Particles, large and small, are widely used in a range of industrial applications, consumer products and healthcare. Recent advances in particle analysis technologies and instrumentation have been crucial in ensuring optimal particle performance, stability, and safety.
Introduction to nanoparticles
Particles – small, discrete portions of matter – surround us. Consumer products that are used on a daily basis such as sun screen, cosmetics, shampoos/conditioners, kids’ toys etc. have nano- and micron-sized particles incorporated into them to improve their performance, strength, and stability. Because such particles are now so commonly used, technologies for assessing their safety, environmental impact, stability etc. are critically important.
Historical techniques for particle analysis
It’s interesting to note that despite their current importance, particles and particle analysis are not a new phenomenon. In fact, particles have been studied, separated, and analyzed for thousands of years. The technologies back then were often limited to separating and sizing visible particles and relied on fundamental physical properties of the particle such as size and weight. One specific technique was sieving, or filtering particles through meshes with different pore sizes to separate out particles based on their size. Another technique was sedimentation, which relies on differences in particle density to cause denser particles to settle out of water more quickly than less dense particles. A common example of sedimentation at work is panning for gold. The heavier gold particles quickly settle to the bottom of the pan and the dirt, sand, and other lighter particles can be skimmed off the top.
A more recent development in particle analysis involves using imaging techniques to measure particle size. Initially, standard photography was used but subsequent improvements in imaging technologies enabled first light microscopy and then electron microscopy to record images of smaller and smaller particles. These images are then used to assess particle size, shape and to compare them to other materials or standards of known size.
Scattering technologies for analyzing particles
Optical, laser-based techniques, such as laser diffraction, Dynamic Light Scattering (DLS), Static Light Scattering (SLS), and Electrophoretic Light Scattering (ELS), were introduced in the 1970s. These techniques have now become standard laboratory technologies for measuring the size, zeta potential, and molecular mass of particles ranging from the sub-nanometer to millimeter size range.
Advances in scattering technologies
More recently, one aspect of improving particle analysis has been to develop combination technologies and instruments that provide multiple parameters or measurements of a simple sample. One example is Dynamic Light Scattering (DLS) combined with Raman spectroscopy to assess the size and chemical make-up of particle suspensions. Another combination is DLS combined with various imaging and microscopy techniques to provide both size and a visual image of the particle. A more recent combination measurement is DLS and ELS combined with a light transmittance measurement. Transmittance, or the amount of light traveling through the sample, enables us to assess certain information about the sample stability as well as to assess whether the sample is appropriate for DLS or ELS measurements. Additionally, the light transmittance can guide the user or instrument as to the optimal angle of analysis.
Advances in electrophoretic light scattering
Additionally, improvements have also been made on the DLS and ELS technologies themselves. Specific to ELS, the Phase Analysis Light Scattering (PALS) technology was developed to improve the sensitivity of zeta potential analysis and to determine the sign of the charge of the particles being analyzed. More recently, an improvement on PALS, called Continuously Monitored Phase Analysis Light Scattering (cmPALS), incorporates an additional monitor on the frequency modulator to ensure that any non-linearities in the modulator or unwanted Doppler effects are eliminated. This thus enables faster and more sensitive zeta potential measurements, as well as measurements at higher conductivities/salt concentrations. This is particularly important when analyzing protein therapeutics, antibodies or other sensitive samples that are prone to degradation during zeta potential analysis.
In addition to the ELS or zeta potential technology, a number of technical advancements have been made to the instrumentation and cuvettes. Lower volume cuvettes, cuvettes for zeta potential analysis in organic solvents etc. have all been developed to improve the flexibility of the technique and expand the types of samples that can be analyzed. Additionally, a new, omega-shaped cuvette has been developed to prevent gradients in the potential from being applied to the sample. This specific shape provides a straight, rather than U-shaped, measuring channel which prevents a higher potential being applied to portions of the sample, again preserving sensitive samples from degradation.
In terms of the DLS technology itself, the optics, detectors, and basic technology have not changed much over the past 10 to15 years. However, new advances have been made in the analysis algorithms, which apply a differential weighting to high vs. low quality data. The end effect of this improvement is improved resolution of mixed particle samples, even resolving complex three-component mixtures into separate peaks.
Particle analysis and separations have been performed for thousands of years. The technologies involved have certainly come a long way since the gold rush days of the late 1800s and new technologies, instruments, and improvements on those technologies have been and continue to be developed. The range of samples that can be analyzed is now wider than ever before and the future of particle analysis is brighter than ever.
Specifically, the Litesizer™ 500 from Anton Paar enables a number of these cutting-edge particle and protein analysis measurements including the cmPALS technology, transmittance analysis, and improved particle size distribution algorithms.