The first step of the scientific method is also the most important: observation. Yet this can often be deceptively difficult. In no field is this truer than biology, where one must be able to observe the actions of any given cell in a vast population. Scientists generally use microscopes with either a wide field or narrow zoom, but this creates a trade-off. To demonstrate this, imagine you are using your cell phone to take a picture. You can zoom in over a small area to see a single object, but that will limit your sight over the rest of the field. You can zoom out to get more in frame, but you won’t be able to see any one particular object very well. This is the struggle traditional microscopes give researchers attempting to observe cells. Researchers need to see a great many cells with a high degree of clarity, yet most technologies offer only one or the other: a few cells in high definition or a wide field of view.

Yang Liu and Hongqiang Ma

This was the issue that bioengineering professors Yang Liu, a Cancer Center at Illinois (CCIL) member, and Hongqiang Ma set out to solve. They invented a solution with affordable parts and named it the Omni-Mesoscope. This device has the rare ability to see many cells with clarity. “The system captures a large number of images like Google Earth,” explains Yang, “examining the details of sub-cellular structure within each cell across large areas. This represents a significant advancement in the ability to observe cellular processes at a high spatial and temporal resolution, without the traditional trade-offs.”

The Omni-Mesoscope works by blending two technologies from different disciplines. It uses an off-the-shelf macro lens, originally designed for a stereoscope, with a large-format camera traditionally used in astronomy. This makes the Omni-Mesoscope not only effective, but affordable, and therefore accessible to researchers worldwide. The Omni-Mesoscope is also multi-functional, combining label-free quantitative phase imaging with high-content fluorescence microscopy.

Schematics of the Omni-Mesoscope system

The Omni-Mesoscope allowed observation of important behaviors of drug resistant cancer cells, such as polyploid formation and cell cannibalism. Polyploid cells in particular play a critical role in understanding drug resistance in chemotherapy because cells use polyploid formation as a survival strategy during chemotherapy. The wide field of view enabled the team to look for cells exhibiting these behaviors over an extensive cell population, allowing for the detection of more potential events. Such a system also helps generate a massive dataset for developing artificial intelligence models aimed at predicting cell behaviors. It will eventually be used to better predict how specific tumors will react to drug therapies, paving the way for more personalized and effective cancer treatments.

The potential applications of the Omni-Mesoscope are vast. Due to its ability to monitor cellular dynamic and sub-cellular morphology at high resolutions, the device could be used for large-scale drug screening. Yang explains, “The response of cancer cells to chemotherapy drugs is very heterogeneous. Some cells may die, while others may use various strategies to evade the drug’s effects, displaying a wide range of cellular responses and morphologies. The ability of the Omni-Mesoscope to monitor all cells simultaneously becomes crucial when studying these responses.” Other potential applications include examining neurons, monitoring stem cell function, and 3D profiling of tissues in-vivo imaging.

Yang ended the interview with a call for collaboration. “I invite researchers both from our Illinois campus and across the country to explore collaboration opportunities with us. We are committed to fostering partnerships that enhance the development and application of label-free and multiscale imaging techniques.”

 

Editor’s Notes:

The original story, written by Ben Libman, can be found here.

You can see the full paper here.