Ambient Ionization Mass Spectrometry Based on Laser Ablation-Carbon Fiber Corona Discharge Ionization

Metabolites are the regulated end products present in cells, tissues, or organisms. As an important class of metabolites in living organisms, lipids play critical roles in numerous biological processes. Lipids not only constitute the main components of cellular membranes and serve as energy storage substances, but also participate in disease development, cancer progression, and the maintenance of body homeostasis in the form of signaling messengers and immunomodulators. Therefore, obtaining comprehensive and accurate information on lipid composition, abundance, and spatial distribution networks is of significant practical importance for elucidating their biological functions, discovering potential disease biomarkers, and understanding pathological mechanisms. Mass spectrometry (MS), owing to its high sensitivity, high throughput, and high resolution, is widely employed in metabolomics or lipidomics. MS-based lipidomics approaches play a vital role in revealing lipid-molecule interactions, disease progression, and metabolic dysregulation. The ion source is often regarded as the heart of the mass spectrometer. The efficient ionization of target analytes is a prerequisite for MS analysis, and the characteristics of the ion source also significantly influence the accuracy, reproducibility, and reliability of MS determination. Current lipidomics research predominantly focuses on the analysis of phospholipids, which are abundant in cells and readily ionizable, whereas systematic investigations into other moderately to low-polarity lipids with important physiological activities remain insufficient. Ionization techniques based on atmospheric pressure chemical ionization (APCI) enable the effective ionization of low-polarity compounds. The APCI ionization mechanism can be summarized as gas-phase chain reactions mediated by excited reactive species, achieving analyte ionization through processes such as proton transfer, Penning ionization, and charge exchange. Sample pretreatment procedures also significantly affect the throughput and efficiency of mass spectrometry analysis. Ambient ionization mass spectrometry allows for the effective detection of target analytes while simplifying pretreatment procedures, extending the interdisciplinary application scope of mass spectrometry. In this study, an ambient ion source based on laser ablation-carbon fiber corona discharge (LACFCD) was developed. The ion source consists of a laser desorption module and a post-ionization module based on carbon fiber corona discharge. Laser ablation-carbon fiber corona discharge mass spectrometry (LACFCD-MS) obviates the need for complex pretreatment procedures, enabling rapid identification of lipids on the skin surface. A total of 13 categories (49 species) of lipids were identified, including triglycerides, long-chain fatty acids, long-chain fatty alcohols, very-long-chain fatty acids, cholesterol and its derivatives, and eicosanoid precursors, demonstrating promising potential for high-throughput and rapid screening applications. Furthermore, the spatial metabolomics data from mouse liver tissue were acquired using LACFCD-MS. The spatial distribution maps of 23 lipid species in mouse liver tissue were obtained, revealing the biological processes including energy conversion, signal transduction, and localized pathology. This demonstrates its potential for resolving tissue spatial metabolic heterogeneity, correlating morphology with molecular function, and discovering potential pathological subregion biomarkers. This study also has certain limitations. Primarily, it did not achieve direct in-situ detection of skin surface lipids, requiring the use of copper-coated glass slides as intermediate sample carriers. Future integration with diverse sample desorption modules may enable real-time, in-situ lipidomics analysis. Additionally, the exploration of molecular interaction patterns in spatial lipidomics was incomplete, as a comprehensive assessment of the interactions among different lipid molecules and their corresponding physiological significance was not conducted.