High-throughput screening approaches are utilized by pharmaceutical companies to rapidly evaluate new and/or existing chemical entities for desired effects on cells or cellular processes. Through the use of automated robotics, liquid handling, imaging, and data analysis systems, researchers can quickly conduct thousands of experiments to identify ‘hits’ for appropriate biological responses. This is most commonly accomplished through the screening of 2-dimensional cellular/tissue systems in micro-well plates, with more recent advances focused on the transition to microfluidics or lab-on-a-chip-based screening methods to reduce reagent volumes. These approaches are limited in physiological significance by the 2-D nature of the assay and/or unnatural interactions of cells with synthetic materials (e.g., plastics, polymers, etc.) used in fabricating the high throughput system. Given these constraints, such studies are typically short-term in nature, offering limited insight into conditions that require long-term culture and concurrent longitudinal analysis of cellular systems (e.g., neurodegenerative disorders).


Our approach is to develop a high-throughput system based on our 3-dimensional bioengineered brain tissue models. By using these tissue engineered systems to recapitulate native tissue architecture, cellular composition, and function, particularly using patient-derived cells, we can achieve a higher level of fidelity to the in vivo condition in a high-throughput, in vitro system, leading to an increase in the accuracy of pharmacological ‘hits’ during screening. Importantly, these 3D tissues can be maintained over extended time in culture (e.g., >1 year) and these systems are compatible with both real-time imaging and terminal analysis methods. This includes interfacing with imaging modes to track changes in metabolism and tissue structure, array methodologies for measuring neuronal signals, and systems for sampling and analyzing metabolites in real-time. This  system offers an innovative method for the in vitro study of neurological disorders and the potential for break-through drug discoveries. This approach can be also utilized for multiple tissue types (e.g., brain, intestine, cornea, skin, etc.), further demonstrating the broad applicability of developing this technology platform.