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Local extracellular signaling is central for cellular interactions and organizations. We report a novel sensing technique to interrogate extracellular signaling at the subcellular level. We developed an in situ immunoassay based on giant optical enhancement of a tunable nano-plasmonic-resonator array fabricated by nanoimprint lithography. Our nanoplasmonic device significantly increases the signal-to-noise ratio to enable the first time submicrometer resolution quantitative mapping of endogenous cytokine secretion. Our study shows a markedly high local interleukin-2 (IL-2) concentration within the immediate vicinity of the cell which finally validates a decades-old hypothesis on autocrine physiological concentration and spatial range. This general sensing technique can be applied for a broad range of cellular communication studies to improve our understanding of subcellular signaling and function.

Subcellular Resolution Mapping of Endogenous Cytokine Secretion by Nano-Plasmonic-Resonator Sensor Array