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 30/06/2020 Jennifer Louise Redmond
 
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 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 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