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11-May-2022 - Max-Planck-Institut für die Physik des Lichts


A NEW METHOD FOR EXPLORING THE NANO-WORLD


A LARGE STEP FORWARD IN THE CHARACTERIZATION OF NANOPARTICLES: ONE POSSIBLE
APPLICATION OF THIS TECHNIQUE MAY BE TO IDENTIFY ILLNESSES

The painting called Several Circles by Vasily Kandinsky (1926) wonderfully
depicts a typical situation, where nanoparticles of different sizes and material
coexist in a sample. iNTA offers a particularly high resolution in identifying
these populations.

Zoom in

‹ ›

Scientists at the Max Planck Institute for the Science of Light (MPL) and
Max-Planck-Zentrum für Physik und Medizin (MPZPM) in Erlangen present a large
step forward in the characterization of nanoparticles. They used a special
microscopy method based on interfereometry to outperform existing instruments.
One possible application of this technique may be to identify illnesses.

Nanoparticles are everywhere. They are in our body as protein aggregates, lipid
vesicles, or viruses. They are in our drinking water in the form of impurities.
They are in the air we breath as pollutants. At the same time, many drugs are
based on the delivery of nanoparticles, including the vaccines we have been
recently given. Keeping with the pandemics, quick tests used for the detection
the SARS-Cov-2 are based on nanoparticles too. The red line, which we monitor
day by day, contains myriads of gold nanoparticles coated with antibodies
against proteins that report infection.

Technically, one calls something a nanoparticle when its size (diameter) is
smaller than one micrometer (one thousandth of a millimeter). Objects of the
order of one micrometer can still be measured in a normal microscope, but
particles that are much smaller, say smaller than 0.2 micrometers, become
exceedingly difficult to measure or characterize. Interestingly, this is also
the size range of viruses, which can become as small as 0.02 micrometers.

Over the years, scientists and engineers have devised a number of instruments
for characterizing nanoparticles. Ideally, one wants to measure their
concentration, assess their size and size distribution, and determine their
substance. A high-end example is an electron microscope. But this technology has
many shortcomings. It is very bulky and expensive, and the studies take too long
because samples have to be carefully prepared and be put into vacuum. And even
then, it remains difficult to determine the substance of the particles one sees
in an electron microscope.

A quick, reliable, light 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 for examining smaller nanoparticles, e.g., much smaller than 0.1
micrometer (or otherwise said 100 nm).

A group of researchers at the Max Planck Institute for the Science of Light and
Max-Planck-Zentrum für Physik und Medizin have now invented a new device that
offers a big leap in the characterization of nanoparticles. The method is called
iNTA, short for Interferometric Nanoparticle Tracking Analysis. Their results
are reported in the May issue of the internationally magazine Nature Methods.

The method is based on the interferometric detection of the light scattered by
individual nanoparticles that wander around in a liquid. In such a medium,
thermal energy perpetually moves particles in random directions. It turns out
that the space that a particle explores in a given time correlates with its
size. In other words, small particles move “faster” and cover a bigger volume
than large particles. The equation that describes this phenomenon – the
Stokes-Einstein relation - dates back to the beginning of the last century and
since then has found use in many applications. In a nutshell, if one could
follow a nanoparticle and collect statistics about its jittery trajectory, one
could deduce its size. So, the challenge is to record very fast movies of tiny
particles wizzing by.

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

The applications of the new method are manifold. A particularly exciting line of
applications concerns nano-sized vehicles that are secreted from cells, the
so-called extracellular vesicles. These are made of a lipid shell, much like a
nano soap bubble. But the shell and the inner liquid also contain proteins,
which tell us about the origin of the vesicles, i.e. from which organ or
cellular process. When the protein amount and/or the vesicle size deviate from
the normal range, it could be that the person is ill. Therefore, it is very
important to find ways to characterize extracellular vesicles.

The researchers at the MPL and MPZPM are now working on developing a bench-top
system to enable scientists worldwide to benefit from the advantages of iNTA.

Original publication
 * Kashkanova, A.D., Blessing, M., Gemeinhardt, A. et al. Precision size and
   refractive index analysis of weakly scattering nanoparticles in
   polydispersions. Nat Methods (2022)

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