Development and evaluation of a gold nanourchin (GNU)-based sandwich architecture for SERS immunosensing in liquid

Nanosensors represent a class of emerging promising nanotools that can be used for the rapid, sensitive and specific detection of relevant molecules such as biomarkers of cancer or other diseases. The sensing platforms that rely on the exceptional physical properties of colloidal gold nanoparticles have gained a special attraction and various architectural designs were proposed with the aim of rapid and real-time detection, identification and monitoring of the capturing events. Moreover, biomarker sensing in liquid samples allows a more facile implementation of the nanosensors by circumventing the need for invasive practices such as biopsies, in favor of non-invasive investigations with potential for use as point-of-care assays. Herein, we propose a sandwich-type surface enhanced Raman scattering (SERS) immuno-nanosensor which is aimed for detecting and quantifying Carcinoembryonic antigen-related cell adhesion molecule 5 (CEA-CAM5), a protein involved in intercellular adhesion and signaling pathways that acts as a tumor marker in several types of cancer. For constructing the proposed system, colloidal gold nano spheres (GNS) and gold nano-urchins (GNU) were chemically synthesized, labeled with SERS active molecules, conjugated with polymers, functionalized with antibodies as capturing substrates and tested in two different sensing configurations: pairs of GNUs-GNUs and GNUs-GNSs. When the target antigen is present in the analyte solution, nanoparticle bridging occurs and a subsequent amplification of the characteristic Raman signal of the label molecule appears due to the formation of hot-spots in interparticle gaps. The capability of observing small analyte concentrations in liquid samples with an easy-to-handle portable Raman device makes the proposed system feasible for rapid, non-invasive and cost-effective clinical or laboratory use.