Brain-Organoid-on-Chip & Irrigated Skin (PoC) Applications

Program:

• Use Case #1: Brain-organoid-on-Chip, in collaboration with SupBiotech & CEA
• Key results
• Paves the way for blood-brain barrier modeling
• Use Case #2: Irrigated SKin (Proof of Concept)
• Key results
• Q&A Session

More details:

Brain-Organoid-on-Chip

Over recent years, cerebral organoids have emerged as relevant three-dimensional in vitro models of human cerebral cellular organization and development. Nevertheless, the implementation of organoids for drug screening requires reproducibility and scalability. To address this challenge, we combine cerebral organoid culture with a microfluidic device (NETRI’s Duplex Well) to create a Brain Organoid-on-Chip platform. This innovative approach improves cerebral organoid reproducibility, and thus predictability, facilitating industrial transferability for applications in neurodevelopmental toxicity testing and drug screening. Our experimental strategy is based on optimizing cortical organoid culture conditions (protocol adapted from) in the device, which comprises two compartments, a 3D culture chamber, and a perfusion channel allowing medium diffusion, separated by a porous membrane. We established a robust protocol for maintaining cortical organoids on-chip in culture for up to 3 months, by testing different organoid introduction time points and medium renewal methods. On-chip cortical organoids were compared with control organoids grown in a conventional support, in terms of morphology, growth, cytoarchitecture, and transcript expression levels. This was performed using two different cell lines, to exemplify the universality of the observed improvements. We also performed preliminary neurotoxicological studies by treating cortical organoids on-chip with neuroprotective (vanillin) and toxic (biphenyl-2-ylamine) compounds, alongside the establishment of a prediction algorithm for neurotoxicity evaluations. On-chip cortical organoids exhibited characteristic morphology, cell types, cytoarchitectures, and RNA expression levels expected after 60 days of culture. Compared with control organoids, on-chip organoids displayed enhanced intra- and inter-batch reproducibility in terms of size, growth profile, and cytoarchitectural organization. This was observed with both cell lines. Preliminary data on organoids exposed to a toxic compound showed dose-response neurotoxicity and highlights the potential of this platform in predicting neurotoxicity. Our proposed Brain Organoid-on-Chip platform enables cortical organoid culture and improves organoid reproducibility, meeting the needs of neurological preclinical studies. This platform paves the way for using brain organoids in toxicological assessments, such as developmental neurotoxicity, and drug screening.

Irrigated skin

We will present a proof-of-concept of our irrigated skin model using our Duplex Well chip and a co-culture of keratinocytes and endothelial cells.