MSGID: 1:317/3 643633f7   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Nanoplasmonic imaging reveals real-time protein secretion    
      
     Date:   
         April 11, 2023   
     Source:   
         Ecole Polytechnique Fe'de'rale de Lausanne   
     Summary:   
         Researchers have used a nanoplasmonics approach to observe the   
         real-time production of cell secretions, including proteins and   
         antibodies; an advancement that could aid in the development of   
         cancer treatments, vaccines, and other therapies.   
      
      
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   FULL STORY   
   ==========================================================================   
   Cell secretions like proteins, antibodies, and neurotransmitters play   
   an essential role in immune response, metabolism, and communication   
   between cells.   
      
   Understanding cell secretions is key for developing disease treatments,   
   but current methods are only able to report the quantity of secretions,   
   without any detail as to when and where they are produced.   
      
      
   ==========================================================================   
   Now, researchers in the BIOnanophotonic Systems Laboratory (BIOS) in   
   the School of Engineering and at the University of Geneva have developed   
   a novel optical imaging approach that gives a four-dimensional view of   
   cell secretions in both space and time. 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 secretions as they are being produced, while observing cell   
   shape and movement.   
      
   As it provides an unprecedentedly detailed view of how cells function and   
   communicate, the scientists believe their method, recently published   
   in Nature Biomedical Engineering, has "tremendous" potential for   
   pharmaceutical development as well as fundamental research.   
      
   "A key aspect of our work is that it allows us to screen cells   
   individually in a high-throughput fashion. 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," says BIOS head   
   Hatice Altug.   
      
   A million sensing elements At the heart of the scientists' method is a 1   
   cm2nanoplasmonic chip composed of millions of tiny holes, and hundreds   
   of chambers for individual cells. The chip is made of a nanostructured   
   gold substrate covered with a thin polymer mesh.   
      
   Each chamber is filled with a cell medium to keep the cells alive and   
   healthy during imaging.   
      
   "Cell secretions are like the words of the cell: they spread out   
   dynamically in time and space to connect with other cells. Our technology   
   captures key heterogeneity in terms of where and how far these 'words'   
   travel," says BIOS PhD student and first author Saeid Ansaryan.   
      
   The nanoplasmonics part comes in thanks to a light beam, which causes   
   the gold electrons to oscillate. The nanostructure is engineered so   
   that only certain wavelengths can penetrate it. When something --   
   like protein secretion - - occurs on the chip's surface to alter the   
   light passing through, the spectrum shifts. A CMOS (Complementary Metal   
   Oxide Semiconductor) image sensor and an LED translate this shift into   
   intensity variations on the CMOS pixels.   
      
   "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," says 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," Altug says.   
      
   Screening for cell fitness Because the method bathes the cells in a   
   nutritious cell medium, and does not require the toxic fluorescent labels   
   used by other imaging technologies, the cells under study can easily be   
   recovered. This gives the method great potential for use in developing   
   pharmaceutical drugs, vaccines, and other treatments; for example, to   
   help researchers understand how cells respond to different therapies at   
   the individual level.   
      
   "As the amount and pattern of secretions produced by a cell are a proxy   
   for determining their overall effectiveness, we could also imagine   
   immunotherapy applications where you screen patient immune cells to   
   identify those that are most effective, and then create a colony of   
   those cells," says Ansaryan.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Stem_Cells # Lymphoma # Immune_System # Lung_Cancer #   
                   Brain_Tumor # Nervous_System # Cancer # Sickle_Cell_Anemia   
       * RELATED_TERMS   
             o Stem_cell_treatments o Adult_stem_cell o   
             Monoclonal_antibody_therapy o Stem_cell o Colorectal_cancer   
             o Cancer o Protein o DNA   
      
   ==========================================================================   
   Story Source: Materials provided by   
   Ecole_Polytechnique_Fe'de'rale_de_Lausanne. Original written by Celia   
   Luterbacher. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Saeid Ansaryan, Yen-Cheng Liu, Xiaokang Li, Augoustina Maria   
      Economou,   
         Christiane Sigrid Eberhardt, Camilla Jandus, Hatice Altug. High-   
         throughput spatiotemporal monitoring of single-cell secretions via   
         plasmonic microwell arrays. Nature Biomedical Engineering, 2023;   
         DOI: 10.1038/s41551-023-01017-1   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230411105840.htm   
      
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