Athena Chien
BME PhD Defense Presentation
Date: 2026-06-11
Time: 9:00 AM - 11:00 AM
Location / Meeting Link: IBB 1128 (Suddath Room)
Committee Members:
Craig Forest, PhD (Advisor); Nael McCarty, PhD; Aniruddh Sarkar, PhD; Omer Inan, PhD; Kapil Bharti, PhD
Title: Rapid and Subcellular Impedance Spectroscopy for Epithelial Barrier Dynamics
Abstract:
Epithelial tissues form selective barriers that maintain distinct environments in organs from the eye to the pancreas. Damage to these barriers is implicated in diseases affecting hundreds of millions of people — including macular degeneration, celiac disease, diabetic nephropathy, cystic fibrosis-related diabetes, and acute wheezing illness. Dysfunction of a single transport route — apical, basolateral, or paracellular — can be sufficient to drive disease pathogenesis, yet conventional electrophysiology techniques cannot resolve these individual pathways. This dissertation develops a progression of impedance-based approaches that advance from intracellular to purely extracellular measurement while achieving pathway-level resolution of epithelial transport. We first introduce three-probe electrochemical impedance spectroscopy (3P-EIS), which combines intracellular voltage recording with extracellular impedance to independently quantify the resistance and capacitance of apical, basolateral, and paracellular routes. To eliminate the complexity of intracellular recording, we then develop a purely extracellular method based on a two-resistor, two-capacitor (RCRC) circuit model that captures impedance properties missed by commercial instruments and achieves sub-minute temporal resolution. This reveals discovery of a previously unreported transient capacitance response during neutrophil transmigration in a cystic fibrosis-related diabetes model. Finally, we demonstrate that the two fitted RCRC time constants encode membrane-specific information, with basolateral perturbations reflected in τ₁ and apical perturbations in τ₂, validated pharmacologically on 16HBE monolayers. Applied to cystic fibrosis cells treated with elexacaftor/tezacaftor/ivacaftor, this approach — coined extracellular electrochemical impedance spectroscopy (EEIS) — detects restoration of apical CFTR function. EEIS provides a scalable, non-invasive route to resolving apical and basolateral transport with implications for high-throughput therapeutic screening in cystic fibrosis and other epithelial diseases.
