The number of circulating tumor cells (CTCs) in blood is strongly correlated with the progress of metastatic cancer and can be used as a diagnostic tool to improve staging, therapy-monitor and recurrence detection. Current FDA-approved device to detect CTCs is based on immunostaining with limitations in sensitivity range, high-cost per analysis and lack of viable cell isolation. Other techniques are emerging, though none of them reached clinical validation. Here, we present an unexplored label-free method exploiting the abnormal metabolic behaviour of cancer cells (extracellular acidification, lactate production, Warburg effect). We demonstrate a single-cell analysis technique to measure the secretion of lactic acid and acidification of extracellular medium of individual, living tumor cells compartmentalized in microfluidically prepared monodisperse, pL droplets and implement the method in a high-throughput semi-automated prototype, able to detect spiked tumor cells in blood. We finally show promising data from blood sample of metastatic cancer patients.
