On-chip cell culture

Scientific Leader: Anne-Marie Haghiri-Gosnet

Principal investigator: Gilgueng Hwang

Postdocs: Julie Lachaux, Martina Ugrinic

Recently, advanced in vitro microfluidic cell culture systems have emerged that are capable of replicating the complex three-dimensional architectures of tissues and organs.

The first microfluidic physiological function studied was the oxygenation/decarbonation of blood. The fluidic oxygenator that has been developed in the context of the RHU-ANR BioArtLung H2020 project (in collaboration with Prof. O. Mercier – Marie - Lannelongue hospital) is an innovative microfluidic device for blood oxygenation as a durable method of replacing lung function in patients with end-stage, refractory lung disease. In the field of microfluidic oxygenators, maximizing the efficiency of gas exchange while increasing blood flow remains a major challenge. We have designed a 4-inch PDMS microfluidic oxygenator that maximizes gas exchange surface area and can be stacked on multiple levels to improve maximum blood flow to be processed. The height of blood channels has been optimized to reduce pressure drop and enhance gas exchange at high volumetric blood flow rate up to 15 ml/min.  This microfluidic oxygenator is manufactured by a layer-by-layer assembly based on a wet bonding method [European patent EP18 306 405.4 - “microfluidic gas exchange devices and methods for making same”. filed October 29, 2018, internationally extended wo2020 / 089116a1 - May 7, 2020]. High gas exchange efficiency up to blood flow rates of 15 ml / min was obtained (see Figure). The corresponding article is currently under review in Lab-on-a-Chip [A compact integrated microfluidic oxygenator with high gas exchange efficiency designed for sustainable endothelialization, submitted to Lab Chip].

Finally, with blood injectors designed to dramatically reduce shear stress, a flow protocol based on cord blood-derived endothelial progenitor cells is shown to produce sustainable endothelialization since cells are maintained viable for up to 2 weeks after initial seeding.

These microfluidic devices represent valid biological models for investigating the mechanism and function of human tissue structures, as well as studying the onset and progression of diseases, such as cancer.

In this context, in collaboration with P. Couvreur and S. Mura (équipe 7 – Institut Galien Paris Sud), we are developing a tumor-on-a-chip as an innovative 3D in vitro model of pancreatic cancer able to recreate the complex physiology of the tumor microenvironment (µF-3D-Nano project funded by NanoSaclay Labex). The PDMS microfluidic-based platform allows a spatially controlled triple co-culture of Panc-1 tumor spheroids, fibroblasts and endothelial cellsembedded in fibrin-collagen hydrogels. Understanding the efficacy of anticancer drugs on spheroids is the main goal of this running project.