Contact ion activation: A new approach to enhanced mass spectrometry imaging

Mass spectrometry is one of the most sensitive techniques, but the desorption approaches (for example ToF-SIMS), which are used to detect and image chemical changes in solid samples, have poor efficiencies of converting molecules to ions in the analytical process. Besides, they generate fragments. The former reduces detection sensitivities and the latter makes spectral interpretations difficult, especially when using the technique in a non-targeted mode. There is considerable room for development in this area, as currently only one in a thousand molecules are ionised at best, and these are broken into fragments that are spread across the spectrum. This proposal aims to develop an analytical tool that will enhance the ionization probabilities of surface molecules and yield more easily interpretable, diagnostically significant mass spectra. This will enable us to examine molecular processes at close quarters at the site of its activity (in situ), with high sensitivities of detection, and understand the changes that take place at the chemical level. We propose to investigate a novel ion activation approach that will significantly enhance the capability of mass spectrometry imaging, especially ToF-SIMS imaging. We will achieve this through controlled vapour mediated and plasma mediated proton transfer reactions as methods to a) increase the ionization probability of molecules on surfaces, whilst preserving their spatial distribution on the sample surface and b) increase their diagnostic value for in situ biochemical characterisations. We will focus on developing the technology for detecting and imaging metabolites (small molecules that participate and mediate several cellular processes) in biological cells and tissues, for non-targeted analysis, such as in situ metabolomics. However, this will have a wider application, in other areas, such as polymer analysis. The proposed work is the development of an enabling technology that will enhance the capability of mass spectrometry imaging of organic surfaces, especially for studying biological systems. It will also provide a new avenue for further developments of mass spectrometric detections, in general. This investigation will have wider implications in biological and biomedical sciences, by enabling potentially new discoveries to be made.

This proposal aims to develop an analytical tool that will enable high resolution chemical images to be generated with highly resolved molecular information from organic and biological sample surfaces. This will have a considerable impact on research in different fields including, chemistry, biology, biomedical sciences, medicine, plant and animal sciences, ecology, etc., as it will enable molecular mechanisms to be delineated in situ, at high data resolutions. Currently we do not have such a tool to sensitively detect changes in the chemical makeup of complex samples, such as biological tissues, without the addition of extrinsic compounds to aid in the detection. This is more so when using the tool in a discovery mode to seek knowledge in a non-targeted approach. ToF-SIMS is an established technique in the semiconductor industry, but its application to image biochemical make up from biological surfaces has been possible only recently, thanks to advances in polyatomic ion clusters that give sufficient secondary ion yields and minimal surface induced damage, enabling biomolecular information to be captured. In this proposed work, we will develop the technique to enable metabolic changes in biological systems to be detected in situ, by enhancing the ionization probabilities of molecules and minimising fragmentary information. This will enable, for instance, biological and biomedical researchers to understand metabolic processes in plants and animals, discover novel pathways/molecular mechanisms and open new avenues for mediations (for example, therapies) that will have wider socio-economic significance. The proposed work will have immediate relevance to biological scientists, who will benefit from a valuable tool with enhanced capabilities to look at molecular mechanisms at high resolutions in situ. This will enhance knowledge and scientific advancements in their respective fields. For example, plant scientists may be able to use the tool to understand how plants behave in response to environmental stress, to understand the bottlenecks in improving plant yield, and to study disease resistance and which molecular mechanisms to mediate. This will help address global issues such as food security, animal welfare, human wellbeing, heath and disease prevention, etc. It will enable further development of mass spectrometry imaging to study biological systems, and can be extended to other areas such as biomedical sciences to effect discoveries and to monitor disease progression, for example. In this regard, the academic community involved in developing imaging mass spectrometry will benefit from this investigation. The proposed work will employ a PDRA skilled in physical sciences who will be trained in ToF-SIMS analysis and its development and application to study biological systems. The proposed project will provide a very good opportunity for the development of multidisciplinary skill sets for the individual who can seek employment in the academic or non-academic sectors. The proposed work has the potential to lead to patentable technologies with opportunities for commercial exploitation of scientific knowledge and attracting R & D investment from global businesses. Instrument manufacturers interested in the technique (most mass spectrometry manufacturers and suppliers) will benefit from the findings as it will help them in improving and developing the instruments that enable the technique to be more widely adopted by the biological community, in the long term. The findings will showcase the technological edge of UK science. Although it doesn't have a direct socio-economic impact, enabling the aforementioned developments will eventually lead to socio-economic benefits, for example in addressing food security, human health, social welfare, environmental sustainability, and economic developments.