Cancer cells rely heavily on aerobic glycolysis and exhibit high levels of glucose uptake and lactate release via a phenomenon commonly referred to as the Warburg effect. However, despite the emerging importance of altered metabolism in cancer, there are currently no tools to measure glucose uptake and lactate release on a single cell level in a real-time, multiplexed manner. While bulk measurements only provide average cellular values, single-cell techniques allow a means to measure cell-to-cell variance and population heterogeneity, which is particularly important in cancer diagnosis. We present here a multimodal droplet microfluidic method that allows the fast and quantitative determination of lactate release and radiolabeled glucose (FDG) uptake in many single cells. Using passive forces, droplet encapsulated cells are positioned in an array above a scintillator plate. The single-cell lactate release rate is determined from the increase in droplet fluorescence as the lactate is enzymatically converted to a fluorescent product (see Fig). Intracellular radiotracers are imaged by capturing individual flashes of visible light that are produced as individual positrons (emitted during radioactive decay) traverse the scintillator plate below the droplet array, in a process known as radioluminescence microscopy. We are thus able to capture quantitative fluorescence and radioluminescence data on a single cell level. We demonstrate that it is possible to simultaneously measure the lactate release and FDG concentration from the exact same cell, thus providing us with the ability to correlate these two important metabolic biomarkers. This platform has enabled precise and quantitative measurements of metabolic activity in single cancer cells that can yield novel information about the factors influencing cell-to-cell metabolic heterogeneity and assist in the identification of unusual subpopulations or rare malignant cancer cells.

Droplet microfluidic platform for the determination of single-cell lactate release and [18F] fluorodeoxyglucose uptake

253rd National Meeting (2017)

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