| Neurobiological systems span a wide dimensional range. I will present three examples of scale-driven methodological development in biological systems to demonstrate the utility of applied engineering approaches for neurobiological applications and provide direction for future study. Concepts in computational modeling, microfluidic cell culture platforms, and MRI phantoms are examined---from the scale of a single synapse to long distance cortical connections.;A single synapse model was developed using a Monte Carlo simulation environment to study biophysically realistic mechanisms of spike timing dependent plasticity (STDP). A deterministic model of spatiotemporal intracellular calcium detection was extended to include subunit-specific receptor kinetics. Using STDP-based stimulus protocols, global and local molecular time courses were then produced for NR2A and NR2B knockout models.;To study network-level oscillatory activity, a model of spatially-constrained networks was created based on cyclic geometry to look at the effects of circumference and track-width on spontaneous network activity. Transverse wave activity was demonstrated and characterization methods were established based around wave velocity and origin.;Microfluidic technology provides an experimental means to study network organization and activity in vitro. I will present work towards an integrated microfluidic control platform combining multiple design strategies to address the intrinsic spatiotemporal resolution of neurons. Microfluidic devices fabricated using multilayer soft-lithography with internal valves to direct multiple laminar fluid flows were controlled with a dynamic pressure platform to create targeted hydrodynamic streams. Devices were characterized for arbitrary profile generation, repeatability, flow rate stability, and lid-driven flow using multimodal sensory feedback and analysis.;Finally, I will present a microfluidic application for cortical connectivity measures. A microfluidic phantom for diffusion-weighted magnetic resonance imaging was developed for validation studies of long-distance cortical white matter connections. The diffusion phantom provides a reliable physical structure with which high-resolution fiber tractography algorithms can be tested against. The diffusion phantom was fabricated using conventional photolithographic techniques with an internal channel network that mimics white matter fiber tracts and crossings. I show preliminary mapped tracts to the features inside of the phantom via post-processing of diffusion-weighted images. |
