Transporter-Mimicking MXene for Uric Acid Capture and Sensing in Biofluids

Uric acid (UA) is closely associated with a broad spectrum of metabolic diseases and neurodegenerative disorders, so its detection is crucial for disease diagnosis, staging, and therapeutic evaluation. However, the detection of UA in biofluids remains challenging because of its broad physiological concentration range, strong interference from coexisting species, and increasing requirement of decentralized point-of-care testing. Herein, we report an MXene-based biomimetic strategy by imitating the structure of human urate transporter 1 (URAT1) to realize highly selective, wide-range, and point-of-care detection of UA. The MXene was synthesized by a covalent interlayer reconstruction method, in which covalent bonds were introduced between nanosheets through nucleophilic substitution reaction with quaternary ammonium to precisely control the interlayer spacing, thus mimicking the binding pocket of URAT1. The surface was tailored to reproduce π-π stacking, hydrogen-bonding, and electrostatic interactions in URAT1 responsible for UA capture. This MXene can not only capture and enrich UA but also modulate its redox behavior, leading to accelerated reaction kinetics and amplified electrochemical response. As a result, the electrochemical detection yielded a high sensitivity, a wide linear range, a low detection limit, outstanding selectivity, and antimatrix interference ability. The biomimetic sensor was then integrated with a portable device for rapid and point-of-care detection of UA, realizing fingertip-blood testing at home for management of metabolic diseases, perioperative measurement in cerebrospinal fluid, blood and urine for disease diagnosis, and postoperative outcomes. We believe this biomimetic strategy can translate the concept of transporter-mediated molecular capture into high-performance molecular sensing.