Ultrasensitive SERS detection of cytokines through specific binding and multiple reporter molecules.

Interleukins (IL) play a vital part in molecular recognition as well as immune response, and their excessive or inappropriate production can lead to inflammatory and cardiovascular diseases, etc., which are harmful to human physical and mental health. Thus, there is a pressing need to develop a strategy for the rapid and highly sensitive detection of such low concentration substances. In this study, we developed a Surface enhanced Raman spectroscopy (SERS) immunosensor for qualitative and quantitative analysis of multiple cytokines (IL-1, IL-4 and IL-6). Three Raman reporters were modified on gold nanoparticles and coupled with corresponding antibodies to form immunoprobes. The silver nanospace folded rods were prepared by tilted angle deposition technique, connected with antibodies to form an immunosensor. When the target antigen appeared on the immunosensor, it would specifically bind with the antibody to form a "sandwich" structure. Respectively, the detection limits of IL-6, IL-1 and IL-4 were 1.00 pg/mL, 0.93 pg/mL and 1.00 pg/mL. The three inflammatory factors were successfully distinguished and predicted by machine learning. In addition, we detected and calculated the recovery of IL-6 cytokines in saliva samples. The method can achieve quantitative detection and qualitative differentiation of target detectors in a wide concentration range. Meanwhile, it has the advantages of rapidity, simplicity and high specificity, which has a broad application prospect in biomedical field.