Modeling and measuring metabolism of cancer spheroids in hanging drops
Use of integrated enzymatic glucose biosensors to conduct measurements within hanging-drops hosting carcinoma spheroids and a physics-based model to describe analyte consumption and transport.
As 3D in vitro tissue models become more pervasive, their built-in nutrient, metabolite, compound, and waste gradients need to be measured. Using hanging-drop-integrated enzymatic glucose biosensors, we conducted electrochemical current measurements within hanging-drop compartments hosting colorectal carcinoma spheroids as reported in a recent article in the journal Microsystems & Nanoenineering (N. Rousset, R. Sandoval, M. Modena, A. Hierlemann, P. Misun, "Modeling and measuring glucose diffusion and consumption by colorectal cancer spheroids in hanging drops using integrated biosensors", Microsystems & Nanoengineering 2022, 8, 14). We developed a physics-based mathematical model of analyte consumption and transport, considering (1) diffusion and enzymatic conversion of glucose to form hydrogen peroxide (H2O2) by the glucose-oxidase-based hydrogel functionalization of our biosensors at the microscale; (2) H2O2 oxidation at the electrode surface, leading to amperometric H2O2 readout; (3) glucose diffusion and glucose consumption by cancer cells in a spherical tissue model at the microscale; (4) glucose and H2O2 transport in our hangingdrop compartments at the macroscale; and (5) solvent evaporation, leading to glucose and H2O2 upconcentration. Our model relates the measured currents to the glucose concentrations generating the currents. The low limit of detection of our biosensors (0.4 ± 0.1 μM), combined with our current-fitting method, enabled us to reveal glucose dynamics within the hanging-drop system. Precise glucose consumption measurements will help to translate in vitro 3D tissue model results to in vivo.
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