Design for an automated system for research on genetic diseases

Abstract

Human induced pluripotent stem cells (hiPSCs) offer the possibility to model human disease and study their behavior. They help scientists discover early disease-causing events in cells and are therefore used in discoveries about premature aging, congenital heart disease, cancer, and disorders connected to fetal development. Because of their characteristics, pluripotent cells can be employed to create any cell of the body and since they are derived by patient cells, potentially they can be manipulated to manufacture healthy cells for transplants. At present, the generation of iPSCs is very labor-intensive, requiring daily monitoring and handling of iPSCs. Researches have to be trained in every detail of the process, constantly monitor and bring further the development of the cells. This is a limiting factor for the generation of a high number of iPS lines and human handling can also include variables of imprecision that can make the process last longer. Automation is the solution adopted to overcome these struggles and increase production throughput. Existing automated models are expensive and rigid systems that require additional expenses in order to satisfy the change of needs of an IPSC producing facility. At the moment there are a limited number of systems for the automated production of IPSC cell lines. However, these robots are not able to readapt to changes of the process, or of the spaces where they are installed and do not follow exactly the process needs of every facility. In order to satisfy these needs, starting from the analysis of the processes used at the IPS Core Facility at Erasmus MC, the RXF system was developed. The system design objective has been reached by combining several fronts of investigation. On one side, the process of production has been initially investigated in order to identify functional needs. The results of this analysis have been merged with observations of the daily activities and work organization of the laboratory, which contributed to the understanding of the human factors necessary within biological production. An extensive comparative analysis of other automated systems has been conducted in order to identify the system structure that comes closest to the needs of the IPS Core Facility production necessities. Further analysis and realignment have been conducted on the final components to be embedded. On the other side, ideation sessions, and considerations on modularity, management of throughput and composition lead to the development of system architecture concepts. The combination of these two research sides and synthesis of the strengths of four initial concepts lead to one final proposition for the architecture layout of the automated system for IPSC production: the RXF. This is a system composed of three modules, each of which is used during one section of the overall IPSC production process, giving possibilities of repurposing the remaining modules for other processes.