Project NanoINHAL

What happens when we breathe in nanoparticles emitted by a laser printer, for example? Could these nanoparticles damage the respiratory tract or perhaps even other organs? To answer these questions, Fraunhofer researchers are developing the “NanoCube” exposure device. The Nanocube’s integrated multi-organ chip set up in the laboratory of the Technical University of Berlin (TU Berlin) and by its spin-off organization “TissUse” detects interaction between nanoparticles and lung cells, the uptake of nanoparticles into the bloodstream and possible effects on the liver.

Simulations help to optimize development

But how can aerosols, in particular nanoparticles, be directed towards lung cells in such a way that a specified quantity is deposited on the cell surface? This is where the expertise of Fraunhofer SCAI comes in: The researchers studied this point and similar aspects in a simulation. They had to overcome special challenges in the process: For example, the physical and numerical models required for a detailed simulation of nanoparticles are significantly more complex than for particles with larger diameters. This, in turn, causes a significant increase in computing time.

But the time and effort are worth it, because the computationally intensive simulation helps to optimize the real-life test system. Let’s take an example: As mentioned above, the aerosol has to flow through a line from which several branches extend downward to direct the nanoparticles onto the multi-organ chips, with conditions at the sampling points that are as identical as possible. The inertial forces of the nanoparticles are low, however, so the particles would be less likely to move out of the diverted flow path and onto the cell surface. Gravity alone is not sufficient in this case. The researchers resolve the issue by exploiting the phenomenon of thermophoresis. “This relates to a force in a fluid with a temperature gradient that causes the particles to migrate to the cooler side,” explains Dr. Carsten Brodbeck, Project Manager at Fraunhofer SCAI. “By allowing the aerosol to flow through the line in a heated state, while the cells are cultivated naturally at body temperature, the nanoparticles move towards the cells, which the simulation clearly shows.”

The researchers also used simulations to investigate how to achieve the highest possible temperature gradient without damaging the cells and how the corresponding device should be constructed. They also examined how different flow speeds and supply line geometries would affect uptake. The temperature distribution in the exposure device was optimized by selecting different materials, making adjustments to the
geometry and modifying the cooling and heating design. “Using simulations, we can quickly and easily change the boundary conditions and understand the effects of these changes. We can also see things that would remain hidden in experiments,” explains Brodbeck.

The basic technological problems have been solved. Now, the initial prototype of the NanoCube exposure device, including a multi-organ chip, is expected to be ready in the fall, after which the first experiments with the system will be carried out. For now, the researchers at Fraunhofer are using reference particles instead of aerosols from printers, for example, nanoparticles from zinc oxide or what is known as “carbon black”, i.e. the black pigment in printing ink. In future practical applications, the measuring system is to be set up wherever the nanoparticles are produced, for example, next to a laser printer.

Innovative test system for toxic effects

The NanoINHAL project will see the creation of an innovative test system that can be used to investigate the toxic effects of airborne nanoparticles on cells in the respiratory tract and lungs, as well as on downstream organs such as the liver. Due to the combination of two organ systems in a microphysiological system, it will also be possible to study the uptake and distribution of nanoparticles in the organism. In the future, the test system will provide data on the long-term effects of inhaled nanoparticles as well as their biokinetics. This will play a major role in assessing the potential health  hazard posed by such particles.