Surface-enhanced Raman Scattering System Research Articles

Ag-Coated Ternary Layered Double Hydroxide as a High-Performance SERS Sensor for Aldehydes.

Volatile organic compounds (VOCs) are common environmental pollutants and important biomarkers for early diagnosis of lung cancer. However, aldehydes are difficult to detect directly due to their small Raman scattering cross-section and gaseous phase. Here, a Ag-coated ternary layered double hydroxide (LDH) was designed for the detection and identification of various aldehydes. The specific surface area of CoNi-LDH was increased by doping Fe3+, which provides abundant active sites to capture gas molecules. Furthermore, the energy band gap (Eg) was decreased due to the local amorphous FeCoNi-LDH with an extended band tail, promoting the excitonic transition of Fe0.07(CoNi)0.93-LDH. In addition, the Fermi level of Ag prevented the recombination of electron-hole pairs of Fe0.07(CoNi)0.93-LDH, providing a new bridge for charge transfer between the substrate and the molecule. Ag/Fe0.07(CoNi)0.93-LDH presented excellent surface-enhanced Raman scattering (SERS) performance for aldehyde VOCs by modification with 4-aminothiophenol (4-ATP) to capture aldehydes and realized the detection of benzaldehyde (BZA) at 10 ppb. The enhancement and Raman shift of the b2 mode indicated the contribution of chemical enhancement to the SERS system, so the substrate presented good uniformity. The recycling of the SERS substrate is realized based on the reversibility of the Schiff base reaction. These results manifested that Ag/FeCoNi-LDH has a wide prospect in the application in the trace detection of aldehydes.

Interpreting chemical enhancements of surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) provides orders of magnitude of enhancements to weak Raman scattering. The improved sensitivity and chemical information conveyed in the spectral signatures make SERS a valuable analysis technique. Most of SERS enhancements come from the electromagnetic enhancement mechanism, and changes in spectral signatures are usually attributed to the chemical enhancement mechanism. As the electromagnetic mechanism has been well studied, we will give an overview of models related to the chemical mechanism, which explain the Raman response in terms of electronic transitions or induced electron densities. In the first class of models based on electronic transitions, chemical enhancements are attributed to changes in transitions of the molecule and new charge transfer transitions. The second class of models relate chemical enhancements to charge flows near the molecule–metal interface by partitioning the induced electron density of the SERS system in real space. Selected examples will be given to illustrate the two classes of models, and connections between the models are demonstrated for prototypical SERS systems.

Chemical Mechanism-Dominated and Reporter-Tunable Surface-Enhanced Raman Scattering via Directional Supramolecular Assembly.

Molecular resonance can be strengthened by charge transfer, profiting chemical mechanism (CM)-related surface-enhanced Raman scattering (SERS). Herein a supramolecular assembly enabled SERS system is established by functionalizing para-sulfonatocalix[4]arene (pSC4) onto Au3Cu nanocrystals (NCs). Due to the cooperation of Au and Cu, pSC4 is directionally assembled on the surface of Au3Cu NCs via van der Waals force, enabling photoinduced and hydrogen bond-induced charge transfer, which remarkably enhances the Raman scattering of methylene blue (MB) captured by pSC4. In particular, for the C-N and C-C stretching of MB, the contributions of resonance Raman scattering increase up to 80%. In addition, the SERS system is able to display affinities of different host-guest interactions, and further employed to evaluate effects of drugs for Alzheimer's disease. In this work, charge transfer is realized by performing supramolecular assembly on the surface of plasmonic nanomaterials, providing an avenue to design CM-related and reporter-tunable SERS systems.

Multi-path remote-excited surface plasmon resonance of a hollow gold nanosheet studied using FDTD simulations

Multi-path remote-excited surface-enhanced Raman scattering (SERS) could be achieved in a two-dimensional hollow gold nanosheet (HGNS) structure. This structure typically contains one hollow and regular cavity located concentrically in the middle of a gold nanosheet (GNS), which forms such as Triangle-Triangle (T-T) or Hexagon-Hexagon (HH) HGNS. As for T-T HGNSs, if we focused the exciting incident laser on one vertex of the outer-solid-triangle (OST) or inner-hollow-triangle (IHT), the localized surface plasmon resonance (LSPR) could be achieved on other remote vertexes. Because of this hollow cavity (e.g. IHT in T-T HGNSs), the maximum quad-path remote-excited SERS system could be developed. The optical property of equilateral triangular and solid GNS (SGNS) is comparatively simple and symmetric. However, after a hollow triangle cavity is formed within GNS, it can be used to modulate LSPR and bring in a new coupling effect between OST and IHT. FDTD simulations have shown that a red-shift of LSPR peak with the increase of IHT size were observed. Compared with single-path-excitation, the remote signal of LSPR scattering at wavelength around 0.76 μm can be enhanced, under the optimum coupling polarization, by over 228 %, 597 % and 1155 % for dual-, triple- and quad-path-excitation respectively. At given LSPR peak (e.g. around 1.061 μm), this enhancement can be doubled once again at least. Furthermore, a remarkable polarization-dependent anisotropic property in T-T HGNS was observed owing to strong OST-IHT couplings, which exhibits great potential application in remote SERS, remote sensing and optical waveguide switch.

Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprint

Wearable sweat sensors with various sensing systems can provide noninvasive medical diagnostics and healthcare monitoring. Here, we demonstrate a wearable microfluidic nanoplasmonic sensor capable of refreshable and portable recognition fingerprint information of targeted biomarkers including urea, lactate, and pH in sweat. A miniature, thin plasmonic metasurface with homogeneous mushroom-shaped hot spots and high surface-enhanced Raman scattering (SERS) activity is designed and integrated into a microfluidics platform. Compared to conventional wearable SERS platforms with the risk of mixed effect between new and old sweat, the microfluidic SERS system allows sweat administration in a controllable and high temporal-resolution fashion, providing refreshable SERS analysis. We use a portable and customized Raman analyzer with a friendly human-machine interface for portable recognition of the spectroscopic signatures of sweat biomarkers. This study integrates epidermal microfluidics with portable SERS molecular recognition, presenting a controllable, handy, and dynamical biofluid sensing system for personalized medicine.

All-fiber surface-enhanced Raman scattering detection system combining an integrated microfluidic chip and micro-lensed fiber.

It is a challenge to perform simple and rapid detection of substances due to their complex structure. Biochemical molecules play a vital role in human health and environmental testing. Surface-enhanced Raman scattering (SERS) detection has the characteristics of strong specificity and real-time performance. At present, most SERS systems are expensive and not portable. Here, we demonstrate a SERS detection system with all-fiber connection, combined with a microfluidic chip and micro-lenses. Compared with the conventional SERS system that uses the spatial optical path, the devices in our system are connected by optical fibers, making the system more stable and operable. Besides, the microfluidic chips are introduced to further improve the system integration and stability. Owing to the micro-lensed fiber probe, the detected Raman signal intensity is increased by 2-3 times. We anticipate that the presented work will lead toward a rapid and portable SERS system and corresponding detection system. It also lays the foundation for real-time recognition in various complex environments in the design of a future optical fiber system.

Multiple valence states of Fe boosting SERS activity of Fe3O4 nanoparticles and enabling effective SERS-MRI bimodal cancer imaging

Developing novel nanoparticle-based bioprobes utilized in clinical settings with imaging resolutions ranging from cell to tissue levels is a major challenge for tumor diagnosis and treatment. Herein, an optimized strategy for designing a Fe3O4-based bioprobe for dual-modal cancer imaging based on surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI) is introduced. Excellent SERS activity of ultrasmall Fe3O4 nanoparticles (NPs) was discovered, and a 5 × 10−9 M limit of detection for crystal violet molecules was successfully obtained. The high-efficiency interfacial photon-induced charge transfer in Fe3O4 NPs was promoted by multiple electronic energy levels ascribed to the multiple valence states of Fe, which was observed using ultraviolet–visible diffuse reflectance spectroscopy. Density functional theory calculations were utilized to reveal that the narrow band gap and high electron density of states of ultrasmall Fe3O4 NPs significantly boosted the vibronic coupling resonances in the SERS system upon illumination. The subtypes of cancer cells were accurately recognized via high-resolution SERS imaging in vitro using the prepared Fe3O4-based bioprobe with high sensitivity and good specificity. Notably, Fe3O4-based bioprobes simultaneously exhibited T1-weighted MRI contrast enhancement with an active targeting capability for tumors in vivo. To the best of our knowledge, this is the first report on the use of pure semiconductor-based SERS-MRI dual-modal nanoprobes in tumor imaging in vivo and in vitro, which has been previously realized only using semiconductor–metal complex materials. The non-metallic materials with SERS–MRI dual-modal imaging established in this report are a promising cancer diagnostic platform, which not only showed excellent performance in early tumor diagnosis but also possesses great potential for image-guided tumor treatment.

A novel and controllable SERS system for crystal violet and Rhodamine B detection based on copper nanonoodle substrates

Copper nanostructures have attracted more and more attention due to low preparation cost, similar thermal conductivity and optical characteristics to silver nanostructures. A novel macroscopic dendritic copper nanonoodles with the length of 3–50 mm prepared by solid-state ionics method at 10 μA direct current electric field (DCEF) using fast ionic conductor RbCu4Cl3I2 films was reported. The surface-enhanced Raman scattering (SERS) performance of prepared copper nanonoodles was detected by crystal violet (CV) and rhodamine B (RB) aqueous solution as analyte molecules. The results present that the copper nanonoodles assembled by short-range order copper nanowires and the diameters of nanowires changed from 20 nm to 80 nm, many regularly arranged nanoparticles with the diameter from 5 to 10 nm existed on the prepared copper nanonoodles, which lead to the nanonoodles have high surface roughness. The copper nanonoodles contain only Cu element, no O element and the fractal dimension of copper nanonoodles is 1.355 because of macroscopic dendritic structures. The prepared copper nanonoodles composed of pure Cu have high surface roughness and the free electrons on the rough copper nanonoodles resonate with the atomic nuclei inside the copper nanonoodles to form a locally enhanced electromagnetic field under the excitation of incident light, so the limiting concentrations for CV and RB detected by the prepared copper nanonoodles are as low as 1 × 10−11 mol/L and 1 × 10−12 mol/L, respectively. The centimeter-scale copper nanonoodles with low limiting concentration of analyte molecules can be used to detect harmful food additives.

Intelligent SERS Navigation System Guiding Brain Tumor Surgery by Intraoperatively Delineating the Metabolic Acidosis

Surgeons face challenges in intraoperatively defining margin of brain tumors due to its infiltrative nature. Extracellular acidosis caused by metabolic reprogramming of cancer cells is a reliable marker for tumor infiltrative regions. Although the acidic margin‐guided surgery shows promise in improving surgical prognosis, its clinical transition is delayed by having the exogenous probes approved by the drug supervision authority. Here, an intelligent surface‐enhanced Raman scattering (SERS) navigation system delineating glioma acidic margins without administration of exogenous probes is reported. With assistance of this system, the metabolites at the tumor cutting edges can be nondestructively transferred within a water droplet to a SERS chip with pH sensitivity. Homemade deep learning model automatically processes the Raman spectra collected from the SERS chip and delineates the pH map of tumor resection bed with increased speed. Acidity correlated cancer cell density and proliferation level are demonstrated in tumor cutting edges of animal models and excised tissues from glioma patients. The overall survival of animal models post the SERS system guided surgery is significantly increased in comparison to the conventional strategy used in clinical practice. This SERS system holds the promise in accelerating clinical transition of acidic margin‐guided surgery for solid tumors with infiltrative nature.

Hand-Held Raman Spectrometer-Based Dual Detection of Creatinine and Cortisol in Human Sweat Using Silver Nanoflakes.

The conventional tissue biopsy method yields isolated snapshots of a narrow region. Therefore, it cannot facilitate comprehensive disease characterization and monitoring. Recently, the detection of tumor-derived components in body fluids─a practice known as liquid biopsy─has attracted increased attention from the biochemical research and clinical application viewpoints. In this vein, surface-enhanced Raman scattering (SERS) has been identified as one of the most powerful liquid-biopsy analysis techniques, owing to its high sensitivity and specificity. Moreover, it affords high-capacity spectral multiplexing for simultaneous target detection and a unique ability to obtain intrinsic biomolecule-fingerprint spectra. This paper presents the fabrication of silver nanosnowflakes (SNSFs) using the polyol method and their subsequent dropping onto a hydrophobic filter paper. The SERS substrate, which comprises the SNSFs and hydrophobic filter paper, facilitates the simultaneous detection of creatinine and cortisol in human sweat using a hand-held Raman spectrometer. The proposed SERS system affords Raman spectrometry to be performed on small sample volumes (2 μL) to identify the normal and at-risk creatinine and cortisol groups.

Modification of a SERS-active Ag surface to promote adsorption of charged analytes: effect of Cu2+ ions

This work studies the impact of the electrostatic interaction between analyte molecules and silver nanoparticles (Ag NPs) on the intensity of surface-enhanced Raman scattering (SERS). For this, we fabricated nanostructured plasmonic films by immobilization of Ag NPs on glass plates and functionalized them by a set of differently charged hydrophilic thiols (sodium 2-mercaptoethyl sulfonate, mercaptopropionic acid, 2-mercaptoethanol, 2-(dimethylamino)ethanethiol hydrochloride, and thiocholine) to vary the surface charge of the SERS substrate. We used two oppositely charged porphyrins, cationic copper(II) tetrakis(4-N-methylpyridyl) porphine (CuTMpyP4) and anionic copper(II) 5,10,15,20-tetrakis(4-sulfonatophenyl)porphine (CuTSPP4), with equal charge value and similar structure as model analytes to probe the SERS signal. Our results indicate that the SERS spectrum intensity strongly, up to complete signal disappearance, correlates with the surface charge of the substrate, which tends to be negative. Using the data obtained and our model SERS system, we analyzed the modification of the Ag surface by different reagents (lithium chloride, polyethylenimine, polyhexamethylene guanidine, and multicharged metal ions). Finally, all those surface modifications were tested using a negatively charged oligonucleotide labeled with Black Hole Quencher dye. Only the addition of copper ions into the analyte solution yielded a good SERS signal. Considering the strong interaction of copper ions with the oligonucleotide molecules, we suppose that inversion of the analyte charge played a key role in this case, instead of a change of charge of the substrate surface. Changing the charge of analytes could be a promising way to get clear SERS spectra of negatively charged molecules on Ag SERS-active supports.

Octahedral silver oxide nanoparticles enabling remarkable SERS activity for detecting circulating tumor cells.

The detection of circulating tumor cells (CTCs) is a crucial tool for early cancer diagnosis, prognosis, and postoperative evaluation. However, detection sensitivity remains a major challenge because CTCs are extremely rare in peripheral blood. To effectively detect CTCs, octahedral Ag2O nanoparticles (NPs) with high dispersibility, good biocompatibility, remarkable surface-enhanced Raman scattering (SERS) enhancement, and obvious enhancement selectivity are designed as an SERS platform. Ag2O NPs with many oxygen vacancy defects are successfully synthesized, which exhibit an ultra-high SERS enhancement factor (1.98×106) for 4-mercaptopyridine molecules. The remarkable SERS activity of octahedral Ag2O NPs is derived from the synergistic effect of the surface defect-promoted photo-induced charge transfer (PICT) process and strong vibration coupling resonance in the Ag2O-molecule SERS complex, greatly amplifying the molecular Raman scattering cross-section. The promoted PICT process is confirmed using ultraviolet-visible (UV-Vis) absorption spectroscopy, demonstrating that obvious PICT resonance occurs in Ag2O SERS system under visible light. An additional growth step of SERS bioprobe is proposed by modifying the Raman signal molecules and functional biological molecules on Ag2O NPs for CTC detection. The Ag2O-based SERS bioprobe exhibits excellent detection specificity for different cancer cells in rabbit blood. Importantly, the high-sensitivity Ag2O-based SERS bioprobe satisfies the requirement for rare CTC detection in the peripheral blood of cancer patients, and the detection limit can reach 1 cell per mL. To our knowledge, this study is the first time that a semiconductor SERS substrate has been successfully utilized in CTC detection. This work provides new insights into CTC detection and the development of novel semiconductor-based SERS platforms for cancer diagnosis.

A label-free SERS sensor for the detection of Hg2+ based on phenylacetylene functionalized Ag nanoparticles

The development of a facile, rapid, precise, and ultrasensitive assay for the detection of mercury ions (Hg2+) is an urgent problem to be solved because excessive Hg2+ poses a great threat to human health and the ecological environment. Herein, a novel surface-enhanced Raman scattering (SERS) sensor which employed phenylacetylene (PA) as a label-free probe was established. The PA functionalized silver nanoparticles (PA-AgNPs) produced an intense SERS signal in the Raman-silent region, which effectively avoided the interference of solvent and overcame the signal overlap problem. In the presence of Hg2+, the PA molecules separated from the Ag surface due to the strong coordination between the alkynyl group and Hg2+, which resulted in a significant SERS signal attenuation. Basing on the proposed SERS platform, a linear relationship with a wide range from 10–10 to 10–8 M and a low detection limit of 87.6 pM were obtained. Besides, the selectivity and reproducibility of the SERS system were also investigated. What’s more, we applied the SERS sensor to analyze Hg2+ in lake water with high accuracy and excellent recovery. The obtained results demonstrated that the established SERS platform is expected to be a promising alternative tool for the determination of Hg2+ in practical application.

Hydrated Ionic Liquids Boost the Trace Detection Capacity of Proteins on TiO2 Support.

Trace detection based on surface-enhanced Raman scattering (SERS) has attracted considerable attention, and exploiting efficient strategies to stretch the limit of detection and understanding the mechanisms on molecular level are of utmost importance. In this work, we use ionic liquids (ILs) as trace additives in a protein-TiO2 system, allowing us to obtain an exceptionally low limit of detection down to 10–9 M. The enhancement factors (EFs) were determined to 2.30 × 104, 6.17 × 104, and 1.19 × 105, for the three systems: one without ILs, one with ILs in solutions, and one with ILs immobilized on the TiO2 substrate, respectively, corresponding to the molecular forces of 1.65, 1.32, and 1.16 nN quantified by the atomic force microscopy. The dissociation and following hydration of ILs, occurring in the SERS system, weakened the molecular forces but instead improved the electron transfer ability of ILs, which is the major contribution for the observed excellent detection. The weaker diffusion of the hydrated IL ions immobilized on the TiO2 substrate did provide a considerably greater EF value, compared to the ILs in the solution. This work clearly demonstrates the importance of the hydration of ions, causing an improved electron transfer ability of ILs and leading to an exceptional SERS performance in the field of trace detection. Our results should stimulate further development to use ILs in SERS and related applications in bioanalysis, medical diagnosis, and environmental science.

In situ synthesis of hybrid zinc oxide-silver nanoparticle arrays as a powerful active platform for surface-enhanced Raman scattering detection

Micro-structured molecular semiconductor film-based surface-enhanced Raman scattering (SERS) probes are an important analytical tool for both fundamental and technological research. This study proposed a novel zinc oxide (ZnO)-based, three-dimensional (3D) semiconductor nanoflower (NF) superstructure probe with unique physicochemical properties, including engineered hotspots allowing an arrangement of metallic nanoparticles (NPs), as a means to analyse target molecules. By changing the size, high-density hotspots distributed throughout the nanopetal-like ‘nanorods’ of ZnO supports. When used to analyse crystal violet (CV), there were synergistic effects of silver (Ag), ZnO, and CV molecules in the synthesised ZnONFs@Ag-CV SERS system. The SERS results revealed that the plasmonic surfaces of the self-assembled hotspots on the 3D ZnO superstructures provided effective molecular interactions between the ZnONFs@Ag platform and the Raman probe molecule. These interactions influenced the configuration and detection performance of SERS. Moreover, the performance was closely associated with enhancement of the electromagnetic mechanism and the charge transfer contribution in the platform between the semiconductor, metallic NPs, and the analyte molecules. As a result, the characteristic CV peaks were obvious even at a low concentration of 10 −10 M. In a mixture of two probes, the ZnONFs@Ag chip provided an outstanding selectivity in the quantitative and qualitative evaluation of each target molecule at low concentrations. The synthesised 3D ZnONFs@Ag heterostructure chip possesses excellent practical reproducibility and represents a promising candidate for chemical and biomedical inspection.

Chemometrics coupled 4-Aminothiophenol labelled Ag-Au alloy SERS off-signal nanosensor for quantitative detection of mercury in black tea.

Black tea like other food crops is prone to mercury ion (Hg2+) contamination right from cultivation to industrial processing. Due to the dangerous health effects posed even in trace contents, sensitive detection and quantification sensors are required. This study employed the surface-enhanced Raman scattering (SERS) enhancement property of 4-aminothiophenol (4-ATP) as a signal turn off approach functionalized on Ag-Au alloyed nanoparticle to firstly detect Hg2+ in standard solutions and spiked tea samples. Different chemometric algorithms were applied on the acquired SERS and inductively coupled plasma-mass spectrometry (ICP-MS) chemical reference data to select effective wavelengths and spectral variables in order to develop models to predict the Hg2+. Results indicated that Ag-Au/4-ATP SERS sensor combined with ant colony optimization partial least squares (ACO-PLS) exhibited the best correlation efficient and minimum errors for Hg2+ standard solutions (Rc=0.984, Rp=0.974, RMSEC=0.157μg/mL, RMSEP=0.211μg/mL) and spiked tea samples (Rc=0.979, Rp=0.963, RMSEC=0.181μg/g and RMSEP=0.210μg/g). The limit of detection of the proposed sensor was 4.12×10-7μg/mL for Hg2+ standard solutions and 2.83×10-5μg/g for Hg2+ spiked tea samples. High stability and reproducibility with relative standard deviation of 1.14% and 0.84% were detected. The potent strong relationship between the SERS sensor and the chemical reference method encourages the application of the developed chemometrics coupled SERS system for future monitoring and evaluation of Hg2+ in tea.

A particle-based microfluidic molecular separation integrating surface-enhanced Raman scattering sensing for purine derivatives analysis

Based on its highly specific and non-invasive features, surface-enhanced Raman scattering (SERS) has been applied for analytical chemistry or biological applications, such as identification of chemical compositions, cells or bacteria. However, if the targeted sample consists of multiple compounds, the corresponded SERS spectra would be quite difficult to analyze. To address above problems, we developed a particle-based microfluidic molecular separation (PMMS) integrating SERS substrate to separate complicate molecule mixture followed by in situ SERS detection. The platform consists of an automatic microfluidic control system to precisely control the sample and reagent flow in the PMMS–SERS device, composed of a 5-µm particle-packed separation column followed by a two-dimensional Ag nanostructural substrate. To proof-of-concept, we first tested the molecule separation functionality using the mixture of fluorescent FITC and R6G dyes. Later, we introduced the hypoxanthine and adenine mixture—main purine metabolites of E. coli—into the system for on-chip separation, identification, and quantification based on acquired SERS signatures. Overall, the miniaturized PMMS–SERS system enables an easy-to-use and sensitive analyte detection, which could be beneficial in applications requiring bacteria identification and quantification, such as environmental monitoring, AST, and drug development.

Detection of Pesticide Residues Using Nano-SERS Chip and a Smartphone-Based Raman Sensor

Nowadays, detection of pesticide residues is generally conducted in the laboratory using large-scale equipment such as liquid chromatography mass spectrometry, etc. These detection methods usually require a complicated pre-treatments and professional operators, which are time-consuming and expensive. Surface-enhanced Raman scattering (SERS) technology makes trace detection of pesticide residues implementable, but currently the devices for SERS on the market are all large-scale and rapid detection of pesticide residues has not been achieved yet. In this paper, a novel SERS system integrated with a cellphone is designed for the detection of pesticide residues. In the current system, the SERS chip is inserted directly onto the, and measurement of pesticide residues can be conducted by one-click through the cellphone application. We achieved successfully detection of 12 kinds of pesticides with characteristic Raman spectra and the limit of detection was less than 10 ppm, which makes rapid and on-site detection of pesticide residues feasible in future point of care test applications.

A facile and robust SERS platform for highly sensitive and reproducible detection of uracil-DNA glycosylase using target-activated plasmonic coupling

The self-assembly plasmonic nanoparticles with effective coupling have drawn considerable interest in quantitative surface-enhanced Raman scattering (SERS) detection, which facilitate their practical applications in chemical and biomolecular analysis. Herein, we report the development of a robust, sensitive and reproducible SERS platform for Uracil-DNA glycosylase (UDG) quantification using target-activated plasmonic coupling. This system consists of DNA substrates and Raman dyes-decorated gold nanoparticles (AuNPs) that functions as a target-recognition and SERS signal-output tool, and two kinds of enzymes, exonuclease I (Exo I) and endonuclease IV (Endo IV) that are utilized to degrade DNA substrates on AuNPs for controllable self-assembly of plasmonic nanoparticles. On account of this skilled design of SERS system, self-assembled hot spots with uniform interparticle gap and narrow enhancement factors (EFs) can be readily and repeatedly constructed by target-activated dual enzymatic cleavage reaction, which allows highly sensitive and reproducible SERS sensing of target UDG. Under optimized experimental conditions, the proposed biosensor exhibits excellent analytical performance toward the detection of UDG with a detection limit of 4.29 × 10−4 U mL−1 within a linear range of 1.0 × 10−3 U mL−1 to 10 U mL−1 for UDG, along with a favorable specificity and reproducibility. In addition, the practical applicability of this biosensor is demonstrated by the detection of UDG in cell extracts with satisfactory results. Hence, the target-activated plasmonic coupling-based strategy indeed creates a robust and convenient platform for UDG identification and related biomedicine research and clinical diagnosis.

Highly reproducible and fast detection of 6-thioguanine in human serum using a droplet-based microfluidic SERS system

6-thioguanine is an anticancer drug with narrow safe dose range and intense toxic reactions, so it is urgently necessary to evaluate its clinical usage. Reproducibility and analysis speed are important factors to take into account when analyzing drug concentration in body fluids. In this work, we fabricated a droplet-based microfluidic chip for detecting 6-thioguanine in human serum by using the surface-enhanced Raman scattering (SERS) technique. The easily-prepared Au nanoparticles were used as SERS substrates, and reagent mixing and signal acquiring happened in droplets one by one. This assay device is endowed with the superiority in improving determination repeatability with coefficient of variation of no more than 5% (n = 25) and high speed of 10 s each assay. The SERS peak at 1295 cm−1 originated from N1-C6 stretching vibration mode of purine ring was selected for quantitating 6-thioguanine. The signals indicated a satisfied linear relationship with the concentrations of 6-thioguanine in the range of 0.010 μM to 10 μM, with a detection limit of 0.032 μM. The droplet-based microfluidic SERS system was successfully applied for credible and rapid analysis of 6-thioguanine in human serum, and is pretty promising for performing the therapeutic drug monitoring.