Investigating the Mechanics of the Mammalian Cochlear Partition Using a Novel Microfluidic Devic

The cochlea is the mammalian hearing organ that encodes sound information into neural impulses. The cochlea utilizes a multitude of electro-mechanical mechanisms that provide tuning and amplification in order to better resolve frequencies and amplitudes of sounds over a wide range. According to prevailing theory, the tuning and amplification are achieved within the sensory epithelium known as the organ of Corti, comprised of sensory receptor cells and supporting cells. Research into cochlear biophysics has aimed at not only identifying but understanding the role that each of these mechanisms has toward overall cochlear function. Unfortunately, there are few approaches to observe the organ of Corti mechanics, which has delayed the advancement of hearing science. In vivo studies have the advantage of the preservation of the natural physiological conditions of cochlear tissues, but due to the small size and 3-D coiled geometry of the cochlea, they offer limited experimental flexibility and control. On the other hand, in vitro approaches offer significant experimental freedom, but suffer from a lack of physiological conditions.;The first goal of this thesis work was to develop and validate a new experimental approach that combined the advantages of both in vivo and in vitro approaches, while minimizing the drawbacks from each. A microfluidic chamber device, fabricated using standard stereolithography techniques, replaces the function of the fluid-filled cochlear compartments. A membrane or tissue sample placed over a small slit opening separates fluid spaces in the top and bottom compartments of the microchamber. With the addition of an electrode pair on either side of the slit opening, the microchamber mimics the electrochemical separation of the scala media and scala tympani fluid spaces. The microchamber is also capable of applying both static and dynamic fluid pressures to slit samples (across a range of audible frequencies). Different measurement methods such as laser interferometry, a paired dual photodiode, and image correlation analysis are used to measure slit sample responses to electrical or mechanical stimulation. Artificial membranes were used to verify the feasibility of accurately measuring the mechanical properties of slit samples.;The second goal of the thesis work was to extend the microchamber approach to measure the mechanical properties of isolated segments of the organ of Corti complex placed over the slit. More specifically, I aimed to measure the stiffness of the organ of Corti complex from apical locations, where measurements are rare. Furthermore, I measured the organ of Corti complex stiffness in response to fluid pressure, better approximating the natural mechanical condition than previous stiffness measurements which have exclusively used compliant microprobes. I measured a mean compliance of 115 nm/Pa at a location 9 mm from the gerbil cochlear base using both hydrodynamic and hydrostatic stimulation. In order to facilitate comparison of my results with others', a computational model of the organ of Corti complex was used. The model showed that the experimentally-measured compliance compared favorably with the lower bound of past stiffness measurements at similar cochlear locations.