Advancing elemental analysis by collision/reaction cell technology and micro-droplet calibration for bioimaging applications by LA-ICP-TOFMS

Background: Bioimaging applications by laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) require comprehensive elemental analysis spanning the entire mass range. Within biological systems, endogenous elements are critical for maintaining metal homeostasis in cells, a fundamental aspect in disease progression when disrupted. Additionally, elements from the higher mass range may originate from various sources such as metal-tags for immuno-mass spectrometry, nanoparticles, or metal-based anticancer drugs. This study assesses the efficacy of collision/reacton cell (CCT) mode for simultaneously analysing elements across the complete mass spectrum. Furthermore, we demonstrate the accuracy of the LA-ICP-TOFMS methodology through the analysis of serum reference material. Results: Our findings demonstrate that the CCT mode outperforms the standard/no gas mode for LA-ICP-TOFMS measurements, particularly in quantifying endogenous elements susceptible to interferences. Through the analysis of picolitre-volume micro-droplet standards and serum reference material (deposited as micro-droplets), we observed accurate quantification of elements such as iron and selenium, with isotope ratios closely resembling natural compositions. As key advantage, the utilization of the CCT mode eliminated the need for labor-intensive post-data processing, streamlining analytical procedures. Additionally, the CCT mode also provided enhanced sensitivity (factor of 1.5-2) for elements in the higher mass range compared to the standard mode, without compromising the sensitivity for endogenous elements. Significance: We successfully integrated Seronorm serum reference material-containing micro-droplets into LAICPMS bioimaging workflows for quality control, enabling validated measurements of key biological elements. The use of the CCT mode is highly recommended for bioimaging applications that address the analysis of elements across the entire mass range.