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Label-free, real-time monitoring of cytochrome C drug responses in microdissected tumor biopsies with a multi-well aptasensor platform
Science Advances ( IF 11.7 ) Pub Date : 2024-09-06 , DOI: 10.1126/sciadv.adn5875 Tran N H Nguyen 1 , Lisa F Horowitz 1 , Timothy Krilov 1 , Ethan Lockhart 1 , Heidi L Kenerson 2 , Taranjit S Gujral 3 , Raymond S Yeung 2 , Netzahualcóyotl Arroyo-Currás 4 , Albert Folch 1
Science Advances ( IF 11.7 ) Pub Date : 2024-09-06 , DOI: 10.1126/sciadv.adn5875 Tran N H Nguyen 1 , Lisa F Horowitz 1 , Timothy Krilov 1 , Ethan Lockhart 1 , Heidi L Kenerson 2 , Taranjit S Gujral 3 , Raymond S Yeung 2 , Netzahualcóyotl Arroyo-Currás 4 , Albert Folch 1
Affiliation
Functional assays on intact tumor biopsies can complement genomics-based approaches for precision oncology, drug testing, and organs-on-chips cancer disease models by capturing key therapeutic response determinants, such as tissue architecture, tumor heterogeneity, and the tumor microenvironment. Most of these assays rely on fluorescent labeling, a semiquantitative method best suited for single-time-point assays or labor-intensive immunostaining analysis. Here, we report integrated aptamer electrochemical sensors for on-chip, real-time monitoring of cytochrome C, a cell death indicator, from intact microdissected tissues with high affinity and specificity. The platform features a multi-well sensor layout and a multiplexed electronic setup. The aptasensors measure increases in cytochrome C in the supernatant of mouse or human microdissected tumors after exposure to various drug treatments. Because of the sensor’s high affinity, it primarily tracks rising concentrations of cytochrome C, capturing dynamic changes during apoptosis. This approach could help develop more advanced cancer disease models and apply to other complex in vitro disease models, such as organs-on-chips and organoids.
中文翻译:
使用多孔适体传感器平台对显微解剖肿瘤活检中的细胞色素 C 药物反应进行无标记实时监测
对完整肿瘤活检的功能分析可以通过捕获关键的治疗反应决定因素(例如组织结构、肿瘤异质性和肿瘤微环境)来补充基于基因组学的精准肿瘤学、药物测试和芯片上器官癌症模型的方法。大多数这些测定依赖于荧光标记,这是一种最适合单时间点测定或劳动密集型免疫染色分析的半定量方法。在这里,我们报告了集成适体电化学传感器,用于对完整显微解剖组织中的细胞色素 C(一种细胞死亡指标)进行片上实时监测,具有高亲和力和特异性。该平台具有多孔传感器布局和多路电子装置。适体传感器测量小鼠或人类显微解剖肿瘤在接受各种药物治疗后上清液中细胞色素 C 的增加。由于传感器具有高亲和力,它主要跟踪细胞色素 C 浓度的上升,捕获细胞凋亡过程中的动态变化。这种方法可以帮助开发更先进的癌症疾病模型,并应用于其他复杂的体外疾病模型,例如芯片上的器官和类器官。
更新日期:2024-09-06
中文翻译:
使用多孔适体传感器平台对显微解剖肿瘤活检中的细胞色素 C 药物反应进行无标记实时监测
对完整肿瘤活检的功能分析可以通过捕获关键的治疗反应决定因素(例如组织结构、肿瘤异质性和肿瘤微环境)来补充基于基因组学的精准肿瘤学、药物测试和芯片上器官癌症模型的方法。大多数这些测定依赖于荧光标记,这是一种最适合单时间点测定或劳动密集型免疫染色分析的半定量方法。在这里,我们报告了集成适体电化学传感器,用于对完整显微解剖组织中的细胞色素 C(一种细胞死亡指标)进行片上实时监测,具有高亲和力和特异性。该平台具有多孔传感器布局和多路电子装置。适体传感器测量小鼠或人类显微解剖肿瘤在接受各种药物治疗后上清液中细胞色素 C 的增加。由于传感器具有高亲和力,它主要跟踪细胞色素 C 浓度的上升,捕获细胞凋亡过程中的动态变化。这种方法可以帮助开发更先进的癌症疾病模型,并应用于其他复杂的体外疾病模型,例如芯片上的器官和类器官。