Imaging of fast-moving single cells with adaptive single pixel detection

点击翻译按钮获取中文摘要

Development of an untargeted technique capable of rapidly detecting cell populations at a single cell level is a sought after next-generation technology that faces various challenges.It is thus our vision that a mass spectrometric system that facilitates unlabelled, multi-omic analysis can be developed with the following design criteria: 1. the biochemical coverage to match the power of low throughput methods (~500 proteins, 200 metabolites and 300 lipid species)2. analysis of up to 10,000 mammalian cells (or other single-cell organisms)/second We have thus proposed a new design addressing these challenges by using cell-containing liquid droplets produced by a flow focusing mechanism, and the in-droplet chemical digestion is followed by picosecond resonant infrared laser evaporation prior to mass spectrometric analysis of the produced gaseous organic ions. A major research problem to be solved is the accurate evaporation of the incoming cells/organisms which is expected to travel at a speed of at least 1m/s and the content of the droplets needs to be verified to avoid 'false positives', hence spatial information in real-time is needed.An ultrafast imaging set-up capable of capturing the spatial information of the moving cells at a rate that is at least on the order of 10^4 frames per second will thus be constructed to facilitate the succeeding mass spectrometric analysis and to provide additional biophysical information at a single cell level. Instead of costly array detectors that generally have limited availability and differing performance characteristics across the application spectrum, single pixel detection (SPD) offers a robust alternative solution for the problem at hand.