Development and characterization of mechanically actuated microtweezers for use in a single-cell neural injury model
Wester, Brock Andrew
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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.