EPFL researchers use nanoplasmonic techniques (Nanoplasmonic imaging reveals protein secretion in real time) to observe the real-time production of cellular secretions, including proteins and antibodies; advances that may contribute to the development of cancer treatments, vaccines and other treatments.
Secretions such as proteins, antibodies and neurotransmitters play an important role in the immune response, metabolism and communication between cells. Understanding cellular secretions is important for developing treatments for diseases, but current methods can only predict the amount of secretions, without details about when and where they are produced.
Today, researchers from the BIONanophotonic Systems Laboratory (BIOS) of the Faculty of Engineering Sciences at the University of Geneva have developed a new imaging system (Nanoplasmonic imaging reveals protein secretion in real time) that provides a four-dimensional view of cellular secretion in space and time. By placing individual cells in microscopic wells inside a nanostructured gold chip, and causing a phenomenon called plasmon resonance on the chip, they are able to charting secretions as they are produced, while observing cell shape and movement.
Because it provides unprecedented detail of cell function and communication, scientists believe that their method, recently published in Nature Biomedical Engineering, has “extreme” potential for drug development and basic research. “An important part of our work is that it allows us to analyze individual cells in large production. The collective pattern of responses of many cells does not reflect their diversity… and in biological systems, all different, from the immune response to cancer cells. That is why cancer is so difficult to treat,” says BIOS manager Hatice Altug.
A million senses
At the heart of the scientists’ system is a 1 cm2 nanoplasmonic chip made up of millions of tiny holes and hundreds of cells for each cell. The chip consists of nanostructured gold particles coated with a fine polymer mesh. Each cell is filled with cells to keep cells alive and healthy during painting. “The secrets of the cell are like the words of the cell: they spread quickly in time and space to connect with other cells. Our technology captures the different points in the order where and where the “words” is underway, says BIOS PhD student and first author Saeid Ansaryan. The nanoplasmonic part is involved because of the light that causes the gold electrons to move. The nanostructure is designed so that only certain wavelengths can penetrate it. When something – such as protein secretion – acts on the surface of the chip to change the light passing through it, the spectrum changes. CMOS (Metal Oxide Semiconductor) image sensors and generators convert this change into energy changes in CMOS pixels. “The beauty of our device is based on the fact that the nanoholes distributed over the entire surface transform any point into a tactile object. This allows us to see the spatial pattern of proteins released regardless of the cell’s location,” Ansaryan explains. The process allowed scientists to gain insight into two important cell processes – cell division and cell death – and to breed strong B cells from human donors that secrete antibodies.
“We saw cell contents released during two types of cell death, apoptosis and necroptosis. In the latter, the content is transferred in an asymmetrical chip, resulting in an image signature or fingerprint. “This has never been demonstrated before at the level of a single cell,” says Altug.
Cell Fitness Research
Since this method washes cells with nutrients and does not require the toxic fluorescent markers used by other imaging technologies, the cells being studied can recover quickly. This gives this system great potential to develop drugs, vaccines and other treatments; for example, to help researchers understand how cells react to different treatments at an individual level. “Since the quantity and order of the secret produced by the cell is an indicator of its overall effectiveness, we can also imagine a rapid immunotherapy where you examine the cells that fight immune system to identify the most effective ones, and create compounds of these cells,” says Ansaryan.
Source: EPFL
