development of novel micro-embossing methods and microfluidic designs for biomedical applications

DEVELOPMENT OF NOVEL MICRO-EMBOSSING METHODS AND MICROFLUIDIC DESIGNS FOR BIOMEDICAL APPLICATIONS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University By Chunmeng Lu, M.S ***** The Ohio State University 2006 Dissertation Committee: Approved by Dr L James Lee, Adviser Dr Allen Yi _ Adviser Dr Avraham Benatar Chemical Engineering Graduate Program UMI Number: 3230881 UMI Microform 3230881 Copyright 2006 by ProQuest Information and Learning Company All rights reserved This microform edition is protected against unauthorized copying under Title 17, United States Code ProQuest Information and Learning Company 300 North Zeeb Road P.O Box 1346 Ann Arbor, MI 48106-1346 ABSTRACT The goal of this study is to develop novel microfabrication methods and microfluidic devices for BioMEMS applications The emphasis is on the development of new hot embossing techniques, the design of microfluidic functions and biocompatible packaging methods for polymeric microfluidic chips First, two unconventional hot embossing techniques were developed: laser assisted and sacrificial template based hot embossing In laser assisted embossing, localized micro patterning can be achieved on polymer surfaces with a cycle time of less than minute due to the localized heating, which is comparable with that of micro injection molding The sacrificial template based hot embossing solved the de-molding issue involved in conventional hot embossing especially for high aspect ratio microstructures Embossing of microstructures with aspect ratio of was demonstrated successfully and the possibility of laser assisted embossing in conjunction with sacrificial template embossing was investigated A fishbone microvalve was designed based on the concept of superhydrophobicity such that the valve function remains after protein blocking, a required step in some enzyme-linked immuno-sorbent assays (ELISA) applications to prevent non-specific binding Compared with another type of super-hydrophobic microvalve ii developed based on the micro-/nano structure formation by chemical synthesis, the fishbone valve can be easily incorporated into the microfluidic designs Polymer compact-disk (CD) microfluidic platform integrated with different fluidic features was designed and fabricated We have demonstrated successfully that flow sequencing can be achieved on a CD-like microfluidic platform For packaging microfluidic platforms, a new interstitial bonding technique has been developed, which bonds the polymer-based microfluidic platforms without introducing any alien materials in to microchannels This method can easily bond biochips with complex flow patterns, but in a relatively smaller size A multi-channel DNA sequencing chip was demonstrated experimentally Another bonding method, CO2 assisted bonding, was also demonstrated for bonding a 5-inch CD platform By applying a thin PLGA interlayer, the CD platform can be bonded at low temperature and low pressure to achieve a hermetic bonding ELISA tests showed that both bonding methods have no or little effect on the activity of preloaded proteins, which is essential for microfluidic designs that requires preloading of some regents such as proteins, antibody/antigen and cells iii Dedicated to my wife iv ACKNOWLEDGMENTS First I would like to express my sincere appreciations to my adviser, Professor L James Lee, for his invaluable guidance, discussions, supports and encouragements throughout my five years stay at The Ohio State University Many thanks to him for his frequent discussions with me about my general research directions and technical details which not only expanded my horizons but also stimulated my creativity and imagination I would also like to acknowledge Professor L James Lee for bringing me into this wonderful field and provide financial support to me I would like to thank Dr Avraham Benatar, Dr David Grewell, and Ms Miranda Marcus for their valuable discussion and generous help in my experiments related to laser heating Thanks go to Professors Allen Yi, Avarham Benatar, and John C Byrd for serving on my dissertation committee and for their invaluable comments and suggestions, to Paula and Stacy for proofreading all the manuscripts I submitted for publishing Thanks also go to my collaborators, Dr Hank Wu, Dr Chu-hua Chen, and all other friends in Ritek, Taiwan, on the CD-ELISA project To all the fellow graduate students in our lab, especially to those who collaborated with me (Yi-Je Juang, Chee-Guan Koh, Yong Yang, Jingjiao Guang, Shengnian Wang, Yubing Xie, Ling Li, Xia Cao, Hongyan He and etc.), I would say thank you very much v for your friendship and I cherish the moments we shared together very much! Experimental assistances from Dr Mark Ming-cheng Cheng and Derek Ditmer in MicroMD are greatly appreciated I also want to give my special thanks to Paul Green and Leigh Edward for their endless help on the machining and other supporting efforts in my experimental work Last but not least, I want to thank my family for their love and dedications for encouraging and supporting me Great appreciations to my wife, Chunyan, for her love, accompany, encouragement, and support through all these years vi VITA August 16, 1971 .Born in Xushui, Hebei, P.R China September 1989 - July 1993 B.S Mechanical Engineering, Beijing University of Chemical Tech Beijing, P.R China July 1993 - July 1998 Mechanical Engineer, Hebei Aika Packaging Materials Co Ltd Shijiazhuang, Hebei, P.R China Sept 1998 - June 2001 M.S Mechanical Engineering The Institute of Plastics Machiner and Engineering (IPME) in Beijing University of Chemical Tech Beijing, P.R China September 2001 – August 2002 University Fellowship Chemical and Biomolecular Engineering The Ohio State University Columbus, Ohio, USA September 2002 – Present Graduate Research Associate Chemical and Biomolecular Engineering The Ohio State University Columbus, Ohio, USA PUBLICATIONS Chunmeng Lu, Yi-Je Juang, L James Lee, David Grewell, Avraham Benatar, Analysis of laser/IR-assisted microembossing, Polymer Engineering & Science, 45(5), 661-668 (2005) vii Yi-Je Juang, Xin Hu, Shengnian Wang, L James Lee, Chunmeng Lu and Jingjiao Guan, Electrokenetic Interactions in Mcroscale Cross-slot Flow, Applied Physics Letters, 87, 244105-244105-3 (2005) David Grewell, Chunmeng Lu, Abbass Mokhtarzadeh, Avraham Benatar and L James Lee, Feasibility of selected methods for embossing micro-features in thermoplastics, (SPE 2003, Nashville) Chunmeng Lu and L James Lee, Numerical simulation of Laser/IR Assisted MicroEmbossing (SPE 2004, Chicago) David Grewell, Chunmeng Lu, L James Lee and Avraham Benatar, Infrared microembossing of thermoplastics (SPE 2004, Chicago) Chunmeng Lu, L James Lee, David Grewell and Avraham Benatar, Sacrificial material assisted laser welding of polymeric micro channels (SPE 2005, Boston) Hae Woon Choi, Chunmeng Lu, L James Lee and Dave Farson, Femtosecond laser micromachining of internal microfluidic channels in PMMA, (ASPE 2005, OSU) Chunmeng Lu, Yi-Je Juang and L James Lee, Numerical simulation of Laser/IRassisted Micro-Embossing in Polymer (Numiform 2004, OSU) Chunmeng Lu and L James Lee, Numerical simulation of Laser/IR-assisted MicroEmbossing in Polymer (PPS-20, Akron, USA) 10 Chunmeng Lu and L James Lee, Sacrificial mold embossing for high density/aspect ratio micro-/nano structures (PPS-22, Yamagata, Japan) 11 Michael W Bobem, Chunmeng Lu, Kurt W Koelling and L James Lee, Fundamental processing characteristics in polymer micro/nano molding (SPE 2006, Charlotte, USA) 12 Chunmeng Lu and L James Lee, Sacrificial mold embossing for high density, high aspect ratio micro/nano structures (SPE 2006, Charlotte, USA) 13 Chunmeng Lu and L James Lee, Micro-valve based on super-hydrophobicity (SPE 2006, Charlotte, USA) viii 14 Kittichai Sojiphan, Miranda Marcus, Hae Woon Choi, Chunmeng Lu, Avraham Benatar and L James Lee, Beam Shaping with Diffractive Optics for Laser MicroMachining of Plastics with a Femtosecond Laser (SPE 2006, Charlotte, USA) 15 L James Lee, Chunmeng Lu, Yi-Je Juang and Shang-Tian Yang, Interstitial bonding for plastic microfluidic chips, US Provisional Patent Application, 60/741,697, Dec 2, 2005 16 L James Lee, Chunmeng Lu, Yi.-Je Juang and Shang-Tian Yang, Design of superhydrophobic valve for plastic microfluidic chips, US Porvisional Patent Application, 60/738,096, Nov 18, 2005 FIELDS OF STUDY Major Field: Chemical Engineering Minor: Microfluidics and Polymer Microfabrication ix Elwenspoek M., Lammerink T S., Miyake J R., and Fluitman J H J., “Towards integrated microliquid handling systems,” J Micromech Microeng., 4, pp 227-245 (1994) Erbil H Y., Demirel A L., 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polymeric microfluidic. .. design and implementation of necessary microfluidic functions; integration of these functions with complete automation; and development of cost-effective manufacturing technology [Madou 2001] Microfluidics... platforms without denaturing the preloaded proteins and contaminating the microfluidic channels 1.3 Outline Chapter contains a comprehensive literature review of microfabrication and and microfluidics