Novel Imaging Method Helps Reveal Spheroid Cellular Dynamics

Researchers from Tohoku University in Japan have developed a new method to electrochemically monitor the respiratory activity of cultured cells.  Their use of electrochemiluminescence imaging to capture spheroid respiratory activity is described in a Biosensors and Bioelectronics paper.

For the study, spheroids were placed on a gold electrode dosed in luminescent solution. The team then applied stepped electric potential—the energy needed to convert oxygen—to the set up where the solution was then sensitized to produce luminescence, which is dependent on oxygen concentration. The spheroids glowed brightly, surrounded by a ring of darkness where oxygen concentration was low due to gas exchanges. This process was named potential step-based electrochemiluminescence (ECL) imaging.

"As living spheroids consume oxygen to produce energy, the respiratory activity was elegantly visualized by the distribution of luminescence around the spheroids," said Kaoru Hiramoto, first author of the paper.

The researchers used a digital camera to visualize multiple spheroids with a single shot, demonstrating both the high spatial resolution of their system, as well as the low background noise.

"The system offers high throughput analysis of spheroids, in addition to highly improving resolution of the images compared to conventional electrode array devices," said co-corresponding authors Kosuke Ino and Hitoshi Shiku. "The system offers novel insights into electrochemical devices and imaging systems for cell spheroids."

ECL imaging is still in the development phase. The team plans to improve the sensitivity and selectivity, as well as analyze other data that might be collected in the system, such as cellular metabolites attached to the electrode. They also plan to use the system to investigate more complicated biological models, as well as patient-derived cell spheroids.

"To the best of our knowledge, this is the first attempt to visualize the respiratory activity of spheroids by direct conversion of oxygen concentration into ECL imaging," Ino said. "The features of the proposed system—high spatial resolution with the ability for simultaneous imaging of multiple spheroids—are promising for transplantation research and drug screening utilizing cell spheroids."