Researchers at the University of Geneva have developed a novel optical imaging approach that provides a four-dimensional view of cell secretions in real-time, including their spatial and temporal dynamics.
By using a nanostructured gold-plated chip and inducing plasmonic resonance in individual cells, this breakthrough method allows for mapping secretions as they are being produced, while also observing cell shape and movement. Unlike current methods that only report secretion quantity, this approach offers unprecedented insights into cellular function and communication, with potential applications in pharmaceutical development and fundamental research. By accounting for cellular heterogeneity and enabling high-throughput screening of individual cells, this approach has implications for understanding immune responses, metabolism, and disease treatments.
Geneva researchers develop optical imaging approach for real-time, four-dimensional view of cell secretions. Nanostructured gold-plated chip induces plasmonic resonance, enabling mapping of secretions during production, while observing cell shape and movement.
Scientists believe their recently published method in Nature Biomedical Engineering, which provides unprecedented detail on cell function and communication, has "tremendous" potential for pharmaceutical development and fundamental research. By allowing high-throughput screening of individual cells, the method addresses the heterogeneity of biological systems, from immune responses to cancer cells, providing valuable insights for more effective cancer treatment, according to BIOS head Hatice Altug.
A million sensing elements
The scientists' method centers around a nanoplasmonic chip, just 1 cm2 in size, containing millions of tiny holes and individual cell chambers. Made of nanostructured gold and covered with a thin polymer mesh, each chamber is filled with cell medium to maintain cell viability during imaging.
This technology allows for capturing the dynamic spread of cell secretions, often likened to the words of cells, in terms of their location and distance, revealing important heterogeneity, according to BIOS PhD student and first author Saeid Ansaryan.
The nanoplasmonic aspect of the method involves the use of a light beam that induces oscillation of gold electrons on the chip's surface. The nanostructure of the chip is designed to selectively allow certain wavelengths of light to penetrate it. When cellular events, such as protein secretion, occur on the chip's surface and alter the transmitted light, the spectrum shifts. This shift is then detected by a CMOS image sensor and an LED, which translate it into intensity variations on the CMOS pixels.
Ansaryan explains that the unique feature of their apparatus is that the nanoholes distributed across the entire chip surface turn every spot into a sensing element. This enables observation of spatial patterns of released proteins regardless of the position of the cell, allowing for detailed mapping of cell secretions in space and time.
The new imaging approach has enabled the researchers to observe and study crucial cellular processes such as cell division and cell death. They were able to visualize the content released by cells during two different types of cell death, apoptosis and necroptosis. In necroptosis, the content was released in an asymmetric burst, resulting in a unique image signature or fingerprint. This groundbreaking observation of cell death at the single-cell level has never been achieved before, highlighting the unprecedented capabilities of the developed method in providing detailed insights into cellular events.
Screening for cell fitness
The non-toxic nature of the imaging method, which does not require the use of fluorescent labels and allows the cells to be bathed in a nutritious cell medium, makes it possible to easily recover the cells after imaging. This feature of the method has tremendous potential for use in pharmaceutical drug development, vaccine research, and other treatments. For example, the method could be used to understand how individual cells respond to different therapies, allowing for personalized treatment approaches. Additionally, the amount and pattern of secretions produced by cells can be used as an indicator of their effectiveness, which opens up possibilities for screening patient immune cells to identify the most effective ones and creating a colony of those cells for immunotherapy applications. This highlights the promising applications of this novel imaging approach in advancing therapeutic development and personalized medicine.
Ansaryan, S., et al. (2023). High-throughput spatiotemporal monitoring of single-cell secretions via plasmonic microwell arrays. Nature Biomedical Engineering. doi.org/10.1038/s41551-023-01017-1