Traumatic brain injury (TBI) affects 1.4 million people a year in the United States alone and despite the fact that 96% of people survive a TBI, the health and socioeconomic consequences can be grave, partially due to the fact that very few clinical treatments are available to reduce the damage and subsequent dysfunction following TBI. To better understand the various mechanical, electrical, and chemical events during neural injury, and to elucidate specific cellular events and mechanisms that result in cell dysfunction and death, new high-throughput models are needed to recreate the environmental conditions during injury. This thesis project focuses on the creation of a novel and clinically relevant single-cell injury model of traumatic brain injury (TBI). The implementation of the model requires the development of a novel injury device that allows specialized micro-interfacing functionality with neural micro environments, which includes the induction of prescribed strains and strain rates onto neural tissue, such as groups of cells, individual cells, and cell processes. The device consists of a high-resolution micro-electro-mechanical-system (MEMS) microtweezer microactuator tool that is introducible into both biological and aqueous environments and can be proximally positioned to specific targets in neural tissue and neural culture systems. This microtweezer, which is constructed using traditional photolithography and micromachining processes, is controllable by a custom developed software-automated controller that incorporates a high precision linear actuator and utilizes a luer-based microtool docking interface. The injury studies will include examination of intracellular calcium concentration over the injury time course to evaluate neuronal plasma membrane permeability, which is a significant contributor to secondary injury cascades following initial mechanical insult. Mechanical strain and strain rate input tolerance criteria will also be used to determined thresholds for cellular dysfunction and death.

Cette thèse propose de réaliser des micro/nano-pinces magnétiques articulées dont l'actionnement à distance est obtenu par l'application d'un champ magnétique. Cette idée innovante consiste à relier par l'un de leurs côtés deux microparticules magnétiques parallélépipédiques à l'aide d'une nano-charnière en or flexible. Destinées à des applications biotechnologiques et médicales, ces pinces ont pour finalité de capturer des micro/nano-objets ciblés biochimiquement pour y appliquer et mesurer des forces. Le défi de ce projet était de mener, à partir d'une idée simple, un ensemble d'études à la fois théoriques et technologiques, pour aboutir à une première preuve de concept. Dans ce but, un modèle analytique a d'abord été construit pour prédire le comportement magnéto-mécanique des pinces en fonction de divers paramètres physiques. Ensuite, un procédé de fabrication inspiré des techniques de la microélectronique a été développé pour parvenir à la réalisation d'un prototype de pince fonctionnel. Enfin, l'ouverture par l'action d'un champ magnétique de pinces fixées à un substrat, a pu être démontrée à l'aide d'une expérience originale installée dans un microscope électronique à balayage. Les résultats de ces expériences, en bon accord avec nos prédictions théoriques, ont permis de quantifier le comportement mécanique de la nano-charnière en or. Fixées à un substrat, ces pinces forment un réseau de micro-surfaces réfléchissantes qui trouveront des applications en microfluidique (bio-puces) ou en nano-physique. Libérées en solution, les pinces pourraient être employées de manière originale en micro-manipulation d'objets biologiques ou diagnostic et thérapie cellulaire. / The objective of this thesis was to elaborate magnetic micro/nano-tweezers remotely actuable by the application of a magnetic field. This innovative idea consists in binding two parallelepiped magnetic microparticles by one of their sides with a flexible gold nano-hinge. Intended for biotechnological and medical applications, these tweezers aim at capturing biochemically targeted micro/nano-objects, in order to exert forces on them and perform force measurements. In this project starting from a simple idea, the challenge was to carry out theoretical and technological studies leading to a first proof of concept. To this end, an analytical model was first elaborated to predict the magneto-elastic behavior of the tweezers, depending on various physical parameters. Then, a fabrication process inspired from microelectronic techniques was developed to complete a functional prototype of tweezers. Finally, the remote actuation of such tweezers, kept attached to a substrate, by the application of a magnetic field, was demonstrated using an original experiment set up inside a scanning electron microscope. These experiments yielded results in good agreement with our theoretical predictions and allowed the quantification of the gold nano-hinge elastic behavior. Attached to a substrate, these tweezers constitute an array of reflective micro-surfaces, which can find applications in microfluidics (biochips) or in nano-physics. Released in solution, the tweezers could be used in an original way for biological objects micro-manipulation or cell diagnostic and the