Negative Magnetophoresis Focusing Microchips Online-Coupled with ICP–MS for High-Throughput Single-Cell Analysis

• Published in: Analytical chemistry (Washington) Vol. 94; no. 18; pp. 6649 - 6656
• Main Authors: Chen, Zhenna, Chen, Beibei, He, Man, Hu, Bin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.05.2022
• Subjects: Cell density; Chemistry; Droplets; Dwell time; Fabrication; Flow velocity; Heterogeneity; Inductively coupled plasma mass spectrometry; Integrated circuits; Mass spectrometry; Mass Spectrometry - methods; Mass spectroscopy; Microchannels; Nanoparticles; Saline solutions; Semiconductors; Single-Cell Analysis - methods; Spectrum Analysis; Trace elements; Trace Elements - analysis; Vapor phases; Zinc; Zinc Oxide
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.1c04216

High-throughput single-cell analysis is critical to elucidate the cell heterogeneity. Recently, droplet microchips using oil/gas phases to generate single-cell encapsulated droplets have been combined with inductively coupled plasma–mass spectrometry (ICP–MS) for determination of trace elements in single cells with a throughput of dozens of cells per min. To improve the sample throughput and avoid the oil phase introduced into ICP–MS, herein, a negative magnetophoresis focusing microchip was established and online-coupled to ICP–MS for single-cell analysis. MCF-7 cells in the paramagnetic salt solution were introduced into the designed focusing microchannel, in which they were focused into a single stream under both the magnetic repulsion force and inertial lift force, and then were introduced into ICP–MS for online single-cell analysis. The important parameters including the chip design, the concentration of the paramagnetic salt solution, flow rate, cell density, and dwell time were optimized. Under the optimal conditions, a high sample throughput of 1390 cells min–1 was obtained. The established online analytical system was applied to study the uptake behaviors of MCF-7 cells for Zn2+ and ZnO nanoparticles (NPs) at a single-cell level. The single-cell analysis results indicate that MCF-7 cells displayed more remarkable heterogeneity when they were treated with ZnO NPs, and the uptake content of ZnO NPs by MCF-7 cells was less than that of Zn2+. Compared with other droplet microdevice-ICP–MS analysis systems, the developed system has the advantages of simple design and fabrication, no organic phase, a high throughput, and a low sample consumption (only 5 μL).