| Summary: | For the first time, a novel NiFe<sub>2</sub>O<sub>4</sub>/paper-based magnetoelastic (ME) biosensor was developed for rapid, sensitive, and portable detection of human serum albumin (HSA). Due to the uniquely magnetoelastic effect of NiFe<sub>2</sub>O<sub>4</sub> nanoparticles and the excellent mechanical properties of the paper, the paper-based ME biosensor transforms the surface stress signal induced by the specific binding of HSA and antibody modified on the paper into the electromagnetic signal. The accumulated binding complex generates a compressive stress on the biosensor surface, resulting in a decrease in the biosensor’s static magnetic permeability, which correlates to the HSA concentrations. To improve the sensitivity of the biosensor, the concentration of NiFe<sub>2</sub>O<sub>4</sub> nanofluid and the impregnated numbers of the NiFe<sub>2</sub>O<sub>4</sub> nanofluid-impregnated papers were optimized. The experimental results demonstrated that the biosensor exhibited a linear response to HSA concentrations ranging from 10 μg∙mL<sup>−1</sup> to 200 μg∙mL<sup>−1</sup>, with a detection limit of 0.43 μg∙mL<sup>−1</sup>, which is significantly lower than the minimal diagnosis limit of microalbuminuria. The NiFe<sub>2</sub>O<sub>4</sub>/paper-based ME biosensor is easy to fabricate, and allows the rapid, highly-sensitive, and selective detection of HSA, providing a valuable analytical device for early monitoring and clinical diagnosis of microalbuminuria and nephropathy. This study shows the successful integration of the paper-based biosensor and the ME sensing analytical method will be a highly-sensitive, easy-to-use, disposable, and portable alternative for point-of-care monitoring.
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