Integration of blood separation and multiple-cytokine detection using a combined paper centrifugation–SERS immunoassay method

Abstract

Excellent detection capability, a simple assay procedure, and easy device acquisition are three key factors to analyze biomarkers for disease diagnosis using a point-of-care device in resource-limited settings or in emergency situations. However, constructing a platform with the simultaneous presence of these factors to sense multiple biomarkers remains a challenge. In the spirit of “frugal science”, a simple method is developed by combining a low-cost portable paper centrifuge with surface-enhanced Raman scattering (SERS) immunoassay for sample pretreatment and multiple-cytokine (IL-6, IL-1, and TNF-α) detection. The paper centrifuge can achieve rapid blood separation as a commercial centrifuge and also concentrate sandwich immune composites to generate abundant hot spots, thus enhancing the SERS signal. By analyzing three prospective cytokines (IL-6, IL-1, and TNF-α) closely related to tumors, the combined paper centrifugation–SERS immunoassay method realizes sensitive assays with detection limits down to 0.86, 0.42 and 0.22 pg/mL. Meanwhile, the proposed approach possesses capabilities of specific recognition and accurate quantitative detection for three cytokines in serum. Hence, the constructed multifunctional SERS platform is expected to be applied in the development of decentralized and battery-free diagnostic devices in facility-limited areas and field settings.