Microfluidic cell culture array

Microfabrication technology enables the engineering of cell culture environments in ways not achievable using current methods. It has long been postulated that the cellular microenvironment is crucial for nearly all living functions, such as differentiation, organogenesis, physiological function, cell-cell communication, and signal transduction and regulation. However, researchers have not been able to reliably control cell culture parameters in an efficient in vitro platform. Crucial aspects of cell culture control include: nutrient mass transport, cell-cell contacts, rapid or long term modulation of culture conditions, and maintenance of steady state conditions.

The primary goal of this research is to investigate methods to approximate the in vivo cell growth environment in order to better reproduce physiological functions in an experimental platform. Currently, the major thrust of this research involves controlling the mass transport mechanisms in microfabricated cell culture units. As a model, cells in the body are typically supplied with nutrients from a constant flow of nutrients through the microvasculature. Most tissue cells themselves are actually isolated from this mass flow, and receive nutrient/waste transport via diffusion through capillary walls. This situation was approximated using a microfluidic design. By designing the fluidic resistance through the unit, it was possible to isolate cells in a “tissue space” isolated from convective mass transport (see figure). This allows the localization of cells in culture as well as insulating them from fluidic stresses such as shear, which are normally not experienced in vivo (with the exception of endothelial cells). A byproduct of this design is that since the cells are isolated in the growth regions, the fluid flow through the array is well behaved and predictable, allowing the analysis of multiple cell growth conditions in parallel.

By using microfluidic design to tailor the cell culture environment, it is hoped that a more accurate in vitro experimental platform can be developed for biomedical research. Currently, we are investigating the biological effects of altering cell culture mass transport parameters in various cell lines. This line of research will continue to expand into questions on the effects of cell-cell communication, and tissue specific responses in primary cells.