Highly scalable and standardized organ-on-chip platform with TEER for biological barrier modeling.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Tissue Barriers Pub Date : 2024-10-01 Epub Date: 2024-02-12 DOI:10.1080/21688370.2024.2315702
Hoang-Tuan Nguyen, Siiri-Liisa Rissanen, Mimosa Peltokangas, Tino Laakkonen, Jere Kettunen, Lara Barthod, Ragul Sivakumar, Anniina Palojärvi, Pauliina Junttila, Jussi Talvitie, Michele Bassis, Sarah L Nickels, Sara Kalvala, Polina Ilina, Päivi Tammela, Sarka Lehtonen, Jens C Schwamborn, Sebastien Mosser, Prateek Singh
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Abstract

The development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, the non-standardized design of these chips and perfusion control systems has been a barrier to quantitative high-throughput screening (HTS). Here we present a scalable OOC microfluidic platform for applied kinetic in vitro assays (AKITA) that is applicable for high, medium, and low throughput. Its standard 96-well plate and 384-well plate layouts ensure compatibility with existing laboratory workflows and high-throughput data collection and analysis tools. The AKITA plate is optimized for the modeling of vascularized biological barriers, primarily the blood-brain barrier, skin, and lung, with precise flow control on a custom rocker. The integration of trans-epithelial electrical resistance (TEER) sensors allows rapid and repeated monitoring of barrier integrity over long time periods. Together with automated liquid handling and compound permeability testing analyses, we demonstrate the flexibility of the AKITA platform for establishing human-relevant models for preclinical drug and precision medicine's efficacy, toxicity, and permeability under near-physiological conditions.

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具有高度可扩展性和标准化的片上器官平台,可利用 TEER 进行生物屏障建模。
新疗法的开发因缺乏预测性和与患者相关的体外模型而受到阻碍。片上器官(OOC)技术有可能重现生理特征,并为组织和疾病建模带来巨大希望。然而,这些芯片和灌注控制系统的非标准化设计一直是定量高通量筛选(HTS)的障碍。在这里,我们提出了一种可扩展的 OOC 微流体平台,用于应用动力学体外检测(AKITA),适用于高、中、低通量。其标准的 96 孔板和 384 孔板布局确保了与现有实验室工作流程以及高通量数据采集和分析工具的兼容性。AKITA 孔板针对血管生物屏障(主要是血脑屏障、皮肤和肺部)建模进行了优化,可在定制摇杆上实现精确的流量控制。通过集成跨上皮电阻(TEER)传感器,可对屏障完整性进行长时间的快速重复监测。通过自动液体处理和化合物渗透性测试分析,我们展示了 AKITA 平台在建立临床前药物和精准医疗的药效、毒性和渗透性人体相关模型方面的灵活性。
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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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