Unlike traditional fluorescence imaging, which requires external light that can damage cells or obscure the probe signal, bioluminescence is a self-contained process resulting in a gentle glow, making it particularly suitable for high-sensitivity measurements over long durations. However, the main downside has been the low intensity of this light, which has generally required researchers to use specialized microscopes equipped with sensitive detectors such as the electron-multiplying CCD (EMCCD). Unfortunately, such instruments often provide limited resolution and restricted views, making it difficult to track cellular changes in detail.
A new camera technology for low-light detection called the quanta image sensor (QIS) offers a promising solution. Jian Cui’s team found that a recently developed QIS camera possesses exceptional sensitivity and greatly outperforms a state-of-the-art EMCCD camera when directly compared. However, to fully exploit the capabilities of the QIS, lead author and PhD student Ruyu Ma and team introduced a new microscope design inspired by telescopes. The integrated “QIScope” offers significantly improved signal-to-noise ratio, spatial resolution, field of view, and dynamic range compared to the state of the art. Plus, its design facilitates integration with other imaging modalities, such as epifluorescence, phase contrast, and differential interference contrast.
Importantly, the Cui team and Helmholtz Munich collaborators including Gil Westmeyer and Dong-Jiunn Jeffery Truong of the Institute of Synthetic Biomedicine and Sebastian Doll of the Institute of Metabolism and Cell Death, showed that the QIScope enables challenging live-cell measurements such as tracking of intracellular and extracellular vesicles and the dynamics of low-abundance proteins over long durations.
The QIScope expands the application spectrum of bioluminescence imaging and offers a valuable tool for a wide range of biological research, including studies of organoids, tissues, and cellular dynamics. As such, by overcoming the limitations of traditional methods, the QIScope enables researchers to delve deeper into the intricacies of cellular behavior and to gain new insights into fundamental biological processes.