Issue 8, 2021

High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows

Abstract

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro, therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools. Here we present an OOC platform with advanced culture capabilities supporting a variety of human tissue models including liver, vascular, gastrointestinal, and kidney. The platform has 96 devices per industry standard plate and compatibility with contemporary high-throughput data collection tools. Specifically, we demonstrate programmable flow control over two physiologically relevant flow regimes: perfusion flow that enhances hepatic tissue function and high-shear stress flow that aligns endothelial monolayers. In addition, we integrate electrical sensors, demonstrating quantification of barrier function of primary gut colon tissue in real-time. We utilize optical access to the tissues to directly quantify renal active transport and oxygen consumption via integrated oxygen sensors. Finally, we leverage the compatibility and throughput of the platform to screen all 96 devices using high content screening (HCS) and evaluate gene expression using RNA sequencing (RNA-seq). By combining these capabilities in one platform, physiologically-relevant tissues can be generated and measured, accelerating optimization of an in vitro model, and ultimately increasing predictive accuracy of in vitro drug screening.

Graphical abstract: High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows

Supplementary files

Article information

Article type
Paper
Submitted
27 Janv. 2021
Accepted
20 Marts 2021
First published
08 Apr. 2021
This article is Open Access
Creative Commons BY-NC license

Lab Chip, 2021,21, 1454-1474

High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows

H. Azizgolshani, J. R. Coppeta, E. M. Vedula, E. E. Marr, B. P. Cain, R. J. Luu, M. P. Lech, S. H. Kann, T. J. Mulhern, V. Tandon, K. Tan, N. J. Haroutunian, P. Keegan, M. Rogers, A. L. Gard, K. B. Baldwin, J. C. de Souza, B. C. Hoefler, S. S. Bale, L. B. Kratchman, A. Zorn, A. Patterson, E. S. Kim, T. A. Petrie, E. L. Wiellette, C. Williams, B. C. Isenberg and J. L. Charest, Lab Chip, 2021, 21, 1454 DOI: 10.1039/D1LC00067E

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