A Glomerular Basement Membrane-on-a-Chip Model for Investigating Charge-Selective Transport Across the Human Filtration Barrier

Hemodialysis is a life-sustaining therapy that mimics the kidney’s in vivo ultrafiltration process outside the body. However, during dialysis, blood–membrane interactions activate the coagulation cascade and complement system, leading to protein adsorption on the membrane surface, impaired filtration, and adverse patient outcomes. This underscores the need for biocompatible membranes that better replicate the functional characteristics of the native glomerular filtration barrier. Charge is a major determinant of solute and protein transport across the glomerular basement membrane (GBM) in vivo and also influences fouling and protein adsorption during dialysis, yet its role remains insufficiently studied. To address this gap, we developed a human cell–based, PES membrane microfluidic GBM-on-a-chip and quantified charge-dependent transport to inform the design of more selective and hemocompatible dialysis membranes. AB 8/13 podocyte monocultures, ciGEnCs endothelial monocultures, and podocyte–endothelial co-culture chips were maintained under static conditions, with flow applied only during the charged dextran perfusion. Before perfusion, confocal imaging confirmed continuous monolayers and podocyte–endothelial contact in co-culture. Charge selectivity was assessed by perfusing fluorescent 10 kDa dextrans of defined charge (cationic, anionic, neutral) as individual injections through monoculture and co-culture configurations, with an equal-parts mixture additionally perfused in co-culture. Permeation was quantified fluorometrically as percent permeated. Neutral dextran permeated readily across all configurations, whereas charged species exhibited configuration-dependent transport behavior. Podocyte monocultures preferentially hindered anionic dextran, while ciGEnCs monocultures showed modest and nearly symmetric selectivity, consistent with incomplete barrier maturation in isolation. In co-culture chips, differential permeability of charged dextrans was observed in the single-solute experiments, a pattern that deviated from classical GBM charge selectivity and likely reflects combined effects of convective transport and interactions with the PES support membrane. In contrast, under mixed-charge conditions the system reproduced the expected physiological trend, with anionic dextran exhibiting the highest retention. These findings suggest that intermolecular electrostatic interactions among co-present macromolecules may reveal a more physiologically relevant filtration response under complex solute conditions.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Biomedical Engineering

Grantor

University of Saskatchewan

Year dc:date.issued

2026

Author dc:creator

• Pardawala, Nakiya

Advisor dc:contributor.advisor

• Abdelrasoul, Amira

Committee members dc:contributor.committeemember

• Peters, Reisha
• Meda, Venkatesh
• Lin, Yen Han
• Shoker, Ahmed

• Hemodialysis, Microfluidics, Organ-on-a-chip, Kidney, Glomerular basement membrane, Cell culture, Podocytes.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10388/18174

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/18174