Novel SERS labels: Rational design, functional integration and biomedical applications

Driven by the growing demand for healthcare and point-of-care test applications, next-generation diagnostic tools of diseases require sensing platforms that enable rapid, quantitative readout of analytes with excellent specificity and sensitivity. Although label-free detection permits simplicity, flexibility and high specificity, it has usually poor throughput, limited sensitivity and requires professional instrumentation. Label-based detection using optical labels overcomes many of these drawbacks and has been demonstrated to be an effective alternative for improved sensing performances. The current research focus has been directed towards innovating high-performance optical labels for ultrasensitive biosensing and disease diagnostics in place of conventional optical labels. Surface-enhanced Raman scattering (SERS) labels have proven to be excellent labels for biosensing because of their merits in many aspects, such as flexibility, less interference from biological matrices, high photostability, easy multiplex encoding, etc. These fantastic features make SERS labels particularly suitable for ultrasensitive detection of disease biomarkers in body fluids and targeted imaging of diseased cells and tissues, respectively. In this Review, we introduce the design and deployment of SERS labels for ultrasensitive detection, and summarize recent research progress in the development of SERS label-based sensing platforms and their applications in disease biomarker detection, targeted cellular imaging and spectroscopic detection of tumor lesions. First, we will discuss the design principles and comprehensive considerations of SERS labels, and the on-demand integration of functionalities. Next, we introduce the design of SERS sensing platforms on basis of SERS labels for ultrasensitive and selective detection of diverse pathology-related biomarkers, including proteins, nucleic acids, small molecules and inorganic ions. In addition, through the rational incorporation of targeting ligands on SERS labels, novel SERS probes are created for targeting near-infrared (NIR) imaging and spectroscopic detection of tumor, taking advantages of large NIR light penetration depth, high brightness, stability, etc. Our and other research efforts have demonstrated the promising potential of SERS label-based sensing platforms for detection of diverse circulating biomarkers for non-invasive disease diagnostics and deep-tissue spectroscopic detection of tumor. It is believed that this review will motivate further exploration of clinical applications of SERS labels in near future.