This research project aims to combine the unique and powerful capabilities of two exciting, rapidly evolving fields, plasmonics and nanopores, for the analysis of single DNA molecules. More specifically, recent advances in nanoplasmonics will be utilized to enable label-free, single-molecule trapping and sequencing of DNA using nanopores. A novel type of synthetic nanostructure will be developed to strongly focus light to very high intensity in a nanometer-dimension spot where a solid-state nanopore is created. Through that spot, a DNA molecule will be translocated in a controlled way, allowing the detection of the sequence of the DNA fragments that are sequentially exposed to the intense optical fields of the plasmonic hot spot. The unique aspect of the program is the use of plasmonic tweezers to control DNA in solid-state nanopores. This novel approach to advancing DNA through the nanopore simultaneously enables DNA sequence detection through surface-enhanced Raman spectroscopy. Because locally confined plasmonic fields enhance Raman scattering many orders of magnitude and because of the direct relationship of Raman spectra to the underlying molecular structure, sequence detection will be possible directly, without any labeling. The project's team is a synergetic combination of experts in biomolecular modeling (UIUC), nanopore experiments (TU Delft) and plasmonic sensing (TU Delft).
The specific aims of the projects are to (i) use a plasmonic field to trap DNA in solid-state nanopores, (ii) develop a method to transport DNA through plasmonic nanopores in discrete, ultimately single-nucleotide steps, and (iii) detect the nucleotide sequence of trapped and moving DNA molecules by means of Raman spectroscopy.

Public Health Relevance

This project aims to develop a novel method to sequence human DNA to make it an affordable and rapid medical procedure. The method can, ultimately, enable accurate medical diagnostics of genetic and multifactorial diseases, early detection of cancer, development of drugs tailored to individual genetic makeup and will facilitate the use of DNA sequencing in biomedical research.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01HG007406-02
Application #
8728989
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Schloss, Jeffery
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Physics
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Champaign
State
IL
Country
United States
Zip Code
61820
Yoo, Jejoong; Wilson, James; Aksimentiev, Aleksei (2016) Improved model of hydrated calcium ion for molecular dynamics simulations using classical biomolecular force fields. Biopolymers 105:752-63
Carson, Spencer; Wilson, James; Aksimentiev, Aleksei et al. (2016) Hydroxymethyluracil modifications enhance the flexibility and hydrophilicity of double-stranded DNA. Nucleic Acids Res 44:2085-92
Belkin, Maxim; Aksimentiev, Aleksei (2016) Molecular Dynamics Simulation of DNA Capture and Transport in Heated Nanopores. ACS Appl Mater Interfaces 8:12599-608
Comer, Jeffrey; Aksimentiev, Aleksei (2016) DNA sequence-dependent ionic currents in ultra-small solid-state nanopores. Nanoscale 8:9600-13
Bhattacharya, Swati; Yoo, Jejoong; Aksimentiev, Aleksei (2016) Water Mediates Recognition of DNA Sequence via Ionic Current Blockade in a Biological Nanopore. ACS Nano 10:4644-51
Wilson, James; Sloman, Leila; He, Zhiren et al. (2016) Graphene Nanopores for Protein Sequencing. Adv Funct Mater 26:4830-4838
Belkin, Maxim; Chao, Shu-Han; Jonsson, Magnus P et al. (2015) Plasmonic Nanopores for Trapping, Controlling Displacement, and Sequencing of DNA. ACS Nano 9:10598-611
Li, Yi; Nicoli, Francesca; Chen, Chang et al. (2015) Photoresistance switching of plasmonic nanopores. Nano Lett 15:776-82
Li, Chen-Yu; Hemmig, Elisa A; Kong, Jinglin et al. (2015) Ionic conductivity, structural deformation, and programmable anisotropy of DNA origami in electric field. ACS Nano 9:1420-33
Pud, Sergii; Verschueren, Daniel; Vukovic, Nikola et al. (2015) Self-Aligned Plasmonic Nanopores by Optically Controlled Dielectric Breakdown. Nano Lett 15:7112-7

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