Establishment of MS LOC platform and its pilot application in clinical lipidomics

Lipidomics has demonstrated significant potential for disease diagnosis and prediction. The development and optimization of a robust mass spectrometry (MS) platform for lipidome analysis is critically important, as it can facilitate biomarker discovery, cohort testing, and performance evaluation in clinical lipidomics studies. In this work, we developed a high-throughput and reliable platform, termed MS Lab on a Chip (MS LOC), which integrates the MetArray chip, an automated lipidomics pretreatment protocol, and the reflectron matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) instrument. The MetArray chip, produced through a mass production process, exhibited exceptional stability as an MS substrate. The integration of automated lipid pretreatment and MS detection processes ensures high throughput, stability and efficiency during sample preparation. The analysis of various lipid standards and different types of biological samples enabled comprehensive investigation of lipid features and annotation using the MS LOC. Furthermore, a small cohort study, consisting of hepatocellular carcinoma (HCC) and non-HCC groups, was conducted on this platform, providing preliminary validation of its performance and suggesting that this platform offers a comprehensive protocol for clinical lipidomics testing.