Massachusetts-based Marine Biological Laboratory (MBL) has developed a hybrid microscope that enables scientists to simultaneously image the 3D orientation and position of molecules in cells.

The new microscope is designed to image molecules such as labelled proteins inside cells.

It combines a molecular-orientation measuring tool, polarised-fluorescence technology, with a dual-view light-sheet microscope (diSPIM), known for imaging along the depth axis of a sample.

According to the Marine Biological Laboratory, this microscope has powerful applications. These include imaging proteins as they change their 3D orientation in response to their environment.

Imaging molecules in the spindle of a dividing cell is another key application.

Marine Biological Laboratory senior scientist and study co-author Rudolf Oldenbourg said: “With traditional microscopy, including polarised light, you can study the spindle quite nicely if it’s in the plane perpendicular to the viewing direction. As soon as the plane is tilted, the readout becomes ambiguous.”

The Marine Biological Laboratory, which is an affiliate of the University of Chicago, aims to speed up its system to observe how the position and orientation of structures in live samples change over time. It also hopes future fluorescent probes will allow researchers to image a wider range of biological structures.

The concept for this microscope was first developed in 2016 by microscopy innovators at MBL.

The diSPIM microscope features two imaging paths that meet at a right angle, allowing dual-view illumination and imaging. This design improves depth resolution and provides greater control over polarisation compared to other microscopes.

The Marine Biological Laboratory said that its research team equipped the diSPIM with liquid crystals, enabling them to change the direction of input polarisation.