Microscope mode secondary ion mass spectrometry imaging with a Timepix detector.

In-vacuum active pixel detectors enable high sensitivity, highly parallel time- and space-resolved detection of ions from complex surfaces. For the first time, a Timepix detector assembly was combined with a secondary ion mass spectrometer for microscope mode secondary ion mass spectrometry (SIMS) imaging. Time resolved images from various benchmark samples demonstrate the imaging capabilities of the detector system. The main advantages of the active pixel detector are the higher signal-to-noise ratio and parallel acquisition of arrival time and position. Microscope mode SIMS imaging of biomolecules is demonstrated from tissue sections with the Timepix detector.

[1]  B. Hagenhoff,et al.  Influence of primary ion bombardment conditions on the emission of molecular secondary ions , 2004 .

[2]  Tyler Greer,et al.  Mass spectrometry imaging for drugs and metabolites. , 2011, Journal of proteomics.

[3]  J. Vickerman,et al.  The role of molecular weight on the ToF‐SIMS spectra of PMMA using Au+ and C60+ primary ions , 2010 .

[4]  Nicholas Lockyer,et al.  A C60 primary ion beam system for time of flight secondary ion mass spectrometry: its development and secondary ion yield characteristics. , 2003, Analytical chemistry.

[5]  B. van der Heijden,et al.  A Gigabit per second read-out system for Medipix Quads , 2011 .

[6]  G. Morrison,et al.  Peer Reviewed: A Subcellular Imaging by Dynamic SIMS Ion Microscopy. , 2000 .

[7]  M. Pellin,et al.  Mass spectrometry on the nanoscale with ion sputtering based techniques: What is feasible , 2007 .

[8]  Alfons Hester,et al.  A high-resolution scanning microprobe matrix-assisted laser desorption/ionization ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron resonance mass spectrometer. , 2008, Rapid communications in mass spectrometry : RCM.

[9]  R. Odom,et al.  Matrix-enhanced secondary ion mass spectrometry:  a method for molecular analysis of solid surfaces. , 1996, Analytical chemistry.

[10]  A. Wucher.  Molecular secondary ion formation under cluster bombardment: A fundamental review , 2006 .

[12]  V. M. Collado,et al.  Dynamics of secondary ion emission: Novel energy and angular spectrometry , 2002 .

[13]  D. Weibel,et al.  C60 cluster ion bombardment of organic surfaces , 2004 .

[14]  A. Ewing,et al.  ToF-SIMS imaging with cluster ion beams , 2004 .

[15]  R. Heeren,et al.  Mass spectrometric imaging for biomedical tissue analysis. , 2010, Chemical reviews.

[16]  M. Vrakking,et al.  High dynamic range bio-molecular ion microscopy with the Timepix detector. , 2011, Analytical chemistry.

[17]  Nicholas E. Manicke,et al.  Latent Fingerprint Chemical Imaging by Mass Spectrometry , 2008, Science.

[18]  Benjamin P Bowen,et al.  Mass spectrometry-based metabolomics, analysis of metabolite-protein interactions, and imaging. , 2010, BioTechniques.

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

[20]  A. Ewing,et al.  Atomic and molecular imaging at the single-cell level with TOF-SIMS. , 1997, Analytical chemistry.

[21]  L. McDonnell,et al.  High-spatial resolution mass spectrometric imaging of peptide and protein distributions on a surface. , 2004, Analytical chemistry.

[22]  R. Cooks,et al.  Forensic applications of ambient ionization mass spectrometry , 2009, Analytical and bioanalytical chemistry.

[23]  M. Vrakking,et al.  Fast, high resolution mass spectrometry imaging using a medipix pixelated detector , 2010, Journal of the American Society for Mass Spectrometry.

[24]  Daniel Turecek,et al.  Pixelman: a multi-platform data acquisition and processing software package for Medipix2, Timepix and Medipix3 detectors , 2011 .

[25]  L. Sumner,et al.  Current and emerging mass-spectrometry technologies for metabolomics , 2008 .

[26]  R. Dinapoli,et al.  Medipix2: A 64-k pixel readout chip with 55-/spl mu/m square elements working in single photon counting mode , 2001 .

[27]  Rafael Ballabriga,et al.  Timepix, a 65k programmable pixel readout chip for arrival time, energy and/or photon counting measurements , 2007 .

[28]  I. Fournier,et al.  On-tissue protein identification and imaging by MALDI-Ion mobility mass spectrometry , 2010, Journal of the American Society for Mass Spectrometry.

[29]  Thomas Hankemeier,et al.  Analytical strategies in lipidomics and applications in disease biomarker discovery. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[30]  R. Murphy,et al.  Lipidomics and imaging mass spectrometry. , 2011, Biochimica et Biophysica Acta.

[31]  D. Weibel,et al.  Development of a C60+ ion gun for static SIMS and chemical imaging , 2003 .

[32]  Liam A McDonnell,et al.  Imaging mass spectrometry. , 2007, Mass spectrometry reviews.

[33]  M. Campbell,et al.  10 years of the Medipix2 Collaboration , 2011 .

[34]  M. Setou,et al.  Imaging mass spectrometry for lipidomics. , 2011, Biochimica et biophysica acta.

[35]  A. Altelaar,et al.  Direct molecular imaging of Lymnaea stagnalis nervous tissue at subcellular spatial resolution by mass spectrometry. , 2005, Analytical chemistry.

[36]  Jonathan Stauber,et al.  Perspectives for imaging mass spectrometry in the proteomics landscape , 2009, Proteomics.

[37]  O. Ovchinnikova,et al.  Combined chemical and topographic imaging at atmospheric pressure via microprobe laser desorption/ionization mass spectrometry-atomic force microscopy. , 2009, Rapid communications in mass spectrometry : RCM.

[38]  Josef Uher,et al.  Data acquisition and processing software package for Medipix2 , 2006 .

[39]  P. Dankers,et al.  C60+ secondary ion microscopy using a delay line detector. , 2010, Analytical chemistry.

[40]  M. Clench,et al.  Matrix-assisted laser desorption/ionization-ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections. , 2008, Analytical chemistry.

[41]  Wouter Ruythooren,et al.  The RELAXd project: Development of four-side tilable photon-counting imagers , 2008 .

[42]  Ivo Klinkert,et al.  Biological Tissue Imaging with a Position and Time Sensitive Pixelated Detector , 2012, Journal of The American Society for Mass Spectrometry.

[43]  N. Winograd.  The Magic of Cluster SIMS , 2005 .

[44]  B. Långström,et al.  In Vitro Imaging Techniques in Neurodegenerative Diseases , 2007, Molecular Imaging and Biology.

[45]  Markus Stoeckli,et al.  MALDI mass spectrometric imaging of biological tissue sections , 2005, Mechanisms of Ageing and Development.

[46]  Julia Laskin,et al.  IonCCD™ for Direct Position-Sensitive Charged-Particle Detection: from Electrons and keV Ions to Hyperthermal Biomolecular Ions , 2011, Journal of the American Society for Mass Spectrometry.

[47]  B. Spengler,et al.  AP-MALDI imaging of neuropeptides in mouse pituitary gland with 5μm spatial resolution and high mass accuracy , 2011 .

[48]  L. McDonnell,et al.  Peptide and protein imaging mass spectrometry in cancer research. , 2010, Journal of proteomics.