Microfluidic Chip for Modeling Ultrafiltration Failure

Mastriani, Isabella; Breen, Sydney; Bolshakov, Roman; Mello, Antone

Student Work

Microfluidic Chip for Modeling Ultrafiltration Failure

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Chronic kidney disease (CKD) causes gradual loss of kidney function in approximately 15% of U.S. adults, where treatment options are either a full organ transplant or routine dialysis treatments for life. Dialysis is conventionally performed through the kidneys as seen with hemodialysis, or through the peritoneum as seen in peritoneal dialysis. Peritoneal dialysis (PD) is oftentimes more favorable for patients due to the ability to complete treatments at home rather than in a hospital environment. Patients must ultimately switch to hemodialysis after several years of undergoing PD due to a buildup of bio-incompatible fluids that lead to stiffening and fibrosis of the membrane that blocks the proper filtration of waste. This phenomenon is known as ultrafiltration failure (UFF), and has four characteristic stages of progressive fibrotic states. Ultrafiltration failure is thought to occur so frequently with PD due to physiological changes, including fibrosis, and increased lymphatic vascular growth in the peritoneum from repeat exposure to dialysate fluid. In the current clinical and research sphere, there is a limited understanding on the overall mechanisms behind Type III UFF in the peritoneum, which decreases the feasibility of peritoneal dialysis as a long-term treatment option for a larger percentage of patients. Currently there is no comprehensive in vitro model to study UFF. A microfluidic device could play that role. Working from a previous iteration of this project’s three-chamber chip model, objectives were created to progress toward a fully comprehensive in vitro model. The project specifically focused on improving hydrogel retention, achieving pathophysiological stiffness for the hydrogel, and using a syringe pump to modify flow rate/filtration. The device was designed as a high-throughput model that can be cellularized in the future to better reflect physiological conditions of Type III UFF in a laboratory setting to aid researchers in learning more about this condition, providing a basis for interstitial flow and filtration through a hydrogel with in vivo-like stiffness. The most current iteration, the modified-microgroove three-chamber microfluidic chip, consists of a hydrogel chamber in the center, flanked by a dialysate chamber mimicking dialysate fluid flow and a vascular chamber that mimics blood flow. The vascular chamber accommodates for blood analog fluid flow through a syringe pump system to mimic peritoneal capillary function. For the middle hydrogel portion, multiple crosslinkers were used and tested in hopes of increasing their likeness to the peritoneum in terms of stiffness and permeability more closely than previous iterations. Crosslinkers used and tested were comprised of a bovine collagen hydrogel (Telocol®-10), glutaraldehyde and Telocol®-10 crosslinks at four different concentrations and a sodium alginate/calcium chloride that achieved an average stiffness of 6.57 kPa akin to the fibrotic peritoneum after approximately three months of PD treatment. The dialysate chamber acts as a fluid reservoir where waste products from the blood analog diffuse across the hydrogel and can be removed after the appropriate dwell time. This model is able to mimic in vivo properties of the peritoneum in regards to stiffness and filtration rate through the chip. The chip is accessible for laboratories, as it is able to fit on a standard microscope with clear visibility. In addition, it is also able to be produced with simple components found within a standard lab. The components of the chip are reusable with a PFOCTS treatment, which reduces some of the costs associated with the chip. A need to further investigate the porosity of these hydrogels, as well as a way to seed and retain them has been identified. These points provide the future direction of the project.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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