Modeling and measuring glucose consumption by cancer spheroids in hanging drops using integrated biosensors

Abstract

As 3D in vitro tissue models become more pervasive, their built-in concentration gradients increase biological relevance at the cost of analysis simplicity. Investigating metabolism heterogeneity resulting from these gradients requires invasive methods and time-consuming analyses. An alternative is measuring concentrations around microtissues with biosensors. Our hanging-drop-integrated enzymatic glucose biosensors electrochemically measure analyte concentration within hanging-drop compartments hosting single cancer spheroids. We developed an analytical model correlating measured sensor currents and glucose concentrations. Our biosensors' low limit of detection, combined with our current-fitting method, allowed us to infer glucose distributions within cancer spheroids, which will help to translate in vitro tissue results to in vivo.