【公開日：2023.08.01】【最終更新日：2023.05.22】
課題データ / Project Data
課題番号 / Project Issue Number
22KT1140
利用課題名 / Title
マイクロ流体デバイスを応用した先端計測技術の開発
利用した実施機関 / Support Institute
京都大学
機関外・機関内の利用 / External or Internal Use
内部利用（ARIM事業参画者以外）/Internal Use (by non ARIM members)
技術領域 / Technology Area
【横断技術領域 / Cross-Technology Area】（主 / Main）加工・デバイスプロセス/Nanofabrication（副 / Sub）-
【重要技術領域 / Important Technology Area】（主 / Main）マルチマテリアル化技術・次世代高分子マテリアル/Multi-material technologies / Next-generation high-molecular materials（副 / Sub）-
キーワード / Keywords
マイクロ流体デバイス,成形/Molding,リソグラフィ/Lithography,3D積層技術/ 3D lamination technology
利用者と利用形態 / User and Support Type
利用者名（課題申請者）/ User Name (Project Applicant)
平井 義和
所属名 / Affiliation
京都大学 大学院工学研究科
共同利用者氏名 / Names of Collaborators in Other Institutes Than Hub and Spoke Institutes
ARIM実施機関支援担当者 / Names of Collaborators in The Hub and Spoke Institutes
江崎裕子
利用形態 / Support Type
（主 / Main）機器利用/Equipment Utilization（副 / Sub）-
利用した主な設備 / Equipment Used in This Project
KT-103：レーザー直接描画装置
KT-104：高速マスクレス露光装置
KT-107：厚膜フォトレジスト用スピンコーティング装置
KT-110：レジスト現像装置
KT-253：簡易RIE装置
報告書データ / Report
概要（目的・用途・実施内容）/ Abstract (Aim, Use Applications and Contents)
To clarify the physiological and pathological roles of gut-liver-axis (GLA) in the human body, a GLA microphysiological system (GLA-MPS) holds great potential. However, in current GLA-MPSs, the importance of a physiologically relevant flow for gut and liver cells’ cultivation is not fully addressed. In addition, the integration of individual organ perfusion, circulation flow, and organ tissue functions in a single device has not been achieved. Here, we introduce a GLA-MPS by integrating two cell culture chambers with individually applied perfusion flows and a circulation channel with an on-chip pneumatic micropump under cell culture chambers via a porous membrane for interconnecting them.
実験 / Experimental
Figure 1 shown the chip fabrication process in detail. Figure 2 shown the cell-based assay for tissue generation and disease modeling.
結果と考察 / Results and Discussion
We analysed the fluid shear stress (FSS) with computational fluid dynamics simulations and confirmed that the physiologically relevant FSS could be applied to the gut (Caco-2) and liver (HepG2) cells (Fig. 2a). Furthermore, the expression of functional proteins such as zonula occludes 1 (in Caco-2) and albumin (in HepG2) was enhanced. To demonstrate the GLA interaction, the inflammatory bowel disease was recapitulated by applying lipopolysaccharide for only Caco-2 cells. The inflammatory proteins, such as inducible nitric oxide synthase, were induced in Caco-2 and HepG2 cells (Fig. 2b). The presented GLA-MPS can be adapted as an advanced in vitro model in various applications for disease modelling associated with inter-tissue interactions, such as inflammatory disease.
図・表・数式 / Figures, Tables and Equations
Figure 1. The chip fabrication process. The resist mold was fabricated from standard photolithography. The following process was the method of PDMS multilayer fabrication.
Figure 2. The Gut-liver-Axis microphysiological system for inflammatory bowel disease modeling. (a) The fabricated chips with functional gut-liver cells; (b) the inflammatory protein expression in each cell stimulus conditions for inflammatory bowel disease modeling. No stim: control group. LPS: lipopolysaccharide, inflammation factor. Dex: dexamethasone, anti-inflammation drug.
その他・特記事項（参考文献・謝辞等） / Remarks(References and Acknowledgements)
・Biomicrofluidicsの2022年7月号の表紙に採用
成果発表・成果利用 / Publication and Patents
論文・プロシーディング（DOIのあるもの） / DOI (Publication and Proceedings)
口頭発表、ポスター発表および、その他の論文 / Oral Presentations etc.
- (1) Jiandong Yang, Satoshi Imamura, Yoshikazu Hirai, Toshiyuki Tsuchiya, Osamu Tabata, Ken-ichiro Kamei, "Gut-Liver-Axis Microphysiological System for Studying Cellular Fluidic Shear Stress and Inter-Tissue Interaction," Biomicrofluidics, 16 (2022), 044113
特許 / Patents
特許出願件数 / Number of Patent Applications：0件
特許登録件数 / Number of Registered Patents：0件