Type 2 diabetes is the most common metabolic disease, and insulin resistance plays a role in the pathogenesis of the disease. Because completely functional mitochondria are necessary to obtain glucose-stimulated insulin from pancreatic beta cells, dysfunction of mitochondrial oxidative pathway could be involved in the development of diabetes. As a simple animal model, Caenorhabditis elegans renders itself to investigate such metabolic mechanisms because it possesses insulin/insulin-like growth factor-1 signaling pathway similar to that in humans. Currently, the widely spread agarose pad-based immobilization technique for fluorescence imaging of the mitochondria in C. elegans is laborious, batchwise, and does not allow for facile handling of the worm. To overcome these technical challenges, we have developed a single-channel microfluidic device that can trap a C. elegans and allow to image the mitochondria in body wall muscles accurately and in higher throughput than the traditional approach. In specific, our microfluidic device took advantage of the proprioception of the worm to rotate its body in a microfluidic channel with an aspect ratio above one to gain more space for its undulation motion that was favorable for quantitative fluorescence imaging of mitochondria in the body wall muscles. Exploiting this unique feature of the microfluidic chip-based immobilization and fluorescence imaging, we observed a significant decrease in the mitochondrial fluorescence intensity under hyperglycemic conditions, whereas the agarose pad-based approach did not show any significant change under the same conditions. A machine learning model trained with these fluorescence images from the microfluidic device could classify healthy and hyperglycemic worms at high accuracy. Given this significant technological advantage, its easiness of use and low cost, our microfluidic imaging chip could become a useful immobilization tool for quantitative fluorescence imaging of the body wall muscles in C. elegans.

中文翻译：

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使用微流控芯片在高血糖条件下对秀丽隐杆线虫体壁肌肉中的线粒体进行定量荧光成像。

2型糖尿病是最常见的代谢性疾病，胰岛素抵抗在该病的发病机制中发挥作用。因为从胰腺β细胞中获得葡萄糖刺激的胰岛素需要功能齐全的线粒体，所以线粒体氧化途径的功能障碍可能与糖尿病的发展有关。作为一个简单的动物模型，秀丽隐杆线虫可以研究这种代谢机制，因为它拥有与人类相似的胰岛素/胰岛素样生长因子-1 信号通路。目前，广泛传播的基于琼脂糖垫的固定化技术用于线虫线粒体的荧光成像费力，分批进行，并且不允许轻松处理蠕虫。为了克服这些技术挑战，我们开发了一种单通道微流体装置，可以捕获线虫并允许准确地以比传统方法更高的吞吐量对体壁肌肉中的线粒体进行成像。具体而言，我们的微流体装置利用蠕虫的本体感受在纵横比大于 1 的微流体通道中旋转其身体，为其波动运动获得更多空间，这有利于对体壁肌肉中的线粒体进行定量荧光成像. 利用基于微流控芯片的固定和荧光成像的这一独特特征，我们观察到在高血糖条件下线粒体荧光强度显着降低，而基于琼脂糖垫的方法在相同条件下没有显示任何显着变化。使用来自微流体设备的这些荧光图像训练的机器学习模型可以高精度地对健康蠕虫和高血糖蠕虫进行分类。鉴于这一显着的技术优势、易用性和低成本，我们的微流体成像芯片可以成为一种有用的固定工具，用于对人体壁肌肉进行定量荧光成像。C. 线虫。