The purpose of this project is to develop a high speed device for sequencing a single strand DNA (ssDNA). The proposed device represents an alternative to nanopore sequencing with enhanced control capabilities both in translocation and detection. The central component of our device is a nanoscale quadrupole Paul trap that will be used for isolation, trapping, and localization of DNA and integrated with a detection circuitry for rapid sequencing of ssDNA. The proposed work builds on two important results from preliminary molecular dynamics and quantum-mechanical simulations. The first result confirms that a nanoscale quadrupole Paul trap is capable of effectively confining ions in an aqueous environment. The second result concerns the discovery of a quasi-resonant tunneling regime that results in several orders of magnitude increase in the transverse tunneling current using nitrogen doped carbon nanotube (CNT) electrodes. We envision designing a prototype nanoscale quadrupole Paul trap that can be used to explore various detection schemes based on the measurement of the transverse tunneling current and local capacitance. Specifically, to arrive at the best detection scheme to be integrated with the Paul trap in the final form of the sequencing device the feasibility of the following two novel detection schemes will be determined by modeling and experimental testing;(1) a radio-frequency single-electron transistor (RF SET), and (2) a nitrogen doped-CNT to measure the resonant tunneling current through the gap. To reduce device complexity the preliminary studies of the detection schemes will be performed separately from the Paul trap device. An advantage of a nanofabricated Paul trap is that a visible pathway for massively parallel sequencing device can be identified by using arrays of Paul traps. Device fabrication is further simplified by relaxation of critical dimension control that stems from the fact that the nm-size electrostatic trapping volume is much smaller than the fabricated dimensions (20-100nm). Direct sequencing using electronic measurements is potentially orders of magnitude faster than existing methods. The proportionally lower cost enables this technology to be used in everyday clinical practice for genome-based medical treatments. PROJECT

Public Health Relevance

An efficacious platform technology to sequence human genome by AC/DC electrical detection of DNA bases while DNA is translocated through a quadrupole nanogap. This will lead to a device that is capable for accurate genome sequencing many times cheaper and faster than currently available and will pave the way for in situ clinical practice of genome-based medical treatments.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HG004764-02
Application #
7676234
Study Section
Special Emphasis Panel (ZHG1-HGR-N (M1))
Program Officer
Schloss, Jeffery
Project Start
2008-08-19
Project End
2011-11-30
Budget Start
2009-06-01
Budget End
2011-11-30
Support Year
2
Fiscal Year
2009
Total Cost
$362,265
Indirect Cost
Name
UT-Battelle, LLC-Oak Ridge National Lab
Department
Type
DUNS #
099114287
City
Oak Ridge
State
TN
Country
United States
Zip Code
37831
Park, Jae Hyun; Guan, Weihua; Reed, Mark A et al. (2012) Tunable aqueous virtual micropore. Small 8:907-12
Park, Jae Hyun; Krstic, Predrag S (2012) Stability of an aqueous quadrupole micro-trap. J Phys Condens Matter 24:164208
Guan, Weihua; Joseph, Sony; Park, Jae Hyun et al. (2011) Paul trapping of charged particles in aqueous solution. Proc Natl Acad Sci U S A 108:9326-30
Guan, Weihua; Park, Jae Hyun; Krstic, Predrag S et al. (2011) Non-vanishing ponderomotive AC electrophoretic effect for particle trapping. Nanotechnology 22:245103
Park, Jae Hyun; Krsti, Predrag S (2011) Control Of Screening Of A Charged Particle In Electrolytic Aqueous Paul Trap. AIP Conf Proc 1336:150-153
Korkin, Anatoli; Krstic, Predrag; Miskovic, Zoran et al. (2010) Nanoscale Science and Technology for Electronics, Photonics and Renewable Energy Applications: Selected Papers from NGC2009 & CSTC2009 conference (http://asdn.net/ngc2009/). Nanoscale Res Lett 5:453
Joseph, Sony; Guan, Weihua; Reed, Mark A et al. (2010) A long DNA segment in a linear nanoscale Paul trap. Nanotechnology 21:015103