Magnetic Resonance Force Microscopy Christian Degen Department of Physics ETH Zurich Switzerland CIMST Summer School  From Andreas Trabesinger  Wikipedia  NMR MRI Xray light Electron microscopy Scale
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Magnetic Resonance Force Microscopy Christian Degen Department of Physics ETH Zurich Switzerland CIMST Summer School From Andreas Trabesinger Wikipedia NMR MRI Xray light Electron microscopy Scale

Subramaniam Current Opini on in Microbiology 8 316 2005 1 100 nm 1nm Scanning Probe Microscopy Magnetic Resonance Imaging Low Energy h 10 26 Joule High Resolution 0110 Nanometers brPage 3br Outline Basics of Scanning Probe Microscopy Magnetic reso

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Magnetic Resonance Force Microscopy Christian Degen Department of Physics ETH Zurich Switzerland CIMST Summer School From Andreas Trabesinger Wikipedia NMR MRI Xray light Electron microscopy Scale




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Presentation on theme: "Magnetic Resonance Force Microscopy Christian Degen Department of Physics ETH Zurich Switzerland CIMST Summer School From Andreas Trabesinger Wikipedia NMR MRI Xray light Electron microscopy Scale"— Presentation transcript:


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Magnetic Resonance Force Microscopy Christian Degen Department of Physics, ETH Zurich, Switzerland CIMST Summer School 2013 From Andreas Trabesinger / Wikipedia
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NMR MRI X-ray light Electron microscopy Scale of things Super-resolution microscopy Free Electron Laser Electron Tomography Nano-MRI 1m 1mm S. Subramaniam, Current Opini on in Microbiology 8, 316 (2005). 1 - 100 nm 1nm Scanning Probe Microscopy Magnetic Resonance Imaging Low Energy: h ~ 10 -26 Joule High Resolution: 0.1-10 Nanometers
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Outline Basics of Scanning Probe Microscopy

Magnetic resonance force microscopy (MRFM): MRI Imaging with Nanometer Resolution Toward (true) single particle imaging in structural biology The Silicon (111) Surface F. Giessibl
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Heinrich Rohrer, Gerd Binnig (IBM Zurich) 1986 for their design of the scanning tunneling microscope Scanning tunneling microscopy (STM) Prof. Christian Degen nm 05
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STM Apparatus Control Voltages Tunneling Current Amplifier Tip-Sample Distance Feedback Computer XYZ Piezo Scanner Tunneling Voltage STM Tip 0.2 mm Electrochemically Etched Tungsten tip
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Fe atoms on Cu

surface Xe atoms on Ni surface
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www.research.ibm.com/art icles/madewithatoms.shtml Variations of Scanning Probe Microscopy Scanning Tunneling Microscope (STM) Atomic Force Microscope (AFM) Near-field Scanning Optical Microscope (NSOM) Magnetic Force Microscope (MFM) Scanning Sensors (Hall, SQuID, Diamond spins, )
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Atomic imaging and manipulation on surfaces True atomic resolution F. Giessibl et al. DNA + restriction endonuclease Magnetic bits on a hard disk L. Folks, IBM Silicon (111) tip cantilever Force Microscopy Force spectroscopy Si, Sn and Pb on Si(111)

substrate Sugimoto, Custance 2007 Si Sn Pb Topographic AFM image Elements distinguished by different chemical forces
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Magnetic Resonance Imaging (MRI) True 3D imaging Chemically selective Non-destructive We want to be able to resolve a single nuclear spin! BUT Requires 10 12 -10 18 nuclei (atoms) per voxel Magnetic Resonance Tomograph Generates RF pulses Detects RF signal Generate magnetic field gradient (~10 T/m) to localize signal with ~0.1 mm resolution
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10 Best inductive MRI: ~3 m resolution Sensitivity ~ 10 12 hydrogen nuclei Coil Sensitive detection

with RF microcoil Glass capillary Ciobanu, Pennington et al. (2002) Magnetic Resonance Force Microscopy
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11 Magnetic resonance force microscopy (MRFM) molecule field gradient spin magnetic moment resonant slice B(x,y,z) = rf (2.71 Tesla) rf field frequency rf (115 MHz) magnetic field lines Best cantilever force sensor ~10 -18 Single proton spin ~10 -20 Single electron spin ~10 -17 Chemical bond breaking ~10 -8 ...10 -11 2 electrons, 100 nm apart ~10 -14 Magnetic tip Cantilever John Sidles 1991 Early MRFM Zuger et al, JAP (1995) H in Ammoniumnitrat T = 300 K Optisch MRFM 1995

3D nuclear MRI with ~3 m resolution Sensitivity ~ 10 12 hydrogen nuclei
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12 Early MRFM Rugar et al. Nature (2004) Silicon cantilever 0.2 m Magnet (SmCo) Temperature: 1.6 Kelvin 2004 Detection of single electron spin with ~ 25 nm resolution Sensitivity ~ 10 hydrogen nuclei Laser interferometer Ultrasensitive cantilever Magnetic tip Sample (containing H spins) Present Magnetic Resonance Force Microscope Stripline producing RF field (115 MHz) Resonant slice (2.7 Tesla)
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13 Basics of Magnetic Resonance Force Microscopy 120 m k = 86 N/m f = 2.6 kHz Q = 50,000 at

4K Ultrasensitive cantilevers 100 nm thick shaft 1 m thick mass loading aN fQ TkB thermal 1 Hz bandwidth
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14 Paolo Navaretti Collaboration: Martino Poggio (Basel) rf rf tip Cu microstrip FeCo tip Si substrate Magnetic gradient: ~5 million T/m RF-field: 3 mT at 0.2 mW power Magnetic nanotip + RF stripline Millikelvin MRFM Microscope 1 cm 5 cm
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15 Cryogenic MRFM Cryostat operating at 0.08 4.2 K High vacuum (<10 -6 mbar) Magnetic field 0-6 Tesla Examples of NanoMRI - Imaging
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16 Laser interferometer Ultrasensitive cantilever Magnetic tip

Sample (containing H spins) Present Magnetic Resonance Force Microscope Stripline producing RF field (115 MHz) Resonant slice (2.7 Tesla) 1 Nanoscale MRI of virus particles Tobacco mosaic virus: 18 nm diameter 300 nm long
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17 100 nm 3D force signal of virus particles d = 34 nm 46 nm 59 nm 71 nm force signal F(r) = spin density (r) point spread function P(r-r) proton spins 1min per point spin noise image 99 3D Nano-MRI of Tobacco Mosaic Virus 30 nm Virus particles layer of adsorbed water / hydrocarbons Cross-section showing depth resolution 6 nm Detail from one horizontal

slice 50 nm 3D MRFM reconstruction showing H density Scanning electron micrograph 500 nm 500 nm CLD, PNAS (2009)
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18 3D image of Tobacco Mosaic Virus MRFM proton scan data at va rious tip-sample distances d = 34 nm 46 nm 59 nm 71 nm 100 nm 100 nm 100 nm After image reconstruction One slice from the 3D reconstruction showing H density Scanning electron micrograph Carbon nanotubes 500 nm Silicon cantilever CNT 50 nm CNT Scanning electron micrograph Nano-MRI H. J. Mamin, Nano. Lett. (2009) H density
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19 Other nuclei: 23 Na, 27 Al, 29 Si, 51 V, 69 Ga, 71 Ga, 75

As, 113 In, 115 In 0 25 50 75 100 125 NMR frequency (MHz) Signal (a.u.) 13 31 19 DNA Stearic acid CaF = 2.6 T Elemental selectivity Summary and Outlook Is 5 nm resolution sufficient for structural imaging? What about the cryogenic environment? Why use MRFM, given powerful established techniques (X-Ray, NMR and EM) Combines 3D resolution of MRI with nanoscale resolution of AFM Sensitive to about 10 hydrogen atoms, compared to 1012 for conventional NMR/MRI Achieved 3D imaging of single biological object (virus particle) with ~5 nm resolution Concerns MRFM Achievements
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Outline Recent steps toward single-molecule imaging Temperature: 77 K Cryo-EM vs. Nano-MRI Cryo-electron microscopy Nano-MRI Example: Tobacco Mosaic Virus Degen et al., PNAS (2009) Frank, Annu. Rev. Biophys. (2002) Example: Ribosome Resolution: 10 - 20 A few days of data taking 30k particles needed for averaging Contrast: Heavy atoms Temperature: < 1 K Resolution: ca. 40 - 80 7 days of data taking Single particle! Contrast: H, 13 C,
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21 Cryo Electron Microscopy 3D reconstruction 20 nm 70S ribosomes of E. coli, Frank, Annu. Rev. Biophys. (2002) fully hydrated structures can

be imaged at cryogenic temperatures significant structural information can be obtained with 10-20 resolution Strategy for imaging quarternary structure of protein assemblies 5 nm resolution Atomic structure Strategy 1: Resolution Strategy 2: Contrast Strategy 3: Fitting/Reconstruction Example: Dengue virus 1 nm resolution Contrast (isotopes)
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22 MRFM Signal-to-noise Ratio Number of spins in voxel Magnetic moment Magnetic gradient currently up to 5 MT/m Minimum detectable force by cantilever Spin relaxation time Total measurement time Commercial AFM cantilever Typical MRFM

cantilever 225 Alternative Cantilevers ~ 3 kHz ~ 10 -4 N/m km min
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23 Commercial AFM cantilever Typical MRFM cantilever Nanowire cantilever 225 10 ~ 3 kHz ~ 10 -4 N/m ~ 500 kHz ~ 10 -4 N/m Nanowire-based MRFM Nichol, Budakian (2013)
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24 Nanowire-based MRFM Electron Micrograph MRFM Image Nichol, Budakian (2013) 100-800 nm thickness 10 Single-crystal diamond cantilevers Diamond cantilevers Quartz substrate Diamond membrane 100 Excellent mechanical quality factor: Q ~ 6000000 (Silicon: Q ~ 60000)
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25 Ladder resonators 80 - 150 nm Test

devices made from silicon 30x lower spring constant 10x lower mass Strategy for imaging quarternary structure of protein assemblies 5 nm resolution Atomic structure Strategy 1: Resolution Strategy 2: Contrast Strategy 3: Fitting/Reconstruction Example: Dengue virus 1 nm resolution Contrast (isotopes)
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26 What about samples? Size: 10-100 nm (MDa GDa) Polymorphic, Disordered Difficult to isolate, crystallize, dissolve, HIV 200 nm Amyloid fibrils Nuclear pore complex Membrane proteins Heat shock proteins Tobacco mosaic virus (revisited) 100 nm Protein coat (2130 subunits)

Central core with RNA
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27 Synthesis of partially labeled TMV particles 5678910 pH 0.0 0.2 0.4 0.6 0.8 ionic ength Labeled protein fragments from bacteria Labeled TMV Protein disks 17.5kDa 600kDa 42MDa Other fragments Romana Schirhagl Collaboration: Richard Kammerer (PSI) Sample attachment GaAs NW glued to Ultrasensitive cantilever 1 Pulled Polystyrene Tips w/ 6nm Au nanoparticles 10 200 nm 50 nm Brad Moores Ye Tao
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28 Magnetic Resonance Force Microscopy (MRFM) MRFM: Utilizes scanning probe microscopy to perform Nano-MRI with ~5 nm spatial resolution True

single particle imaging for structural biology: No averaging, no radiati on damage, no crystallization Rich image contrast known from clinical MRI Summary