How to choose the right tool for nanoparticle concentration measurements

by Jonathan Mehtala, Tuesday, 8th April 2025

Comparing concentration measurements between the NanoSight Pro and Zetasizer Ultra

As a Field Application Scientist, I am often asked some form of the following question: Between NanoSight Pro and Zetasizer Advance Ultra, what is the “better” technology to measure particle concentration? My answer to this question is always the same: It depends.

This is an understandable question, because at first glance, it may not be clear what the differences are between the two instruments. Both Zetasizer and NanoSight instruments use light scattering to measure particles in a liquid and Brownian motion to determine hydrodynamic size. However, the particle concentration measurement principles between the two technologies are fundamentally different.

While both instruments measure particle concentration in particles per milliliter (particles/mL), the differences between the two technologies lend themselves to different ideal sample types, mainly relating to size and polydispersity. This blog will explore how these systems compare and contrast to help you make the best choice for your nanoparticle characterization needs.

NanoSight Pro: visualize & quantify particles in real-time

Using nanoparticle tracking analysis (NTA) to directly count particles in a known three-dimensional scattering volume, NanoSight Pro excels at measuring particle size in the range of 30-500 nm diameter (refractive index-dependent) and 10⁷-10⁹ particles/mL for concentration. NanoSight Pro is best able to count particles in polydisperse samples, because concentration is determined directly from measured particle counts, and both dim and bright particles are counted equally.

Zetasizer Advance Ultra: multi-parameter analysis of nanoparticles

Polydispersity has a larger influence on the Zetasizer Advance Ultra particle concentration measurement, because concentration is calculated from the measured size, and polydispersity can influence size accuracy of two neighboring peaks. However, the lower sizing limit of detection for the Ultra is much lower than NanoSight Pro and can easily measure particles as small as 1 nm diameter.

Sample viscosity is also an important property for the Zetasizer Advance Ultra particle concentration measurement. Although viscosity is used in both technologies to determine a hydrodynamic size from the measured diffusion coefficient, it affects particle concentration on the Zetasizer Ultra because concentration is calculated from size, whereas NanoSight measures particle concentration independent from viscosity.

NanoSight Pro OR Zetasizer Advance: which is right for you?

While both instruments deliver exceptional performance, their core technologies and features cater to different needs:

Feature	NanoSight Pro	Zetasizer Advance Ultra
Core Technology	Nanoparticle Tracking Analysis (NTA)	Multi Angle Dynamic Light Scattering (MADLS)
Size Range	10 nm – 1000 nm	0.3 nm – 10 µm
Concentration Analysis	Yes, with real-time visualization	Yes, with bulk sample averaging
Additional Metrics	Fluorescence detection	Zeta potential, molecular weight
Key Applications	> Extracellular vesicles > Lipid nanoparticles > Viruses >50 nm, e.g. lentivirus > Nanobubbles	> Proteins > Lipid nanoparticles > Viruses from 20 nm, e.g. AAVs > Charged nanoparticles in colloids > Small, monodisperse nanoparticles

Choose NanoSight Pro if you:

Need to visualize and track individual particles for high resolution sizing.

Measure the size and concentration of nanoparticles.

Work with heterogeneous samples, such as extracellular vesicles, or larger viruses like Lentivirus, MVA, etc.

Require fluorescence detection for subpopulation analysis.

Choose Zetasizer Advance if you:

Focus on smaller particles, proteins, or polymers.

Require a broader size range for diverse sample types.

Need multi-parameter insights, including size, concentration, zeta potential and molecular weight.

Complementary tools for maximum insights

For many common applications, such as purified liposomes, polystyrene latex, and other monodisperse nanoparticles, both instruments are likely to excel and produce identical particle concentration results. The ideal instrument to track nanoparticle concentration may change with the stage of drug development or purification level, as sample properties vary from early research to in-process development, all the way to the final drug product. For cases like these, it is valuable to have both the NanoSight and Zetasizer operating in the same lab.

If you are still unsure which technology best suits your needs, just reach out and a member of our team will be happy to help you further.