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Paving the way for High-throughput Organoid ENgineering using Integrated acoustiX

Project description

Advanced organoid engineering techniques to boost disease and drug development research

Cerebral organoids are 3D self-assembled structures derived from human induced pluripotent stem cells, replicating both the structure and function of the human foetal brain. Organoids could replace existing 2D in vivo cell cultures and animal models for diagnostic and treatment purposes, but this has not yet been realised owing to a lack of suitable preparation methods. The EU-funded PHOENIX project aims to develop a seamless organoid engineering pipeline to investigate reproducibility, controlled maturation and vascularisation of cerebral organoids. Using acoustophoresis, a method of manipulating particles and cells by ultrasound, researchers will seek to achieve ordered encapsulation of stem cells in hydrogel droplets. They will also develop a microfluidic platform where the cells will be differentiated under fully controlled conditions.

Objective

The aim of PHOENIX is to use my expertise in microsystems engineering to close critical technology gaps in organoid generation. Cerebral organoids are 3D self-assembled structures derived from human induced pluripotent stem cells, replicating both structure and function of the human foetal brain. Organoids have the potential to replace existing 2D cell cultures and animal models, but this has not yet been realised due to rudimentary preparation methods.

In PHOENIX, three important technology gaps will be addressed: reproducibility, controlled maturation and vascularisation. I aim to build on my pioneering research on droplet acoustofluidics and the scientific output of my ERC Starting Grant to develop three microfluidic modules that at the end of the project shall be integrated into a seamless organoid engineering pipeline. The technology in focus is acoustophoresis, a method to manipulate particles and cells by ultrasound. This will be used to achieve ordered encapsulation of stem cells in hydrogel droplets and develop a microfluidic platform where the cells can be differentiated under fully controlled conditions. Finally, two-photon writing will be used to integrate a vascular network with the organoid constructs to form an important delivery architecture for nutrients and blood components. PHOENIX will be focused on both technology development and thorough biological characterisation of the resulting organoids to demonstrate both expected, and unexpected, benefits of transferring organoid generation on-chip.

Collaborations have been established with Prof. Christine Mummery and Dr. Valeria Orlova, both at LUMC, NL as well as Dr. Anna Falk at KI, SE to provide expertise in complementary fields of this highly interdisciplinary project. The expected output of PHOENIX is a microfluidic technology that enables high-throughput generation of cerebral organoid with a multi-regional structure and vascularisation in a direct process.

Host institution

UPPSALA UNIVERSITET
Net EU contribution
€ 2 832 500,00
Address
VON KRAEMERS ALLE 4
751 05 Uppsala
Sweden

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Region
Östra Sverige Östra Mellansverige Uppsala län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 832 500,00

Beneficiaries (1)