NCS-FO: A microfluidic MEMS approach to study force-induced changes in neurons

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CBET - 1631656Turner, KimberlyThe brain is a highly plastic organ, capable of learning, remembering and adapting. However, it is also a plastic material with mechanical properties of strength, hardness, and impact resistance. A major challenge in neuroengineering is to understand the biophysical properties of the brain and how these differ between individuals. In particular, how do differences in the mechanical properties of the brain alter the experience of force and the consequences of impact? A major limitation in the systematic study of force on the brain has been the inability to reliably apply impacts or pressure to individual cells. The uHammer project aims to develop just such a highly engineered tool for the application of force to individual neural cells. These single cell studies will allow us to compare individual differences in neural responses to force, including changes in cell mechanics, structure, viability, and gene expression. This project, a collaboration between industry and multi-faceted academic team, will support the Ph.D. work of two graduate students, hold a workshop to bring together top researchers interested in this important societal problem, and train undergraduate research interns, while attempting to unlock some of the mysteries surrounding the brain today.The focus of this work is to probe the mechanical properties of neural tissue and the subsequent effects on function. To examine the consequences of force on neurons, a device must apply precise forces to single cells over a few microseconds. No existing devices provide these force and temporal responses, and developing such a device would enable broad, new classes of cellular measurements. The development of a MEMS based device (the uHammer) that uses time gated magnetic actuation to deliver milliNewton impact forces to single cells in a high throughput fashion, will enable these measurements. The device, capitalizing on recent advances in micro and nanoscale transduction, microfluidics, and analytical techniques, will allow cells to be monitored in real-time and collected after impact for analysis. The uHammer will enable entirely new classes of experiments, in which the biological consequences of impact loading can be recorded and monitored as a function of force amplitude, direction, duration, and time after loading. The focus is to develop a significantly improved understanding of the role of impact and pressure loading on individual neurons, neural progenitors, and brain tissue. The technical goals are to Design, fabricate and test a tool (the uHammer) able to apply physiologically relevant loads to single cell, optimize the device for high-throughput manipulation of neural stem cells, and quantify the effect of impact on single cell mechanics, structure, viability, colony formation and gene expression. The uHammer team of engineers, neuroscientists, biologists and industry leaders is able to tackle these challenging questions, while also providing a unique learning environment for undergraduates and graduate students. The multidisciplinary uHammer team has the ability to design new technology with the end user in mind, enable new scientific discovery, and transform it into therapies and treatments. The proposed technology will enable experiments that are not presently possible, and the link to and commitment from industrial partner Owl Biomedical, will enable rapid commercial developments. With these partnerships and goals in hand, UCSB is poised to make game-changing breakthroughs on problems including traumatic brain injury (TBI) and Alzheimers disease