“…The mean CRP level in the blood under physiological conditions is 0.1–10 mg/L but will elevate to thousand times during cell damage or inflammation, and the half-life of CRP in serum is about 19 h. Rapidly and precisely, detecting the changes in CRP concentration is vital for monitoring the disease progresses and prognosis. − A diverse range of methodologies have been developed for CRP sensing, including fluorescence, SPR, , SERS, quantum dots, , and electrochemical and optical approaches. − They are all generally important and sensitive for the CRP test with a low detection limit, while these design strategies are generally indirect measurements combined with specific interactions between CRP and aptamer or antibody. ,− Recently, Paolo Actis’s group employed the DNA origami nanopore for CRP sensing via aptamer binding, and the modeling of CRP in the microchannel has been done as well . Unlike the reported work, we introduced a nanopore-based technique for direct label-free identification of the conformations of CRP and its aptamer-binding complex, at the single-molecule level with a detection limit as low as 0.3 ng/μL.…”