Toward Sensitive and Reliable Surface-Enhanced Raman Scattering Imaging: From Rational Design to Biomedical Applications.

Early specific detection through indicative biomarkers and precise visualization of lesion sites are urgent requirements for clinical disease diagnosis. However, current detection and optical imaging methods are insufficient for these demands. Molecular imaging technologies are being intensely studied for reliable medical diagnosis. In the past several decades, molecular imaging with surface-enhanced Raman scattering (SERS) has significant advances from analytical chemistry to medical science. SERS is the inelastic scattering generated from the interaction between photons and substances, presenting molecular structure information. The outstanding SERS virtues of high sensitivity, high specificity, and resistance to biointerference are highly advantageous for biomarker detection in a complex biological matrix. In this work, we review recent progress on the applications of SERS imaging in clinical diagnostics. With the assistance of SERS imaging, the detection of disease-related proteins, nucleic acids, small molecules, and pH of the cellular microenvironment can be implemented for adjuvant medical diagnosis. Moreover, multimodal imaging integrates the high penetration and high speed of other imaging modalities and imaging precision of SERS imaging, resulting in final complete and accurate imaging outcomes and exhibiting robust potential in the discrimination of pathological tissues and surgical navigation. As a promising molecular imaging technology, SERS imaging has achieved remarkable performance in clinical diagnostics and the biomedical realm. It is expected that this review will provide insights for further development of SERS imaging and promote the rapid progress and successful translation of advanced molecular imaging with clinical diagnostics.