This proposal aims to develop technology for dramatically increasing the sensitivity of magnetic resonance imaging. The goal is to develop a """"""""molecular microscope"""""""" to detect, analyze, and image nanoscale entities of relevance to biomedicine. Tools for determining protein structure are central to biological research. Improved tools for determining the three dimensional structure of large macromolecules and aggregate structures are urgently needed. A majority of proteins are not well suited for analysis by current methods because they cannot be isolated in large enough quantities or because they do not form crystals. In this proposal we present plans for developing a cantilever-based molecular microscope that can determine the structure of a single copy of a protein, a task which no current technology can achieve. Such an instrument would revolutionize structural biology, dramatically impacting a broad spectrum of biological processes, disorders, and diseases. ? ? In this proposal we detail a stepwise approach to developing a molecular microscope for imaging single ? biomolecules based on a marriage of atomic force microscope and magnetic resonance imaging technologies.
Our specific aims are: (1) To detect nuclear magnetic resonance in a new way, as a change in the spring constant of a magnetically tipped microcantilever, (2) Fabricate and characterize nanomagnets suitable for single-proton cantilever detected magnetic resonance. Explore experimentally the minimum forces and spring constant changes that can be detected when a thin, ultrasensitive, silicon microcantilever is brought close to a surface, and (3) Develop and test magnetic resonance imaging protocols suited to small ensembles of nuclear spins. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM070012-01
Application #
6710808
Study Section
Special Emphasis Panel (ZRG1-BBCB (50))
Program Officer
Lewis, Catherine D
Project Start
2004-06-01
Project End
2009-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
1
Fiscal Year
2004
Total Cost
$243,583
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Issac, Corinne E; Gleave, Christine M; Nasr, Paméla T et al. (2016) Dynamic nuclear polarization in a magnetic resonance force microscope experiment. Phys Chem Chem Phys 18:8806-19
Chen, Lei; Longenecker, Jonilyn G; Moore, Eric W et al. (2013) Magnetic Resonance Force Microscopy Detected Long-Lived Spin Magnetization. IEEE Trans Magn 49:3528-3532
Chen, Lei; Longenecker, Jonilyn G; Moore, Eric W et al. (2013) Long-lived frequency shifts observed in a magnetic resonance force microscope experiment following microwave irradiation of a nitroxide spin probe. Appl Phys Lett 102:132404
Alexson, Dimitri A; Hickman, Steven A; Marohn, John A et al. (2012) Single-shot nuclear magnetization recovery curves with force-gradient detection. Appl Phys Lett 101:022103
Lee, Sanggap; Moore, Eric W; Marohn, John A (2012) A Unified Picture of Cantilever Frequency-Shift Measurements of Magnetic Resonance. Phys Rev B Condens Matter Mater Phys 85:165447-165453
Longenecker, Jonilyn G; Mamin, H J; Senko, Alexander W et al. (2012) High-gradient nanomagnets on cantilevers for sensitive detection of nuclear magnetic resonance. ACS Nano 6:9637-45
Lee, Sanggap; Moore, Eric W; Hickman, Steven A et al. (2012) Switching through intermediate states seen in a single nickel nanorod by cantilever magnetometry. J Appl Phys 111:83911-839117
Longenecker, Jonilyn G; Moore, Eric W; Marohn, John A (2011) Rapid serial prototyping of magnet-tipped attonewton-sensitivity cantilevers by focused ion beam manipulation. J Vac Sci Technol B Nanotechnol Microelectron 29:32001
Moore, Eric W; Lee, Sanggap; Hickman, Steven A et al. (2010) Evading surface and detector frequency noise in harmonic oscillator measurements of force gradients. Appl Phys Lett 97:
Hickman, Steven A; Moore, Eric W; Lee, SangGap et al. (2010) Batch-fabrication of cantilevered magnets on attonewton-sensitivity mechanical oscillators for scanned-probe nanoscale magnetic resonance imaging. ACS Nano 4:7141-50

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