Gold nanostructures encoded by non-fluorescent small molecules in polyA-mediated nanogaps as universal SERS nanotags for recognizing various bioactive molecules

Surface-enhanced Raman scattering (SERS) has recently been used to design novel nanoprobes called SERS tags which hold great promise for the fields of biosensing and nanomedicine. More recent advances have shed new light on the synthesis of uniform nanostructures with interior nanogaps for stable SERS enhancement. However, producing interior nanogap-based SERS nanotags directly and controllably with strong and stable multiplex SERS signals as well as developing a multiplex analytical platform to recognize different types of bioactive molecules still remain highly challenging. To address this challenge, we herein develop a novel approach for the direct synthesis of nanogap-based universal SERS nanotags by mediating poly-adenine (polyA) and encoding non-fluorescent small molecules. The universal nanotags were then functionalized by different types of biological probes and used as SERS nanoprobes to recognize various bioactive molecules. To the best of our knowledge, this is the first example of using SERS nanotags to develop a simultaneous multianalysis platform for all of the major types of bioactive analytes, including nucleic acids, proteins and small molecules. Furthermore, the nanotags show great promise for fluorescence-SERS bimodal bioanalysis and bioimaging.