Scientists have developed many different microscope imaging techniques, but they all have their advantages and disadvantages. Electron microscopy can reveal intricate details on the surface of a specimen, but it cannot be used on living cells because the intensity of the electron beam can damage the sample. Other methods, such as fluorescence microscopy, will not harm the sample, but at the cost of resolution.
Therefore, for this new study, EPFL researchers started by developing their own imaging technology. It is based on an existing technology called scanning probe microscopy (SPM), which uses a probe tip to penetrate the sample to map its surface. However, this is invasive to cells, so the EPFL team replaced this probe with a glass nanopore to measure the flow of ions without touching the sample. They call this method Scanning Ion Conductivity Microscopy (SICM).
The team combined this new SICM technology with an existing technology called random optical wave imaging, which can peek inside cells and observe various molecules and processes inside. The combination of these two technologies allows scientists to take high-definition three-dimensional images of the inside and outside of cells at the same time.
The author of the study, Samuel Mendes Leitão, said: “The membrane of a cell is where it interacts with the surrounding environment. It is where many biological processes and morphological changes occur, such as during cell infection. Our system allows researchers to analyze the inside of the cell. Align the molecules of each other and map them to the dynamics of the membrane.”
Perhaps most importantly, they can monitor the process over time, from under a second to several days in scale. In the test, the team was able to observe the movement, communication, differentiation of mammalian cells, phagocytosis of molecules through their membranes, and bacterial infections.
Researchers say this new technology will be a very useful tool in infection biology, immunology, and neurobiology, but it can also find applications in other fields such as energy science to help produce solar fuels and other things.