Technical Lead – James Sturm, Princeton University
This project provides the overarching model and technology for the Princeton PS-OC. The project uses the “microhabitat patch” (MPH) technology developed on a microfluidic chip platform at Princeton to allow the culturing of cells in highly confining interconnected and asymmetric microenvironments.
A tumor micro-environment is highly stressful. We believe that these increased stress levels actually enhance the evolution and adaption of cancer cells. Cancer cells not only thrive under conditions of low oxygen, but also acquire resistance to most chemotherapies they are in contact with.
In traditional cancer studies, environmental stress is usually homogeneous in space and static in time. In order to better study cancer cell evolution under stress, we have designed 2- and 3-D devices which allow administration of a number of chemical and mechanical stressors in a variety of complex spatial patterns and under a wide temporal range. The micro-devices are designed using a system of pumps and valves which allow locally-specific and precisely-controlled administration of chemical stressors.
Experiments using on-chip dynamic stress control for studying cancer cell evolution
In ongoing experiments we develop a microfluidic chip with embedded dynamic traps to generate dynamic heterogeneous microenvironments. Based on polydimethylsiloxane (PDMS) flexible diaphragms, these traps are able to enclose and shield cancer cells or to expose them to external environmental stress. Digital controls for each trap determine the nutrition, antibiotics, CO2/O2 conditions, and temperatures to which the trapped cells are exposed. The conditions can be varied in intensity and duration in each trap independently. The chip can also output cells for trap-specific sequencing and other biological analysis.