2D Ti3C2Tx MXene nanozymes based electrochemical MicroRNA biosensor and application to early diagnosis of sepsis-associated acute kidney injury

Abstract MicroRNA detection-based molecular diagnostic methods offer a favorable pathway for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI), which is crucial for reducing mortality and improving patient outcomes. In this work, a highly sensitive electrochemical biosensor was fabricated for the determination of serum miR-452-5p, an emerging biomarker for SA-AKI, leveraging the novel Ti 3 C 2 T x MXene nanozymes and catalytic hairpin assembly isothermal amplification. Surprisingly, the two-dimensional Ti 3 C 2 T x MXene nanozymes demonstrated remarkable electro-catalytic activity towards choline, wihch was attributed to the strong adsorption interaction between the oxygen atoms on the Ti 3 C 2 T x MXene surface and the hydroxyl group of choline. Based on above-mentioned characteristic of Ti 3 C 2 T x MXene nanozymes, a cascading catalytic amplification strategy by integrating Ti 3 C 2 T x MXene with alkaline phosphatase using phosphorylcholine chloride as the substrate was designed, thereby achieving highly efficient electrochemical signal amplification. The electrochemical biosensing approach exhibited remarkable sensitivity for miR-452-5p detection, with a linear response over a concentration range from 0.1 fM to 10 nM and a low detection limit of 0.09 fM. Additionally, the developed electrochemical biosensor for direct serum miR-452-5p detection present a diagnostic efficiency of 96% in clinical samples analysis, highlighting its strong potential for the early detection and risk assessment of SA-AKI. Graphical Abstract