scholarly journals MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure

2019 ◽  
Vol 5 (10) ◽  
pp. eaax5851 ◽  
Author(s):  
Leeat Keren ◽  
Marc Bosse ◽  
Steve Thompson ◽  
Tyler Risom ◽  
Kausalia Vijayaragavan ◽  
...  
Keyword(s):  
Single Molecule ◽  
Spatial Information ◽  
Dynamic Range ◽  
Ion Beam ◽  
Time Of Flight ◽  
Tissue Structure ◽  
Regional Variability ◽  
Flight Mass Spectrometry ◽  
Cellular Phenotypes ◽  
And Function

Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements. We image fields of view up to 800 μm × 800 μm at resolutions down to 260 nm with sensitivities approaching single-molecule detection. We leverage these properties to interrogate intrapatient heterogeneity in tumor organization in triple-negative breast cancer, revealing regional variability in tumor cell phenotypes in contrast to a structured immune response. Given its versatility and sample back-compatibility, MIBI-TOF is positioned to leverage existing annotated, archival tissue cohorts to explore emerging questions in cancer, immunology, and neurobiology.

Constant-Fraction Discrimination/Boxcar Integrator for Plasma Source Time-of-Flight Mass Spectrometry

1995 ◽  
Vol 49 (5) ◽  
pp. 660-664 ◽  
Author(s):  
Pengyuan Yang ◽  
David P. Myers ◽  
Gangqiang Li ◽  
Gary M. Hieftje
Keyword(s):  
Mass Spectrometry ◽  
Inductively Coupled Plasma ◽  
Dynamic Range ◽  
Detection System ◽  
Signal To Noise Ratio ◽  
Time Of Flight ◽  
Plasma Source ◽  
Flight Mass Spectrometry ◽  
Lower Amplitude ◽  
Boxcar Integrator

A constant-fraction discrimination (CFD) system has been combined with a boxcar integrator for detection in inductively coupled plasma/time-of-flight mass spectrometry. The discriminator provides gating logic for the boxcar integrator when an incoming ion signal occurs, but discriminates against electronic or background noise of lower amplitude. As a result, the combination can effectively reject noise and accumulate analyte signal, rather than relying on an averaging process to reduce noise levels. The signal-to-noise ratio is therefore enhanced in this operation compared with the conventional boxcar method. The dynamic range of the detection system is at least five orders of magnitude.

scholarly journals Characterization of online high dynamic range imaging for laser-driven ion beam diagnostics using visible light

2017 ◽  
Vol 3 (2) ◽  
pp. 343-346
Author(s):  
Franz Englbrecht ◽  
Felix Balling ◽  
Thomas Federico Rösch ◽  
Matthias Würl ◽  
Florian Hans Lindner ◽  
...  
Keyword(s):  
Spatial Information ◽  
Dynamic Range ◽  
Ion Beam ◽  
Complementary Metal Oxide Semiconductor ◽  
Laser Pulses ◽  
High Dynamic Range ◽  
Oxide Semiconductor ◽  
Beam Diagnostics ◽  
Spatially Resolved ◽  
Single Frame

AbstractLaser-driven acceleration of particle beams is an emerging modality under research for biomedical applications. The spatially resolved diagnostics of laser-accelerated proton bunches is crucial for their application. The RadEye detector, featuring up to 10 cm x 5 cm area of online complementary metal-oxide-semiconductor (CMOS) detector made of 48 μm pixels, is established for x-ray, proton and ion beam diagnostics. We exploit the usually undesired ‘Image lag’ phenomenon of incomplete pixel reset to generate 2D-images with a larger dynamic range than the single frame range of 12-bit. Using 532 nm laser pulses and computer simulations for single-slit diffraction, calibration factors to stack multiple readouts were successfully derived to quantitatively reconstruct spatial information about an optical beam and hence extend the dynamic range of the detector compared to a single frame. The final goal is focus quantification for a permanent magnet quadrupole system for protons and terawatt (TW-class) laser focus diagnostics.

scholarly journals Focused Ion Beam Fabrication of Solidified Ferritin into Nanoscale Volumes for Compositional Analysis Using Time-of-Flight Mass Spectrometry Methods

2010 ◽  
Vol 16 (S2) ◽  
pp. 1860-1861 ◽  
Author(s):  
M Greene ◽  
TJ Prosa ◽  
DJ Larson ◽  
TF Kelly
Keyword(s):  
Mass Spectrometry ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Time Of Flight ◽  
Compositional Analysis ◽  
Flight Mass Spectrometry

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.

Time-of-flight mass spectrometry with an electrospray ion beam

1992 ◽  
Vol 64 (18) ◽  
pp. 2084-2089 ◽  
Author(s):  
James G. Boyle ◽  
Craig M. Whitehouse
Keyword(s):  
Mass Spectrometry ◽  
Ion Beam ◽  
Time Of Flight ◽  
Flight Mass Spectrometry

scholarly journals Structural Analysis of Coal Fly Ash Particles by means of Focused-Ion-Beam Time-of-Flight Mass Spectrometry

2004 ◽  
Vol 2 ◽  
pp. 45-51 ◽  
Author(s):  
Tetsuo Sakamoto ◽  
Kazuaki Shibata ◽  
Kazunari Takanashi ◽  
Masanori Owari ◽  
Yoshimasa Nihei
Keyword(s):  
Mass Spectrometry ◽  
Fly Ash ◽  
Structural Analysis ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Coal Fly Ash ◽  
Time Of Flight ◽  
Flight Mass Spectrometry

scholarly journals Complementary Maps for Location and Environmental Structure in CA1 and Subiculum

2021 ◽  
Author(s):  
Jacob M Olson ◽  
Alexander B Johnson ◽  
Lillian Chang ◽  
Emily L Tao ◽  
Xuefei Wang ◽  
...  
Keyword(s):  
Spatial Information ◽  
Dynamic Range ◽  
Spatial Working Memory ◽  
Activity Patterns ◽  
Memory Task ◽  
Structural Features ◽  
Brain Regions ◽  
Unique Role ◽  
Path Structure ◽  
And Function

AbstractThe dorsal subiculum lies among a network of interconnected brain regions that collectively map multiple spatial and orientational relationships between an organism and the boundaries and pathways composing its environment. A unique role of the subiculum in spatial information processing has yet to be defined despite reports of small neuron subpopulations that encode relationships to specific boundaries, axes of travel, or locations. We examined the activity patterns among populations of subiculum neurons during performance of a spatial working memory task performed within a complex network of interconnected pathways. Compared to neurons in hippocampal sub-region CA1, a major source of its afferents, subiculum neurons were far more likely to exhibit multiple firing fields at locations that were analogous with respect to path structure and function. Subiculum neuron populations were also found to exhibit a greater dynamic range in scale of spatial representation and for persistent patterns of spiking activity to be aligned to transitions between maze segments. Together, the findings indicate that the subiculum plays a unique role in spatial mapping, one that complements the location-specific firing of CA1 neurons with the encoding of emergent and recurring structural features of a complex path network.

A NEW GRIDLESS ION OPTICS FOR HIGH RESOLUTION TIME-OF-FLIGHT MASS SPECTROMETER

2005 ◽  
Vol 19 (15n17) ◽  
pp. 2621-2626 ◽  
Author(s):  
A. BHOWMICK ◽  
W. C. J. CARVALHO ◽  
A. V. KORGAONKAR ◽  
J. V. YAKHMI ◽  
V. C. SAHNI
Keyword(s):  
High Resolution ◽  
Mass Spectrometer ◽  
Dynamic Range ◽  
Time Of Flight ◽  
High Time Resolution ◽  
Resolution Time ◽  
Ion Optics ◽  
Flight Mass Spectrometer ◽  
Flight Mass Spectrometry ◽  
Wire Meshes

Wire meshes commonly used as transmission grids in ion optical configurations has certain unavoidable disadvantages. Apart from the loss in transmission, there are small angle deflections while the ions are passing close to the wires. This is important for high resolution time-of-flight mass spectrometry as this effect impairs both the dynamic range and the resolution. The amount of deflection from various commercially available grids are determined from simulation calculations on representative wire grids. Gridless designs of ion optics are becoming more popular in recent times for sophisticated and sensitive measurements. Here we report such a device for time of flight mass spectrometer that also assists in perpendicular ionization. This ion optics together with a gridless ion reflector gives a high time resolution of more than 40000.

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