The first appeal of clinical assay is always accurate and rapid. For alkaline phosphatase (ALP) monitoring in medical treatment, a rapid, reliable surface-enhanced Raman scattering (SERS) test kit is designed based on a “hot spots” amplification strategy. Consisting of alkyne-tagged Au nanoparticles (NPs), Ag+, and enzyme substrate, the packaged test kit can achieve one-step clinical assay of ALP in human serum within several minutes, while the operation is simple as it directly inputs the sample into the test kit. Here, Ag+ ions are adsorbed onto the surface of Au core due to electrostatic interaction between Ag+ and the negatively charged donor surface, then enzymatic biocatalysis of ALP triggers the reduction of Ag+ and subsequently silver growth occurs on every Au core surface in a controllable manner, forming “hot spots” between the Au core and Ag shell, in which the SERS signal of alkyne Raman reporters would be highly amplified. Meanwhile, ALP mediates a redox reaction of Ag+ as well as the dynamic silver coating process so the increase of SERS intensity is well-controlled and can be recognized with increasing amounts of the targets. Instead of conventional NP aggregation, this leads to a more reproducible result. In particular, the distinct Raman emission from our self-synthesized alkyne reporter is narrow and stable with zero background in the Raman silent region, suffering no optical fluctuation from biosystem inputs and the detection results are therefore reliable with a limit of detection of 0.01 U/L (2.3 pg/mL). Along with ultrahigh stability, this SERS test kit therefore is an important point-of-care candidate for a reliable, efficacious, and highly sensitive detection method for ALP, which potentially decreases the need for time-consuming clinical trials.Keywords: alkaline phosphatase; one-step clinical assay; rapid detection; self-assembly on single NP; SERS; test kit;

Field, reliable, and ultrasensitive detection of dipicolinic acid (DPA), a general biomarker of bacterial spores and especially Bacillus anthracis, is highly desirable but still challenging in current biometric security emergency response system. Herein we report an environmentally safe mercury(II) ions-mediated and competitive coordination interaction based approach for rationally designed surface-enhanced Raman scattering (SERS)-active gold nanoparticles (AuNPs), enabling rapid, ultrasensitive and zero-background detection of DPA without the pretreatment of samples. By means of competitiveness, these papain-capped gold nanoparticles (P-AuNPs) are induced to undergo controllable aggregation upon the addition of Hg2+ ions and DPA with a concentration range (1 nM∼8 μM), which correspondingly cause quantitative changes of SERS intensity of cresyl violet acetate (CVa) conjugated AuNPs. The decreased Raman intensity obtained by subtracting two cases of additives that contain only Hg2+ and the mixture of Hg2+ and DPA is proportional to the concentration of DPA over a range of 1 nM∼8 μM (R2 = 0.9824), with by far the lowest limit of detection (LOD) of 67.25 pM (0.01 ppb, S/N = 3:1). Of particular significance, mercury(II) ions actually play two roles in the process of measurements: a mediator for two designed competitive ligands (DPA and papain), and also a scavenger for the possibly blended ligands due to the different interaction time between DPA and the interferent with Hg2+ ions, which guarantees the interference-free detection of DPA even under real conditions.

•Simple and rapid label-free SERS detection of Hg2+.•2,5-Dimercapto-1,3,4-thiadiazole acts as both interior label and target acquisition.•Coordination rationale of 2,5-Dimercapto-1,3,4-thiadiazole and Hg2+ clarified.•Ultrahigh sensitivity and selectivity were achieved by strong Hg2+-N coordination.Unbiodegradable toxic Hg2+ accumulates in ecological systems and results in contaminated food chain, exposing us to high level pollution and healthy risk. Here, monolayer 2,5-Dimercapto-1,3,4-thiadiazole (DMcT) functionalized Au@Ag nanoparticles (NPs) were controllably constructed as a label-free SERS probe. Based on them, we can perform rapid and easy Hg2+ identification with high sensitivity and selectivity over competing analytes. Remarkably, DMcT acted as both interior label and target acquisition. Since DMcT showed intrinsic Raman signal when attached to substrates surface, it can be employed for quantification instead of extra conventional signal label. Also, we’ve demonstrated that DMcT coordinated on the surface of Au@Ag NPs as bidentate ligand with both the thiocarbonyl sulfur atoms while the nitrogen atoms on the different sides of the molecule were devoted to Hg2+ recognition. Owing to the strong coordination between Hg2+ and nitrogen atoms, as low as 10 pM Hg2+ can be detected. The probe responded a good linear relationship ranging from 0.05 to 100 nM and the limit of detection is ~3 orders of magnitude lower than the United States Environmental Protection Agency (USEPA)-defined limit (10 nM) in drinkable water (EPA: Washington, DC, 2001). Furthermore, our suggested platform is highly effective to perform real samples detection. Utilizing the environmental water from East Lake, Wuhan, it resulted in better accuracy over the conventional standard method.

Field and pretreatment-free detection of heavy-metal ions in organic polluted water is important but still challenging in current water pollution emergency response systems. Here we report a polyadenine–DNA-mediated approach for a rationally designed alkyne-coded surface-enhanced Raman scattering (SERS) test kit, enabling rapid and simultaneous detection of Hg2+ and Ag+ by a portable spectrometer, impervious to organic interferences. Because of the formation of thymine (T)–Hg2+–T and cytosine (C)–Ag+–C, highly recognizable SERS signals are rapidly detected when two different alkyne-labeled gold nanoparticles (AuNPs) are induced to undergo controllable bridging upon the addition of low-volume targets. For multiplex detection through a portable spectrometer, the limits of detection reach 0.77 and 0.86 nM for Hg2+ and Ag+, respectively. Of particular significance, the proposed C≡C-containing Raman reporters provide an extremely effective solution for multiplex sensing in a spectral silent region, when the hyperspectral and fairly intense optical noises originating from lower wavenumber region (<1800 cm–1) are inevitable under complex ambient conditions.Keywords: alkyne; metal ions; organic-rich water sample; probe; SERS; test kit

The alkyne tags possess unique interference-free Raman emissions but are still hindered for further application in the field of biochemical labels due to its extremely weak spontaneous Raman scattering. With the aid of computational chemistry, herein, an alkyne-modulated surface-enhanced Raman scattering (SERS) palette is constructed based on rationally designed 4-ethynylbenzenethiol derivatives for spectroscopic signature, Au@Ag core for optical enhancement and an encapsulating polyallylamine shell for protection and conjugation. Even for the pigment rich plant cell (e.g., pollen), the alkyne-coded SERS tag can be highly discerned on two-dimension distribution impervious to strong organic interferences originating from resonance-enhanced Raman scattering or autofluorescence. In addition, the alkynyl-containing Raman reporters contribute especially narrow emission, band shift-tunable (2100–2300 cm–1) and tremendously enhanced Raman signals when the alkynyl group locates at para position of mercaptobenzene ring. Depending on only single Raman band, the suggested alkyne-modulated SERS-palette potentially provides a more effective solution for multiplex cellular imaging with vibrant colors, when the hyperspectral and fairly intense optical noises originating from lower wavenumber region (<1800 cm–1) are inevitable under complex ambient conditions.

We report on a continuous and non-invasive approach in vivo to monitor arterial blood pH based on the laser trapping and Raman detection of single live erythrocytes. A home-built confocal laser tweezers Raman system (LTRS) is applied to trace the live erythrocytes at different pH values of the extracellular environment to record their corresponding Raman changes in vitro and in vivo. The analysis results in vitro show that when the extracellular environment pH changes from 6.5 to 9.0, the Raman intensity ratio (R1603, 1616 = I1603/I1616) of single erythrocytes decrease regularly; what is more, there is a good linear relationship between these two variables, and the linearity is 0.985, which is also verified successfully via in vivo Raman measurements. These results demonstrate that the Raman signal of single live erythrocytes is possible as a marker of the extracellular pH value. This in vivo and quantitative Raman-pH sensor of arterial blood will be an important candidate for monitoring the acid–base status during the treatment of ill patients and in some major surgeries because of its continuous and non-invasive characters.

Nitrites (NO2− ions) in food and drink play an important role in human health but require complicated operations before detection. Herein, we present a rationally designed SERS-enabled micro-chamber that comprised a drawn glass capillary with a tiny orifice (∼50 μm) at the distal tip, wherein the gold nanoparticles (Au NPs) are compactly coated on the inner wall surface. In this chamber, nitrites specifically trigger a pH and laser irradiance-dependent diazotization starting from p-aminothiophenol (PATP) absorbed onto the surface of Au NPs to form p,p′-dimercaptoazobenzene (DMAB) molecules, in which the presence of NO2− ions above 30.7 μM (1.38 ppm) in the siphoned liquid sample can be identified relying on SERS peak (1141 cm−1) intensity of the emerging azo moiety. Except for pH conditions, laser irradiance is more important but easily neglected in previous studies, which is capable of preventing generation of errors when the detection sensitivity was pursued through increasing the laser power. In this case, several real samples (rather than simple water samples), including honey, pickled vegetable and fermented bean curd, had been successfully detected accurately through such a convenient sampling micro-chamber. The SERS-enabled device could potentially be facilely incorporated with portable Raman instruments for a special application of food inspection in rapid and field analysis of NO2− ions.

We herein present a simple and surfactant-free synthetic strategy for the preparation of core–shell Fructus Broussonetia-like Au@Ag@Pt nanoparticles (FBNPs) via a combination of galvanic replacement and reagent reduction, in which a chitosan (CS)-mediated epitaxial growth of Pt multi-branches occurs on cresyl violet labeled Au core–Ag shell nanoparticles (NPs) at room temperature. The as-prepared novel nanostructures exhibit an enzyme mimetic activity due to the formation of a Fructus Broussonetia-shaped Pt shell, the absence of surfactants and the positively charged CS molecules intertwined within the outermost Pt NPs. Relying on the high sensitivity of resonance-enhanced Raman scattering and the highly efficient intrinsic peroxidase-like activity of FBNPs, H2O2 was detected with a wide detection window from 10 pM to 100 μM when utilizing 3,3′,5,5′-tetramethylbenzidine (TMB) as the substrate. Based on the H2O2–TMB catalytic oxidation system a simple, sensitive, selective and universal platform has been extended for the detection of all peroxidase-related analytes. For example, glucose at a concentration range of 1 nM to 200 μM was detected in the presence of glucose oxidase with a limit of detection of 1 nM.

Methane-oxidizing bacteria (MOB) are a unique group of gram-negative bacteria that are proved to be biological indicator for gas prospecting since they utilize methane as a sole source of carbon and energy. Herein the feasibility of a novel and efficient gas prospecting method using Raman spectroscopy is studied. Confocal Raman spectroscopy is utilized to establish a Raman database of 11 species of methanotrophs and other closely related bacteria with similar morphology that generally coexist in the upper soil of natural gas. After strict and consistent spectral preprocessing, Raman spectra from the whole cell area are analyzed using the combination of principal component analysis (PCA) and Mahalanobis distance (MD) that allow unambiguous classification of the different cell types with an accuracy of 95.91%. The discrimination model based on multivariate analysis is further evaluated by classifying Raman spectra from independently cultivated bacteria, and achieves an overall accuracy of 94.04% on species level. Our approach using Raman spectroscopy in combination with statistical analysis of various gas reservoirs related bacteria provides rapid distinction that can potentially play a vital role in gas exploration.

•A non-invasive and comprehensive analysis of Chinese enamels from the Imperial Palace of China.•The major ingredient of the cloisonné enamel and the painted enamel was discussed for the first time.•Elemental analysis-aided Raman spectroscopy is useful with regard to the restoration cultural relic.Two kinds of enamels, including Chinese cloisonné wares from Fuwang chamber and gourd-shaped painted enamels decorations from the Forbidden City, in the Imperial Palace of China, are investigated by micro-Raman spectroscopy in combination with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and energy-dispersive X-ray fluorescence (EDXRF) in order to examine and analyze the composition of the glaze layer in each case. In this study the excitation is employed with either a NIR laser (785 nm) or a red laser (632.8 nm) in order to effectively eliminate the interference of background fluorescence and resonance effect. We have identified that the major matrix ingredients of the cloisonné wares are lead-based potash-lime silicate glasses while lead-potash silicate glass matrix is the main constituent for the painted enamels. Eight different colored areas of glaze layer also have been discussed in detail due to the distinct colors including turquoise, deep blue, yellow, white, red, pink, deep green and pale green. Their identification based on Raman data will be useful with regard to rapid and on site analysis and the restoration of the enamel decorations.

Novel three-dimensional (3D) nano-assemblies of noble metal nanoparticle (NP)–infinite coordination polymers (ICPs) are conveniently fabricated through the infiltration of HAuCl4 into hollow Au@Ag@ICPs core–shell nanostructures and its replacement reaction with Au@Ag NPs. The present 3D nano-assemblies exhibit highly efficient and specific intrinsic oxidase-like activity even without adding any cosubstrate.

We report the first microsampling device for reliably quantitative, label-free and separation-free detection of multicomponents of surface organic residues (SORs) by means of a quality controllable surface-enhanced Raman scattering (SERS)-enabled micropipette. The micropipette is comprised of a drawn glass capillary with a tiny orifice (∼50 μm) at the distal tip, where the specially designed nanorattles (NRs) are compactly coated on the inner wall surface. SERS signals of 4-mercapto benzoic acid (MBA) anchored inside the internal gap of NRs could be used to evaluate and control the quality of micropipettes and, therefore, allow us to overcome the limitations of a reliably quantitative SERS assay using traditional substrates without an internal standard. By dropping a trace extraction agent on targeting SORs located on a narrow surface, the capillary and SERS functionalities of these micropipettes allow on-site microsampling via capillary action and subsequent multiplex distinction/detection due to their molecularly narrow Raman peaks. For example, 8 nM thiram (TMTD), 8 nM malachite green (MG), and 1.5 μM (400 ppb) methyl parathion (MPT) on pepper and cucumber peels have been simultaneously detected in a wide detection range. The portable SERS-enabled device could potentially be facilely incorporated with liquid–liquid or solid phase micro-extracting devices for a broader range of applications in rapid and field analysis of food/public/environment security related SORs.

Anisotropic metallic nanoparticles (NPs) possess unique optical properties, which lend them to applications such as surface-enhanced Raman scattering (SERS). However, their preparation by an efficient, biocompatible and high yield synthetic method is still challenging. In this work, we demonstrate a simple and reproducible way to produce chitosan (CS) encapsulated gold–silver nanoflowers by sequentially adding chitosan, chloroauric acid, silver nitrate, and ascorbic acid to water at room temperature. This is a one-pot, seed- and surfactant-free synthetic method, which is simple and credible. CS is used to modulate the size of NPs, while AgNO3 is introduced to improve the monodispersity and homogeneity of NPs. Highly sensitive, spectrally and physically stable SERS tags are developed in virtue of the cooperative effect of CS and Ag+. Cresyl violet (CV) is applied as a Raman reporter to test the SERS property of NPs, and the results demonstrated that the nanoflowers exhibited stronger and more stable SERS signals than those of spherical gold nanoparticles. Importantly, after being modified by tumor cell-specific targeting ligands (folic acid), the sensitive and stable labeled nanoflowers are applied for cancer cell targeting and SERS imaging.

•Enlarged detection window for SERS heparin detection.•Higher reliability as the redispersion of SERS-based NPs was found.•Excellent selectivity due to the highest negative charge density of heparin and great sensitivity due to SERS.A sequential ‘on/off’ dual mode SERS assay platform for heparin with wider detection window and higher reliability is constructed based on electrostatic forces, in which the highly protonated chitosan encapsulated p-Mercaptobenzoic acid coated Au@Ag core–shell nanoparticles undergo sequential aggregation/segregation upon the additive of heparin with a limit of detection of 43.74 ng/mL (5.69 U/mL) and a continuous concentration range of 50–800 ng/mL (6.5–104 U/mL), which are lower in sensitivity and wider in detection window than the most reported assay for heparin. Remarkably, the latter declined window over a range of 350–800 ng/mL in contrast, which has not reported before, is extremely important in reliable and practical assay of heparin.

Noble metal nanoparticles (NPs) are spontaneously enfolded by aqueous coordination networks generated by reacting 2,5-dimercapto-1,3,4-thiadiazole (DMcT) with silver nanostructures in zero-oxidation state, and finally form novel hollow Au@Ag@infinite coordination polymers core–shell nanostructures (Au@Ag@void@ICPs). In this synthesis, DMcT molecules not only act as the bridging ligands but also directly oxidize Ag0 to Ag+ ions for the formation of amorphous DMcT–Ag ICPs. And, the sizes of the shell and void of Au@Ag@void@ICPs can be facilely tuned by modulating the amount of DMcT and the size ratio of Au@Ag NPs, respectively. Due to the high structural tailorability of DMcT–Ag ICPs, multi-encapsulation of Au@Ag NPs with either small organic molecules or biological macromolecules (e.g., enzymes) can be achieved to fabricate multi-functional core–shell nanostructures. A case in point is that a highly sensitive biosensor of H2O2 with a wider detection window has been constructed based on the prepared metal NPs–ICPs–enzyme composites and resonance Raman scattering. This study provides not only a new template for tailoring hollow core–shell nanomaterials but also a versatile platform for chemical (bio) sensing.

We describe a highly sensitive and spectrally stable surface-enhanced Raman scattering (SERS) tag for live cell imaging based on carbon-encapsulated gold nano-aggregates (CEGNAs). Our findings reveal that controlling the synthesis of the gold nano-aggregate core can be achieved under the mediation of cetyltrimethylammonium bromide (CTAB) through electrostatic forces and hydrophobic interactions, and as the number of particles in the aggregates increase, the relative SERS activity also increases hugely.

The manuscript has investigated the application of near-infrared (NIR) spectroscopy for differentiation gastric cancer. The 90 spectra from cancerous and normal tissues were collected from a total of 30 surgical specimens using Fourier transform near-infrared spectroscopy (FT-NIR) equipped with a fiber-optic probe. Major spectral differences were observed in the CH-stretching second overtone (9000–7000 cm−1), CH-stretching first overtone (6000–5200 cm−1), and CH-stretching combination (4500–4000 cm−1) regions. By use of unsupervised pattern recognition, such as principal component analysis (PCA) and cluster analysis (CA), all spectra were classified into cancerous and normal tissue groups with accuracy up to 81.1%. The sensitivity and specificity was 100% and 68.2%, respectively. These present results indicate that CH-stretching first, combination band and second overtone regions can serve as diagnostic markers for gastric cancer.Graphical abstractHighlights► Major spectral differences were observed in three regions. ► Unsupervised pattern recognition techniques (PCA and CA) were used. ► The sensitivity, specificity and accuracy were 100%, 68.2% and 81.1%, respectively.

Herein we describe a novel “turn-off” biosensing strategy for thrombin detection based on Surface Enhanced Raman scattering (SERS) and the mediation of spacing between 4-mercaptobenzoic acid (4-MBA) labeled gold nanoparticles (AuNPs). The multiple arginine peptides that initiated gold nano-aggregates incorporating Raman reporter molecules due to the formation of “Hot Spots”, are induced to disband by the addition of thrombin in which the peptides are catalytically cleaved into fragments and thus SERS signals of 4-MBA are sharply declined because of the weakened ability of fragments to induce aggregation. Through this strategy, a novel “turn-off” SERS biosensor for thrombin based on enzymatic amplification is established with sensitivity, selectivity and simplicity as AuNPs and peptides are easily accessible. Compared with non-enzymatic amplification based methods, this newly proposed method has improved sensitivity. The limit of detection was 160 fM (at the ratio of signal to noise, S/N=3:1). Further, controlled experiments showed that the method exhibited good selectivity over other proteases. The method demonstrated the capability and the potential for application in complex matrix and future biomarker development. The results also presented the potential and superiority of SERS biosensor based on signal amplification.Highlights► “Turn-off” SERS-based enzymatic assay is newly proposed. ► The method works on catalytic property of thrombin to cleave multi-arginine peptides. ► Ultrasensitive detection of target was achieved together with potential of use in complex matrix.

In the present study, silica nanoparticles with resonance Raman scattering (RRS) properties were utilized to construct a novel resonance Raman scattering tag for in vivo cellular imaging. β-Carotene, a native pigment insoluble in water, was for the first time encapsulated in silica nanoparticles through a simple one-step procedure in which β-carotene was enriched in the micelle of cetyltrimethylammonium bromide (CTAB) and simultaneously enclosed during the hydrolysis of tetraethylorthosilicate (TEOS). The particles were characterized by using X-ray diffraction, transmission electron microscopy (TEM), and Raman spectroscopy. Results showed that the size distribution of β-carotene doped silica nanoparticles (CSNPs), which were highly dispersible in aqueous solution, was fairly uniform in the range of 60 to 200 nm. Due to the advantages of highly stable and repeatable RRS signals of doped β-carotene, a simple cellular imaging approach based on this novel Raman tag has been preliminarily achieved. This paper demonstrated that resonance Raman scattering tags are important candidates for biological applications considering their high biocompatibility and spectral stability.

A longitudinal study was established to investigate bone compositional information in spinal cord injury (SCI) rat model.Raman spectroscopy was applied to detect the distal femur and humeri of SCI, sham-operated (SO), and age-matched control (CON) male Sprague-Dawley (SD) rats at first, second, third, and fifth weeks after surgery. One-way ANOVA and Tukey’s HSD post hoc multiple comparison tests were used to analyze the longitudinal data of mineral to matrix ratio and carbonate substitution.Relative mineral decrease was found in SCI group by more than 20% in femur and approximately 12% in humeri compared with CON group. No significant changes in carbonate substitution were observed.Severe bone loss in the early stage of SCI was confirmed by a continuous decrease of the mineral to collagen matrix ratio. The decrease in the humeri suggested hormone level variations might participate in the etiology of SCI-induced osteoporosis.

In this study, β-carotene, a resonance Raman active substance, was introduced into the large pore channel of rod-like SBA-15 for the first time. This novel resonance Raman active material has been characterized by small angle X-ray scattering (SAXS) and Brunauer–Emmett–Teller (BET) surface area analysis. The adsorption process did not show any influence on the microstructure of SBA-15 as well as its physicochemical characters. Excited by 514.5 nm laser, the resonance Raman signals of the products were demonstrated as well-defined Raman peaks at 1009, 1158 and 1514 cm−1, which should be assigned to the methyl rock (C–CH3), carbon single-bond stretch (C–C) and carbon double-bond stretch (CC) normal modes, respectively. In addition, the internal standard method was utilized by resonance Raman spectroscopy to determine the adsorption capacity of mesoporous silicas for β-carotene using the results of UV–vis spectroscopy as a reference.

Five triphenyl phosphonium salts including N-phenylacetamidyl triphenyl phosphonium chloride (1), N-phenylpropanamidyl triphenyl phosphonium chloride (2), ethyl 2-methylacetatyl triphenyl phosphonium chloride (3), ethyl butyryl triphenyl phosphonium chloride (4) and hexadecyl triphenyl phosphonium bromide (5) were synthesized and then were characterized by FT-Raman spectroscopy. Surface-enhanced Raman spectroscopy (SERS) in conjunction with electronic absorption spectroscopy was employed to study their interaction with DNA. The decreasing of Raman intensity at 1000, 1029, 1103 and 1588 cm−1 from compound 5 indicated that this compound has affinity for DNA. This was probably because compound 5 inserted into DNA and a new conjugated system was formed. The results of electronic absorption spectra were coincident with those of SERS. On the other hand, compound 5 showed a significant higher inhibitory rate on human cervix cancer cells. The targets of the compounds in the anti-cancer process were discussed. The mechanism of the anti-cancer process of compound 5 might be related to its interaction with DNA.

Novel three-dimensional (3D) nano-assemblies of noble metal nanoparticle (NP)–infinite coordination polymers (ICPs) are conveniently fabricated through the infiltration of HAuCl4 into hollow Au@Ag@ICPs core–shell nanostructures and its replacement reaction with Au@Ag NPs. The present 3D nano-assemblies exhibit highly efficient and specific intrinsic oxidase-like activity even without adding any cosubstrate.

We describe a highly sensitive and spectrally stable surface-enhanced Raman scattering (SERS) tag for live cell imaging based on carbon-encapsulated gold nano-aggregates (CEGNAs). Our findings reveal that controlling the synthesis of the gold nano-aggregate core can be achieved under the mediation of cetyltrimethylammonium bromide (CTAB) through electrostatic forces and hydrophobic interactions, and as the number of particles in the aggregates increase, the relative SERS activity also increases hugely.

In the present study, silica nanoparticles with resonance Raman scattering (RRS) properties were utilized to construct a novel resonance Raman scattering tag for in vivo cellular imaging. β-Carotene, a native pigment insoluble in water, was for the first time encapsulated in silica nanoparticles through a simple one-step procedure in which β-carotene was enriched in the micelle of cetyltrimethylammonium bromide (CTAB) and simultaneously enclosed during the hydrolysis of tetraethylorthosilicate (TEOS). The particles were characterized by using X-ray diffraction, transmission electron microscopy (TEM), and Raman spectroscopy. Results showed that the size distribution of β-carotene doped silica nanoparticles (CSNPs), which were highly dispersible in aqueous solution, was fairly uniform in the range of 60 to 200 nm. Due to the advantages of highly stable and repeatable RRS signals of doped β-carotene, a simple cellular imaging approach based on this novel Raman tag has been preliminarily achieved. This paper demonstrated that resonance Raman scattering tags are important candidates for biological applications considering their high biocompatibility and spectral stability.

Anisotropic metallic nanoparticles (NPs) possess unique optical properties, which lend them to applications such as surface-enhanced Raman scattering (SERS). However, their preparation by an efficient, biocompatible and high yield synthetic method is still challenging. In this work, we demonstrate a simple and reproducible way to produce chitosan (CS) encapsulated gold–silver nanoflowers by sequentially adding chitosan, chloroauric acid, silver nitrate, and ascorbic acid to water at room temperature. This is a one-pot, seed- and surfactant-free synthetic method, which is simple and credible. CS is used to modulate the size of NPs, while AgNO3 is introduced to improve the monodispersity and homogeneity of NPs. Highly sensitive, spectrally and physically stable SERS tags are developed in virtue of the cooperative effect of CS and Ag+. Cresyl violet (CV) is applied as a Raman reporter to test the SERS property of NPs, and the results demonstrated that the nanoflowers exhibited stronger and more stable SERS signals than those of spherical gold nanoparticles. Importantly, after being modified by tumor cell-specific targeting ligands (folic acid), the sensitive and stable labeled nanoflowers are applied for cancer cell targeting and SERS imaging.