Direct detection of microRNA in liquid biopsies from single cancer spheroids

Exploring cancer heterogeneity is crucial for both understanding cancer and developing prognostic tools to monitor cancer progression during treatment through the liquid biopsy concept. Herein, a nanoparticle-based "dispersible electrodes" biosensor was used to detect ultra-low concentrations of microRNA-155 (miRNA-155) from a single breast cancer spheroid for the first time. The results from the sensor were comparable to the standard real-time polymerase chain reaction analysis, but in a much shorter detection time and without any sample purification or amplification. Owing to the unique ability of the sensor to measure biomarker expression from unaltered and undiluted cancer liquid biopsy from a single cancer spheroid, we then tracked dynamic changes in miRNA-155 expression in a single spheroid treated with the anti-cancer drug doxorubicin. The ability to track dynamic biomarker changes in a single cancer spheroid opens the door to understanding key biological processes such as response to treatment on the cellular and molecular levels, paving the way for adapting liquid biopsy insights to guide oncologists and more personalised treatment strategies.