It costs less than 1,000 euros and can make active SARS-CoV-2 viruses visible: Together with an international team from Jena, Tromsoe, and Oslo, junior researcher Benedict Diederich has constructed a DIY microscope that uses a smartphone and special photonic waveguide chips to deliver high-resolution ­images beyond the optical ­resolution limit.

Using a lens from a standard Blu-ray player that can be positioned with nanometer precision, the researchers couple a laser beam into the single-mode waveguide. A fluorescent sample lies on the waveguide; this can be visualized using Total Internal Reflection Flourescent Microscopy (TIRFm). "The intensity in the TIRF range and the sensitivity of the cell phone camera are large enough to detect individual molecules," explains Benedict Diederich; for example, using direct Stochastic Optical Reconstruction Microscopy (dSTORM).

The researchers use antibodies to bind the fluorescent molecules to the skeleton of a cell or to the spike proteins of the SARS-CoV-2 virus. By localizing many of these proteins, they can achieve resolution in the range of less than 80 nm.

"From a variation in the excitation pattern and the associated change in the emission signal, we can use machine learning algorithms to further increase the resolution in live-cell images," Diederich says. The cell phone handles both image processing and control of the 3D-printed microscope.

The complete device into a handy box and thus fits well in an incubator or in a high-security laboratory. There, it could be used to visualize living cells, for example, or to look at how viruses enter cells. "It's ideal if you don't want to bring the sample to the microscope, but the microscope to the sample," says Diederich, who successfully completed his Ph.D. at Leibniz IPHT and the University of Jena in early 2021 (A microscope for everyone, p. 28).

"Safety labs with super-resolution microscopes, that's an exclusive combination that only exists in very few research facilities in the world," he explains. The building instructions for the DIY nanoscope, meanwhile, are open source, along with the cell phone software. This has already been used to build several devices outside Leibniz IPHT.