Unlocking the Potential of Organ-on-Chip Models through Pumpless and Tubeless Microfluidics.

Microfluidic organs-on-chips are rapidly being developed toward eliminating the shortcomings of static in vitro models and better addressing basic and translational research questions. A critical aspect is the dynamic culture environment they provide. However, the associated inherent requirement for controlled fluid shear stress (FSS) and therefore the need for precise pumps limits their implementation. To address this issue, here a novel approach to manufacture pumpless and tubeless organs-on-chips is reported. It relies on the use of a hydrophilic thread to provide a driving force for the perfusion of the cell culture medium through constant evaporation in the controlled conditions of a cell incubator. Well-defined and tuneable flow rates can be applied by adjusting the length and/or diameter of the thread. This approach for the preparation of an intestine-on-chip model based on the Caco-2 cell line is validated. Five days culture under 0.02 dyn·cm-2 shear conditions yield monolayers similar to those prepared using a high-precision peristaltic pump. A pumpless device can also be used to delineate the effect of FSS on the phenotype of adenocarcinomic human alveolar basal epithelial A549 cells. It is anticipated that the pumpless approach will facilitate and herefore increase the use of organs-on-chips models in the future.