The biomedical potential of high precision zinc isotope analysis
File(s)
Author(s)
Moore, Rebekah E. T.
Type
Thesis
Abstract
Interdisciplinary research is becoming more prevalent in the study of the human body, with clinicians and bio-medical researchers working with mathematicians, engineers and in this instance, geochemists. This work investigates the feasibility of using techniques originally developed by geochemists, for biomedical research. More specifically, this work used microwave assisted acid digestion and anion exchange chromatography in a metal-free environment to isolate Zn from biological reference materials and clinical samples for high precision stable isotope analysis by multiple collector inductively coupled plasma mass spectrometry.
The technique was used to isotopically characterise (i) concentration-certified biological reference materials (human blood serum, hair and urine, bovine muscle, pig kidney and fish muscle), (ii) urine from healthy people and (iii) malignant and benign breast cancer tumours and healthy breast tissues. Two of the reference materials were used for quality control in the other investigations. Urine was chosen to complement Zn isotope data for blood and processes responsible for isotopic variations
over time and between people were investigated. Major and trace element concentrations were also determined for the urine samples, using ICP-MS. The breast tissues were analysed to ascertain
whether the technique has potential as a diagnostic or prognostic tool.
The reference materials were sufficiently homogenous for isotope analysis. The range in Zn isotope compositions of urine was considerably larger than that of blood and it was hypothesised that this variation is due to either (i) fractionation induced by homeostatic control of Zn in the kidneys or (ii) urine having the Zn isotope composition of small molecules from the blood that are filtered by the kidneys (without inducing fractionation), which may originally vary due to diet and other factors. The results of the final study suggest the Zn isotope fractionation associated with breast cancer is local to breasts and is not manifest in the wider body.
The technique was used to isotopically characterise (i) concentration-certified biological reference materials (human blood serum, hair and urine, bovine muscle, pig kidney and fish muscle), (ii) urine from healthy people and (iii) malignant and benign breast cancer tumours and healthy breast tissues. Two of the reference materials were used for quality control in the other investigations. Urine was chosen to complement Zn isotope data for blood and processes responsible for isotopic variations
over time and between people were investigated. Major and trace element concentrations were also determined for the urine samples, using ICP-MS. The breast tissues were analysed to ascertain
whether the technique has potential as a diagnostic or prognostic tool.
The reference materials were sufficiently homogenous for isotope analysis. The range in Zn isotope compositions of urine was considerably larger than that of blood and it was hypothesised that this variation is due to either (i) fractionation induced by homeostatic control of Zn in the kidneys or (ii) urine having the Zn isotope composition of small molecules from the blood that are filtered by the kidneys (without inducing fractionation), which may originally vary due to diet and other factors. The results of the final study suggest the Zn isotope fractionation associated with breast cancer is local to breasts and is not manifest in the wider body.
Version
Open Access
Date Issued
2017-08
Date Awarded
2018-03
Advisor
Rehkamper, Mark
Sponsor
Imperial College London
Publisher Department
Earth Science & Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)