Although particle sizing is a mature technology, methods based on ultrasound and light scattering have been evolving slowly toward the characterization of ever-smaller particles, well into the nanometer size domain. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) remain the gold standards for both sizing and characterization, but these methods are too expensive for most labs and require highly-trained operators.

What’s more important is that SEM and TEM sample preparation is arduous and statistical significance is limited by the number of particles within the field that a user or camera can count. So while these methods are superb for analyzing a single or small number of particles, they don’t cut it in high-throughput industrial settings.

The ability to characterize eversmaller particles is a direct response to discoveries in nanotechnology and nanomaterials, from which numerous products have arisen. The approval of next-generation drugs will depend much on our ability to size and characterize nanoparticles. Standards are beginning to emerge from ASTM and ISO on nanotech metrology as well as related environmental health issues.

Instrument makers are focusing on higher resolution and throughput for particles below 100 nm in diameter. “Traditionally, this has only been possible using dynamic light scattering or electron microscopy,” says Matthew N. Rhyner, Ph.D., technical product manager at Beckman Coulter (Brea, CA). “But DLS is an inherently low-resolution technique because it is an ensemble method—it analyzes a large number of particles at once, rather than individual particles.”

Emerging methods focus on discrete particle analysis, which affords much higher resolution and more detailed information on particle characteristics. These techniques rely on imaging technologies, which have progressed tremendously over the last two decades, thanks to advances in optics and digital photography. Imaging fills the huge gap between knowledge of a simple diameter or cross-section measurement and properties critical to a particle’s behavior.

Take an ensemble of rod-shaped particles, for example. The particles show up as a distribution of “sphere equivalents” when analyzed by light scattering, depending on what part of the rod the laser “sees.” In contrast, a Coulter counter, which detects changes in electrical resistance, reports only volumes particles displace, so the readout will be monodisperse.

The method will not tell you if the particle is a sphere or a cylinder, however. That requires an imaging step.

Irregularly shaped but uniformly manufactured nanoparticles are increasingly important in optics, electronics, and consumer products. Quality control during their manufacture demands knowledge of their size or volume, and shape.

One reason is that nanoscale particles behave differently from macroscale materials. Physical forces or moisture can cause particles to clump. When analyzed by size alone, agglomerates will appear as larger particles. That may cause a batch of mineral or food additives to go back to the mill instead of to process development, where the real cause of the sizing issue needs to be addressed.

Similarly, a batch may appear perfect at the plant, but when it reaches a customer, sizing reveals it to be out of spec. Imaging is the most reliable way to determine if the material was milled incorrectly or if some other factor is at work.

Multisizer™ 4 COULTER COUNTER®

  • Provides size distributions in number, volume and surface area in one measurement, with an overall sizing range of 0.4 μm to 1600 μm, by using the Coulter Principle
  • Response is unaffected by particle color, shape, composition or refractive index
  • A Digital Pulse Processor (DPP) provides ultra-high resolution, multiple channel analysis and accuracy that is unattainable by other technologies

Beckman Coulter


  • Analyzes key particle physical properties including size and zeta potential
  • Capable of performing size measurements at both right angle and backscatter
  • Allows particle size measurements with a variety of cells and sample volumes down to 10 μL
  • Zeta potential cells can typically measure hundreds of samples before replacement

Horiba Scientific

Mastersizer 3000

  • Features an extended dynamic range that spans 0.01 to 3500 microns
  • Provides high performance with a small footprint
  • Boasts well-engineered sample dispersion accessories, including an entirely novel dry powder dispersion unit
  • Driven by friendly and intuitive software

Malvern Instruments

Nanoparticle Characterization System

  • Features optimized locators, enabling the user to easily position the measurement cell
  • An optional blue laser improves imaging capability; fluorescence filters can be added when working with suitably labeled particles
  • Features an EMCCD (electron multiplying CCD) featuring 37 full frames per second