Issue 9, 2019

A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions

Abstract

Microphysiological systems (MPSs) are dynamic cell culture systems that provide micro-environmental and external cues to support physiologically relevant, organ-specific functions. Recent progresses in MPS fabrication technologies have enabled the development of advanced models to capture microenvironments with physiological relevance, while increasing throughput and reducing material-based artefacts. In addition to conventional cell culture systems, advanced MPSs are emerging as ideal contenders for disease modeling and incorporation into drug screening. Since liver is a central organ for drug metabolism, liver-on-chip models have been developed to recapitulate hepatic microenvironment with varying complexities, while allowing long-term culture. Recently, we have developed a novel thermoplastic, oxygen-permeable MPS for primary human hepatocyte (PHH) culture. Herein, we have adapted and extended the MPS to a) a 96 microfluidic array (PREDICT-96 array) and b) integrated a novel, ultra-low volume, re-circulating pumping system (PREDICT-96 pump) – collectively known as the PREDICT-96 platform. The PREDICT-96 platform conforms to the industrial standard 96-well footprint and enables media re-circulation. First, we demonstrate the introduction of PHHs into the PREDICT-96 array using standard handling procedures for multi-well plates and allow cells to stabilize in static conditions. Next, we introduce recirculating flow into the bottom channel (using PREDICT-96 pump) to mimic mass transport in vivo. Our results indicate an increase in metabolic and secretory functions of PHHs in the PREDICT-96 platform, and their maintenance over 10 days of flow. Furthermore, long-term culture with fluid flow allows for the periodic introduction of media components (e.g., fatty acids, cytokines) and capture cellular responses to chronic stimuli. The low-volume footprint of the pump and small media volume in the MPS allow for the interrogation of hepatic responses incorporating secretion feedback to a stimulus, which is essential for disease model development and drug interrogation. We envision future development of this liver model to incorporate key primary hepatic cells, multi-cellular co-cultures and adaptation, integration with high-throughput analytical tools.

Graphical abstract: A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
16 nov 2018
Accepted
28 feb 2019
First published
05 mrt 2019

Lab Chip, 2019,19, 1556-1566

A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions

K. Tan, P. Keegan, M. Rogers, M. Lu, J. R. Gosset, J. Charest and S. S. Bale, Lab Chip, 2019, 19, 1556 DOI: 10.1039/C8LC01262H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements