A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies

There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements. This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids. Six patient-derived xenograft (PDX) tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures. To further demonstrate the potential for miniaturization and multiplexing, we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations. These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device. Overall, we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device. This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited, such as following the acquisition of biopsy specimens obtained by fine-needle aspiration. Researchers in the United States have developed a microfluidic system for culturing ovarian cancer organoids. The use of microfluidics makes it possible to create cultures starting from a smaller number of cells than existing approaches. The team compared the new approach to standard techniques and found that the resulting cultures were superior in terms of viability, proliferation, and phenotype expression. Building on this framework, the researchers developed an 8-chamber microfluidic device which could be seeded serially and then used for parallel testing of different drug concentrations. The device required with fewer than 100,000 cells, which is insufficient to test multiple conditions using existing approaches. The ability to work reliably with small cells numbers makes this microfluidic platform well-suited for personalized drug testing when the sample material is limited.