Cheng Zong

Label-Free Surface-Enhanced Raman Spectroscopy Detection of DNA with Single-Base Sensitivity

Direct, label-free detection of unmodified DNA is a great challenge for DNA analyses. Surface-enhanced Raman spectroscopy (SERS) is a promising tool for DNA analyses by providing intrinsic chemical information with a high sensitivity. To address the irreproducibility in SERS analysis that hampers reliable DNA detection, we used iodide-modified Ag nanoparticles to obtain highly reproducible SERS signals of single- and double-strand DNA in aqueous solutions close to physiological conditions. The phosphate backbone signal was used as an internal standard to calibrate the absolute signal of each base for a more reliable determination of the DNA structure, which has not been achieved before. Clear identification of DNA with single-base sensitivity and the observation of a hybridization event have been demonstrated.

Mechanism of Cellular Uptake of Graphene Oxide Studied by Surface-Enhanced Raman Spectroscopy

The last few years have witnessed rapid development of biological and medical applications of graphene oxide (GO), such as drug/gene delivery, biosensing, and bioimaging. However, little is known about the cellular uptake mechanism and pathway of GO. In this work, surface-enhanced Raman scattering (SERS) spectroscopy is employed to investigate the cellular internalization of GO loaded with Au nanoparticles (NPs) by Ca Ski cells. The presence of Au NPs on the surface of GO enables detection of enhanced intrinsic Raman signals of GO inside the cell. The SERS results reveal that GO is distributed inhomogeneously inside the cell. Furthermore, internalization of Au-GO into Ca Ski cells is mainly via clathrin-mediated endocytosis, and is an energy-dependent process.

Rational Design and Synthesis of γFe2O3@Au Magnetic Gold Nanoflowers for Efficient Cancer Theranostics

An γFe2 O3 @Au core/shell-type magnetic gold nanoflower-based theranostic nano-platform is developed. It is integrated with ultrasensitive surface-enhanced Raman scattering imaging, high-resolution photo-acoustics imaging, real-time magnetic resonance imaging, and photothermal therapy capabilities.

Cu–Au alloy nanotubes with five-fold twinned structure and their application in surface-enhanced Raman scattering

Cu–Au alloy nanostructures have received considerable attention in recent years due to their widespread use in applications such as catalysis, photonics and surface-enhanced Raman scattering (SERS) detection. In this article, a template-based strategy has been developed to synthesize Cu–Au nanotubes with five-fold twinned structure by using Cu nanowires as templates and AuPPh3Cl as Au precursors in the organic phase of oleylamine. It was verified that high quality Cu–Au alloy nanotubes could result from the Cu–Au alloy effect, the Kirkendall effect, and the galvanic replacement reaction. It was also demonstrated that the Cu–Au alloy nanotubes may have potential applications in SERS detection because of their good stability and convenience for building “hot spots”.

Transient Electrochemical Surface-Enhanced Raman Spectroscopy: A Millisecond Time-Resolved Study of an Electrochemical Redox Process.

The pursuit of techniques with a high time resolution together with molecular signature information at the electrochemical interfaces has never stopped in order to explicitly monitor and understand the dynamic electrochemical processes. Here, we developed a transient electrochemical surface-enhanced Raman spectroscopy (TEC-SERS) to monitor the structural evolution of surface species at a time resolution that equals the transient electrochemical methods (e.g., cyclic voltammetry and chronoamperometry), so that the Raman signal with the molecular signature information and the electrochemical current signal can be precisely correlated. The technique was employed to study the redox process of nile blue on Ag surfaces. We revealed an interesting two-rate constant process and a peculiar increase of the absolute intensity during the reduction of nile blue on the Ag surface, which both related to the dissociation of nile blue aggregates and the follow-up reduction. Therefore, we were able to uncover the processes that are impossible to observe by conventional steady state SERS methods. The ability to provide a time resolution shorter than the charging time of the double layer capacitance with molecular fingerprint information has unprecedented significance for investigation of both reversible and irreversible electrochemical processes.

Clean and modified substrates for direct detection of living cells by surface-enhanced Raman spectroscopy

Iodide adsorption and electrochemical negative potential desorption were proposed and compared to obtain clean SERS substrates. The two methods can effectively eliminate the interference of surface impurities in the SERS detection. SERS signals of membranes of living cells with a good reproducibility have been obtained.

Plasmonic photoluminescence for recovering native chemical information from surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) spectroscopy has attracted tremendous interests as a highly sensitive label-free tool. The local field produced by the excitation of localized surface plasmon resonances (LSPRs) dominates the overall enhancement of SERS. Such an electromagnetic enhancement is unfortunately accompanied by a strong modification in the relative intensity of the original Raman spectra, which highly distorts spectral features providing chemical information. Here we propose a robust method to retrieve the fingerprint of intrinsic chemical information from the SERS spectra. The method is established based on the finding that the SERS background originates from the LSPR-modulated photoluminescence, which contains the local field information shared also by SERS. We validate this concept of retrieval of intrinsic fingerprint information in well controlled single metallic nanoantennas of varying aspect ratios. We further demonstrate its unambiguity and generality in more complicated systems of tip-enhanced Raman spectroscopy (TERS) and SERS of silver nanoaggregates.

Surface Plasmon-Coupled Directional Enhanced Raman Scattering by Means of the Reverse Kretschmann Configuration

Surface-enhanced Raman scattering (SERS) is a unique analytical technique that provides fingerprint spectra, yet facing the obstacle of low collection efficiency. In this study, we demonstrated a simple approach to measure surface plasmon-coupled directional enhanced Raman scattering by means of the reverse Kretschmann configuration (RK-SPCR). Highly directional and p-polarized Raman scattering of 4-aminothiophenol (4-ATP) was observed on a nanoparticle-on-film substrate at 46° through the prism coupler with a sharp angle distribution (full width at half-maximum of ∼3.3°). Because of the improved collection efficiency, the Raman scattering signal was enhanced 30-fold over the conventional SERS mode; this was consistent with finite-difference time-domain simulations. The effect of nanoparticles on the coupling efficiency of propagated surface plasmons was investigated. Possessing straightforward implementation and directional enhancement of Raman scattering, RK-SPCR is anticipated to simplify SERS instruments and to be broadly applicable to biochemical assays.

Raman Imaging from Microscopy to Nanoscopy, and to Macroscopy

Raman spectroscopy can not only provide intrinsic fingerprint information about a sample, but also utilize the merits of the narrow bandwidth and low background of Raman spectra, offering itself as a promising multiplex analytical technique. Raman microscopy has become particularly attractive recently because it has demonstrated itself as an important imaging technique for various samples, from biological samples and chemical systems to industrially important silicon-based wafers. In this Concept article, some of the most recent advances in Raman imaging techniques are critically reviewed, and the advantages and problems associated with the current techniques are discussed. Particular emphasis is placed on its future directions, from both the technical and application sides.

Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges

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.