Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.
Program in Cell Biology, Hospital for Sick Children, Peter Gilgan Center for Research and Learning, Toronto, ON, M5G 0A4, Canada.
Nat Commun. 2021 Feb 1;12(1):724. doi: 10.1038/s41467-020-20639-6.
Recent advances in cell-free synthetic biology have given rise to gene circuit-based sensors with the potential to provide decentralized and low-cost molecular diagnostics. However, it remains a challenge to deliver this sensing capacity into the hands of users in a practical manner. Here, we leverage the glucose meter, one of the most widely available point-of-care sensing devices, to serve as a universal reader for these decentralized diagnostics. We describe a molecular translator that can convert the activation of conventional gene circuit-based sensors into a glucose output that can be read by off-the-shelf glucose meters. We show the development of new glucogenic reporter systems, multiplexed reporter outputs and detection of nucleic acid targets down to the low attomolar range. Using this glucose-meter interface, we demonstrate the detection of a small-molecule analyte; sample-to-result diagnostics for typhoid, paratyphoid A/B; and show the potential for pandemic response with nucleic acid sensors for SARS-CoV-2.
无细胞合成生物学的最新进展催生了基于基因回路的传感器，它们具有提供分散式和低成本分子诊断的潜力。然而，如何以实际可行的方式将这种传感能力交到用户手中仍然是一个挑战。在这里，我们利用血糖仪——最广泛应用的即时检测传感设备之一——作为这些分散式诊断的通用读取器。我们描述了一种分子翻译器，它可以将传统基于基因回路的传感器的激活转化为葡萄糖输出，而这种葡萄糖输出可以被现成的血糖仪读取。我们展示了新的生糖报告系统的开发、多重报告输出以及对低至皮摩尔级别的核酸靶标的检测。使用这种血糖仪接口，我们演示了对小分子分析物的检测、伤寒、副伤寒 A/B 的样本到结果的诊断，并展示了用于 SARS-CoV-2 的核酸传感器的大流行应对潜力。
