Particle Characterization: Tools & Methods
by Michael Levin, Ph. D., Metropolitan Computing Corp.
Particle size analysis has been recognized as an indispensable tool in research and QC laboratories throughout the world. In recent years, scientists and engineers began using computerized Dynamic Image Analysis (DIA) for particle size verification (to support or substitute estimates obtained by other methods) and for shape characterization. Using DIA, important information on particle morphology, optical density, agglomeration and sample contamination can be obtained. Particle shape characterization is indispensable for controlling polymorph contamination, flowability of powders, milling efficiency, circularity of particles comprising a printer toner, dissolution of active drug Asubstances, and so on.
To quantify the size of non-spherical particles, a notion of equivalent diameter (e.g., diameter of a sphere with the volume equal to that of a measured particle) is employed. And yet, it is easy to imagine some odd-shaped objects, needles, and rods having the same calculated equivalent diameter. Some additional shape parameters that can be derived from DIA are listed below.
Ferret Diameter
The longest chord of the projection of the object at a specific angle. Minimum, maximum and average Ferret diameter can be determined from a set of ferrets measured once every five degrees. Area
The area of a particle (pixel-wise precision).
Perimeter
The outer contour of a particle, including the internal perimeter if the object has holes.
Shape Factor
Shape factor reflects the smoothness of an object. A value close to 1 indicates that the object is smooth and round. A value close to 0 means that it is elongated and/or rough. Aspect Ratio
The ratio of the width to the height of an image. More formally, it is the ratio of the minimum ferret diameter to a maximum ferret diameter. This parameter quantifies the “squareness” or “roundness” of an object. The aspect ratio of 1 represents a circle or a square, while a line has aspect ratio close to 0.
Many major particle sizing techniques assume sphericity and generate shape-biased results.
SievingSieves (or "screens") are used to separate particles by means of standardized rectangular or round openings of uniform size. Simple and inexpensive, sieving inspires great confidence in the results. However, it is usually labor intensive and limited to relatively coarse particles. Long thin particles will give very different results when compared to spherical particles of the same weight. The longer the measurement, the smaller the answer, as particles orientate themselves to fall through the sieve.
Sedimentation
This technique is using light or X-ray beams to determine the speed of particles falling in a suspension liquid. The particle size is then expressed in terms of the equivalent spheres which have the same settling speed in laminar flow conditions. The technique has had excellent reproducibility but it is very slow compared to other methods. It is obvious that objects of different shape will have different settling speeds, and therefore sedimentation generates distributions that are accurate only for spherical particles.
Laser Diffraction
Figure 1. Ankersmid CIS-100S particle size and shape analysis system. |
In this method, a laser beam passes through a sample of particles, and light intensity data is collected at different scattering angles away from the axis of the laser beam. The method gained immense popularity in recent years because it is versatile, fast, highly reproducible and relatively simple to use. Both the Fraunhofer approximation and Mie theory used by laser diffraction methods for calculations of light scattering patterns are based on the assumption of sphericity of the measured particles. Non-spherical particles have diffraction patterns which differ considerably from the spheres of equivalent diameter. The laser diffraction method is precise but patently inaccurate for particles with low aspect ratio. Someone said: "Precision is telling the same story over and over again. Accuracy is telling the truth…"
Laser Obscuration
The laser obscuration method as implemented by Ankersmid, a Dutch company, involves a focused He-Ne laser beam rotating with a constant frequency by a wedge prism. Since the angular velocity is known, the size of each individual particle can be calculated from the duration and form of the signal. As flexible, fast and precise as the laser diffraction, laser obscuration technique does not rely on the assumption of particle sphericity.
The laser system is supplemented by a high-speed camera for a sophisticated DIA. The ability to visualize moving particles in conjunction with laser measurements provides important information on aggregation and shape.
Figure 2. Aspect ratio distribution for a mixture of spheres and rods.
Click to enlarge. |
Powerful pre-processing tools, such as threshold selection of object brightness, shape filters, and morphological operations allow streamlined statistical assessment of dozens of parameters, including equivalent diameter, aspect ratio, shape factor, ferret diameters, curling index, fibre length, fibre width, etcMichael Levin is the President and CEO of Metropolitan Computing Corporation(MCC). Prior to forming MCC in 1985, Dr. Levin was a consultant to such pharmaceutical companies as Merck, Sandoz, and Warner-Lambert. He received his Ph.D. in BioMathematics (1980) from University of Washington in Seattle. He is a member of the American Association of Pharmaceutical Scientists (AAPS), International Society for Pharmaceutical Engineering (ISPE), and Biomedical Engineering Society (BMES).
For additional information on the technologies discussed in this article, see www.ParticleSize.com.