Microfluidics and “Organs-on-chip”: is it possible to mimic blood vessels?
Anne-Marie Haghiri (C2N)
“Organs-on-a-chip” aim to capture key functions that are indispensable for the physiological functioning of a specific organ by mimicking the tissue elements that perform these functions in vivo. In this context, microfluidics offers the ability to reconstruct in vitro biological microenvironments with all the biophysical and biochemical expected parameters including cellular coatings. Along this talk, I will focus on microfluidic devices aiming to mimic blood microvessels based on two complementary approaches.
The first approach concerns the microfluidic wearable artificial lung that recovers on chip the physiological function of breath. A microfluidic oxygenator mainly consists of three layers with a thin gas permeable membrane sandwiched between a blood microcapillaries network and a gas network. To meet clinical demands, such device must therefore meet certain requirements, which are 1/ support high blood flow without reducing the gas transfer efficiency, 2/ minimize pressure drop and shear stress in the blood module, 3/ enhance hemocompatibility by coatings. Our device has been designed at the 4-inch wafer scale with very dense curved blood and oxygen microcapillaries separated by a 15 µm-thick porous membrane . Such design allows reducing both priming volume while maintaining efficient gas exchange. Biomimetic blood flow paths with low shear rate also promotes sustainable endothelialization since cells can be maintained viable for up to 2 weeks after initial seeding. The simplicity of connecting different units in the stacked architecture has also been demonstrated for 3- or 5-unit stacked devices that exhibit remarkable performance with low primary volume, high oxygen uptake and carbon dioxide release and high flow rate up to 80 ml/min .
The second more conventional approach consists to generate microvasculature directly inside the chip where a tumor model is growing. Here, we developed a simple method to fabricate high aspect ratio 3D microfluidic devices, as geometrically optimized microenvironment for long-term culture and vascularization of 3D tumor models (i.e., spheroids). The role of the height of the central chamber on the growth of a heterotypic pancreatic tumor spheroid, made of cancer cells and fibroblasts is under study. We recently demonstrated that a 500µm-thick microfluidic chamber promotes more gradual cell growth and migration, thanks to the availability of space for spheroid evolution. Finally, I will conclude on the importance of innovative design/architecture coupled with adapted microfabrication processes.
 A-M. Haghiri-Gosnet, Lyas Djeghlaf, Julie Lachaux, Alisier Paris, Gilgueng Hwang, European Patent EP18306405.4 (29 Oct. 2018) « Microfluidic gas exchange devices and methods for making same »
 Julie Lachaux, Gilgueng Hwang, Nassim Arouche, Sina Naserian, Abdelmounaim Harouri, V. Lotito, C. Casari, T. Lok, J B. Menager, J. Issard, J. Guihaire, C. V. Denis, P. J. Lenting, A. I. Barakat, G. Uzan, O. Mercier, Anne Marie Haghiri-Gosnet, Lab Chip, 2021, 21, 4791 DOI:10.1039/d1lc00356a
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