Cuong Cao

Highly sensitive, uniform, and reproducible surface-enhanced Raman spectroscopy from hollow Au-Ag alloy nanourchins.

A hierarchical nanoparticle strategy to simultaneously gain super Raman signal amplification, high uniformity, and reproducibility is presented. Using hollow Au-Ag alloy nanourchins, an ultrahigh sensitivity, e.g., down to 1 fM concentrations for DEHP molecule is obtained. A small standard deviation of <10% is achieved by simply dropping and evaporating sub-100 nm nanourchins onto a substrate.

A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor

Herein, we present the use of a single gold nanorod sensor for detection of diseases on an antibody-functionalized surface, based on antibody-antigen interaction and the localized surface plasmon resonance (LSPR) λ(max) shifts of the resonant Rayleigh light scattering spectra. By replacing the cetyltrimethylammonium bromide (CTAB), a tightly packed self-assembled monolayer of HS(CH(2))(11)(OCH(2)CH(2))(6)OCH(2)COOH(OEG(6)) has been successfully formed on the gold nanorod surface prior to the LSPR sensing, leading to the successful fabrication of individual gold nanorod immunosensors. Using prostate specific antigen (PSA) as a protein biomarker, the lowest concentration experimentally detected was as low as 111 aM, corresponding to a 2.79 nm LSPR λ(max) shift. These results indicate that the detection platform is very sensitive and outperforms detection limits of commercial tests for PSA so far. Correlatively, its detection limit can be equally compared to the assays based on DNA biobarcodes. This study shows that a gold nanorod has been used as a single nanobiosensor to detect antigens for the first time; and the detection method based on the resonant Rayleigh scattering spectrum of individual gold nanorods enables a simple, label-free detection with ultrahigh sensitivity.

Metamaterials-based label-free nanosensor for conformation and affinity biosensing.

Analysis of molecular interaction and conformational dynamics of biomolecules is of paramount importance in understanding their vital functions in complex biological systems, disease detection, and new drug development. Plasmonic biosensors based upon surface plasmon resonance and localized surface plasmon resonance have become the predominant workhorse for detecting accumulated biomass caused by molecular binding events. However, unlike surface-enhanced Raman spectroscopy (SERS), the plasmonic biosensors indeed are not suitable tools to interrogate vibrational signatures of conformational transitions required for biomolecules to interact. Here, we show that highly tunable plasmonic metamaterials can offer two transducing channels for parallel acquisition of optical transmission and sensitive SERS spectra at the biointerface, simultaneously probing the conformational states and binding affinity of biomolecules, e.g., G-quadruplexes, in different environments. We further demonstrate the use of the metamaterials for fingerprinting and detection of the arginine-glycine-glycine domain of nucleolin, a cancer biomarker that specifically binds to a G-quadruplex, with the picomolar sensitivity.

Homogenous growth of gold nanocrystals for quantification of PSA protein biomarker

We report on another alternative sensing platform for the detection of protein biomarker (PSA-ACT complex) based on homogenous growth of Au nanocrystals in solution phase. The immuno-recognition event is translated into the gold nanoparticle growth signal which can be intuitively recognized by an unaided eye, or quantitatively measured by an UV-vis spectrophotometric analysis. Surface plasmonic signature and kinetics of the Au nanogrowth in the homogenous phase containing of HAuCl(4), AA, and CTAB have also been studied to provide suitable parameters for the immunoassay. As a result, detection limit of PSA-ACT complex was determined to be 10fM. The result indicated that this is a very sensitive, robust, simple, and economic strategy to detect protein biomarkers, and it has great potential to detect other biological interactions.

Dual Enlargement of Gold Nanoparticles: From Mechanism to Scanometric Detection of Pathogenic Bacteria

A mechanism of dual enlargement of gold nanoparticles (AuNPs) comprising two steps is described. In the first step, the AuNPs are enlarged by depositing Au atoms on their crystalline faces. In this process, the particles are not only enlarged but they are also observed to multiply: new Au nuclei are formed by the budding and division of the enlarged particles. In the second step, a silver enhancement is subsequently performed by the deposition of silver atoms on the enlarged and newly formed AuNPs to generate bimetallic Au@Ag core-shell structures. The dual nanocatalysis greatly enhances the electron density of the nanostructures, leading to a stronger intensity for colorimetric discrimination as well as better sensitivity for quantitative measurement. Based on this, a simple scanometric assay for the on-slide detection of the food-born pathogen Campylobacter jejuni is developed. After capturing the target bacteria, gold-tagged immunoprobes are added to create a signal on a solid substrate. The signal is then amplified by the dual enlargement process, resulting in a strong color intensity that can easily be recognized by the unaided eye, or measured by an inexpensive flatbed scanner. In this paper, dual nanocatalysis is reported for the first time. It provides a valuable mechanistic insight into the development of a simple and cost-effective detection format.

Seedless synthesis of octahedral gold nanoparticles in condensed surfactant phase

We report a seedless synthetic method of gold octahedral nanoparticles in an aqueous phase. Eight facets with {111} crystalline structures of octahedral nanoparticles could be formed in an aqueous medium when the gold salt was reduced by ascorbic acid at room temperature in the presence of cetyltrimethylammonium bromide as a shape-inducing agent, and hydrogen peroxide as a reaction promoter. The growth kinetics and surface crystalline structures were characterized by UV-vis spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy.

Tailoring alphabetical metamaterials in optical frequency: plasmonic coupling, dispersion, and sensing.

Tailoring optical properties of artificial metamaterials, whose optical properties go beyond the limitations of conventional and naturally occurring materials, is of importance in fundamental research and has led to many important applications such as security imaging, invisible cloak, negative refraction, ultrasensitive sensing, and transformable and switchable optics. Herein, by precisely controlling the size, symmetry, and topology of alphabetical metamaterials with U, S, Y, H, U-bar, and V shapes, we have obtained highly tunable optical response covering visible-to-infrared (vis-NIR) optical frequency. In addition, we show a detailed study on the physical origin of resonance modes, plasmonic coupling, the dispersion of resonance modes, and the possibility of negative refraction. We have found that all the electronic and magnetic modes follow the dispersion of surface plasmon polaritons; thus, essentially they are electronic- and magnetic-surface-plasmon-polaritons-like (ESPP-like and MSPP-like) modes resulted from diffraction coupling between localized surface plasmon and freely propagating light. On the basis of the fill factor and formula of magnetism permeability, we predict that the alphabetical metamaterials should show the negative refraction capability in visible optical frequency. Furthermore, we have demonstrated the specific ultrasensitive surface enhanced Raman spectroscopy (SERS) sensing of monolayer molecules and femtomolar food contaminants by tuning their resonance to match the laser wavelength, or by tuning the laser wavelength to match the plasmon resonance of metamaterials. Our tunable alphabetical metamaterials provide a generic platform to study the electromagnetic properties of metamaterials and explore the novel applications in optical frequency.

Detection of pathogen based on the catalytic growth of gold nanocrystals

A homogenous detection of pathogen (Giardia lamblia cysts) based on the catalytic growth of gold nanoparticles (AuNPs) has been studied. In this study, centrifugal filters were employed as tools to concentrate and separate the pathogen cells, and moreover amplify the detection signal. The catalytic growth of gold nanoparticles was verified to be positively related to gold seeds concentration. On this basis, homogenous detection of the pathogenic bacteria in liquid phase was established by means of conjugating antibody to gold seeds. Under the given experimental condition, detection limit of G. lamblia cysts was determined as low as 1.088 x 10(3) cells ml(-1). The additional nonspecific binding tests were also conducted to verify the detection specificity. This sensing platform has been proved to be a sensitive, reliable and simple method for large-scale pathogen detection, and provide valuable insight for the development of gold nanocrystals based colorimetric biosensors.

Gold-based optical biosensor for single-mismatched DNA detection using salt-induced hybridization

In this study, a gold nanoparticle (Au-NP)-based detection method for sensitive and specific DNA-based diagnostic applications is described. A sandwich format consisting of Au-NPs/DNA/PMP (Streptavidin-coated MagnetSphere Para-Magnetic Particles) was fabricated. PMPs captured and separated target DNA while Au-NPs modified with oligonucleotide detection sequences played a role in recognition and signal production. Due to the much lower stability of mismatched DNA strands caused by unstable duplex structures in solutions of relatively low salt concentration, hybridization efficiency in the presence of different buffers was well investigated, and thus, the optimized salt concentration allowed for discrimination of single-mismatched DNA (MMT) from perfectly matched DNA (PMT). Therefore, quantitative information concerning the target analyte was translated into a colorimetric signal, which could easily and quantitatively measured by low-cost UV-vis spectrophotometric analysis. The results indicated this to be a very simple and economic strategy for detection of single-mismatched DNA strands.

Pre-storage of gelified reagents in a lab-on-a-foil system for rapid nucleic acid analysis

Reagent pre-storage in a microfluidic chip can enhance operator convenience, simplify the system design, reduce the cost of storage and shipment, and avoid the risk of cross-contamination. Although dry reagents have long been used in lateral flow immunoassays, they have rarely been used for nucleic acid-based point-of-care (POC) assays due to the lack of reliable techniques to dehydrate and store fragile molecules involved in the reaction. In this study, we describe a simple and efficient method for prolonged on-chip storage of PCR reagents. The method is based on gelification of all reagents required for PCR as a ready-to-use product. The approach was successfully implemented in a lab-on-a-foil system, and the gelification process was automated for mass production. Integration of reagents on-chip by gelification greatly facilitated the development of easy-to-use lab-on-a-chip (LOC) devices for fast and cost-effective POC analysis.