Next Generation Electrophoretic Light Scattering system demonstrated at Pittcon 2018

ENLIGHTEN SCIENTIFIC’s knowledge of the measurement of zeta potential using electrophoretic light scattering (ELS) is unsurpassed by any manufacturer of commercial equipment or academic researchers.
 
How can I make such a bold claim?
 
I invented Phase Analysis Light Scattering (PALS) in the late 1980s. I worked with Brookhaven Instruments Corporation to develop their ZetaPALS instrument – the successor to the highly popular ZetaPlus instrument. The ZetaPALS was launched in the late 1990s, some years ahead of the other manufacturers of PALS-based light scattering instruments.

PALS has become the de facto method for measuring zeta potentials of charged particles in a wide range of liquid media. At least five companies market electrophoretic light scattering (ELS) instruments that use variants of PALS. This illustrates my preeminence in this field.

 

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Commercial importance

Zeta potentials in nonpolar media for nanoparticle dispersions and other colloidal systems
The primary goal for developing PALS was to measure very small electrophoretic mobilities in nonpolar media such as aliphatic hydrocarbons. The original instrument was able to measure mobilities as low as 10-12m2s-1V-1 – justifying my claim that PALS can “measure electrophoretic mobilities three orders of magnitude lower than any existing instrument”.

Commercial vendors make the same claim. Little experimental evidence exists to support this for their implementations of PALS.

There is no basis to assume that all commercial instruments will yield the same results for a given sample. Many differences exist particularly regarding electrode configuration and data sampling.

Caution is required when comparing measurements from different instruments, including those within a vendor’s line of instruments, such as Malvern Panalytical’s Zetasizer range.

 

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Zeta potentials in high conductivity aqueous media
Primary commercial interest for PALS is the measurement of zeta potential of particles dispersed in high conductivity aqueous media. PALS’ predecessor – laser Doppler electrophoresis (LDE) – is not able to perform measurements under such conditions. i.e., salt concentrations (ionic strengths) greater than 10mmol.dm-3.

As before, there isn’t much evidence to show that each implementation yields comparable results.

PALS can measure small displacements of particles such as in weak electric fields – which are necessary for measurement in high salt concentration media. But an important price is paid for this ability. It measures a mean zeta potential whereas LDE can determine a distribution of zeta potentials.

PALS measurements are only valid if the sample has a monomodal zeta potential distribution

This presents a problem. How can the sample’s zeta potential distribution be assumed monomodal? It can’t. A judgement call is required based on the knowledge of the colloidal properties.

PALS measurements are meaningless if the sample has more than one zeta potential mode

Does this mean that commercial instruments are of questionable value for samples at high conductivities? It depends. If you want to measure accurate zeta potentials – yes. If you have identified zeta potential as a critical quality attribute then it may be valid to use the instrument as long as QbD-type principles are used for method development.

 

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Is there a solution?

No vendor has resolved the issue in the two decades since the launch of the first commercial PALS instrument

Commercial manufacturers are aware of the fundamental limitations outlined above but have not been able to come up with a solution. The technique has not progressed in 30 years. Customers are unaware of this critical weakness.

ENLIGHTEN SCIENTIFIC has solved this problem

Within 6 months of its formation, ENLIGHTEN SCIENTIFIC solved this problem. My Next Generation Electrophoretic Light Scattering system (NG-ELS) is able to measure high ionic strength samples (e.g., up to 4 molar KCl(aq) solution) using both LDE and PALS methods. Zeta potential distributions and high-precision mean zeta potentials are measured simultaneously. Electrical impedance information is used to identify and correct for electrode polarization effects.

NG-ELS is currently in the PCT patent application process.
 

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This ground-breaking advance in the measurement of zeta potential via light scattering was presented to the American Chemical Society at its August 2018 National Meeting in Boston. The presentation is available here. Experimental data demonstrate the gross underestimation of zeta potential using a Malvern Panalytical Zetasizer Nano ZS.
For zeta potential measurements of samples at salt concentrations greater than 10mmol.dm-3, all you can say is:

“My sample has a zeta potential of at least X mV but only if it has a monomodal zeta potential distribution – which I don’t know!”

How can I help you?
Best practices training

Commercial instruments are typically sold as black boxes and their customers are encouraged to use simple applications to make the measurements. This is a significant risk for obtaining credible data especially for aqueous samples at salt concentrations greater than 10mmol.dm-3. Without an understanding of a vendor’s implementation, it is not possible to troubleshoot unexpected results.

I can work with you to give better understanding of the principles of LDE and PALS measurements, how instrument parameters can influence results, and how to interpret data particularly under challenging conditions.

This training can be onsite or remote via Skype or similar.

Contact me to discuss your needs

 

Method development

The black box nature of commercial instruments often involves automatic selection of important instrument parameters. The problem with this is that some samples may have an apparent zeta potential that is dependent upon some of the parameters. Users are mostly unaware of this.

Development of analytical methods such as for quality control release testing using a Quality-by-Design (QbD) approach requires generation of a response surface for the measurement process. This is seldom done for light scattering instruments.

I can help you identify the appropriate region of a response surface that will maximize the robustness and confidence of zeta potential data.

I have developed proprietary data analysis methods that can identify and correct for parameter-dependent data.

Contact me to discuss your needs

 

Data analysis

I want to provide you with the tools to assess the credibility of your measurements.

In my experience, misinterpretation of results is can easily occur. Commercial instruments are designed to present users with condensed information often with the intent of providing a single page report. This may include individual and mean values of electrophoretic mobilities and descriptive statistics. Graphic phase functions and distributions may be included for PALS and LDE measurements, respectively.

The challenge is to know how to gauge the fidelity of a measurement. This is not the same as “quality” values that some instruments report. Rather it relates to any instrument issues that reduce the accuracy of the measurement. This is an issue for particles dispersed in nonpolar media, or aqueous media where the ionic strength exceeds 10mmol.dm-3. The latter poses the greater concern due to the significant electrochemical phenomena present under such conditions.

Some instruments – such as the Malvern Panalytical Zetasizer Nano ZS – record detailed voltage and current data that can be reviewed following the measurement. My experience shows that this information is only used to confirm the uniformity of the electric field. The NG-ELS system records similar information but can use it to quantify electrode polarization and electrolysis. The presence of either will result in an underestimation of the measured zeta potential. NG-ELS can apply a correction. Commercial instruments cannot. I can show you how to interpret detailed instrument reports and assess the validity of a measurement.

Other factors are important to ensure confident interpretation of measurement results:
 

  • Zeta potential is calculated from electrophoretic mobility which is the measured property. Various mathematical models can be used to calculate the zeta potential. The choice – and relevance – of model varies according to the make and model of the instrument. For most aqueous samples, most of the models are inappropriate. This is largely unknown or acknowledged.
  • The algorithms for calculating zeta potential distributions via LDE vary according to the make and model of the instrument.
  • PALS measurements can be performed using sinusoidal electric fields (per the original instrument) or square wave electric fields. I have demonstrated that under high ionic strength conditions, the measured zeta potential is dependent on the shape of the waveform.

The above comments explain why the black box nature of commercial instruments can lead to misinterpretation of results. I have detected adverse electrochemical phenomena for two commercial instruments and they are likely to occur in all instruments. The manufacturers appear to have not identified the issues and/or are unaware that they exist. I have a unique understanding of the causal factors and – more importantly – can identify their presence. I can show you how to detect undesirable phenomena and gauge the validity of a measurement.

Contact me to discuss your needs

 

Suitability for high ionic strength

Determination of zeta potential at physiological ionic strengths and higher (>0.15mol.dm-3) is becoming increasingly important in industries such as waste water treatment, desalination, and dispersions for intravenous administration of nanomedicines and other nanomaterials. Commercial instruments fail to make measurements under such conditions with acceptable confidence. Only my NG-ELS system is capable of this. Some instruments will make measurements but the results are meaningless. Only PALS can be used. The NG-ELS system can use the LDE method, too.

Currently, there is only one NG-ELS instrument. So how can you measure zeta potentials at very high ionic strengths with your commercial instrument? This is the wrong question. We should ask if it is possible to use a commercial instrument to make surrogate measurements in lieu of the availability of NG-ELS.

I will measure your samples and determine a response surface relating measured zeta potential to various instrument parameters. This includes factors close to those of the commercial instrument. I determine if these latter ones are credible and if a correction factor can be applied. If successful, an appropriate method can be developed for the commercial instrument. This approach is of most value when measuring zeta potential as a critical quality attribute since the absolute value is not required.

Contact me to discuss your needs

 

NG-ELS analysis

I can measure your samples using my NG-ELS system. There are several reasons you should consider this:

  • Too high ionic strength preventing using a commercial instrument as a surrogate for NG-ELS
  • Quantification of electrochemical effects such as polarization and electrolysis
  • Wider choice of electrode materials
  • Determination of zeta potential distributions via LDE
  • Use of square wave and sinusoidal electric fields for PALS
  • Measurement by the inventor of PALS and NG-ELS

Use of the NG-ELS system allows the confidence level of a measurement to be determined in a superior way to commercial instruments.

I can determine if electrophoretic light scattering is a suitable method for your samples or not.

Contact me to discuss your needs

Commercial instruments with PALS capability

These are the currently available commercial instruments that implement the PALS method for zeta potential estimation. Some also feature the older LDE technique. Other instruments are available that only incorporate LDE.

Nicomp ZLS Z3000
Particle Sizing Systems
8203 Kristel Circle
Port Richey FL 34668
United States

NanoBrook ZetaPALS
Brookhaven Instruments Corporation
750 Blue Point Road
Holtsville NY 11742
United States

Mobius
Wyatt Technology Corporation
6330 Hollister Ave
Santa Barbara CA 93117
United States

DelsaMax PRO
Beckman-Coulter Inc
Life Sciences Division Headquarters
5350 Lakeview Parkway S Drive
Indianapolis IN 46268
United States

Zetasizer Nano ZS, Pro, Ultra
Malvern Panalytical Inc
117 Flanders Road
Westborough MA 01581-1042
United States