digitalMALDI: A Single-Particle–Based Mass Spectrometric Detection System for Biomolecules

Abstract

The development of a real-time system for characterizing individual biomolecule-containing aerosol particles presents a transformative opportunity to monitor respiratory conditions, including infections and lung diseases. Existing molecular assay technologies, although effective, rely on costly reagents, are relatively slow, and face challenges in multiplexing, limiting their use for real-time applications. To overcome these challenges, we developed digitalMALDI, a laser-based mass spectrometry system designed for single-particle characterization. digitalMALDI operates as a near real-time platform that directly samples aerosols, bypassing the need for complex and time-consuming sample preparation. To demonstrate the feasibility of this approach, intact insulin protein was used as a representative target. Results showed that digitalMALDI is capable of detecting 1 pg of insulin protein in single aerosol particles, suggesting that the system has a broad application for disease diagnosis, environmental monitoring, and biosecurity management.