Automation and High Throughput Technologies
Currently, the performance of long-term in-vitro assays using microphysiological systems, like Multi-Organ-Chips, require high manual effort and work force. This makes it still difficult to use them for high-throughput testing and the adaption to industrial needs, where reproducibility and standardization of microphysiological assays are essential demands. Moreover, automation will facilitate the use of microphysiological systems for regulatory purposes.
Here we present, for the first time, a fully automated robotic platform for the standardized long-term cultivation of TissUse’s Multi-Organ-Chips. One robot can culture up to 24 Multi-Organ-Chips simultaneously, providing customized incubation, systemic pulsatile media circulation, regular media exchange, substance application and microscopic analysis for each Multi-Organ-Chip. Four levels of interactive handling features were developed to ensure these functions. The Multi-Organ-Chips are inserted into a heating platform providing an adjustable constant temperature from 36 to 40°C. All liquid handling procedures are performed under sterile conditions inside a tailor-made class II safety cabinet. An automated provisioning system integrated into a refrigerator beneath the safety cabinet can hold a minimum of 66 well plates of various sizes and deliver them to the liquid handling system on demand. Cell culture media or substances are pre-heated to 37°C and applied with high pipetting accuracy using single use tips. The robot runs autonomously for a minimum of 4 days before a restock of disposables (e.g. pipet tips) is necessary. Media samples extracted from the Multi-Organ-Chips are stored at 4°C for further analysis. An actuated full sized microscopic unit beneath the Multi-Organ-Chips allows for routine optical analyses such as bright field imaging and fluorescence measurements at any chosen time point. Images are analyzed automatically using data processing software. A dedicated robot assay planning software enables the intuitive and time efficient input of new assay information. The software also checks for assay feasibility and will provide instructions for equipping the system with the respective Multi-Organ-Chips and consumables. All features ensure that in near future the platform will also be able to operate the TissUse Human-on-a-Chip in the near future.