Surface-enhanced Raman Spectroscopy Platform Research Articles

High-Speed Fluctuation Analysis of Silver-Nanoparticle SERS in Solutions.

We analyzed the fluctuation of surface-enhanced Raman spectra with a temporal resolution of 25 ms using a conventional electron-multiplying charge-coupled device camera experimental setup. The signal-to-noise ratio of the spectra was improved using density-based spatial cluster analysis with noise. Silver nanoparticles (AgNPs) with different sizes were dispersed as surface-enhanced Raman spectroscopy platforms in violet aqueous solutions. The movement of AgNPs and the fluctuation of the spectra were characterized. The fluctuation (signal ON and OFF) was evaluated on the basis of the time intervals between ON and OFF timing. The behavior of each AgNP solution was explained by a two-dimensional random walk model, which means that the phenomenon was mainly governed by the Brownian motion of the AgNPs in the solution. The fluctuation was also compared among three different Raman modes, one of which showed anomalous behavior.

Ultrasensitive detection of L-phenylalanine on DC magnetron sputtered bismuth thin films using label-free SERS method

Quantitative imbalances in monomers such as amino acids, nucleotides etc. act as biomarkers for various health conditions like cancer, Alzheimer’s, genetic disorders etc. Different atmospheric annealed bismuth (Bi) thin films deposited by DC magnetron sputtering were compared to select a better Surface Enhanced Raman Spectroscopy (SERS) platform. The tailored morphology favoured confining of localized surface plasmon resonance (LSPR) between close-packed Bi nanoparticles. The Multiple SPRs (Mult. SPRs) from interband plasmonic transitions are majorly present in the ultraviolet (UV)-near-visible region making the film a promising UV- SERS platform. The varied annealing’s have tuned the SPR and are supported by the colour changes of Bi films. The Raman modes confirmed the chemical stability the films. XPS etching revealed the metallic state of the optimized Bi-D-PDV2 film. The preliminary SERS applications on Rhodamine 6 G (RH6G) selected a Bi-D-PDV2 film with an enhancement factor (EF) of ∼4 ×105. This optimized film used for L-phenylalanine (Phe) detection, resulted in enhanced sensitivity of ∼2 ×106 EF with a sub-micromolar (0.1 μM) limit of detection (LOD). The ultra-sensitive responses in the sub-μM level from the optimized Bi thin film for standard as well as biomolecule is reported for the first time to the best extent of knowledge. The potential responses from the optimized film gives promising response for its use in ultra-sensitive bio detections even down to single molecular level in future.

A breakthrough in phytochemical profiling: ultra-sensitive surface-enhanced Raman spectroscopy platform for detecting bioactive components in medicinal and edible plants.

A perennial challenge in harnessing the rich biological activity of medicinal and edible plants is the accurate identification and sensitive detection of their active compounds. In this study, an innovative, ultra-sensitive detection platform for plant chemical profiling is created using surface-enhanced Raman spectroscopy (SERS) technology. The platform uses silver nanoparticles as the enhancing substrate, excess sodium borohydride prevents substrate oxidation, and methanol enables the tested molecules to be better adsorbed onto the silver nanoparticles. Subsequently, nanoparticle aggregation to form stable "hot spots" is induced by Ca2+, and the Raman signal of the target molecule is strongly enhanced. At the same time, deuterated methanol was used as the internal standard for quantitative determination. The method has excellent reproducibility, RSD ≤ 1.79%, and the enhancement factor of this method for the detection of active ingredients in the medicinal plant Coptis chinensis was 1.24 × 109, with detection limits as low as 3 fM. The platform successfully compared the alkaloid distribution in different parts of Coptis chinensis: root > leaf > stem, and the difference in content between different batches of Coptis chinensis decoction was successfully evaluated. The analytical technology adopted by the platform can speed up the determination of Coptis chinensis and reduce the cost of analysis, not only making better use of these valuable resources but also promoting development and innovation in the food and pharmaceutical industries. This study provides a new method for the development, evaluation, and comprehensive utilization of both medicinal and edible plants. It is expected that this method will be extended to the modern rapid detection of other medicinal and edible plants and will provide technical support for the vigorous development of the medicinal and edible plants industry.

Amplified Sciences PanCyst Pro Panel to accurately identify non-mucinous pancreatic cyst fluid.

617 Background: Pancreatic cysts are rarely symptomatic, and, consequently, are detected incidentally during routine imaging analyses for unrelated disorders. Guidelines for diagnosis of pancreatic cysts rely on imaging and supportive analyses of fluid extracted during endoscopic ultrasound with fine-needle aspiration (EUS-FNA). Unfortunately, currently available protein markers and assays are not sufficiently accurate to rule-out patients in whom a non-mucinous pancreatic cyst has formed. Since non-mucinous pancreatic cysts seldom progress to cancer, this patient population is at risk of being subjected to the severe physical, emotional, and financial burdens associated with unwarranted surveillance, testing, and possible surgical intervention. Furthermore, identification of mucinous pancreatic cysts does not establish the risk of progression to cancer (rule-in) or the need for surgical intervention. Methods: To address the unmet needs in pancreatic cyst diagnosis, Amplified Sciences has combined a panel of markers with a clinically translated surface enhanced Raman spectroscopy (SERS)-based protease activity assay as a rule-out diagnostic tool. The tri-analyte panel was tested on a cohort of 185 retrospective samples gathered from three separate institutions (UPMC, IU Health, and UCSF) and consumed only 12 µL of cyst fluid per sample. The goals of this study were to establish the negative predictive value (NPV) of this panel prior to translation to a CLIA-regulated laboratory and create a preliminary algorithm for analysis. Results: The results of this statistically powered study show that protease activity outperforms carcinoembryonic antigen (CEA), a current standard diagnostic marker for pancreatic cyst fluid, in sensitivity, specificity, and NPV. Furthermore, in combination, the tri-analyte panel identifies non-mucinous pancreatic cysts with 99% sensitivity and a negative predictive value >95%. Conclusions: These results support the use of this panel in clinical settings as a diagnostic tool to rule-out patients from surgical intervention, as well as the use of SERS as an optical detection mode for clinical diagnostics. Future work will continue to address the unmet need for improved diagnostic information through multiplexed analyses of markers that consume comparatively minimal volume of pancreatic cyst fluid samples. Studies will also seek to build on the SERS platform by introducing more dyes, substrates, assays, and analytical methods. Amplified Sciences would like to acknowledge significant efforts to build the clinical samples cohort from Gina Zhu, Kelli Ifuku, and Dr. Kimberly Kirkwood from USCF, Christine Decapite and Dr. Randall Brand from UPMC, and Michele Yip-Schneider and Dr. C. Max Schmidt from IU Health.

Dynamic repulsive interaction enables an asymmetric electron-phonon coupling for improving Raman scattering.

Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.

Sub-70 nm surface structures on femtosecond laser irradiated GaAs in distilled water and sensing application.

This study reveals the possibility of distinct ablation mechanisms at different radial positions of the ablated track on GaAs when ablated with femtosecond pulses in distilled water. From the center to the edges of the ablated track, fascinating features such as micron-sized cones, nano-pores, and nano-ripple trenches (average size of 60-70 nm) were observed. The requirement for simulations incorporating the variations in a Gaussian beam fluence and dynamics of the melt flow/surrounding media is discussed. Deep-subwavelength structures, i.e., nano-ripple trenches with a ripple size of ∼λ/11 are achieved on the GaAs surface in this study. Further, these GaAs surface structures acted as excellent hybrid surface-enhanced Raman spectroscopy platforms upon gold coating.

Microwave synthesis of molybdenene from MoS2

Dirac materials are characterized by the emergence of massless quasiparticles in their low-energy excitation spectrum that obey the Dirac Hamiltonian. Known examples of Dirac materials are topological insulators, d-wave superconductors, graphene, and Weyl and Dirac semimetals, representing a striking range of fundamental properties with potential disruptive applications. However, none of the Dirac materials identified so far shows metallic character. Here, we present evidence for the formation of free-standing molybdenene, a two-dimensional material composed of only Mo atoms. Using MoS2 as a precursor, we induced electric-field-assisted molybdenene growth under microwave irradiation. We observe the formation of millimetre-long whiskers following screw-dislocation growth, consisting of weakly bonded molybdenene sheets, which, upon exfoliation, show metallic character, with an electrical conductivity of ~940 S m−1. Molybdenene when hybridized with two-dimensional h-BN or MoS2, fetch tunable optical and electronic properties. As a proof of principle, we also demonstrate applications of molybdenene as a surface-enhanced Raman spectroscopy platform for molecular sensing, as a substrate for electron imaging and as a scanning probe microscope cantilever.

SERS study of classical and newly β-lactams-metal complexation based on in situ laser-induced coral reefs-like silver photomicroclusters: In vitro study of antibacterial activity

The influence of metal complexation of two polar β-lactam antibiotics was investigated using surface enhanced Raman spectroscopy (SERS) technique. SERS method was applied to track the structural changes and the degradation behaviour of the studied compounds upon Zinc (II) ions-complexation. In situ laser-induced coral reefs-like photomicroclusters have been utilized as a SERS platform. The produced coral reefs-like photomicroclusters were characterized using scanning electron microscopy (SEM) and transmission electron microscope (TEM). The antibacterial efficiency of the antibiotics was investigated and compared before and after metal complexation using two techniques; agar well diffusion and growth curve. To provide a detailed elucidation of the complexation reaction, mass fragmentation of metal- antibiotics complexes was investigated using liquid chromatography/mass spectrometric (LC/MS) technique. It was found that metal complexation of classical β-lactam antibiotic (Ticarcillin) promoted the rate of its degradation, leading to a decrease of the antibacterial efficiency. On the other side, the antibacterial activity of the newly developed β-lactam (Faropenem) has been greatly enhanced via metal-complexation reaction.

Single-Cell Analysis and Classification according to Multiplexed Proteins via Microdroplet-Based Self-Driven Magnetic Surface-Enhanced Raman Spectroscopy Platforms Assisted with Machine Learning Algorithms.

A microdroplet-based surface-enhanced Raman spectroscopy (microdroplet SERS) platform was constructed to envelop individual cells in microdroplets, followed by the SERS detection of their extracellular vesicle-proteins (EV-proteins) via the in-drop immunoassays by use of immunomagnetic beads (iMBs) and immuno-SERS tags (iSERS tags). A unique phenomenon is found that iMBs can start a spontaneous reorientation on the probed cell surface based on the electrostatic force-driven interfacial aggregation effect, which leads EV-proteins and iSERS tags to be gathered from a liquid phase to a cell membrane interface and significantly improves SERS sensitivity to the single-cell analysis level due to the formation of numbers of SERS hotspots. Three EV-proteins from two breast cancer cell lines were collected and further analyzed by machine learning algorithmic tools, which will be helpful for a deeper understanding of breast cancer subtypes from the view of EV-proteins.

Significantly increased Raman enhancement enabled by hot-electron-injection-induced synergistic resonances on anisotropic ReS2 films.

Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). However, a poor detection sensitivity hinders their practical application. Exciton resonance (μex) can improve SERS significantly by lending intensity to nearby charge-transfer resonance. Coincidentally, for ReS2, the enhanced μex can be achieved through the injection of excited-state electrons which can adjust the energy band to the SERS detection range. Moreover, ReS2 has strong anisotropic properties, which adds an additional dimension for SERS. Therefore, ReS2 is an ideal candidate to realize highly sensitive anisotropic SERS. In this paper, the metallic T phase of ReS2 is introduced to the semiconducting Td phase by phase engineering. The photoinduced electron tunneling from the T phase to the Td phase can tune exciton emissions to the visible region, which effectively facilitates the photoinduced charge transfer processes. With RhB as the probe molecule, the synergistic resonance effects improve the limit of detection to 10-9 M with the enhancement factor up to about 108. Meanwhile, the obtained ultrasensitive SERS substrates also show good uniformity, stability as well as unique anisotropy. Our results open a new perspective in the improvement of the SERS performance.

Two-step aggregation of gold nanoparticles based on charge neutralization for detection of melamine by colorimetric and surface-enhanced Raman spectroscopy platform.

A colorimetric and surface-enhanced Raman scattering (SERS) signal amplification platform based on 2-step aggregation of gold nanoparticles (AuNP) was constructed for the sensitive detection of melamine. In this study, the positively charged SYBR Green I was used for the first step of aggregation of AuNP, via charge neutralization, to obtain small-sized AuNP aggregates. The positively charged SYBR Green I decreased the negative charges of the surface of AuNP, which was beneficial to the aggregation of AuNP. In addition, the melamine could aggregate AuNP by decreasing the negative charges of the surface of AuNP and self-assemble with each other on the surface of AuNP by hydrogen bonds. Therefore, the second efficient aggregation of small-sized AuNP aggregates could be achieved with melamine at low concentration, resulting in significant signal changes of color and SERS. The sensitivity of a colorimetric (0.60 mg/L) and SERS (0.089 mg/L) platform, based on 2-step aggregation of AuNP, was 15 and 2.2 times higher than that based on 1-step aggregation of AuNP for detecting melamine.

A one-step, tunable method of selective reactive sputter deposition as a wrinkling approach for silver/polydimethylsiloxane for electrically conductive pliable surfaces

The wrinkle period and morphology of a metal thin film on an elastic substrate is typically controlled by modifying the substrate before carrying out additional metal deposition steps. Herein, we show that a simultaneously selective and reactive sputtering plasma that modifies the surface of a polydimethylsiloxane (PDMS) substrate while not reacting with the metal during the deposition process decreases the wrinkle wavelength and induces additional wrinkling components and features such as ripples or folds. The selective reaction of the nitrogen plasma with PDMS functionalizes the siloxane surface into silicon oxynitride. This hardens the immediate surface of PDMS, with a quadratic increase in the Young’s modulus as a function of the sputtering flow ratio. The increase in the critical strain mismatch and the corresponding presence of folds in the nitrogen-modified wrinkled silver film form a suitable plasmonic platform for surface-enhanced Raman spectroscopy (SERS), yielding an enhancement factor of 4.8 × 105 for detecting lipids. This enhancement is linked to the emergence of electromagnetic hotspots from surface plasmon polariton coupling between the folds/wrinkles, which in turn enables the detection of low concentrations of organics using SERS. Furthermore, when strained, the nitrogen-modified wrinkles enhance electrical conductivity by a factor of 12 compared with unmodified films. Finally, the optical properties of the substrate can be tuned by altering the N2 content. The simple addition of nonreactive nitrogen to silver sputtering enables simultaneous PDMS hardening and growth of the silver film and together provide a new avenue for tuning wrinkling parameters and enhancing the electrical conductivity of pliable surfaces.

A disposable ultrasensitive surface enhanced Raman spectroscopy biosensor platform fabricated from biodegradable zein nanofibers

AbstractIn this paper, a natural polymer, zein, is converted into a disposable and environmentally friendly surface enhanced Raman spectroscopy (SERS) biosensor platform to detect toxins. First, protein nanofiber mats were fabricated using electrospinning. Next, the surface of the fibers was decorated with metallic nanoparticles to create hotspots for the detection of the target molecule. Four types of metallic nanoparticles were tested for sensitivity optimization: gold, silver, silver‐shelled‐gold, and a mixture of gold and silver nanoparticles. Silver‐shelled‐gold nanoparticles gave the highest SERS intensity, and at the concentration of 1012 particles/ml, the highest enhancement factor (EF) of 2.49 × 106 was reached, which is the highest EF ever reported for a zein‐based biodegradable platform. Acrylamide was used as the model food carcinogenic toxin and its detection with this nanofiber‐based platform gave a limit of detection of 2.06 ng/ml. This LOD is 104 times lower than the limit of detection that was achieved previously with a zein‐based SERS platform. Other sensitive analytical methods (GC–MS and LC–MS/MS) gave LODs of 5–10 and 20–50 ng/ml for acrylamide, much higher than the method used in this study. This sensitivity is much lower than any other previous attempts to detect acrylamide with biodegradable sensors.

Plasmonic Superlattice Membranes Based on Bimetallic Nano-Sea Urchins as High-Performance Label-Free Surface-Enhanced Raman Spectroscopy Platforms.

On the basis of an abundance of elemental plasmonic nanocrystals identifiable by their unique morphology and intrinsic optoelectronic properties, it is necessary to rationally tailor the structural parameters to optimize the functionalities of nanoassemblies for application as plasmonic circuits/devices. Among them, the plasmonic superlattice membrane has emerged as a novel optically active metamaterial, which is constructed by nanocrystals at a two-dimensional (2D) plane with a highly ordered structure and strong plasmonic coupling interactions. Here, we report on the fabrication of a novel plasmonic superlattice membrane using bimetallic core-shell nano-sea urchins (Nano-SEUs) as meta-atoms. Under the guidance of soft-ligand balancing in conjugation with drying-mediated self-assembly at the air/water interface, well-defined giant 2D superlattices with total lateral dimensions of up to 5 mm wide and 80 nm thick have been synthesized, corresponding to an aspect ratio of 62 500. Programmable morphology control over the Nano-SEUs has been achieved in high yield by rationally tuning the spiky branches as well as the thickness of the silver shell, allowing systematic variation of the plasmonic properties of the membrane. Such superlattice membranes exhibited a strong and reproducible surface-enhanced Raman spectroscopy (SERS) signal that originates from interparticle coupling and electric (E)-field enhancement, enabling an enhancement factor of up to 106. We also demonstrated that the fabricated membrane allows the label-free SERS detection of dopamine from 0.1 nM to 1 μM. Thus, this giant Nano-SEU assembled superlattice membrane can be used as a SERS substrate for on-spot biomarker detection, which paves a robust and inexpensive avenue for highly sensitive and reliable biomedical sensing and diagnostics.

Three dimensional porous Expanded Graphite/Silver Nanoparticles nanocomposite platform as a SERS substrate

Surface enhanced Raman spectroscopy (SERS) is a promising technique for food safety, medical diagnostics and bio-sensing applications, and environmental protection. However, high production costs due to need of sophisticated equipments, relatively poor stability of the present substrates and repeatability problems limit the use of SERS as a routine analysis technique. Hybrid SERS substrates composed of noble metal nanoparticles and graphene-based materials have gained a significant importance since they combine the surface plasmon resonance property of the metal nanoparticles, and the ability of acting as a protective layer for metal nanoparticles against oxidation, SERS enhancement through charge transfer mechanism, flexibility, excellent optical permeability and superior mechanical strength of graphene-based materials. Herein, three dimensional (3D) porous expanded graphite (EG) decorated with silver nanoparticles (AgNPs) was fabricated as a low cost and easy-to-produce SERS platform. 3D and highly porous structure of the EG/AgNPs nanocomposites provided fast penetration of solvent into the substrate, eliminating coffee-ring effect and enabling one to perform fast SERS measurements, as well as allowing to decorate more metal nanoparticles/adsorb more analyte molecules due to high specific surface area. The detection limit of the EG/AgNPs substrates for Rhodamine 6G (R6G) was determined as 10-11 M and the enhancement factor was estimated to be 2.7 × 106. The peaks of 10-11 M R6G was detected even after one month, indicating a high stability and long lifetime of the substrate. This highly stable, sensitive, cost-effective and easy-to-produce EG/AgNPs nanocomposite substrate exhibit a great potential to promote application of SERS for routine analyses.

Ultrasensitive Plasmon-Free Surface-Enhanced Raman Spectroscopy with Femtomolar Detection Limit from 2D van der Waals Heterostructure.

Two-dimensional (2D) materials have been promoted as an ideal platform for surface-enhanced Raman spectroscopy (SERS), as they mitigate the drawbacks of noble metal-based SERS substrates. However, the inferior limit of detection has limited the practical applicability of 2D material-based SERS substrates. Here, we synthesize uniform large-area ReOxSy thin films via solution-phase deposition without post-treatments and demonstrate a graphene/ReOxSy vertical heterostructure as an ultrasensitive SERS platform. The electronic structure of ReOxSy can be modulated by changing the oxygen concentration in the lattice structure, obtaining efficient complementary resonance effects between ReOxSy and the probe molecule. In addition, the oxygen atoms in the ReOxSy lattice generate a dipole moment on the thin-film surface, which increases the electron transition probability. These synergistic effects outstandingly enhance the Raman effect in the ReOxSy thin film. When ReOxSy forms a vertical heterostructure on a graphene as the SERS substrate, the enhanced charge-transfer and exciton resonances improve the limit of detection to the femtomolar level, while achieving remarkable flexibility, reproducibility, and operational stability. Our results provide important insights into 2D material-based ultrasensitive SERS based on chemical mechanisms.

Hybrid films of reduced graphene oxide modified with gold nanorods and its study as surface-enhanced Raman spectroscopy platform

In this work, spin-assisted hybrid films of graphene oxide (GO) modified with gold nanorods (Au NRs) were prepared, with a subsequent chemical reduction (RGO). The Au NRs were homogeneously distributed on GO edges and surface, showing a strong interaction between both nanomaterials. The RGO/Au NRs hybrid films were used as substrate for detection studies of crystal violet by surface enhancement Raman spectroscopy (SERS). The results demonstrate that the hybrid RGO/Au NRs films prepared by the spin coating technique have great potential as SERS substrates using low amounts of nanomaterials displaying an enhancement factor of 103.

Surface-Enhanced Raman Spectroscopy on Hybrid Graphene/Gold Substrates near the Percolation Threshold.

Graphene is a promising platform for surface-enhanced Raman spectroscopy (SERS)-active substrates, primarily due to the possibility of quenching photoluminescence and fluorescence. Here we study ultrathin gold films near the percolation threshold fabricated by electron-beam deposition on monolayer CVD graphene. The advantages of such hybrid graphene/gold substrates for surface-enhanced Raman spectroscopy are discussed in comparison with conventional substrates without the graphene layer. The percolation threshold is determined by independent measurements of the sheet resistance and effective dielectric constant by spectroscopic ellipsometry. The surface morphology of the ultrathin gold films is analyzed by the use of scanning electron microscopy (SEM) and atomic force microscopy (AFM), and the thicknesses of the films in addition to the quartz-crystal mass-thickness sensor are also measured by AFM. We experimentally demonstrate that the maximum SERS signal is observed near and slightly below the percolation threshold. In this case, the region of maximum enhancement of the SERS signal can be determined using the figure of merit (FOM), which is the ratio of the real and imaginary parts of the effective dielectric permittivity of the films. SERS measurements on hybrid graphene/gold substrates with the dye Crystal Violet show an enhancement factor of ~105 and also demonstrate the ability of graphene to quench photoluminescence by an average of ~60%.

Gold-nanoisland-decorated titanium nanorod arrays fabricated by thermal dewetting approach

Solid-state dewetting is a simple and versatile technique for fabricating plasmonic-nanostructure-decorated platforms. However, understanding of the optical properties of these platforms and the effect of the three-dimensional (3D) morphology of the underlying substrate on the dewetting of metallic thin films is still needed for developing effective platforms for further applications. Herein, the authors report gold (Au)-nanoisland-decorated 3D titanium dioxide (TiO2) nanorod (TiNR) arrays fabricated through the thermal dewetting approach. It is demonstrated that the plasmonic behavior of the fabricated platforms can be manipulated by controlling both the initial gold film thickness and annealing temperature. Furthermore, the fabricated platforms exhibited Raman signal enhancement of up to ∼102 for the probe molecule methylene blue. The surface characteristics of the fabricated platforms were evaluated for biological interactions. For this purpose, osteogenic cells (Saos-2) were seeded on the samples. It was found that the cell behavior was improved on the anisotropic micro–nano pattern of TiNRs and gold-coated TiNR films because of features such as topography and surface chemistry. The authors’ results clearly offer simple but important guidance for the creation of surface-enhanced Raman spectroscopy platforms and tissue-integration devices as biomaterials for real-life applications.

Porous SiO2@Ni@C and Au nanocages as surface-enhanced Raman spectroscopy platform with use of DNA structure switching for sensitive detection of uracil DNA glycolase

In this work, SiO2@Ni@C nanosphere and Au nanocages (AuNCs) platform with use of target-induced DNA structure switching strategy was utilized to construct a surface-enhanced Raman spectroscopy (SERS) biosensor to analyze trace amounts of uracil DNA glycolase (UDG). In details, we utilized NH2-functioned SiO2@Ni@C nanosphere to immobilize abundant hairpin DNA (R) due to the large surface area and abundant adsorption sites. In the presence of the target UDG, they could specifically recognize and hydrolyze the uracil bases, generating apyrimidinic (AP) sites to induce DNA structure switching process, which could reconfigure hairpin DNA (R) to hairpin DNA (R′). Then the generated R′ could capture complementary DNA S1 bonded to the toluidine blue-Au nanocages (AuNCs-TB). With the increasing amount of UDG, more SiO2@Ni@C-NH2-R′ would be obtained and coupled with TB-AuNCs-S1 to produce a stronger Raman signal. Based on this simple protocol, the SERS assay could achieve sensitive UDG detection in a concentration range from 5 × 10−5 U mL−1 to 1 U mL−1 with a detection limit down to 3.2 × 10−5 U mL−1. Therefore, this SERS-based assay gives a new strategy for SERS detection which may have potential application for ultrasensitive detection of other protein biomarkers.