Development of a robotic-assisted handling and manipulation system for the high-scale bioproduction of 3D-bioprinted organ-on-a-chip devices

Abstract

Organs-on-a-chip (OoCs) have proven to mimic the basic physiological behavior of organs and the influence of therapeutics on them in greater detail than conventional models, resulting in enormous projected market growth rates. However, the breakthrough to profitable commercialization of that technology has not yet been achieved, partly because the production process chain is characterized by a high proportion of manual laboratory work. The present work addresses this point. Utilizing affordable components, a demonstrator was developed that can be integrated into an existing 3D-bioprinting system and enables the automated production of perfusion-ready OoC devices starting from pre-fabricated injection-molded microfluidic chips. To this end, a corresponding process chain was first defined, and an expandable, configurable algorithm was developed and validated in the form of a finite state machine (FSM). This algorithm controls a modified 4-axis robot arm that covers the steps upstream and downstream of the printing process in the manufacturing process and achieves success rates of up to 100 %. A virtual interface between the robot and printer enables mutual communication and full integration of the algorithm into the process chain. Steps that pose a challenge for the automation of the process chain and appropriate countermeasures and optimizations were identified. This lays the foundation for scaling and standardizing the automated production of OoCs.