COMBINED OPTICAL STIMULATION AND ELECTRICAL RECORDING IN IN VIVO NEUROMODULATION BY JING WANG B. Sc., NANJING UNIVERSITY, 2004 M. Eng., NANJING UNIVERSITY, 2006 Sc. M., BROWN UNIVERSITY, 2008 SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN THE DEPARTMENT OF PHYSICS AT BROWN UNIVERSITY PROVIDENCE, RHODE ISLAND MAY 2012 i @ Copyright 2012 by Jing Wang ii This dissertation by Jing Wang is accepted in its present form by the Department of Physics as satisfying the dissertation requirement for the degree of Doctor of Philosophy Date _____________ _________________________ Arto V. Nurmikko, Advisor Recommended to the Graduate Council Date _____________ _________________________ Rebecca D. Burwell, Reader Date _____________ _________________________ James M. Valles, Jr, Reader Approved by the Graduate Council Date _____________ _________________________ Peter M. Weber, Dean of the Graduate School iii VITA Jing Wang was born in Jiangxi, China on October 2nd, 1983. She received her B. Sc. and M. Eng. in Material Science and Engineering from Nanjing University in 2004 and 2006. She subsequently started her graduated study at Brown University and received her Sc. M. in Physics in May 2008. Her scientific publications include: PEER REVIEWED PUBLICATIONS Jing Wang, Fabien Wagner, David A. Borton, Jiayi Zhang, Ilker Ozden, Rebecca D. Burwell, Arto V. Nurmikko, Rick van Wagenen, Ilka Diester, and Karl Deisseroth, “Integrated Device for Combined Optical Neuromodulation and Electrical Recording for Chronic In Vivo Applications”. Journal of Neural Engineering, 9: 016001, (2012). Jing Wang, Ilker Ozden, Mohamed Diagne, Fabien Wagner, David Borton, Benjamin Brush, Naubahar Agha, Rebecca Burwell, David Sheinberg, Ilka Diester, Karl Deisseroth, Arto Nurmikko “Approaches to Optical Neuromodulation from Rodents to Non-Human Primates by Integrated Optoelectronic Devices”, Invited paper, Conf Proc IEEE Eng Med Biol Soc., (2011). Jing Wang, David A. Borton, Jiayi Zhang, Rebecca D. Burwell, and Arto V. Nurmikko, “A Neurophotonic Device for Stimulation and Recording of Neural Microcircuits”, Conf Proc IEEE Eng Med Biol Soc. 2935-8 (2010). Qiang Zhang, Cuong Dang, Hayato Urabe, Jing Wang, Shouheng Sun, and Arto Nurmikko “Large ordered arrays of single photon sources based on II-VI semiconductor colloidal quantum dot”, Optics Express 16: 19592-19599 (2008). Jing Wang, Zheng-Bin Gu, Ming-Hui Lu, Di Wu, Chang-Sheng Yuan, Shan-Tao Zhang, Yan-Feng Chen, Shi-Ning Zhu, and Yong-Yuan Zhu, “Giant magnetoresistance in transition-metal-doped ZnO films”, Applied Physics Letter 88: 252110 (2006). Zheng-Bin Gu, Minghui Lu, Jing Wang, Di Wu, Shan-Tao Zhang, Xiang-Kang Meng, Yong-Yuan Zhu, Shi-Ning Zhu, and Yan-Feng Chen, Xiao-Qing Pan. “Structure, iv optical, and magnetic properties of sputtered Mn and N-codoped ZnO films”, Applied Physics Letters 88: 082111 (2006). Zheng-Bin Gu, Chang-Sheng Yuan, Ming-Hui Lu, Jing Wang, Di, Wu, Shan-Tao Zhang, Shi-Ning Zhu, Yong-Yuan Zhu, and Yan-Feng Chen, “Magnetic and transport properties of (Mn,Co)-codoped ZnO films prepared by radio-frequency magnetron cosputtering”, Journal of Applied Physics 98: 053908 (2005). v ACKNOWLEDGMENTS I would like to truly thank my advisor, Professor Arto Nurmikko, whose support, guidance and encouragement have been invaluable. His enthusiasm and dedication in research have always been inspiring to me. My sincere gratitude must go to Dr. İlker Özden, who has become my best friend and whose accompanyment has been the highlight of my graduate life. He has been an excellent scientist, great mentor and humorous friend. I would like to thank Professor Rebecca Burwell for her guidance and encouragement in research. Her vibrant energy, generosity and patience have always been unforgettable to me. I would like to thank the members of the Nurmikko lab: Dr. Cuong Dang, Dr. Joonhee Lee, Dr. Dave Borton, Fabien Wagner, Dr. Ming Yin, Dr. Juan Aceros, Sunmee Park, Farah Laiwalla, Andy Blaeser, Ben Brush, Yao Lu, Naubahar Agha, Travis May, Jacob Komar, Rizwan Huq, Kwangdong Roh, Chris Heelan, Christopher Bull, Dr. Qiang Zhang, Dr. Yoon-Kyu Song. Dr. Tolga Atay, Dr. Jiayi Zhang, Dr. Hayato Urabe, Dr. Heng Xu, Dr. Yanqiu Li, Dr. Hyunjin Kim, and all the friends at Brown who have been great professional and companions. I would like to thank all the members of Burwell lab and Connors lab: Dr. Scott Cruikshank, Dr. Tim Zolnik, Dr. Sharon Furtak, Kristin Kerr, Dr. Jonathan Ho, Devon Poeta and Fang-Chi Yang for their generous help and discussion. I would like to thank all the members of Sheinberg lab and Donoghue lab: Valerie Yorgan, Dr. Ji Dai, Dr. Dan Brooks and Dr. Carlos Vargas-Irwin for being inspiring and supportive all the time. I would like to thank Dr. Harper and the Brown IACUC, Tony McCormick, Micheal Jibitsky, Sandra Van Wagoner, Barbara Dailey and John Lee for their excellent technical and administrative support. Thank you everyone here at Brown! vi To my family who are the source of joy and strength within me. 献给爸爸妈妈和王佳！ vii Table of Contents CHAPTER 1 INTRODUCTION ..................................................................................... 1 CHAPTER 2 DEVICE CONCEPT OF THE SINGLE COAXIAL OPTRODE ............ 6 2. 1 The fabrication of the single coaxial optrode ................................................... 7 2. 2 Electrical and optical characterization of the optrode ..................................... 11 2. 3 Stimulation and recording functionality of the optrode .................................. 18 2. 4 In-situ fluorescence detection using the single coaxial optrode ..................... 23 2. 5 Summary ......................................................................................................... 26 CHAPTER 3 LIGHT DELIVERY AND LIGHT INDUCED EFFECTS IN BRAIN TISSUE 27 3. 1 Optical Properties of Neural Tissue ................................................................ 27 3. 2 Monte Carlo Simulation of Light in Brain Tissue .......................................... 33 3. 3 Summary ......................................................................................................... 47 CHAPTER 4 RECORDING FUNCTIONALITY OF THE COAXIAL OPTRODE ... 48 4. 1 Electromagnetic field generated by the neuronal activity............................... 49 4. 2 Sensitivity field of electrode. .......................................................................... 54 4. 3 Modeling the recording sensitivity field of optrode using finite element (FE) method 58 4. 4 Discussion ....................................................................................................... 69 CHAPTER 5 NEURONAL CORRELATES OF SPATIAL INFORMATION RECORDED USING THE MEA DEVICES ................................................................... 70 viii 5. 1 Introduction ..................................................................................................... 71 5. 2 Behavioral Training ........................................................................................ 76 5. 3 Surgery ............................................................................................................ 77 5. 4 Data Acquisition ............................................................................................. 78 5. 5 Result and Discussion ..................................................................................... 79 CHAPTER 6 INTEGRATED DEVICE FOR COMBINED OPTICAL NEURO- MODULATION AND ELECTRICAL RECORDING FOR CHRONIC IN VIVO APPLICATIONS .............................................................................................................. 83 6. 1 Introduction ..................................................................................................... 83 6. 2 Materials and Methods .................................................................................... 86 6. 3 Results ............................................................................................................. 95 6. 4 Summary ....................................................................................................... 113 CHAPTER 7 CONCLUSION AND FUTURE WORKS ........................................... 115 SUPPLEMENTARY Chapter: Large Scale Ordered Structures of Single Photon Sources Based on II-VI Semiconductor Colloidal Quantum Dots ............................................... 119 8. 1 Introduction ................................................................................................... 120 8. 2 Methods and Results: QD array fabrication and characterization ................ 123 8. 3 Summary ....................................................................................................... 134 APPENDIX ..................................................................................................................... 136 BIBLIOGRAPHY ........................................................................................................... 143 ix List of Figures Figure 2.1 Concept of the single coaxial optrode device. ............................................................................... 8 Figure 2.2 Photograph of the illumination pattern from a coaxial single optrode device, ............................. 13 Figure 2.3 (a) An electric double layer forms at the tip, which is a capacitor effectively ............................ 15 Figure 2.4 An example of in vivo optrode recording, measured from an anesthetized rat. ........................ 19 Figure 2.5 Peri-stimulus time histograms (bottom in