Double Immobilized Superhydrophobic and Lubricated Slippery Surface with Antibacterial and Antifouling Properties.

A "double immobilized" superhydrophobic and lubricated slippery surface was prepared by simultaneously immobilizing lubricating oil and bactericide molecules. The coordination function of metal organic frameworks (MOFs) was utilized to immobilize trimesic acid, a fungicide, as a ligand of the MOF by the cathodic electrodeposition technique. Aminated silicone oil was used as a lubricating oil and was immobilized to the superhydrophobic MOF film by the curing reaction with isocyanates. This technique is a facile strategy to conductive substrates for fabricating superhydrophobic and lubricated slippery surfaces with satisfactory antibacterial and antifouling properties.

Raman inks based on triple-bond-containing polymeric nanoparticles for security.

Developing security inks with spectral outputs/multiple colors, which have unique identification characteristics, is of great importance in enhancing the anti-counterfeiting strength of ink anti-counterfeiting technology. Herein, a print-driven triple-bond coding mode is proposed for the first time. Two kinds of triple-bond-containing polymeric nanoparticles (NPs) with Raman shifts at 2227 and 2241 cm-1 have been designed into printable ink, and the decimal coding output can be easily obtained by reasonably adjusting the proportions of the two polymeric NPs. Single Raman scattering inks can be used as invisible inks to print monochromatic patterns and words that the decoder can read out. According to the two-dimensional pixels of the graphics decoder, invisible colorful graphics can be printed with mixed inks under different polymer proportions. More interestingly, three-dimensional invisible patterns with stronger anti-counterfeiting strength can also be obtained in the double-layer anti-counterfeiting patterns with different proportions of ink by the spatial complementary coding mode. It is predicted that more security inks associated with triple-bond Raman signals will spur the application of the anti-counterfeiting field.

Photoreduced Ag+ surrounding single poly(4-cyanostyrene) nanoparticles for undifferentiated SERS sensing and killing of bacteria.

Developing a rapid, low cost and sensitive sensing strategy for undifferentiated detection and fast killing of bacterial pathogens are critical to alleviating bacteria infections. Here, we propose a direct photoreduction method to synthesize the SERS tag by integrating poly(4-cyanostyrene) nanoparticles (NPs) and silver ions, which are applied as bio-sensing system for bacteria sensing and fast killing. Under a focused laser spot, silver ions on the surface of the poly(4-cyanostyrene) NPs could be photoreduced into Ag NPs, thereby causing the Raman signal amplification of poly(4-cyanostyrene) NPs up to 40 times, and there is a good linear correlation between the Raman intensity of poly(4-cyanostyrene) NPs and different concentrations of Ag+. Moreover, 4-mercaptophenylboronic acid, performing the same recognition function for both the Gram-positive and Gram-negative bacteria, is used as bridge between the bacteria and Ag+ by the inherent chemical bonding. Based on further constructed bio-sensing system, we achieved the quick count and killing of both Gram-positive bacteria, e.g., Staphylococcus aureus (S. aureus), and Gram-negative bacteria, e.g., Escherichia coli (E. coli). Notably, the sensing strategy can detect at least ∼100 cells of E. coli, ∼10 cells of S. aureus and ∼10 cells of their mixture in less than 40 min. The detection accuracy for actual samples can also reach over 80% and the bacteria were entirely killed by Ag+ after the detection, avoiding bacterial contamination in the environment. This novel method is anticipated to perform as a simple yet effective tool for fast and sensitive bacteria counting and killing.

Rational synthesis of Three-Layered plasmonic nanocomposites of copper Sulfide/Gold/Zinc-Doped Prussian blue analogues for improved photothermal disinfection and wound healing.

Bacteria-infected wounds have imposed serious challenges in human health whereas the abuse of antibiotics makes bacteria drug-resistant and becoming more and more difficult to deal with. Herein, we developed a drug-free three-layered photothermal bactericide from inside to outside consisting of copper sulfide (CuS), gold (Au) and zinc-doped Prussian blue analogues (ZnPBA) (named as CuS@Au@ZnPBA). The CuS@Au@ZnPBA was demonstrated to possess remarkably-improved photothermal property and excellent biosafety. Local heat generated by CuS@Au@ZnPBA under the irradiation of 808 nm laser enables efficient bacteria ablation in vitro and in a mouse model of cutaneous wound infection. Meanwhile, the released zinc ions (Zn2+) could upregulate the genes involved in collagen deposition to accelerate wound healing. Overall, the finely-designed nanocomposites can serve as a promising kind of antibacterial alternative to current antibiotic therapies against bacterial wound infections.

A functional peptide-mediated colorimetric assay for mercury ion based on dual-modified gold nanoparticles.

In the work, a rapid and accurate biosensor for mercury ions (Hg2+) was constructed, with which aggregation of dual-modified (DGPFHR- and CALNN-) gold nanoparticles (D/C-AuNPs) could be triggered by the high specificity of peptides to Hg2+. The given peptide DGPFHR possesses great capability of capturing Hg2+, accompanied by the conformational folding. Under the circumstances, D/C-AuNPs were employed as the detection probes to accomplish the quantitative analysis of Hg2+. This is primarily because the specific Hg2+-induced folding of peptides reduces the electrostatic repulsion and steric hindrance, thus accelerating the AuNPs aggregation. The principle and application potential of this proposal was proved by evidence. And the results demonstrated that Hg2+ ions could be selectively detected as low as 28 nM with a linear range of 100-800 nM. In consideration of superior simplicity, selectivity, accuracy and stability, the protocol was advantageous over other projects in practical measurement of various water samples.

Precise Encoding of Triple-Bond Raman Scattering of Single Polymer Nanoparticles for Multiplexed Imaging Application.

Stimulated Raman scattering (SRS) microscopy in combination with innovative tagging strategies offers great potential as a universal high-throughput biomedical imaging tool. Here, we report rationally tailored small molecular monomers containing triple-bond units with large Raman scattering cross-sections, which can be polymerized at the nanoscale for enhancement of SRS contrast with smaller but brighter optical nanotags with artificial fingerprint output. From this, a class of triple-bond rich polymer nanoparticles (NPs) was engineered by regulating the relative dosages of three chemically different triple-bond monomers in co-polymerization. The bonding strategy allowed for 15 spectrally distinguishable triple-bond combinations. These accurately structured nano molecular aggregates, rather than long-chain macromolecules, could establish a universal method for generating small-sized biological SRS imaging tags with high sensitivity for high-throughput multi-color biomedical imaging.

Promoted "Click" SERS Detection for Precise Intracellular Imaging of Caspase-3.

Although homogeneous detection of some biomolecules has been of great significance in clinical assay, it faces great challenges in achieving precise in situ imaging of biomolecules. In addition, nonspecific adsorption between probes and biomolecules and low sensitivity are still unfathomed problems. Herein, we developed a promoted "Click" surface enhanced Raman scattering (SERS) strategy for realizing highly selective homogeneous detection of biomolecules by simultaneous dual enhanced SERS emissions, obtaining mutually confirmed logical judgment. Taking caspase-3 as one of the biotargets, we have realized highly selective homogeneous detection of caspase-3 using this strategy, and precise intracellular imaging of caspase-3 can be in situ monitored in living cells or during cell apoptosis. In detail, polyA-DNA and the Asp-Glu-Val-Asp (DEVD)-containing peptide sequence were modified into alkyne and nitrile-coded Au nanoparticles (NPs). During the cell apoptosis process, the generated caspase-3 would lead to the cleavage of the tetra-peptide sequence DEVD, thereby removing the negative protection part from the peptide on Au NPs. Interestingly, two different triple bond-labeled Au NPs can be connected together through DNA hybridization to form SERS "hotspot", resulting in simultaneously enlarged triple bond Raman signals. Moreover, we found that the SERS intensity was positively related with caspase-3 concentration, which has a wide linear range (0.1 ng/mL to 10 µg/mL) and low detection limit (7.18 × 10-2 ng/mL). Remarkably, these simultaneously enlarged signals by "Click" SERS could be used for more precise imaging of caspase-3, providing mutually confirmed logical judgment based on two spliced SERS emissions, especially for their relative intensity.

A straightforward and reliable evaluation of Ag(I) binding affinity mediated by a peptide ligand for constructing an efficient sensing platform.

The reliable determination of the Ag(I) affinity for biomolecules is an essential issue in the fields of structural analysis and sensor design. However, the urgent problem confronting researchers is lack of a direct and accurate Ag(I) affinity evaluation as a reference standard for ligand analysis. We communicated here a straightforward and high-efficiency method of measuring Ag(I) affinity exactly on the basis of the unique calculation algorithm and the design of a special peptide RFPRDD (P) as Ag(I) binding motif. According to UV-vis competition between the corresponding complexes (AgP) and biomolecules (peptides, amino acids and ssDNA), the decrease of the signature at 300 nm characteristic of AgP was obtained for quantitative analysis. The primary advantages of this strategy were the widespread application, high accuracy and reference significance, which were corroborated by theoretical calculations. To identify its potential in biosensing, two kinds of testing models for Ag(I) were proposed by AgBP2-decorated and Ag4-decorated gold nanoparticles, the detection limits of which were 2 nM and 75 nM respectively. By contrast of the sensing property of the functional peptides (AgBP2, Ag4), we afforded evidence that this conception could be regarded as an evaluation criterion for the selection and performance optimization of sensitive elements, thereby holding a dominant position in the biosensors.

On-site and quantitative SERS detection of trace 1, 2, 3-benzotriazole in transformer oil with colloidal lignin particles-based green pretreatment reagents.

Since 1, 2, 3-Benzotriazole (BTA) is one of the most commonly used metal passivators in transformer oil, on-site and quantitative detection of BTA plays a significant role in fast evaluation of the performance of the insulating oil. Herein, we proposed a cycle-growth synthetic protocol for yielding two-dimensional (2D) plane-based surface-enhanced Raman scattering (SERS) substrates with tunable optical property and controllable interparticle distance, and an extraction material, so called colloidal lignin particles (CLPs), for the fast separation of BTA from oil matrix. After BTA from transformer oil were adsorbed by hydrophilic CLPs, highly reproducible SERS signal of BTA can be obtained by dropping on the substrate. The characteristic Raman shift at 1386 cm-1 of BTA has been selected to establish a good linearity between its relative intensity and concentration in the range of 1-300 mg/L, and the detection limit for BTA was down to 0.12 mg/L. Moreover, the time consumption for the whole detection process of real sample including sample pretreatment and SERS measurements was less than 30 min. It is highly expected that the combination of CLPs with SERS can accomplish the on-site detection of trace BTA in transformer oil.

The small silver nanoparticle-assisted homogeneous sensing of thiocyanate ions with an ultra-wide window based on surface-enhanced Raman-extinction spectroscopy.

For the first time, we present an original sensing strategy with an ultra-wide detection window from 17 nM to 20 mM to detect SCN- ions. Initially, we investigated the clustering and optical properties of noble metal sol nanoparticles (NPs) due to the competitive interaction of thiocyanate ions (SCN-) and cetyltrimethylammonium bromide (CTAB) under weak acidic conditions, and found that different dimensions and scales of nanoclusters containing the alkyne-embedded Au@Ag NPs and relatively small Ag NPs could be achieved by the mediation of CTAB through electrostatic forces and hydrophobic interaction, in which SCN- could be covalently bonded with the silver surface of NPs to form a compact molecular layer (-Ag-S-C[triple bond, length as m-dash]N), and CTAB could only occupy remaining sites. In this process, we found that SCN- always runs counter to CTAB and tends to dissolve nanoclusters, so that they occupy the exposed surface of NPs in nanoclusters rather than the binding sites of one another. Remarkably, when the concentration of SCN- initially increased, two highly recognizable SERS emissions, which were assigned to alkyne reporter molecules (2208 cm-1) and C[triple bond, length as m-dash]N of SCN- (2110 cm-1), respectively, were rapidly detected, and their ratios (I2110/I2208) increased linearly proportional to the concentration of SCN- over a range of 17 nM to 172 µM, with a limit of detection (LOD) of 10 nM. With the further increase of SCN-, small Ag NPs started to desorb from the surface of individual Au@Ag NPs and dissociated in the solution but did not contribute to SERS signals. Instead, the surface plasmon resonance (SPR) peak of pure silver NPs at 385 nm increased gradually in the range from 0.5 to 20 mM with an LOD of 0.2 mM. Of particular significance, this simple sensor in conjunction with surface-enhanced Raman-extinction spectroscopy can be used for the rapid detection of extensive samples with an ultra-wide detection window, such as body fluids (saliva, urine, and serum) and food (milk powder and brassica vegetables), which is far superior to that of ion chromatography (IC).

Fine synthesis of Prussian-blue analogue coated gold nanoparticles (Au@PBA NPs) for sorting specific cancer cell subtypes.

Multiplex surface-enhanced Raman scattering (SERS) detection of markers without background in tumor biosystems has its superiority over other optical methods. Herein, we reported a strategy of quantitative discrimination of two breast cancer cell subtypes. Based on our previous studies, two kinds of Prussian blue analogue coated gold nanoparticles (Au@PBA NPs) were designed and synthesized by the replacement of Fe2+ with Pb2+ or Cu2+. Therefore, two distinct SERS emissions of C≡N bonds at 2122 cm-1 and 2176 cm-1 have been acquired. When modified with aptamers of epithelial cell adhesion molecule (EpCAM) and epidermal growth factor receptor (EGFR), which are both expressed in MCF-7 and MDA-MB-231 cell lines but in different levels, the SERS nanoprobes simultaneously identified the relative expression of these biomarkers on the cell surface, providing a good example for ratiometric detection in biosystems without any interference. Each surface marker of tumor cells corresponds to a single SERS emission. Thus, each subtype could be described in a molecular profiling way through duplex C≡N bonds-based SERS emission, which is more advanced than traditional flow cytometry method.

Recent advances in plasmonic Prussian blue-based SERS nanotags for biological application.

The reliability and reproducibility of surface-enhanced Raman scattering (SERS) technology is still a great challenge in bio-related analysis. Prussian blue (PB)-based SERS tags have attracted increasing interest for improving these deficiencies due to its unique Raman band (near 2156 cm-1) in the Raman-silent region, providing zero-background bio-Raman labels without interference from endogenous biomolecules. Moreover, the stable PB shell consisting of multiple layers of CN- reporters ensure a stable and strong Raman signal output, avoiding the desorption of the Raman reporter from the plasmonic region by the competitive adsorption of the analyte. More importantly, they possess outstanding multiplexing potential in biological analysis owing to the adjustable Raman shift with unique narrow spectral widths. Despite more attention having been attracted to the structure and preparation of PB-based SERS tags for their better biological applications over the past five years, there is still a great challenge for SERS suitable for applications in the actual environment. The biological applications of PB-based SERS tags are comprehensively recounted in this minireview, mainly focusing on quantification analysis, multiple-spectral analysis and cell-imaging joint phototherapy. The prospects of PB-based SERS tags in clinical diagnosis and treatment are also discussed. This review aims to draw attention to the importance of SERS tags and provide a reference for the design and application of PB-based SERS tags in future bio-applications.

Nucleic Acid Hybridization-Based Noise Suppression for Ultraselective Multiplexed Amplification of Mutant Variants.

The analysis of mutant nucleic acid (NA) variants can provide crucial clinical and biological insights for many diseases. Yet, existing analysis techniques are generally constrained by nonspecific "noise" signals from excessive wildtype background sequences, especially under rapid isothermal multiplexed target amplification conditions. Herein, the molecular hybridization chemistry between NA bases is manipulated to suppress noise signals and achieve ultraselective multiplexed detection of cancer gene fusion NA variants. Firstly, modified locked NA (LNA) bases are rationally introduced into oligonucleotide sequences as designed "locker probes" for high affinity hybridization to wildtype sequences, leading to enrichment of mutant variants for multiplexed isothermal amplification. Secondly, locker probes are coupled with a customized "proximity-programmed" (SERS) readout which allows precise control of hybridization-based plasmonic signaling to specifically detect multiple target amplicons within a single reaction. Moreover, the use of triple bond Raman reporters endows NA noise signal-free quantification in the Raman silent region (≈1800-2600 cm-1 ). With this dual molecular hybridization-based strategy, ultraselective multiplexed detection of gene fusion NA variants in cancer cellular models is actualized with successful noise suppression of native wildtype sequences. The distinct benefits of isothermal NA amplification and SERS multiplexing ability are simultaneously harnessed.

A laser metallurgy route for the batch preparation of mm-scale 3D silver/graphite heteronanoclusters in air.

We report a batch preparation of mm-scale 3D Ag hetero-nanoclusters which exhibit an excellent surface plasmon resonance ability via facile laser metallurgy. Under laser irradiation, the porous AgI-based coordination network crystals were instantly converted into 3D graphite-encapsulated Ag hetero-nanoclusters with uniform sizes and gaps in several seconds. The obtained hetero-nanoclusters exhibited superior 3D confocal laser energy utilization compared with the other 0D, 1D and 2D SERS substrates, solving the bottleneck caused by laser focusing deviation in the SERS active depth. The mass-produced SERS devices were ultra-sensitive for the detection of life and industrial organic pollutants in terms of low detection and enriched capacity.

On-Site and Quantitative Detection of Trace Methamphetamine in Urine/Serum Samples with a Surface-Enhanced Raman Scattering-Active Microcavity and Rapid Pretreatment Device.

Here, it reports a high-throughput detection method for reliably quantitative analysis of illegal drugs in complex biological samples by means of a surface-enhanced Raman scattering (SERS) active microcavity and rapid pretreatment device. Based on the well-made hemispherical microcavities that regularly distributed on a glass array, the quality-controllable microcavity device is fabricated by the compact self-assembly of core-shell nanopeanuts (CSNPs) onto the inside surface. Both the CSNPs with a quantifiable internal standard signal of crystal violet acetate anchored inside their gap and the well-made microcavity referred to the physical amplification of the microscale groove surface will do well in trace analysis, which will allow us to realize the accurately quantitative SERS analysis of targeted analytes spread on the bottom area of the microcavity array. As an example, 0.8 nM malachite green and 160 ppb methamphetamine (MATM) have been successively detected in a wide range as standard, while even 0.01 ppm MATM mixed in the urine/serum samples has been efficiently tested by the microcavity device equipped with a rapid pretreatment device (manual monolithic column syringe needle). All of the above suggest that the SERS-active microcavity equipped with a rapid pretreatment device has potential in the on-site quick test of trace amounts of illegal drugs in bodily fluid samples or other field analysis of food sanitation, environmental safety, and public health.

Monodispersed plasmonic Prussian blue nanoparticles for zero-background SERS/MRI-guided phototherapy.

Surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI)-guided phototherapy are new breakthroughs in cancer therapeutics due to their complementary advantages, such as enhanced imaging spatial resolution and depth. Herein, we synthesized monodispersed Prussian blue-encapsulated gold nanoparticles (Au@PB NPs), in which the plasmonic gold core plus coordination polymer of cyanide (C[triple bond, length as m-dash]N) and iron ions coincidently become a superexcellent contrast agent for both MRI and zero-background SERS imaging. PB, as a signal source for MR and SERS, can be easily assembled onto single Au NPs, of which iron ions possess high relaxation efficiency for in vivo MRI, e.g., the longitudinal and transversal relaxation efficiency values are 0.86 mM-1 s-1 (r1) and 5.42 mM-1 s-1 (r2), respectively. Furthermore, with the help of the plasmonic enhancement of the gold core, the C[triple bond, length as m-dash]N groups exhibit a specific, strong, and stable (3S) SERS emission in the Raman-silent region (1800-2800 cm-1), allowing accurate in vivo imaging at the single or even subcellular level. More importantly, PB has remarkable absorption properties in the near infrared region, and can be used as a photosensitizer for photothermal (PT) and photodynamic (PD) therapy simultaneously. Hence, the ideal integration of a plasmonic Au core and PB shell into a single monodispersed MR-guided NP, with zero-background SERS signals, is an important candidate for both tumor navigation and in situ PT/PD treatment guided by SERS/MR dual-mode imaging.

Combined Surface-Enhanced Raman Scattering Emissions for High-Throughput Optical Labels on Micrometer-Scale Objects.

High-throughput optical labeling technologies have become increasingly important with the growing demands for molecular detection, disease diagnosis, and drug discovery. In this thought, a series of CN-bridged coordination polymer encapsulated gold nanoparticles have been developed as a universal and interference-free optical label through a facile and auxiliary agent-free self-assembly route. Moreover, surface-enhanced Raman scattering (SERS) emissions of CN-bridge can be tuned flexibly by simple replacement of Fe2+/Fe3+ with other metal ions relying on the synthesis of three Prussian blue analogues encapsulated gold nanoparticles (Au@PBA NPs). Thus, three distinct Raman frequencies have been acquired, which merely replaced the metal irons. On the basis of the potential supermultiplex optical label, space-confined surface-enhanced Raman scattering (SERS) emissions have been realized. Relying on "Abbe theorem", the focused laser allows the pure and single triple bond-coded SERS emissions to be combined into a unique and independent output, so-called "combined SERS emission" (c-SERS), if the Au@PBA NPs were confined into one micrometer-scale object. This study demonstrated c-SERS may simultaneously provide 2n - 1 optical labels only using n single emissions in the Raman-silent region for micrometer-size objects.

Accurate Clinical Diagnosis of Liver Cancer Based on Simultaneous Detection of Ternary Specific Antigens by Magnetic Induced Mixing Surface-Enhanced Raman Scattering Emissions.

Establishing an accurate, simple, and rapid serodiagnosis method aiming for specific cancer antigens is critically important for the clinical diagnosis, therapy, and prognostication of cancer. Currently, surface-enhanced Raman scattering (SERS) readout techniques challenge fluorescent-based detection methods in terms of both optical stability and more importantly multiple detection capability, which become more desirable for clinical diagnostics. We thus started using an interference-free mixing SERS emission (m-SERS) readout to simultaneously indicate, for the first time, three specific liver cancer antigens, including α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and ferritin (FER), even in one clinical serum sample. Here, three triple bonds (C≡N and C≡C) coded SERS tags contribute separate SERS emissions located at 2105, 2159, and 2227 cm-1, respectively; must have one-to-one correspondence from AFP, to FER, to CEA, In the process of detection, the mature double antibody sandwich allows the formation of microscale core-satellite assembly structure between a magnetic bead (MB) and single SERS tags, and therefore a pure and single SERS emission can be observed under the routine excitation laser spot. Because of the action of magnetic force, the uniform 3D packing of SERS tags absorbed MBs will in contrast generate a so-called m-SERS signals. With the help of enrichment and separation by MBs, the proposed m-SERS immunoassay provides an extremely rapid, sensitive, and accurate solution for multiplex detection of antigens or other biomarkers. Herein, the limit of detection (LOD) for simultaneous m-SERS detection of AFP, CEA, and FER was 0.15, 20, and 4 pg/mL, respectively. As expected for 39 clinical serum samples, simultaneous detection of ternary specific antigens can significantly improve the accuracy of liver cancer diagnosis.

Total Aqueous Synthesis of Au@Cu2-x S Core-Shell Nanoparticles for In Vitro and In Vivo SERS/PA Imaging-Guided Photothermal Cancer Therapy.

Both accurate tumor navigation and nanostructures with high photothermal (PT) conversion efficiency are important but remain challenging to achieve in current biomedical applications. This study reports an anion exchange-based facile and green approach for synthesizing Au@Cu2-x S core-shell nanoparticles (NPs) in an aqueous system. In addition to the PT effect of the suggested NPs, the surface-enhanced Raman scattering (SERS) is also significantly improved due to the tailored localized surface plasmon resonance coupling between the Au metal core and the Cu2-x S semiconductor shell. Using an epitaxial strategy, Au@Cu2 O NPs are first obtained by the in situ reduction of cupric hydroxide on a cresyl violet acetate-coated Au core; then, Au@Cu2-x S NPs are obtained via anion exchange between the S2- and Cu2 O shell. Both the Cu/S atomic ratio and the Cu2-x S shell thickness can be adjusted conveniently. Hence, the ideal integration of the plasmonic Au core and Cu2-x S shell into a single unit is conducive not only to highly efficient PT conversion but also to the construction of a SERS-based navigator. This new type of SERS-guided NP, with enhanced photoacoustic signals, is an important candidate for both accurate tumor navigation and nondestructive PT treatment guided in vivo by two modes of optical imaging.

Rational synthesis of hollow cubic CuS@Spiky Au core-shell nanoparticles for enhanced photothermal and SERS effects.

Hollow cubic CuS@Spiky Au core-shell nanoparticles (NPs) were rationally synthesized both for guided highly efficient damage to cancer cells by the photothermal effect and for the real-time monitoring of biochemical responses during cellular apoptosis, totally based on label-free SERS intracellular imaging.