Qiuming Yu

Inverted size-dependence of surface-enhanced Raman scattering on gold nanohole and nanodisk arrays.

Surface-enhanced Raman scattering (SERS) on gold nanohole and nanodisk arrays with precisely controlled size and spacing fabricated via electron beam lithography was investigated. These nanostructures exhibit strong SERS signals at 785 nm excitation but not at 514 nm. When the edge-to-edge distance is maintained, enhancement increases for nanoholes but decreases for nanodisks as diameter is increased. It is shown that the observed enhancement results from the local surface plasmon resonance wavelength shifts to the near-infrared regime as nanohole diameter increases. The large tolerance on dimensions and the empty space confined by nanoholes suggest promise for their use as a functional component in sensing, spectroscopy, and photonic devices.

Effect of Film Thickness on the Antifouling Performance of Poly(hydroxy-functional methacrylates) Grafted Surfaces

The development of nonfouling biomaterials to prevent nonspecific protein adsorption and cell/bacterial adhesion is critical for many biomedical applications, such as antithrombogenic implants and biosensors. In this work, we polymerize two types of hydroxy-functional methacrylates monomers of 2-hydroxyethyl methacrylate (HEMA) and hydroxypropyl methacrylate (HPMA) into polymer brushes on the gold substrate via surface-initiated atom transfer radical polymerization (SI-ATRP). We systematically examine the effect of the film thickness of polyHEMA and polyHPMA brushes on their antifouling performance in a wide range of biological media including single-protein solution, both diluted and undiluted human blood serum and plasma, and bacteria culture. Surface plasmon resonance (SPR) results show a strong correlation between antifouling property and film thickness. Too thin or too thick polymer brushes lead to large protein adsorption. Surfaces with the appropriate film thickness of ∼25-45 nm for polyHPMA and ∼20-45 nm for polyHEMA can achieve almost zero protein adsorption (<0.3 ng/cm(2)) from single-protein solution and diluted human blood plasma and serum. For undiluted human blood serum and plasma, polyHEMA brushes at a film thickness of ∼20-30 nm adsorb only ∼3.0 and ∼3.5 ng/cm(2) proteins, respectively, while polyHPMA brushes at a film thickness of ∼30 nm adsorb more proteins of ∼13.5 and ∼50.0 ng/cm(2), respectively. Moreover, both polyHEMA and polyHPMA brushes with optimal film thickness exhibit very low bacteria adhesion. The excellent antifouling ability and long-term stability of polyHEMA and polyHPMA brushes make them, especially for polyHEMA, effective and stable antifouling materials for usage in blood-contacting devices.

pH responsive properties of non-fouling mixed-charge polymer brushes based on quaternary amine and carboxylic acid monomers.

In this work, we report a tunable mixed-charge copolymer surface containing positively charged quaternary amine monomers ([2-(acryloyloxy)ethyl] trimethyl ammonium chloride, TMA) and negatively-charged carboxylic acid monomers (2-carboxy ethyl acrylate, CAA). The non-fouling properties of this copolymer coating depend on environmental pH. The surface has charge neutrality under neutral and basic conditions, and is positively charged under acidic conditions due to the protonation of the carboxylic acid group. This transition in surface charge with respect to pH allows the surface to be switched from bacteria-adhesive to bacteria-resistant. We demonstrate that the bacteria adhered to the surface under acidic conditions can be easily released as bulk pH increases. This tunable surface can be used to collect a contaminant and then be externally stimulated to release the contaminant, to allow for analysis of its composition. Its bacteria attraction and release property makes it very promising for decontamination and biomedical applications.

Multifunctional magnetic–plasmonic nanoparticles for fast concentration and sensitive detection of bacteria using SERS

Multifunctional magnetic-plasmonic Fe(3)O(4)-Au core-shell nanoparticles (Au-MNPs) were prepared for simultaneous fast concentration of bacterial cells by applying an external point magnetic field, and sensitive detection and identification of bacteria using surface-enhanced Raman spectroscopy (SERS). We demonstrated that a spread of a 10 μL drop of a mixture of 10(5) cfu/mL bacteria and 3 μg/mL Au-MNPs on a silicon surface can be effectively condensed into a highly compact dot within 5 min by applying an external point magnetic field, resulting in 60 times more concentrated bacteria in the dot area than on the spread area without concentration. Surrounded by dense uniformly packed Au-MNPs, bacteria can be sensitively and reproducibly detected directly using SERS. The principle component analysis (PCA) showed that three different Gram-negative bacterial strains can be clearly differentiated. We also demonstrated that the condensed multifunctional Au-MNPs dot can be used as a highly sensitive SERS-active substrate and a limit of detection better than 0.1 ppb was obtained in detection of small molecules such as 4-mercaptopyrine. This novel platform significantly simplifies the concentration and detection process, which holds great promise for applications in food safety, environmental monitoring, medical diagnoses, and chemical and biological threat detections.

Controlled Hierarchical Architecture in Surface-initiated Zwitterionic Polymer Brushes with Structurally Regulated Functionalities

Hierarchical polymer films with structurally regulated functionalities are achieved by integrating 2D and 3D structures to enable ultralow nonspecific protein binding and high loading of molecular recognition elements, such as antibodies.

Surface-enhanced Raman scattering on gold quasi-3D nanostructure and 2D nanohole arrays

A new method was developed to fabricate unique gold quasi-3D plasmonic nanostructures on poly(dimethylsiloxane) PDMS and 2D nanohole arrays on silicon as surface-enhanced Raman scattering (SERS) substrates using electron beam lithography (EBL) with negative tone resist Ma-N 2403 and soft lithography. The size and shape of nanopillars fabricated by EBL were well controlled via different beam conditions. An enhancement factor (EF) as high as 6.4 x 10(5) was obtained for 4-mercaptopyridine molecules adsorbed on the gold quasi-3D nanostructure array on PDMS with 400 nm diameter, 100 nm spacing and 300 nm depth, while no enhancement was observed for the gold 2D nanohole array on silicon with the same diameter and spacing. The experimental results were confirmed by finite-difference time-domain (FDTD) calculations. Furthermore, the calculated total electric fields showed that the strong SERS exhibited by the gold quasi-3D nanostructure arrays on PDMS is due to the strong localized electric fields at the gold-air interface of the bottom gold nanodisc. The strong and reproducible SERS spectroscopy for molecules adsorbed on precisely controlled gold quasi-3D nanostructure arrays on PDMS makes it possible for the integration of SERS-active nanopatterns into microfluidic devices as chemical and biological sensors with molecular specificity.

Sensitive and Fast Detection of Fructose in Complex Media via Symmetry Breaking and Signal Amplification Using Surface-Enhanced Raman Spectroscopy

A new strategy is proposed to sensitively and rapidly detect analytes with weak Raman signals in complex media using surface-enhanced Raman spectroscopy (SERS) via detecting the SERS signal changes of the immobilized probe molecules on SERS-active substrates upon binding of the analytes. In this work, 4-mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-three-dimensional plasmonic nanostructure array (Q3D-PNA) SERS substrate to detect fructose. The molecule of 4-MPBA possesses three key functions: molecule recognition and reversible binding of the analyte via the boronic acid group, amplification of SERS signals by the phenyl group and thus shielding of the background noise of complex media, and immobilization on the surface of SERS-active substrates via the thiol group. Most importantly, the symmetry breaking of the 4-MPBA molecule upon fructose binding leads to the change of area ratio between totally symmetric 8a ring mode and nontotally symmetric 8b ring mode, which enables the detection. The detection curves were obtained in phosphate-buffered saline (PBS) and in undiluted artificial urine at clinically relevant concentrations, and the limit of detection of 0.05 mM was achieved.

A Robust Graft-to Strategy To Form Multifunctional and Stealth Zwitterionic Polymer-Coated Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs) are a new class of carrier materials promising for drug/gene delivery and many other important applications. Stealth coatings are necessary to maintain their stability in complex media. Herein, a biomimetic polymer conjugate containing one ultralow fouling poly(carboxybetaine) (pCBMA) chain and one surface-adhesive catechol (DOPA) residue group was efficiently grafted to the outer surface of SBA-15 type MSNs using a convenient and robust method. The cytotoxicity of SBA-15-DOPA-pCBMAs was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results showed no significant decrease in cell viability at the tested concentration range. Macrophage cell uptake studies revealed that the uptake ratios of SBA-15-DOPA-pCBMAs were much lower than that of parent MSNs. Furthermore, inductively coupled plasma mass spectrometry (ICP-MS) analysis results showed that after SBA-15-DOPA-pCBMAs were conjugated with a targeting cyclo-[Arg-Gly-Asp-d-Tyr-Lys] (cRGD) peptide, uptake by bovine aortic endothelial cells (BAECs) was notably increased. Results indicated that cRGD-functionalized MSNs were able to selectively interact with cells expressing αvβ3 integrin. Thus, MSNs with DOPA-pCBMAs are promising as stealth multifunctional biocarriers for targeted drug delivery or diagnostics.

Cellulose Paper Sensors Modified with Zwitterionic Poly(carboxybetaine) for Sensing and Detection in Complex Media

Poly(carboxybetaine) (PCB) functionalized cellulose paper was used as a paper-based microfluidic device. The results showed that the PCB modified paper sensor was able to achieve (a) more rapid and sensitive glucose detection from undiluted human serum compared to bare cellulose and (b) specific antigen detection via covalently immobilized antibodies.

Functionalizable and Ultrastable Zwitterionic Nanogels

Multifunctional biomimetic nanogels based on zwitterionic poly(carboxybetaine methacrylate) (pCBMA) were synthesized by inverse microemulsion free-radical polymerization. pCBMA nanogels exhibited excellent stability in 100% fetal bovine serum. Dextran labeled with fluorescein isothiocyanate (FITC-dextran) was encapsulated in nanogels as a model drug. Encapsulated FITC-dextran exhibited controlled release from the pCBMA nanogel. Additionally, pCBMA nanogels carry abundant carboxylate groups as functional groups used to conjugate ligands to the nanogels for targeted drug delivery. Flow cytometry results obtained showed that pCBMA nanogels conjugated with cyclo[Arg-Gly-Asp-D-Tyr-Lys] ligands dramatically improved the nanogel uptake by primary human umbilical vein endothelium cells. Functionalizable zwitterionic pCBMA nanogels hold great potential as targeted drug-delivery vectors for biomedical applications.