scholarly journals Particles in Biopharmaceutical Formulations, Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins, Viruses, Vaccines and Cells

Author(s):  
Alexandra Roesch ◽  
Sarah Zölls ◽  
Daniela Stadler ◽  
Constanze Helbig ◽  
Klaus Wuchner ◽  
...  
2021 ◽  
Vol 167 ◽  
pp. 309-325
Author(s):  
Arun Butreddy ◽  
Karthik Yadav Janga ◽  
Srinivas Ajjarapu ◽  
Sandeep Sarabu ◽  
Narendar Dudhipala

Author(s):  
R. E. Herfert

Studies of the nature of a surface, either metallic or nonmetallic, in the past, have been limited to the instrumentation available for these measurements. In the past, optical microscopy, replica transmission electron microscopy, electron or X-ray diffraction and optical or X-ray spectroscopy have provided the means of surface characterization. Actually, some of these techniques are not purely surface; the depth of penetration may be a few thousands of an inch. Within the last five years, instrumentation has been made available which now makes it practical for use to study the outer few 100A of layers and characterize it completely from a chemical, physical, and crystallographic standpoint. The scanning electron microscope (SEM) provides a means of viewing the surface of a material in situ to magnifications as high as 250,000X.


Author(s):  
R.W. Horne

The technique of surrounding virus particles with a neutralised electron dense stain was described at the Fourth International Congress on Electron Microscopy, Berlin 1958 (see Home & Brenner, 1960, p. 625). For many years the negative staining technique in one form or another, has been applied to a wide range of biological materials. However, the full potential of the method has only recently been explored following the development and applications of optical diffraction and computer image analytical techniques to electron micrographs (cf. De Hosier & Klug, 1968; Markham 1968; Crowther et al., 1970; Home & Markham, 1973; Klug & Berger, 1974; Crowther & Klug, 1975). These image processing procedures have allowed a more precise and quantitative approach to be made concerning the interpretation, measurement and reconstruction of repeating features in certain biological systems.


Author(s):  
Simon Thomas

Trends in the technology development of very large scale integrated circuits (VLSI) have been in the direction of higher density of components with smaller dimensions. The scaling down of device dimensions has been not only laterally but also in depth. Such efforts in miniaturization bring with them new developments in materials and processing. Successful implementation of these efforts is, to a large extent, dependent on the proper understanding of the material properties, process technologies and reliability issues, through adequate analytical studies. The analytical instrumentation technology has, fortunately, kept pace with the basic requirements of devices with lateral dimensions in the micron/ submicron range and depths of the order of nonometers. Often, newer analytical techniques have emerged or the more conventional techniques have been adapted to meet the more stringent requirements. As such, a variety of analytical techniques are available today to aid an analyst in the efforts of VLSI process evaluation. Generally such analytical efforts are divided into the characterization of materials, evaluation of processing steps and the analysis of failures.


Author(s):  
M.P. Thomas ◽  
A.R. Waugh ◽  
M.J. Southon ◽  
Brian Ralph

It is well known that ion-induced sputtering from numerous multicomponent targets results in marked changes in surface composition (1). Preferential removal of one component results in surface enrichment in the less easily removed species. In this investigation, a time-of-flight atom-probe field-ion microscope A.P. together with X-ray photoelectron spectroscopy XPS have been used to monitor alterations in surface composition of Ni3Al single crystals under argon ion bombardment. The A.P. has been chosen for this investigation because of its ability using field evaporation to depth profile through a sputtered surface without the need for further ion sputtering. Incident ion energy and ion dose have been selected to reflect conditions widely used in surface analytical techniques for cleaning and depth-profiling of samples, typically 3keV and 1018 - 1020 ion m-2.


Author(s):  
J. I. Bennetch

In a recent study of the superplastic forming (SPF) behavior of certain Al-Li-X alloys, the relative misorientation between adjacent (sub)grains proved to be an important parameter. It is well established that the most accurate way to determine misorientation across boundaries is by Kikuchi line analysis. However, the SPF study required the characterization of a large number of (sub)grains in each sample to be statistically meaningful, a very time-consuming task even for comparatively rapid Kikuchi analytical techniques.In order to circumvent this problem, an alternate, even more rapid in-situ Kikuchi technique was devised, eliminating the need for the developing of negatives and any subsequent measurements on photographic plates. All that is required is a double tilt low backlash goniometer capable of tilting ± 45° in one axis and ± 30° in the other axis. The procedure is as follows. While viewing the microscope screen, one merely tilts the specimen until a standard recognizable reference Kikuchi pattern is centered, making sure, at the same time, that the focused electron beam remains on the (sub)grain in question.


Author(s):  
Richard S. Chemock

One of the most common tasks in a typical analysis lab is the recording of images. Many analytical techniques (TEM, SEM, and metallography for example) produce images as their primary output. Until recently, the most common method of recording images was by using film. Current PS/2R systems offer very large capacity data storage devices and high resolution displays, making it practical to work with analytical images on PS/2s, thereby sidestepping the traditional film and darkroom steps. This change in operational mode offers many benefits: cost savings, throughput, archiving and searching capabilities as well as direct incorporation of the image data into reports.The conventional way to record images involves film, either sheet film (with its associated wet chemistry) for TEM or PolaroidR film for SEM and light microscopy. Although film is inconvenient, it does have the highest quality of all available image recording techniques. The fine grained film used for TEM has a resolution that would exceed a 4096x4096x16 bit digital image.


Author(s):  
Julia T. Luck ◽  
C. W. Boggs ◽  
S. J. Pennycook

The use of cross-sectional Transmission Electron Microscopy (TEM) has become invaluable for the characterization of the near-surface regions of semiconductors following ion-implantation and/or transient thermal processing. A fast and reliable technique is required which produces a large thin region while preserving the original sample surface. New analytical techniques, particularly the direct imaging of dopant distributions, also require good thickness uniformity. Two methods of ion milling are commonly used, and are compared below. The older method involves milling with a single gun from each side in turn, whereas a newer method uses two guns to mill from both sides simultaneously.


Author(s):  
G. Remond ◽  
R.H. Packwood ◽  
C. Gilles ◽  
S. Chryssoulis

Merits and limitations of layered and ion implanted specimens as possible reference materials to calibrate spatially resolved analytical techniques are discussed and illustrated for the case of gold analysis in minerals by means of x-ray spectrometry with the EPMA. To overcome the random heterogeneities of minerals, thin film deposition and ion implantation may offer an original approach to the manufacture of controlled concentration/ distribution reference materials for quantification of trace elements with the same matrix as the unknown.In order to evaluate the accuracy of data obtained by EPMA we have compared measured and calculated x-ray intensities for homogeneous and heterogeneous specimens. Au Lα and Au Mα x-ray intensities were recorded at various electron beam energies, and hence at various sampling depths, for gold coated and gold implanted specimens. X-ray intensity calculations are based on the use of analytical expressions for both the depth ionization Φ (ρz) and the depth concentration C (ρz) distributions respectively.


Author(s):  
W. W. Davison ◽  
R. C. Buchanan

Yttria stabilized zirconia (YSZ) has become a significant technological material due to its high ionic conductivity, chemical inertness, and good mechanical properties. Temperatures on the order of 1700°C are required, however, to densify YSZ to the degree necessary for good electrical and mechanical properties. A technique for lowering the densification temperature is the addition of small amounts of material which facilitate the formation of a liquid phase at comparatively low temperatures. In this study, sintered microstructures obtained from the use of Al2O3 as a sintering aid were examined with scanning, transmission, and scanning transmission microscopy (SEM, TEM, and STEM).


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