Microwell array-based opto-electrochemical detections revealing co-adaptation of rheological properties and oxygen metabolism in budding yeast

Microdevices composed of microwell arrays integrating nanoelectrodes (OptoElecWell) were developed to achieve dual high-resolution optical and electrochemical detections on single Saccharomyces cerevisiae budding yeast cells. Each array consists in 1.6 x 105 microwells of 8 {micro}m diameter and 5 {micro}m height, with a platinum nanoring electrode for in-situ electrochemistry, all integrated on a transparent thin wafer for further high-resolution live-cell imaging. After optimizing the filling rate, 32% of cells were effectively trapped within microwells. This allowed to analyse S. cerevisiae metabolisms associated with basal respiration while simultaneously measuring optically other cellular parameters. In this study, we focused on the impact of glucose concentration on respiration and intracellular rheology. We found that while oxygen uptake rate decreased with increasing glucose concentration, diffusion of tracer nanoparticles increased. Our OptoElecWell based respiration methodology provided similar results compared to the commercial gold-standard Seahorse XF analyser, while using 20 times lesser biological samples, paving the way to achieve single cell metabolomics. In addition, it facilitates an optical route to monitor the contents within single cells. The proposed device, in combination with the dual detection analysis, opens up new avenues for measuring cellular metabolism, and relating it to various cellular physiological and rheological indicators at single cell level.