Metal Organic Frameworks Combining CoFe2O4 Magnetic Nanoparticles as Highly Efficient SERS Sensing Platform for Ultrasensitive Detection of N-Terminal Pro-Brain Natriuretic Peptide.

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been demonstrated to be a sensitive and specific biomarker for heart failure (HF). Surface-enhanced Raman spectroscopy (SERS) technology can be used to accurately detect NT-proBNP at an early stage for its advantages of high sensitivity, less wastage and time consumption. In this work, we have demonstrated a new SERS-based immunosensor for ultrasensitive analysis of NT-proBNP by using metal-organic frameworks (MOFs)@Au tetrapods (AuTPs) immobilized toluidine blue as SERS tag. Here, MOFs@AuTPs complexes were utilized to immobilize antibody and Raman probe for their excellent characteristics of high porosity, large surface area, and good biocompatibility which can obviously enhance the fixing amount of biomolecule. To simplify the experimental operation and improve the uniformity of the substrate, Au nanoparticles functionalized CoFe2O4 magnetic nanospheres (CoFe2O4@AuNPs) were further prepared to assemble primary antibody. Through sandwiched antibody-antigen interactions, the immunosensor can produce a strong SERS signal to detect NT-proBNP fast and effectively. With such design, the proposed immunosensor can achieve a large dynamic range of 6 orders of magnitude from 1 fg mL(-1) to 1 ng mL(-1) with a detection limit of 0.75 fg mL(-1). And this newly designed amplification strategy holds high probability for ultrasensitive immunoassay of NT-proBNP.