Multiplexed Ion Beam Imaging: Insights into Pathobiology

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Candace C. Liu ◽  
Erin F. McCaffrey ◽  
Noah F. Greenwald ◽  
Erin Soon ◽  
Tyler Risom ◽  
...  
Keyword(s):  
Cell Function ◽  
Secondary Ion Mass Spectrometry ◽  
Ductal Carcinoma ◽  
Ion Beam ◽  
Automated Image Analysis ◽  
Annual Review ◽  
Publication Date ◽  
Imaging Data ◽  
New Era ◽  
Multiplexed Imaging

Next-generation tools for multiplexed imaging have driven a new wave of innovation in understanding how single-cell function and tissue structure are interrelated. In previous work, we developed multiplexed ion beam imaging by time of flight, a highly multiplexed platform that uses secondary ion mass spectrometry to image dozens of antibodies tagged with metal reporters. As instrument throughput has increased, the breadth and depth of imaging data have increased as well. To extract meaningful information from these data, we have developed tools for cell identification, cell classification, and spatial analysis. In this review, we discuss these tools and provide examples of their application in various contexts, including ductal carcinoma in situ, tuberculosis, and Alzheimer's disease. We hope the synergy between multiplexed imaging and automated image analysis will drive a new era in anatomic pathology and personalized medicine wherein quantitative spatial signatures are used routinely for more accurate diagnosis, prognosis, and therapeutic selection. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Developments and Ongoing Challenges for Analysis of Surface-Bound Proteins

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tobias Weidner ◽  
David G. Castner
Keyword(s):  
Molecular Structure ◽  
Photoelectron Spectroscopy ◽  
Secondary Ion Mass Spectrometry ◽  
Structural Information ◽  
Computational Techniques ◽  
Annual Review ◽  
Publication Date ◽  
Sum Frequency ◽  
Small Proteins ◽  
Sum Frequency Generation Spectroscopy

Proteins at surfaces and interfaces play important roles in the function and performance of materials in applications ranging from diagnostic assays to biomedical devices. To improve the performance of these materials, detailed molecular structure (conformation and orientation) along with the identity and concentrations of the surface-bound proteins on those materials must be determined. This article describes radiolabeling, surface plasmon resonance, quartz crystal microbalance with dissipation, X-ray photoelectron spectroscopy, secondary ion mass spectrometry, sum frequency generation spectroscopy, and computational techniques along with the information each technique provides for characterizing protein films. A multitechnique approach using both experimental and computation methods is required for these investigations. Although it is now possible to gain much insight into the structure of surface-bound proteins, it is still not possible to obtain the same level of structural detail about proteins on surfaces as can be obtained about proteins in crystals and solutions, especially for large, complex proteins. However, recent results have shown it is possible to obtain detailed structural information (e.g., backbone and side chain orientation) about small peptides (5–20 amino sequences) on surfaces. Current studies are extending these investigations to small proteins such as protein G B1 (∼6 kDa). Approaches for furthering the capabilities for characterizing the molecular structure of surface-bound proteins are proposed. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 14 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Polyphenol Exposure, Metabolism, and Analysis: A Global Exposomics Perspective

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Ian Oesterle ◽  
Dominik Braun ◽  
David Berry ◽  
Lukas Wisgrill ◽  
Annette Rompel ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Biological Fluids ◽  
Human Biomonitoring ◽  
Research Direction ◽  
Annual Review ◽  
Publication Date ◽  
New Era ◽  
Health Related ◽  
Biotransformation Products ◽  
Exposure Levels

Polyphenols are generally known for their health benefits and estimating actual exposure levels in health-related studies can be improved by human biomonitoring. Here, the application of newly available exposomic and metabolomic technology, notably high-resolution mass spectrometry, in the context of polyphenols and their biotransformation products, is reviewed. Comprehensive workflows for investigating these important bioactives in biological fluids or microbiome-related experiments are scarce. Consequently, this new era of nontargeted analysis and omic-scale exposure assessment offers a unique chance for better assessing exposure to, as well as metabolism of, polyphenols. In clinical and nutritional trials, polyphenols can be investigated simultaneously with the plethora of other chemicals to which we are exposed, i.e., the exposome, which may interact abundantly and modulate bioactivity. This research direction aims at ultimately eluting into a true systems biology/toxicology evaluation of health effects associated with polyphenol exposure, especially during early life, to unravel their potential for preventing chronic diseases. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Cell Tracking Profiler – a user-driven analysis framework for evaluating 4D live-cell imaging data

2020 ◽  
Vol 133 (22) ◽  
pp. jcs241422
Author(s):  
Claire Mitchell ◽  
Lauryanne Caroff ◽  
Jose Alonso Solis-Lemus ◽  
Constantino Carlos Reyes-Aldasoro ◽  
Alessandra Vigilante ◽  
...  
Keyword(s):  
Image Analysis ◽  
Cell Tracking ◽  
Cell Function ◽  
Ground Truth ◽  
Time Lapse ◽  
Automated Image Analysis ◽  
Imaging Data ◽  
Cell Behaviour ◽  
Muscle Stem Cell

ABSTRACTAccurate measurements of cell morphology and behaviour are fundamentally important for understanding how disease, molecules and drugs affect cell function in vivo. Here, by using muscle stem cell (muSC) responses to injury in zebrafish as our biological paradigm, we established a ‘ground truth’ for muSC behaviour. This revealed that segmentation and tracking algorithms from commonly used programs are error-prone, leading us to develop a fast semi-automated image analysis pipeline that allows user-defined parameters for segmentation and correction of cell tracking. Cell Tracking Profiler (CTP) is a package that runs two existing programs, HK Means and Phagosight within the Icy image analysis suite, to enable user-managed cell tracking from 3D time-lapse datasets to provide measures of cell shape and movement. We demonstrate how CTP can be used to reveal changes to cell behaviour of muSCs in response to manipulation of the cell cytoskeleton by small-molecule inhibitors. CTP and the associated tools we have developed for analysis of outputs thus provide a powerful framework for analysing complex cell behaviour in vivo from 4D datasets that are not amenable to straightforward analysis.

How Many Cell Types Are in the Kidney and What Do They Do?

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Michael S. Balzer ◽  
Tibor Rohacs ◽  
Katalin Susztak
Keyword(s):  
Interstitial Cell ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Cell Type ◽  
Acid Base Balance ◽  
New Era ◽  
Type Definition ◽  
Base Balance ◽  
Different Cell Types

The kidney maintains electrolyte, water, and acid-base balance, eliminates foreign and waste compounds, regulates blood pressure, and secretes hormones. There are at least 16 different highly specialized epithelial cell types in the mammalian kidney. The number of specialized endothelial cells, immune cells, and interstitial cell types might even be larger. The concerted interplay between different cell types is critical for kidney function. Traditionally, cells were defined by their function or microscopical morphological appearance. With the advent of new single-cell modalities such as transcriptomics, epigenetics, metabolomics, and proteomics we are entering into a new era of cell type definition. This new technological revolution provides new opportunities to classify cells in the kidney and understand their functions. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Cell Tracking Profiler: a user-driven analysis framework for evaluating 4D live cell imaging data

2019 ◽  
Author(s):  
Claire Mitchell ◽  
Lauryanne Caroff ◽  
Alessandra Vigilante ◽  
Jose Alonso Solis-Lemus ◽  
Constantino Carlos Reyes-Aldasoro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Shape ◽  
Cell Tracking ◽  
Cell Function ◽  
Ground Truth ◽  
Automated Image Analysis ◽  
Imaging Data ◽  
Cell Behaviour ◽  
Reduction Methods

AbstractAccurate measurements of cell morphology and behaviour are fundamentally important for understanding how disease, molecules and drugs affect cell function in vivo. Using muscle stem cell (muSC) responses to injury in zebrafish as our biological paradigm we have established a ground truth for muSC cell behaviour. This revealed that variability in segmentation and tracking algorithms from commonly used programs are error-prone, leading us to develop a fast semi-automated image analysis pipeline that allows user defined parameters for segmentation and correction of cell tracking. Cell Tracking Profiler (CTP) operates through the freely available Icy platform, and allows user-managed cell tracking from 3D time-lapsed datasets to provide measures of cell shape and movement. Using dimensionality reduction methods, multiple correlation and regression analyses we identify myosin II-dependent parameters of muSC behaviour during regeneration. CTP and the associated statistical tools we have developed thus provide a powerful framework for analysing complex cell behaviour in vivo from 4D datasets.SummaryAnalysis of cell shape and movement from 3D time-lapsed datasets is currently very challenging. We therefore designed Cell Tracking Profiler for analysing cell behaviour from complex datasets and demonstrate its effectiveness by analysing stem cell behaviour during muscle regeneration in zebrafish.

scholarly journals Vascularized Microfluidics and Their Untapped Potential for Discovery in Diseases of the Microvasculature

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
David R. Myers ◽  
Wilbur A. Lam
Keyword(s):  
Biomedical Engineering ◽  
Blood Cells ◽  
Online Publication ◽  
State Of The Art ◽  
Annual Review ◽  
Publication Date ◽  
New Era ◽  
Complex Interactions ◽  
Microvascular Diseases

Microengineering advances have enabled the development of perfusable, endothelialized models of the microvasculature that recapitulate the unique biological and biophysical conditions of the microcirculation in vivo. Indeed, at that size scale (<100 μm)—where blood no longer behaves as a simple continuum fluid; blood cells approximate the size of the vessels themselves; and complex interactions among blood cells, plasma molecules, and the endothelium constantly ensue—vascularized microfluidics are ideal tools to investigate these microvascular phenomena. Moreover, perfusable, endothelialized microfluidics offer unique opportunities for investigating microvascular diseases by enabling systematic dissection of both the blood and vascular components of the pathophysiology at hand. We review ( a) the state of the art in microvascular devices and ( b) the myriad of microvascular diseases and pressing challenges. The engineering community has unique opportunities to innovate with new microvascular devices and to partner with biomedical researchers to usher in a new era of understanding and discovery of microvascular diseases. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Atomic force microscopy (AFM) of the topography of silicon surfaces exposed to ion beams

1992 ◽  
Vol 50 (2) ◽  
pp. 1132-1133
Author(s):  
Mark Denker ◽  
Jennifer Wall ◽  
Mark Ray ◽  
Richard Linton
Keyword(s):  
Secondary Ion Mass Spectrometry ◽  
Incidence Angle ◽  
Ion Beam ◽  
Depth Profiling ◽  
Depth Resolution ◽  
Ion Beams ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Trace Impurities ◽  
Energy Dose

Reactive ion beams such as O2+ and Cs+ are used in Secondary Ion Mass Spectrometry (SIMS) to analyze solids for trace impurities. Primary beam properties such as energy, dose, and incidence angle can be systematically varied to optimize depth resolution versus sensitivity tradeoffs for a given SIMS depth profiling application. However, it is generally observed that the sputtering process causes surface roughening, typically represented by nanometer-sized features such as cones, pits, pyramids, and ripples. A roughened surface will degrade the depth resolution of the SIMS data. The purpose of this study is to examine the relationship of the roughness of the surface to the primary ion beam energy, dose, and incidence angle. AFM offers the ability to quantitatively probe this surface roughness. For the initial investigations, the sample chosen was <100> silicon, and the ion beam was O2+.Work to date by other researchers typically employed Scanning Tunneling Microscopy (STM) to probe the surface topography.

Investigations of Leakage Paths in Sub-0.35μm DRAM Products Using Advanced Focused Ion Beam Techniques

1998 ◽  
Author(s):  
H. Lorenz ◽  
C. Engel
Keyword(s):  
Focused Ion Beam ◽  
Cell Function ◽  
Dielectric Breakdown ◽  
Ion Beam ◽  
Electrical Characterization ◽  
Floating Gate ◽  
Leakage Path ◽  
Contrast Technique ◽  
Voltage Contrast

Abstract Due to the continuously decreasing cell size of DRAMs and concomitantly diminishing thickness of some insulating layers new failure mechanisms appear which until now had no significance for the cell function. For example high resistance leakage paths between closely spaced conductors can lead to retention problems. These are hard to detect by electrical characterization in a memory tester because the involved currents are in the range of pA. To analyze these failures we exploit the very sensitive passive voltage contrast of the Focused Ion Beam Microscope (FIB). The voltage contrast can further be enhanced by in-situ FIB preparations to obtain detailed information about the failure mechanism. The first part of this paper describes a method to detect a leakage path between a borderless contact on n-diffusion and an adjacent floating gate by passive voltage contrast achieved after FIB circuit modification. In the second part we will demonstrate the localization of a DRAM trench dielectric breakdown. In this case the FIB passive voltage contrast technique is not limited to the localization of the failing trench. We can also obtain the depth of the leakage path by selective insitu etching with XeF2 stopped immediately after a voltage contrast change.

Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Elliott S. Chiu ◽  
Sue VandeWoude
Keyword(s):  
Immune Modulation ◽  
Viral Infections ◽  
Viral Evolution ◽  
Endogenous Retroviruses ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Self Tolerance ◽  
Vertebrate Hosts ◽  
Insight Into

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Advancing Socioeconomic Rights Through Interdisciplinary Factfinding: Opportunities and Challenges

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sarah Knuckey ◽  
Joshua D. Fisher ◽  
Amanda M. Klasing ◽  
Tess Russo ◽  
Margaret L. Satterthwaite
Keyword(s):  
Human Rights ◽  
Mixed Methods ◽  
Social Science ◽  
Science Volume ◽  
Lessons Learned ◽  
Limited Resources ◽  
Annual Review ◽  
Publication Date ◽  
Socioeconomic Rights ◽  
Human Rights Movement

The human rights movement is increasingly using interdisciplinary, multidisciplinary, mixed-methods, and quantitative factfinding. There has been too little analysis of these shifts. This article examines some of the opportunities and challenges of these methods, focusing on the investigation of socioeconomic human rights. By potentially expanding the amount and types of evidence available, factfinding's accuracy and persuasiveness can be strengthened, bolstering rights claims. However, such methods can also present significant challenges and may pose risks in individual cases and to the human rights movement generally. Interdisciplinary methods can be costly in human, financial, and technical resources; are sometimes challenging to implement; may divert limited resources from other work; can reify inequalities; may produce “expertise” that disempowers rightsholders; and could raise investigation standards to an infeasible or counterproductive level. This article includes lessons learned and questions to guide researchers and human rights advocates considering mixed-methods human rights factfinding. Expected final online publication date for the Annual Review of Law and Social Science, Volume 17 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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