A Simple and Robust Microfluidic Glomerular Filtration Barrier-on-a-Chip Platform for Investigating Drug-Induced Nephrotoxicity

The glomerulus is the filtering unit of the kidney, and the glomerular filtration barrier (GFB) is responsible for filtering waste, retaining plasma protein, and maintaining fluid balance. Drug-induced nephrotoxicity is characterized by dysfunction of the GFB and is a main obstacle in the new therapeutic screening process. This paper presents the simple and robust SLAS (Society of Laboratory Automation and Society) standard format-based microfluidic GFB-on-a-chip (GFBoC). We formed and cultured the GFB by aligning human glomerular mesangial cells (gMCs), podocytes, and glomerular endothelial cells (gECs) on each side of a conventional transwell membrane as the glomerular basement membrane (GBM). This provides facile loading/unloading of the GFB transwell into the microfluidic chip, enabling its cultivation under pump-/tubing-less perfusion flow and additional off-chip bioanalysis. It also allows various and multiple experiments in parallel in a conventional incubator at moderate operation complexity. Glomerular selective permeability of the GFB was characterized by filtration and leakage of the representative macromolecule, albumin, via the GFB, while the drug doxorubicin affected the GFB during cultivation in the GFBoC. This demonstrated that the GFBoC has potential as a simple, robust, and efficient platform for the multiple testing of nephrotoxicity and kidney disease drugs in parallel.