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Quanta Image Sensors Boost Bioluminescence Signals for Live Cell Microscopy






NEUHERBERG, Germany,— A microscope built with quanta image sensor (QIS) technology will allow researchers to visualize bioluminescence signals in living cells in detail and over long durations. Researchers at Helmholtz Munich and the Technical University of Munich (TUM) developed the QIScope instrument to overcome the constraints of bioluminescence imaging. The device uses highly sensitive camera technology that is able to detect extremely low levels of light.

Bioluminescence offers an alternative to fluorescence that is less harsh for live-cell imaging, but the use of bioluminescence is limited by its low intensity. Specialized instruments, such as electron-multiplying charge-coupled device microscopes, compensate for the faint emission in bioluminescence by sacrificing spatial resolution, field of view, and dynamic range.

The researchers harnessed the full potential of the QIS camera technology by developing an optical system that combines features of a telescope with those of a microscope. Inspired by the Keplerian telescope, the design maximizes signal detection using the QIS, while maintaining a high field of view. The design also allows for modularity, enabling multimodal imaging with epifluorescence.

The QIScope captured images of cellular bioluminescence with modestly improved signal-to-noise ratio and substantially higher spatial resolution, field of view, and dynamic range compared to electron-multiplying charge-coupled device, a state-of-the-art bioluminescence system. The capabilities exhibited by the QIScope could support challenging experiments previously not possible using bioluminescence.

“To take full advantage of the sensor’s capabilities, we took inspiration from the optical layout of telescopes,” researcher Ruyu Ma said. “By combining this approach with the QIS camera, we created a system that can reveal cellular processes with a clarity and sensitivity that was not possible with the state-of-the-art system.”

The researchers used the QIScope to track fine-scale dynamics in living cells, such as the movement of vesicles and the behavior of low-abundance proteins, over extended periods (greater than 18 h), with minimal toxicity and probe bleaching.

All the components of the QIScope were obtained commercially and can be modified and integrated with other imaging modalities.

The construction, performance, and capabilities of the QIScope could make bioluminescence an accessible, viable technique for live-cell imaging at high spatiotemporal resolution. And, by addressing key limitations of traditional bioluminescence imaging, the QIScope provides researchers with a valuable tool for studying a range of biological systems, from single cells to organoids and tissue models. Its ability to reveal subtle and long-term changes in cell behavior could support progress in diverse research areas, including cell biology, disease modeling, and drug discovery.

“It also integrates other imaging methods such as epifluorescence and, in principle, phase contrast," said researcher Jian Cui, who led the study. "This opens the door to observing living systems with much less disturbance, which is essential for understanding complex biological processes in health and disease.”


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