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

Azizgolshani, H ; Coppeta, J. R ; Vedula, E. M ; Marr, E. E ; Cain, B. P ; Luu, R. J ; Lech, M. P ; Kann, S. H ; Mulhern, T. J ; Tandon, V ; Tan, K ; Haroutunian, N. J ; Keegan, P ; Rogers, M ; Gard, A. L ; Baldwin, K. B ; de Souza, J. C ; Hoefler, B. C ; Bale, S. S ; Kratchman, L. B ; Zorn, A ; Patterson, A ; Kim, E. S ; Petrie, T. A ; Wiellette, E. L ; Williams, C ; Isenberg, B. C ; Charest, J. L

Lab on a chip, 2021-04, Vol.21 (8), p.1454-1474 [Periódico revisado por pares]

England: Royal Society of Chemistry

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Título:
High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows
Autor: Azizgolshani, H ; Coppeta, J. R ; Vedula, E. M ; Marr, E. E ; Cain, B. P ; Luu, R. J ; Lech, M. P ; Kann, S. H ; Mulhern, T. J ; Tandon, V ; Tan, K ; Haroutunian, N. J ; Keegan, P ; Rogers, M ; Gard, A. L ; Baldwin, K. B ; de Souza, J. C ; Hoefler, B. C ; Bale, S. S ; Kratchman, L. B ; Zorn, A ; Patterson, A ; Kim, E. S ; Petrie, T. A ; Wiellette, E. L ; Williams, C ; Isenberg, B. C ; Charest, J. L
Assuntos: Colon ; Compatibility ; Computational fluid dynamics ; Data collection ; Flow control ; Fluid flow ; Form factors ; Gene expression ; Gene sequencing ; Human tissues ; Industry standards ; Model accuracy ; Model testing ; Optimization ; Oxygen consumption ; Oxygen probes ; Real time ; Ribonucleic acid ; RNA ; Screening ; Sensors ; Shear stress
É parte de: Lab on a chip, 2021-04, Vol.21 (8), p.1454-1474
Notas: 10.1039/d1lc00067e
Electronic supplementary information (ESI) available. See DOI
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Descrição: 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. 96 microfluidic devices with independent electrical readouts are coupled with 192 micropumps to make a high-throughput organ-on-chip platform.
Editor: England: Royal Society of Chemistry
Idioma: Inglês

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

England: Royal Society of Chemistry

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