Browsing by Author "Sizer, Jeremy"

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    DIABLO biomarker data (Detection of Infectious Agents By Laser Optics)
    (Cranfield University, 2019-04-04 13:25) Walton, Chris; Fowler, Dawn; Sizer, Jeremy; Patel, MItesh
    DIABLO - Detection of Infectious Agents By Laser Optics The aim of this project is to identify potential biomarkers for Clostridium difficile infection (CDI) in the stool of patients suffering with unexplained diarrhoea. It forms a part of a larger project aimed at developing an instrument for the point-of-care diagnosis of CDI, so an important aspect of this work is determination of markers which can be accessed rapidly (within a few minutes) from the sample with little or no prior sample preparation. The file "DIABLO Biomarker data.zip" contains the results of laboratory analysis of samples taken at Guy's and St Thomas' NHS Foundation Trust. Data are provided as SPSS and Excel files with a Word document containing explanatory notes on methods and data analysis. An early report of some of the results can be found in "Volatile biomarkers - poster.pdf".
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    Faecal volatile biomarkers of Clostridium difficile infection
    (PLOS (Public Library of Science), 2019-04-15) Patel, Mitesh; Fowler, Dawn; Sizer, Jeremy; Walton, Christopher
    Care of patients with potential CDI can involve isolation and use of antibiotics, often before a definitive diagnosis is available, impacting healthcare resource and contributing to antibiotic resistance. There is anecdotal evidence that the faeces of CDI patients have a distinctive odour, while it is well-established that changes in the gut microbiota are associated with changes in the volatile organic compounds (VOC) produced. A total of twenty-four candidate volatile biomarkers were identified from a review of the literature including in vitro, animal and human studies. Using thermal desorption-gas chromatography-time-of flight mass spectrometry (TD-GC-ToFMS), VOC emission rates were determined on stored frozen stool samples from 53 CDI-positive and 53 CDI-negative patients with unexplained diarrhoea which had previously been diagnosed using enzymatic and nucleic acid amplification tests. Sample preparation was limited to placement of a subsample in an appropriate container. Compounds exhibiting a statistically significant difference (p < 0.05) in emission rate between the CDI-positive and–negative groups and a corresponding area under the receiver-operator characteristic curve (ROC) >0.7 were considered potentially indicative of CDI. Seven compounds were so identified: propan-1-ol (ROC 0.75), 3-methylbutanal (ROC 0.84), ethyl propionate (ROC 0.81), hexanoic acid (ROC 0.73), 4-methylphenol (ROC 0.81), dodecane (ROC 0.80) and indole (ROC 0.85). A number of potential volatile biomarkers of CDI can be sampled rapidly and with little prior preparation from faecal samples of patients with diarrhoea. Of these 4-methylphenol (p-cresol) is of particular interest as it has been anecdotally linked to CDI and is closely related to the biology and virulence of Clostridium difficile. This approach shows promise for the rapid, point-of-care diagnosis of CDI with good sensitivity and specificity.
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    Mid-IR spectroscopic instrumentation for point-of-care diagnosis using a hollow silica waveguide gas cell
    (International Society for Optics and Photonics - SPIE, 2017-02-17) Francis, Daniel; Hodgkinson, Jane; Walton, Christopher; Sizer, Jeremy; Black, Paul; Livingstone, Beth; Fowler, Dawn P.; Patel, Mitesh K.; Tatam, Ralph P.
    Laser spectroscopy provides the basis of instrumentation developed for the diagnosis of infectious disease, via quantification of organic biomarkers that are produced by associated bacteria. The technology is centred on a multichannel pulsed quantum cascade laser system that allows multiple lasers with different wavelengths to be used simultaneously, each selected to monitor a different diagnostic biomarker. The instrument also utilizes a hollow silica waveguide (HSW) gas cell which has a very high ratio of interaction pathlength to internal volume. This allows sensitive detection of low volume gas species from small volume biological samples. The spectroscopic performance of a range of HSW gas cells with different lengths and bore diameters has been assessed using methane as a test gas and a best-case limit of detection of 0.26 ppm was determined. The response time of this cell was measured as a 1,000 sccm flow of methane passed through it and was found to be 0.75 s. These results are compared with those obtained using a multi-pass Herriot cell. A prototype instrument has been built and approved for clinical trials for detection of lung infection in acute-care patients via analysis of ventilator breath. Demonstration of the instrument for headspace gas analysis is made by monitoring the methane emission from bovine faeces. The manufacture of a hospital-ready device for monitoring biomarkers of infection in the exhaled breath of intensive care ventilator patients is also presented.