Micro-Sampling of Biological Tissue by Substrate-Mediated Laser Ablation: Toward Spatially-Resolved Proteomics at µm Scale

International audienceSince the pioneering works of R. Caprioli in 1997, conventional mass spectrometry imaging (MSI) tools resultingfrom Matrix-Assisted Laser Desorption/Ionization (MALDI) is widely used in various fields of -omics research (e.g.lipidomics, proteomics, metabolomics...) because of its high spatial resolution and detection sensitivity. However, dueto the inherent complexity of the biological tissue it has certain limitations. One of the major drawbacks of thetechnique is the limited capability of detecting and identifying minority compounds, notably proteins, directly ontissue. Various strategies have been developed to overcome this issue. All require a micro-sampling step. Differenttechniques have been specifically applied for this purpose like laser capture microdissection, liquid extraction orparafilm assisted microdissection (PAM) [1]. However, the spatial resolution of these techniques is typically about1mm and it is a real challenge to develop a tool with a sufficient yield to reduce the size of the sampled area.We have explored the potential of a new micro-sampling technique based on an indirect substrate-mediated laserablation (SMLA) mechanism which permits the use of low deposited energy while preserving the biological content.Taking advantage of this effect, analyses of micro-sampled tissue was performed, demonstrating the identification ofsignificant number of proteins [2]. Furthermore, SMLA was confronted to PAM in order to show its efficiency. Ourobjective is now to increase the spatial resolution up to µm scale. This requires the characterization of the SMLAmechanism to optimize the ablation yields. We present here recent advances in this field including systematic studiestaking into account the physico-chemical parameters of various substrates who highlights the role of the ablation ofthe substrate in the SMLA mechanism [3] and the study of the plume dynamic by shadowgraphy used to improve thecapture yield of the ablated material