Comparative Analysis of Conventional Cell Lysis Techniques to Electrochemical Cell Lysis Using the Liquid Microjunction Surface Sampling Probe

Abstract Cell lysis is a critical step in the analysis of cellular components. Conventional mechanical and chemical methods present trade-offs between throughput, scalability, and sample integrity. Electrochemical lysis (ECL) is a promising alternative that uses low-potential electrolysis (2–5 V) of phosphate-buffered saline (PBS) to disrupt membranes while minimizing sample perturbation and solvent consumption. Here, we evaluate ECL against conventional lysis methods (bead milling, sonication, chemical lysis, and freeze–thaw) using combined microbiological, electrochemical, and mass spectrometric (MS) characterization, including ambient MS via the liquid microjunction surface sampling probe (LMJ-SSP) and liquid chromatography-MS/MS (LC–MS/MS). ECL produced lysates with greater replicate reproducibility and biomolecular diversity than conventional methods. Integration of ECL with the LMJ-SSP MS enabled rapid characterization with minimal sample preparation.