Highly sensitive and reproducible SERS substrate based on ordered multi-tipped Au nanostar arrays for the detection of myocardial infarction biomarker cardiac troponin I

Acute myocardial infarction (AMI) is a severe cardiovascular disease, for which early diagnosis is critical for reducing mortality and improving patient outcomes. Cardiac troponin I (cTnI) is widely recognized as the "gold standard" biomarker for AMI due to its high specificity and sensitivity. The concentration of cTnI correlates directly with different stages of AMI. Therefore, the accurate detection of cTnI concentration is of paramount importance. However, the low concentration of cTnI in biological fluids requires ultrasensitive detection methods. In this study, we developed a sandwiched surface enhanced Raman scattering (SERS)-based biosensor composed of SERS-immune substrate, target antigen, and SERS nanotags and realized sensitive and accurate detection of cTnI. The SERS-immune substrate features an ordered, multi-tipped monolayer of Au nanostars fabricated using a three-phase interfacial self-assembly method and 4-(2-hydroxyerhyl)piperazine-1-erhanesulfonic acid (HEPES) buffer modification. Compared to Au nanosphere SERS substrates, the Au nanostar SERS substrates exhibited about a 3-fold increase in Raman enhancement and demonstrated good uniformity and batch stability. This novel SERS detection platform, leveraging dual plasmonic enhancement from both the SERS-immune substrate and SERS nanotags, achieves detection of cTnI with a limit of detection (LOD) as low as 9.09 pg mL^-1 and a relative standard deviation (RSD) as low as 11.24%. Thus, the Au nanostar SERS substrates developed in this study demonstrate significant potential for rapid and accurate detection of cTnI.