Methods and systems to simultaneously monitor cancer cell viability and collective migration in three dimensions

A method of screening a test compound for anti-metastatic properties, the method comprising:

• adding a tumor spheroid-collagen solution to a central matrix channel of a microfluidic culture chip;
• polymerizing biomimetic collagen within the tumor spheroid-collagen solution to form a biomimetic collagen matrix;
• adding a first amount of a test compound media to an upper injection port of the microfluidic culture chip;
• adding a second amount of the test compound media to a lower injection port of the microfluidic culture chip wherein the second amount is less than the first amount;
• staining the microfluidic culture chip with a fluorescence compound, wherein the staining creates labeled tumor spheroids;
• and
• performing Z-stack confocal imaging using a laser scanning microscope to form Z-stacks and to assess anti-gravitational migration of the labeled tumor spheroids within the collagen matrix thereby screening the test compound for anti-metastatic properties.

A system for screening a compound for anti-metastatic properties against renal cell carcinoma (RCC), the system comprising:

• a microfluidic culture chip, wherein the microfluidic culture chip comprises at least 2 sites per chip, each site containing injection ports for a central matrix channel and parallel media channels flanking the sites, and posts with gaps in between on each side of the matrix channel separating the central matrix channel and parallel media channels;
• a biomimetic collagen-RCC tumor spheroid matrix in the central matrix channel of the microfluidic culture chip, wherein collagen within the collagen-RCC tumor spheroid matrix is polymerized and comprises 4-20 tumor spheroids/μL;
• and
• an upper injection port and a lower injection port, each comprising a test compound media with a pressure gradient between the upper injection port and the lower injection port.