Abstract
Microphysiological systems (MPSs), including organ-on-a-chip (OoC), have attracted attention as a novel method for estimating the effects and side effects of drugs in drug discovery. To reproduce the dynamic in vivo environment, previous MPSs were connected to pump systems to perfuse culture medium. Therefore, most MPSs are not user-friendly and have poor throughput. We aimed to develop a kinetic pump integrated microfluidic plate (KIM-Plate) by applying the stirrer-based micropump to an open access culture plate to improve the usability of MPSs. The KIM-Plate integrates six multiorgan MPS (MO-MPS) units and meets the ANSI/SBS microplate standards. We evaluated the perfusion function of the kinetic pump and found that the KIM-Plate had sufficient agitation effect. Coculture experiments with PXB cells and hiPS intestinal cells showed that the TEER of hiPS intestinal cells and gene expression levels related to the metabolism of PXB cells were increased. Hence, the KIM-Plate is an innovative tool for the easy coculture of highly conditioned cells that is expected to facilitate cell-based assays in the fields of drug discovery and biology because of its usability and high throughput nature.
Highlights
Microphysiological systems (MPSs), including organ-on-a-chip (OoC), which can reproduce the in vivo blood flow and organ/tissue structure by culturing cells on a microfabrication technology-based chip, are attracting attention as a technology that will revolutionize drug research and development [1,2,3,4]
We have developed a kinetic pump integrated microfluidic plate (KIMPlate) by applying the stirrer-based kinetic pump to an open access culture plate to improve the usability of multiorgan MPS (MO-MPS)
The fluorescence intensity ratio increased with time at 2500–6500 rpm, and the rate of increase in the fluorescence intensity ratio improved with the increase in the rotation speed of the kinetic pump
Summary
Microphysiological systems (MPSs), including organ-on-a-chip (OoC), which can reproduce the in vivo blood flow and organ/tissue structure by culturing cells on a microfabrication technology-based chip, are attracting attention as a technology that will revolutionize drug research and development [1,2,3,4]. MPSs are expected to become powerful tools for predicting pharmacokinetics in various organs and tissues, such as absorption, distribution, metabolism, and excretion (ADME) and drug effects including toxicity. In addition to single-organ models [5,6,7,8,9,10,11], multiorgan MPSs (MO-MPSs) have been proposed to evaluate interorgan interactions by coculturing cells derived from multiple organs and tissues [12,13,14,15,16]. Micromachines 2021, 12, 1007 pharmacokinetics, because they can evaluate drug effects according to drug concentrations that change with time [17,18]. A market report by Yole estimated the MPS market revenue to be less than USD 7.5 million in 2016; the MPS market has the potential to grow tremendously in the medium to long term and become a multibilliondollar market due to its potential to help save billions of dollars annually by bridging the gap between preclinical and clinical trials required for drug development [20]
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