Sensor Instrumented Blood-brain-barrier-on-a-chip for nanocarrier screeninG – SIBorG

The blood-brain barrier (BBB) hampers the development of innovative drugs and nanovectors to treat neuro-pathologies. The SIBorG project will develop an organ-on-chip-like in-vitro physiological microsystem, as an alternative to animal testing. The BBB-on-chip will be perfused to mimic the blood flow, and instrumentalized with biosensors for an integrated detection of nanocarriers transport. The project is dividing into 5 objectives, supported by preliminary results combining the multidisciplinary expertise of the coordinator and her team.

1) Development of the BBB-on-chip. The combination of two methodologies will allow the 3D coculture of human brain cells. They will organized as a vascularized tissue in a hydrogel of extracellular matrix (previously developed by the coordinator). The barrier function will be validated in dynamic under a physiologically pertinent shear stress.
2) Comparison of the BBB in a healthy versus pathological context. The microchip will be adapted to the microenvironment of a glioblastoma multiforme (BBTBoC for blood-brain-tumor-barrier-on-chip). This is the most common, but also the most aggressive brain tumor.
3) Instrumentalization of the BBB-on-chip. Transparent piezo-electrical substrates (lithium niobiate) will be used as integrated biosensors. The nanocarriers transport through the BBB and a micro-processed porous membrane will be specifically detected.
4) Screening of the transport and therapeutic efficiency. Besides the transport, the nanocarriers will be assessed for their delivery specificity, and their toxicity towards targeted and off-target cells. The goal is the dosage adjustment to prevent the heavy side-effects of those chemotherapeutic treatments.
5) The last objective is the management and valorization of the produced knowledges, with a diffusion in the scientific community, but also towards the general public to share about the health issues and innovative solutions that can bring the SIBorG project.