Automation and High Throughput Technologies
Multidrug resistance arises when a small population of cells in a tumor undergo changes in cellular phenotype that allow them to evade a particular treatment. We are developing a novel 3D paper-based culture screening platform that can stratify cells within tumor-like structures based on either environmental or phenotypic differences. Unlike other 3D culture platforms, we are able to rapidly separate (within seconds) discrete cell populations based on the location.
Our platform involves stacking cell- or extracellular matrix (ECM)-laden paper scaffolds together to create a 3D tissue-like structure, which models the tumor microenvironment with defined gradients of oxygen, waste, and nutrients. The stacks are disassembled by peeling the paper scaffolds apart to isolate each discrete sub-population for downstream analyses of cell viability, protein and transcript levels, or drug metabolism. Our system is also highly customizable by: i) altering the size, number, or shape of available seeding areas by wax printing seeding boundaries onto each scaffold; ii) manipulating gradients by changing seeded cell density, stack thickness, or limiting exchange with culture medium; or iii) enabling either monoculture and co-culture setups, which allows the user to simulate a wide variety of in vivo conditions based on the research of interest.