Construction of a Scanning Ion-Conductance Microscope for Tip-Enhanced Raman Spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) has been developed by using atomic force microscopy and scanning tunneling microscopy since its birth in the early 2000s. Because, in principle, any scanning probe microscopy (SPM) can be combined with TERS, there is an increasing interest in extending TERS to other SPMs, especially the liquid-phase ones, targeting applications in biological or catalytic systems. We present the design, construction, and characterization of a laser-coupled scanning ion-conductance microscope (SICM) integrated with TERS for near-field spectroscopy under liquid environments. Key design elements include a full sample-scanning SICM, optics for TERS, and noise-isolating methods. The SICM-TERS system demonstrates direct-current and alternating-current SICM imaging modes on polydimethylsiloxane (PDMS) structures. Furthermore, the TERS capability was tested using silica-nanosphere-grafted PDMS. This work illustrates the feasibility and performance of SICM-TERS as a versatile tool for label-free nanoscale spectroscopy, opening new possibilities for real-time, analysis of soft matter, electrochemical, and biological systems.