journal article·2020-06-23

Direct DNA Methylation Profiling with an Electric Biosensor

Deependra Kumar Ban, Yushuang Liu, Zejun Wang, Srinivasan Ramachandran, Nirjhar Sarkar, Ze Shi, Wenhan Liu, Abhijith G. Karkisaval, Erick Martinez-Loran, Feng Zhang, Gennadi Glinsky, Prabhakar R. Bandaru, Chunhai Fan, Ratnesh Lal

ACS Nano· Volume 14· Issue 6
Publisher page

Abstract

DNA methylation is one of the principal epigenetic mechanisms that control gene expression in humans, and its profiling provides critical information about health and disease. Current profiling methods require chemical modification of bases followed by sequencing, which is expensive and time-consuming. Here, we report a direct and rapid determination of DNA methylation using an electric biosensor. The device consists of a DNA-tweezer probe integrated on a graphene field-effect transistor for label-free, highly sensitive, and specific methylation profiling. The device performance was evaluated with a target DNA that harbors a sequence of the methylguanine-DNA methyltransferase, a promoter of glioblastoma multiforme, a lethal brain tumor. The results show that we successfully profiled the methylated and nonmethylated forms at picomolar concentrations. Further, fluorescence kinetics and molecular dynamics simulations revealed that the position of the methylation site(s), their proximity, and accessibility to the toe-hold region of the tweezer probe are the primary determinants of the device performance.
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Research context

OpenAlex topics: Energy Harvesting in Wireless Networks · Opportunistic and Delay-Tolerant Networks · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Mechanical and Aerospace Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States

School of Life Science, Inner Mongolia Agricultural University, 306 Zhaowuda Road, Hohhot 010018, China

CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China

Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States

Materials Science and Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States

Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States

State Key Laboratory of Respiratory Disease, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital, Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China

Institute of Engineering in Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China

Funding

National Institute on Aging · Department of Mechanical and Aerospace Engineering, University of California, San Diego

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