Nanoporous glass membranes fabricated by femtosecond laser micromachining for in vitro lab-on-chip applications

Developing effective treatments for neurodegenerative diseases such as Alzheimer’s requires advanced in vitro models that accurately replicate physiological barriers like the blood-brain barrier (BBB). Lab-onchip (LOC) platforms offer powerful tools to mimic these complex biological interfaces, enabling precise study disease mechanisms and evaluating therapeutic strategies. To effectively simulate the BBB, membranes with pore sizes in the range of a few hundred of nanometers are essential to ensure selective permeability and sterility. In this context, glass-based membranes integrated into LOC devices provide superior chemical stability, biocompatibility, and optical clarity compared to conventional polymers, which suffer from molecule absorption and autofluorescence. However, fabricating nanoscale features in glass presents significant challenges. To address this, we employ femtosecond laser irradiation combined with wet chemical etching. Through a fine tuning of the irradiation parameters, combined with a tight focusing condition, enables the fabrication of sub-400 nm diameter through-holes after selective etching in NaOH of the modified regions. This approach allows nanoscale machining beyond traditional ultrafast laser micromachining limits. The membranes pores size and homogeneity will be optically and morphologically characterized. Their permeability performance will be assessed through gas permeability tests using a two-chamber custom made sealed device. To validate biocompatibility and functionality, 3D cellular scaffolds will be fabricated via two-photon polymerization (2PP) directly onto the membrane surface. This glass membranes offers a reliable, biocompatible, and optically transparent solution for LOC and biosensing applications requiring precise molecular filtration and sterile separation.