Polystyrene Encapsulated SERS Tags as Promising Standard Tools: Simple and Universal in Synthesis; Highly Sensitive and Ultrastable for Bioimaging.

Surface coating determined the sensitivity and stability of surface-enhanced Raman scattering (SERS) tags in bioanalysis. The reported various coatings suffered from the drawbacks of a lack of rigidity, stability, or synthesis versatility. Herein, we demonstrated robust polystyrene (PS) coated SERS tags that could be prepared by an easy and universal approach. Taking advantages of biocompatible, transparent, compact properties of PS shell, the coated tags showed satisfactory sensitivity, biocompatibility, and superior structural stability in cell and in vivo imaging applications. More importantly, the PS coating strategy allowed for the encapsulation of SERS tags encoded with not only thiolated but also nonthiolated Raman reporters without loss of sensitivity, as exemplified in the synthesis of 9 different resonant dye-encoded tags. Moreover, the coating of SERS tags with various kinds of substrates was achieved via the same standard protocol. Comparing with widespread silica coated tags, the PS coated ones were more stable in harsh conditions and had an easily expanded ultrasensitive (resonant) tags library with much lower cost (no need of expensive sulfhydryl/isothiocyano reporters with limited types), illustrating great promise as standard analytical tools of commercialized value for bioanalysis, medical diagnostics, and environmental science studies.

Photoinduced electron transfer from polymer-templated Ag nanoclusters to G-quadruplex-hemin complexes for the construction of versatile biosensors and logic gate applications.

In this paper, fluorescent Ag nanoclusters (Ag NCs) templated by hyperbranched polyethyleneimine (PEI) are utilized as a versatile probe through the photoinduced electron transfer (PET) between PEI-Ag NCs and G-quadruplex-hemin complexes. In the presence of hemin and target molecule, the specific conjugation with its aptamer induces the conformational change of the DNA sequence, releasing the G-quadruplex sequence part. Once the G-quadruplex-hemin complexes are introduced, electron transfer from the PEI-Ag NCs to G-quadruplex-hemin complexes occurs, resulting in fluorescence quenching. Through changing the sensing DNA sequence, this novel PET system enables the specific detection of target DNA and adenosine triphosphate (ATP) with the wide linear range of 1-200 nM and 5-500 nM, respectively, and the corresponding limit of detection as low as 0.3 nM for target DNA and 1.5 nM for ATP. In addition, the proposed method is successfully applied to the determination of ATP in human serum samples with satisfactory recoveries, and a logic gate is fabricated using target molecules and hemin as inputs and the fluorescence signal of PEI-Ag NCs as an output.

A resonance Rayleigh scattering sensor for sensitive differentiation of telomere DNA length and monitoring special motifs (G-quadruplex and i-motif) based on the Ag nanoclusters and NAND logic gate responding to chemical input signals.

BACKGROUND: Differentiation of telomere length is of vital importance because telomere length is closely related with several deadly diseases such as cancer. Additionally, G-quadruplex and i-motif formation in telomeric DNA have been shown to act as a negative regulator of telomere elongation by telomerase in vivo and are considered as an attractive drug target for cancer chemotherapy. RESULTS: In this assay, Ag nanoclusters templated by hyperbranched polyethyleneimine (PEI-Ag NCs) are designed as a new novel resonance Rayleigh scattering (RRS) probe for sensitive differentiation of telomere length and monitoring special motifs (G-quadruplex and i-motif). In this assay, free PEI-Ag NC probe or DNA sequence alone emits low intensities of RRS, while the formation of PEI-Ag NCs/DNA complexes yields greatly enhanced RRS signals; however, when PEI-Ag NCs react with G-quadruplex or i-motif, the intensities of RRS exhibit slight changes. At the same concentration, the enhancement of RRS signal is directly proportional to the length of telomere, and the sensitivity of 64 bases is the highest with the linear range of 0.3-50 nM (limit of detection 0.12 nM). On the other hand, due to the conversion of telomere DNA molecules among multiple surrounding conditions, a DNA logic gate is developed on the basis of two chemical input signals (K+ and H+) and a change in RRS intensity as the output signal. CONCLUSION: Our results indicate that PEI-Ag NCs can serve as a novel RRS probe to identify DNA length and monitor G-quadruplex/i-motif through the different increasing degrees of RRS intensity. Meanwhile, the novel attributes of the nanoprobe stand superior to those involving dyes or labeled DNA because of no chemical modification, low cost, green, and high efficiency.

Rational Construction of Fluorescence Turn-Off Fluorinated Carbon Fiber/Ag Composites and Their Anticancer and Antibacterial Activities.

Although fluorinated carbon fiber/Ag composites possess unique structure and special charge distribution and exhibit great potential in numerous fields, their synthesis has long been a headache because of inert chemistry bonds, low surface energy, and easy aggregation. Herein, we first demonstrate a fresh concept of constructing the nanoscale hydrosoluble fluorinated carbon fiber oxide (FCO)/Ag composite and then integrate it as a highly effective targeting nanocarrier and photothermal therapy and antibacterial agent. Chemical introduction of oxygen allows us to controllably deposit Ag nanoparticles (AgNPs) for the first time and further facilitates surface modification with folic acid prelinked bovine serum albumin to induce targeted endocytosis toward tumor cells. The structure adjustment of FCO into nanosize and the decoration of AgNPs endow the composite with much better photothermal property than fluorinated carbon materials, and FCO/Ag also serves as an effective fluorescence quencher for doxorubicin, realizing visual monitor of drug adsorption processes by "turn-off" fluorescence. Meanwhile, both in vitro and in vivo results reveal greatly improved cancer therapeutic effects than single therapy. What is more is that the synergistic interactions of lipophilic fluorine and AgNPs also ensure highly effective antibacterial activity. Our study integrates FCO/Ag as an emerging drug carrier that exhibits excellent targeted efficiency and high photothemal property and reports its unprecedented experimental example in both antibacterial- and anticancer-combined chemo-photothermal therapy.

Permanently Positively Charged Stable Isotope Labeling Agents and Its Application in the Accurate Quantitation of Alkylphenols Migrated from Plastics to Edible Oils.

A new permanently positively charged stable isotope labeling (SIL) agent pair, 4-(((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)-N,N,N-trimethylbenzenaminium iodide(DPTBA) and its deuterated counterpart d3-DPTBA, was designed and synthesized. The SIL agents were applied to the liquid chromatography-tandem mass spectrometry analysis of alkylphenols. Light labeled standards and heavy labeled samples were mixed and analyzed simultaneously. Matrix effect which mainly occurred during the ionization process was minimized because of the identical ionization processes between samples and standards. Meanwhile, derivatization made alkylphenols be positively charged, and thus the sensitivity was enhanced. The limits of detection were in the range of 1.5-1.8 ng/L, and the limits of quantitation were in the range of 4.8-6.1 ng/L. The developed method was applied to analyze alkylphenols migrated from plastics to edible oils. The recoveries for all analytes were in the range of 88.6-95.3%, while the matrix effects for all analytes were in the range of 96.2-99.6%.

Core-shell magnetic molecularly imprinted polymers used rhodamine B hydroxyproline derivate as template combined with in situ derivatization for the specific measurement of L-hydroxyproline.

In this work, a novel core-shell magnetic molecularly imprinted polymers (MMIPs) for the measurement of L-Hydroxyproline (Hyp) in dairy products was prepared. The derivative of Hyp using N-hydroxysuccinimidyl rhodamine B ester (RBS) as derivatization reagent was employed as template to prepare RBS-Hyp-MMIPs (Fe3O4@MIPs for RBS-Hyp). A new analytical procedure of in situ derivatization with MMIPs (ISD-MMIPs) has been developed for the specific extraction and determination of Hyp in dairy products by ultra high performance liquid chromatography tandem mass spectrometry. The RBS-Hyp-MMIPs was characterized by fourier transform infrared spectrometer and transmission electron microscopy, and evaluated by adsorption experiments. The adsorption process followed Langumuir adsorption isotherm with maximum adsorption capacity of RBS-Hyp on RBS-Hyp-MMIPs at 96 mg/g. In addition, RBS-Hyp-MMIPs showed a short equilibrium time (15.0 min), rapid magnetic separation (5 s) and high stability (retained 95.3% after six cycles). Under the optimized conditions, good linearity was observed with the limits of detection (S/N > 3) and limits of quantification (S/N > 10) at 0.1 and 0.5 ng/mL, respectively. On account of the specific extraction performance of RBS-Hyp-MMIPs, not any interference peak from real sample matrix was observed in the chromatograms of milk powder, liquid milk and milk drink. The proposed procedure was successfully applied for selective determination of Hyp from dairy products with satisfactory validation results, which is of great significance to food safety.

A tunable pH-sensing system based on Ag nanoclusters capped by hyperbranched polyethyleneimine with different molecular weights.

In this assay, a tunable pH sensing system was developed based on Ag nanoclusters (Ag NCs) capped by hyperbranched polyethyleneimine (PEI) with different molecular weights (abbreviated as Ag NC-PEIs). For instance, when the molecular weight of PEI was 600 or 1800, the fluorescence intensities of Ag NCs exhibited a linear fashion over the pH range 4.10-7.96; when the molecular weight of PEI was 25,000, the pH linear range was from 4.78 to 7.96; when the molecular weight of PEI was 70,000, the pH linear range was 6.09-8.95. According to the molecular weight of PEI 600/1800, 25,000, and 70,000, the color change point was pH 4.10-4.78, 5.33-6.09, and 6.09-6.80, respectively. Therefore, Ag NC-PEI 600 and 1800 were proper to acid conditions; Ag NC-PEI 25,000 was sensitive to weak acid media; while Ag NC-PEI 70,000 was adapted to neutral solution. The tunable and selective color change points brought an excellent feature of Ag NC-PEIs as visual pH indicators, which was flexible and applicable to a variety of environments. Besides, the ratios of absorbance at 415 nm and 268 nm of Ag NCs also showed linear relationships with pH variations. Therefore, there were three ways of this system for sensing pH values, including fluorescence assay, ultraviolet-visible measurement, and visual detection, suggesting that this tunable pH-sensing platform was more feasible, reliable, and accurate.

Hollow PDA-Au nanoparticles-enabled signal amplification for sensitive nonenzymatic colorimetric immunodetection of carbohydrate antigen 125.

A novel colorimetric immunoassay was designed for the sensitive detection of carbohydrate antigen 125 (CA125). The success of this immunoassay relies on the use of hollow polydopamine-gold nanoparticles (PDA-Au) for signal amplification to achieve sensitive nonenzymatic colorimetric detection. In particular, PDA-Au was used as a stable and sensitive label and aminated-Fe3O4 magnetic nanoparticles (Fe3O4 NPs) were employed to immobilize capture antibody (Ab1) and acted as a separable immunosensing probe. PDA-Au exhibited high catalytic performance towards p-nitrophenol reduction and thus resulted in significant color change and UV/vis signal variations. The immunoassay was performed based on sandwich protocol. As compared to pure Au nanoparticles, the signal amplification and sensitivity of PDA-Au-based assay was significantly improved. For instance, the dynamic range of the developed colorimetric immunoassay for CA125 was 0.1-100 U/mL with a detection limit of 0.1 U/mL at S/N=3. In addition, this immunoassay was also tested for the analysis of clinical serum samples, which demonstrated its potential for practical diagnostic applications.

Chemodosimeter-based fluorescent detection of L-cysteine after extracted by molecularly imprinted polymers.

A chemodosimeter-based fluorescent detection method coupled with molecularly imprinted polymers (MIPs) extraction was developed for determination of L-cysteine (L-Cys) by combining molecular imprinting technique with fluorescent chemodosimeter. The MIPs prepared by precipitation polymerization with L-Cys as template, possessed high specific surface area of 145 m(2)/g and good thermal stability without decomposition lower than 300 °C, and were successfully applied as an adsorbent with excellent selectivity for L-Cys over other amino acids, and enantioselectivity was also demonstrated. A novel chemodosimeter, rhodamine B1, was synthesized for discriminating L-Cys from its structurally similar homocysteine and glutathione as well as various possibly co-existing biospecies in aqueous solutions with notable fluorescence enhancement when adding L-Cys. As L-Cys was added with increasing concentrations, an emission band peaked at 580 nm occurred and significantly increased in fluorescence intensity, by which the L-Cys could be sensed optically. High detectability up to 12.5 nM was obtained. An excellent linearity was found within the wide range of 0.05-50 µM (r=0.9996), and reasonable relative standard deviations ranging from 0.3% to 3.5% were attained. Such typical features as high selectivity, high sensitivity, easy operation and low cost enabled this MIPs-fluorometry to be potentially applicable for routine detection of trace L-Cys.

Signal amplification strategy for sensitive immunoassay of prostate specific antigen (PSA) based on ferrocene incorporated polystyrene spheres.

A new kind of signal amplification strategy based on ferrocene (Fc) incorporated polystyrene spheres (PS-Fc) was proposed. The synthesized PS-Fc displayed narrow size distribution and good stability. PS-Fc was applied as label to develop immunosensors for prostate specific antigen (PSA) after the typical sandwich immunoreaction by linking anti-PSA antibody (Ab2) onto PS-Fc. After the fabrication of the immunosensor, tetrahydrofuran (THF) was dropped to dissolve PS and release the contained Fc for the following stripping voltammetric detection. PS-Fc as a new electrochemical label prevented the leakage of Fc and greatly amplified the immunosensor signal. In addition, the good biocompatibility of PS could maintain the bioactivity of the antibodies. The response current was linear to the logarithm of PSA concentration in the range from 0.01 ng mL(-1) to 20 ng mL(-1) with a detection limit of 1 pg mL(-1). The immunosensor results were validated through the detection of PSA in serum samples with satisfactory results.