"Rapid spatial and temporal controlled signal delivery over large cell culture areas"

Jules J. VanDersarl: Alexander M. Xu and Nicholas A. Melosh; Lab Chip, 08/01/11.

Additional Authors: Alexander M. Xu and Nicholas A. Melosh


Controlled chemical delivery in microfluidiccellculture devices often relies on slowly evolving diffusive gradients, as the spatial and temporal control provided by fluid flow results in significantcell-perturbation. In this paper we introduce a microfluidic device architecture that allows for rapid spatial and temporal soluble signal delivery over largecellculture areas without fluid flow over thecells. In these devices thecellculture well is divided from a microfluidicchannellocated directly underneath the chamber by a nanoporousmembrane. This configuration requires chemical signals in the microchannel to only diffuse through the thinmembraneinto largecellculture area, rather than diffuse in from the sides. The spatial chemical pattern within the microfluidicchannelwas rapidly transferred to thecellculture area with good fidelity through diffusion. The cellular temporalresponse toa step-function signal showed thatdyereached thecellculture surface within 45 s, and achieved a static concentration in under 6 min. Chemical pulses of less than one minute were possible by temporally alternating the signal within the microfluidicchannel, enabling rapid flow-free chemical microenvironment control for largecellculture areas.