scholarly journals Revealing the cell-material interface with nanometer resolution by FIB-SEM

2017 ◽  
Author(s):  
Francesca Santoro ◽  
Wenting Zhao ◽  
Lydia-Marie Joubert ◽  
Liting Duan ◽  
Jan Schnitker ◽  
...  

The interface between biological cells and non-biological surfaces profoundly influences cellular activities, chronic tissue responses, and ultimately the success of medical implants. Materials in contact with cells can be plastics, metal, ceramics or other synthetic materials, and their surfaces vary widely in chemical compositions, stiffness, topography and levels of roughness. To understand the molecular mechanism of how cells and tissues respond to different materials, it is of critical importance to directly visualize the cell-material interface at the relevant length scale of nanometers. Conventional ultrastructural analysis by transmission electron microscopy (TEM) often requires substrate removal before microtome sectioning, which is not only challenging for most substrates but also can cause structural distortions of the interface. Here, we present a new method for in situ examination of the cell-to-material interface at any desired cellular location, based on focused-ion beam milling and scanning electron microscopy imaging (FIB-SEM). This method involves a thin-layer plastification procedure that preserves adherent cells as well as enhances the contrast of biological specimen. We demonstrate that this unique procedure allows the visualization of cell-to-material interface and intracellular structures with 10nm resolution, compatible with a variety of materials and surface topographies, and capable of volume and multi-directional imaging. We expect that this method will be very useful for studies of cell-to-material interactions and also suitable for in vivo studies such as examining osteoblast adhesion and new bone formation in response to titanium implants.

ACS Nano ◽  
2017 ◽  
Vol 11 (8) ◽  
pp. 8320-8328 ◽  
Author(s):  
Francesca Santoro ◽  
Wenting Zhao ◽  
Lydia-Marie Joubert ◽  
Liting Duan ◽  
Jan Schnitker ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e57405 ◽  
Author(s):  
Bohumil Maco ◽  
Anthony Holtmaat ◽  
Marco Cantoni ◽  
Anna Kreshuk ◽  
Christoph N. Straehle ◽  
...  

Nanoscale ◽  
2017 ◽  
Vol 9 (13) ◽  
pp. 4383-4387 ◽  
Author(s):  
K. Keevend ◽  
M. Stiefel ◽  
A. L. Neuer ◽  
M. T. Matter ◽  
A. Neels ◽  
...  

1998 ◽  
Vol 4 (3) ◽  
pp. 308-316 ◽  
Author(s):  
R. Hull ◽  
J. Demarest ◽  
D. Dunn ◽  
E.A. Stach ◽  
Q. Yuan

We discuss the application of ion microscopy and in situ electron microscopy to the study of electronic and optical materials and devices. We demonstrate how the combination of in situ transmission electron microscopy and focused ion beam microscopy provides new avenues for the study for such structures, enabling extension of these techniques to the study of dopant distributions, nanoscale stresses, three-dimensional structural and chemical reconstruction, and real-time evolution of defect microstructure. We also discuss in situ applications of thermal, mechanical, electrical, and optical stresses during transmission electron microscopy imaging.


2013 ◽  
Vol 19 (1) ◽  
pp. 85-92 ◽  
Author(s):  
K. Lepinay ◽  
F. Lorut

AbstractThree-dimensional focused ion beam/scanning electron microscopy (FIB/SEM tomography) is currently an important technique to characterize in 3D a complex semiconductor device or a specific failure. However, the industrial context demands low turnaround time making the technique less useful. To make it more attractive, the following study focuses on a specific methodology going from sample preparation to the final volume reconstruction to reduce the global time analysis while keeping reliable results. The FIB/SEM parameters available will be first analyzed to acquire a relevant dataset in a reasonable time (few hours). Then, a new alignment strategy based on specific alignment marks [using tetraethoxylisane (TEOS) and Pt deposition] is proposed to improve the volume reconstruction speed. These points combined represent a considerable improvement regarding the reliability of the results and the time consumption (gain of factor 3). This method is then applied to various case studies illustrating the benefits of the FIB/SEM tomography technique such as the precise identification of the origin of 3D defects, or the capability to perform a virtual top-down deprocessing on soft material not possible by any mechanical solution.


Author(s):  
Ching Shan Sung ◽  
Hsiu Ting Lee ◽  
Jian Shing Luo

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.


Author(s):  
H.J. Ryu ◽  
A.B. Shah ◽  
Y. Wang ◽  
W.-H. Chuang ◽  
T. Tong

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.


Sign in / Sign up

Export Citation Format

Share Document