NanoSight comparison: which solutions can be used for nanoparticle analysis?

A NanoSight comparison should first start from the laboratory’s real need. NanoSight is an NTA platform, meaning Nanoparticle Tracking Analysis, designed to observe individual particles in suspension, track their Brownian motion and derive a size distribution as well as particle concentration.

This technology is widely used for extracellular vesicles, exosomes, viral vectors, lipid nanoparticles, nanobubbles and colloidal formulations. However, it is not always the simplest solution for every use case. Depending on sample type, concentration, available volume, expected throughput or fluorescence requirements, other methods may be more suitable for routine work.

Understanding the NanoSight principle

NanoSight is based on nanoparticle tracking analysis. Particles are illuminated by a laser and individually visualized through scattered light. The software tracks their movement in the liquid and uses this motion to calculate their size.

This approach provides an important advantage over ensemble methods such as DLS. It does not only provide a global average, but a particle-by-particle reading. It can therefore better observe a heterogeneous population, a broad distribution or the presence of subpopulations.

NanoSight Pro also adds features designed to secure the workflow: flow analysis, particle visualization, advanced analysis software, interchangeable laser modules and fluorescence options. Fluorescence can be useful to identify labeled subpopulations or connect a fluorescent signal to a given population.

Identifying NTA strengths

NTA remains relevant when the laboratory needs detailed information on size and concentration of nanoparticles in suspension. It is particularly useful for directly visualizing particles and checking result consistency from videos.

This visualization capability is valuable when samples are precious, complex or sensitive to aggregation. Users can see whether larger particles, aggregates or debris are affecting the analysis. This provides qualitative control that some more automated methods do not always offer.

Fluorescence is another strength. When available, it makes it possible to work on labeled particles, biomarkers, cargos or subpopulations. For laboratories studying extracellular vesicles or complex biological particles, this information can be central.

Spotting daily-use limitations

The main challenge with NanoSight is not only technical. It is related to daily use. NTA measurement depends on sample preparation quality, dilution, acquisition settings and result interpretation.

A sample that is too concentrated can make tracking difficult. A sample that is too diluted may not contain enough usable particles. Very small, weakly scattering or low-refractive-index particles may also be harder to detect than more visible standards.

Sample volume must also be considered. NanoSight Pro states a minimum volume of 250 µL, which may be acceptable for many projects, but more restrictive when material is rare or expensive. For some uses, especially process development or rapid control, workflow simplicity and low volume become important criteria.

What a more direct method changes

A label-free method without fluidic circulation follows another logic. Interferometric microscopy, for example, measures particles in a static droplet, without daily laser setup, labeling, calibration or acquisition settings.

An instrument such as Videodrop SC can measure particle concentration and a number distribution from 5 to 10 µL of sample in less than one minute. This approach becomes relevant when the laboratory needs to process many samples, monitor a process, check concentration or rapidly control a batch.

The limitation is clear: this method does not replace fluorescence and does not reach as low as some NTA configurations. It is therefore better suited to rapid size and concentration analysis than to work requiring biological identification through labeling.

Comparing available technologies

PlatformPrinciplePublished rangeChargeFluorescenceMain use
NanoSight – Malvern PanalyticalNTA10-1000 nm – 10^6-10^9 p/mLNoYes, depending on configurationSize, concentration, fluorescence
Videodrop – Myriade LabILMAround 80-500 nm – 10^8-10^10 p/mLNoNoFast counting, low volume, process monitoring
ZetaView – Particle MetrixNTA10-1000 nm – 10^5-10^9 p/mLYesYes, up to 11 channelsMultiparametric analysis, zeta, colocalization
Exoid – IzonTRPS40 nm-11 µmYesNoResolution, charge and particles below 80 nm
NanoAnalyzer – NanoFCMNano-flow cytometry40-1000 nmNoYesBiological particle phenotyping
Virus Counter – SartoriusFluorescence-based counting5 x 10^5-1 x 10^9 p/mLNoRequiredSpecific viral counting

This table shows that NanoSight does not have one single direct competitor. The choice depends on the priority parameter: fluorescence, charge, speed, low volume, resolution or ease of use.

Choosing according to particle size

The critical size of the population to be measured must be assessed before any comparison. NanoSight covers a broad range, with a stated lower limit of 10 nm depending on sample and configuration. In practice, very small or weakly scattering particles may remain more difficult to track than larger and more contrasted particles.

If the laboratory regularly works on populations close to or below 80 nm, NanoSight may need to be compared with methods capable of reaching very low sizes, such as some TRPS approaches. If particles are mainly above 80 nm, a faster method may cover a large share of routine control needs.

The choice should therefore not be limited to the maximum range stated in a datasheet. It should consider the real nature of the particles, their refractive index, their concentration and the objective of the analysis.

Choosing according to fluorescence needs

Fluorescence can make a major difference. If the laboratory needs to identify subpopulations, track markers or distinguish particles according to their composition, an NTA platform equipped with fluorescence remains relevant.

In this case, a label-free solution cannot provide the same level of information. It can count and size detectable particles, but it cannot confirm biological identity through a fluorescent signal.

However, if fluorescence is rarely used, NanoSight may be mobilized for relatively simple size and concentration measurements. A faster and less demanding complementary technology can then help absorb routine controls and reserve NanoSight for analyses that truly justify its advanced functions.

Choosing according to throughput and available volume

Analysis throughput is often underestimated. A laboratory performing a few expert measurements per week does not have the same needs as a team that must control many samples every day.

For occasional analyses, NanoSight can provide detailed and visual data. For repeated measurements, preparation, cleaning, dilution and settings may become more demanding. The 250 µL minimum volume must also be compared with methods that work with only a few microliters.

When samples are rare, expensive or difficult to produce, low volume becomes a strong operational advantage. In this case, a complementary method can help preserve material while maintaining high throughput.

Organizing uses between expertise and routine

The best solution is not always to replace NanoSight. In many laboratories, it is more relevant to distribute use cases. NanoSight can remain dedicated to analyses requiring visualization, fluorescence, subpopulation validation or in-depth study of complex samples.

A more direct method can handle rapid controls: concentration monitoring, batch comparison, aggregation checks, stability control or dilution guidance before more detailed analysis.

This organization avoids using an expert platform for all simple measurements. It improves throughput, reduces operator time and reserves the most complete instruments for questions that truly require their level of information.

Comparing NanoSight according to real laboratory needs

The NanoSight comparison should be built around practical use cases. If the main need concerns size, concentration, visualization and fluorescence, NanoSight keeps a strong position. If the priority is fast counting, low volume, simplicity or process monitoring, a complementary method may be more coherent.

The laboratory must therefore analyze the critical particle size, concentration level, measurement frequency, labeling requirements, available volume and acceptable daily complexity.

A NanoSight comparison should not oppose technologies in an abstract way. It should help determine which platform answers which question, and under which conditions a faster or simpler solution can improve analytical organization.