University of Illinois researchers have developed a new imaging technique that needs no dyes or other chemicals, yet renders high-resolution, three-dimensional, quantitative imagery of cells and their internal structures using conventional microscopes and white light.
Called white-light diffraction tomography (WDT), the imaging technique opens a window into the life of a cell without disturbing it and could allow cellular biologists unprecedented insight into cellular processes, drug effects and stem cell differentiation.
The team, led by electrical and computer engineering and bioengineering professor Gabriel Popescu, published their results in the journal Nature Photonics. “One main focus of imaging cells is trying to understand how they function, or how they respond to treatments, for example, during cancer therapies,” Popescu said. “If you need to add dyes or contrast agents to study them, this preparation affects the cells’ function itself. It interferes with your study. With our technique, we can see processes as they happen and we don’t obstruct their normal behavior.”
Because it uses white light, WDT can observe cells in their natural state without exposing them to chemicals, ultraviolet radiation, or mechanical forces – the three main methods used in other microscopy techniques. White light also contains a broad spectrum of wavelengths, thus bypassing the interference issues inherent in laser light – speckles, for example.
The 3-D images are a composite of many cross-sectional images, much like an MRI or CT image. The microscope shifts its focus through the depth of the cell, capturing images of various focus planes. Then the computer uses the theoretical model and compiles the images into a coherent three-dimensional rendering.
See a video showcasing examples of the 3D images.
“With this imaging we can tell at what scale things within the cell are transported randomly and at what scale processes are actually organized and deterministic,” Popescu said. “At first glance, the dynamics looks pretty messy, but then you look at it – we stare at movies for hours and hours – and you realize it all makes sense. Everything is organized perfectly at certain scales. That’s what makes a cell alive. Randomness is just nature’s way to try new things.”
Next, the researchers hope to pursue cross-disciplinary collaborations to explore applications of WDT in biology as well as expansions of the imaging optics demonstrated in WDT. For example, they are using WDT to watch stem cells as they differentiate in hopes of better understanding how they turn into different cell types. Since stem cells are so sensitive, only a chemical-free, non-invasive, white-light technique such as WDT could be used to study them without adverse effects.