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Microfluidic system for multi-analyte monitoring of metabolites in 3D cell cultures

December 2021
University of Freiburg, Freiburg, Germany
Three-dimensional cell cultures with patient-derived stem cells are essential in vitro models for more efficient and personalised cancer therapy. Currently, culture conditions and metabolite concentrations, especially hypoxia, in microphysiological systems are often not continuous and accessible in situ. However, understanding and standardizing the cellular microenvironment is key to successful in vitro models. Here, we developed a microfluidic organ-on-chip platform for matrix-based, heterogeneous 3D cultures with fully integrated electrochemical chemosensor and biosensor arrays for the energy metabolites oxygen, lactate, and glucose. Advanced microstructures enable easy cell matrix integration, compartmentalization and microfluidic access. Patient-derived, triple-negative breast cancer stem cells develop into tumor organoids in a heterogeneous spheroid culture on the chip. The system thereby enables on-chip multi-analyte metabolite monitoring under dynamic conditions in a matrix-based culture for more than a week and comprehensive control of culture conditions, including hypoxia, and simultaneous verification by integrated sensors. Responses to changes in culture conditions and exposure to anticancer drugs, such as metabolite consumption and production rates, could be quantitatively recorded in real-time. The approach highlights the importance of continuous in situ metabolite monitoring in 3D cell cultures with respect to standardization and control of culture conditions and drug screening in cancer research. Overall, the results highlight the potential of microsensors in organ-on-chip systems for a successful application, e.g. in personalised medicine.
Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures
Andreas Weltin
#1321
Added on: 12-22-2021
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