Department of Mechanical Engineering, University of Texas at Austin, Austin, TX, USA.
Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA.
Sci Rep. 2023 Jul 12;13(1):11268. doi: 10.1038/s41598-023-38212-8.
Organoids are three-dimensional structures of self-assembled cell aggregates that mimic anatomical features of in vivo organs and can serve as in vitro miniaturized organ models for drug testing. The most efficient way of studying drug toxicity and efficacy requires high-resolution imaging of a large number of organoids acquired in the least amount of time. Currently missing are suitable platforms capable of fast-paced high-content imaging of organoids. To address this knowledge gap, we present the OrganoidChip, a microfluidic imaging platform that incorporates a unique design to immobilize organoids for endpoint, fast imaging. The chip contains six parallel trapping areas, each having a staging and immobilization chamber, that receives organoids transferred from their native culture plates and anchors them, respectively. We first demonstrate that the OrganoidChip can efficiently immobilize intestinal and cardiac organoids without compromising their viability and functionality. Next, we show the capability of our device in assessing the dose-dependent responses of organoids' viability and spontaneous contraction properties to Doxorubicin treatment and obtaining results that are similar to off-chip experiments. Importantly, the chip enables organoid imaging at speeds that are an order of magnitude faster than conventional imaging platforms and prevents the acquisition of blurry images caused by organoid drifting, swimming, and fast stage movements. Taken together, the OrganoidChip is a promising microfluidic platform that can serve as a building block for a multiwell plate format that can provide high-throughput and high-resolution imaging of organoids in the future.
类器官是自组装细胞聚集体的三维结构，模拟体内器官的解剖特征，可作为药物测试的体外微型器官模型。研究药物毒性和疗效最有效的方法是在最短的时间内对大量类器官进行高分辨率成像。目前缺少的是能够快速进行高通量类器官高内涵成像的合适平台。为了解决这一知识空白，我们提出了 OrganoidChip，这是一种微流控成像平台，采用独特的设计来固定类器官，以便进行终点快速成像。该芯片包含六个平行的捕获区域，每个区域都有一个分级和固定室，用于接收从其天然培养板转移过来的类器官并分别固定它们。我们首先证明 OrganoidChip 可以有效地固定肠和心脏类器官，而不会影响其活力和功能。接下来，我们展示了我们的设备在评估类器官对多柔比星处理的活力和自发性收缩特性的剂量依赖性反应方面的能力，并获得了与芯片外实验相似的结果。重要的是，该芯片使类器官的成像速度比传统成像平台快一个数量级，并且可以防止由于类器官漂移、游动和快速的载物台运动而导致的模糊图像的获取。总之，OrganoidChip 是一种很有前途的微流控平台，可以作为未来高通量和高分辨率成像的多孔板格式的构建模块。
