Thesis

The design and development of a high-throughput ATR-FTIR serum diagnostics platform

Downloadable Content

Download PDF
Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2020
Thesis identifier
  • T15870
Person Identifier (Local)
  • 201562175
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy has demonstrable clinical ability and is well poised to address numerous clinical needs in virtue of operative ease, sample versatility, non-destructive testing, and good diagnostic prediction capabilities. Technical barriers stand in the way of clinical implementation, namely lack of high-throughput capabilities. Samples are individually deposited, prepared, analysed, then removed from a fixed Internal Reflection Element (IRE) amounting to a workflow bottleneck. IRE substrates are typically expensive and unamenable to manufacture and thus resigned to this workflow. We developed a low cost and disposable silicon (Si) IRE (SIRE) and universal infrared spectrometer accessory module enabling high-throughput analysis with high spectral quality and reproducibility. Spectral reproducibility was optimised through characterisation of intrinsic and extrinsic optical variance sources and subsequent mitigation. Si impurity variance had little impact on spectral reproducibility. Optimised batch sample preparation procedure and surface treatment diminished extrinsic variances. SIREs maintain comparable performance to a Diamond IRE in the detection and quantitation of archetypal carbohydrates, lipids, and proteins at clinically relevant concentrations demonstrating effectiveness across the biochemical ‘fingerprint’ region. A 300% increase in sample throughput over a conventional Diamond IRE was achieved. Sepsis, SIRS, and control patient samples were discriminated using spectra acquired from SIREs to demonstrate clinical suitability. A random forest classifier of sepsis (n=43), SIRS (n=59), and control (n=46) constructed from serum samples analysed on SIREs achieved high negative predictive value (93.55%), positive predictive value (76.08%), sensitivity (84.15%), specificity (90.43%), and accuracy (81.98%) for the detection of sepsis.
Advisor / supervisor
  • Baker, Matthew James
Resource Type
Note
  • This thesis was previously held under moratorium from 22nd April 2021 until 22nd April 2023
DOI
Date Created
  • 2020
Former identifier
  • 9912983990602996

Relations

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PDF of thesis T15870 2021-07-02 Public Download