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Precisely targeted delivery of cells and biomolecules within microchannels using aqueous two-phase systems

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Abstract

Laminar and pulsatile flow of aqueous solutions in microfluidic channels can be useful for controlled delivery of cells and molecules. Dispersion effects resulting from diffusion and convective disturbances, however, result in reagent delivery profiles becoming blurred over the length of the channels. This issue is addressed partially by using oil-in-water phase systems. However, there are limitations in terms of the biocompatibility of these systems for adherent cell culture. Here we present a fully biocompatible aqueous two-phase flow system that can be used to pattern cells within simple microfluidic channel designs, as well as to deliver biochemical treatments to cells according to discrete boundaries. We demonstrate that aqueous two-phase systems are capable of precisely delivering cells as laminar patterns, or as islands by way of forced droplet formation. We also demonstrate that these systems can be used to precisely control chemical delivery to preformed monolayers of cells growing within channels. Treatments containing trypsin were localized more reliably using aqueous two-phase delivery than using conventional delivery in aqueous medium.

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Acknowledgements

The authors would like to thank Dr. Tommaso Bersano-Begey for designing the Braille computer interface. The authors would also like to thank NSF (CMMI 0700232 and DBI 0852802) and MEST NRF (WCU-R322008000200540) for funding as well as NIH (TEAM Tissue Engineering and Regeneration Training Grant NIDCR DE007057) for a postdoctoral fellowship to JPF.

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Correspondence to Shuichi Takayama.

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Frampton, J.P., Lai, D., Sriram, H. et al. Precisely targeted delivery of cells and biomolecules within microchannels using aqueous two-phase systems. Biomed Microdevices 13, 1043–1051 (2011). https://doi.org/10.1007/s10544-011-9574-y

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