A berberine induced disassembly towards zwitterionic surfactant as mimicking cell membrane for light-scattering sensing and logic devices.

A label-free light-scattering sensor for berberine determination was developed based on Gemini zwitterionic surfactant as logic devices. Amphiphilic phosphodiesters quaternary ammonium nanoparticles (PQANPs) with bionic phosphate ester structure were selected as a model for mimicking cell membrane. PQANPs self-assembled and formed the micelle structure, emitting strong light-scattering signal. Interestingly, the addition of berberine induced remarkable decrease of light-scattering attribute to its interfering behavior of PQANPs aggregation. Disassembly of PQANPs could be triggered due to electrostatic interaction and hydrophobic force between PQANPs and berberine. The berberine attached to the PQANPs surface and generated nanocomposites, resulting in significant reduce of light-scattering signal. Hence, it generated a strong light-scattering signal variation according to the change of the concentration of target. Our proposed light-scattering on-off sensor could be applied for berberine detection with detection limit of 27 nM. Moreover, a logic gate system was constructed based on PQANPs sensor with berberine and the interfering substances as the inputs and the light-scattering intensity as an output, which could hold great potential application in future clinical diagnosis and drug analysis.

Target-Activating and Toehold Displacement Ag NCs/GO Biosensor-Mediating Signal Shift and Enhancement for Simultaneous Multiple Detection.

Herein, we demonstrate that a new multicolor silver nanoclusters/graphene oxide (Ag NCs/GO) hybrid material, upon target response, undergoes a configuration transformation, based on entropy-driven enzyme-free toehold-mediated strand displacement reaction, achieving emission shift and enhancement. To realize the aim above, two different synthesis routes (route I and II) of synthesizing fluorescent Ag NCs for constructing toehold displacement Ag NCs/GO biosensor is designed and performed. Influenza A virus subtype genes (H1N1 and H5N1) as a model can efficiently initiate the operation of entropy-driven displacement reaction, resulting in activatable fluorescence. Red-emitting and green-emitting Ag NCs tethering the complementary sequence of H1N1 (pDNA1) and H5N1 (pDNA2) are indirectly immobilized on GO surface through binding with capture DNA (cDNA1 and cDNA2), respectively, forming multicolor pDNA-Ag NCs/GO nanohybrid materials. However, they do not exhibit nearly fluorescence signals attributed to energy transfer from donor Ag NCs to acceptor GO. Upon adding targets H1N1 and H5N1 (tDNA1 and tDNA2), pDNA1-Ag NCs and pDNA2-Ag NCs detach from GO, based on toehold-mediated strand displacement reaction, which interferes the energy transfer and leads to significant fluorescence enhancement. More interestingly, the activatable process is accompanied by remarkable hypsochromic shift (19 nm) or bathochromic shift (21 nm) emission with quite high fluorescence recovery rates (823.35% and 693.62%). Therefore, based on these phenomena, a novel multiple approach has been developed with the assistance of toehold displacement and Ag NCs/GO nanohybrid materials. As for the remarkable emission recovery and multichannel signal, the proposed approach displays the promising application prospect in accurate diagnosis and treatment.

Dual-Channel Logic Gates Operating on the Chemopalette ssDNA-Ag NCs/GO Nanocomposites.

In this work, we demonstrate that the emission wavelength and intensity of silver nanoclusters (Ag NCs) can be facilely tuned by the configuration transformation from the adsorption of Ag NCs to the graphene oxide (GO) surface to the desorption of Ag NCs from GO. Bicolor Ag NCs tethering the complementary sequence of influenza A virus genes are prepared, named green-emitting G-Ag NCs-CH5N1 (530 nm) and red-emitting R-Ag NCs-CH1N1 (589 nm). As for the high affinity of the complementary fragment of genes to GO, the adsorption of Ag NCs to GO leads to the formation of G-Ag NCs-CH5N1/GO and R-Ag NCs-CH1N1/GO nanocomposites, leading to fluorescent quenching due to energy transfer. By conjugating complementary sequences as capturing probes for targets, the formation of genes/Ag NC duplex-stranded structures results in the desorption of Ag NCs from GO, activating the fluorescence signal. More interestingly, compared with sole single-stranded DNA-templated fluorescent Ag NCs (ssDNA-Ag NCs), the activatable emission wavelength of the G-Ag NCs-CH5N1/H5N1 complex exhibits a notable red shift (555 nm) with a 49% recovery rate, while that of the R-Ag NCs-CH1N1/H1N1 complex shows a distinct blue shift (569 nm) with a 200% recovery rate. Via target-responsive configuration transformation of Ag NCs/GO hybrid materials, the emission wavelength and intensity of Ag NCs are effectively regulated. Based on the output changes according to different input combinations, novel dual-channel logic gates for multiplex simultaneous detection are developed by using the tunable color and intensity of ssDNA-Ag NCs. Our observation may open a new path for multiplex analysis in a facile and rapid way combining the logic gate strategy.

Construction of FRET biosensor for off-on detection of lead ions based on carbon dots and gold nanorods.

Exploring new energy donor/acceptor pairs for constructing FRET system has important research significance. In this study, a FRET assembly by using carbon dots (CDs) as energy donor and gold nanorods (Au NRs) as energy acceptor has been proposed through covalent bond interactions by taking advantage of cysteamine as a bridge. The assembly is characterized by UV-vis absorption spectra, fluorescence spectra, FT-IR spectra and TEM images, revealing that Au NRs successfully absorbed on the surface of CDs. As for the occurrence of FRET process from CDs to Au NRs, the fluorescence signal of CDs-cysteamine-Au NRs assembly quenched significantly. Interestingly, Pb2+ ions could bind completely with cysteamine and disturbed the FRET process, which activated fluorescence signal of the system. Based on these experimental phenomena, CDs-cysteamine-Au NRs assembly was performed as an off-on FRET biosensor for Pb2+ ions. The linear range obtained is from 0 to 155 µM with the detection limit of 0.05 µM. Moreover, the FRET-based sensor exhibited high selectivity to the analyte Pb2+ ions against other interference substances. Furthermore, the present approach was successfully applied to detect Pb2+ ions in real samples, which suggested its potential applications in environmental monitoring.

Target-activatable gold nanoparticle-based aptasensing for protein biomarkers using stimuli-responsive aggregation.

An ultrasensitive and selective light-scattering (LS) aptasensor for prostate specific antigen (PSA) was developed based on bifunctional DNA decorated gold nanoparticles (Au NPs) by use of target stimuli-responsive assembly. Both binding sequence poly adenine (poly(dA), Domain I) and the recognition sequence aptamer (Domain II) of bifunctional ssDNA were in favor of the sensitivity for the fabricated light-scattering aptasensor due to modulated the lateral spacing of DNA on Au NPs surface and possessed strong antigen binding affinity, respectively. And they efficiently promoted the Au NPs aggregation and activated the signal of light-scattering of aptasensor. The formation of aptamer-PSA complex induced conformational transformation of the aptamer on the surface of the Au NPs-based aptasensor and then tuned the interparticle distance of gold nanoparticle assemblies. The larger scattering particles, the higher light-scattering intensity. Target stimuli-responsive aggregation behavior of Au NPs lit up the light-scattering signal of aptasensor. As the concentration of PSA increased, the light-scattering intensity gradually enhanced. The aptasensor response for PSA detection was in the linear range from 0.01 ng/mL to 20 ng/mL with the detection limit of 2 pg/mL. The thiol-free Au NPs-based light-scattering aptasensor has exceptional performances with ultrasensitivity and high selectivity besides the advantage of economic and facile fabrication. Moreover, the proposed target-activated aptasensor was applied for the detection of PSA in serum samples and demonstrated great potential in clinical applications.

Phosphodiesters quaternary ammonium nanoparticles as label-free light scattering probe for turn-off detection of tyrosine.

In this contribution, a new highly sensitive and selective sensor of the determination of tyrosine has been proposed based on the downturn effect of light scattering (LS) using phosphodiesters quaternary ammonium nanoparticles (PQANPs). Phosphodiesters quaternary ammonium (PQA), one of Gemini zwitterionic surfactants, self-aggregated into the micelle named as PQANPs, which generated strong LS signal in aqueous solution under the optimum condition. Interestingly, the powerful LS intensity of PQANPs with the maximum peak located at 391 nm significantly decreased after introducing trace amount of tyrosine. The decreased value of the LS intensity of the PQA-tyrosine system (ΔILS) was in proportion to tyrosine concentration in the ranges from 5.5 × 10-8 mol/L to 4.68 × 10-6 mol/L, with a detection limit of 1.38 × 10-8 mol/L. Based on this decreased LS situation, the novel approach of the determination of tyrosine was first developed. The reaction mechanism for the interaction between PQANPs and tyrosine was also investigated. Moreover, the proposed LS assay was applied to the detection of tyrosine concentration in human serum and urine samples with satisfactory results.

Fluorescence Enhancement of Terminal Amine Assembled on Gold Nanoclusters and Its Application to Ratiometric Lysine Detection.

Ratiometric fluorescent sensors have emerged as an attractive tool for analytical sensing and optical imaging due to their providing a built-in self-calibration for environmental effects. However, cumbersome processes of nanoparticles modified with fluorophores for constructing traditional ratiometric sensors limit their further application. Herein, we report a facile and label-free strategy for constructing a ratiometric sensor based on an aggregation-induced-emission (AIE)-active amine-terminated small molecule on the surface of gold nanoclusters (AuNCs). Intrinsic fluorescence of the terminal primary amine of the small molecule lysine resulting from AIE was first observed in the presence of glutathione-stabilized gold nanoclusters (GSH-AuNCs). Using lysine as both the fluorophore and the analyte, the synthesized GSH-AuNCs showed a good lysine-responsive ratiometric property. The AIE-active dual-emitting fluorescence property of the GSH-AuNCs/lysine complex made it feasible to achieve ratiometrically detection of the analyte without conjugated fluorogen. This AIE-active GSH-AuNC-based biosensor possesses high selectivity, rapid response, and excellent photostability. Moreover, the strategy opens a new pathway for the construction of a label-free ratiometric fluorescent sensor with various applications.

Silver Nanoclusters Beacon as Stimuli-Responsive Versatile Platform for Multiplex DNAs Detection and Aptamer-Substrate Complexes Sensing.

An activatable silver nanoclusters beacon (ASNCB) was synthesized through a facile one-pot approach and applied for multiplex DNAs, small molecule, and protein sensing. Multifunctional single-stranded DNA sequences are rationally designed and used for ASNCB in situ synthesis. Via target-responsive structure transformation of ASNCB, target recognition induced ASNCB conformational transition and lit up the fluorescent signal of silver nanoclusters. By further implementing two different color ASNCBs (520 and 600 nm), the parallel multiplexed analysis of two target genes (Influenza A virus genes H1N1 and H5N1) is achieved. Additionally, with the introduction of aptamer for the design of the molecular beacon, the detections of small molecule adenosine triphosphate (ATP) and biomacromolecule thrombin have also been realized. This is the first time that an activatable fluorescent silver nanoclusters (Ag NCs)-based probe and the target recognition have been integrated into a single process, which provides a versatile platform for different analytes in a facile way. The successful application of our proposed ASNCB in real sample analysis and ATP imaging in living cells further displayed its promising potential for fluorescence sensing.

A novel biosensor for copper(ii) ions based on turn-on resonance light scattering of ssDNA templated silver nanoclusters.

A new ultrasensitive biosensor for copper(ii) ions was developed based on turn-on resonance light scattering (RLS) of ssDNA templated silver nanoclusters through anti-galvanic reduction (AGR). In our experimental assay, ultra-small size fluorescent C-rich ssDNA templated silver nanoclusters (C-rich ssDNA-Ag NCs) exhibit direct reduction of copper(ii) ions to elemental copper (Cu0) and the resulting Cu0 formed copper nanoparticles on the surface of C-rich ssDNA-Ag NCs spontaneously. The process produced Ag/Cu alloy nanoparticles with larger diameters, turning-on RLS signal of C-rich ssDNA-Ag NCs. As the concentration of Cu2+ ions increased, the RLS signal of C-rich ssDNA-Ag NCs gradually enhanced. The present method achieves the detection of Cu2+ ions in a linear range of 5 × 10-9 M to 7.5 × 10-7 M with a detection limit of 2 nM. Moreover, RLS spectrum, TEM image, fluorescence spectrum, X-ray photoelectron spectroscopy (XPS), and MALDI-TOF mass spectrometry were carried out for investigating the mechanism of the biosensor. The present strategy of constructing a biosensor based on AGR of metal nanoclusters paves a new way to design novel RLS probes.

An anti-galvanic replacement reaction of DNA templated silver nanoclusters monitored by the light-scattering technique.

An anti-galvanic replacement reaction (AGRR) of copper(II) ions reduced by ultra-small ssDNA-templated silver nanoclusters forming Ag-Cu alloy nanoparticles was observed. The reaction is against the classic galvanic theory and was monitored sensitively by the light-scattering technique.

DNA-functionalized silver nanoclusters as a chemopalette: tunable fluorescence for turn-on detection of cysteine.

A strategy for rapid synthesis of a chemopalette of fluorescent Ag nanoclusters based on efficient directors by only incorporating mutated bases of a C-rich ssDNA as template was proposed and used as a new fluorescence turn-on highly selective and sensitive detection method for cysteine without the interference of GSH and Hcy.

A new light-scattering sensor for screening G-quadruplex stabilizers based on DNA-folding-mediated assembly of gold nanoparticles.

In this contribution, we constructed a biosensor for screening G-quadruplex stabilizers based on the assembly of gold nanoparticles functionalized with guanine-rich (G-rich) ssDNA using a light-scattering technique. We synthesized a series of metal-terpyridine complexes and investigated their affinity for quadruplex-DNA using the biosensor. Using the ratio of intensity of the light-scattering peak (I-I0)/I0, it can intuitively present the sequence of ability of stabilizing G-quadruplex DNA as follows: complex 1 > complex 3 > MTX > complex 2 > complex 5 > complex 6 > complex 7 > complex 4 > methyl green > TO > complex 8 > cisplatin. As our method allows the quantitative analysis of stabilizer affinity, EC50 values obtained are 4.8, 5.3, 6.1, 6.6, 6.7, 18.2, 20.2, 21.5, 32.2, 41.5 and 48.1 µM for complex 1, complex 3, MTX, complex 2, complex 5, complex 6, complex 7, complex 4, methyl green, TO and complex 8, respectively. The results have been verified by G-quadruplex fluorescent intercalator displacement (G4-FID) analysis. The proposed approach is a simple, convenient, intuitive and highly sensitive assay for screening G-quadruplex stabilizers. Our developed biosensor provides a promising tool for screening anticancer drugs.

In situ selective N-alkylation of pendant pyridyl functionality in mixed-valence copper complexes with methanol and copper(II) bromide.

The reactions of CuBr(2) with pyridyl 2,2':6',2''-terpyridine ligands in methanol yielded four copper complexes under solvothermal conditions. The self-assembly processes were accompanied by designing bitopic precursor ligands and increasing the stoichiometric metal-ligand ratio. In the four resulting complexes, the pendant pyridyl groups of pyridylterpyridine were selectively in situ N-methylated and yielded the 4'-(N-methylpyridinium)-2,2':6',2''-terpyridine cations, including the 2-position pyridyl group which is difficult to be N-alkylated due to the steric problem. Partial divalent copper atoms were reduced to cuprous ones in the solvothermal reactions, which made the mixed-valence copper atoms coexist in each compound. The mixed-valence complexes have a varied dimensionality (from 2D to 0D) and the Cu(I)Br cluster, which can be controlled by changing the metal-ligand ratio. Theoretical studies show that the nucleophilic attack of the nitrogen atom in the pendant pyridyl is more facile than others of terpyridine. A possible mechanism was also proposed.

A highly selective and sensitive on-off sensor for silver ions and cysteine by light scattering technique of DNA-functionalized gold nanoparticles.

DNA-functionalized gold nanoparticles are shown to act as a light-scattering switch. Ag(+) ion turns on the switch through the DNA-Au NPs conjugates based on the formation of cytosine-Ag(+)-cytosine base pairs, whereas cysteine turns off the light-scattering signal because it competitively binds to Ag(+).