Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex analysis, and the measurements can be conveniently made under ambient and aqueous conditions. These merits make SERS a very promising technique for studying complex biological systems, and SERS has attracted increasing interest in biorelated analysis. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biological questions, and solve fatal clinical problems. SERS applications in bioanalysis involve the complex interactions of plasmonic nanomaterials with biological systems and their environments. The reliability becomes the key issue of bioanalytical SERS in order to extract meaningful information from SERS data. This review provides a comprehensive overview of bioanalytical SERS with the main focus on the reliability issue. We first introduce the mechanism of SERS to guide the design of reliable SERS experiments with high detection sensitivity. We then introduce the current understanding of the interaction of nanomaterials with biological systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. We further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomolecules, to pathogens, to living cells, and we discuss the potential interferences from experimental design, measurement conditions, and data analysis. In the end, we give an outlook of the key challenges in bioanalytical SERS, including reproducibility, sensitivity, and spatial and time resolution.

Organic–inorganic perovskite solar cells have attracted tremendous attention because of their remarkably high power conversion efficiencies. To further improve device performance, it is imperative to obtain fundamental understandings on the photo-response and long-term stability down to the microscopic level. Here, we report the quantitative nanoscale photoconductivity imaging on two methylammonium lead triiodide thin films with different efficiencies by light-stimulated microwave impedance microscopy. The microwave signals are largely uniform across grains and grain boundaries, suggesting that microstructures do not lead to strong spatial variations of the intrinsic photo-response. In contrast, the measured photoconductivity and lifetime are strongly affected by bulk properties such as the sample crystallinity. As visualized by the spatial evolution of local photoconductivity, the degradation process begins with the disintegration of grains rather than nucleation and propagation from visible boundaries between grains. Our findings provide insights to improve the electro-optical properties of perovskite thin films towards large-scale commercialization.

Extracellular pH (pHe) is an important regulating factor that determines many cellular processes, including proliferation, differentiation, and apoptosis. In our previous work, we developed 4-MPy (4-mercaptopyridine) modified Au nanoparticles as intracellular pH sensors based on surface-enhanced Raman spectroscopy (SERS). We herein modified a Au-nanoparticle-assembled solid SERS substrate with 4-MPy molecules for in situ pHe sensing during apoptosis. We found a more acidic extracellular environment of cancer cells than that of normal cells from the pH imaging. We then in situ investigated the temporal and spatial evolution of pHe of cancer cells after addition of transforming growth factor-β (TGF-β). The pHe showed a fast decrease at the beginning, followed by a slow decrease until the complete loss of cellular functions, and the pH values in and out of the cells became similar. This work shows that our SERS substrate combined with an in situ cell culture system is well suitable for in situ pHe sensing during cell processes and will be a promising technique for understanding more pHe-related biological and pathological issues.

Molecular imprinting technology has been widely applied to various fields, owing to unique features of structure predictability, recognition specificity and application universality. Microorganism imprinting has attracted significant interests attributing to the high selectivity, simplicity rapidity, and excellent stability as well as low cost and eco-friendliness. Herein, we purpose to review the recent advances of MIT for microorganism analysis, concerning imprinting methods, analytical detection methods and typical applications. Various imprinting methods including direct and indirect imprinting for microorganism-MIPs preparation are comprehensively summarized. MIPs based biosensors containing fluorescence, electrochemical, piezoelectric and surface plasmon resonance for analytical detection of microorganisms is highlighted. Representative applications of microbiological imprinting are discussed, involving detection and quantification of bacteria, identification of bacterial species, and determination of yeast growth status. Finally, we propose the remaining challenges and future perspectives to accelerate the development and utilization of MIT in microorganism analysis and thereby push forwards microorganism identification and determination.