Recyclable magnetic nanoparticles combined with TiO2 enrichment and “Off” to “On” SERS assay for sensitive detection of alkaline phosphatase

As an important enzyme in human tissues, abnormally alkaline phosphatase (ALP) is strongly associated with many diseases, particularly breast and prostate cancer. In this study, we proposed a rapid and sensitive surface-enhanced Raman scattering (SERS)-based biosensor for ALP detection. The biosensor utilized Fe3O4@Au@TiO2 nanoparticles (FAT NPs) as magnetic separation and enrichment materials to enrich grafted mediator Ag-4-mercaptophenylboronic acid (4-MPBA)-ascorbic acid 2-phosphate (AAP) NPs to form FAT-(AAP-4-MPBA-Ag) NPs, and 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) was used as the internal standard tag molecule to prepare Au@DTNB@Ag as the signal source. The phosphate group in AAP was cleaved by ALP to form ascorbic acid (AA), which acts as a receptor for the boric acid to adsorb the 4-MPBA-Au@DTNB@Ag NPs. When the switch was “Off” to “On”, the Au@DTNB@Ag NPs were used to significantly improve the sensitivity of the proposed SERS platform, enabling detection as low as 1.17U/L of target ALP with a good linear range (R 2 = 0.991) of 2–10 U/L. Furthermore, the platform successfully detected ALP from 2 % human serum. The recoveries were 99.5–106 %. In addition, FAT-(AAP-4-MPBA-Ag) NPs could be transformed into FAT NPs to achieve recyclability by ultrasonication in acidic environments. Overall, this sensitive and fast SERS platform has promising potential for accurate and efficient identification of ALP from human serum.