Triple-Band NIR-II Fluorescent Nanoprobe-Based Lateral Flow Immunoassay Biosensor for Point-of-Care Testing of Acute Kidney Injury

Rapid and accurate diagnosis of early-stage acute kidney injury (AKI) is critically important for improving patients’ short-term survival rates and reducing the risk of long-term kidney disease. As a prominent, fast, quantitative diagnostic tool, the fluorescent lateral flow immunoassay (LFA) has been widely applied for precise clinical diagnostics. Nevertheless, the conventional fluorescent (FL) probes are hampered by the autofluorescence interference, which constrains the sensitivity of LFA. Herein, we first designed and synthesized efficient FL nanoprobes (RENPs) with three distinct FL emission peaks across the NIR-II subregions: NIR-II (900–1100 nm), NIR-IIa (1300–1400 nm), and NIR-IIb (1500–1700 nm), and the related design strategy and the luminous mechanism were also fully discussed. Benefiting from the synergistically enhanced FL signals, low autofluorescence, and excellent photostability of the triple-band RENP probes, an advanced NIR-II LFA biosensor has been developed for the detection of Cystatin C (CysC), an AKI-sensitive biomarker. The proposed NIR-II LFA biosensor showed good linearity in the range of 0.42–7.70 mg L –1, and the limit of detection (LOD) was as low as 0.34 mg L –1, which is 3.2 times lower than the clinical cutoff value. Furthermore, it also exhibited excellent correlation ( R 2 = 0.9959, n = 60) with commercial diagnostic kits (LETIA method) in clinical practicality. Overall, the developed NIR-II LFA biosensor employing the triple-band RENP probes demonstrates enhanced detection performance, encompassing high sensitivity, accuracy, and specificity, while simultaneously having characteristics of rapidity, simplicity, and low cost, which holds high potential for the early diagnosis of AKI in POCT.