Optical Microscopy-Guided Laser Ablation Electrospray Ionization Ion Mobility Mass Spectrometry: Ambient Single Cell Metabolomics with Increased Confidence in Molecular Identification

Single cell analysis is a field of increasing interest as new tools are continually being developed to understand intercellular differences within large cell populations. Laser-ablation electrospray ionization mass spectrometry (LAESI-MS) is an emerging technique for single cell metabolomics. Over the years, it has been validated that this ionization technique is advantageous for probing the molecular content of individual cells in situ. Here, we report the integration of a microscope into the optical train of the LAESI source to allow for visually informed ambient in situ single cell analysis. Additionally, we have coupled this ‘LAESI microscope’ to a drift-tube ion mobility mass spectrometer to enable separation of isobaric species and allow for the determination of ion collision cross sections in conjunction with accurate mass measurements. This combined information helps provide higher confidence for structural assignment of molecules ablated from single cells. Here, we show that this system enables the analysis of the metabolite content of Allium cepa epidermal cells with high confidence structural identification together with their spatial locations within a tissue.

Remote ablation chamber for high efficiency particle transfer in laser ablation electrospray ionization mass spectrometry

Improved remote ablation chamber for particle transfer in LAESI mass spectrometry.

Laser Ablation Electrospray Ionization Time-of-Flight Mass Spectrometry for Direct Analysis of Biological Tissue

Direct analysis and identification of biological tissue is significant for clinical applications. In this study, porcine liver and kidney have been analyzed using laser ablation electrospray ionization time-of-flight mass spectrometry (LAESI-TOFMS). This method showed good reproducibility for the same types of tissue and is capable of distinguishing different tissue species. The margin assessment was also performed using porcine renal tissue, and the response time was less than 6 s. Furthermore, human hepatocarcinoma tissue and normal tissue were identified using this method. Our results indicate that LAESI-TOFMS is a feasible approach for direct identification of tumor tissue and potential for assessment of the resection margin.