Novel applications of stable isotope tracing methods in biomedical and environmental sciences
Author(s)
Larner, Fiona Claire
Type
Thesis
Abstract
The use of multiple-collector inductively coupled plasma mass spectrometry
(MC-ICP-MS) for trace element stable isotope ratio analysis has been well established
within geochemistry since its conception. The utilization of this high precision
technique has since progressed to some environmental applications; however, the use
of this tool in biological and biomedical work is limited to few studies. The aim of
this thesis is to establish viable techniques to enable high precision isotope analyses of
Cu and Zn in biological media, and demonstrate these methods via several
collaborative pilot studies across biomedicine and ecotoxicology. For this, a new
method for the separation of copper from biological materials to enable accurate and
precise Cu isotope analyses (±0.10 ‰) has been developed. This has been applied to a
study that, with the use of a 65Cu enriched stable isotope tracer, shows that
abnormalities of the human copper metabolism exist in those with Parkinson’s
disease. The first Zn isotope analyses of various engineered ZnO nanomaterials
(NMs) has been performed, which in conjunction with an extensive literature survey
and modelling studies, has shown that highly selective and sensitive detection of ZnO
NMs can only be achieved with the use of purpose made isotopically labelled ZnO
NMs. This is in part due to the high natural background levels of this element and
relatively low Zn concentrations involved in ecotoxicologically relevant exposures.
This concept has been successfully implemented to investigate ZnO NM uptake by an
estuarine invertebrate, and has shown that Zn from ZnO nanoparticles is bioavailable
to these organisms. These pilot studies have shown that there is vast scope for high
precision isotope analyses of trace metals in life sciences, and support the transition of
such investigations to full-scale studies.
(MC-ICP-MS) for trace element stable isotope ratio analysis has been well established
within geochemistry since its conception. The utilization of this high precision
technique has since progressed to some environmental applications; however, the use
of this tool in biological and biomedical work is limited to few studies. The aim of
this thesis is to establish viable techniques to enable high precision isotope analyses of
Cu and Zn in biological media, and demonstrate these methods via several
collaborative pilot studies across biomedicine and ecotoxicology. For this, a new
method for the separation of copper from biological materials to enable accurate and
precise Cu isotope analyses (±0.10 ‰) has been developed. This has been applied to a
study that, with the use of a 65Cu enriched stable isotope tracer, shows that
abnormalities of the human copper metabolism exist in those with Parkinson’s
disease. The first Zn isotope analyses of various engineered ZnO nanomaterials
(NMs) has been performed, which in conjunction with an extensive literature survey
and modelling studies, has shown that highly selective and sensitive detection of ZnO
NMs can only be achieved with the use of purpose made isotopically labelled ZnO
NMs. This is in part due to the high natural background levels of this element and
relatively low Zn concentrations involved in ecotoxicologically relevant exposures.
This concept has been successfully implemented to investigate ZnO NM uptake by an
estuarine invertebrate, and has shown that Zn from ZnO nanoparticles is bioavailable
to these organisms. These pilot studies have shown that there is vast scope for high
precision isotope analyses of trace metals in life sciences, and support the transition of
such investigations to full-scale studies.
Date Issued
2012
Date Awarded
2012-09
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Rehkamper, Mark
Weiss, Dominik
Sampson, Barry
Valsami-Jones, Eugenia
Publisher Department
Earth Science and Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)