Cellular secretions such as proteins, antibodies, and neurotransmitters play an essential role in the immune response, metabolism, and communication between cells. Understanding cell secretions is key to developing disease treatments, but current methods can only report the amount of secretions, without any details about when and where they are produced.
Now, researchers at the BIOnanophotonic Systems (BIOS) Laboratory at the Faculty of Engineering and the University of Geneva have developed a new optical imaging approach that offers a four-dimensional view of cell secretions in both space and time. . By placing individual cells in microscopic wells on a nanostructured gold-plated chip and then inducing a phenomenon called plasmonic resonance on the surface of the chip, they can map the secretions as they are produced, while observing the shape and movement of the cells.
By providing an unprecedented detailed view of how cells work and communicate, the scientists believe their method, recently published in Nature Biomedical Engineeringit has “tremendous” potential for pharmaceutical development as well as fundamental research.
“A key aspect of our work is that it allows us to examine cells individually with high throughput. Collective measurements of the average response of many cells do not reflect their heterogeneity…and in biology, everything is heterogeneous, from immune responses to cells That’s why cancer is so difficult to treat,” says Hatice Altug, head of BIOS.
One million sensor elements
At the heart of the scientists’ method is a 1 cm2 nanoplasmonic chip made up of millions of tiny holes and hundreds of chambers for individual cells. The chip is made of a nanostructured gold substrate covered with a fine polymer mesh. Each chamber is filled with cell medium to keep cells alive and healthy during imaging.
“Cellular secretions are like the words of the cell: they spread dynamically in time and space to connect with other cells. Our technology captures the key heterogeneity in terms of where and how far these ‘words’ travel,” says the student. of BIOS PhD and first author Saeid Ansaryan.
The nanoplasmonic part enters thanks to a beam of light, which causes the gold electrons to oscillate. The nanostructure is designed so that only certain wavelengths can penetrate it. When something, like protein secretion, occurs on the surface of the chip to alter the light that passes through, the spectrum changes. A CMOS (Complementary Metal Oxide Semiconductor) image sensor and LED translate this change into intensity variations in the CMOS pixels.
“The beauty of our apparatus is that the nanoholes distributed over the entire surface transform each point into a sensing element. This allows us to observe the spatial patterns of the released proteins regardless of the position of the cell,” says Ansaryan.
The method has allowed scientists to glimpse two essential cellular processes, cell division and cell death, and to study delicate antibody-secreting B cells from human donors.
“We saw how cell contents were released during two forms of cell death, apoptosis and necroptosis. In the latter, the contents are released in an asymmetric burst, resulting in an image signature or fingerprint. This never it had previously been shown in a single cell.” level,” says Altug.
Cell fitness detection
Because the method bathes cells in a nutritive cell medium and does not require the toxic fluorescent labels used by other imaging technologies, the cells under study can be easily recovered. This gives the method great potential for use in the development of drugs, vaccines, and other treatments; for example, to help researchers understand how cells respond to different therapies on an individual level.
“Since the amount and pattern of secretions produced by a cell are a proxy for its overall efficacy, we could also envision immunotherapy applications in which a patient’s immune cells are examined to identify those that are most effective and then it creates a colony of those cells,” says Ansaryan.