scholarly journals Secretory Vesicles Are the Principal Means of SARS-CoV-2 Egress

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2047
Author(s):  
Sébastien Eymieux ◽  
Rustem Uzbekov ◽  
Yves Rouillé ◽  
Emmanuelle Blanchard ◽  
Christophe Hourioux ◽  
...  
Keyword(s):  
Extracellular Space ◽  
Secretory Pathway ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Vero Cells ◽  
Secretory Vesicles ◽  
Transmission Electron ◽  
Sem Study ◽  
Intracellular Compartments ◽  
Cellular Compartments

The mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) egress, similar to those of other coronaviruses, remain poorly understood. The virus buds in intracellular compartments and is therefore thought to be released by the biosynthetic secretory pathway. However, several studies have recently challenged this hypothesis. It has been suggested that coronaviruses, including SARS-CoV-2, use lysosomes for egress. In addition, a focused ion-beam scanning electron microscope (FIB/SEM) study suggested the existence of exit tunnels linking cellular compartments rich in viral particles to the extracellular space resembling those observed for the human immunodeficiency (HIV) in macrophages. Here, we analysed serial sections of Vero cells infected with SARS-CoV-2 by transmission electron microscopy (TEM). We found that SARS-CoV-2 was more likely to exit the cell in small secretory vesicles. Virus trafficking within the cells involves small vesicles, with each generally containing a single virus particle. These vesicles then fuse with the plasma membrane to release the virus into the extracellular space. This work sheds new light on the late stages of the SARS-CoV-2 infectious cycle of potential value for guiding the development of new antiviral strategies.

Low Energy Ar Ion Milling of FIB TEM Specimens from 14 nm and Future FinFET Technologies

2018 ◽  
Author(s):  
C.S. Bonifacio ◽  
P. Nowakowski ◽  
M.J. Campin ◽  
M.L. Ray ◽  
P.E. Fischione
Keyword(s):  
Field Effect Transistor ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Specimen Preparation ◽  
Ion Milling ◽  
Transmission Electron ◽  
High Resolution Tem ◽  
Effect Transistor ◽  
20 Nm ◽  
Argon Ion

Abstract Transmission electron microscopy (TEM) specimens are typically prepared using the focused ion beam (FIB) due to its site specificity, and fast and accurate thinning capabilities. However, TEM and high-resolution TEM (HRTEM) analysis may be limited due to the resulting FIB-induced artifacts. This work identifies FIB artifacts and presents the use of argon ion milling for the removal of FIB-induced damage for reproducible TEM specimen preparation of current and future fin field effect transistor (FinFET) technologies. Subsequently, high-quality and electron-transparent TEM specimens of less than 20 nm are obtained.

TEM Sample Preparation Tricks for Advanced DRAMs

2015 ◽  
Author(s):  
Ching Shan Sung ◽  
Hsiu Ting Lee ◽  
Jian Shing Luo
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Sample Preparation ◽  
Integrated Circuit ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Tem Analysis ◽  
Cross Sectional ◽  
Transmission Electron ◽  
Characterization Of Materials

Abstract Transmission electron microscopy (TEM) plays an important role in the structural analysis and characterization of materials for process evaluation and failure analysis in the integrated circuit (IC) industry as device shrinkage continues. It is well known that a high quality TEM sample is one of the keys which enables to facilitate successful TEM analysis. This paper demonstrates a few examples to show the tricks on positioning, protection deposition, sample dicing, and focused ion beam milling of the TEM sample preparation for advanced DRAMs. The micro-structures of the devices and samples architectures were observed by using cross sectional transmission electron microscopy, scanning electron microscopy, and optical microscopy. Following these tricks can help readers to prepare TEM samples with higher quality and efficiency.

Focused Ion Beam Analysis of Low-K Dielectrics

2000 ◽  
Author(s):  
H. J. Bender ◽  
R. A. Donaton
Keyword(s):  
Electron Microscope ◽  
Cross Section ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Single Step ◽  
Specimen Preparation ◽  
Transmission Electron ◽  
Beam Analysis ◽  
Low K ◽  
Scanning Electron

Abstract The characteristics of an organic low-k dielectric during investigation by focused ion beam (FIB) are discussed for the different FIB application modes: cross-section imaging, specimen preparation for transmission electron microscopy, and via milling for device modification. It is shown that the material is more stable under the ion beam than under the electron beam in the scanning electron microscope (SEM) or in the transmission electron microscope (TEM). The milling of the material by H2O vapor assistance is strongly enhanced. Also by applying XeF2 etching an enhanced milling rate can be obtained so that both the polymer layer and the intermediate oxides can be etched in a single step.

Fin Level Defect Isolation Inside a FinFET Using Electron Beam Alteration of Current Flow

2017 ◽  
Author(s):  
H.J. Ryu ◽  
A.B. Shah ◽  
Y. Wang ◽  
W.-H. Chuang ◽  
T. Tong
Keyword(s):  
Electron Microscopy ◽  
Electron Beam ◽  
Focused Ion Beam ◽  
Current Flow ◽  
Ion Beam ◽  
The Body ◽  
Complete Understanding ◽  
Root Cause ◽  
Transmission Electron ◽  
Defect Isolation

Abstract When failure analysis is performed on a circuit composed of FinFETs, the degree of defect isolation, in some cases, requires isolation to the fin level inside the problematic FinFET for complete understanding of root cause. This work shows successful application of electron beam alteration of current flow combined with nanoprobing for precise isolation of a defect down to fin level. To understand the mechanism of the leakage, transmission electron microscopy (TEM) slice was made along the leaky drain contact (perpendicular to fin direction) by focused ion beam thinning and lift-out. TEM image shows contact and fin. Stacking fault was found in the body of the silicon fin highlighted by the technique described in this paper.

Transmission Electron Microscopy (TEM) Specimen Preparation Technique using Focused Ion Beam (FIB): Application to Material Characterization of Chemical Vapor Deposition of Tungsten (W) and Tungsten Silicides (WSix)

1997 ◽  
Author(s):  
K. Doong ◽  
J.-M. Fu ◽  
Y.-C. Huang
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Chemical Vapor Deposition ◽  
Vapor Deposition ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Chemical Vapor ◽  
Specimen Preparation ◽  
Preparation Technique ◽  
Transmission Electron

Abstract The specimen preparation technique using focused ion beam (FIB) to generate cross-sectional transmission electron microscopy (XTEM) samples of chemical vapor deposition (CVD) of Tungsten-plug (W-plug) and Tungsten Silicides (WSix) was studied. Using the combination method including two axes tilting[l], gas enhanced focused ion beam milling[2] and sacrificial metal coating on both sides of electron transmission membrane[3], it was possible to prepare a sample with minimal thickness (less than 1000 A) to get high spatial resolution in TEM observation. Based on this novel thinning technique, some applications such as XTEM observation of W-plug with different aspect ratio (I - 6), and the grain structure of CVD W-plug and CVD WSix were done. Also the problems and artifacts of XTEM sample preparation of high Z-factor material such as CVD W-plug and CVD WSix were given and the ways to avoid or minimize them were suggested.

To Eliminate Curtain Effect of FIB TEM Samples by a Combination of Sample Dicing and Backside Milling

2014 ◽  
Author(s):  
Jian-Shing Luo ◽  
Hsiu Ting Lee
Keyword(s):  
Sample Preparation ◽  
Focused Ion Beam ◽  
Preparation Method ◽  
Low Cost ◽  
Ion Beam ◽  
Sample Preparation Method ◽  
Site Specific ◽  
Dual Beam ◽  
Transmission Electron

Abstract Several methods are used to invert samples 180 deg in a dual beam focused ion beam (FIB) system for backside milling by a specific in-situ lift out system or stages. However, most of those methods occupied too much time on FIB systems or requires a specific in-situ lift out system. This paper provides a novel transmission electron microscopy (TEM) sample preparation method to eliminate the curtain effect completely by a combination of backside milling and sample dicing with low cost and less FIB time. The procedures of the TEM pre-thinned sample preparation method using a combination of sample dicing and backside milling are described step by step. From the analysis results, the method has applied successfully to eliminate the curtain effect of dual beam FIB TEM samples for both random and site specific addresses.

A Methodology to Reduce Ion Beam Induced Damage in TEM Specimens Prepared by FIB

2002 ◽  
Author(s):  
Chin Kai Liu ◽  
Chi Jen. Chen ◽  
Jeh Yan.Chiou ◽  
David Su
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Sample Preparation ◽  
Integrated Circuit ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Specimen Preparation ◽  
Tem Analysis ◽  
Sensitive Issue ◽  
Transmission Electron

Abstract Focused ion beam (FIB) has become a useful tool in the Integrated Circuit (IC) industry, It is playing an important role in Failure Analysis (FA), circuit repair and Transmission Electron Microscopy (TEM) specimen preparation. In particular, preparation of TEM samples using FIB has become popular within the last ten years [1]; the progress in this field is well documented. Given the usefulness of FIB, “Artifact” however is a very sensitive issue in TEM inspections. The ability to identify those artifacts in TEM analysis is an important as to understanding the significance of pictures In this paper, we will describe how to measure the damages introduced by FIB sample preparation and introduce a better way to prevent such kind of artifacts.

BiCMOS Die Sort Yield Improvement from Isolation of a Localized Defect Mechanism and Precision TEM Cross Section

1997 ◽  
Author(s):  
J. Douglass ◽  
T. D. Myers ◽  
F. Tsai ◽  
R. Ketcheson ◽  
J. Errett
Keyword(s):  
Electron Microscopy ◽  
Cross Section ◽  
Focused Ion Beam ◽  
Yield Loss ◽  
Process Analysis ◽  
Ion Beam ◽  
Yield Improvement ◽  
Transmission Electron ◽  
Defect Mechanism ◽  
Water Residue

Abstract This paper describes how the authors used a combination of focused ion beam (FIB) microprobing, transmission electron microscopy (TEM), and data and process analysis to determine that localized water residue was causing a 6% yield loss at die sort.

3D Observation of Elemental Distribution of Si-Device using a Dedicated FIB/STEM System

2005 ◽  
Author(s):  
T. Yaguchi ◽  
M. Konno ◽  
T. Kamino ◽  
M. Ogasawara ◽  
K. Kaji ◽  
...  
Keyword(s):  
Focused Ion Beam ◽  
Ion Beam ◽  
Three Dimensional ◽  
Elemental Distribution ◽  
Multivariate Statistical ◽  
X Ray ◽  
Sample Rotation ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
Elemental Maps

Abstract A technique for preparation of a pillar shaped sample and its multi-directional observation of the sample using a focused ion beam (FIB) / scanning transmission electron microscopy (STEM) system has been developed. The system employs an FIB/STEM compatible sample rotation holder with a specially designed rotation mechanism, which allows the sample to be rotated 360 degrees [1-3]. This technique was used for the three dimensional (3D) elemental mapping of a contact plug of a Si device in 90 nm technology. A specimen containing a contact plug was shaped to a pillar sample with a cross section of 200 nm x 200 nm and a 5 um length. Elemental analysis was performed with a 200 kV HD-2300 STEM equipped with the EDAX genesis Energy dispersive X-ray spectroscopy (EDX) system. Spectrum imaging combined with multivariate statistical analysis (MSA) [4, 5] was used to enhance the weak X-ray signals of the doped area, which contain a low concentration of As-K. The distributions of elements, especially the dopant As, were successfully enhanced by MSA. The elemental maps were .. reconstructed from the maps.

Physical Failure Analysis Techniques for Front-End-of-Line Defect Analysis

2016 ◽  
Author(s):  
Dirk Doyle ◽  
Lawrence Benedict ◽  
Fritz Christian Awitan
Keyword(s):  
Cross Section ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Gate Oxide ◽  
Top Down ◽  
New Techniques ◽  
First Case ◽  
Transmission Electron ◽  
Scanning Transmission

Abstract Novel techniques to expose substrate-level defects are presented in this paper. New techniques such as inter-layer dielectric (ILD) thinning, high keV imaging, and XeF2 poly etch overflow are introduced. We describe these techniques as applied to two different defects types at FEOL. In the first case, by using ILD thinning and high keV imaging, coupled with focused ion beam (FIB) cross section and scanning transmission electron microscopy (STEM,) we were able to judge where to sample for TEM from a top down perspective while simultaneously providing the top down images giving both perspectives on the same sample. In the second case we show retention of the poly Si short after removal of CoSi2 formation on poly. Removal of the CoSi2 exposes the poly Si such that we can utilize XeF2 to remove poly without damaging gate oxide to reveal pinhole defects in the gate oxide. Overall, using these techniques have led to 1) increased chances of successfully finding the defects, 2) better characterization of the defects by having a planar view perspective and 3) reduced time in localizing defects compared to performing cross section alone.

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