Visually activated VIS-Fb probes emit fluorescence only when bound to their target, dramatically reducing background signals in live-cell imaging and enabling high-clarity multicolor visualization.

The VIS-Fbs platform enables multicolor molecular imaging to illuminate proteins inside living cells and animals with unprecedented clarity, supporting high-precision visualization with minimal background.

A collaboration between Albert Einstein College of Medicine and the Salk Institute reports engineered fluorescent nanobodies—VIS-Fbs—that light up only upon target binding, greatly reducing background noise in live-cell imaging.

The study lists Axel Nimmerjahn and Vladislav Verkhusha as co-corresponding authors and was published in Nature Methods on April 22, 2026, with authors from Salk, Einstein College of Medicine, and collaborators, funded by NIH, foundations, and other organizations.

Publication details note the Nature Methods report on April 22, 2026, highlighting support from multiple funding agencies and foundations.

The Nature Methods paper emphasizes VIS-Fbs’ potential to study cell signaling, development, and disease progression with greater precision, underscoring the platform’s flexibility for diverse biological questions.

The VIS-Fb platform’s broad applications span cancer, neurodegenerative and infectious diseases, developmental biology, and neurobiology, advancing both basic research and translational medicine.

In mouse and zebrafish models, the system achieves precise imaging of CNS activity in neurons and astrocytes during behavior, and tracks developmental and drug-response dynamics in zebrafish embryos.

Validated across diverse mammalian cell types and in vivo in mice and zebrafish, enabling calcium signaling imaging in neurons/astrocytes and real-time developmental/pharmacological responses in zebrafish.

Demonstrated applications include high-contrast neuronal and astrocyte activity imaging in mice during behavior, and rapid developmental changes in zebrafish embryos with signaling-modulating drug responses.

The platform is modular, integrating over twenty fluorescent proteins and biosensors across various nanobody scaffolds, enabling rapid customization for targets, environments, and readouts, with some variants supporting optogenetic control.

This modular design allows swapping nanobody modules or fluorescent proteins to tailor VIS-Fb probes for different targets and outputs, supporting multicolor imaging and functional readouts.