Magnetic Resonance Force Microscopy Christian Degen Department of Physics, ETH Zurich, Switzerland CIMST Summer School 2014
From Andreas Trabesinger / Wikipedia
Scale of things 1m 1mm 1µm 1-100 nm 1nm light MRI Electron microscopy X-ray NMR Super-resolution microscopy Free Electron Laser Electron Tomography Nano-MRI S. Subramaniam, Current Opinion in Microbiology 8, 316 (2005).
Outline Basics of Scanning Probe Microscopy Magnetic resonance force microscopy (MRFM): MRI Imaging with Nanometer Resolution Outlook towards structural biology
The Silicon (111) Surface F. Giessibl
1986 Heinrich Rohrer, Gerd Binnig (IBM Zurich) for their design of the scanning tunneling microscope
Prof. Christian Degen Scanning tunneling microscopy (STM) I e L / λ λ 0.05nm
STM Apparatus Control Voltages XYZ Piezo Scanner Tunneling Current Amplifier Tip-Sample Distance Feedback Tunneling Voltage Computer
STM Tip 0.2 mm Electrochemically Etched Tungsten tip
Fe atoms on Cu surface
Xe atoms on Ni surface
www.research.ibm.com/articles/madewithatoms.shtml
Variations of Scanning Probe Microscopy Scanning Tunneling Microscope (STM) Atomic Force Microscope (AFM) Magnetic Force Microscope (MFM) Near-field Scanning Optical Microscope (NSOM) Scanning Sensors (Hall, SQuID, Diamond spins, )
Force Microscopy True atomic resolution Atomic imaging and manipulation on surfaces Silicon (111) cantilever tip F. Giessibl et al. DNA + restriction endonuclease Magnetic bits on a hard disk L. Folks, IBM
Magnetic Resonance Imaging (MRI) True 3D imaging Chemically selective Non-destructive BUT Requires 10 12-10 18 nuclei (atoms) per voxel We want to be able to resolve a single nuclear spin!
Magnetic Resonance Tomograph Generates RF pulses Detects RF signal Generate magnetic field gradient (~10 T/m) to localize signal with ~0.1 mm resolution
Best inductive MRI: ~3 µm resolution Sensitive detection with RF microcoil Coil Glass capillary Ciobanu, Pennington et al. (2002) Sensitivity ~ 10 12 hydrogen nuclei
Magnetic resonance force microscopy
Magnetic resonance force microscopy (MRFM) Cantilever John Sidles 1991 molecule field gradient resonant slice B(x,y,z) = ω rf /γ (2.71 Tesla) rf field frequency ω rf magnetic field lines Magnetic tip B F = z µ z z (115 MHz) z spin magnetic moment Best cantilever force sensor Single proton spin Single electron spin ~10-18 N ~10-20 N ~10-17 N Chemical bond breaking ~10-8...10-11 N 2 electrons, 100 nm apart ~10-14 N
Early MRFM 1995 3D nuclear MRI with ~3 µm resolution Ammonium Nitrate T = 300 K 100 µm Optisch 1 H MRFM Zuger et al, JAP (1995) Sensitivity ~ 10 12 hydrogen nuclei
2004 Early MRFM Detection of single electron spin with ~ 25 nm resolution Silicon cantilever Temperature: 1.6 Kelvin 0.2 µm Magnet (SmCo) Rugar et al. Nature (2004) Sensitivity ~ 10 6 hydrogen nuclei
Present Magnetic Resonance Force Microscope Ultrasensitive cantilever B 0 Laser interferometer Sample (containing 1 H spins) Resonant slice (2.7 Tesla) Magnetic tip Stripline producing RF field (115 MHz)
Basics of Magnetic Resonance Force Microscopy
Ultrasensitive cantilevers 120 µm 100 nm thick shaft F thermal = 2k TkB πfq B w 4 an 1 µm thick mass loading k = 86 µn/m f = 2.6 khz Q = 50,000 at 4K 1 Hz bandwidth
Magnetic nanotip + RF stripline Cu microstrip B tip FeCo tip B rf i rf Si substrate Magnetic gradient: ~5 million T/m RF-field: 3 mt at 0.2 mw power Paolo Navaretti Collaboration: Martino Poggio (Basel)
Millikelvin MRFM Microscope 1 cm 5 cm
Cryogenic MRFM Cryostat operating at 0.08 4.2 K High vacuum (<10-6 mbar) Magnetic field 0-6 Tesla
Imaging: Principle and Examples
Imaging by 3D raster scanning Ultrasensitive cantilever B 0 Laser interferometer Sample (containing 1 H spins) Resonant slice (2.7 Tesla) Magnetic tip Stripline producing RF field (115 MHz)
Nanoscale MRI of virus particles 1 µm Tobacco mosaic virus: 18 nm diameter 300 nm long
3D force signal of virus particles d = 34 nm 46 nm 59 nm 71 nm 100 nm proton spins 1min per point spin noise image force signal F(r) = spin density ρ(r ) * point spread function P(r-r )?
3D MRFM reconstruction showing 1 H density 3D Nano-MRI of Tobacco Mosaic Virus Detail from one horizontal slice Y Scanning electron micrograph 6 nm 50 nm Cross-section showing depth resolution Z Virus particles z y x 500 nm 500 nm 30 nm layer of adsorbed water / hydrocarbons CLD, PNAS (2009)
Iterative Landweber reconstruction Experimental data Trial object Convolution with PSF Mock data Error? multiply by α, add to trial object Convolution with PSF
Iterative Landweber reconstruction Experimental data Trial object Convolution with PSF Mock data Error multply by α, add to trial object Convolution with PSF
3D image of Tobacco Mosaic Virus MRFM proton scan data at various tip-sample distances d = 34 nm 46 nm 59 nm 71 nm 100 nm After image reconstruction One slice from the 3D reconstruction showing 1 H density Scanning electron micrograph 100 nm 100 nm
Scanning electron micrograph Carbon nanotubes 500 nm Nano-MRI Silicon cantilever z x y 50 nm CNT CNT 1 H density H. J. Mamin, Nano. Lett. (2009)
Nanowire coated with CaF 2 and hydrocarbons 2um Single Isotope Sweep: 1 H InAs NW CaF 2 coating on this side Single Isotope Sweep: 19 F ~1nm hydrocarbon adsorbate layer around NW
Multi-slice acquisition of Nanowire 116 MHz 0 nm 125 250 nm 117 MHz 118 MHz 119 MHz 120 MHz z x 121 MHz
Outlook
Strategy for imaging quarternary structure of protein assemblies 1 nm resolution 5 nm resolution Atomic structure Strategy 1: Resolution Strategy 2: Contrast A B C Strategy 3: Fitting/Reconstruction Example: Dengue virus Contrast (isotopes)
Tobacco mosaic virus (revisited) Protein coat (2130 subunits) 100 nm Central core with RNA
Synthesis of partially labeled TMV particles 0.8 Other fragments ionic strength (M) 0.6 0.4 42MDa Protein disks Labeled protein fragments from bacteria 0.2 Labeled TMV 600kDa 17.5kDa 0.0 5 6 7 8 9 10 ph Romana Schirhagl Collaboration: Richard Kammerer (PSI)
How 3D will an image be? Influenza virus (H1N1) 100 nm http://homepage.usask.ca
Example Reconstruction of Influenza Virus Object (hydrogen density) Expected MRFM images (for two different point spread functions) z x Reconstructed Object Image is 400x200 nm 2 Sampling grid is 4 nm
Summary and Outlook MRFM Achievements Combines 3D resolution of MRI + nanoscale resolution of AFM Sensitivity ~10 4 hydrogen atoms (conventional NMR/MRI: ~10 12 ) Demonstrated imaging of virus particle with ~5 nm resolution Concerns Is 5 nm resolution sufficient for structural imaging? No. Need <2 nm What about the cryogenic environment? Fine. See Cryo-EM Why use MRFM, given powerful established techniques (X-Ray, NMR and EM) MRFM is truly single particle Rich MRI image contrast