Title: Development of a minaturised, low-cost, optical eNO sensor for asthma monitoring
Funder: Department of Health (England)

Abstract: Background Asthma is a disorder of variable airways obstruction, characterised by eosinophilic inflammation. However, assessment has been limited by techniques that are time consuming and distressing to the patient. Exhaled NO is surrogate biomarker for eosinophilic airways inflammation and is increased in patients with asthma. Exhaled NO (eNO) is an easy and rapidly noninvasive investigation, which has clinical utility in asthma diagnosis and monitoring to effectively guide management. A number of eNO analysers based on both electrochemical/chemiluminesence measurements are commercially available, ranging in price from £3.5k to £30k which has limited their clinical applicability. We aim to produce a, low-cost, miniaturised alternative chemiluminescence detector employing new photodiode technology. Aims The development of a miniaturised prototype system for chemiluminscence-based measurement of exhaled nitrogen monoxide (eNO) for asthma monitoring/diagnosis and adjusting therapy. 1. Develop microfluidics breath capture and ozone generation system. 2. Develop optical detection system using photodiode detection of chemiluminesence resulting from reaction of eNO with ozone. The photodiode detector will reduce the size and critically the costs of detector by replacing the photomultiplier tubes used in standard eNO analysers. 3. Fabricate integrated sensor/breath analysis prototypes. 4. Compare performance of low-cost sensor with expensive existing market systems 5. Comparative clinical studies to assess validity, sensitivity and specificity of low-cost sensor against existing techologies. Plan of Investigation Exhaled NO can be detected via its reaction with ozone, resulting in the generation of light in the form of chemiluminesence, which can subsequently be measured. Existing eNO analysers use expensive photomultiplier tubes in bulky desktop systems Instead, we will develop a low-cost, miniaturised sensor using a photodiode to detect the chemiluminesence. This will be integrated with an airflow system which routes breath and ozone into a miniaturised reaction chamber. Microfluidics and sensor optics will be fabricated using semiconductor Micro-Electro-Mechanical-Systems (MEMS) based processing techniques. Following fabrication of the prototype device, it will be compared in terms of sensitivity and specificity with existing commercially available technologies and trialled in clinical studies. Potential Impact Exhaled NO is a non-invasive test which can be used in asthma diagnosis, monitoring and treatment. Clinical evidence shows that eNO guided management results in better control of asthma exacerbations than standard strategies. Benefits are greatest for patients with more severe asthma where hospitalisation may be required. Optimisation of this technology is needed in terms of specificity, sensitivity and cost-effectiveness in order to be developed as a useful clinical tool. Providing this facility at a low-cost to patients and the NHS whilst matching the performance of current systems would give real and immediate benefits. The miniaturised sensor would also allow patients to monitor themselves in their own home increasing the uptake, distribution and impact of this technology.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY