Michael Kulik und Andreas Elanzew, Fraunhofer IPT, Aachen
The biomedical prospects of human induced pluripotent stem cells (hiPSCs) have created an urgent need for standardized and automated processes for reprogramming and expansion of hiPSC lines from large patient cohorts. This need can be met by the StemCellFactory (www.stemcellfactory.de), a large system integration that automates and controls all required cell culture steps, ranging from adult human dermal fibroblast (HF) expansion via feeder-free, Sendai virus-based reprogramming to clonal selection and enzyme-free expansion of the obtained hiPSC clones and lines.
This requires a highly flexible control software with extensive data management, robust device integration/communication and a metrology based process control, which is at the same time user friendly. For this purpose a control software was developed, which allows the user to run the factory manually but also in an automated mode. All integrated devices are connected to the control software and provide device specific services, which are used for different process steps. Complete processes were programed and parametrized by using function blocks and saved as a sequences. The programmed sequences were applied on multititer plates and scheduled. To achieve a complete automated run of multititer plates with patient specific cells threshold based decision logics are implemented that compute and translate the acquired data during the process and adapts the workflow according to the measured results. Eventually, extensive biological validation was performed to confirm that automatically expanded hiPSCs remain pluripotent upon automated long-term (10 passages) cultivation. In summary our data show that analysis of in-process generated data largely facilitates automation of highly dynamic cell culture processes.
