Detection of VOCs by SERS for Disease Diagnosis

The detection of volatile organic compounds (VOCs) has recently found application in the diagnosis of diseases, such as cancer, liver disease, diabetes, respiratory conditions and gastrointestinal disease. VOC detection is a rapid, sensitive, selective and non-invasive approach that can be applied in point-of-care (POC) diagnostics for the real-time detection and monitoring of medical conditions. VOCs are generated in the human body as a result of biological pathways such as carbohydrate metabolism, lipid metabolism and oxidative stress. Therefore, changes in the profile of VOCs can be indicative of altered metabolic processes or liver function and can therefore be useful in diagnosing disease. VOCs are emitted in urine, blood, skin, saliva and exhaled breath, so they can be readily monitored in diagnostic tests. Analysis of exhaled breath is a particularly non-invasive, patient-friendly approach and the profile of VOCs from breath samples allows chemical fingerprinting for the detection and monitoring of disease.

Generally, VOC detection is carried out by techniques such as gas chromatography (GC) and mass spectrometry (MS). However, these can be time-consuming, costly, limited in portability and require complicated analysis. Development of low-cost, portable devices for the sensitive detection of VOCs from breath samples is an attractive area of research due to the potential advantages in medical diagnostics. This project aims to develop a SERS-based gas sensing device for the POC analysis of breath samples. SERS is an attractive technique for this application as it is sensitive, specific, quantitative and can be used for the simultaneous detection of multiple analytes. Additionally, portable instrumentation has been developed that allows the application of SERS at the point-of-use, with results obtainable almost instantaneously.

Objectives
(1) Initial work on this project would be the design and fabrication of a suitable SERS substrate to provide signal enhancement, followed by the investigation of appropriate capture molecules to selectively bind target analytes from samples, development of suitable sample transfer mechanisms, and finally, the optimisation of the detection methods to ensure maximum sensitivity. Initial targets, ethylene and acetone, have been selected as they have been identified as suitable breath biomarkers.
(2) Optimisation experiments will then be carried out using solutions of ethylene and acetone before moving to more complex mixtures and eventually patient breath samples. A key step is the efficient binding of the target analytes to the SERS-active substrate. We will use our expertise in surface modification to identify and screen a panel of suitable capture molecules such as peptides, aptamers and thiols with diverse physicochemical properties (hydrophobic, hydrophilic, charged, neutral, etc.). The most suitable binding molecules will provide efficient sensing capabilities for target VOCs and the sensitivity of SERS detection will be compared with alternative techniques, with the aim of achieving detection limits comparable to those of mass spectrometry but with the advantages of rapid and portable analysis.
(3) Detection will be extended to a range of VOCs related to disease so that the techniques can be applied for the diagnosis and monitoring of various health conditions.