A new 3D imaging technique, which requires no dyes, can give high-resolution, 3D, quantitative imagery of cells and their internal structures — all with the use of 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 of University of Illinois researchers, 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,’ said Popescu. ‘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 behaviour.’

As it uses white light, WDT can observe cells in their natural state without exposing them to chemicals, UV 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 (e.g. speckles).

The 3D 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 3D rendering.

The greatest potential of WDT, according to the researchers, is the ability to study cells in three dimensions over time. Since the cells are not altered, they can be imaged repeatedly, allowing researchers a glimpse into the dynamics of a cell as it goes about its life, or as it is treated with a new drug.

‘As a cell grows we can see the change in all three dimensions,’ said Taewoo Kim, a graduate student and first author. ‘We can see the dynamics of the cell in 3D, which hasn’t been done in a quantitative manner. For example, we could see, in the span of a minute or over a cell’s lifetime, how it grows and how the things in the cell move around.’

WDT uses a component that adds onto a conventional phase contrast microscope, a common piece of equipment in biology labs, without altering the microscope itself. The researchers used conventional microscopes with the intention of making these new optics principles easily accessible for biologists. The researchers hope that this will allow rapid large-scale adoption of WDT, and Popescu founded a startup company, Phi Optics, to help achieve that goal.