Open-Source System for Real-Time Functional Assessment of In Vitro Filtration Barriers

被引:0
|
作者
Fallon, Tess K. [1 ,3 ]
Zuvin, Merve [1 ]
Stern, Alan D. [1 ]
Anandakrishnan, Nanditha [1 ]
Daehn, Ilse S. [1 ]
Azeloglu, Evren U. [1 ,2 ]
机构
[1] Icahn Sch Med Mt Sinai, Barbara T Murphy Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Pharmacol Sci, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA
[3] Columbia Univ, Dept Elect Engn, 500 W 120th St, New York, NY 10027 USA
关键词
Open science; Fluorescence sensor; Glomerulus; Functional assay; Microfluidics; Organ-on-chip; Kidney-on-chip; CHRONIC KIDNEY-DISEASE; DIFFUSION; MEMBRANE; CHIP;
D O I
10.1007/s10439-023-03378-9
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The integrity of the barrier between blood and the selective filtrate of solutes is important for homeostasis and its disruption contributes to many diseases. Microphysiological systems that incorporate synthetic or natural membranes with human cells can mimic biological filtration barriers, such as the glomerular filtration barrier in the kidney, and they can readily be used to study cellular filtration processes as well as drug effects and interactions. We present an affordable, open-source platform for the real-time monitoring of functional filtration status in engineered microphysiological systems. Using readily available components, our assay can linearly detect real-time concentrations of two target molecules, FITC-labeled inulin and Texas Red-labeled human-serum albumin, within clinically relevant ranges, and it can be easily modified for different target molecules of varying sizes and tags. We demonstrate the platform's ability to determine the concentration of our target molecules automatically and consistently. We show through an acellular context that the platform enables real-time tracking of size-dependent diffusion with minimal fluid volume loss and without manual extraction of media, making it suitable for continuous operational monitoring of filtration status in microphysiological system applications. The platform's affordability and integrability with microphysiological systems make it ideal for many precision medicine applications, including evaluation of drug nephrotoxicity and other forms of drug discovery.
引用
收藏
页码:327 / 341
页数:15
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