Principal Investigator Joel Voldman
Project Website http://www-mtl.mit.edu/researchgroups/mems/docs/2007/BioChempage39.pdf
The stem-cell microenvironment is influenced by several factors including cell-media, cell-cell, and cell-matrix interactions. Although conventional cell-culture techniques have been successful, they offer poor control of the cellular microenvironment. To enhance traditional techniques, we have designed a microscale system to perform massively parallel cell culture on a chip.
To control cell-matrix and cell-cell interactions, we use dielectrophoresis (DEP), which uses non-uniform AC electric fields to position cells on or between electrodes. We present a novel microfabricated DEP trap designed to pattern large arrays of single cells. We have experimentally validated the trap using polystyrene beads and cells, showing excellent agreement with our model predictions. In addition, by placing interdigitated electrodes between the traps, we can prevent cells from sticking to the substrate outside the traps.
To control cell-media interactions, we have developed a microfluidic device for culturing adherent cells over a logarithmic range of flow rates. The device controls flow rates via a network of geometrically-set fluidic resistances connected to a syringe-pump drive. We use microfluidic perfusion to explore the effects of continuous flow on the soluble microenvironment. We cultured mESCs in standard serum-containing media across a 2000° -- range of flow rates. On day 1, colony areas were roughly constant along the axis of perfusion, implying negligible nutrient depletion. However, by day 3, we observed a significant decrease in colony size along the axis of perfusion at mid-range flow rates. At higher flow rates, colonies were uniformly large along the axis of perfusion, implying that nutrient depletion was not significant above certain flow rates.
This microfabricated system will serve as an enabling technology that can be used to control the cellular microenvironment in precise and unique ways, allowing us to perform novel cell biology experiments at the microscale.