Improvement in the sensitivity of LA-ICP-MS bioimaging by addition of nitrogen to the argon carrier gas

Abstract

Elemental bioimaging of low abundant elements via laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is hampered by a lack of sensitivity. Novel solutions for specific applications have been developed, however there is a need for more universal approaches. Here we investigated the addition of N₂ to the ICP carrier gas to increase sensitivity, defined as signal-to-background, for the majority of biologically relevant elements. A gelatine standard that contained 38 elements across the mass range was ablated with increasing amounts of N₂ added to the carrier gas post-ablation. The results show that while all elements examined had an increase in signal intensity, some elements did not have a resultant increase in signal-to-background. Sc, V, Mn, Fe, and Se exhibited reductions in signal-to-background ratios across all N₂ flow rates examined, with the remaining elements experiencing signal-to-background increases from 1.2–7.8×, depending on the N₂ flow rate and element. An optimum N₂ flow rate was determined for the analysis of all elements, and used to image endogenous elements in a mouse brain, and antibody-conjugated elements in a quadriceps muscle section. These images confirmed that the addition of N₂ to the carrier gas increased the signal-to-background of the analysis, improving image resolution for endogenous elements and low abundant analytes used for immuno-mass spectrometry imaging of biomarkers. These findings offer a promising avenue for advancing the capabilities of LA-ICP-MS in bio-imaging applications.