Abstract: A DNA-based nanosensor system performs photoacoustic detection of cytokines. Cytokine receptors and a photoacoustic reporter dye are used in the nanosensor for cytokine detection, which can be reversible, and can be performed continuously, in vivo, in real time. Upon receptor binding to the cytokine, the DNA structure of the nanosensor closes to induce controlled dye stacking for photoacoustic application/interrogation, resulting in an increase in photoacoustic signal in the presence of the detected cytokine. The open or closed state of the sensor can be determined through differential signals as detected with photoacoustic imaging. A system using the nanosensor performs simultaneous multiplexed cytokine imaging, in the form of an inline and removable system paired with a clinical photoacoustic instrument. Cytokines can be detected in animal research use and in human point-of-care use.