Flow characterization of a microfluidic device to selectively and reliably apply reagents to a cellular network.

A three-dimensional microfluidic device has been successfully fabricated and the flow streams characterized for eventual use in studying communication in an in vitro network of nerve cells. The microfluidic system is composed of two layers of channels: a lower layer for the delivery of pharmacological solutions and an upper layer of channels used to direct the flow of the pharmacological solution streams and perfuse the cells with media and nutrients. Flow profiles have been characterized with computational fluid dynamics simulations, confocal fluorescence microscopy, and carbon-fiber amperometry, which have been used to map changes in flow profiles at different bulk flow rates. Ultimately, the microfluidic system and incorporated cell network will show how networked neurons adapt, compensate, and recover after being exposed to different chemical compounds.

[1]  Stephen P. DeWeerth,et al.  Microfabrication technologies for a coupled three-dimensional microelectrode, microfluidic array , 2007 .

[2]  C. Culbertson,et al.  Chemical analysis of single mammalian cells with microfluidics. Strategies for culturing, sorting, trapping, and lysing cells and separating their contents on chips. , 2007, Analytical chemistry.

[3]  Eberhard Bodenschatz,et al.  Flow photolysis for spatiotemporal stimulation of single cells. , 2007, Analytical chemistry.

[4]  Claire Wyart,et al.  Constrained synaptic connectivity in functional mammalian neuronal networks grown on patterned surfaces , 2002, Journal of Neuroscience Methods.

[5]  Shaoqun Zeng,et al.  Long-term recording on multi-electrode array reveals degraded inhibitory connection in neuronal network development. , 2007, Biosensors & bioelectronics.

[6]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[7]  S. Böcker-Meffert,et al.  Spatially resolved non-invasive chemical stimulation for modulation of signalling in reconstructed neuronal networks , 2006, Journal of The Royal Society Interface.

[8]  Miles A Whittington,et al.  Fast network oscillations induced by potassium transients in the rat hippocampus in vitro , 2002, The Journal of physiology.

[9]  Jason B Shear,et al.  Parallel chemical dosing of subcellular targets. , 2006, Analytical chemistry.

[10]  A. Folch,et al.  Biology on a chip: microfabrication for studying the behavior of cultured cells. , 2003, Critical reviews in biomedical engineering.

[11]  Matsuhiko Nishizawa,et al.  Localized chemical stimulation of cellular micropatterns using a porous membrane-based culture substrate , 2005 .

[12]  A. Offenhäusser,et al.  Patterning chemical stimulation of reconstructed neuronal networks. , 2006, Analytica chimica acta.

[13]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[14]  Nancy L Allbritton,et al.  CRITICAL REVIEW www.rsc.org/loc | Lab on a Chip Analysis of single mammalian cells on-chip , 2006 .

[15]  Andreas Offenhäusser,et al.  Synaptic plasticity in micropatterned neuronal networks. , 2005, Biomaterials.

[16]  Yoonkey Nam,et al.  Active 3-D microscaffold system with fluid perfusion for culturing in vitro neuronal networks. , 2007, Lab on a chip.

[17]  D. Hoyer,et al.  Involvement of the Sst 1 Somatostatin Receptor Subtype in the Intrahypothalamic Neuronal Network Regulating Growth Hormone Secretion : An in Vitro and in Vivo Antisense Study , 2000 .

[18]  M Tedesco,et al.  In vitro cortical neuronal networks as a new high-sensitive system for biosensing applications. , 2005, Biosensors & bioelectronics.

[19]  E. Pothos,et al.  D2-Like Dopamine Autoreceptor Activation Reduces Quantal Size in PC12 Cells , 1998, The Journal of Neuroscience.

[20]  T. Park,et al.  Integration of Cell Culture and Microfabrication Technology , 2003, Biotechnology progress.