Bioreactor on a chip: a microfluidic device for closed production of human dendritic cells

Abstract

We have exploited the unique physics available in microfluidic devices to engineer a platform capable of integrating all critical elements of cell therapy into a microfluidic device. The platform can be used to isolate, count, identify and culture cells on a device in a closed Current Good Manufacturing Practice-compatible system. We have used the culture and isolation of human mature dendritic cells (DCs) as our model system, demonstrating each critical element in manufacturing a therapeutic product. We used the system to immunomagnetically isolate CD14+ cells from peripheral blood mononuclear cells, perform on-chip enumeration and surface marker characterization to confirm purity of isolation (mean, 98.6 ± 1.6%) and culture cells in the presence of cytokines to drive differentiation to CD83+ mature DCs. Successful DC maturation was confirmed using on-chip surface marker characterization (positive CD83 expression) with process yields comparable to conventional DC production. The technology presented is the first demonstration of a chip bioreactor capable of recapitulation of all critical elements of cell therapy manufacturing. Its closed nature, scalability and integration of both manufacturing and release testing show the potential for a new approach to industrialization and rapid distribution of cell therapies.