Naihao Chiang

The ability to conduct nanoscale imaging and in situ chemical analysis in liquid environments can greatly benefit biological and soft materials research. Scanning ion-conductance microscopy (SICM) is one of the most popular non-contact techniques for imaging and manipulating living cells and soft substrates in their native environments, using ionic current feedback to enable gentle and precise mapping. On the other hand, tip-enhanced Raman scattering (TERS) has achieved label-free, molecularly specific nanoscale characterization via plasmonic enhancement provided by the probe tip. Recent developments in both techniques have made it possible to combine SICM with TERS. The resulting hybrid SICM-TERS can enable simultaneous, correlated mapping of topography in liquid environments. This review provides an overview of SICM and TERS leading up to the development of SICM-TERS, including their respective principles, instrumental developments, and current state of the art. Additionally, it discusses how combining these two techniques enables new opportunities for real-time, minimally invasive investigations of dynamic biological processes and complex interfacial phenomena under native conditions. As probe durability and multimodal microscopy integration improve, SICM-TERS is expected to take a more versatile role in correlative nanoscale imaging in the future. This will have a major impact on nanomedicine, biology, and materials research.

Catheter-related infections (CRIs) pose a significant threat to patient safety; therefore, the development of effective strategies to prevent and treat these infections is imperative. In this study, a photothermal system based on gold-silver nanoshell (AuAgNSh)-modified catheter surfaces was developed for the rapid eradication of the pathogenic bacterium Enterococcus faecalis (E. faecalis) using near-infrared (NIR) irradiation. The morphology and elemental composition of AuAgNShs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). The optical and photothermal properties were acquired by ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy and thermographic imaging with an IR camera, respectively. Bacterial survival studies on AuAgNSh-modified surfaces irradiated with and without NIR light were evaluated using a colony-formation assay. The results demonstrated that AuAgNSh-modified surfaces, when illuminated with NIR light, effectively killed E. faecalis on silicone surfaces in less than 10 min. The system is stable and reusable throughout multiple cycles and has the potential to serve as a rapid, localized adjunct to traditional antibiotic therapy for CRIs. By harnessing the thermal energy produced by AuAgNShs in response to NIR irradiation, this hyperthermia technique can potentially serve as a broad-spectrum antibiotic that kills adhered pathogens rapidly.

Plasmonic nanopipets, which are functionalized with plasmonic nanomaterials, are widely used in near-field spectroscopy to enhance the optical processes. The fabrication and screening processes of these nanopipets are critical for their intended applications. Here, an easy-to-implement fabrication scheme based on high-vacuum sputtered gold island films was reported. Additionally, the process of using surface-enhanced Raman spectroscopy (SERS) to evaluate the plasmonic enhancement of nanopipets was described for near-infrared laser excitation, and it could be readily applied to other optical windows. These results indicated that the reported plasmonic nanopipets can be used as Tip-SERS probes. Finally, the scanning ion-conductance microscopic tip-enhanced Raman spectroscopy was demonstrated with the optimized plasmonic nanopipet. Together with density functional theory simulation, the observed near-field Raman spectra were analyzed and assigned. These plasmonic nanopipets can be used to investigate a range of surface science problems in heterogeneous electrochemical interfaces, as well as in soft and biomimetic materials.

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, in situ analysis of soft matter, electrochemical, and biological systems.

Colloidal plasmonic metasurfaces are emerging as versatile platforms for advancing nanophotonic applications, whose rational design of increasing complexity allows for tailoring and integrating advanced plasmonic and photonic optical properties. Traditional lithographic techniques limit crystallographic and chemical adaptability, hindering the dynamic tuning of optical properties. In this work, a template‐assisted self‐assembly approach for achieving plasmonic metasurfaces using colloidal silver nanoparticle arrays and a thin film of core–shell CdSe/ZnS quantum dots are demonstrated. This system leverages plasmonic surface lattice resonances to create open nanophotonic cavities that enhance the two‐photon excited emission process. The near‐field interactions within these nanophotonic structures offer spectral tunability and efficient light–matter coupling. Moreover, using synthetic nanoparticles enables the integration of a rich library in nanoparticles’ size, shape, and composition, positioning them as promising candidates for compact and scalable photonic devices targeting nonlinear optical processes, advanced sensing, and dynamic light manipulation.

Scanning ion conductance microscopy (SICM) is a powerful surface imaging tool used in the electrolytic environment. Tip-enhanced Raman spectroscopy (TERS) can give more information in addition to the morphology provided by the SICM by utilizing label-free Raman spectroscopy aided by the localized plasmonic enhancement from the metal-coated probes. In this study, the integration of SICM with TERS is demonstrated through employing a silver-coated plasmonic nanopipette. Leveraging a two-dimensional (2D) molybdenum disulfide (MoS₂) as a model system, the SICM-TERS enhancement factor was estimated to be ∼10⁵, supported by finite-difference time-domain (FDTD) simulation. Moreover, the subnanometer distance dependence SICM-TERS study reveals the tensile stress and structural changes caused by the nanopipette. These findings illustrate the potential of SICM-TERS for providing comprehensive morphological and chemical insights into electrolytic environments, paving the way for future investigations of electrocatalytic and biological systems.

Colloidal metasurfaces are emerging as promising candidates for the development of functional chemical metamaterials, combining the undisputed control over crystallography and surface chemistry achieved by synthetic nanochemistry with the scalability and versatility of colloidal self‐assembly strategies. In light of recent reports of colloidal plasmonic materials displaying high‐performing optical cavities, this Minireview discusses the use of this type of metamaterials in the specific context of non‐linear optical phenomena and non‐linear molecular spectroscopies. Our attention is focused on the opportunities and advantages that colloidal nanoparticles and self‐assembled plasmonic metasurfaces can bring to the table compared to more traditional nanofabrication strategies. Specifically, we believe that future work in this direction will express the full potential of non‐linear molecular spectroscopies to explore the chemical space, with a deeper understanding of plasmon‐molecule dynamics, plasmon‐mediated processes, and surface‐enhanced chemistry.

Stimulating interest in science at an early age is important for STEM education. This work details an educational activity utilizing the anthocyanins found in butterfly pea flowers (Clitoria ternatea). This activity was developed for use in official classroom settings, online, and/or at-home with parental or educator guidance. Primary and high school students aged 7 to 14 performed a straightforward extraction of anthocyanin pH indicators from Clitoria ternatea with hot water. Students were able to use this indicator and its vast range of colors to compare the acidities and basicities of different household solutions. Most of the recorded responses show that students used reasoning from the indicator and a subsequent chemical reaction to correctly differentiate acids from bases and compare their strengths. Overall, this activity’s application of nontoxic and easily accessible indicators from the butterfly pea flower assisted in introducing young students to various concepts in acid–base chemistry, including acid/base strength and pH, solute dissolution, neutralization reactions, and qualitative analysis.