Since size dictates so many properties of materials, particle size measurement is critical for many industries. Particle size governs dissolution rates of solids, absorption and suspension properties of drugs, the homogeneity of mixtures, color properties of paints, and much more.
One of the emerging applications for particle sizing is nanomaterials, a subset of nanotechnology. Nanomaterials— defined as particles smaller than 100 nm—has been the subject of much research in materials, electronics, chemistry, and biology. In the pharmaceutical industry, developers are investigating nano-sized drug particles as a strategy for making insoluble drugs more accessible to metabolic processes.
Particles larger than about 100 microns in one dimension are often sized by sieving through woven mesh screens. Sieving provides approximate values for particle size distributions between certain values, for example 200 and 300 microns, 300 and 400 microns, etc.
Wire mesh sieves are stacked, with the largest diameter sieve at the top, and placed atop a shaker. At the end of a run, particles are counted or weighed within each size range. Sonic sieving, wet sieving, and air jet sieving are variations of traditional sieving that accommodate powders with particles significantly finer than 100 microns.
Gilbert Vial, product manager at Shimadzu Scientific Instruments (Columbia, MD), notes that sieving is widespread in industrial labs that need answers quickly about product quality. “Sieving is imprecise but can be used as a quick check and followed up with more sophisticated methods if needed.”
Microscopy is another old but reliable sizing technique. Microscope sizing provides a great deal of information about particle size, shape, aggregation, and crystalline or noncrystalline state. But despite advances in automation and digitization, microscopy remains tedious and slow and requires human intervention, and its lower limit of detection of about 200 nm introduces sampling anomalies. “You can’t do a microscope sizing run in two minutes as you can with light scattering systems,” says Mr. Vial.
Let there be light
Modern particle sizing is based on light scattering (LS) techniques, of which there are several variants.
Joe Wolfgang, diffraction product manager for the Americas at Malvern Instruments (Westborough, MA), estimates the sweet spot for light scattering in particle sizing to be from 1 nm to around 2 millimeters.
Malvern specializes in LS measurements for particles ranging in size from about 1 nm to 2,000 microns. Within this category, diffraction or low-angle light scattering is suitable for particles measuring from about 20 nm to several mm and may substitute for sieving (and vice versa, although LS generally provides more information).
Diffraction works with either dry powders or liquid suspensions. Suspension measurements employ ultrasound, surfactants, or other chemical agents to prevent particles from aggregating, and are straightforward provided the particles are completely insoluble. “Wet” measurements take between two and three minutes, dry samples about 30 seconds.
Dynamic light scattering (DLS) measures a larger scattering angle and operates at 1 nm to about 10 microns. DLS is typically used to measure suspensions or solutions of particles or molecules in a liquid—for example, dissolved proteins, polymers, micelles, and carbohydrates in solution or as particles (aggregates), as well as emulsions or dispersions of molecules or nanoparticles.
DLS’s primary measurement is not actually size. As a result of Brownian motion, smaller particles move more rapidly through liquids than do larger particles. DLS measures this motion and translates it to particle size.
Within the size overlap region of the instruments, DLS characterizes more concentrated suspensions or emulsions than does diffraction, but the latter works better for larger particles.
Some interesting properties may be gleaned from light-scattering-based particle sizing:
- Zeta potential—electrical potential of colloids, indicating the likelihood that they will aggregate or remain suspended
- Hydrodynamic radius—the apparent size of the hydrated particle
- Molecular weight, conformation, and state of aggregation
- Second virial coefficient—a measure of weak protein-protein interactions
Overlap in size domains for instrument lines is necessary if suppliers wish to cover the range of particles that their customers are likely to encounter. It is not unusual for vendors to offer systems that measure, for example, from 0.5 nm to 200 nm, 10 nm to 250 microns, and 0.1 micron to 3 mm.
What to look for
Diffraction instruments have been available for more than three decades, and all those currently marketed perform basic measurements fairly well. Mr. Wolfgang therefore recommends that customers pay particular attention to an instrument’s ease of use, and the level of customer support they can expect from their vendor. “These factors are particularly important as companies downsize, and highly skilled workers become scarcer.”
Angelo DePalma holds a Ph.D. in organic chemistry and has worked in the pharmaceutical industry. You can reach him at email@example.com.
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