Self-blinking dyes restore nanobody use in super-resolution microscopy

An international research team led by the University of Göttingen and the University Medical Center Göttingen (UMG) reported that self-blinking dyes can be combined with nanobodies for super-resolution microscopy. The results were published in Nano Letters in 2026, according to Phys.org. Nanobodies are extremely small antibody fragments that bind to specific molecules; when labeled with dyes, they can be used as probes to enhance super-resolution microscopy.

According to Phys.org, conventional blinking dyes often perform poorly when attached to nanobodies, limiting their practical advantages. Conventional dyes can also blink, but they usually need specially prepared chemical buffers and carefully controlled imaging conditions, and one of the most widely used dyes produces poor image quality with nanobodies. "Nanobodies offer excellent precision, but their use in super-resolution microscopy has been limited by the poor performance of conventional blinking dyes," said Dr. Felipe Opazo at the Center for Biostructural Imaging of Neurodegeneration (BIN) at UMG.

A self-blinking dye is a fluorescent molecule that switches on its own between a bright "on" state and a dark "off" state. Phys.org reported that this blinking is essential for super-resolution microscopy because it allows individual fluorescent molecules to be detected one after another and localized very precisely. "Combining nanobodies with self-blinking dyes preserves high labeling accuracy while restoring robust blinking, making super-resolution imaging simpler, more reproducible and easier to use," Opazo said.

The team demonstrated that the approach works across different super-resolution microscopy techniques, including some of the most precise fluorescence microscopy techniques currently available, according to Phys.org. The report stated that successful application in the MINFLUX microscope highlights the method's potential, from conventional super-resolution microscopy to cutting-edge nanoscopy. Phys.org reported that the approach simplifies experiments and increases the throughput of super-resolution microscopy.

"Our goal is to make super-resolution microscopy easier to use beyond specialized microscopy labs," said Dr. Roman Tsukanov, senior postdoctoral researcher at Göttingen University. He said self-blinking dyes make the imaging workflow much more straightforward and lower the barrier to entry into the field for researchers who are not microscopy experts, including biologists, chemists, clinicians and those in other fields of research.