Jun 26 – 30, 2022
Europe/Berlin timezone

A blocked split-plot experiment to detect the influential steps in a cell-based bioassay

Jun 27, 2022, 3:20 PM
20m
EL5

EL5

Design and analysis of experiments CONTRIBUTED Design of Experiment 2

Speaker

Alexandre Bohyn (KU Leuven)

Description

Over the last decade, 3-dimensional in vitro cell-based systems, like organs-on-chips, have gained in popularity in the pharmaceutical industry because they are physiologically relevant and easily scalable for high-throughput measurements. We wish to detect influential steps in a cell-based bio-assay using the OrganoPlate® platform developed by the company Mimetas BV. The cells are to form tubular structures grown against an extra-cellular matrix inside the wells of the culture plate. The matrix is created according to a specific protocol. Given that the quality of the matrix strongly influences the tightness of the tubular cell structures, we want to identify which of 8 factors involving features of the protocol affect that tightness. The budget is limited to 32 runs in total. As one plate can accommodate 8 runs, the runs must be spread out over 4 plates. Two factors are time-related, which makes them hard-to-change and creates a split-plot structure in the experiment. Further, batches of extra-cellular matrix material are shared among different runs. In addition, the experimenters wanted to keep track of possible edge effects on the plates based on insights from previous high-throughput platforms, so there is a need to block the runs over the positions on the plate. These features give rise to a complicated error structure and a division of the factor effects of the factors in groups with different standard errors. We developed a fractional factorial design that is compatible with the error structure so that it provides the information needed to optimize the protocol for creating the extra-cellular matrix.

Keywords organs-on-chips, screening experiment, fractional factorial design

Primary authors

Alexandre Bohyn (KU Leuven) Peter Goos (KU Leuven, Universiteit Antwerpen) Prof. Eric Schoen (KU Leuven) Dr Chee Ng (Mimetas) Mrs Kristina Bishard (Mimetas) Mrs Manon Haarmons (Mimetas) Dr Sebastian Trietsch (Mimetas)

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