The Horizon Prizes celebrate the most exciting, contemporary chemical science at the cutting edge of research and innovation. They are awarded to teams or collaborations who are opening up new directions and possibilities in their field, through ground-breaking scientific developments.
The Molecular Flow Sensor Team, a multidisciplinary team of chemists, physiologists, computer modellers, and clinicians, won the prize for the development of a novel device for lung function measurement: a molecular flow sensor for non-invasive breath analysis to provide measurements of respiratory disease and cardiac output.
The prize recognises the fruits of a longstanding collaboration - the first proof of concept paper to demonstrate it was possible to use laser absorption spectroscopy in-line for respired gas analysis was published by the team in 2011. The original problem was to establish if oxygen consumption could be measured accurately in an open circuit setting when the inspired level of oxygen is high, such as in patients undergoing invasive mechanical ventilation in critical care.
DPAG’s Professor Peter Robbins said: “In principle, the sum is simple. Subtract the oxygen breathed out from the oxygen breathed in, and you have the oxygen consumption. However, when breathing pure oxygen, around 19 molecules are breathed out for every 20 breathed in. So, an error in measurement between inspiration and expiration of even 1 molecule in 20 (5%) is catastrophic when it comes to the calculation. Thus the target – which we subsequently met – was to produce a device with an error between inspiration and expiration of less than 1 in 500 molecules.”
Sometime after starting work on this device, the investigators hypothesised that it should be possible to use the highly precise, highly time resolved measures of gas exchange to infer much more about cardiopulmonary function in individuals than simply their rate of oxygen consumption. To realise this, the investigators built a computational model of the lung and the circulation based around conservation of matter. The breathing of the model can be driven to match the precise respiratory flows recorded from individuals, including the inspired gas composition, and the detailed time profile of the gas coming out the model can be compared with that measured using the molecular flow sensor. Using an optimisation process, the parameters of the model can then be progressively adjusted to minimise the difference between the model and the data for the expired gas compositions. With this method, the investigators were able to establish a set of parameter values that describe a particular individual’s physiology. Researchers christened the process ‘computed cardiopulmography’.
The sensor has since been used as a tool in several respiratory medical studies, including measuring the lung function of asthma. Research has shown that an asthma patient’s particular parameter values predict whether a hospital physician will maintain or escalate a patient’s therapy. GSK have funded the investigators to explore how this technology can track treatment response in relation to the new biologic therapies that have been developed for treating more severe asthma. The EPSRC, together with the Cystic Fibrosis Trust, have provided support for a related study in children with cystic fibrosis. The team has also been using the device in post-COVID patients to gain insights into the sustained effects of severe COVID infection on the lung. All the results so far point to the effectiveness of the sensor in early diagnosis and management of lung disease.
Professor Robbins said: “I particularly hope the sensor will enable physicians to identify disease earlier, including sub-clinical disease, with the ultimate aim that it will facilitate therapeutic intervention to prevent the development of chronic airways diseases. If this sounds like science fiction, think how the development of the sphygmomanometer to measure blood pressure at the end of the 19th century ultimately paved the way for antihypertensive therapy that so successfully prevents patients from having heart attacks and strokes. As always, there is clearly much still to do.”
The Molecular Flow Sensor Team comprises members of several departments across the Medical Sciences (MSD) and Mathematics and Physical Sciences (MPLS) Divisions, including DPAG, the Department of Chemistry, the Oxford University Hospitals NHS Trust, the Department of Computer Science, the Nuffield Department of Medicine, and the Nuffield Department of Clinical Neurosciences. The Department would like to congratulate DPAG’s team members: Asma Alamoudi, Dr Matthew Frise, Dr Chris Fullerton, Snapper Magor-Elliott, David O'Neill, Timothy Pragnell, Professor Peter Robbins, Dr Peter Santer, and Dr Nick Talbot.
More information about the Team, including a Q&A on the project, can be found on the RSC website's 'The Molecular Flow Sensor Team' page.
The Team joins another group and five other individuals from the University of Oxford who have won prestigious prizes at this year’s RSC Awards. More information on the MPLS website.