Figure 15 (A) Scanning and (B) transmission electron micrographs of particles from the same population, indicating the smoothing effect of gold coating in the scanning electron micrograph.

Image Analysis

One of the earliest imaging systems to be used in conjunction with microscopy was the Quantimet Model 720 system, an automated image analyzer [102,103]. The pattern recognition modules of the image-analyzing computer allowed features to be classified by orientation-independent size criteria, such as area and perimeter. By application of a wide range of complex shape, size, and density criteria, it was also possible to separate features by shape.

More recently, the Brinkmann Model 2010, shown schematically in Fig. 16, has been used for "on-line" determinations of particle size. It combines a scanning laser and particle size analyzer, based on time of transition, with a shape analyzer. A video camera takes still images every 3 sec. Samples in any state can be measured by interchanging sample modules. The He-Ne laser beam passes through a rotating wedge prism that rotates the beam. The rotating beam goes through the sample and falls on a photodiode that measures beam intensity. When a particle interrupts the beam, the time of interaction, along with the rotational speed of the beam, can be translated into the particle diameter.

Shape Factors and Particle Morphology

Image analysis techniques have also been used to derive information concerning particle shape. The topic of shape factors and particle morphology has been of considerable interest to aerosol scientists. Some particle measurement techniques require a correction factor that accounts for the particle shape, to allow interpretation of the data. A range of approaches have resulted in a number of shape-factor definitions, many of which have been named after their proponents. The most recent approaches to assessing shape factors appear to derive from Fourier or fractal analysis of particle boundaries. It is impossible to do justice to the wealth of literature on this subject in this brief discussion. However, some references are given that may be reviewed at leisure [104-119]. Many physicochemical factors, such as surface area, density, charge, and wettability, are related to the particle surface, and these have implications for particle flow, aggregation, aerodynamic, and dissolution behavior. The shape of particles is known to play an important role in the generation, deposition, and therapeutic activity of aerosol particles [118-121]. The impact of shape on the investigation of materials that pose a respirable hazard suggests that this may be a useful approach pharmaceutically [112]. It is, therefore, worth considering the information on particle shape that is available from image analysis [122].

Other instruments using principles similar to those described previously are the Optomax V image analysis system (Optomax, Burlington, MA) and Imageplus (Dapple Systems, Sunnyvale, CA). This is by no means a comprehensive list of companies supplying equipment of this nature.

Figure 16 Schematic of the laser optic measuring system used in an imaging analyzer. (With permission of Brinkmann Instruments.)
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