Drug treatment of breast cancer tumoroids in an automated microfluidic system
A recent paper from Cromwell et al. in Burow lab in Tulane university modeling multifunctional profile of breast cancer tumoroids to investigate the effect of relative anti-cancer drugs on tumoroid phenotype and cell metabolism function. Authors initially cultured cells isolated from patients in conventional cell culture dishes and later in a low attachment U-shaped wells. They used magnetic nanoparticles to coat tumors into “flowchip wells”. The wells are connected to other wells with different reagents through microchannels, flow of reagents is controlled by pneumatic pumps.
Results
They concluded that exposed tumors by drugs had different phenotypes like lower average intensities of stainings and cellular areas showing less cell viability. Moreover, Lactate secretion increased during drug treatment which showed the cells notably shifted their metabolic pathway and tumors underwent anaerobic glycolysis. The result of energy metabolism was measured by ATP based luminance assay.
Digestible of the paper Cromwell, E. F., et al. (2022). “Multifunctional profiling of triple-negative breast cancer patient-derived tumoroids for disease modeling.” SLAS Discovery 27(3): 191-200. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.
Method
The authors used Pu⋅MA System and flowchips, tumoroids were formed from primary cells isolated from a patient-derived tumor, TU-BcX-4IC
– Tumoroid incorporation: The tumoroids were transferred with NanoShuttle to the wells
– Perfusion/refreshing method: Reagent exchanges were done automatically through the microfluidic channels using pre-loaded automation protocols
– On-chip read-outs: On-chip monitoring, Live-dead staining, End-point microscopy
– Off-chip read-outs: Immuno-Histo chemistry
Strong points :
+ Highly heterogenous phenotype of breast cancer primary cell.
+ automated sampling assay
+ Different drug treatment with different mechanisms of action.
Nothing is perfect, some improvement points:
– Lack of physiological tumor microenvironment
– Still labor-intensive preparation of tumoroids
Conclusion and outlook
This tumor on a chip platform is not only suitable for oncology applications but also can be used for liver toxicology, functional cardio-assays, intestinal inflammation, and other important areas.
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