Three-dimensional nanoscale molecular imaging by extreme ultraviolet laser ablation mass spectrometry

Analytical probes capable of mapping molecular composition at the nanoscale are of critical importance to materials research, biology and medicine. Mass spectral imaging makes it possible to visualize the spatial organization of multiple molecular components at a sample's surface. However, it is challenging for mass spectral imaging to map molecular composition in three dimensions (3D) with submicron resolution. Here we describe a mass spectral imaging method that exploits the high 3D localization of absorbed extreme ultraviolet laser light and its fundamentally distinct interaction with matter to determine molecular composition from a volume as small as 50 zl in a single laser shot. Molecular imaging with a lateral resolution of 75 nm and a depth resolution of 20 nm is demonstrated. These results open opportunities to visualize chemical composition and chemical changes in 3D at the nanoscale.

[1]  M. P. Smith,et al.  The New Frontier. , 1984, RNABC news.

[2]  P. Dorrestein,et al.  Microbial metabolic exchange in 3D , 2013, The ISME Journal.

[3]  Margaret King,et al.  State of the art and perspectives , 2004, Machine Translation.

[4]  Libor Juha,et al.  Ablation of organic polymers by 46.9-nm-laser radiation , 2005 .

[5]  Raman Sankar,et al.  Growth, optical, thermal and dielectric studies of an amino acid organic nonlinear optical material: l-Alanine , 2009 .

[6]  B. L. Henke,et al.  X-Ray Interactions: Photoabsorption, Scattering, Transmission, and Reflection at E = 50-30,000 eV, Z = 1-92 , 1993 .

[7]  Fabian Svara,et al.  High-reactivity matrices increase the sensitivity of matrix enhanced secondary ion mass spectrometry. , 2011, Analytical chemistry.

[8]  E. Anderson.  Specialized electron beam nanolithography for EUV and X-ray diffractive optics , 2006, IEEE Journal of Quantum Electronics.

[9]  J. Vickerman.  Molecular imaging and depth profiling by mass spectrometry--SIMS, MALDI or DESI? , 2011, The Analyst.

[10]  B. Garrison,et al.  Microscopic Insights into the Sputtering of Ag{111} Induced by C60 and Ga Bombardment , 2004 .

[11]  L. Hanley,et al.  Light and molecular ions: the emergence of vacuum UV single-photon ionization in MS. , 2009, Analytical chemistry.

[12]  E. Niehuis,et al.  Dual beam depth profiling of polymer materials: comparison of C60 and Ar cluster ion beams for sputtering , 2013 .

[13]  Oleg A. Prokopyev,et al.  APPLICATIONS IN BIOMEDICINE , 2006 .

[14]  B. Lai,et al.  Trace metal imaging with high spatial resolution: applications in biomedicine. , 2011, Metallomics : integrated biometal science.

[15]  C. Menoni,et al.  Photoionized plasmas created by soft x-ray laser irradiation of solid targets , 2008, 2008 Conference on Lasers and Electro-Optics and 2008 Conference on Quantum Electronics and Laser Science.

[16]  S. Boxer,et al.  Phase Separation of Lipid Membranes Analyzed with High-Resolution Secondary Ion Mass Spectrometry , 2006, Science.

[17]  Richard M. Caprioli,et al.  MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. , 2008, Analytical chemistry.

[18]  R. Caprioli,et al.  Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS. , 2012, Journal of mass spectrometry : JMS.

[19]  B. Garrison,et al.  Mesoscale energy deposition footprint model for kiloelectronvolt cluster bombardment of solids. , 2006, Analytical chemistry.

[20]  Richard M. Caprioli,et al.  3D imaging by mass spectrometry: a new frontier. , 2012, Analytical chemistry.

[21]  Richard M Caprioli,et al.  Molecular imaging of proteins in tissues by mass spectrometry , 2008, Proceedings of the National Academy of Sciences.

[22]  Alex Henderson,et al.  Three-dimensional mass spectral imaging of HeLa-M cells--sample preparation, data interpretation and visualisation. , 2011, Rapid communications in mass spectrometry : RCM.

[23]  J. Sabine Becker,et al.  Bioimaging of metals in brain tissue from micrometre to nanometre scale by laser ablation inductively coupled plasma mass spectrometry: State of the art and perspectives , 2010 .

[24]  Michael Karas,et al.  Matrix‐assisted laser desorption ionization mass spectrometry , 1991 .

[25]  Charles R. Hoffer,et al.  A New Frontier , 1989 .

[26]  F. Höök,et al.  Spatial-resolution limits in mass spectrometry imaging of supported lipid bilayers and individual lipid vesicles. , 2010, Analytical chemistry.

[27]  R. Caprioli,et al.  Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS. , 2012, Journal of mass spectrometry : JMS.

[28]  C S Menoni,et al.  Nanometer-scale ablation with a table-top soft x-ray laser. , 2006, Optics letters.

[29]  J. Rocca,et al.  Demonstration of a desk-top size high repetition rate soft x-ray laser. , 2005, Optics express.

[30]  N. Winograd,et al.  Molecular sputter depth profiling using carbon cluster beams , 2010, Analytical and bioanalytical chemistry.

[31]  Bernhard Spengler,et al.  Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: Instrumentation for sub-micrometer resolved LDI and MALDI surface analysis , 2002, Journal of the American Society for Mass Spectrometry.

[32]  M. Karas,et al.  Ultraviolet–laser desorption/ionization mass spectrometry of femtomolar amounts of large proteins , 1989 .