Localized chemical release from an artificial synapse chip.

A device that releases chemical compounds in small volumes and at multiple, well defined locations would be a powerful tool for clinical therapeutics and biological research. Many biomedical devices such as neurotransmitter-based prostheses or drug delivery devices require precise release of chemical compounds. Additionally, the ability to control chemical gradients will have applications in basic research such as studies of cell microenvironments, stem cell niches, metaplasia, or chemotaxis. We present such a device with repeatable delivery of chemical compounds at multiple locations on a chip surface. Using electroosmosis to drive flow through microfluidic channels, we pulse minute quantities of a bradykinin solution through four 5-microm apertures onto PC12 cells and show stimulation of individual cells using a Ca(2+)-sensitive fluorescent dye. We also present basic computational results with experimental verification of both fluid ejection and fluid withdrawal by imaging pH changes by using a fluorescent dye. This "artificial synapse chip" is a prototype neural interface that introduces a new paradigm for neural stimulation, with eventual application in treating macular degeneration and other neurological disorders.

[1]  Howard H. Hu,et al.  Numerical simulation of electroosmotic flow. , 1998, Analytical chemistry.

[2]  A. Spradling,et al.  Stem cells find their niche , 2001, Nature.

[3]  Henry R. Bourne,et al.  Cell polarity: A chemical compass , 2002, Nature.

[4]  David M. Bloom,et al.  Ion Channels and Lipid Bilayer Membranes Under High Potentials Using Microfabricated Apertures , 2002 .

[5]  T. Yanagida,et al.  Single-Molecule Analysis of Chemotactic Signaling in Dictyostelium Cells , 2001, Science.

[6]  Elise C. Kohn,et al.  The microenvironment of the tumour–host interface , 2001, Nature.

[7]  M. Monje,et al.  Irradiation induces neural precursor-cell dysfunction , 2002, Nature Medicine.

[8]  W. Mark Saltzman,et al.  Transplantation of brain cells assembled around a programmable synthetic microenvironment , 2001, Nature Biotechnology.

[9]  J. Arevalo,et al.  Glaucoma after Pars Plana Vitrectomy and Silicone Oil Injection for Complicated Retinal Detachments , 2003 .

[10]  L. Greene,et al.  Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[11]  L. Loew,et al.  An image-based model of calcium waves in differentiated neuroblastoma cells. , 2000, Biophysical journal.

[12]  T. Takano,et al.  Beyond the role of glutamate as a neurotransmitter , 2002, Nature Reviews Neuroscience.

[13]  M. Poo,et al.  The cell biology of neuronal navigation , 2001, Nature Cell Biology.

[14]  M. Cima,et al.  A controlled-release microchip , 1999, Nature.

[15]  Brian Vastag Future eye implants focus on neurotransmitters. , 2002, JAMA.

[16]  S. DeVries,et al.  Bipolar Cells Use Kainate and AMPA Receptors to Filter Visual Information into Separate Channels , 2000, Neuron.

[17]  J. Weiland,et al.  Intraocular retinal prosthesis , 2006, IEEE Engineering in Medicine and Biology Magazine.

[18]  R. Masland The fundamental plan of the retina , 2001, Nature Neuroscience.

[19]  D. Burgreen,et al.  Efficiency of Pumping and Power Generation in Ultrafine Electrokinetic Systems , 1965 .

[20]  Weihong Tan,et al.  Probing intracellular dynamics in living cells with near-field optics , 1999, Journal of Neuroscience Methods.

[21]  David Tosh,et al.  How cells change their phenotype , 2002, Nature Reviews Molecular Cell Biology.

[22]  Haifan Lin The stem-cell niche theory: lessons from flies , 2002, Nature Reviews Genetics.