Labelling Cells with a Switch

Researchers of the Cell Engineering group at the Institute of Biological and Medical Imaging, have succeeded in specifically labelling cells for optoacoustic imaging with "switchable" proteins and transferring the new approach to commercially available standard optoacoustic devices. The new method has now been published in the journal "Science Advances".

Photo-switching principle. Illumination of two wavelengths drives a chromophore between an ON- and OFF- state, creating a modulation that can be used for the separation of the signal from background. Bottom right: Cut through a volume rendering of a tumor on the back of a live mouse, labeled with photo-switching proteins (blue) infiltrated by bacteria labeled with a different photo-switching protein (red). All scalebars 1 mm. Image: Mishra et al. | SciAdv

Optoacoustic imaging allows high-resolution in vivo imaging well beyond the capabilities of other imaging methods. Helmholtz Zentrum München is leading in the development and commercialization of Optoacoustic techniques which already provides unique insight into disease states, foremost cancer but also atherosclerosis, inflamed bowl disease or psoriasis. In several cases Optoacoustic imaging developed by institute director Vasilis Ntziachristos already made the step into clinical practice. In contrast the use of the method in research and life-sciences imaging is still limited by difficulties to visualize specific cells in the body of e.g. a live mouse.

Here, researchers of the Cell Engineering group at the Institute of Biological and Medical Imaging recently made an essential step. The team headed by Andre C. Stiel now showed transgene contrast to label cells specifically and allow also small cell number to be detected deep in the live animal. The labels are based on proteins which can be reversibly switched between two states by light as first author Kanuj Mishra explains. This switching allows a unique separation of the labeled cells from the surrounding background – making the latter virtually invisible. The researchers also developed analysis algorithms based on machine-learning techniques that allow to readily image organisms with labeled cells in standard commercial optoacoustic equipment, making this approach immediately available to other researchers. In their publications in Science Advances the team already showed some examples of visualization ranging from tumor cells in the body or brain of mice to immune-cell populations.

The team still works on improving the detection sensitivity, which is currently in the thousands of cells, but the vision is clearly to be able to visualize small number or even single cells in unperturbed longitudinal measurements deep in a live mouse, for instance to observe the organization of cells of the immune system in a whole tumor, as Andre C. Stiel explains.


K. Mishra et al.: Multiplexed whole animal imaging with reversibly switchable optoacoustic proteins. Science Advances 6/24. DOI: 10.1126/sciadv.aaz6293

Further reading:

K. Mishra, Analytical Chemistry, 2019

A.C. Stiel & X.L Déan-Ben, Optics Letters, 2015