Microfluidics Based Neuronal Aggregate Culturing Device for High Throughput Drug Screening

Abstract

Neurodegenerative diseases are extremely debilitating and affect a large portion of the population. Quality care for diseases such as multiple sclerosis relies heavily on the development of therapeutic agents by pharmaceutical companies. Currently neuronal drug development processes are time consuming and costly. This has led to a lack of commercially available drugs targeted at the nervous system. This thesis presents a novel neuronal cell microfluidic chip in response to this problem. In many neurodegenerative diseases, demyelination of the axons plays a critical role. This thesis presents a novel way to improve the efficiency of a neuronal cell aggregate device for myelination studies. The device is fabricated using traditional lithography techniques to pattern three inch SU-8 wafers. These wafers are then used as the master molds for the fabrication of polydimethylsiloxane (PDMS) devices. The device incorporates multiple normally closed micro valves. Fabrication of neuronal aggregate trapping structures is necessary and required the use of Inductively Coupled Plasma (ICP) to etch trenches in silicon. Neuronal aggregates are loaded into the device and trapped in a specific culturing chamber by pillar trapping structures. Unused aggregates are reflowed through the device until all the aggregate trapping sites are full. The aggregates are then cultured for multiple weeks. During culturing, myelin is produced by the aggregates. The goal of the device is to enhance drug testing related to the myelination of neurons and limit the need of animal models for such drug testing. This thesis focuses on the creation of a device that is able to reflow the unused neuronal aggregates back through the trapping chambers.