Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor

• Published in: Nature communications Vol. 8; no. 1; pp. 14902 - 10
• Main Authors: Xu, Shicai, Zhan, Jian, Man, Baoyuan, Jiang, Shouzhen, Yue, Weiwei, Gao, Shoubao, Guo, Chengang, Liu, Hanping, Li, Zhenhua, Wang, Jihua, Zhou, Yaoqi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.03.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/61/32; 639/301/357/918/1052; 639/638/11/511; 9/10; Biology; Biomarkers; Biosensing Techniques; Biosensors; Carbon; Cost-Benefit Analysis; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA Probes - chemistry; Fabrication; Genetic diversity; Graphene; Graphite - chemistry; High-Throughput Screening Assays - economics; High-Throughput Screening Assays - instrumentation; Humanities and Social Sciences; Hybridization; Kinetics; Limit of Detection; Miniaturization; Models, Chemical; multidisciplinary; Nanowires; Nucleic Acid Hybridization; Reproducibility of Results; Science; Sensors; Transistors; China
• DOI: 10.1038/ncomms14902
• ISSN: 2041-1723

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. Monitoring DNA binding and single-base mismatches accurately in real time is difficult, especially for miniaturized devices. Here the authors report a graphene field-effect transistor array capable of reliably measuring DNA hybridization kinetics and affinity at the picomolar level.