Photochemistry

The interface between living cells and synthetic chip platforms is a critical one wherein the cellular phenotype must be preserved to generate useful signals. While some cell types retain tissue-specific features on a flat (2-D) surface, it has become increasingly apparent that a 3-D physical environment will be required for others. We have established two related methods for creating living cell arrays that are encapsulated within a poly(ethylene glycol)-based hydrogel to create a local 3-D microenvironment. First, ‘photopatterning' selectively crosslinks hydrogel microstructures containing living cells with 100 micron feature size (Liu et al, 2002; Albrecht et al, 2005) . Second, ‘electropatterning' utilizes dielectrophoretic forces to position cells within a prepolymer solution prior to crosslinking, forming cell patterns with micron resolution ( Albrecht et al, 2004, Albrecht et al, 2005) . We further combine these methods to obtain hierarchical control of cell positioning over length scales ranging from microns to centimeters as seen in the Figure below. This level of microenvironmental control should enable the fabrication of next-generation cellular microarrays in which robust 3-D cultures of cells are presented with appropriate physical and chemical cues and, consequently, report on cellular responses that resemble in vivo behavior.

Panel a demonstrates electropatterned green cells immobilized in a 500 micron domain, surrounded by a field of randomly-organized red cells. Panel b illustrates a heterogeneous mixture of two cell types in mixed aggregates within a hydrogel construct. (Albrecht et al, 2005)