Concept: Surface plasmon resonance
The staining of neurons with silver began in the 1800s, but until now the great resolving power of the laser scanning confocal microscope has not been utilized to capture the in-focus and three-dimensional cytoarchitecture of metal-impregnated cells. Here, we demonstrate how spectral confocal microscopy, typically reserved for fluorescent imaging, can be used to visualize metal-labeled tissues. This imaging does not involve the reflectance of metal particles, but rather the excitation of silver (or gold) nanoparticles and their putative surface plasmon resonance. To induce such resonance, silver or gold particles were excited with visible-wavelength laser lines (561 or 640 nm), and the maximal emission signal was collected at a shorter wavelength (i.e., higher energy state). Because the surface plasmon resonances of noble metal nanoparticles offer a superior optical signal and do not photobleach, our novel protocol holds enormous promise of a rebirth and further development of silver- and gold-based cell labeling protocols.
We report an enhancement in the efficiency of organic solar cells via the incorporation of gold (Au) or silver (Ag) nanoparticles (NPs) in the hole-transporting buffer layer of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), which was formed on an indium tin oxide (ITO) surface by the spin-coating of PEDOT:PSS-Au or Ag NPs composite solution. The composite solution was synthesized by a simple in situ preparation method which involved the reduction of chloroauric acid (HAuCl4) or silver nitrate (AgNO3) with sodium borohydride (NaBH4) solution in the presence of aqueous PEDOT:PSS media. The NPs were well dispersed in the PEDOT:PSS media and showed a characteristic absorption peak due to the surface plasmon resonance effect. Organic solar cells with the structure of ITO/PEDOT:PSS-Au, Ag NPs/poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PC61BM)/LiF/Al exhibited an 8% improvement in their power conversion efficiency mainly due to the enlarged surface roughness of the PEDOT:PSS, which lead to an improvement in the charge collection and ultimately improvements in the short-circuit current density and fill factor.
A novel class of small molecule inhibitors for plasminogen activator inhibitor type 1 (PAI-1)(2), represented by AZ3976, was identified in a high through-put screening campaign. AZ3976 displayed an IC(50) value of 26 µM in an enzymatic chromogenic assay. In a plasma clot lysis assay, the compound was active with an IC(50) of 16 µM. Surprisingly, AZ3976 did not bind to active PAI-1, but bound to latent PAI-1 with a K(D) of 0.29 µM at 35 °C and a binding stoichiometry of 0.94, as measured by isothermal calorimetry. Reversible binding was confirmed by surface plasmon resonance (SPR) direct binding experiments. The X-ray structure of AZ3976 in complex with latent PAI-1 was determined to 2.4 Å resolution. The inhibitor was bound in the flexible joint region with the entrance to the cavity located between α-helix D and β-strand 2A. A set of SPR experiments revealed that AZ3976 inhibited PAI-1 by enhancing the latency transition of active PAI-1. Since AZ3976 only had measurable affinity for latent PAI-1, we propose that its mechanism of inhibition is based on binding to a small fraction in equilibrium with active PAI-1, a latent-like pre-latent form, from which latent PAI-1 is then generated more rapidly. This mode of action, with induced accelerated latency transition of active PAI-1 may, together with supporting X-ray data, provide improved opportunities for small molecule drug design in the hunt for therapeutically useful PAI-1 inhibitors.
Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII(a), which does not bind VWF. Nano-LC-mass spectrometry analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or FVIIIa. However, Lys773 of peptide Ser766-Leu774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser764-Arg782, which comprises the first 18 amino acid residues of mature VWF, showed a differential modification of both Lys773 and the alpha amino group of Ser764. To verify the role of Lys773 and the N-terminal Ser764 for FVIII binding, we employed VWF variants in which either Lys773 or Ser764 was replaced by an alanine. Surface plasmon resonance analysis and competition studies revealed that VWF-K773A exhibits reduced binding to FVIII and FVIII light chain, which harbors the VWF binding site. In contrast, VWF-S764A revealed more effective binding to FVIII and FVIII light chain as compared to WT-VWF. The results of our study show that the N-terminus of VWF is critical for the interaction with FVIII, and that the residues Ser764 and Lys773 have an opposite role in the binding mechanism.
We report an electrophoretic deposition method for the fabrication of gold nanoparticle (GNP) thin films as sensitive surface-enhanced Raman scattering (SERS) substrates. In this method, GNP sol, synthesized by a seed-mediated growth approach, and indium tin oxide (ITO) glass substrates were utilized as an electrophoretic solution and electrodes, respectively. From the scanning electron microscopy analysis, we found that the density of GNPs deposited on ITO glass substrates increases with prolonged electrophoresis time. The films possess high mechanical adhesion strength and exhibit strong localized surface plasmon resonance (LSPR) effect by showing high SERS sensitivity to detect 1 x 10-7 M rhodamine 6 G in methanol solution. Finally, the relationship between Raman signal amplification capability and GNP deposition density has been further investigated. The results of our experiment indicate that the high-density GNP film shows relatively higher signal amplification capability due to the strong LSPR effect in narrow gap regions between the neighboring particles on the film.
In this work, we focused on the label-free detection of simple protein binding using near-infrared light-responsive plasmonic nanoshell arrays with a controlled interparticle distance. The nanoshell arrays were fabricated by a combination of colloidal self-assembly and subsequent isotropic helium plasma etching under atmospheric pressure. The diameter, interparticle distance, and shape of nanoshells can be tuned with nanometric accuracy by changing the experimental conditions. The Au, Ag, and Cu nanoshell arrays, having a 240-nm diameter (inner, 200-nm polystyrene (PS) core; outer, 20-nm metal shell) and an 80-nm gap distance, exhibited a well-defined localized surface plasmon resonance (LSPR) peak at the near-infrared region. PS@Au nanoshell arrays showed a 55-nm red shift of the maximum LSPR wavelength of 885 nm after being exposed to a solution of bovine serum albumin (BSA) proteins for 18 h. On the other hand, in the case of Cu nanoshell arrays before/after incubation to the BSA solution, we found a 30-nm peak shifting. We could evaluate the difference in LSPR sensing performance by changing the metal materials.
With growing concerns about health issues worldwide, elegant sensors with high sensitivity and specificity for virus/antigens (Ag) detection are urgent to be developed. Homogeneous immunoassays (HIA) are an important technique with the advantages of small sample volumes requirement and pretreatment-free process. HIA are becoming more favorable for the medical diagnosis and disease surveillance than heterogeneous immunoassays. An important subset of HIA relies on the effect of fluorescence resonance energy transfer (FRET) via a donor-acceptor (D-A) platform, e.g., quantum dots (QDs) donor based FRET system. Being an excellent plasmonic material, silver triangular nanoplates (STNPs) have unique advantages in displaying surface plasmon resonance in the visible to near infrared spectral region, which make them a better acceptor for pairing with QDs in a FRET-based sensing system. However, the reported STNPs generally exhibited broad size distributions, which would greatly restrict their application as HIA acceptor for high detection sensitivity and specificity purpose. In this work, uniform STNPs and red-emitting QDs are firstly applied to construct FRET nanoplatform in the advanced HIA and further be exploited for analyzing virus Ag. The uniform STNPs/QDs nanoplatform based medical sensor provides a straightforward and highly sensitive method for Ag analysis in homogeneous form.
It is rarely the case that a single electron affects the behaviour of several hundred thousands of atoms. Here we demonstrate a phenomenon where this happens. The key role is played by topological insulators-materials that have surface states protected by time-reversal symmetry. Such states are delocalized over the surface and are immune to its imperfections in contrast to ordinary insulators. For topological insulators, the effects of these surface states will be more strongly pronounced in the case of nanoparticles. Here we show that under the influence of light a single electron in a topologically protected surface state creates a surface charge density similar to a plasmon in a metallic nanoparticle. Such an electron can act as a screening layer, which suppresses absorption inside the particle. In addition, it can couple phonons and light, giving rise to a previously unreported topological particle polariton mode. These effects may be useful in the areas of plasmonics, cavity electrodynamics and quantum information.
Integrated chemical and biological sensors give advantages in cost, size and weight reduction and open new prospects for parallel monitoring and analysis. Biosensors based on nanoelectromechanical systems (NEMS) are the most attractive candidates for the integrated platform. However, actuation and transduction techniques (e.g. electrostatic, magnetomotive, thermal or piezoelectric) limit their operation to laboratory conditions. All-optical approach gives the possibility to overcome this problem, nevertheless, the existing schemes are either fundamentally macroscopic or excessively complicated and expensive in mass production. Here we propose a novel scheme of extremely compact NEMS biosensor monolithically integrated on a chip with all-nanophotonic transduction and actuation. It consists of the nanophotonic waveguide and the nanobeam cantilever placed above the waveguide, both fabricated in the same CMOS-compatible process. Being in the near field of the strongly confined photonic or plasmonic mode, cantilever is efficiently actuated and its response is directly read out using the same waveguide, which results in a very high sensitivity and capability of single-molecule detection even in atmosphere.
MicroRNAs are short noncoding RNAs consisting of 18-25 nucleotides that target specific mRNA moieties for translational repression or degradation, thereby modulating numerous biological processes. Although microRNAs have the ability to behave like oncogenes or tumor suppressors in a cell-autonomous manner, their exact roles following release into the circulation are only now being unraveled and it is important to establish sensitive assays to measure their levels in different compartments in the circulation. Here, an ultrasensitive localized surface plasmon resonance (LSPR)-based microRNA sensor with single nucleotide specificity was developed using chemically synthesized gold nanoprisms attached onto a solid substrate with unprecedented long-term stability and reversibility. The sensor was used to specifically detect microRNA-10b at the attomolar (10(-18) M) concentration in pancreatic cancer cell lines, derived tissue culture media, human plasma, and media and plasma exosomes. In addition, for the first time, our label-free and nondestructive sensing technique was used to quantify microRNA-10b in highly purified exosomes isolated from patients with pancreatic cancer or chronic pancreatitis, and from normal controls. We show that microRNA-10b levels were significantly higher in plasma-derived exosomes from pancreatic ductal adenocarcinoma patients when compared with patients with chronic pancreatitis or normal controls. Our findings suggest that this unique technique can be used to design novel diagnostic strategies for pancreatic and other cancers based on the direct quantitative measurement of plasma and exosome microRNAs, and can be readily extended to other diseases with identifiable microRNA signatures.