Advancements in modelling human blood brain-barrier on a chip.

The human Blood Brain Barrier (hBBB) is a complex cellular architecture separating the blood from the brain parenchyma. Its integrity and perfect functionality are essential for preventing neurotoxic plasma components and pathogens enter the brain. Although vital for preserving the correct brain activity, the low permeability of hBBB represents a huge impediment to treat mental and neurological disorders or to address brain tumors. Indeed, the vast majority of potential drug treatments are unable to reach the brain crossing the hBBB. On the other hand, hBBB integrity can be damaged or its permeability increase as a result of infections or in presence of neurodegenerative diseases. Currentin vitrosystems andin vivoanimal models used to study the molecular/drug transport mechanism through the hBBB have several intrinsic limitations that are difficult to overcome. In this scenario, Organ-on-Chip (OoC) models based on microfluidic technologies are considered promising innovative platforms that combine the handiness of anin vitromodel with the complexity of a living organ, while reducing time and costs. In this review, we focus on recent advances in OoCs for developing hBBB models, with the aim of providing the reader with a critical overview of the main guidelines to design and manufacture a hBBB-on-chip, whose compartments need to mimic the 'blood side' and 'brain side' of the barrier, to choose the cells types that are both representative and convenient, and to adequately evaluate the barrier integrity, stability, and functionality.

Potential of CO2-laser processing of quartz for fast prototyping of microfluidic reactors and templates for 3D cell assembly over large scale.

Carbon dioxide (CO2)-laser processing of glasses is a versatile maskless writing technique to engrave micro-structures with flexible control on shape and size. In this study, we present the fabrication of hundreds of microns quartz micro-channels and micro-holes by pulsed CO2-laser ablation with a focus on the great potential of the technique in microfluidics and biomedical applications. After discussing the impact of the laser processing parameters on the design process, we illustrate specific applications. First, we demonstrate the use of a serpentine microfluidic reactor prepared by combining CO2-laser ablation and post-ablation wet etching to remove surface features stemming from laser-texturing that are undesirable for channel sealing. Then, cyclic olefin copolymer micro-pillars are fabricated using laser-processed micro-holes as molds with high detail replication. The hundreds of microns conical and square pyramidal shaped pillars are used as templates to drive 3D cell assembly. Human Umbilical Vein Endothelial Cells are found to assemble in a compact and wrapping way around the micro-pillars forming a tight junction network. These applications are interesting for both Lab-on-a-Chip and Organ-on-a-Chip devices.