Optoelectronic Data and Code Library

Abstract— Pluripotent cell types retain several characteristics that make them optimal cell source material for applications in drug development, disease modeling, and therapeutic applications. Human induced pluripotent stem cells (hiPSCs) are currently the most accessible cell source material to cultivate and derive cell-based therapeutic solutions at scale. However, a disconnect exists between quality characteristics of phenotype in the pluripotent state, and downstream metrics for efficacy. Bridging this gap is a major challenge to overcome– Given the plasticity of this cell type, environmental conditioning plays a critical role in guiding phenotype. The objective of this work is to present a scale-down, highly parallelizable approach to acquiring real-time data to inform metrics of hiPSC phenotype throughout the biomanufacturing process. Our methods focused on the development of an optoelectronic instrumentation suite capable of measuring pH, dissolved oxygen, and cell density as important surrogates for phenotype in an optimized hiPSC scale-down expansion bioprocess system. We evaluated system performance through control experiments and targeted perturbation of environmental conditions during hiPSC cultivation, with our results showing promising results. We were successful in obtaining continuous, integrated parametric data throughout cultivation and estimating metabolic characteristics of hiPSC phenotype. In conclusion, this system functions as a proof-of-concept translational tool for development of predictive models and monitoring strategies around the elucidation of phenotypic dynamics within hiPSC biomanufacturing. The significance of this work is in its contribution to closing the gap in our understanding of how upstream phenotype intersects with downstream functionality, in pursuit of global optima in hiPSC biomanufacturing for regenerative medicine.