神經科學(neuroscience)是個重要且值得深入研究的領域，從解釋單顆神經細胞如何工作，到神經網絡的連結性、學習和記憶的機制，和相關疾病的防治研究。利用在培養皿裡生長(或是培養在體外環境下)的簡單神經網絡，都可以進行簡單神經細胞的電生理研究。更進一步我們可以利用培養在微電極陣列上的更複雜的神經網路，來進行高階神經網絡的訊息傳遞研究，如認知和情感。

　　在平常散亂分佈的神經細胞培養中，本論文將提供一個模板，將神經細胞分佈在事先規劃好的網格上，並且使其生長出的軸足沿著規劃的路徑生長連結。並且在每個網格點上貼附的細胞數量，控制在一小群(四到五個神經元)。神經元網絡在研究上，把尺度縮小到一小群神經細胞間，觀察及探討小群神經元個體間訊號傳遞的機制。

　　在此模板的製作上，首先利用本實驗室所具有的新穎SU-8厚膜光阻製程技術(UV-LIGA)來製作其模具，再翻模成所需的PDMS 模板。在模具製作上，先針對出不同大小及形狀的光罩開孔，利用繞射原理模擬計算出，所對應的曝光顯影後的結構的形狀及高度。以模擬的結果，決定出模具結構所需要光罩開孔的形狀及大小。其結構的設計會影響到翻模的問題、occupancy rate、最後細胞落入的個數。本論文會針對其問題進行一些討論。最後將PDMS 模板運用於神經細胞培養，來驗證結構的設計是否能符合神經細胞培養的條件，以及是否達到一小群成熟神經元網絡的形成。

[1] R. Pizzi, G. Cino, F. Gelain, D. Rossetti, A. Vescovi, “Learning in human
neural networks on microelectrode arrays”, BioSystems, vol. 88, p1-15, 2007
[2] Chao-Yi Dong, Jisoon Lim, Yoonkey Nam, Kwang-Hyun Cho, “Systematic
analysis of synchronized oscillatory neuronal networks reveals an enrichment for
coupled direct and indirect feedback motifs”, bioinformatics, vol. 25, no. 13,
p1680-1685, 2009
[3] Andrew F.M. Johnstone, Guenter W. Gross, Dieter G. Weiss, Olaf H.-U.
Schroeder, Alexandra Gramowski, Timothy J. Shafer, “Microelectrode arrays:
A physiologically based neurotoxicity testing platform for the 21stcentury”, NeuroToxicology, vol. 31, p331–350, 2010
[4] J. Pine, “Recording Action Potentials from Cultured Neurons with Extracellular Microcircuit Electrodes”, Journal of Neuroscience Methods, Vol.2, p19-31, 1980.
[5] Conrad D. James, Andrew J.H. Spence, Natalie M. Dowell-Mesfin, Rift J. Hussain, Karen L. Smith, Harold G. Craighead, Michael S. Isaaxson, William Shain, and James N. Turner, “Extracellular Recording from Patterned Neuronal Ntworks Using Planar Microelectrode Arrays”, IEEE Transaction on Biomedical Engineering, Vol.51, No.9, 2004.
[6] Sang Beom Jun, Matthew R. Hynd, Natalie Dowell-Mesfin, Karen L. Smith, James N. Turner, William Shain, Sung June Kim, “Low-density neuronal networks cultured using patterned poly-l-lysine on microelectrode arrays”, Journal of Neuroscience Methods, vol.160, p317-326, 2007.
[7] Milan Mrksich, Laura E. Dike, Joe Tien, Donald E. Ingber, George M. Whitesides,
“Using Microcontact Printing to Pattern the Attachment of Mammalian Cells to
Self-Assembled Monolayers of Alkanethiolates on Transparent Films of Gold and Silver”
[8] L. Kam, W. Shain, J. N. Turner, R. Bizios, ”Axonal outgrowth of hippocampal neurons on micro-scale networks of polylysine-conjugated laminin”, Biomaterials, vol. 22, p1049-1054, 2001
[9] A.K. Vogt, G.J. Brewer, A. Offenh□usser, “Connectivity Patterns in Neuronal Networks of Experimentally Defined Geometry”, Tissue Engineering, vol.11(11-12), p1757-1767, 2005.
[10] Van N. Truskett, Michael P.C. Watts, “Trends in imprint lithography for
biological applications”, TRENDS in Biotechnology, vol.24, no.7, 2006
[11] Anna K. Magnusson, Pontus Linderholm, Christian Vieider, Mats Ulfendahl,
Anna Erlandsson, “Surface Protein Patterns Govern Morphology, Proliferation,
and Expression of Cellular Markers but Have No Effect on Physiological
Properties of Cortical Precursor Cells”, Journal of Neuroscience Research,
vol.86, p2363–2375, 2008
[12] Emmanuel Delamarche, Christian Donzel, Fadhil S. Kamounah, Heiko Wolf,
Matthias Geissler, Richard Stutz, Patrick Schmidt-Winkel, Bruno Michel,
Hans Joぴrg Mathieu, Kjeld Schaumburg, “Microcontact Printing Using Poly(dimethylsiloxane) Stamps Hydrophilized by Poly(ethylene oxide) Silanes”, Langmuir, vol. 19, p8749-8758, 2003
[13] Gregory S. Ferguson, le Manoj K. Chaudhury, lb Hans A. Biebuyck,
George M. W hitesides, “Monolayers on Disordered Substrates: Self- Assembly of Alkyltrichlorosilanes on Surface-Modified Polyethylene and Poly( dimethylsiloxane)”, Macromolecules, vol. 26, p5870-5875, 1993
[14] John C. Changa, Gregory J. Brewerb, Bruce C. Wheeler, “A modified
microstamping technique enhances polylysine transfer and neuronal cell
patterning”, Biomaterials, vol. 24, p2863–2870, 2003
[15] Conrad D. James, Andrew J. H. Spence, Natalie M. Dowell-Mesfin, Rifat J.
Hussain, Karen L. Smith, Harold G. Craighead. “Extracellular Recordings From
Patterned Neuronal Networks Using Planar Microelectrode Arrays”, IEEE
TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol. 51, No. 9,
p1640-1647, 2004.
[16] Michael P. Maher, Jerome Pine, John Wright, Yu-Chong Tai, “The neurochip: a
new multielectrode device for stimulating and recording from cultured neurons”,
Journal of Neuroscience Methods, Vol. 87, p45–56, 1999
[17] J. Erickson, A. Tooker, Y.C. Tai, J. Pine, “Caged neuron MEA: A system for
long-term investigation of cultured neural network connectivity”, Journal of
Neuroscience Methods, vol.175, p1–16, 2008
[18] G. Zeck and P. Fromherz, “Noninvasive neuroelectronic interfacing with synaptically connected snail neurons immobilized on a semiconductor chip”, Proc. Natl. Acad. Sci. USA 98 (18), p10457–10462, 2001
[19] Alon Greenbauma, Sarit Anavab, Amir Ayali, Mark Sheina, Moshe David-Pura, Eshel Ben-Jacobc, Yael Haneina, “One-to-one neuron–electrode interfacing”, Journal of Neuroscience Methods, vol.182, p219–224, 2009
[20] H Huang and C Fu, “Different fabrication methods of out-of-plane polymer
hollow needle arrays and their variations”, J. Micromech. Microeng., vol.17, p393–402, 2007
[21]H Huang, W Yang, T Wang, T Chuang and C Fu, “3D high aspect ratio microstructures fabricated by one step UV lithography”, J. Micromech. Microeng., vol.17, p291–296, 2007