Passive controlled flow for Parkinson's disease neuronal cell culture in 3D microfluidic devices

Controlled flow within a lab-on-a-chip is a critical element of successfully implementing culture protocols for differentiation and maintenance of stem cell derived neurons in microfluidic devices. There have been a multitude of passive pumping technologies that have been successfully used to control the flow within a lab-on-a-chip. However, most of which were only able to generate flow for very few minutes, while the most successful ones were able to achieve around an hour of flow. This is not convenient for culture protocols requiring constant flow, as hourly media changes will have to be conducted. Herein, we present a design technique adapted for the OrganoPlate, a cell culture plate fully compatible with laboratory automation, which allows its redimension to achieve over 24 h of flow. This technique uses a similarity model of a target cell type and a simple fluid flow mathematical prediction model to iterate to the optimum dimensions within some manufacturing constraints. This technique has the potential to be applied to many cell types to generate optimum design for their culture. We applied this technique to design a 3D microfluidic device, dynamically optimised for neuronal cell culture.