Interferometric Nanoparticle Tracking Analysis

In the characterization of nanoparticles, researchers at the Max Planck Institute for the Science of Light (MPL) and Max-Planck-Zentrum für Physik und Medizin (MPZPM) in Erlangen have made a substantial discovery.

The painting called Several Circles by Vasily Kandinsky (1926) wonderfully depicts a typical situation, where nanoparticles of different sizes and materials coexist in a sample. iNTA offers a particularly high resolution in identifying these different populations. Image Credit: © Max Planck Institute for the Science of Light.

The researchers used a unique microscopy technique based on interfereometry that significantly outperforms current instruments. One probable application of this method could be to detect illnesses.

Nanoparticles are all over the place. They are in the human body as lipid vesicles, protein aggregates, or viruses. They are in the drinking water as impurities. They can be found in the air as pollutants.

Additionally, several drugs are based on the delivery of nanoparticles, including the vaccines administered recently to combat the pandemic. To keep up with the pandemic, rapid tests employed for SARS-Cov-2 detection are also based on nanoparticles. The red line, which we monitor step by step, comprises multitudes of gold nanoparticles covered with antibodies against proteins that reveal the infection.

Theoretically, one refers to a substance as a nanoparticle when its size (diameter) is smaller than 1 μm (one-thousandth of a millimeter). Objects of the order of 1 μm can still be measured in a standard microscope, but particles that are a lot smaller, for instance, smaller than 0.2 μm, become extremely challenging to characterize or measure. Intriguingly, this is also the range of the size of a virus, which can be as small as 0.02 μm.

Through the years, researchers and engineers have developed several instruments for characterizing nanoparticles. Preferably, the focus is to assess their concentration, measure their size and size distribution, and establish their substance.

A sophisticated example is an electron microscope. But this technology comes with several inadequacies. It is bulky and costly, and research investigations take a long time as samples have to be meticulously prepared and placed in a vacuum. Still, it is challenging to establish the substance of the particles one views in an electron microscope.

A rapid, dependable, light and handy device that can be employed in the physician’s office or in the field would have a major impact. A few commercial optical instruments provide such solutions, but their precision and resolution have been inadequate for inspecting smaller nanoparticles, eg, a lot smaller than 0.1 μm (or 100 nm).

A team of scientists at the Max Planck Institute for the Science of Light and Max-Planck-Zentrum für Physik und Medizin has currently invented a new device that provides a giant leap in nanoparticle characterization. The technique is termed Interferometric Nanoparticle Tracking Analysis or iNTA. Their findings have been reported in the internationally well-known magazine Nature Methods (May issue).

The technique is formulated on the interferometric detection of the light dispersed by separate nanoparticles that move around in a liquid. In this medium, thermal energy constantly moves particles in haphazard directions. It emerges that the space that a particle travels in a particular time draws a parallel with its size.

Simply put, small particles travel “faster” and encompass a bigger volume than big particles. The equation that illustrates this occurrence — the Stokes-Einstein relation — goes back to the start of the last century and since then has been employed in a number of applications.

Briefly, if one could trail a nanoparticle and gather statistics about its edgy trajectory, one could infer its size. Therefore, the challenge is to capture very rapid movies of minute particles whizzing by.

Researchers at MPL have formulated a unique microscopy technique over the past 20 years, called interferometric scattering (iSCAT) microscopy. This method is highly sensitive to spotting nanoparticles.

By employing iSCAT to resolve the issue of diffusing nanoparticles, the MPL team understood that they can beat the current commercial instruments. The new technology possesses a specific edge in decoding combinations of nanoparticles with varying sizes and diverse materials.

The new technique has diverse applications. A principally stimulating range of applications concerns nano-sized vehicles that are discharged from cells, the so-called extracellular vesicles. These are composed of a lipid shell, quite like a nano soap bubble. But the inner liquid and the shell also comprise proteins, which inform us about the source of the vesicles, ie, from which cellular process or organ.

When the quantity of protein and/or the size of the vesicle diverging from the standard range, it could be inferred that the person is ill. Thus, it is essential to discover techniques to characterize extracellular vesicles.

The scientists at the MPZPM and MPL are currently looking into creating a bench-top system to support researchers globally to benefit from the advantages of iNTA.

Journal reference:

Kashkanova, AD, et al. (2022) Precision size and refractive index analysis of weakly scattering nanoparticles in polydispersions. Nature Methods. doi.org/10.1038/s41592-022-01460-z.

Source: https://mpl.mpg.de

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