Shandong Provincial Key Laboratory of Biophysics, College of Physics and Electronic Information, Dezhou University, Dezhou 253023, China.
Institute for Glycomics and School of Information and Communication Technology, Griffith University, Parklands Drive, Southport, Queensland 4222, Australia.
Nat Commun. 2017 Mar 21;8:14902. doi: 10.1038/ncomms14902.
Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array.
可靠地确定 DNA 杂交和单碱基错配的结合动力学和亲和力在系统生物学、个性化和精准医学中起着至关重要的作用。标准工具是基于光学的传感器，这些传感器难以低成本操作和小型化以实现高通量测量。已经开发出基于纳米线场效应晶体管的生物传感器，但可靠且具有成本效益的制造仍然是一个挑战。在这里，我们证明了图案化的多个石墨烯单晶畴通道可以可靠且灵敏地测量随时间和浓度变化的 DNA 杂交动力学和亲和力，对 DNA 的检测限低至 10 pM。它可以实时定量区分单碱基突变。开发了一个分析模型来估计探针密度、杂交效率和传感器的最大响应。研究结果表明，通过使用集成的、小型化的、全电子多路复用的、基于石墨烯的 DNA 阵列，有望实现具有成本效益的高通量筛选候选药物、遗传变异和疾病生物标志物。
