Mechanism of Surface-Enhanced Raman Scattering Based on 3D Graphene–TiO₂ Nanocomposites and Application to Real-Time Monitoring of Telomerase Activity in Differentiation of Stem Cells

With a burst development of new nanomaterials for plasmon-free surface-enhanced Raman scattering (SERS), the understanding of chemical mechanism (CM) and further applications have become more and more attractive. Herein, a novel SERS platform was specially designed through electrochemical deposition of graphene onto TiO 2 nanoarrays (EG–TiO 2 ). The developed EG–TiO 2 nanocomposite SERS platform possessed remarkable Raman activity using copper phthalocyanine (CuPc) as a probe molecule. X-ray photoelectron spectroscopy measurement revealed that the chemical bond Ti–O–C was formed at the interface between graphene and TiO 2 in EG–TiO 2 nanocomposites. Both experimental and theoretical results demonstrated that the obvious Raman enhancement was attributed to TiO 2 -induced Fermi level shift of graphene, resulting in effective charge transfer between EG–TiO 2 nanocomposites and molecules. Taking advantage of a marked Raman response of the CuPc molecule on the EG–TiO 2 nanocomposite surface as well as specific recognition of CuPc toward multiple telomeric G-quadruplex, EG–TiO 2 nanocomposites were tactfully employed as the SERS substrate for selective and ultrasensitive determination of telomerase activity, with a low detection limit down to 2.07 × 10 –16 IU. Interestingly, the self-cleaning characteristic of EG–TiO 2 nanocomposites under visible light irradiation successfully provided a recycling ability for this plasmon-free EG–TiO 2 substrate. The present SERS biosensor with high analytical performance, such as high selectivity and sensitivity, has been further explored to determine telomerase activity in stem cells as well as to count the cell numbers. More importantly, using this useful tool, it was discovered that telomerase activity plays an important role in the proliferation and differentiation from human mesenchymal stem cells to neural stem cells. This work has not only established an approach for gaining fundamental insights into the chemical mechanism (CM) of Raman enhancement but also has opened a new way in the investigation of long-term dynamics of stem cell differentiation and clinical drug screening.