LOW VOLTAGE, MEMS-BASED REFLECTIVE AND REFRACTIVE OPTICAL SCANNERS FOR ENDOSCOPIC BIOMEDICAL IMAGING By ANKUR JAIN A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2006 UMI Number: 3228738 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion.
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Box 1346 Ann Arbor, MI 48106-1346 Copyright 2006 by Ankur Jain To my parents, Ranjan and Poonam, to my brother Prateek, and to my fiancée Kavitha for their constant love, unwavering support, confidence and encouragement. ACKNOWLEDGMENTS I would like to thank my advisor, Dr. Huikai Xie, for the constant support and guidance he has given me over the past few years. I first met Huikai in August 2002, and subsequently joined his research group as a PhD student in the fall semester.
I am grateful for all the insight he has provided, and am thankful to him for introducing me to the areas of MEMS and endoscopic biomedical imaging. I have personally gained technical expertise, as well as professional know-how through my interactions with him, and | will forever be indebted to him for mentoring me towards becoming a better microsystems technology engineer. The research presented in this dissertation was also painstakingly reviewed by other members of my PhD committee, Dr. Toshikazu Nishida, Dr.
Ramakant Srivastava, and Dr. William Ditto, and for that I am grateful. I have enjoyed many conversations with Dr. Nishida, both personally and professionally.
Working as a graduate teaching assistant for Dr. Srivastava was a pleasure, and I am grateful for our personal friendship. Ditto has provided me with unique insights related to the biomedical application aspect of this project. I want to acknowledge technical and personal discussions with Dr.
Mark Sheplak and Dr. David Arnold, as their advice helped improve my research work and their pleasant company at MEMS conferences is always welcome. Further appreciation goes out to Dr. Peter Zory for his valuable friendship, for always being a mentor, and for his indispensable lessons on how to maintain a good research notebook.
IV The Biophotonics and Microsystems Lab (BML) located in 136 Larsen Hall was home to this project, and I am indebted to my BML group members. Special thanks go out to Hongwei Qu for teaching me the ropes in the cleanroom, and to Shane Todd for helping me with electrothermal modeling. Hongwei has always beena pillar of support within BML, and I enjoyed working with him on various projects. Shane worked with me on various micromirror projects, and I have benefited greatly from our professional interactions and personal friendship.
I would like to acknowledge support from Anthony Kopa, both personally and also for using my 2-D micromirror for imaging purposes. Other BML members who aided me during the course of my research include Deyou Fang, Maojiao He, Mi Huang, Mingliang Wang, Ben Caswell and the newcomers Kemiao “Alex” Jia and Lei Wu. Alex and Lei have proven to be worthy successors for my project, and I will value their camaraderie. All BML members work great as a team, and I have so many good memories about the multilingual jokes told in the lab, and the parties and sports that we all participated in.
BML is just part of the much bigger microsystems group at the University of Florida, known as the Interdisciplinary Microsystems Group (IMG). I am grateful to all IMG members for their support-group-like environment and technical expertise. In particular, I would like to thank my colleagues Venkat Chandrasekaran, Stephen Horowitz, Anurag Kasyap, Chris Bahr, David Martin, Ryan Holman, Erin Patrick, Israel Boniche, Janhavi Agashe, Sheetal Shetye, Jian “Jackie Chan” Liu, Yawei Li, Vijay Chandrasekharan, Lee Hunt, Tai-An Chen, Karthik Kadirvel, Robert Taylor, Brandon Bertolucci, Champak Das and Zheng Xia, to name a few. Venkat introduced me to the world of wire-bonding, while Dave, Ryan and Chris kept our IMG server running 24/7.
Thanks go to Anurag for helping me with the vibrometer, to Erin for help with the PCB milling machine, and to Israel and Janhavi for AutoCAD assistance. I thank Brandon and the Ultimate Frisbee gang for relentlessly organizing sporting events that helped to upkeep the morale of IMG. Finally, credit is due to all other IMG members for general technical assistance, and for maintaining a lively work environment in the office, lab and even inside the cleanrooms. This work would not be complete without help from our external collaborators.
Yingtian Pan and Zhenguo Wang at the State University of New York at Stony Brook for validating the use of my micromirrors for endoscopic optical coherence tomographic (OCT) imaging. I am grateful that they invited me to visit their lab so that I could witness OCT imaging using my endoscopically-packaged micromirrors. Two- photon excitation fluorescence imaging and second harmonic generation nonlinear optical imaging experiments using my micromirrors were demonstrated in collaboration with Dr. Min Gu and Ling Fu at the Swinburne University of Technology, Australia.
I thank Ling for the many hours she has put into this project, and for her personal friendship. I would also like to thank Dr. Michael Bass and Te- Yuan Chung from CREOL, University of Central Florida, Orlando, for letting me use their thermal imager for my research. The MEMS device fabrication was done using the facilities provided by the University of Florida Nanofabrication Facilities (UFNF) and by the UF Microfabritech center.
Therefore, I appreciate the support provided by the UFNF staff Al Ogden, Ivan Kravchenko, Bill Lewis and the UF Microfabritech staff. Scanning electron microscopy (SEM) and white light profilometry were performed using the equipment at the Major vi Analytical Instrumentation Center (MAIC) at the University of Florida. I wish to thank Dr. Luisa Dempere, Wayne Acree, Andrew Gerger and Brad Willenberg of the MAIC for their assistance.
Special thanks go to Tanya Riedhammer who helped me with the Variable-Pressure SEM for imaging my photoresist microlenses. I also want to acknowledge our administrative assistant, Joyce White, for her help and support. Finally, I am eternally grateful to my family and friends for their constant support and encouragement. I would like to thank my parents, Ranjan and Poonam, and my brother, Prateek, for their confidence in me, for their endless love and support, and for keeping me debt-free all through graduate school.
I want to thank my fiancée Kavitha, for all her love, support, advice, and also for all the car rides to school she provided that ultimately helped my research. Thanks are due to my friends Anuradha Ventakesan and Boman Irani who kept me going throughout graduate school. I also want to acknowledge my friends Kanak Behari Agarwal and Himanshu Kaul whose learned advice helped me through the “mid-PhD crisis”. The MEMS-based endoscopic biomedical imaging project at the University of Florida has been supported by the National Science Foundation Biophotonics Program through award number BES-0423557, and by the Florida Photonics Center for Excellence.
vil TABLE OF CONTENTS page ACKNOWLEDGMENTS 21188 6 ‹‹.1 Limitations of Conventional Cancer Diagnosis Methodologles.2 Emerging Optical Coherence Tomography .3 MEMS-based OCT”. HH HH TH gu ng TH HH ng nàn 4 1.4 MEMS-based OCM.c tk HT HH HH TH TH HH HH rệt 6 1. 9 IS luin9 on. 10 2 OPTICAL BIOIMAGING METHODOLOGIES.1 Optical Coherence Tomographyy.1 OCT System Ïesig1n.- cv nn*nn vn TH TH TH kế re 13 2.2 Key Imaging ParaInef€fS.- ác HH1 2 HH ng ng HH khu 17 2.3 Internal Organ OCT [Imaging.
- c cnn nh ng Hết 20 2.2 Optical Coherence MICTOSCODY. Gv HS ng HT TH ng HE ky nhy 24 2.1 Bench-Top OCM na ---::Öö+1Ã1ÈÐ555.2 MEMS-based OCM 1n.3 Non Linear Optical [maging. eee ee ceecceneeeeeeeneeeseceeeeeeenseseeeeeeeeseeeeeeaees 29 2.1 Two-Photon Excitation Fluorescence [maging.2 Second Harmonic Generation Imaging .3 Nonlinear Optical Imaging System Design .4 Endoscopic Nonlinear Optical Imaging .5 MEMS-based Endoscopic Nonlinear Optical Imaging. ELECTROTHERMAL MICROMIRRORS AND ENDOSCOPIC OCT ñ 6n.
Q11 21119 1121119111911 vn kg HT k tệp 40 3.2 Electrothermal Actuation and ÏÖeSIữn.3 Microfabrication PTOC€SS. HH SH TH TH HH tyu 46 3.4 Bimorph Actuation and Theoretical AnaÌyS1S.1 One-Dimensional Electrothermal MICTOIITTOF.2 Two-dimensional Electrothermal MICrOTmITTOY.3 Laser scanning €Xp€TIINII.6 Micromirror PackaØ1ng. cà v19 v11 TH 1g 19k ng TH TK k tyu 63 3.7 MEMS-based Endoscopic OCT [maging .- --cc c cv vn nay65 3.1 MEMS-based OCT System Ïesign. ác 1k1 SH HH Hy re65 3.2 OCT Imaging ReSuÏfS.
ác c1 2v v1 TH vn T1 ng nh nhờ 71 3. c1 ng TH ki Ti ni ng in gi ngà gà Tà kg vết 73 LARGE-VERTICAL-DISPLACEMENT MICROMIRRORS AND NON- LINEAR OPTICAL TMAGTNG. ác HH Ho HH HH nhe75 4.1 LVD Microactuator €SIET. uc vn 1 119 111 11 0 11x HH g1 g1 1 1E hy 77 VD 0.
ác tt HH HH TH ng ng TH HH HH Hrrkt 80 4.2 Equivalent Circuit Model.2 Frequency response/resonant SCanning.- SG 119v KT HH HH HH Hà 92 4.1 Mirror Design oo.1 Bi-directional SCannInng .ccccc cv HH HH ớt 94 4.2 Two-dimensional dynamic scannIng.3 Vertical displacement motIOT.4 MEMS Mirror-based Nonlinear EndOSCODV. uc vn nhe 102 4.1 Nonlinear Optical Imaging SYSf€Tm.- c1 2211112112 111 11 11111 x11 1xx xe yệt 104 AS SUImAYV. HH ng TK ng kg ng TH tk ki tr 107 MICROLENS SCANNERS AND OPTICAL CONFOCAL MICROSCOPY.1 LVD Microlens S€afiIY.- - c1 SH n9 HH kg HH ty 109 5.1 Microlens Scanner ÏeSIgØ1.-- n vn SH vn 1 chờ 111 5.2 Fabricated Microlens ŠSCanTI€T.2 Millimeter-Range LVD Microlens Scanner .-c kh nh key 119 5.1 Millimeter-Range Scanner ÏeSiỹ1.2 Fabrication PTOC€SS. án ng HH HH ng nh ghi ng Hy 121 5.3 LVD Microlens Packag1ng.
cv 1c 1n SH TH TH TH HH HH ky 152 ho an. A aa sa ha. 134 6 CONCLUSIONS AND FUTURE WORK.1 Research Effort Accomplishments. 158 APPENDIX A NON-CMOS, WAFER LEVEL FABRICATION PROCESS.
140 B ARTICLES GENERATED BY THIS RESEARCH EFEFORT.- 145 LIST OF REFERENCES.- S119 HS g1 TT TT HH Hàng HH th nhu 148 BIOGRAPHICAL SKETCH. 2 L1 1S HH HT TH HH Hết 162 LIST OF TABLES Table page 3-1 Thermomechanical properties of some possible bimorph materials at room /3/185E1011 2202277. acc 45 4-1 Parameters used by the equivalent circuit model of the 1-D LVD micromirror.84 4-2 Actuator characteristics for the 2-D LVD micromirrotr.cceceeeereeeeeeneeeteeees 96 5-1 Microlens charaCf€TISEICS. HH HH ng nghi nh ng nh 113 5-2 Estimated microlens parameters for various desired focal lengths.
126 XI LIST OF FIGURES Figure page 1-1 Schematic of a MEMS-based OCT/OCM system. (a) System block diagram. (b) Optical delay line that uses the LVD micromirror as a reference mirrors for transverse and axial scanning. (c) OCT endoscope that uses a 1-D or 2-D LVD micromurror for transverse scanning of tissue.
(d) OCM endoscope that uses a LVD microlens for axial scanning Of †ISSU€. HH H12 1 11k ghe 7 2-1 OCT schermatiC. Q0 0n ng ng nnnnnn TT n TT ng tà tà tà tà tà tà cà nh tu tu ok vu 13 2-2 OCT tissue scanning modes. ác LH HT HH1 TT ng ng H1 1 Hy ky 15 2-3 Comparison between histology, ultrasound and OCT images of biological tissue.
(a) HE-stained histology, (b) 50-MHz ultrasound, and (c) OCT image of a ¡1 `. 16 2-4 Comparison between ultrasound and OCT images of human coronary artery plaques. (a) Jn vivo OCT image with axial imaging resolution of 13 um.