Flow Through a Micro-Bioreactor in a Neural Interface System

A micro-bioreactor is developed for in vitro, controlled, growth of three-dimensional dissociated neural cultures that enables simultaneous, multipoint, electrical and fluidic interfacing, monitoring and recording of the response signals that are relevant to the studies of traumatic injury. Present experiments focus on the microfluidic system that is used to control the spatial concentration of nutrients and stimuli in the incubated tissue. The three-dimensional cellular environment in a micro-bioreactor is controlled by means of convective and diffusive fluidic processes to improve the neural cell survival rate, direct the cell growth and examine the network formation. To achieve global and local manipulation of the critical cell functions, flow within the reactor is induced from arrays of micro-machined nozzles in planar surfaces and within microscale hydrogel scaffolding. The flow and concentration fields within reactor are analyzed using microscale particle image velocimetry (PIV) and fluorescence. The flow within 25 μm thick layers between microfabricated structures is investigated using image-processing algorithms that are developed to improve spatial resolution by excluding out-of-focus particles. Mixing induced by delivery of stimuli/nutrients and waste extraction is considered by following the time-evolution and spatial propagration of the mixing front between the liquids based on the intensity of reflected light that is previously calibrated with concentration.