Yuexiang Lu

Multidimensional Sensor for Pattern Recognition of Proteins Based on DNA–Gold Nanoparticles Conjugates

We presented an extensible multidimensional sensor with conjugated nonspecific dye-labeled DNA sequences absorbed onto gold nanoparticles (DNA-AuNPs) as receptors. At the presence of target protein, DNA was removed from the surface of AuNPs due to the competitive binding, which resulted in a red-to-blue color change along with salt-induced aggregation of AuNPs for colorimetric analysis and fluorescent turn-on signal of the labeled dye for fluorescence analysis. The orthogonal and complementary fluorescent and colorimetric signals obtained from each protein were applied to distinguish different proteins. By simply changing the DNA sequences, more dual-channel sensing elements could be easily obtained and added into this multidimensional sensor. This enhanced its discriminating power to the proteins. With three sensing elements, our extensible multidimensional sensing platform exhibited excellent discrimination ability. Eleven proteins at the concentration of 50 nM had been classified with accuracies of 100% by using linear discriminant analysis (LDA). Remarkably, two similar proteins [bovine serum albumin (BSA) and human serum albumin (HSA)] at various concentrations and the mixture of these two proteins with different molar ratios had been successfully discriminated in one LDA plot as well. Furthermore, in the presence of human urine sample, 10 proteins at 1.0 μM could also be well-discriminated. The accuracy of discrimination of unknown samples was all 100% for these experiments. This strategy is a complement of the multidimensional sensing system and traditional sensor platform, offering a new way to develop sensitive array sensing systems.

Multidimensional colorimetric sensor array for discrimination of proteins

An extensible multidimensional colorimetric sensor array for the detection of protein is developed based on DNA functionalized gold nanoparticles (DNA-AuNPs) as receptors. In the presence of different proteins, the aggregation behavior of DNA-AuNPs was regulated by the high concentrations of salt and caused different color change; while DNA-AuNPs grew induced by the reduction of HAuCl4 and NH2OH as a reductant on the surface of nanoparticles exhibited different morphologies and color appearance for different proteins. The transducers based on AuNPs modified by specific and nonspecific DNA enables naked-eye discrimination of the target analytes. This extensible sensing platform with only two receptors could simultaneously discriminate ten native proteins and their thermally denatured conformations using hierarchical cluster analysis (HCA) at the concentration of 50nM with 100% accuracy. This opens up the possibility of the sensor array to investigate the different conformational changes of biomacromolecules, and it gives a new direction of developing multidimensional transduction principles based on plasmonic nanoparticle conjugates. Furthermore, the sensing system could discriminate proteins at the concentration of 500nM in the presence of 50% human urine, which indicated this sensor array has great potential ability in analyzing real biological fluids. In addition, the multidimensional colorimetric sensor array is suitable for analysis of target analytes in the resource-restricted regions because of rapid, simple, low cost, and in-field detection with the naked eye.

Continuously evolving ‘chemical tongue’ biosensor for detecting proteins

We developed a unique continuously evolving colorimetric sensor array based on AuNPs decorated by two single-stranded oligonucleotides with different molar ratios for protein discrimination. The number of differential receptors in this sensor array could be easily extended by adjusting the molar ratios of two DNA, resulting in continuously improved discrimination ability. The continuous response data of target samples against our sensing system could be easily obtained and exclude abnormal signals. The sensing system could discriminate twelve proteins at the concentration of 200nM in the presence of 50% human urine with accuracy of 100%, showing feasible potential for diagnostic applications. Remarkably, HSA at various concentrations, the pure Lys and HSA, and the mixture of these two proteins with different molar ratios had been successfully discriminated in LDA plot as well in the presence of human urine sample. This novel strategy will be very promising for the design of cheaper and more reliable sensor arrays for target samples.

Fluorescence sensor array based on amino acids-modulating quantum dots for the discrimination of metal ions

We developed an easily extensible fluorescence sensor array based on amino acids-modulating QDs for the discrimination of nine metal ions. Two amino acids (Glutamine and Arginine) were assembled with two quantum dots including 3-mercaptopropionic acid capped Mn-ZnS QDs (MPA-QDs) and alpha-thioglycerol capped Mn-ZnS QDs (TG-QDs), achieving six across-reactive sensing elements. Amino acids as the modulators imparted the diversity and differential detection of metal ions, because they could bind QDs and also form complexes with metal ions through their carboxyl, amino, and hydroxyl groups. Therefore, the fluorescence response signals for metal ions could be either enhanced or decreased. This sensing system allowed the accurate classification of nine metal ions in pure water at 0.5xa0μM and tap water at 3.0xa0μM. Moreover, two metal ions with different oxidation state Fe3+ and Fe2+, as well as their binary mixtures were well distinguished. Our sensor array was capable of the quantitative analysis of metal ions, showing a linear range from 0.5xa0μM to 20xa0μM for Co2+, Ni2+, Mn2+, and Fe2+. The results demonstrated that the number of sensing elements was easily extensible by using amino acids as QDs regulators. This strategy will provide a new direction to establish the sensitive array sensing systems.

Time-resolved determination of Fe(II) ions using cysteine-bridged Mn-doped ZnS quantum dots as a phosphorimetric probe

AbstractA time-resolved phosphorescence (TRP) is applied to the highly sensitive determination of Fe(II) ions. The method is based on the use of a phosphorescent probe consisting of cysteine-bridged Mn-doped ZnS quantum dots (Mn/ZnS QDs). The presence of cysteine enhances the phosphorescence of the QDs and alsoxa0increases the efficiency ofxa0quenching caused by Fe(II) ions. This results in strongly improved selectivity for Fe(II). The linear response is obtained in the concentration range of 50–1000xa0nM with a 19xa0nM detection limit. Phosphorescence is recorded at excitation/emission peaks of 301/602xa0nm. The interference of short-lived fluorescent and scattering background from the biological fluids is eliminated by using the TRP mode with a delay time of 200xa0μs. The determination of Fe(II) in human serum samples spiked at a 150xa0nM level gave a 92.4% recovery when using the TRP mode, but only 52.4% when using steady-state phosphorescence. This demonstrates that this probe along with TRP detection enables highly sensitive and accurate determination of Fe(II) in serum.n Graphical abstractSchematic of a novel phosphorescent method for the detection of Fe2+ ions based on cysteine-bridged Mn-doped ZnS quantum dots. The sensitivity of this assay greatly increases due to the addition of cysteine. Interferences by short-lived auto-fluorescence and the scattering light from the biological fluids is eliminated by using time-resolved phosphorescence mode.

Lab-on-nanoparticle as a multidimensional device for colorimetric discrimination of proteins

AbstractWe reportxa0on a method for sensitive detection and discrimination of multiple proteins. The peroxidase-like activity of gold nanoparticles (AuNPs) is employed to catalyze the oxidation of 3′,3′,5′,5′-tetramethylbenzidine (TMB) in the presence of H2O2. Depending on the protein, this produces colorations with different absorbance. The catalytic activity of the reaction system is affected because different proteins are absorbed onto the surface of the AuNPs. The absorbance values at 370, 450, and 650xa0nm are different in the presence of different proteins. The array can discriminate 8 proteins at 50xa0nM concentration levels with 100% accuracy. It also can discriminate proteins being present in different concentrations and mixtures with different molar ratios of proteins. Human urine spikes with 8 proteins (Concanavalin A), Cytochrome C, Horseradish peroxidase, Human serum albumin, Myoglobin, Pepsin, Trypsin, Papain) can be differentiated by applying hierarchical cluster analysis. The system also can discriminate proteins at different concentrations and the mixtures with different molar ratios in bovine serum. This indicates that the array has a great potential in terms of analyzing biological fluids.n Graphical abstractWe fabricate a multidimensional colorimetric sensor array based on bare AuNP for proteins discrimination. The peroxidase-like activity of AuNP is employed to catalyze 3,3,5,5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2), which causes multicolor chromogenic system and different characteristic wavelengths with different absorbance values as sensing elements.