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The painting entitled 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 the identification of these different populations. Credit: Max Planck Institute for the Science of Light

Scientists from the Max Planck Institute for Light Science (MPL) and the Max-Planck-Zentrum für Physik und Medizin (MPZPM) in Erlangen present a major step forward in the characterization of nanoparticles. They used a special microscopy method based on interferometry to outperform existing instruments. A possible application of this technique may be the identification of diseases.

Nanoparticles are everywhere. They are found in our body in the form of protein aggregates, lipid vesicles or viruses. They end up in our drinking water as impurities. They are in the air we breathe as pollutants. At the same time, many drugs are based on nanoparticle delivery, including vaccines that have recently been given to us. In connection with pandemics, the rapid tests used for the detection of SARS-Cov-2 are also based on nanoparticles. The red line, which we monitor daily, contains myriads of gold nanoparticles coated with antibodies against proteins that signal infection.

Technically, something is called a nanoparticle when its size (diameter) is less than one micrometer. Micrometer-sized objects can still be measured in a normal microscope, but much smaller particles, say less than 0.2 micrometers, become extremely difficult to measure or characterize. Interestingly, this is also the size range of viruses, which can get as small as 0.02 micrometers.

Over the years, scientists and engineers have developed a number of instruments to characterize nanoparticles. Ideally, one wants to measure their concentration, evaluate their size and particle size distribution, and determine their substance. A high-end example is an electron microscope. But this technology has many shortcomings. It’s very large and expensive, and the studies take too long because the samples have to be carefully prepared and put under vacuum. And even then, it remains difficult to determine the substance of the particles that we see under an electron microscope.

A fast, reliable, lightweight and portable device that can be used in the doctor’s office or in the field would have a huge impact. A few optical instruments on the market offer such solutions, but their resolution and precision have been insufficient to examine smaller nanoparticles, for example much smaller than 0.1 micrometer (or in other words 100 nm).

The distribution of vesicles extracted from the urine of a healthy person as a function of vesicle size and iSCAT contrast (i.e. how strongly they scatter light). Currently, researchers are studying these distributions in conjunction with various diseases. Credit: Max Planck Institute for the Science of Light.

A group of researchers from the Max Planck Institute for Light Science and the Max-Planck-Zentrum für Physik und Medizin have now invented a new device that offers a big step forward in the characterization of nanoparticles. The method is called iNTA, short for Interferometric Nanoparticle Tracking Analysis. Their results are published in the May issue of Natural methods.

The method is based on the interferometric detection of light scattered by individual nanoparticles traveling through a liquid. In such a medium, the thermal energy perpetually moves the particles in random directions. It turns out that the space a particle explores in a given time is correlated to its size. In other words, small particles move “faster” and cover a greater volume than large particles. The equation that describes this phenomenon, the Stokes-Einstein relationship, dates back to the turn of the last century and has since been used in many applications. In a nutshell, if we could follow a nanoparticle and collect statistics on its jerky trajectory, we could deduce its size. So the challenge is to record very fast movies of tiny moving particles.

MPL scientists have developed a special microscopy method over the past two decades known as interferometric scattering microscopy (iSCAT). This technique is extremely sensitive in the detection of nanoparticles. By applying iSCAT to the nanoparticle scattering problem, the MPL group realized that they could outperform existing instruments on the market. The new technology has a particular advantage in deciphering mixtures of nanoparticles of different sizes and of different materials.

The applications of the new method are multiple. A particularly interesting line of applications concerns the nanometric-sized vehicles which are secreted by the cells, the so-called extracellular vesicles. These consist of a lipid shell, much like a nano soap bubble. But the shell and the internal liquid also contain proteins, which tell us about the origin of the vesicles, that is, from which organ or cellular process. When the amount of protein and/or the size of the vesicles deviate from the normal range, the person may be sick. Therefore, it is very important to find ways to characterize extracellular vesicles.

MPL and MPZPM researchers are currently working on the development of a benchtop system to allow scientists around the world to benefit from the advantages of iNTA.


Track the movement of a single nanoparticle


More information:

Vahid Sandoghdar, Precision analysis of the size and refractive index of weakly scattering nanoparticles in polydispersions, Natural methods (2022). DOI: 10.1038/s41592-022-01460-z. www.nature.com/articles/s41592-022-01460-z

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Max Planck Institute for Light Science

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A new method to explore the nano-world (2022, May 9)
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