Nabhan Fakrudin

Helios Scholar

An estimated 3.4 billion people globally are affected by neurological disorders, and that continues to rise due to increased life expectancy. There is a pressing need for predictive in vitro drug delivery models to develop more effective neurotherapeutics and establish safe and effective dosing. The human blood-brain barrier (hBBB) presents a significant obstacle by impeding the delivery of 100% of large and 98% of small molecule drugs to the brain.

Bubble-assisted focused ultrasound (BAFUS), an innovative technology currently in clinical trials, allows transient BBB disruption (BBBD) to deliver neurotherapeutics to the brain. Additionally, organ-on-chip (OoC) models are great in vitro platforms for studying biological barrier models. Our lab has previously developed a ‘US-transparent BBB OoC model’ to simulate BAFUS BBB disruption and recovery of a Caco-2 barrier with a Trans-Epi/Endothelial Electrical Resistance (TEER) of 300-400Ωcm². However, the Caco-2 model lacks the in vivo BBB paracellular transport characteristics with an estimated TEER of ~ 8000Ωcm² and no high-resolution TEER available for real-time barrier disruption monitoring.

This project aims to a. develop a protocol for iPSC-derived Brain Microvascular Endothelial Cells (iBMVECs) to generate BBB in vitro models with TEER close to that in vivo. b. develop a real-time high-resolution (rt-hr) TEER monitoring system, and c. fabricate and test custom electrodes of various metals toward a future high-throughput system. iBMVECs were derived and validated using morphology and BBB characteristic mRNA expression; a TEER of 5500Ωcm² was recorded. rt-hr TEER monitoring was achieved, and the custom-fabricated probes were tested.