Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells

Induced pluripotent stem cells (iPSCSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSCSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSCSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines.