Three-Dimensional-Printed Lateral Extraction Enhanced Desorption Electrospray Ionization Source for Mass Spectrometry

This paper introduces a novel Lateral Extraction Enhanced Desorption Electrospray Ionization (LEE-DESI) source. This source is specifically designed to tackle the crucial issue of electric field interference in dual-channel ambient ionization mass spectrometry (AIMS). By incorporating dual-channel spraying-based desorption and extraction into a 3D-printed chamber with optimized spatial parameters, the system effectively reduces cross-channel interference while boosting ionization efficiency. The desorption spray is responsible for desorbing analytes from untreated samples, and the extraction spray further ionizes more neutral droplets through charge transfer, which substantially enhances sensitivity. Compared with traditional DESI, the LEE-DESI source demonstrates improved detection limits, reproducibility, and operational simplicity, as validated using Rhodamine B, L-arginine, and Angiotensin I, as well as drug standards including methadone, ketamine, and fentanyl. This highlights its potential for high-throughput analysis of complex matrices in proteomics, metabolomics, and biomedical applications.