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Additive Manufacturing for Robust and Affordable Medical Devices

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Additive Manufacturing for Robust and Affordable Medical Devices Additive Manufacturing for Robust and Affordable Medical Devices Daniel Wolozny Dissertation submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Biological Systems Engineering Warren C. Ruder Chenming (Mike) Zhang Xueyang Feng Caleb J. Bashor September 22nd, 2016 Blacksburg, Virginia Keywords: 3D Printing, Thermoplastics, Biosensors, Cell Patterning, Lithography Abstract (Academic) Additive Manufacturing for Robust and Affordable Medical Devices Daniel A. Wolozny Additive manufacturing in the form of 3D printing is a revolutionary technology that has developed within the last two decades. Its ability to print an object with accurate features down to the micro scale have made its use in medical devices and research feasible. A range of life-saving technologies can now go from the laboratory and into field with the application of 3D-printing. This technology can be applied to medical diagnosis of patients in at-risk populations. Living biosensors are limited by being Genetically Modified Organisms (GMOs) from being employed for medical diagnosis. However, by containing them within a 3D-printed enclosure, these technologies can serve as a vehicle to translate life-saving diagnosis technologies from the laboratory and into the field where the lower cost would allow more people to benefit from inexpensive diagnosis. Also, the GMO biosensors would be contained with a press-fit, ensuring that the living biosensors are unable to escape into the environment without user input. In addition, 3D-printing can also be applied to reduce the cost of lab-based technologies. Cell patterning technology is a target of interest for applying more cost-effective technologies, as elucidation of the variables defining cell patterning and motility may help explain the mechanics of cancer and other diseases. Through the use of a 3D-printed stamp, bacterial cells can be patterning without the use of a clean room, thus lowering the entry-barrier for researchers to explore cell patterning. With the commercialization of 3D-printing, an opportunity has arisen to transition life- saving technologies into more cost-effective versions of existing technologies. This would not only allow more research into existing fields, but also to ensure that potentially life-saving technologies reach the people that need them. Abstract (Public) Additive Manufacturing for Robust and Affordable Medical Devices Daniel A. Wolozny 3D-printing is a revolutionary technology developed within the last two decades. Its ability to print an object with accurate features down to the micro scale have made its use in medical devices and research feasible. A range of life-saving technologies can take advantage of 3D- printing to go from bench top technologies into the field. This technology can be applied to medical diagnosis of patients in at-risk populations. Cells are able to detect and react to their environment. We can take advantage of this to design genetically modified cells for disease diagnosis. However, genetically modified cells are heavily regulated and it is thus difficult for use outside the lab. However, by containing them within a 3D-printed enclosure, these technologies can serve as vehicles to translate life-saving diagnosis technologies from the laboratory and into the field where the lower cost would allow more people to benefit from inexpensive diagnosis. Also, the genetically modified biosensors would be contained with a seal, ensuring that the genetically modified cells are unable to escape into the environment without user input. In addition, 3D-printing can also be applied to reduce the cost of lab-based technologies. Cell patterning technology is a target of interest for applying more cost-effective technologies in order to understand how cells self-pattern and move in their environment. This may help explain the mechanics of cancer and other diseases. Through the use of a 3D-printed stamp, bacterial cells can be patterned without the use of expensive facilities, thus lowering the entry-barrier for researchers to explore cell patterning. With the commercialization of 3D-printing, an opportunity has arisen to transition life- saving technologies into more cost-effective versions of existing technologies. This would not only allow more research into existing fields, but also to ensure that potentially life-saving technologies reach the people that need them. Attribution The experiments and related designs for chapter three, four and five were performed by Daniel Wolozny. The manuscript of each chapter is written by Daniel Wolozny and edited and reviewed by Dr. Warren Ruder. The main idea for each chapter was developed by Daniel Wolozny and Dr. Warren Ruder. The modeling of the dose-response curve in appendix H, G, and I was completed with the help and contribution of Keith Heyde. vi Acknowledgements First and foremost, I would like to thank my advisor, Dr. Warren Ruder for his unwavering support of my development, not only as an engineer, but as a professional as well. This Ph.D. could not have been completed without determination and his dedication. I would also like to thank my committee members, Dr. Mike Zhang, Dr. Xueyang Feng and Dr. Caleb Bashor for their support and encouragement. I would also like to thank my colleagues: Sung-Ho Paek, Felicia Scott, Keith Heyde, MaryJoe “M.J.” Rice and John “Jack” Lake. Sung-Ho and Felicia, thank you for the wise words, the advice your help on my road to become a full-fledged professional. Keith, thank you for all the weekend chats in lab! MJ Rice, thank you for your hard work and commitment on my cell patterning project, couldn’t have done it without you! Jack, thank you for all the consultations on my device designs, you should have charged a consultation fee! It has been a pleasure to work alongside you these past few years and I wish you all the best in your future! Finally, I would like to acknowledge my parents, Ruben and Cecilia, who have stood by me throughout the good and the bad in my life and my Ph.D. degree. Thank you for your faith in me and for encouraging me to never give up! vii Table of Contents Attribution ...................................................................................................................................... vi Acknowledgements ....................................................................................................................... vii Table of Contents ......................................................................................................................... viii Chapter 1: Introduction ................................................................................................................... 1 Chapter 2: Literature Review .......................................................................................................... 5 History of Additive Manufacturing............................................................................................. 5 Extrusion Printers and Design of 3D Parts ................................................................................. 6 Materials for 3D Printing ............................................................................................................ 9 3D Printing Medical Devices .................................................................................................... 10 Plastic Design Approaches........................................................................................................ 14 Biosensors ................................................................................................................................. 18 Synthetic Biology...................................................................................................................... 20 Genetically Modified Organisms (GMOs) ............................................................................... 22 Micropatterning for Bacterial Cells .......................................................................................... 23 Microfabrication using Soft Lithography ................................................................................. 24 Conclusion ................................................................................................................................ 29 References ................................................................................................................................. 30 Chapter 3: An Additive Manufacturing Approach that Enables the Field Deployment of Synthetic Biosensors ..................................................................................................................................... 35 viii Abstract ..................................................................................................................................... 36 Introduction ............................................................................................................................... 37 Materials and Methods .............................................................................................................. 42 Cell Culture and Molecular Cloning ..................................................................................... 42 Dose Response Characterization........................................................................................... 42 Design and Fabrication of ABS Devices .............................................................................
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