Researchers at École Polytechnique Fédérale de Lausanne (EPFL) have unveiled a groundbreaking imaging method that utilizes a single-photon avalanche diode (SPAD) camera. This cutting-edge technology allows researchers to measure thousands of molecules in less than a minute. It’s a big improvement over the current methods, which can take an hour to come up with worthy results.
The SPAD camera is made up of close to a million tiny sensors, called SPADs, each able to individually register the impact of a single photon. The SPAD camera has an extraordinary ability to record, process and deliver information at record speed. This, in turn, opens up new opportunities for researchers to probe complex dynamic phenomena across a wide range of molecules more easily.
Transforming Molecular Analysis
Historically, molecular characterization methods have been constrained by small sample sizes and extended turnaround times. The introduction of the SPAD camera system has turned this landscape upside down. With added speed and efficiency of the SPAD camera, researchers can now rapidly gain resolution-rich insights into molecular behavior. This is particularly advantageous for comparing non-homogeneous large sample sizes.
Additionally, the new process uses a novel, multi-angle approach to image capture. It does this by capturing images right after a molecule is excited, and then again only a few nanoseconds after. This approach synchronizes the camera’s frame rate with the timing of the laser pulses. Consequently, it allows for a much clearer comparison and modeling of interactions between molecules.
Nathan Ronceray, the lead researcher on the project, stressed how crucial this synchronization was, saying,
“For instance, the frequency with which the original camera captured images didn’t match the pace of the laser pulses.”
With it, scientists can snap a picture one hundred times per second. With this technique, they are now able to measure the fluorescence lifetime of molecule pairs, providing important information about their spatial relationships at very small scales down to just a few nanometers.
Enhancing Experimental Capabilities
This new measure of creating tumor maps comes with one important benefit. It has the ability to improve multiplexed analyses, measuring a plethora of different parameters in a single sample simultaneously. This capability allows researchers to gain comprehensive insights into complex biological interactions and molecular behaviors that were previously challenging to study.
This approach might be less precise than conventional methods, but it is uniquely advantageous. Its unprecedented speed and broad multiplexing capability, its ability to detect a lot of different molecules at the same time, make it a powerful new tool. As Prof. Aleksandra Radenovic remarked,
“Our method is slightly less accurate than conventional ones but it is faster and can detect an unprecedented number of molecules at once.”
This new, creative approach looks to an imaging technique that’s sat under the radar for more than 35 years. It’s powered by Förster resonance energy transfer (FRET), a phenomenon in which energy transferred between two light-sensitive molecules. Bringing the principles of FRET into the SPAD camera system significantly extends its use as a tool for examining detailed molecular interactions.
Collaborative Efforts in Research
Their successful development of this multifaceted imaging method required extensive collaboration between the Chen, Yang, and Jain research groups. This allowed scientists to work in close collaboration with EPFL’s Laboratory for Biomolecular Modeling, headed by Matteo Dal Peraro. In addition, they collaborated with the research group led by Guillermo Acuña at the University of Fribourg. That multi-disciplinary collaboration has made for robust intellectual creativity and cross-fertilization to the collective benefit of the research.
Radenovic was optimistic about the possibilities of their discovery, saying that the future uses for this technology are unlimited.
“As with any technique, it is difficult to predict its full potential: it will probably be limited only by imagination.”
This single shot SPAD camera approach is able to rapidly characterize thousands of molecules. This capability offers a transformational frontier to disciplines such as materials science, drug discovery and biological research. Future studies have important implications. Researchers are exploring some fascinating, far-reaching potential applications for this breakthrough imaging technology.
