Emerging technologies in mass spectrometry imaging.

Highly parallel, active pixel detectors enable novel detection capabilities for large biomolecules in time-of-flight (TOF) based mass spectrometry imaging (MSI). In this work, a 512 × 512 pixel, bare Timepix assembly combined with chevron microchannel plates (MCP) captures time-resolved images of several m/z species in a single measurement. Mass-resolved ion images from Timepix measurements of peptide and protein standards demonstrate the capability to return both mass-spectral and localization information of biologically relevant analytes from matrix-assisted laser desorption ionization (MALDI) on a commercial ion microscope. The use of a MCP-Timepix assembly delivers an increased dynamic range of several orders of magnitude. The Timepix returns defined mass spectra already at subsaturation MCP gains, which prolongs the MCP lifetime and allows the gain to be optimized for image quality. The Timepix peak resolution is only limited by the resolution of the in-pixel measurement clock. Oligomers of the prote...

High dynamic range bio-molecular ion microscopy with the Timepix detector.

Instrumental developments for imaging and individual particle detection for biomolecular mass spectrometry (imaging) and fundamental atomic and molecular physics studies are reviewed. Ion-counting detectors, array detection systems and high mass detectors for mass spectrometry (imaging) are treated. State-of-the-art detection systems for multi-dimensional ion, electron and photon detection are highlighted. Their application and performance in three different imaging modes – integrated, selected and spectral image detection – are described. Electro-optical and microchannel-plate-based systems are contrasted. The analytical capabilities of solid-state pixel detectors – both charge coupled device (CCD) and complementary metal oxide semiconductor (CMOS) chips – are introduced. The Medipix/Timepix detector family is described as an example of a CMOS hybrid active pixel sensor. Alternative imaging methods for particle detection and their potential for future applications are investigated. Copyright © 2012 John Wiley & Sons, Ltd.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/rcm.6418

Detection systems for mass spectrometry imaging: A perspective on novel developments with a focus on active pixel detectors

We present the first multimass velocity-map imaging data acquired using a new ultrafast camera designed for time-resolved particle imaging. The PImMS (Pixel Imaging Mass Spectrometry) sensor allows...

Multimass velocity-map imaging with the Pixel Imaging Mass Spectrometry (PImMS) sensor: an ultra-fast event-triggered camera for particle imaging.

Since biology is by and large a 3-dimensional phenomenon, it is hardly surprising that 3D imaging has had a significant impact on many challenges in the life sciences. Imaging mass spectrometry (MS) is a spatially resolved label-free analytical technique that recently maturated into a powerful tool for in situ localization of hundreds of molecular species. Serial 3D imaging MS reconstructs 3D molecular images from serial sections imaged with mass spectrometry. As such, it provides a novel 3D imaging modality inheriting the advantages of imaging MS. Serial 3D imaging MS has been steadily developing over the past decade, and many of the technical challenges have been met. Essential tools and protocols were developed, in particular to improve the reproducibility of sample preparation, speed up data acquisition, and enable computationally intensive analysis of the big data generated. As a result, experimental data is starting to emerge that takes advantage of the extra spatial dimension that 3D imaging MS offers. Most studies still focus on method development rather than on exploring specific biological problems. The future success of 3D imaging MS requires it to find its own niche alongside existing 3D imaging modalities through finding applications that benefit from 3D imaging and at the same time utilize the unique chemical sensitivity of imaging mass spectrometry. This perspective critically reviews the challenges encountered during the development of serial-sectioning 3D imaging MS and discusses the steps needed to tip it from being an academic curiosity into a tool of choice for answering biological and medical questions.

Serial 3D imaging mass spectrometry at its tipping point.

https://link.springer.com/content/pdf/10.1007%2Fs13361-011-0120-1.pdf

Digital imaging mass spectrometry.

Methods to visualize the two-dimensional distribution of molecules by mass spectrometric imaging evolve rapidly and yield novel applications in biology, medicine, and material surface sciences. Most mass spectrometric imagers acquire high mass resolution spectra spot-by-spot and thereby scan the object's surface. Thus, imaging is slow and image reconstruction remains cumbersome. Here we describe an imaging mass spectrometer that exploits the true imaging capabilities by ion optical means for the time of flight mass separation. The mass spectrometer is equipped with the ASIC Timepix chip as an array detector to acquire the position, mass, and intensity of ions that are imaged by MALDI directly from the target sample onto the detector. This imaging mass spectrometer has a spatial resolving power at the specimen of (84\pm35) \mu m with a mass resolution of 45 and locates atoms or organic compounds on a surface area up to ~2 cm2. Extended laser spots of ~5 mm2 on structured specimens allowed parallel imaging of selected masses. The digital imaging mass spectrometer proves high hit-multiplicity, straightforward image reconstruction and its potential for high-speed readout at 4 kHz or more. This device demonstrates a simple way of true image acquisition like a digital photographic camera. The technology may enable a fast analysis of biomolecular samples in near future.

Digital Imaging Mass Spectrometry

This contribution reports on measurements with a GEM based TPC using the TimePix CMOS ASIC as a charge collecting readout anode. Tests on a small prototype with a 6mm drift space were performed in a 5 GeV electron beam at DESY. A Si-strip-telescope serves as spatial reference for the measured tracks. Two GEMs of different hole- and pitch-geometries are tested. The point resolution for short drift distances is better than 20 μm. A time resolution as good as 8 ns at 100MHz clock frequency is achieved. Furthermore, experimental studies with an enlarged pixel size are addressed.

Uwe Renz

Papers

Digital imaging mass spectrometry.

Digital Imaging Mass Spectrometry

TPC prototype readout with GEMs and TimePix