Design of a membrane for a lung-on-a-chip device
Design and testing of a membrane concept incorporating a dynamic pore size to study the alveolar-capillary barrier in vitro
S.A.M. den Boer (TU Delft - Mechanical Engineering)
U STAUFER – Mentor (TU Delft - Micro and Nano Engineering)
Massimo Mastrangeli – Mentor (TU Delft - Electronic Components, Technology and Materials)
Robbert Rottier – Mentor (Erasmus MC)
Pouyan Boukany – Graduation committee member (TU Delft - ChemE/Product and Process Engineering)
EL Fratila-Apachitei – Graduation committee member (TU Delft - Biomaterials & Tissue Biomechanics)
C. M. Boutry – Coach (TU Delft - Electronic Components, Technology and Materials)
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Abstract
In vitro models are fundamental in the study of cell behaviour, the physiological function of organs, and their response to drugs and toxins. However, the shortage of accurate and reliable in vitro models calls for the development of in vitro lung models that better recapitulate lung physiology and pathology. Lung-on- a-chip models are promising to this end. To date, most membranes used in these models are made of poly(dimethylsiloxane), which has significant disadvantages. Moreover, there is a need to establish adequate membrane pore sizes throughout the cell culture duration. A design of a novel LOC membrane containing a dynamic membrane pore size to recapitulate the pulmonary alveolar-capillary barrier was designed and its viability evaluated. Poly(octamethylene maleate (anhydride) citrate) (POMaC) is evaluated as a membrane material on its cytotoxicity, biodegradability and imaging properties. For creating a thin and porous membrane, spincoating, moulding and 2-photon polymerization were studied.
The results provide promising support for fabricating a thin membrane. It was concluded that thin, uniform POMaC layers and a conical micropillar mould could be created. Moreover, stiffness of POMaC was in the expected range, and the bioimaging properties were found to be suitable. The degradation results did not support the hypothesis that a structural pore size could increase, which likely impedes the increase of pore diameter necessary for immune cell transmigration. Therefore, a model of the degradation characteristics of POMaC is proposed.