Enzyme-free optical detection of uric acid using corona phase molecular recognition in near-infrared fluorescent single-walled carbon nanotubes

Real-time monitoring of uric acid (UA) is essential for preventing and managing chronic diseases. While enzymatic methods are the clinical standard, they are limited by slow reaction times and strict environmental requirements. Enzyme-free sensors offer alternatives but face challenges in analyte selectivity and clear optical signal readouts. In this study, we developed an enzyme-free UA detection method based on corona phase molecular recognition (CoPhMoRe). We developed a near-infrared (NIR) optical nanosensor by functionalizing single-walled carbon nanotubes (SWCNTs) with single-stranded DNA (ssDNA). Through high-throughput screening, we identified the optimal corona of the sensor as (AAT)₁₀/SWCNT and further optimized it with studying the pH effects to account for the natural pH variation in urine. To facilitate point-of-care (POC) application, we integrated the corona nanosensor with an optical paper strip, achieving a rapid and intense turn-on NIR response up to 4 times stronger when exposed to urine samples containing UA concentrations ranging from 5.7 to 500 μM. Moreover, the corona nanosensor-integrated paper strip exhibited reliable performance even under harsh conditions of 70% relative humidity and 40 °C. This study demonstrates the enzyme-free UA detection capability of SWCNT-based CoPhMoRe in complex biofluids, establishing its potential for future application as an optical test strip in POC diagnostics.