A SERS-based lateral flow assay biosensor for quantitative and ultrasensitive detection of interleukin-6 in unprocessed whole blood

Abstract Detection of a very low amount of cytokines such as interleukin-6 (IL-6) in clinical fluids such as blood is important in biomedical research and clinical applications. A surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) is developed for the quantitative analysis of IL-6. The Raman reporter 5,5′-dithiobis-2-nitrobenzoic acid (DTNB) on gold nano shell with a silica core was employed as the SERS tags. They are shown to perform much better than colloidal gold in LF strips. The IL-6 protein can be detected by this method with very low detection limits by monitoring the intensity of the characteristic Raman peak of the IL-6-conjugated SERS tags at 1332 cm⁻ 1 . Under optimized conditions, the assay works in the 1 pg/mL to 1 μg/mL IL-6 concentration range, and the detection limit is as low as 1 pg/mL in PBS, 5 pg/mL in unprocessed whole blood. This is lower by a factor of 3 compared to colorimetric or fluorimetric methods. The performance of SERS LFA was demonstrated by detection of IL-6 in unprocessed whole blood with comparable performance of the conventional enzyme-linked immunosorbent assay (ELISA).