HIGH THROUGHPUT ANALYSIS OF SINGLE CELLS IN RESPONSE TO MECHANICAL CUES USING DROPLET-BASED MICROFLUIDICS

Abstract

Single cell study is a powerful analytical tool in revealing details that are otherwise masked in an ensemble-averaged bulk analysis. The current single cell analysis techniques either lack of high throughput capability or cell-matrix interaction; yet, both of the factors are critical for attaining data with better physiological relevance. Herein, an integrated droplet-based microfluidics with a continuous flow detection system was developed to tackle the current challenges. The novelty of this work lies in the utilisation of gelatine microspheres as cell carriers to provide adherent cells with both cell-matrix interaction and manoeuvrability. With this platform, (1)Morphological signatures (nuclear size, cell volume, surface area, and F-actin network) of more than 20,000 cells were studied, and (2)Activities of single-cell secreted metalloproteinases integral to cancer progression (MMP2/MMP3/MMP9/ADAM8) were analysed. The developed single cell analysis platform may serve as a robust tool in understanding mechanoresponse and/or drug resistance testing at single cell resolution.