Insights from industry

Introducing MADLS as a New Approach to Light Scattering Particle Size Analysis

An interview with Darrell Bancarz, highlighting Multi-Angle Dynamic Light Scattering as a new approach to overcome challenges in particle sizing.

How are DLS and ELS used to measure particle size and zeta potential?

Dynamic Light Scattering (DLS) measures the diffusion rate of suspended particles or molecules in solution and if we know the dispersant or solvent viscosity, we can calculate the mean particle size, polydispersity and, with enhanced algorithms, produce a particle size distribution.DLS has become a very useful tool in nanoparticle research and production as well as in the life sciences.DLS is quick, non-destructive and is sensitive to the presence of such things as agglomerates – it’s therefore a great tool for checking, is my sample in the form I want it to be in?

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Electrophoretic light scattering (ELS) measures the mobility of a particulate suspension in the presence of an applied electrical field.The mobility rate and the strength of the electrical field are used to determine the charge or zeta potential of the particles – this is useful in predicting their behaviour or the likely stability of a formulation – are my particles likely to aggregate or behave as a stable suspension? Are my particles likely to interact with their target or environment, for instance?

What challenges do researchers face when analyzing particle concentration?

Measuring particle concentration to any degree of accuracy can be very challenging and the challenge increases with decreasing particle size and the type of particle can further complicate matters.For instance, metallic nanoparticles might well be suitable for concentration measurement by sp-ICPMS; but that technique, like many counting techniques, needs to avoid convergent particles in the plasma and dilution may well be necessary. Also, it’s not going to be very effective if your particles are liposomes or viruses or are much below 10-20nm in diameter.

The type of particle often prescribes the technique(s) the researcher can use, for instance UV-Vis for polystyrene perhaps or SAXS for silicas.For particles that are not pure materials the problems become even greater.

How can introducing Multi-Angle Dynamic Light Scattering to a particle measuring system help to overcome these challenges?

MADLS is a new approach to DLS particle sizing that Malvern Panalytical introduced with the new Zetasizer Ultra system. Typically, DLS systems have measured at a single fixed detection angle, say 90 degrees or 173 degrees.MADLS measures the sample at three angles, combines the correlation data and performs a multi-variate analysis of the combined data to produce a single particle size distribution. The benefits are less noise, improved resolution and improved size accuracy, as well as showing less angular dependence.

We had to take this approach in order to provide the resolution and accuracy required to start extracting particle concentration data from a DLS analysis.MADLS-Particle Concentration, as we call it, allows a calibration free measurement of particle concentration of systems with particle sizes up to 500nm.It benefits from a wide concentration range, dilution is often not required, and if ,the sample is not a mixture, it is material independent.

A MADLS Particle Concentration is quick to perform, and if separate size modes are present, provides concentration per size mode.It therefore is an excellent screening tool to gauge particle concentration and then decide if samples are worthwhile taking onto more complex or work intensive techniques. MADLS – Particle Concentration has been particularly of interest with the life science community in measuring the concentration such things as virus vectors but is equally applicable to a wide range of material types.

Please give an introduction to the Zetasizer Ultra and the technology incorporated in it.

The Zetasizer Ultra is Malvern Panalytical’s flagship DLS/ELS system and combines much of our learning over nearly 50 years of building DLS instrumentation.

The ZS Xplorer software that drives our new Zetasizer systems is designed to be easy to use, with sensible defaults based on measurement type, cell type and sample type automatically chosen for the user.The software also offers great flexibility in how a method is set-up and does not confine the user to simple size or zeta only methods.

Both the Zetasizer Pro and Ultra incorporate Adaptive Correlation and an AI driven data quality system. Adaptive correlation benefits the user in being faster to result (we typically see at least a 50% improvement in sample throughput) and provides improvements in data quality by classifying data that is not representative of the sample’s normal state out as transient events.The user needs to make no assumptions about their sample – its all done using statistical analysis techniques and all data is retained so the user has full insight into the process.The transient events and frequency of the same we believe offers greater insight into presence of larger particles that might be of interest – such as protein aggregates – as they are no longer averaged out by all the “normal” data.

The Zetasizer Ultra also has the capability of using ultra low volume capillary sizing cells which give high quality data with as little as 3µL of sample as well as a true extension to the upper size limit that DLS is able to accurately measure.

How does the Non-Invasive Back Scatter technology and MADLS complement each other in the Zetasizer Ultra?

Non-Invasive Back Scatter or NIBS is still the DLS measurement type we see as being the most relevant and useable for the majority of user’s applications. NIBS when it was introduced helped to really make DLS a much more approachable and useable technique as it significantly improved sensitivity and improved the dynamic concentration range that samples were measurable over and did all this in an automated way that emphasised data quality.  

If you have been using DLS as long as I have you will well remember the pain of making multiple dilutions to check for multiple scattering and to find optimal concentration range using traditional 90-degree DLS systems. NIBS took a lot of that sample prep need away and reduced the degree of dilution that is often necessary for a sample.

MADLS we see as providing a more informative measurement – it will require that little bit of extra effort to make sure your sample(s) are suitable and suitably presented – but the user gains in terms of improved accuracy, better resolution, and a more insightful answer as a result, these far outweigh any extra effort required by the MADLS technique and hence users will typically turn to MADLS when they require that extra information

What kinds of samples can the Zetasizer Ultra be applied to? Are there any that are usually difficult for researchers to measure?

Yes, we see a lot of interest in the life sciences for measuring the particle concentration and particle size of proteins, liposomes and viral fragments. These are typically small and difficult to measure the concentration of, so that’s a good example of some sample types.

But we should not ignore the advance that Adaptive Correlation has brought to many other sample types.  It really can make the difference between a set of difficult to interpret, almost random data and a set of data that is far more interpretable and as a result actionable.

In the Zeta analysis arena, the incorporation of Constant Current Zeta mode has made zeta potential measurements in more conductive media, physiological saline for example, more accurate and reliable.

Constant current zeta is in both the Pro and Ultra systems as are the incorporation of user selectable optical filter wheel. This allows users to measure fluorescent samples without impairing overall system sensitivity by having to fit a permanent filter and the polarisers can help screen for potential shape effects, such as rotational diffusion from that of translational diffusion.

About Darrell Bancarz

Darrell's background is in Physical and Environmental Chemistry and he has spent most of his career working within the scientific support laboratories within a number of diverse industry sectors.

Darrell joined Malvern Panalytical (formerly Malvern Instruments) in 2000, and spent most of his time here within and running the Applications Laboratory Services Department supporting Sales and Customer Service Departments.

More recently Darrell moved to the role of Product Manager - Nanomaterials, which is primarily focused on developing and supporting the Zetasizer Product Range within the wider Malvern Panalytical Portfolio.

Disclaimer: The views expressed here are those of the interviewee and do not necessarily represent the views of Limited (T/A) AZoNetwork, the owner and operator of this website. This disclaimer forms part of the Terms and Conditions of use of this website.

Alina Shrourou

Written by

Alina Shrourou

Alina graduated from The University of Manchester with a B.Sc. in Zoology. Alongside her love of animals, Alina discovered a passion for writing and science communication during her degree. In her spare time, Alina enjoys exercising her creative side through baking, as well as going to the gym in order to lessen the guilt of consuming the baked goods.


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