Nanochannels light the way toward new medicine

Detailed knowledge about nature's smallest biological building blocks is needed for the development of new drugs and vaccines. In a completely new way, tiny biological particles can be studied in their natural state with the help of a new microscopy technique.

It takes a lot of time and money to make a medicine or vaccine. It's important to be able to streamline the work by studying how individual proteins interact with each other. The most promising candidates can be found at an earlier stage, thanks to the new microscopy method. The technique can be used to conduct research into how cells communicate with one another by secreting molecule and other biological particles. Our immune response is influenced by these processes.

It is revealing its silhouette.

Since they are the building blocks of everything, biomolecules are important. Researchers need to either mark them with a fluorescent label or attach them to a surface in order to use optical microscopes.

You can't be sure that the surface to which the molecule is attached doesn't affect the molecule's properties. With the aid of our technology, it shows its natural silhouette, which means that we can analyze the molecule just as it is. The new method was developed with researchers in both physics and biology.

The researchers want to study the molecule or particles that are flushed through the chip with the help of the unique microscopy method. The chip is illuminated with light after a test fluid is added. The molecule can be seen on a screen connected to the microscope when it shows up as a dark shadow because of the interaction between the light and the molecule. It is possible for researchers to see but also determine the mass and size of the biomolecule, something that was not previously possible with a single technique.

The new technique was presented in a journal. The Royal Swedish Academy of Engineering Sciences, which every year lists a number of research projects with the potential to change the world, has paid tribute to the progress made. In this year's Venture Cup competition in Western Sweden, the start-up company Envue Technologies was given the "game-changing" prize.

When you need to study the contents of a sample but don't know what it contains, our method makes the work more efficient.

The researchers are trying to find even smaller particles that are not currently visible.

Langhammer says the aim is to further hone our technique so that it can help to increase our basic understanding of how life works.

The technique is explained.

• The molecules or particles that the researchers want to study are placed in a chip containing tiny nano-sized tubes, nanochannels, that are filled with test fluid.
• The chip is secured in a specially adapted optical dark-field microscope and illuminated with visible light.
• On the screen that shows what can be seen in the microscope, the molecule appears as a dark shadow moving freely inside the nanochannel. This is due to the fact that the light interacts with both the channel and the biomolecule. The interference effect that then arises significantly enhances the molecule's optical signature by weakening the light just at the point where the molecule is located.
• The smaller the nanochannel, the greater the amplification effect and the smaller the molecules that can be seen.
• With this technique it is currently possible to analyze biomolecules from a molecular weight of around 60 kilodaltons and upwards. It is also possible to study larger biological particles, such as extracellular vesicles and lipoproteins, as well as inorganic nanoparticles.

More information: Barbora Špačková et al, Label-free nanofluidic scattering microscopy of size and mass of single diffusing molecules and nanoparticles, Nature Methods (2022). DOI: 10.1038/s41592-022-01491-6 Journal information: Nature Methods