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On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures.

ABSTRACT: Multilayered and multicellular structures are indispensable for constructing functional artificial tissues. Engineered vascular-like microstructures with multiple layers are promising structures to be functionalized as artificial blood vessels. In this paper, we present an efficient method to construct multilayer microtubes embedding different microstructures based on direct fabrication and assembly inside a microfluidic device. This four-layer microfluidic device has two separate inlets for fabricating various microstructures. We have achieved alternating-layered microtubes by controlling the fabrication, flow, and assembly time of each microstructure, and as well, double-layered microtubes have been built by a two-step assembly method. Modifications of both the inner and outer layers was successfully demonstrated, and the flow conditions during the on-chip assembly were evaluated and optimized. Each microtube was successfully constructed within several minutes, showing the potential applications of the presented method for building engineered vascular-like microstructures with high efficiency.

SUBMITTER: Yue T

PROVIDER: S-EPMC6953073 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures.

Yue Tao T Liu Na N Liu Yuanyuan Y Peng Yan Y Xie Shaorong S Luo Jun J Huang Qiang Q Takeuchi Masaru M Fukuda Toshio T

Micromachines 20191201 12

Multilayered and multicellular structures are indispensable for constructing functional artificial tissues. Engineered vascular-like microstructures with multiple layers are promising structures to be functionalized as artificial blood vessels. In this paper, we present an efficient method to construct multilayer microtubes embedding different microstructures based on direct fabrication and assembly inside a microfluidic device. This four-layer microfluidic device has two separate inlets for fab ...[more]

PMID: 31805688

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Project description:Multiplexed, sensitive, and on-chip molecular diagnostic assays are essential in both clinical and research settings. In past work, running reactions in nanoliter- to femtoliter-sized volumes such as microwells or droplets has led to significant increases in detection sensitivities. At the same time, hydrogels have emerged as attractive scaffolds for bioassays due to their nonfouling, flexible, and aqueous properties. In this paper, we combine these concepts and develop a novel platform in which hydrogel compartments are used as individually confined reaction volumes within a fluorinated oil phase. We fabricate functional and versatile hydrogel microstructures in microfluidic channels that are physically isolated from each other using a surfactant-free fluorinated oil phase, generating picoliter- to nanoliter-sized immobilized aqueous reaction compartments that are readily functionalized with biomolecules. In doing so, we achieve monodisperse reaction volumes with an aqueous interior while exploiting the unique chemistry of a hydrogel, which provides a solid and porous binding scaffold for biomolecules and is impenetrable to oil. Furthermore, our lithographically defined reaction volumes are readily customized with respect to geometry and chemistry within the same channel, allowing rational tuning of the confined reaction volume on a post-to-post basis without needing to use surfactants to maintain stability. We design and implement a multiplexed signal amplification assay in which gel-bound enzymes turn over small molecule substrate into fluorescent product in the oil-confined gel compartment, providing significant signal enhancement. Using short (20 min) amplification times, the encapsulation scheme provides up to 2 orders of magnitude boost of signal in nucleic acid detection assays relative to direct labeling and does not suffer from any cross-talk between the posts. We ultimately demonstrate up to 57-fold increase in nucleic acid detection sensitivity compared to a direct labeling scheme.

Dataset Information

On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures.

Publications

On-Chip Construction of Multilayered Hydrogel Microtubes for Engineered Vascular-Like Microstructures.

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