scholarly journals Towards Cellular Ultrastructural Characterization in Organ-on-a-Chip by Transmission Electron Microscopy

Applied Nano ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 289-302
Author(s):  
Adrianna Glinkowska Mares ◽  
Natalia Feiner-Gracia ◽  
Yolanda Muela ◽  
Gema Martínez ◽  
Lidia Delgado ◽  
...  

Organ-on-a-chip technology is a 3D cell culture breakthrough of the last decade. This rapidly developing field of bioengineering intertwined with microfluidics provides new insights into disease development and preclinical drug screening. So far, optical and fluorescence microscopy are the most widely used methods to monitor and extract information from these models. Meanwhile transmission electron microscopy (TEM), despite its wide use for the characterization of nanomaterials and biological samples, remains unexplored in this area. In our work we propose a TEM sample preparation method, that allows to process a microfluidic chip without its prior deconstruction, into TEM-compatible specimens. We demonstrated preparation of tumor blood vessel-on-a-chip model and consecutive steps to preserve the endothelial cells lining microfluidic channel, for the chip’s further transformation into ultrathin sections. This approach allowed us to obtain cross-sections of the microchannel with cells cultured inside, and to observe cell adaptation to the channel geometry, as well as the characteristic for endothelial cells tight junctions. The proposed sample preparation method facilitates the electron microscopy ultrastructural characterization of biological samples cultured in organ-on-a-chip device.

2020 ◽  
Vol 50 (1) ◽  
Author(s):  
Yu-Hao Deng

Abstract Sample preparation is significantly important to the high-resolution transmission electron microscopy (HRTEM) characterization of nanomaterials. However, many general organic solvents can dissolve the necessary organic polymer support layer in TEM grid, which causes it difficult to obtain high-quality samples of oil-soluble nanomaterials. In this study, a new sample preparation method for oil-soluble nanomaterials has been developed by using the sublimable material as a transition layer. Experiments also show that there is no damage to TEM grids and high-quality HRTEM images can be obtained via this method. This approach paves the way to applicable HRTEM sample preparation of oil-soluble nanomaterials.


1990 ◽  
Vol 199 ◽  
Author(s):  
F. Shaapur ◽  
M. Park

ABSTRACTA procedure for batch processing of up to four specimens for cross-sectional transmission electron microscopy (X-TEM) has been developed. The technique is essentially an extension of the standard multi-slice composite full disc sample preparation method. However, disc cutting and dimple grinding steps have been eliminated. The trimming, gluing, stacking, and sectioning of the wafers from the original sample material to produce composite transverse sections are identical to those of the standard scheme. Grinding and polishing of the sections are carried out in a batch mode which, in turn, reduces the overall processing time per specimen. The prepared composite foils are mounted on metallic disc grids which provide structural support during ion thinning and microscopy.


2021 ◽  
Author(s):  
Tony Colpaert ◽  
Stefaan Verleye

Abstract Frontside die inspection by Scanning Electron Microscopy (SEM) is critical to investigate failures that appear dispersed over the GaN die surface and that will be very difficult to localize by the typical Focus Ion Beam (FIB) or Transmission Electron Microscopy (TEM) analysis. Frontside sample preparation is; however, extremely challenging if the device was already subjected to sample preparation for backside Photo Emission Microscopy (PEM). In this paper, a novel sample preparation method is presented where all front side layers are removed and only the 5μm GaN die is left for inspection.


Author(s):  
U. Muehle ◽  
A. Lenk ◽  
M. Lehmann ◽  
H. Lichte

Abstract In accordance with the predictions of the International Semiconductor Association, a further decrease in the structural widths of semiconductor devices is expected. For an in-depth characterization of actual structural details, the transmission electron microscopy (TEM)-technique is becoming more and more significant. An urgent requirement is in the visualization of dimensions of the doped regions and estimation of p-n-junctions profile with a high level spatial resolution. The off-axis electron holography, a special TEM-technique, is able to visualize electrically active areas in semiconductors. This article describes a way to achieve sample preparation for TEM-holography from actual memory products and also provides an idea of the potential of this technique for semiconductor failure analysis. It shows that different types and sizes of FET's and testing structures could be visualized by focusing on the physical basics, technical solutions, and sample preparation.


2014 ◽  
Vol 490-491 ◽  
pp. 198-202
Author(s):  
Yu Chen ◽  
Yang Yu ◽  
Wen Cong Zhan ◽  
Er De Wang

The microscopic analysis of 93W-4.9Ni-2.1Fe (wt. %) tungsten heavy alloy by hot-hydrostatic extrusion with severe plastic deformation strengthening were experimentally investigated mainly by transmission electron microscopy. Due to the profound differences in hardness of the tungsten particles and the NiFeW matrix a special TEM specimen preparation method had to be employed.It was shown that the microstructure of the as-extruded alloy was characterized by elongated tungsten particles with refinement cellular sub-structures consisting of high-density dislocations embedded in a binding Ni-Fe-W matrix phase with fine dynamically re-crystallized grains.


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