staff from the Schools of Chemistry, Biological Sciences, Chemical Engineering and Analytical Sciences, Earth and Environmental Sciences and Mechanical, Aerospace and Civil Engineering and external partners (industrial and academic).

The MIB and BBSRC Manchester Synthetic Biology Research Centre (SYNBIOCHEM) located in MIB host an impressive array of specialised infrastructure research facilities, run by dedicated staff that are fully open to the interdisciplinary research community and to external users. These shared facilities include: Biological Mass Spectrometry; Biomolecular Analysis; Protein Expression, Structure and Dynamics; and High Throughput Robotics platforms with state of the art equipment that are support high impact research projects both within the University but also to external academic and industrial collaborations. The new PTR-MS platform will complement these facilities and provide important new capabilities in VOC analytics. The platform will be integrated into the SYNBIOCHEM data management system that allows automated data transfer from the instrument to back-up compute storage and easy remote access for subsequent data processing (see Data Management Plan).

We will establish a multi-user instrument and support infrastructure for sensitive and rapid VOCs analysis to support a wide range of programmes in the UK bioscience community. Our due diligence indicates the bioscience community currently lacks an open access multi-user instrument managed by expert staff to support a wide range of bioscience projects. The proposed instrument/facility would therefore benefit a wide range of users (expert and non-expert) from the UK bioscience community who will have access to the instrumentation supported within the wider analytics facility infrastructure at the Manchester Institute of Biotechnology (MIB).

The research that will be enabled by the acquisition of this new facility will have benefit to: (i) new and existing academic researchers who require a range of molecular interaction data across the remits of BBSRC's committees; (ii) governmental and private sector scientists interested in design novel biological assemblies for applications in biotechnology and industry; (iii) private sector scientists from a number of industries, for example molecular biosciences, and industries involved in synthetic and systems biology, technology development, drug discovery and industries involved in pharmaceuticals production and the wider bioeconomy; (iv) international organisations.

In order to allow the instrumentation to be fully exploited we would ensure that the equipment was fully accessible to all UK academics, who would also benefit from the high level of expertise and training that will be available at Manchester. Access to both internal and external users would be managed by the supporting Senior Experimental Officer (Dr K. Hollywood) and cost recovery mechanisms for open access use managed by the institute's research manager (Dr Louise Barnes) who implements similar cost recovery mechanisms for related facilities in MIB.

The impact of the multi-user facility would be maximised by: (i) organising a project/facility specific workshops around the wider bioanalytical and biophysical capabilities available in the MIB; (ii) generation of a web-portal for work conducted and opportunities for new investigators to the discipline; (iii) including details of the instrumentation on the N8 Shared Research Equipment Inventory to network with industry and via equipment.data.ac.uk; (iii) continuing our industrial collaborations; (iv) presentations to the scientific community via conferences and publications; (v) public engagement.

We will measure the success of our impact activities by the number of: (i) registered users of our community website/podcasts and associated outreach materials; (ii) applications to use the facility; (iii) scientific publications and citations thereof relating to the facility; (iv) participants that attend our workshops and future collaborations with new external partners.