A sensitive sequential 'on/off' SERS assay for heparin with wider detection window and higher reliability based on the reversed surface charge changes of functionalized Au@Ag nanoparticles

A sequential 'on/off' dual mode SERS assay platform for heparin with wider detection window and higher reliability is constructed based on electrostatic forces, in which the highly protonated chitosan encapsulated p-Mercaptobenzoic acid coated Au@Ag core-shell nanoparticles undergo sequential aggregation/segregation upon the additive of heparin with a limit of detection of 43.74 ng/mL (5.69 U/mL) and a continuous concentration range of 50-800 ng/mL (6.5-104 U/mL), which are lower in sensitivity and wider in detection window than the most reported assay for heparin. Remarkably, the latter declined window over a range of 350-800 ng/mL in contrast, which has not reported before, is extremely important in reliable and practical assay of heparin.