Direct Infusion ICP-<i>q</i>MS of Lined-up Single-Cell Using an Oil-Free Passive Microfluidic System

Abstract

When coupled online with mass spectrometry (MS), widely applied water-in-oil droplet-based microfluidics for single cell analysis met problems. For example, the oil phase rumpled the stability, efficiency, and accuracy of MS, the conventional interface between MS and the microfluidic chip suffered the low sample introduction efficiency, and the transportation rates sometimes unmatched the readout dwell times for transient signal acquisition. Considering cells are already "droplets" with hydrophilic surface and elastic hydrophobic membrane, we developed an oil-free passive microfluidic system (OFPMS) that consists of alternating straight-curved-straight microchannels and a direct infusion (<i>d</i>I) micronebulizer for inductively coupled plasma quadrupole-based mass spectrometry (ICP-<i>q</i>MS) of lined-up single-cell. OFPMS guarantees exact single cell isolation one by one just using a thermo-decomposable NH₄HCO₃ buffer, eliminating the use of any oil and incompatible polymer carriers. It is more flexible and facile to adapt to the dwell time of ICP-<i>q</i>MS owing to the adjustable throughput of 400 to 25000 cells/min and the controllable interval time of at least 20 ms between the lined-up adjacent single cells. Quantitative single-cell transportation and high detection efficiency of more than 70% was realized using OFPMS-<i>d</i>I-ICP-<i>q</i>MS exemplified here. Thus, cell-to-cell heterogeneity can be simply uncovered via the determination of metals in the individual cells.