High-Resolution Elemental Bioimaging of Ca, Mn, Fe, Co, Cu, and Zn Employing LA-ICP-MS and Hydrogen Reaction Gas

Imaging of trace metal distribution in tissue sections by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is typically performed using spatial resolutions of 30 μm(2) and above. Higher resolution imaging is desirable for many biological applications in order to approach the dimensions of a single cell. The limiting factor for increasing resolution is sensitivity, where signal-to-noise ratios are poor due to inherent background spectral interferences and reduced sample volume with decreasing laser beam diameter. Several prominent spectral interferences are present for a number of biologically relevant isotopes, including the (40)Ar(16)O(+) spectral interference on (56)Fe(+). We examined if H(2) as a reaction gas could improve the analytical performance of imaging experiments for a range of masses with spectral interferences. At low (<1 mL min(-1)) H(2) flow rates, greater spectral interference due to H(+) adducts was observed for (55)Mn, (57)Fe, and (59)Co. At higher flow rates of up to 3 mL H(2) per minute, the spectral interferences were reduced leading to improvement in limits of analysis for masses with O- and N-based polyatomic interferences. Enhanced sensitivity with the reaction cell allowed construction of high resolution (6 μm(2)) imaging of (56)Fe in the mouse brain that approached the dimensions of single cells.