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Yan Colostate 0053A 10673.Pdf DISSERTATION A CMOS COMPATIBLE OPTICAL BIOSENSING SYSTEM BASED ON LOCAL EVANESCENT FIELD SHIFT MECHANISM Submitted by Rongjin Yan Department of Electrical and Computer Engineering In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Fall 2011 Doctoral Committee: Advisor: Kevin L. Lear David S. Dandy V Chandrasekar Branislav Notaros Copyright by Rongjin Yan 2011 All Rights Reserved ABSTRACT A CMOS COMPATIBLE OPTICAL BIOSENSING SYSTEM BASED ON LOCAL EVANESCENT FIELD SHIFT MECHANISM The need for label-free integrated optical biosensors has dramatically increased in recent years. Integrated optical biosensors have many advantages, including low-cost, and portability. They can be applied to many fields, including clinical diagnostics, food safety, environmental monitoring, and biosecurity applications. One of the most important applications is point-of-care diagnosis, which means the disease could be tested at or near the site of patient care rather than in a laboratory. We are exploring the issues of design, modeling and measurement of a novel chip-scale local evanescent array coupled (LEAC) biosensor, which is an ideal platform for point-of-care diagnosis. Until now, three generations of LEAC samples have been designed, fabricated and tested. The 1st generation of LEAC sensor without a buried detector array was characterized using a commercial near field scanning optical microscope (NSOM). The sample was polished and was end-fire light coupled using single mode fiber. The field shift mechanism in this proof-to- concept configuration without buried detector arrays has been validated with inorganic adlayers[1], photoresist[2] and different concentrations of CRP proteins[3]. Mode beating ii phenomena was predicted by the beam propagation method (BPM) and was observed in the NSOM measurement. A 2nd generation LEAC sensor with a buried detector array was fabricated using 0.35μm CMOS process at the Avogo Technologies Inc., Fort Collins, Colorado. Characterizations with both single layer patternings, including photoresist as well as BSA [4] and immunoassay complexes [5] were done with cooperative efforts from various research groups. The BPM method was used to study the LEAC sensor, and the simulation results demonstrated the sensitivity of the LEAC sensor is 16%/nm, which was proved to match well with the experimental data [6]. Different antigen/antibodies, including mouse IgG and Hspx (a tuberculosis reactive antigen), have been used to test the immunoassay ability of LEAC sensor [7]. Many useful data have been collected by using the 2nd generation LEAC chip. However, during the characterization of the Avago chips, some design problems were revealed, including incompatibility with microfluidic integration, restricted detection region, strong sidewall scattering and uncoupled light interference from the single mode fiber. To address these problems, the 3rd generation LEAC sensor chip with buried detector arrays was designed to allow real-time monitoring and compatibility with microfluidic channel integration. 3rd generation samples have been fabricated in the CSU cleanroom and the mesa detector structure has been replaced with the thin insulator detector structure to solve the problems encountered during the characterizations. PDMS microfluidic channels and a multichannel measurement system consisting of a probe card, a multiplexing/amplification circuit and a LabVIEW program have been implemented into the LEAC system. iii In recent years, outbreaks of fast spreading viral diseases, such as bird flu and H1N1, have drawn a lot of concern of the point-of-care virus detection techniques. To test the virus detection ability of LEAC sensor, 40nm and 200nm polystyrene nanoparticles were immobilized onto the waveguide, and the increased scattered light was collected. Sensitivities of 1%/particle and 0.04%/particle were observed for 200nm and 40nm particles respectively. References: [1] G. Yuan, M. Stephens, D. Dandy, and K. Lear, “Direct imaging of transient interference in a single-mode waveguide using near-field scanning optical microscopy,” IEEE Photonics Technology Letters, vol. 17, Nov. 2005, pp. 2382-2384. [2] G. Yuan, M. Stephens, D.S. Dandy, and K.L. Lear, “Local Evanescent, Array Coupled (LEAC) Biosensor Response to Low Index Adlayers,” Conference on Lasers and Electro- Optics (CLEO), CThL, 2006. [3] R. Yan, G. Yuan, M.D. Stephens, X. He, C.S. Henry, D.S. Dandy, and K.L. Lear, “Evanescent field response to immunoassay layer thickness on planar waveguides,” Applied Physics Letters, vol. 93, 2008, pp. 101110-3. [4] R. Yan, S.P. Mestas, G. Yuan, R. Safaisini, D.S. Dandy, and K.L. Lear, “Label-free silicon photonic biosensor system with integrated detector array,” Lab on a Chip, vol. 9, 2009, pp. 2163-2168. [5] R. Yan, L. Kingry, R. Slayden, and K. Lear, “Demonstration of the immunoassay using local evanescent array coupled biosensor,” SPIE Photonic West 2010, 2010, 7559-14. [6] R. Yan, S.P. Mestas, G. Yuan, R. Safaisini, and K.L. Lear, “Response of Local Evanescent Array-Coupled Biosensors to Organic Nanofilms,” Journal of Selected Topics in Quantum iv Electronics, vol. 15, 2009, pp. 1469-1477. [7] R. Yan, N.S. Lynn, L.C. Kingry, Z. Yi, R.A. Slayden, D.S. Dandy and K.L. Lear, “Waveguide biosensor with integrated detector array for tuberculosis testing,” Applied Physics Letters, vol. 98, 2010, pp. 013702. v ACKNOWLEDGEMENTS I would like to acknowledge the help of a number of individuals who have contributed to this project by providing either valuable suggestions or technical assistance. First, I would like to thank my advisor, Dr. Kevin Lear, for his guidance, understanding, patience, and most importantly, his friendship during my graduate studies at Colorado State University. His investigative and skeptical mind helped me through the whole research project. I would like to thank my committee members, Dr. David Dandy, Dr. V Chandrasekar, and Dr. Branislav Notaros for their valuable comments on my dissertation, especially to Dr. David Dandy for his supports and advices on the LEAC biosensor project. I would also like to thank my friends and colleagues at Colorado State University for their support. Last but not the least; I would like to thank my wife, Minda Le and my parents, for their support through my five years of Ph.D study. Without their support and encouragement, this thesis would definitely not be possible. Rongjin Yan vi TABLE OF CONTENTS Chapter 1 Introduction & motivation…………………………………………………...……...1 1.1 Introduction ………………………………………………………………………………..….1 1.2 Optical waveguide and light source………………………………………………………..….1 1.3 Integrated waveguide biosensing………………….…………………………………………..3 1.4 Research activities………………………………………………………………………….…5 1.4.1 Design…………………………………………………………………..…….……..5 1.4.2 Modeling…………………………………………………………………..………...6 1.4.3 Fabrication….…………………………………………………………………...…7 1.4.3 Measurements…………………………………………………………………...…9 1.5 Outline of the report…………………………………………………………………..…...…11 References…………………………………………………………………..…………….…...…12 Chapter 2 Optical waveguide basics………………….………………………....………..…...13 2.1 Overview of waveguide studies…………………………………………………….……..…13 2.2 Basic concept of optics and waveguides……………………………………………....……..16 2.2.1 Reflection, transmission and phase shift…………………………………….…..…16 2.2.2 Optical waveguides ………………………………………………………….….…19 2.3 Characterization methodologies…………………………………………………………..….27 2.3.1 Far-field scattering measurement……………………………………………..……27 2.3.2 Near field scanning optical microscope……………………………………..……..30 References………………………………………………………………………………………..34 Chapter 3 Review of label-free optical biosesing technologies……………………………36 vii 3.1 Introduction of the biosensing technologies……………….………………………….…...36 3.2 Surface plasmon resonance biosensors………………………………………….….……...42 3.3 Mach-Zehnder Interferometer (MZI) biosensors………………………………...…….…..48 3.4 Ring resonator based biosensors………………………………………………………..…..51 3.5 Local evanescent array coupled (LEAC) biosensor…………………………..………..…..53 References………………………………………………………………………………….…..55 Chapter 4 Biosensor design, sample preparation and experiment setup…………………...58 4.1 local evanescent-field array coupled (LEAC) biosensor………………………….……..…59 4.2 BPM simulation results on LEAC biosensor…………………………………………..…...61 4.3 Sample fabrication……………………………………………………………..……….…..73 4.3.1 Review of the sample without buried detectors……..…………………….….…..73 4.3.2 Avago sample fabrication…………………………………………………….…..75 4.3.3 Fabrication of the 3rd generation LEAC sensors…………………….……………78 4.4 Sample polishing and end-fire light coupling…………………………………………..…..87 4.5 NSOM setup & measurement…………………………………………………………..…..89 4.6 Measurement with buried photodetector arrays………………………………………....…..91 References…………………………………………………………………..……………….…..94 Chapter 5 LEAC biosensor measured using NSOM…………..………………………..……95 5.1 Measurement on basic waveguide structures……………………..……………………..….96 5.1.1 Previous work on single mode and multimode waveguide…………………..…..96 5.1.2 Y-type splitter structure…………………………………..…………………..…..98 5.2 NSOM measurement on LEAC sensor with BSA & immunoassay adlayers…………….104 5.2.1 Previous measurement with pseudo-adlayer & photoresist adlayer ……………104 5.2.2 Immunoassay adlayers measurement………………………………..……….….111 viii References………………………………………………………………………………….…..119 Chapter 6 LEAC measurement with buried detector array…………….……………..…..120 6.1 Previous work on leaky mode buried detector (1st generation LEAC sensor
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