DLD-based on-chip sample handling for label-free single-cell MS cytometry

Single-cell mass spectrometry (MS) plays a pivotal role in biochemical analysis. Its combination with microfluidics has given rise to label-free mass cytometry. Efficient on-chip handling of cell samples is crucial for successful MS cytometry but has been rare. Herein, we propose a passive means for cell sample handling (<i>i.e.</i>, sorting and desalting) using deterministic lateral displacement (DLD), merely by designing hydrodynamic micro-structures. Specifically, two DLD arrays are configured in sequence to focus target cells by size, and then sort target cells and replace their solution with MS extraction solution. In the sample outlet, an electrospray ionization capillary is integrated with an on-chip liquid metal alloy electrode as the ionization source to allow consecutive MS cytometry analysis. With this handy setting, we can achieve sample-in-result-out, <i>i.e.</i>, inject cell solution and collect MS data for target cells. As demonstration, the integrated microfluidic chip was used to handle and analyze three types of cells respectively, collecting satisfactory MS cytometry analysis data to discriminate cell types. We envision that the proposed method sets up a new paradigm in efficient sample handling for single-cell MS analysis, as either a stand-alone module or integrated part of on-chip MS cytometry.