An extremely wide range of molecular species are present in everyday materials such as petroleum, biodegradation materials such as lignin (a precursor to some biofuels), synthetic polymers and plastics, and of course, living organisms have many different types of small molecules (hormones, cell-wall lipids, amino acids, sugars) as well as many large molecules like proteins and DNA. For scientists to be able to use these molecules for new technologies, all of these molecules require detailed molecular structure determination, and mass spectrometry is a key tool in the toolbox of analysis techniques.
The Fourier transform ion cyclotron resonance (FTICR) mass spectrometer is a particularly advanced type of mass spectrometer widely used for ultra-high resolution, mass accuracy, and experiments requiring detailed structural analysis of molecules. Furthermore, the FTICR mass spectrometer is the most versatile type of mass spectrometer with many different ways to observe and characterise the structural detail of molecules. The proposed instrument will also include the ability to fragment ions in different ways thus providing the ability to distinguish molecules which differ in their molecular structure, but not their mass (i.e. isomers - which are extraordinarily common in biomolecules, for example cis- versus trans- fats or different types of sugars). This new instrument will also add substantially improved instrument control and data analysis software and electronics which will also improve data quality and acquisition speed by about a factor of 2-3.
Additionally, in collaboration with the only commercial manufacturer of these instruments, Bruker, we will develop several new technologies that will improve our ability to analyse complex mixtures of molecules. This collaboration with Bruker will enhance the impact of this research by providing a direct route to market for these developments (with appropriate intellectual property protection and licensing), which will allow these developments to be rapidly rolled-out to future and existing FTICR users via Bruker's established commercial distribution routes.
This new instrument will substantially expand our capability to study chemistry and biology, as above, but it will also greatly improve our ability to study small drug molecules, whether natural or synthetic, in their natural, active biological environment. For example, the 'stiffening' of proteins with age is partially due to sugar-related modifications called glycation, which accumulate over time on collagen in the joints, and is particularly common in diabetics which is measured quarterly with the HbA1c clinical assay. This instrument will allow improved study of the biochemical mechanism of formation and positional dependence of such modifications so that we can help inform the medical community on alternatives to enhance healthy living in an aging population. The instrument will also improve our ability to study biofuel production and potential downstream environmental impacts - thus providing the ability to design production to minimize the negative impacts.
This instrument will be set up as a sustainably funded national collaborative mass spectrometry resource, overseen by a Strategic Advisory Board of experienced academics and industrialists and will be made available through various mechanisms to the wider scientific community in science and industry. Projects will be prioritized based on 1) scientific excellence, 2) EPSRC remit, 3) impact, 4) early career researcher access, and 5) all other projects. The new instrument will be made available for these prioritized collaborative or user research projects for at least 250 days per year.
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