Deep Phenotyping of Volatile Organic Compound Biomarkers with cIMS-ToF-MS coupled with a SICRIT ion source.

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The air that we breath out contains thousands of chemicals, called volatile organic compounds (VOCs). The information contained within these chemicals has great potential to help diagnose diseases such as asthma, cancer or even types of infection, as exemplified by several studies that have shown that sniffer dogs (whose noses detect different combinations of these chemicals) can diagnose certain diseases. In addition, VOC emitted in the space above culture and tissue samples acquired from patients, have shown great potential to identify different types of bacterial infection - for example in cystic fibrosis and tuberculosis. VOC in human breath and in the space above tissue samples, also tell us more broadly about the metabolism of bacteria and cells providing important insights when coupled with other metabolomic technologies to help us understand the mechanisms of disease. One of the challenges in the field of VOC analysis is that to develop accurate markers for disease diagnosis, monitoring, and to understand mechanism, we need to be able to identify VOC precisely by confirming their identity and structure using specialist equipment to detect them. Furthermore, for VOC to be useful as diagnostic tests, we need to detect them on devices that can ultimately be taken to a patient setting like a GP surgery or outpatient clinic. Finally, most of the current technologies used to discover new VOC in human breath and tissue samples are off-line and don't provide real time measurements, with results taking several hours to process and being highly analyst dependant.Our consortium based at Imperial College, London, is evaluating a new way to identify VOCs precisely (both their identity and structure), using a technique called cyclic ion mobility coupled with mass spectrometry (cIMS- ToF-MS). Whilst Ion mobility (IM) approaches have been around for over a decade to detect VOC, the proposal here is to use a new form of Ion mobility that is much more powerful at separating VOC species and can analyse the VOC in a much more precise way. The technique that we are using has already been used successfully in other fields - for example, to characterise impurity in complex mixtures such as petrochemicals, to look at how proteins fold and unfold and to deeply characterise drug metabolites that might cause toxicity to humans - to name just a few examples. The technology platform that we are deploying will enable real time (during breathing) analysis and accurate characterisation of VOC, which is critical to developing biomarkers that can ultimately be translated for the benefit of patients to smaller and portable IMS devices in relevant care settings. We will use the cIMS-ToF-MS technology to identify and characterise new VOC biomarkers in lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), cystic fibrosis, rare lung diseases and cancers - across the breadth and depth of selected studies that are ongoing and planned within the Faculty of Medicine at Imperial College, London. Our consortium includes experts in the field of metabolomics including the National Phenome Centre at Imperial College, leading industry partners in the field of breath VOC detection e.g. Owlstone Medical and multiple academic partners in the UK and abroad. We hope to use the technology platform to ultimately bring rapid (within seconds), point of care (GP practice, hospital) breath based biomarkers to the clinic for the benefit of patients with a broad range of diseases.