Characterisation and application of low dispersion cell technology to laser ablation inductively coupled plasma mass spectrometry cancer imaging

The development of low dispersion cell technologies in laser ablation (LA) has led to a rapid advancement to the capabilities that laser ablation can offer as a sampling technique in conjunction with inductively coupled plasma mass spectrometry (ICP-MS). The development of one such prototype laser ablation system was characterised in conjunction with a sector field ICP-MS, investigating several aspects of its performance and also different methods of standardisation utilising gelatine and piezo generated droplets were investigated as tools for accurate quantitative calibration method in future applications. The potential of low dispersion technology was explored in two different cancer focussed diagnostic/pre-screening applications. Firstly, high-speed and high-resolution imaging of Cisplatin doped non-small cell lung cancer explant models was achieved to demonstrate the potential for use as a pre-screening tool. LA-ICP-MS data correlated accurately with H&E and IHC staining methods to help identify resistance and sensitivity to Cisplatin treatment and for the first time identified that carbon deposits found within lung tissues may be detrimental to the effective distribution of Cisplatin. An exploration of potential matrix effects using LA-ICP-MS with PIXE and electric backscattering as complimentary techniques confirmed it was unlikely that matrix effects were solely responsible for the effect. A novel LA-ICP-MS method for the detection and identification of asbestos fibres in models of malignant mesothelioma was also developed as current clinical methods of identification and quantitation remain difficult. A prototype time-of-flight ICP-MS was used in conjunction with a low dispersion LA setup as it allowed for pseudo-simultaneous multi-element analysis. Imaging with 3µm lateral resolution and a sampling rate of 50Hz achieved washout times of ̴10ms. 3 asbestos fibre types were elementally distinguishable from a non-asbestos control and from each other using statistical modelling approaches, showing that LA-ICP-MS has potential for use in a clinical setting to aid asbestos fibre identification.