Fabrication of Ultra-Thin Micro-Porous PDMS Membrane for Cell Co-Culture in Blood Brain Barrier Model on Chip

In vitro human blood-brain barrier (BBB) model is amenable to cellular studies on pathological and drug transport mechanisms related to the central nervous system (CNS). Compared with animal model of human, micro BBB ( $\mu \text{BBB}$ ) based on microfluidic chips is closer to in vivo phenotype and is more reproducible. Porous semipermeable membranes are integral components of the chip model, which provide cellular interfaces and help establish barrier models. This study proposes a convenient and low-cost fabrication method for ultra-thin micro-porous poly(dimethylsiloxane) (PDMS) membrane, which is inspired by paraffin section technique in immunohistochemistry. Microporous PDMS was obtained from the cured emulsion of PDMS pre-polymer containing uniformly dispersed micro-droplets of water. Cured microporous PDMS was embedded in paraffin to enhance the hardness and then sliced into membrane with a paraffin slicing machine. The minimum thickness of the membrane is $10\ \mu \mathrm{m}$ and smallest pore of $1\ \mu \mathrm{m}$ . The pore size and porosity of the membrane can be adjusted by controlling the water content and mixing time. To prove proof-of-concept, the immortalized human cerebral microvascular endothelial cell line (hCMEM/D3) was seeded on the membrane in a BBB-on-chip. This method provides a potential solution to simply prepare customized PDMS membranes for researchers in biomedical laboratory without micromanufacturing equipment.