Sensitive label-free SERS detection of cTnI enabled by epitope molecularly imprinted polymer based on host-guest interaction of cyclodextrin and ferrocene

Cardiac troponin I (cTnI) is a key disease biomarker for acute myocardial infarction; therefore, it is crucial to selectively enrich cTnI in complex samples and accurately detect it. Molecularly imprinted polymers combined with surface-enhanced Raman scattering (MIP-SERS) hold promise for applications in protein detection. However, the technology often suffers from low imprinting efficiency and detection complexity. Herein, we developed an epitope-oriented MIP based on host-guest interaction (hg-EMIP) between β- cyclodextrin and ferrocene, as well as constructed a novel hg-EMIP-label-free SERS assay. The template immobilization was achieved through host-guest recognition, followed by imprinted layer synthesis using multiple functional monomers. The resulting hg-EMIP exhibits high specificity toward cTnI, with superior imprinting factor and reusability. The developed hg-EMIP-label-free SERS assay enables sensitive and rapid detection of cTnI without extrinsic nanotags, possesses a wide linear range (10 −3 -10 3 ng/mL), and can be successfully used for the detection of cTnI in human serum samples. hg-EMIP is promising for the isolation of targets, and label-free SERS assay based on hg-EMIP is highly potential in the area of disease biomarker detection. • A novel EMIP based on host-guest interaction was designed for recognition of cTnI. • β- cyclodextrin/ferrocene host-guest interaction was employed to anchor epitopes. • hg-MIP exhibited high adsorption capacity, excellent selectivity, and sensitivity. • The hg-EMIP-label-free SERS assay displayed excellent detection performances.