Biological Tissue Imaging with a Position and Time Sensitive Pixelated Detector

We demonstrate the capabilities of a highly parallel, active pixel detector for large-area, mass spectrometric imaging of biological tissue sections. A bare Timepix assembly (512 × 512 pixels) is combined with chevron microchannel plates on an ion microscope matrix-assisted laser desorption time-of-flight mass spectrometer (MALDI TOF-MS). The detector assembly registers position- and time-resolved images of multiple m/z species in every measurement frame. We prove the applicability of the detection system to biomolecular mass spectrometry imaging on biologically relevant samples by mass-resolved images from Timepix measurements of a peptide–grid benchmark sample and mouse testis tissue slices. Mass-spectral and localization information of analytes at physiologic concentrations are measured in MALDI-TOF-MS imaging experiments. We show a high spatial resolution (pixel size down to 740 × 740 nm2 on the sample surface) and a spatial resolving power of 6 μm with a microscope mode laser field of view of 100–335 μm. Automated, large-area imaging is demonstrated and the Timepix’ potential for fast, large-area image acquisition is highlighted.

• Publication year

  2012

• Venue

  Journal of the American Society for Mass Spectrometry

• Publication date

  2012-07-27

• Fields of study

  Biology, Physics, Chemistry, Engineering, Medicine

• Identifiers
  DOI 10.1007/s13361-012-0444-5arXiv 1305.5437PMID 22836864
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment

  2014cited by this paper
• Methods for full resolution data exploration and visualization for large 2D and 3D mass spectrometry imaging datasets

  2014cited by this paper
• Emerging technologies in mass spectrometry imaging.

  2012cited by this paper
• Pixel imaging mass spectrometry with fast silicon detectors

  2011cited by this paper
• 10 years of the Medipix2 Collaboration

  2011cited by this paper
• Digital Imaging Mass Spectrometry

  2011cited by this paper
• MCP detector read out with a bare quad Timepix at kilohertz frame rates

  2011cited by this paper
• A Gigabit per second read-out system for Medipix Quads

  2011cited by this paper
• High-Speed MALDI-TOF Imaging Mass Spectrometry: Rapid Ion Image Acquisition and Considerations for Next Generation Instrumentation

  2011cited by this paper
• High dynamic range bio-molecular ion microscopy with the Timepix detector.

  2011cited by this paper
• Imaging Mass Spectrometry Using a Delay-Line Detector

  2010cited by this paper
• Matrix vapor deposition/recrystallization and dedicated spray preparation for high-resolution scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS) of tissue and single cells.

  2010cited by this paper
• A concise review of mass spectrometry imaging.

  2010cited by this paper
• Automated imaging MS: Toward high throughput imaging mass spectrometry.

  2010cited by this paper
• Fast, high resolution mass spectrometry imaging using a medipix pixelated detector

  2010cited by this paper
• Mass Spectrometry Imaging

  2010cited by this paper
• Imaging mass spectrometry: Hype or hope?

  2009cited by this paper
• Fast and automated large-area imaging MALDI mass spectrometry in microprobe and microscope mode

  2009cited by this paper
• Matrix-assisted laser desorption/ionization mass spectrometric imaging of complete rat sections using a triple quadrupole linear ion trap.

  2009cited by this paper
• Combined chemical and topographic imaging at atmospheric pressure via microprobe laser desorption/ionization mass spectrometry-atomic force microscopy.

  2009cited by this paper
• Velocity map imaging using an in-vacuum pixel detector.

  2009cited by this paper
• The RELAXd project: Development of four-side tilable photon-counting imagers

  2008cited by this paper
• 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.

  2008cited by this paper
• A photoelectron-photoion coincidence imaging apparatus for femtosecond time-resolved molecular dynamics with electron time-of-flight resolution of sigma=18 ps and energy resolution Delta E/E=3.5%.

  2008cited by this paper
• A photoelectron-photoion coincidence imaging apparatus for femtosecond time-resolved molecular dynamics with electron time-of-flight resolution of = 18 ps and energy resolution

  2008cited by this paper
• Erratum to “Timepix, a 65 k programmable pixel readout chip for arrival time, energy and/or photon counting measurements” [Nucl. Instr. and Meth. A. 581 (2007) 485 494]

  2008cited by this paper
• High-resolution UV, alpha and neutron imaging with the Timepix CMOS readout

  2008cited by this paper
• Imaging and 3D elemental characterization of intact bacterial spores by high-resolution secondary ion mass spectrometry.

  2008cited by this paper
• Imaging mass spectrometry.

  2007cited by this paper
• Mass spectrometry on the nanoscale with ion sputtering based techniques: What is feasible

  2007cited by this paper
• Timepix, a 65k programmable pixel readout chip for arrival time, energy and/or photon counting measurements

  2007cited by this paper
• Photon-counting X-ray imaging at kilohertz frame rates

  2007cited by this paper
• A read-out system for the Medipix2 chip capable of 500 frames per second

  2006cited by this paper
• Data acquisition and processing software package for Medipix2

  2006cited by this paper
• MALDI-MS imaging of features smaller than the size of the laser beam

  2005cited by this paper
• Infrared mass spectrometric imaging below the diffraction limit.

  2005cited by this paper
• High-spatial resolution mass spectrometric imaging of peptide and protein distributions on a surface.

  2004cited by this paper
• First test measurements of a 64k pixel readout chip working in single photon counting mode

  2003influential reference
• Recoil-ion and electron momentum spectroscopy: reaction-microscopes

  2003cited by this paper
• Imaging mass spectrometry: a new tool to investigate the spatial organization of peptides and proteins in mammalian tissue sections.

  2002cited by this paper
• Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: Instrumentation for sub-micrometer resolved LDI and MALDI surface analysis

  2002cited by this paper
• Medipix2: A 64-k pixel readout chip with 55-/spl mu/m square elements working in single photon counting mode

  2001cited by this paper
• Journal of The American Society for Mass Spectrometry

  1997cited by this paper
• Microscope imaging by time-of-flight secondary ion mass spectrometry

  1992cited by this paper
• Quantitative image acquisition system for ion microscopy based on the resistive anode encoder

  1983cited by this paper

• Improvements in Fast Mass Microscopy for Large-Area Samples

  2024cites this paper
• Development of High Throughput Microscope Mode Secondary Ion Mass Spectrometry Imaging.

  2023cites this paper
• An Orbitrap/Time-of-Flight Mass Spectrometer for Photofragment Ion Imaging and High-Resolution Mass Analysis of Native Macromolecular Assemblies

  2023cites this paper
• van der Waals Semiconductor Empowered Vertical Color Sensor.

  2022cites this paper
• Time-Resolved Imaging of High Mass Proteins and Metastable Fragments Using Matrix-Assisted Laser Desorption/Ionization, Axial Time-of-Flight Mass Spectrometry, and TPX3CAM

  2022cites this paper
• Imaging properties of a multi-reflection time-of-flight mass analyzer

  2021cites this paper
• Spatially Resolved Mass Spectrometry at the Single Cell: Recent Innovations in Proteomics and Metabolomics

  2021cites this paper
• Unique capabilities and applications of Microchannel Plate (MCP) detectors with Medipix/Timepix readout

  2020cites this paper
• Stigmatic imaging of secondary ions in MeV-SIMS spectrometry by linear Time-of-Flight mass spectrometer and the TimePix detector

  2019cites this paper
• MALDI MS Imaging at Acquisition Rates Exceeding 100 Pixels per Second

  2018cites this paper
• Single‐Cell Analysis

  2017cites this paper
• An accessible, scalable ecosystem for enabling and sharing diverse mass spectrometry imaging analyses.

  2016cites this paper
• Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics

  2016cites this paper
• Imaging mass spectrometry: Instrumentation, applications, and combination with other visualization techniques.

  2016cites this paper
• Mass spectrometry-based characterization of endogenous peptides and metabolites in small volume samples.

  2015cites this paper
• 3D imaging of biological specimen using MS.

  2015cites this paper
• Direct ion imaging approach for investigation of ion dynamics in multipole ion guides.

  2015cites this paper
• Recent methodological advances in MALDI mass spectrometry

  2014cites this paper
• Rapid matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging with scanning desorption laser beam.

  2014cites this paper
• Time-Resolved Imaging of the MALDI Linear-TOF Ion Cloud: Direct Visualization and Exploitation of Ion Optical Phenomena Using a Position- and Time-Sensitive Detector

  2014cites this paper
• Fast sensors for time-of-flight imaging applications.

  2014cites this paper
• MALDI mass spectrometry imaging in microscope mode with infrared lasers: bypassing the diffraction limits.

  2014cites this paper
• Toward high spatial resolution sampling and characterization of biological tissue surfaces using mass spectrometry

  2014cites this paper
• A fast microchannel plate-scintillator detector for velocity map imaging and imaging mass spectrometry.

  2014cites this paper
• Experimental Investigation of the 2D Ion Beam Profile Generated by an ESI Octopole-QMS System

  2014cites this paper
• Velocity corrected ion extraction in microscope mode imaging mass spectrometry

  2013cites this paper
• An in-vacuum, pixelated detection system for mass spectrometric analysis and imaging of macromolecules

  2013cites this paper
• MALDI‐Mass Spectrometry Imaging

  2013cites this paper
• High mass resolution tissue imaging at atmospheric pressure using laserspray ionization mass spectrometry

  2013cites this paper
• Ion mobility & mass spectrometric studies of macromolecules required for organism viability

  2013cites this paper
• Matrix-assisted laser desorption ionization imaging mass spectrometry: in situ molecular mapping.

  2013cites this paper
• New ionization processes and applications for use in mass spectrometry

  2013cites this paper
• Microscope mode secondary ion mass spectrometry imaging with a Timepix detector.

  2013cites this paper
• Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging.

  2013cites this paper