AC Electrokinetics and Electrohydrodynamics for the On
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AC Electrokinetics and Electrohydrodynamics for the On-chip Particle Manipulation and Fluid Handling Paresa Modarres Doctor of Philosophy Department of Biomedical Engineering McGill University Montreal, Canada A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Doctor of Philosophy Copyright © Paresa Modarres, April 2020 ABSTRACT The ever-increasing developments and advancements in the field of microfabrication technology for the past two decades have encouraged many applications geared towards miniaturized bioanalytical systems capable of performing independent or concurrent on-chip operations including, pumping, mixing, sample enrichment, thermal cycling and sensing. Reduced reagent consumption, enhanced spatiotemporal control over reaction conditions, the increased surface to volume ratios and ease of process parallelization are some key advantages of miniaturized bioanalytical systems over their counterpart conventional macroscale methods. Enabling physical mechanisms for many on-chip operations often include various gravitational, acoustics, magnetic and electric phenomena. Electrically-induced actuation mechanisms are becoming the method of choice for many specialized applications whereby low power, small footprint and absence of moving parts are desired. Applications of electrically induced actuation mechanisms encompassing classical electrokinetics and electrohydrodynamic forces are the subject of this thesis. Multiple novel biochips were designed, fabricated and characterized for performing cell enrichment, micromixing and nanoparticle synthesis. First, the principle of alternating current (AC) dielectrophoresis (DEP) was utilized for the tunable sorting of synthetic particles and cells. Next, the concepts of AC electroosmosis (ACEO) and electrohydrodynamic were investigated for the micromixing of monophasic and biphasic liquid systems. For the first time, the ACEO-induced fluid actuation mechanism was utilized for devising a phase-controlled field-effect micromixer. The phase-tunability of the micromixer was investigated experimentally and semi-analytically. Finally, electrohydrodynamic-based fluid instabilities were employed for the mixing of solvent and aqueous liquid phases in the context of nanoparticle synthesis. It was demonstrated that electrohydrodynamic-mediated micromixing can be leveraged for the synthesis of high-throughput i and highly monodispersed liposomal batches intended for drug delivery applications. The devised platform and methodology can be applied across many nanoparticle chemistries relying on the principle of nanoprecipitation. Overall, the novel ideas and methodologies introduced in this thesis validated the utility of electrical-based methods for on-chip operations and demonstrated new applications with many potentials for nanoparticle synthesis and drug encapsulation. ii ABRÉGÉ Les développements et les progrès sans cesse croissants dans le domaine de la technologie de micro-fabrication au cours des deux dernières décennies ont encouragé de nombreuses applications axées sur les systèmes bio analytiques miniaturisés capables d’effectuer des opérations sur puce indépendantes ou simultanées, y compris le pompage, le mélange, l’enrichissement et la concentration d’échantillon, le cycle thermique et la détection. La consommation réduite de réactifs, contrôle spatiotemporel amélioré des conditions de réaction, l’augmentation des rapports surface/volume et la facilité de parallélisations du processus sont quelques principaux avantages des systèmes bio analytiques miniaturisés par rapport à leurs méthodes macroscopiques conventionnelles. L’activation de mécanismes physiques pour de nombreuses opérations sur puce comprend souvent divers phénomènes gravitationnels, acoustiques, magnétiques et électriques. Les mécanismes d’actionnement induits électriquement sont les méthodes de choix pour de nombreuses applications spécialisées dans lesquelles une faible puissance, un faible encombrement et l’absence de pièces mobiles sont souhaités. Les applications des mécanismes d’actionnement induits électriquement englobant l’électrocinétique classique et les forces électro hydrodynamiques font le sujet de cette thèse. Plusieurs nouvelles bio puces ont été conçues, fabriquées et caractérisées pour effectuer l’enrichissement cellulaire, micro mélange et la synthèse de nanoparticules. Tout d’abord, le principe de diélectrophorèse CA (DEP) a été utilisé pour le tri accordable des particules synthétiques et cellules. Ensuite, les concepts d’électroosmose AC (ACEO) et d’électro hydrodynamique ont été étudiés pour le micro mélange de systèmes liquides monophasiques et bi phasiques. Pour la première fois, le mécanisme d’actionnement des fluides induit par l’ACEO a été utilisé pour concevoir un micro-mélangeur à effet de champ à phase contrôlée. L’accordabilité de phase du micro-mélangeur à été étudié expérimentalement et semi- iii analytiquement. Enfin, des instabilités fluides électro hydrodynamiques ont été utilisées pour le mélange de phases liquides et aqueuses dans le cadre de la synthèse de nanoparticules. Il a été démontré que le micro mélange à médiation électro hydrodynamique peut être utilisé pour la synthèse des lots liposomiques de haut débit et hautement mono dispersés destinés à des applications d’administration de médicaments. La plate-forme et la méthodologie mises au point peuvent être appliquées à de nombreuses chimies de nanoparticules en s’appuyant sur le principe de la nano précipitation. Dans l’ensemble, les nouvelles idées et méthodologies introduites dans cette thèse ont validé l’utilité des méthodes électriques pour les opérations sur puce et ont démontré de nouvelles applications avec de nombreux potentiels pour la synthèse de nanoparticules et l’encapsulation de médicaments. iv ACKNOWLEDGEMENTS I would like to express my utmost gratitude to my advisor, Professor Maryam Tabrizian, for her guidance and support throughout the course of my PhD study. I will always be grateful for her encouragements, vision and trust that helped me to grow as a curious researcher and critical thinker. I am very thankful to my PhD advisory committee, Dr Satya Prakash and Dr Xinyu Liu, for their valuable insights and guidance at different stages of my PhD program. I am very grateful to all the current and former staff of the McGill Nanotools Microfab for their diligent response to inquiries as well as their help and guidance during the fabrication of microchips. I would also like to thank Pina Sorrini, Nancy Abate and Daniel Caron in the Biomedical Engineering department for always being available and resourceful. Finally, I would like to express my appreciation to Vanessa Kairouz at Université de Montréal for her help with the NSERC-CREATE Continuous Flow Science (CFS) program. I was fortunate to have the company of Biomat’X lab members and I am very thankful for their friendship and support throughout the years. Especially, I like to thank Mina, Saber, Amir, Sameera, Khalil, Laila, Feriel, Rosey, Saadia, Sultan, Meltem, Brandon, Michael, Celine, Antoine, Kaushar, Nick, Reza, Rafael, and Timothy Johns for all the memorable moments we had together. I would also like to extend my gratitude to Rafael and Khalil for their helpful technical discussions on various subjects and Celine for her help with the French translation of thesis abstract. I would like to express my dearest appreciation to my family. I am very grateful to my husband, Dr Aboli, for his unconditional support and encouragement. I also like to thank him for his technical advice and discussions on various topics pertinent to my thesis. Last but not the least, I would like to thank my mother for her endless love and support. v Finally, I would like to acknowledge various grants and funding sources that made this work possible including, Natural Sciences and Engineering Research Council of Canada (NSERC), NSERC-CREATE Integrated Sensor Systems program, NSERC-CREATE Continuous Flow Science program and McGill’s biomedical engineering department. vi CONTRIBUTIONS OF AUTHORS In accordance with the “Guidelines for Thesis Preparation”, this thesis is presented as a collection of manuscripts written by the candidate. The candidate envisioned, designed, and performed experiments. All data collection and analysis were conducted by the candidate. Dr Maryam Tabrizian appears on all publications for partaking in the manuscripts and her guidance and supervisory role throughout the execution of this work. vii TABLE OF CONTENTS ABSTRACT .................................................................................................................................... i ABRÉGÉ ....................................................................................................................................... iii ACKNOWLEDGEMENTS ......................................................................................................... v CONTRIBUTION OF AUTHORS ........................................................................................... vii TABLE OF CONTENTS .......................................................................................................... viii LIST OF FIGURES .................................................................................................................... xii LIST OF TABLES ..................................................................................................................... xix LIST OF ABBREVIATIONS ...................................................................................................