Biosensing with microwave debye relaxation analysis
Author(s)
Basey-Fisher, Toby H.
Type
Thesis
Abstract
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.
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.
Version
Open Access
Date Issued
2013-04
Date Awarded
2013-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Klein, Norbert
Maier, Stefan
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)