Department of Biomedical Engineering, School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China.
Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Anal Chem. 2024 Jun 18;96(24):10092-10101. doi: 10.1021/acs.analchem.4c02075. Epub 2024 Jun 4.
Tumor patients-derived organoids, as a promising preclinical prediction model, have been utilized to evaluate drug responses for formulating optimal therapeutic strategies. Detecting adenosine triphosphate (ATP) has been widely used in existing organoid-based drug response tests. However, all commercial ATP detection kits containing the cell lysis procedure can only be applied for single time point ATP detection, resulting in the neglect of dynamic ATP variations in living cells. Meanwhile, due to the limited number of viable organoids from a single patient, it is impractical to exhaustively test all potential time points in search of optimal ones. In this work, a multifunctional microfluidic chip was developed to perform all procedures of organoid-based drug response tests, including establishment, culturing, drug treatment, and ATP monitoring of organoids. An ATP sensor was developed to facilitate the first successful attempt on whole-course monitoring the growth status of fragile organoids. To realize a clinically applicable automatic system for the drug testing of lung cancer, a microfluidic chip based automated system was developed to perform entire organoid-based drug response test, bridging the gap between laboratorial manipulation and clinical practices, as it outperformed previous methods by improving data repeatability, eliminating human error/sample loss, and more importantly, providing a more accurate and comprehensive evaluation of drug effects.
肿瘤患者衍生类器官作为一种有前途的临床前预测模型，已被用于评估药物反应，以制定最佳治疗策略。检测三磷酸腺苷 (ATP) 已广泛应用于现有的基于类器官的药物反应测试中。然而，所有含有细胞裂解程序的商业 ATP 检测试剂盒只能用于单次时间点的 ATP 检测，从而忽略了活细胞中 ATP 的动态变化。同时，由于单个患者的可行类器官数量有限，因此不可能详尽地测试所有潜在的时间点以寻找最佳时间点。在这项工作中，开发了一种多功能微流控芯片，以执行基于类器官的药物反应测试的所有程序，包括类器官的建立、培养、药物处理和 ATP 监测。开发了一种 ATP 传感器，以首次成功尝试对脆弱类器官的生长状态进行全程监测。为了实现肺癌药物检测的临床应用自动化系统，开发了一种基于微流控芯片的自动化系统，以执行整个基于类器官的药物反应测试，将实验室操作和临床实践联系起来，因为它通过提高数据重复性、消除人为错误/样本损失，更重要的是，提供更准确和全面的药物效果评估，从而优于以前的方法。
