The presence of metals within biological systems has long been associated with physiological and metabolic processes of the body, including synthesis of complex biomolecules, energy production and intracellular signaling. The determination of elemental distributions in cells is therefore critical in advancing our understanding of disease pathogenesis. Of particular interest is the study of cellular responses to external stimuli, specifically for the development of novel drug treatments which minimize or eliminate undesirable side effects. For this purpose, it is necessary to assess how the metabolic state and variations in elemental distributions of a cellular population impact the effectiveness of drugs and susceptibility to infection. In order to carry out this type of research, sensitive instrumentation and accurate analysis methods are required, however current techniques often exhibit severe matrix effects, poor spatial resolution and high cost. Recent advances have focused on the use of Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) and Laser Induced Breakdown Spectroscopy (LIBS), with both techniques adapting the physical process of laser ablation in which a short pulsed laser beam is focused on the sample. The emission of light of a specific wavelength by the elements upon excitation by the laser and the removal of fine ablated particles from the surface of the sample are used for qualitative and quantitative analysis.
This project, funded by the Doctoral College at the University of Surrey and the Natural Environment Research Council (NERC/T009187/1), aims to open the door to new possibilities for cellular research by developing novel methods for biochemical elemental analysis. Investigation of the optimum sample preparation and substrate for the analysis of cells using LIBS has been explored, with issues surrounding sensitivity for intrinsic elemental analysis having been identified. Future work will focus on tackling the analysis of exogenous metals associated with Tuberculosis drugs incorporated into THP-1 cells.