Dual-Mechanism-Driven Strategy for High-Coverage Detection of Serum Lipids on a Novel SALDI-MS Target

Abstract

Serum lipid metabolites have been emerging as ideal biomarkers for disease diagnosis and prediction. In the current stage, nontargeted or targeted lipidomic research mainly relies on a liquid chromatography–mass spectrometry (LC–MS) platform, but future clinical applications need more robust and high-speed platforms. Surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) has shown excellent advantages in the high-speed analysis of lipid metabolites. However, the platform in the positive ion mode is more inclined to target a certain class of lipids, leading to the low coverage of lipid detection and limiting its practical translation to clinical applications. Herein, we proposed a dual-mechanism-driven strategy for high-coverage detection of serum lipids on a novel SALDI-MS target, which is a composite nanostructure comprising vertical silicon nanowires (VSiNWs) decorated with AuNPs and polydopamine (VSiNW-Au-PDA). The performance of laser desorption and ionization on the target can be enhanced by charge-driven desorption coupled with thermal-driven desorption. Simultaneous detection of 236 serum lipids (S/N ≥ 5) including neutral and polar lipids can be achieved in the positive ion mode. Among these, 107 lipid peaks were successfully identified. When combined with VSiNW-Au-PDA and VSiNW chips, 479 lipid peaks can be detected in serum samples in positive and negative ion modes, respectively. Based on the platform, serum samples from 57 hepatocellular carcinoma (HCC) patients and 76 healthy controls were analyzed. After data mining, 14 lipids containing different lipid types (TAG, CE, PC) were selected as potential lipidomic biomarkers. With the assistance of an artificial neural network, a diagnostic model with a sensitivity of 92.7% and a specificity of 96% was constructed for HCC diagnosis.

Accurate Discrimination of Benign Biliary Diseases and Cholangiocarcinoma with Serum Multiomics Revealed by High-Throughput Nanoassisted Laser Desorption Ionization Mass Spectrometry

“…The workflow of serum lipidomics and peptidomics analyses based on the NALDI-MS technique is shown in Figure . In our previous work, we developed a vertical silicon nanowire NALDI-MS technique for high-coverage detection of serum lipid . On this basis, the Lip-Si Array target containing an array of 60 sample loading spots was developed.…”

“…Serum lipid was analyzed by NALDI-MS; the detailed procedure has been described in our previous work. , In brief, the mass spectrum data of the patients and QC samples were obtained with a matrix-free method, in which each extracted serum lipid sample with a volume of 1 μL was loaded on a Lip-Si Array NALDI target (Well-Healthcare Technologies Co. China), which contains an array of sample spots with a vertical silicon nanowire structure. The technology was developed from our previous works. , For comparison, MALDI-MS using two traditional organic matrices (DHB and 9-AA) were performed to acquire serum lipid profile in positive and negative ion modes, respectively. 1 μL of serum lipid extract was premixed with 1 μL of the matrix; then, 1 μL of the resulting mixture was pipetted onto a MALDI target plate and air-dried for further MS analysis.…”

“…The technology was developed from our previous works. 16,20 For comparison, MALDI-MS using two traditional organic matrices (DHB and 9-AA) were performed to acquire serum lipid profile in positive and negative ion modes, respectively. 1 μL of serum lipid extract was premixed with 1 μL of the matrix; then, 1 μL of the resulting mixture was pipetted onto a MALDI target plate and air-dried for further MS analysis.…”

“…In our previous work, we developed a vertical silicon nanowire NALDI-MS technique for high-coverage detection of serum lipid. 16 On this basis, the Lip-Si Array target containing an array of 60 sample loading spots was developed. Each sample loading spot was surrounded by the superhydrophobic surface to effectively confine the droplets of lipid sample extracted by an organic solvent (Figure S2).…”

“…However, chromatographic separation of lipids and peptides using LC-MS platforms is often time-consuming, constituting a major limitation for large-scale clinical disease screening. In our previous work, we developed high-throughput serum lipid and peptide detection platforms based on nanoassisted laser desorption ionization mass spectrometry (NALDI-MS), respectively. , These platforms can not only achieve high-throughput detection of serum lipids and peptides but also meet the detection requirements of low noise background, high coverage, and high reproducibility. In the study, lipids and peptides in serum sample of BBD and CCA patients were profiled by NALDI-MS. 20 lipids and 5 peptides that have diagnostic value for CCA were discovered.…”