Medical Applications of In-line Laser Absorption Spectroscopy

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry

Abstract

This work forms part of an ongoing collaboration between the Ritchie group in Physical Chemistry and the Robbins group in the Department of Physiology and Genetics. Recent work has developed a completely new technique of in-airway molecular sensing using laser absorption spectroscopy. This has changed the experimental precision with which mass balance can be tracked during rebreathing of various molecular species from 1:20 to 1:500 molecules, and has allowed the first detailed measurements of oxygen consumption in patients undergoing surgery, and most recently, those receiving critical care. In collaboration with the Department of Computer Science the researchers have also developed a low order model of the lung's heterogeneity - the log-normal lung - where it is possible to recover the parameters underpinning the heterogeneity of the lung from measurements made using their high fidelity, in-airway molecular flow sensing.
This project will build upon this successful collaboration, with early work aiming to increase the accuracy of the current measurements of oxygen, carbon dioxide and water vapour and then to use this improved instrument in clinical trials. The improved instrument will have an impact in a range of clinical settings. For example, in critical care, accurate measurement of oxygen consumption for patients in shock could be used to give feedback on the success of treatment in real time. In the field of respiratory medicine, measurement of lung function and heterogeneity will be applied to following the progression of diseases such as COPD, cystic fibrosis and interstitial lung disease, as well as informing medical practitioners on a patient's response to therapy. Collaborations in all of these have been formed and clinical trials in at least two of these areas are scheduled to start during the first year of study.
Further advances in physiological phenotyping will then be made by developing new technology to follow exogenous tracer gases, in order to measure aspects of lung function such as lung diffusing capacity. The method relies upon determining the uptake of foreign gases delivered in low quantities to the patient, and analysed in real time by laser absorption techniques within a ventilation tube. In particular, this involves the sensitive analysis of blood soluble and blood insoluble gases (for example, carbon monoxide and methane) with fast time resolution of 10ms. Such studies will allow the current "log-normal" lung model to be extended. In addition, the project has the potential to deliver a non-invasive instrument for measuring cardiac output in anaesthetised and critically ill patients. The validity of currently used invasive procedures, such as pulmonary artery catheterization, is questionable, with several studies suggesting that the associated risks might outweigh the clinical benefits, and the growing consensus is that non-invasiveness should be a paramount feature of the next-generation cardiac output monitors. Foreign gas uptake has been established as a satisfactory method for assessing cardiac output, but the methods of gas analysis have been cumbersome or insensitive, and unsuitable for use with ventilated patients. The instrument that will be developed will enable very low concentrations of these gases to be delivered to the patient and will result in minimal disruption to the ventilation procedures, with the whole optical instrumentation being able to connect with a standard 20 mm diameter ventilation tube with no disturbance to the gas flow.
This project falls firmly within the Clinical Technologies, Sensors and Instrumentation and Optical Devices and Subsystems research areas of the EPSRC. This work should offer clinicians a quick and simple alternative to the invasive methods with which cardiac output is currently measured in surgical and intensive care settings.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509711/1 01/10/2016 30/09/2021
1810789 Studentship EP/N509711/1 01/10/2016 31/12/2020 Jennifer Redmond
 
Description A new technology for lung function testing has been tested on volunteers with cystic fibrosis for the first time. A multiple breath washout test is performed using the novel molecular flow sensor, which monitors gas exchange more accurately than conventional testing. This data is then analysed using the Lognormal Lung Model and the initial results show that the LNL parameters are able to discriminate between people with cystic fibrosis and healthy control subjects. Further recruitment of volunteers has not been possible due to the Covid-19 pandemic, but will continue when possible.

A smaller paediatric molecular flow sensor has also been designed and includes an additional optical channel to allow traces amounts of methane to be measured to allow a washin procedure as a shorter alternative to a nitrogen washout experiment. This is expected to be tested in paediatric patients later this year.
Exploitation Route Possible future applications of this work could include better assessment of lung health in people with CF and better informing clinicians on the response of patients to new treatments or interventions.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Nichol-Young Foundation travel grant
Amount £500 (GBP)
Organisation Nichol Young Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2018 
End 03/2018
 
Description Application of Molecular Flow Sensing and the Lognormal Lung Model to assess lung inhomogeneity in people with CF 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We supplied a Molecular Flow Sensor, built and calibrated by our team. We then took the device to London and demonstrated how to perform washout experiments using the device so that the Brompton team would be able to recruit and study more subjects. As washouts were performed by volunteers at the Royal Brompton Hospital, I prepared the data to run on the Lognormal Lung Model on the ARC system. I then collated and analysed the results.
Collaborator Contribution The team at the Royal Brompton/Imperial College recruited the subjects, conducted the washout tests, took spirometry measurements and ran MBW tests to obtain LCI and other MBW parameters on existing equipment. They then shared the files from the Molecular Flow Sensor and their results from the standard MBW tests with us for further analysis.
Impact None so far, collaboration still ongoing, but patient recruitment has been challenging due to Covid-19 pandemic and the CF population shielding for the past year.
Start Year 2019
 
Description Application of Molecular Flow Sensing and the Lognormal Lung Model to assess lung inhomogeneity in people with CF 
Organisation Royal Brompton Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We supplied a Molecular Flow Sensor, built and calibrated by our team. We then took the device to London and demonstrated how to perform washout experiments using the device so that the Brompton team would be able to recruit and study more subjects. As washouts were performed by volunteers at the Royal Brompton Hospital, I prepared the data to run on the Lognormal Lung Model on the ARC system. I then collated and analysed the results.
Collaborator Contribution The team at the Royal Brompton/Imperial College recruited the subjects, conducted the washout tests, took spirometry measurements and ran MBW tests to obtain LCI and other MBW parameters on existing equipment. They then shared the files from the Molecular Flow Sensor and their results from the standard MBW tests with us for further analysis.
Impact None so far, collaboration still ongoing, but patient recruitment has been challenging due to Covid-19 pandemic and the CF population shielding for the past year.
Start Year 2019
 
Description Collaborative study on measurements lung inhomogeneity 
Organisation University of California, San Diego (UCSD)
Country United States 
Sector Academic/University 
PI Contribution Our research team built and arranged the shipping of our molecular flow sensing device to San Diego. We calibrated and ran the device, completing two washouts per subject (all COPD patients) in the clinical trial. We processed this data using the log-normal lung model to provide measurements of lung inhomogeneity in these patients. These could then be compared to measurements made using MIGET, an invasive technique which is the current gold standard method for determining lung inhomogeneity.
Collaborator Contribution The UCSD researchers organised and recruited patients for the study. They arranged payment for subjects and completed all the MIGET measurements which could then be compared to our measurements using a nitrogen washout protocol and processing the data using the log-normal lung model.
Impact This collaboration was interdisciplinary and involved the Department of Physiology and the Department of Chemistry at the University of Oxford and the Department of Physiology at UCSD. Analysis of the data from this study is still ongoing.
Start Year 2018
 
Description Interviews/videos about research journey for Study Higher Programme 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact I was interviewed by the central university access/outreach team as part of their Study Higher programme, which is targeted at sixth form students from areas with low progression to university. They asked me about the research questions I was working on for my DPhil and the motivation for my research. This was compiled to make a video, which has been uploaded to YouTube, so is generally available to the public.
Year(s) Of Engagement Activity 2020
 
Description Mentoring a Syrian refugee through OXPAND 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I worked with one Syrian refugee through the organisation OXPAND to help her with her work towards the necessary qualifications in Chemistry to enter higher education. She also showed a lot of interest in my research and the idea of pursuing further research after obtaining her undergraduate degree.
Year(s) Of Engagement Activity 2016,2017
 
Description PhD Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact I gave tours around the Oxford Chemistry research laboratories and explained my research to prospective PhD students. This sparked discussion and interest in joining the research team and other related areas of research.
Year(s) Of Engagement Activity 2017
 
Description Poster session for outreach conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 60 pupils attended a poster session as part of a larger oitreach visit to Oxford. I was one of 8 postgraduate students presenting my research to them and encouraging questions and discussion.
Year(s) Of Engagement Activity 2019
 
Description Presentation for Target Oxbridge Outreach Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact I planned and delivered interactive 3 hour chemistry seminar to Sixth Form Students, as part of a university access programme to support students from BME backgrounds. The students reported that it was a very valuable experience and increased their confidence in making a competitive application to study a STEM subject at top universities.
Year(s) Of Engagement Activity 2016
 
Description UNIQ Outreach Residential Programme 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact I worked alongside 3 other student mentors with a group of 50 sixth form students on the UNIQ Chemistry Summer School. All participants are drawn from schools and regions in the UK with low progression rates to higher education. We talked to them about the content covered in their lectures, tutorials and labs and answered all their questions about studying Chemistry at Oxford. As the only postgraduate mentor, I was also able to talk to them about my research and experience of continuing in research after completing my undergraduate degree. Many of the students showed interest, particularly in the opportunity for interdisciplinary research after a Chemistry undergraduate degree.
Year(s) Of Engagement Activity 2016,2017
 
Description Workshop on Oxford Interviews for Target Oxbridge Outreach Programme 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact I conducted mock undergraduate interviews with several BME students identified by the Target Oxbridge Programme. These students come from backgrounds and schools with little or no history of sending students to Oxbridge. This mock interview practice helped increase their confidence in making an application.
Year(s) Of Engagement Activity 2017