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Surface Stress Detection and Mechanism Study with Microcantilever Based Sensor for Biomolecular Monolayers Yue Zhao Iowa State University

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Surface Stress Detection and Mechanism Study with Microcantilever Based Sensor for Biomolecular Monolayers Yue Zhao Iowa State University Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2014 Surface stress detection and mechanism study with microcantilever based sensor for biomolecular monolayers Yue Zhao Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Mechanical Engineering Commons Recommended Citation Zhao, Yue, "Surface stress detection and mechanism study with microcantilever based sensor for biomolecular monolayers" (2014). Graduate Theses and Dissertations. 13690. https://lib.dr.iastate.edu/etd/13690 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Surface stress detection and mechanism study with microcantilever based sensor for biomolecular monolayers by Yue Zhao A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Mechanical Engineering Program of Study Committee: Pranav Shrotriya, Major Professor Sriram Sundararjan Shankar Subramaniam Marit Nilsen-Hamilton Monica Lamm Iowa State University Ames, Iowa 2014 Copyright ©Yue Zhao, 2014. All rights reserved. ii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ....................................................................................... iv ABSTRACT………………………………. .............................................................. v CHAPTER 1 OVERVIEW ................................................................................... 1 CHAPTER 2 LITERATURE REVIEW ............................................................... 3 Micro-Cantilever Based Sensor ........................................................................... 3 Differential Interferometer and Sensor Configurations ....................................... 5 DNA Hybridization Induced Cantilever Deflection ............................................ 8 Mechanism Exploration and Simulation Approaches.......................................... 10 CHAPTER 3 DETECTION OF CANTILEVERDEFLECTION DUE TO MALACHITE GREEN/APTAMER BINDING........................................................ 15 Abstract ................................................................................................................ 15 Introduction ......................................................................................................... 15 Materials and Methods ......................................................................................... 17 Experimental Procedures ..................................................................................... 20 Results .................................................................................................................. 21 Discussions .......................................................................................................... 23 Conclusion ........................................................................................................... 27 CHAPTER 4. MECHANISM STUDY ON CANTILEVER DEFLECTION DUE TO ALKANETHIOL SELF-ASSEMBLED MONOLAYER IMMOBILIZATION ON CANTILEVER SURFACE ................................................................................. 29 Abstract ................................................................................................................ 29 Introduction ......................................................................................................... 30 Surface Stress Measurement ................................................................................ 33 Experimental Results ........................................................................................... 36 Overall Energy of the System due to SAM adsorption........................................ 39 Energy Models Associated with Alkanethiol SAM layer .................................... 40 Energy Models Associated with Gold Substrate ................................................. 41 Simulation Models and Surface Stress Predictions ............................................. 43 Modeling Results and Discussions ...................................................................... 46 Comparison of Numerical Predictions with Experimental Reports ..................... 51 Conclusions ......................................................................................................... 52 CHAPTER 5. CANTILEVER DEFLECTION ASSOCIATED WITH HYBRIDIZATION OF MONOMOLECULAR DNA FILM ................................... 54 Abstract ................................................................................................................ 54 iii Introduction ......................................................................................................... 55 Theoretical Model ................................................................................................ 59 Initial DNA Ensembles ........................................................................................ 64 Cantilever Bending Computation ........................................................................ 66 Simulation Results and Discussions .................................................................... 68 Comparison of Numerical Prediction with Experimental Reports ...................... 74 Conclusions ......................................................................................................... 77 Acknowledgements .............................................................................................. 78 CHAPTER 6. INFLUENCES MOLECULAR CONFIGURATION AND CONFORMATION ON CANTILEVER DEFLECTION ASSOCIATED WITH DNA HYBRIDIZATION ............................................................................... 79 Introduction ......................................................................................................... 79 Experimental Observations .................................................................................. 81 Distributions and Configurations of Hybridized DNA ........................................ 84 Energy Models and Cantilever Bending Predictions ........................................... 87 Model Results ...................................................................................................... 93 Comparison of Numerical Prediction with Experimental Reports ...................... 99 Conclusions ......................................................................................................... 102 CHAPTER 7. CONCLUSIONS ................................................................................ 104 BIBLIOGRAPHY ...................................................................................................... 108 iv ACKNOWLEDGEMENTS First and foremost, I would like to thank my advisor Professor Pranav Shrotriya for his guidance, help and patience during the journey of this project. Without his support, the work could not have been accomplished. I would also like to express my gratitude and appreciation to all my committee members: Professor Sriram Sundararajan, Professor Shankar Subramaniam, Professor Marit Nilsen-Hamilton and Professor Monica Lamm for serving on my POS committee and providing me with all the valuable inputs for my research. My thanks extend to all professors and colleagues in the project, particularly to Professor Marit Nilsen-Hamilton and Professor Baskar Ganapathysubramanian, Dr. Lee Bendickson, Kyungho Kang, Lijie Zhai, Tianjiao Wang, and Zhichen Zhu for many useful discussions, technical and otherwise. I would also like to thank all the lab colleagues, former and present: Kyungho Kang, Dinesh Karyana-Sundaram, Janice Marquardt, Xiao Ma, Zhuoru Wu, Nazita Taghavi, Zhichen Zhu, Zhao Wang, Manan Sevak, and Norma Granados with whom I share and discuss a lot of professional and personal stories. I would like to thank my family for their support and love. Finally, my most sincere thanks go to my parents, Minghui Pan and Yongjiu Zhao who carried me through these years. v ABSTRACT Specific aims of this study are to investigate the mechanism that governs the surface stress generation with hybridization of single stranded DNA (ssDNA) molecules immobilized on micro-cantilevers. The hybridization of DNA on cantilever surfaces leads to configurational change, charge redistribution, and steric hindrance between neighboring hybridized molecules, which result in surface stress change and measureable cantilever deformation. Differential interferometer with two adjacent micro-cantilevers (a sensing/reference pair) was investigated to measure the cantilever deformation. The sensing principle is that binding/reaction of specific chemical or biological species on the sensing cantilever transduces to mechanical deformation. The differential bending of the sensing cantilever respect to the reference cantilever ensures that measured response is insensitive to environmental disturbances. In order to improve the sensitivity for sensing system, new approach of immobilization was utilized to enhance the deformation of the cantilever surface. Immobilization of receptor molecules was modified to use ssDNA with thiol-groups on both 3’ and 5’ ends; therefore both ends of the ssDNA molecules were immobilized to the gold surface and cause stronger surface interactions. To confirm the improvement of
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