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Title: Biosensing with microwave debye relaxation analysis
Author: Basey-Fisher, Toby H.
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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The microwave dielectric response of biological solutions and electrolytes has been investigated for a number of decades though applications that utilise the response are few and far between. The dielectric features of many biological fluids are unique across the microwave spectrum and offer a wealth of possibilities for analysis techniques. This thesis documents the development of broadband and resonant microwave techniques that are suitable for applications in biological fluid analysis. Theoretical models concerning the dielectric properties and electromagnetic interaction with polar liquids such as water are examined. The means to conduct experimental observations of the dielectric spectrum of liquids are reviewed and the ability to conduct measurement on small sample volumes discussed. Broadband spectroscopy from 0.2 to 20 GHz has been performed on the simplest constituent of a biological fluid, water, and compared to literature and theoretical models. Other polar liquids such as ethanol, propanol and methanol were also examined. The impact of ions in solution on the high frequency permittivity was studied, in particular the response of alkali metal chlorides, copper sulphate and zinc sulphide. The temperature dependence of the metal chlorides was found to be highly dependent on the effective hydration radius and subsequently a means of calculating the temperature-dependent hydration radius of lithium and sodium was developed. The respective radii at room temperature were found to be 340 ±39 pm and 215± 21 pm. Relaxation processes from ion-association were examined and confirmed to be present in ions with high charge density. Comparative studies between various biological solutes in aqueous environments demonstrated that many proteins possess unique microwave dielectric spectral features based on bound water and protein-water exchange mechanisms. Two techniques for the differentiation of protein solutions are outlined based on the microwave dielectric spectrum and the relaxation processes associated with protein water. Broadband measurements were conducted from 0.5 to 40 GHz to analyse the dielectric response of whole blood and serum from human and murine donors. Based on the dielectric comparison of serum and whole blood a method for the determination of haemoglobin concentration is presented. A 9.4 GHz dielectric resonator was developed with an integrated microfluidic chip for the determination of haemoglobin concentration in samples as small as 2 microlitres. This was subsequently utilised to monitor the progression of haemoglobin levels in APCmin/+ mice with colon cancer. The results demonstrate the first microwave device with proven haematological diagnostic value with an accuracy that is equivalent to or better than existing commercial techniques (comparative standard deviation 0.85 g/dL to Sysmex system - commercial comparison >1.5 g/dL) and is non-destructive.
Supervisor: Klein, Norbert ; Maier, Stefan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available