Long distance 2D(A) or 3D(B) co-culture devices for secretion based communication. A) Cells are divided by a valve that can separate the two cells and control the secretion of cytokines(A, top)95. To make the cells communicate, the valve is opened so that secreted proteins and conditioned media can be shared between the populations(A, middle). This device could then be coupled with electrode sensors to monitor cell behavior. A schematic of the chip is shown to demonstrate compartments don’t mix when the valve is turned on(A, bottom) B) 3D cell co-culture using hydrogel culture. Cells are loaded in basement membrane extract(BME) gel to compartmentalize the cell104. First, cell A(red) is introduced, then cell B(green) is introduced adjacent to cell A, but without mixing. The middle channel is filled with media to feed the cells. Cytokines, growth factors, and other secreted proteins can then pass through from one cell population to the next by diffusing through the gel. This also allows for cells to migrate through from one gel to the next. 3A. Reproduced from Ref 95 with permission from the Royal Society of Chemistry. 3B. Reproduced from Ref 104 with permission from the Royal Society of Chemistry.