[Reading Science] A Democratic Revolution Has Occurred in the World of Microscopy

German Research Team Develops Sub-1nm Resolution Technology Using Conventional Optical Microscope
Performance Comparable to Billion-Won Electron Microscopes, Low-Income Country Researchers 'Cheer'

"A democratic revolution has occurred in the realm of microscopes."

This is what the scientific community is saying about a recently invented microscopy technology developed by a German research team. It has become possible to observe images with precision comparable to expensive electron microscopes worth billions of won using an inexpensive and ordinary optical microscope.

Optical microscope. Stock photo. Not related to the article.

According to the international academic journal Nature on the 22nd, a research team at the University Medical Center G?ttingen in Germany recently developed a new 'ONE (one-step nanoscale-expansion) optical microscope' technology that breaks the limits of conventional optical microscopes, and published the related paper on the preprint site bioRxiv last month.

Typical optical microscopes cannot observe objects smaller than 200 nanometers (nm). Efforts to overcome this limitation have been ongoing. In 2014, an optical microscopy technology capable of accurately observing down to 10 nm won the Nobel Prize in Chemistry. This technology enhanced resolution by using optical methods to detect fluorescent molecules attached to proteins. In 2015, a research team at MIT in the United States developed expansion microscopy technology, successfully improving resolution to 20 nm. This method involved using absorbent chemicals that swell when absorbing water, similar to those used in diapers, to expand cell tissues and increase the distance between them. This technology has already been adopted by over 1,000 laboratories worldwide, demonstrating high reliability.

The research team developed a technology that can improve resolution much further, to below 1 nm. This level of resolution is sufficient to observe individual proteins, comparable to expensive cryo-electron microscopes or X-ray microscopes costing tens of millions of won. To achieve this, the team first utilized the idea of expansion microscopy. After fixing the protein samples, they added water containing chemicals to swell the sample over 1,000 times, separating molecules at the molecular level. They then combined this with a method that uses heat or enzymes to break down proteins into individual pieces and expand each piece in a specific direction.

Demonstration of the High-Voltage Electron Microscope (HVEM) at the Basic Support Research Institute

Using this method, the team observed the neural cell molecule 'GABAA receptor' and otoferlin protein, known to be involved in auditory signal transmission in the brain. The resulting images closely resembled the structures predicted by Google's AlphaFold deep learning network, an AI for protein structure prediction. This means that even proteins smaller than 1 nm can now be observed with a conventional optical microscope.

Of course, the team's method does not surpass cryo-electron microscopes, which offer resolution close to the atomic scale below 0.2 nm. However, electron microscopes are difficult to handle and expensive, making them hard for scientists to use. The new technology is over 400 times more powerful than conventional optical microscopes and can produce 3D images, allowing detailed views of organelles inside cells. However, electron microscopes only produce black-and-white images, are complex to operate, and can only observe dead organisms. They require high voltage currents, cooling systems, and pose risks of radiation leakage.

The ONE microscopy technology developed by the research team is expected to become a revolutionary tool that allows scientists to quickly and easily examine structures at the molecular level. Especially, many researchers in low- and middle-income countries suffer from limited access to high-performance microscopes, hindering proper research, so this technology is expected to rapidly emerge as an alternative. It will also be a useful tool for those working in well-equipped, wealthy research institutes in developed countries who wish to conduct independent research.