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)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
1R01HG007406-01
Application #
8572877
Study Section
Special Emphasis Panel (ZHG1-HGR-N (M1))
Program Officer
Schloss, Jeffery
Project Start
2013-09-01
Project End
2017-07-31
Budget Start
2013-09-01
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$680,437
Indirect Cost
$89,397
Name
University of Illinois Urbana-Champaign
Department
Physics
Type
Schools of Engineering
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Maffeo, Christopher; Ngo, Thuy T M; Ha, Taekjip et al. (2014) A Coarse-Grained Model of Unstructured Single-Stranded DNA Derived from Atomistic Simulation and Single-Molecule Experiment. J Chem Theory Comput 10:2891-2896
Belkin, Maxim; Chao, Shu-Han; Giannetti, Gino et al. (2014) Modeling thermophoretic effects in solid-state nanopores. J Comput Electron 13:826-838
Maffeo, C; Yoo, J; Comer, J et al. (2014) Close encounters with DNA. J Phys Condens Matter 26:413101
Shankla, Manish; Aksimentiev, Aleksei (2014) Conformational transitions and stop-and-go nanopore transport of single-stranded DNA on charged graphene. Nat Commun 5:5171