Quantum Point Contact Single-Nucleotide Conductance for DNA and RNA Sequence Identification

被引:14
作者
Afsari, Sepideh [1 ,2 ]
Korshoj, Lee E. [1 ,2 ]
Abel, Gary R., Jr. [1 ,2 ]
Khan, Sajida [1 ,2 ]
Chatterjee, Anushree [1 ,3 ]
Nagpal, Prashant [1 ,2 ,3 ,4 ]
机构
[1] Univ Colorado Boulder, Dept Chem & Biol Engn, Boulder, CO 80309 USA
[2] Univ Colorado Boulder, RASEI, Boulder, CO 80309 USA
[3] Univ Colorado Boulder, BioFrontiers Inst, Boulder, CO 80309 USA
[4] Univ Colorado Boulder, Mat Sci & Engn, Boulder, CO 80309 USA
基金
美国国家科学基金会;
关键词
biophysics; STM break junction; single-molecule conductance; single-molecule DNA sequencing RNA sequencing; SCANNING TUNNELING SPECTROSCOPY; TRANSVERSE ELECTRONIC TRANSPORT; SELF-ASSEMBLED MONOLAYERS; MOLECULE CONDUCTANCE; ANCHORING GROUPS; RESISTANCE; JUNCTIONS; ALKANEDITHIOLS; ALKANETHIOLS; NUCLEOBASES;
D O I
10.1021/acsnano.7b05500
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Several nanoscale electronic methods have been proposed for high-throughput single-molecule nucleic acid sequence identification. While many studies display a large ensemble of measurements as "electronic fingerprints" with some promise for distinguishing the DNA and RNA nucleobases (adenine, guanine, cytosine, thymine, and uracil), important metrics such as accuracy and confidence of base calling fall well below the current genomic methods. Issues such as unreliable metal-molecule junction formation, variation of nucleotide conformations, insufficient differences between the molecular orbitals responsible for single nucleotide conduction, and lack of rigorous base calling algorithms lead to overlapping nanoelectronic measurements and poor nucleotide discrimination, especially at low coverage on single molecules. Here, we demonstrate a technique for reproducible conductance measurements on conformation-constrained single nucleotides and an advanced algorithmic approach for distinguishing the nucleobases. Our quantum point contact single-nucleotide conductance sequencing (QPICS) method uses combed and electrostatically bound single DNA and RNA nucleotides on a self-assembled monolayer of cysteamine molecules. We demonstrate that by varying the applied bias and pH conditions, molecular conductance can be switched ON and OFF, leading to reversible nucleotide perturbation for electronic recognition (NPER). We utilize NPER as a method to achieve >99.7% accuracy for DNA and RNA base calling at low molecular coverage (similar to 12X) using unbiased single measurements on DNA/RNA nucleotides, which represents a significant advance compared to existing sequencing methods. These results demonstrate the potential for utilizing simple surface modifications and existing biochemical moieties in individual nucleobases for a reliable, direct, single-molecule, nanoelectronic DNA and RNA nucleotide identification method for sequencing.
引用
收藏
页码:11169 / 11181
页数:13
相关论文
共 43 条
[1]   MinION nanopore sequencing identifies the position and structure of a bacterial antibiotic resistance island [J].
Ashton, Philip M. ;
Nair, Satheesh ;
Dallman, Tim ;
Rubino, Salvatore ;
Rabsch, Wolfgang ;
Mwaigwisya, Solomon ;
Wain, John ;
O'Grady, Justin .
NATURE BIOTECHNOLOGY, 2015, 33 (03) :296-+
[2]   ALIGNMENT AND SENSITIVE DETECTION OF DNA BY A MOVING INTERFACE [J].
BENSIMON, A ;
SIMON, A ;
CHIFFAUDEL, A ;
CROQUETTE, V ;
HESLOT, F ;
BENSIMON, D .
SCIENCE, 1994, 265 (5181) :2096-2098
[3]   The potential and challenges of nanopore sequencing [J].
Branton, Daniel ;
Deamer, David W. ;
Marziali, Andre ;
Bayley, Hagan ;
Benner, Steven A. ;
Butler, Thomas ;
Di Ventra, Massimiliano ;
Garaj, Slaven ;
Hibbs, Andrew ;
Huang, Xiaohua ;
Jovanovich, Stevan B. ;
Krstic, Predrag S. ;
Lindsay, Stuart ;
Ling, Xinsheng Sean ;
Mastrangelo, Carlos H. ;
Meller, Amit ;
Oliver, John S. ;
Pershin, Yuriy V. ;
Ramsey, J. Michael ;
Riehn, Robert ;
Soni, Gautam V. ;
Tabard-Cossa, Vincent ;
Wanunu, Meni ;
Wiggin, Matthew ;
Schloss, Jeffery A. .
NATURE BIOTECHNOLOGY, 2008, 26 (10) :1146-1153
[4]   Electronic Signatures of all Four DNA Nucleosides in a Tunneling Gap [J].
Chang, Shuai ;
Huang, Shuo ;
He, Jin ;
Liang, Feng ;
Zhang, Peiming ;
Li, Shengqing ;
Chen, Xiang ;
Sankey, Otto ;
Lindsay, Stuart .
NANO LETTERS, 2010, 10 (03) :1070-1075
[5]   Measurement of single-molecule conductance [J].
Chen, Fang ;
Hihath, Joshua ;
Huang, Zhifeng ;
Li, Xiulan ;
Tao, N. J. .
ANNUAL REVIEW OF PHYSICAL CHEMISTRY, 2007, 58 (58) :535-564
[6]   Effect of anchoring groups on single-molecule conductance: Comparative study of thiol-, amine-, and carboxylic-acid-terminated molecules [J].
Chen, Fang ;
Li, Xiulan ;
Hihath, Joshua ;
Huang, Zhifeng ;
Tao, Nongjian .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (49) :15874-15881
[7]  
Clarke J, 2009, NAT NANOTECHNOL, V4, P265, DOI [10.1038/NNANO.2009.12, 10.1038/nnano.2009.12]
[8]   Length-dependent transport in molecular junctions based on SAMs of alkanethiols and alkanedithiols: Effect of metal work function and applied bias on tunneling efficiency and contact resistance [J].
Engelkes, VB ;
Beebe, JM ;
Frisbie, CD .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (43) :14287-14296
[9]   Identification of DNA basepairing via tunnel-current decay [J].
He, Jin ;
Lin, Lisha ;
Zhang, Peirning ;
Lindsay, Stuart .
NANO LETTERS, 2007, 7 (12) :3854-3858
[10]  
Heerema SJ, 2016, NAT NANOTECHNOL, V11, P127, DOI [10.1038/nnano.2015.307, 10.1038/NNANO.2015.307]