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仪器设备-功能用途
由于传统模型的不足:传统的体外2D细胞模型和体内动物模型常用于评估药物的安全性和有效性,但它们存在明显的缺点。例如,体内动物模型构建耗时,而体外2D细胞模型缺乏体内微环境,无法进行准确评估。
尽管体外3D细胞模型,如细胞球和类器官具有优势,但它们的培养过程漫长且手动,引入了个体差异和高成本。此外,静态培养中的3D模型缺乏构建微生理系统的流体连接。
作为一种动态多器官微生理系统【微生理系统,也称为器官芯片(organ-on-a-chip)技术】,通过模拟器官功能和不同器官间通信,为研究药物的药效学、药动学和整体药物反应提供了新的视角,在疾病建模和药物筛选方面显示出巨大潜力。
仪器设备-发表文献:
uBerger E, Magliaro C, Paczia N, Monzel AS, Antony P, Linster CL, Bolognin S, Ahluwalia A, Schamborn JC. Millifluidic culture improves human midbrain organoid vitality and differentiation. Lab Chip, 2018, 18, 3172-3183.
vRamachandran S, Schirmer K, Münst B, Heinz S, Ghafoory S, Wölfl S, Simon-Keller K, Marx A, Øie C, Ebert M, Walles H, Braspenning J and Breitkopf-Heinlein K (2015). In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells. PLOS ONE, 10(10), e0139345.
w Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin, Tayebeh Azimi, Marilena Loizidou & Miriam V. Dwek ,Scientific Reports volume 10, Article number: 12020 (2020)
xGeddes, L., Themistou, E., Burrows, J. F., Buchanan, F. J., & Carson, L. (2021). Evaluation of the In Vitro Cytotoxicity and Modulation of the Inflammatory Response by the Bioresorbable Polymers Poly(D,L-lactide-coglycolide) and Poly(L-lactide-co-glycolide). Acta Biomaterialia, 134, 261-275.
ySusanne Reinhold, Christian Herr, Yiwen Yao , Mehdi Pourrostami, Felix Ritzmann. Modeling of lung-liver interaction during infection in a human microfluidic organ-on-a-chip, bioRxiv preprint posted June 5, 2023.
作者利用原代人支气管(HBECs)或肺泡上皮细胞和人肝癌Huh-7细胞,通过Kirkstall Quasi Vivo®器官芯片建立了双器官(肺/肝)微流控系统,开展共培养/刺激试验。将不可分型流感嗜血杆菌(NTHi)和铜绿假单胞菌(PAO1)应用于肺模块。通过dot-blot分析筛选分泌的介质并进行定量。通过mRNA测序,分析肺上皮细菌刺激对肝细胞转录组的影响。

(四)产品用户概况
全球使用Kirkstall Quasi Vivo®器官芯片微生理系统的学术及研究机构已超过100+个,遍布美国、英国、法国、瑞典、奥地利、意大利、荷兰、瑞士、日本等。目前器官芯片微生理系统已成功用于以下类器官模型的构建:
(五)品牌制造商简介
Kirkstall Ltd.成立于 2006 年,是 Braveheart Investment Group plc 的子公司,总部位于英国约克。Kirkstall开发了一种创新的微生理系统的器官芯片模型Quasi Vivo®。作为器官芯片技术的lingdaozhe,Kirkstall已经建立了牛津大学生物医学工程研究所等著名的大学实验室的庞大用户群,产品在全球范围内享有盛誉。
北京基尔比生物科技有限公司是Kirkstall ltd.授权在中国的唯一和独家总代理商,全面负责Kirkstall公司旗下所有产品在中国的销售,市场推广和技术支持等事宜。
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文献和实验approaches have been applied to ensure proper medium supply, namely orbital shaking,11 spinning flasks6 and mini-bioreactors.10 However, applying fluidic systems (micro- or millifluidic) have not been considered, so far. In case of the hMOs, we hypothesize that keeping organoids under continuous orbital shaking as per published protocols5 might not be sufficient to ensure a proper supply of nutrients and oxygen. Therefore, to improve the quality of hMOs we investigated the effects of applying a continuous medium flow during culture. In this study we used the “Quasi Vivo” (QV, Kirkstall, UK) millifluidic system rather than a microfluidic device14 for a number of reasons. First, following the concept of allometry, the size of an organoid should range between approximately 0.5 to 2 mm in order to exhibit physiologically scaled metabolism (oxygen consumption).15,16 In addition, millifluidic systems such as the QV allow the application of relatively high flow rates ensuring proper nutrient and oxygen supply without exposing the organoid to a high shear force due to the flow itself. This is due to a well-like design in which the medium inlet and outlet are located in the chamber lid whereas the organoid is placed a variable distance from the medium inlet.17,18 Finally, given their high volume to surface ratio, millifluidic systems do not require frequent media changes, thus organoid manipulation is reduced to a minimum during culture. Besides various applications in 2D cultures, the QV millifluidic system has been successfully used to culture liver organoids13,19 and 3D cardiac constructs20 derived from human (adult) stem cells. In this study, we established a stable midbrain organoid culture under millifluidic conditions and compared it to the state-of-the-art procedure of continuous orbital shaking using both a computational fluid dynamics (CFD) and an experimental approach. The CFD analysis was performed to determine if differences in calculated oxygen profiles in the two experimental set-ups could be used to expla
JACS|功能化纳米针芯片解析活细胞中 lncRNA 和 RBP的时空交互异质性
在单细胞尺度分辨率下解码 lncRNA-RBP 相互作用的优势。 图 2. MCF-7 和 HLF-1 共培养系统中 LncRNA-RBPs 空间异质性定位 研究人员将 Nano-SpatiaLR 技术应用于结直肠癌细胞,追踪了细胞增殖过程中细胞内 lncRNA 和 RBP 的时间-空间交互异质性动态。发现 lncRNA HOTAIR 及其与 RBP EZH2 和 LSD1 的相互作用在肿瘤生长中具有重要意义,并且这些相互作用在结直肠癌细胞群中显示出独特的空间异质性模式。 图 3. 追踪
气体交换,”Synthecon公司的首席科学家Stephen Navran说。“进入这一系统的细胞很快能够聚集成为3D细胞球体。当然也可以加入多种支架物质使细胞得以粘附。该系统的独特之处在于,在RCCS中维持悬浮3D结构所需的机械力非常小,能够将细胞损伤降到最低。此外,旋转的动态培养比依赖于扩散作用的静态培养系统更具优势,能够是细胞更充分的接触到营养物质和氧气。”据Navran介绍,由于缺乏血液供给,所有3D培养系统都存在一定的局限性。“这通常意味着3D细胞结构的中心部分缺乏氧气和营养,并最终会导致细胞坏死。虽然RCCS
四、微流控类器官芯片:用于研究更复杂的动态过程 核心原理 微流控芯片将类器官、三维基质、血管内皮和免疫细胞整合到可控微通道中,通过持续灌流模拟流体剪切力、物质交换和浓度梯度。 它解决的是传统静态孔板模型难以模拟的动态迁移和血管—组织过程。 典型操作 可以在芯片一侧建立内皮屏障,在邻近区域培养类器官和三维基质,再从模拟“血管腔”的通道中加入免疫细胞,通过实时成像观察细胞黏附、跨内皮迁移和组织浸润。 适用场景 适合研究免疫细胞跨血管迁移、血管—免疫—肿瘤互作、趋化因子梯度以及动态药物暴露
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