Highly specific SNP detection using 2D graphene electronics and DNA strand displacement.
Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine.
Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093;
Michael T
MT
Hwang
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093; Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093;
Preston B
PB
Landon
Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093;
Joon
J
Lee
Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093;
Duyoung
D
Choi
Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093;
Alexander H
AH
Mo
Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093.
Gennadi
G
Glinsky
Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093; Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093; Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093 rlal@ucsd.edu.
Ratnesh
R
Lal
D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D004247:DNA / Q000235:genetics*; D005838:Genotype; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D020641:Polymorphism, Single Nucleotide
D006108:Graphite; D004247:DNA
DNA strand displacement; SNP detection; bioelectronics; electrical biosensor; graphene FET DNA sensor