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Fundamentals of Bacteria-Based Molecular Communication for Internet of Bio-Nanothings FUNDAMENTALS OF BACTERIA-BASED MOLECULAR COMMUNICATION FOR INTERNET OF BIO-NANOTHINGS A Dissertation Presented to The Academic Faculty By Bige Deniz Unluturk In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Electrical and Computer Engineering Georgia Institute of Technology August 2020 Copyright c Bige Deniz Unluturk 2020 FUNDAMENTALS OF BACTERIA-BASED MOLECULAR COMMUNICATION FOR INTERNET OF BIO-NANOTHINGS Approved by: Dr. Ian F Akyildiz, Advisor School of Electrical and Computer Dr. Chuanyi Ji Engineering School of Electrical and Computer Georgia Institute of Technology Engineering Georgia Institute of Technology Dr. A Fatih Sarioglu School of Electrical and Computer Dr. Massimiliano Pierobon Engineering Department of Computer Science Georgia Institute of Technology and Engineering University of Nebraska-Lincoln Dr. Raghupathy Sivakumar School of Electrical and Computer Date Approved: June 18, 2020 Engineering Georgia Institute of Technology I dedicate this thesis, To the loving memory of my father Ali Turgut Unluturk, who planted seeds of curiosity in my mind, and love of science in my soul. To my mother Hatice Unluturk, to my aunt Ayse Savus, to my husband Bircan Bugdayci, for their endless love, support and encouragement. ACKNOWLEDGEMENTS I would like to express my heartiest thanks to Prof. Ian F. Akyildiz, who has been not only my Ph.D. advisor, but also a mentor and a second father for me. He has been there for me during the most difficult times of my life with his invaluable help and endless tolerance, as well as during the most joyful times of my life with his genuine support and encouragement. He is my north star in academic life, showing me the right way whenever I get lost and always there shining brightly as a role model, the epitome of the success arising from the combination of talent and hard-work. He is the star we all shoot for albeit won’t be able to reach. The light of his gifted mind guided me on my research path and his passion for his job inspired me to work harder. He opened up the doors for me to pursue an incredible career I always dreamed of, the one that is changing my life completely, which I’m fully aware that would never realize without his guidance. For this and for countless lessons he taught me both in academic and personal life, I will be forever grateful to him. I would also like to thank my committee members Dr. Raghupathy Sivakumar, Dr. Chuanyi Ji, Dr. Fatih Sarioglu, and Dr. Massimiliano Pierobon who kindly agreed to serve in my Ph.D. Defense Committee. Their invaluable feedback and continuous encouragement have helped me to take the final leap towards the completion of my Ph.D. journey. My sincere and warm thanks go also to the whole Broadband Wireless Networking Laboratory family, to past and current members, Ph.D. students, Post-Docs, visitors, with whom I shared amazing memories throughout my years in lab and forged lifelong friend- ships. The United Nations in the lab opened up my mind to the world and I will never forget these amazing people with unique personalities. Also, my sincere thanks go to all the people I worked with in the projects MoNaCo and INTRABIONETS. I would like to acknowledge the support of National Science Foundation through these projects, which made the completion of this thesis possible. I’m also grateful to Dr. Sasitharan Balasubramaniam for hosting me in Finland and iv Dr. Ilangko Balasingham for hosting me in Norway during my research stays and their contribution to my growth as a researcher. I am very fortunate to be born to a very affectionate and supportive family who values education and knowledge above anything else. They ignited my interest in academia and research, and cleared my path to pursue my dreams. I want to thank my family, my mom Hatice Unluturk, my father Ali Turgut Unluturk, my aunt Ayse Savus for always putting me first in their life. Their love, caring and support are the source of my happiness. Words can not express how grateful I am for all their sacrifices that they have made for me throughout the years. I express my most special thanks to Bircan Bugdayci, my beloved husband who stood by me in every step of the way. Understanding me the best as a PhD himself, Bircan has been my rock, my best friend, and the reason I could see the end of this long and difficult journey. He always motivated me to get out of my comfort zone and gave me full support to follow my dreams even if it meant for us to live in different continents for years. Even from the other side of the ocean, he always knows how to cheer me up, how to calm me down, and how to make me feel loved. He is my source of joy and happiness. My daily conversations with him on our research topics was a staple in my PhD journey. It was a way to organize my thoughts, and exchange ideas with this fellow smart engineer. He greatly contributed to my intellectual growth as a person and as a researcher. He is the best companion in life I could ever ask for with his unconditional love, endless support, brilliant mind, witty sense of humour and positivity. I am forever grateful for his love and support which gives me the strength and the purpose to go through life every day. Lastly, I would like to thank my friends who made the world a better place for me. I would like to express my thanks to my friends and roommates Cansu Tetik and Ayse Selin Cakmak, my good friends Can Temel, Beren Semiz, Gozde Tutuncuoglu, Emre Gursoy, Nil Gurel, Sezen Yucel, Ozan Bicen, Sinan Hersek, Emre Yilmaz, Alper Yildirim, Ulkuhan Guler, Tevhide Ahmadov-Ozkaya. v TABLE OF CONTENTS Acknowledgments . iv List of Tables . xi List of Figures . xii Chapter 1: Introduction . 1 1.1 Background . 3 1.2 Research Objectives . 6 1.3 Organization of the Thesis . 9 Chapter 2: Previous Work . 10 2.1 Internet of NanoThings . 10 2.2 Molecular Communication . 12 2.3 Synthetic Biology . 14 Chapter 3: Genetically Engineered Bacteria Based BioTransceiver . 16 3.1 Motivation and Related Work . 16 3.2 Biochemical Model for Biological Circuits . 19 3.2.1 Chemical Kinetic Model of Gene Regulation . 20 3.2.2 Reaction-Rate Equation Model of Gene Regulation . 22 vi 3.3 Analysis of Regulated Gene Expression . 24 3.3.1 Analog Interpretation of Biological Circuits . 27 3.3.2 Digital Interpretation of Biological Circuits . 27 3.4 Interconnecting Basic Biological Circuit Units . 30 3.4.1 Single Input Single Output Configuration . 30 3.4.2 Multiple Input Single Output Configuration . 30 3.4.3 Single Input Multiple Output Configuration . 31 3.5 Biotransceiver Architecture . 31 3.6 Biological Circuit Design for a Biotransceiver . 33 3.6.1 Transmitter . 33 3.6.2 Sensor . 37 3.6.3 Processor . 37 3.6.4 Receiver . 40 3.7 Numerical Results . 42 3.7.1 Transmitter . 43 3.7.2 Receiver . 44 3.8 Conclusion . 45 Chapter 4: Travelling Wave Channel Models and Impact of Social Behavior for Bacterial Chemotaxis Channel . 47 4.1 Motivation and Related Work . 47 4.2 Traveling Wave Model of Bacterial Chemotaxis . 50 4.2.1 General Bacterial Chemotaxis Model . 50 4.2.2 Traveling Wave Solutions for Strong Attractant Diffusion . 52 vii 4.2.3 Delay and Attenuation . 54 4.3 Data Rate in Bacterial Nanonetworks . 55 4.4 Social Behavior Analysis for Bacterial Channel . 56 4.4.1 Impact of Cooperation on Chemotaxis . 58 4.4.2 Impact of Competition on Chemotaxis . 60 4.4.3 The Impact of Joint Cooperation and Competition . 62 4.5 Numerical Results . 63 4.5.1 Impact of Cooperation . 64 4.5.2 Impact of Competition . 67 4.5.3 Impact of Joint Cooperation and Competition . 69 4.6 Conclusion . 70 Chapter 5: Distributed Modulation Schemes for Bacterial Chemotaxis Channel 72 5.1 Motivations and Related Work . 72 5.2 Related Work . 75 5.3 System Model . 77 5.3.1 Transmission Model . 80 5.3.2 Propagation Model . 81 5.3.3 Reception Model . 87 5.4 Modulation Schemes . 90 5.4.1 Modulation with a Single Receiver . 90 5.4.2 Modulation with Multiple Receivers . 94 5.4.3 Achievable Rate . 98 viii 5.5 Performance Evaluation . 98 5.6 Conclusion . 101 Chapter 6: Microbiome-Gut-Brain Axis as an Infrastructure for Internet of Bio-NanoThings . 104 6.1 Motivations and Related Work . 104 6.2 Analytical Methodology . 107 6.2.1 Physical Channel Models of Communications Through Enteric and Autonomic Nerves, and Muscle Activity . 109 6.2.2 Physical Channel Models of Communications Through the Gut Mi- crobial Community . 112 6.2.3 Communications from/to Nervous System to/from Gut Microbiome 115 6.3 Experimental Methodology . 116 6.3.1 Devices for Experimental Validation of MGBA Channel Models . 117 6.3.2 In vitro Experimental Platform based on Organ-on-a-chip Device . 118 6.3.3 In vivo Experimental Platform . 120 6.3.4 Integrated Network Probe Device Hub . 121 6.3.5 Neural and Molecular Gut Interfaces for the Integrated Network Probe Device . 125 6.4 Internet of Bio-NanoThings Communication Network Infrastructure . 128 6.4.1 Electrical Infrastructure Components . 129 6.4.2 Molecular Infrastructure Components . 130 6.4.3 Biomolecular Intrabody Network Simulator . 131 6.5 Conclusion . 132 Chapter 7: Internet of Bio-NanoThings for Early Detection of Infections . 134 ix 7.1 Motivationd and Related Work . 134 7.2 Development of Bio-NanoThings .
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