Novel imaging approach can map cell secretions in four dimensions

New Delhi: Researchers have developed a novel optical imaging approach that can map four dimensional view of cell secretions in space and time as they are being produced, while observing cell shape and movement. The researchers at the University of Geneva, Switzerland, said that their method provides an unprecedentedly detailed view of how cells function and communicate and thus, had "tremendous" potential for pharmaceutical development as well as fundamental research.

Their method is published in the journal Nature Biomedical Engineering. Understanding cell secretions such as proteins, antibodies, and neurotransmitters, which play an essential role in immune response, metabolism, and communication between cells, is key for developing disease treatments.

However, current methods are capable of reporting only the quantity of secretions with no details about the when and the where.

"Collective measurements of the average response of many cells do not reflect their heterogeneity...and in biology, everything is heterogeneous, from immune responses to cancer cells. This is why cancer is so hard to treat," said Hatice Altug, head of BIOnanophotonic Systems Laboratory, School of Engineering, University of Geneva.

By placing individual cells into microscopic wells in a nanostructured gold-plated chip, and then inducing a phenomenon called plasmonic resonance on the chip's surface, they are able to map four dimensional view of cell secretions while being produced.

Plasmonic resonance is when electrons in a thin metal sheet become excited by light incident on it at a particular angle, and then travel parallel to the sheet.

The researchers' method consists of a chip composed of millions of tiny holes, and hundreds of chambers for individual cells filled with a cell medium to keep cells healthy and alive during imaging. The chip is made of a nanostructured gold substrate covered with a thin polymer mesh.

When something like protein secretion occurs on the chip's surface to alter the light passing through, the spectrum shifts. A Complementary Metal Oxide Semiconductor (CMOS) image sensor and a light-emitting diode (LED) translate this shift into intensity variations on the CMOS pixels. CMOS is a semiconductor technology used in most of today's chips.

"The beauty of our apparatus is that the nanoholes distributed across the entire surface transform every spot into a sensing element. This allows us to observe the spatial patterns of released proteins irrespective of cell position," said BIOS PhD student and first author Saeid Ansaryan.

The method has allowed the scientists to get a glimpse of two essential cellular processes - cell division and cell death - and to study delicate antibody-secreting human donor B-cells.

"We saw the cell content released during two forms of cell death, apoptosis and necroptosis. In the latter, the content is released in an asymmetric burst, resulting in an image signature or fingerprint. This has never before been shown at the single-cell level," said Altug.