Disease modelling is an extremely powerful tool that provides insight to disease pathology in areas of the body that cannot be easily studied. 3D Organoid culture has become a hallmark in disease modelling, especially for specialized tissues of the brain which are impossible to study at the cellular level in an afflicted individual. There is a need to understand the disease mechanisms of genetic-based inner ear hearing loss, and while organoid culture shows great promise, there is one critical limitation. The part of the inner ear most affected by the genetic variation causing deafness is the cochlea, and during development the portion of the brain destined to become the cochlea is exposed to a gradient of growth factors which will promote the specialization of the tissue. Generating a stable concentration gradient of growth factors over long periods of time is extremely difficult using traditional cell culture methods, and therefore, the resulting organoids do not exhibit this specialization that is seen during cochlear development. The proposed Chip design utilizes laminar flow and simple diffusion to generate a concentration gradient. Stock solutions continuously flowed into the chip generates a difference in concentration via laminar flow while simple diffusion occurs to generate a concentration gradient that extends from the region of high growth factor concentration to the region of low growth factor concentration. An organoid exposed to this concentration gradient will undergo specialization similar to that seen during cochlear development, making it a more accurate disease model of genetic-based hearing loss.
