Microfluidic Impedance Cytometry Enabled One‐Step Sample Preparation for Efficient Single‐Cell Mass Spectrometry

Abstract Single‐cell mass spectrometry (MS) is significant in biochemical analysis and holds great potential in biomedical applications. Efficient sample preparation like sorting (i.e., separating target cells from the mixed population) and desalting (i.e., moving the cells off non‐volatile salt solution) is urgently required in single‐cell MS. However, traditional sample preparation methods suffer from complicated operation with various apparatus, or insufficient performance. Herein, a one‐step sample preparation strategy by leveraging label‐free impedance flow cytometry (IFC) based microfluidics is proposed. Specifically, the IFC framework to characterize and sort single‐cells is adopted. Simultaneously with sorting, the target cell is transferred from the local high‐salinity buffer to the MS‐compatible solution. In this way, one‐step sorting and desalting are achieved and the collected cells can be directly fed for MS analysis. A high sorting efficiency (>99%), cancer cell purity (≈87%), and desalting efficiency (>99%), and the whole workflow of impedance‐based separation and MS analysis of normal cells (MCF‐10A) and cancer cells (MDA‐MB‐468) are verified. As a standalone sample preparation module, the microfluidic chip is compatible with a variety of MS analysis methods, and envisioned to provide a new paradigm in efficient MS sample preparation, and further in multi‐modal (i.e., electrical and metabolic) characterization of single‐cells.