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Articles by Stefan Maier in JoVE

 JoVE Immunology and Infection

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis


JoVE 2299 12/18/2010

Department of Surgery, University of Greifswald

The Colon Ascendens Stent Peritonitis (CASP) is a highly standardized model for polymicrobial abdominal sepsis in rodents. This article describes the surgical procedure of CASP. The CASP model and its variants allow the systematic investigation of various problems concerning the subject of sepsis.

Other articles by Stefan Maier on PubMed

Impaired Monocyte IL-12 Production Before Surgery As a Predictive Factor for the Lethal Outcome of Postoperative Sepsis

To investigate whether monocyte paralysis resistant to interferon-gamma (IFN-gamma) costimulation may exist before surgery and postoperative infection and may correlate with the outcome of postoperative sepsis.

Local Detection of Electromagnetic Energy Transport Below the Diffraction Limit in Metal Nanoparticle Plasmon Waveguides

Achieving control of light-material interactions for photonic device applications at nanoscale dimensions will require structures that guide electromagnetic energy with a lateral mode confinement below the diffraction limit of light. This cannot be achieved by using conventional waveguides or photonic crystals. It has been suggested that electromagnetic energy can be guided below the diffraction limit along chains of closely spaced metal nanoparticles that convert the optical mode into non-radiating surface plasmons. A variety of methods such as electron beam lithography and self-assembly have been used to construct metal nanoparticle plasmon waveguides. However, all investigations of the optical properties of these waveguides have so far been confined to collective excitations, and direct experimental evidence for energy transport along plasmon waveguides has proved elusive. Here we present observations of electromagnetic energy transport from a localized subwavelength source to a localized detector over distances of about 0.5 microm in plasmon waveguides consisting of closely spaced silver rods. The waveguides are excited by the tip of a near-field scanning optical microscope, and energy transport is probed by using fluorescent nanospheres.

Cecal Ligation and Puncture Versus Colon Ascendens Stent Peritonitis: Two Distinct Animal Models for Polymicrobial Sepsis

Colon ascendens stent peritonitis (CASP) and cecal ligation and puncture (CLP), two animal models designed to closely mimic the clinical course of intra-abdominal sepsis, were compared. In the past, immunomodulatory therapies developed in animal studies failed to be successful in humans. As a consequence, the established animal sepsis models were criticized. It has been proposed that present models had to be reevaluated, and new, clinically more relevant models should be evolved. CLP procedure was performed puncturing once (CLP[1]) or twice (CLP[2]) the ligated cecum of C57BL/6 mice. In the CASP model, a stent with defined diameter was surgically inserted into the ascending colon. Survival, bacterial load, immunohistochemistry, and serum cytokine levels were analyzed in the groups. Survival after CASP procedure correlated strongly with the stent diameter, whereas the number of punctures in CLP did not significantly change survival rate. Bacterial loads of peritoneal lavage, liver, and lung, as well as serum cytokine levels (tumor necrosis factor, interleukin 1 beta, interleukin 10) steadily increased from 6 to 24 h after the CASP procedure. In contrast, continuously low amounts of bacteria and cytokines were found in CLP mice at any point of time. Twenty-four hours after CLP surgery, the ligated cecum was covered by adhesive small bowel loops, whereas in CASP mice, the intestinal leakage was then still present. The CASP model mimics closely the clinical course of diffuse peritonitis with early and steadily increasing systemic infection and inflammation (systemic inflammatory response syndrome). In contrast, CLP reveals a model of intra-abdominal abscess formation with sustained and minor signs of systemic inflammation.

Intragraft INOS Induction During Human Liver Allograft Rejection Depresses Cytochrome P450 Activity

Allograft function may become impaired during rejection after human liver transplantation. Cytokines induce nitric oxide (NO) production in hepatocytes, Kupffer cells and infiltrating mononuclear cells. NO inhibits cytoplasmatic cytochrome p450 (CYP) enzyme activity in vitro. It is not known whether this mechanism plays a role in vivo. In order to characterize the role of locally produced cytokines in the pathogenesis of liver dysfunction, we analysed human liver transplant biopsy material for the expression of proinflammatory cytokines as well as for NO synthase and we compared these results to the microsomal liver function in vivo [aminopyrine breath test (ABT)] and in vitro (enzymatic analysis of CYP). Microsomal liver function decreased in vivo during rejection while ABT levels decreased by 40% and increased again by 59% after the acute rejection episode. Similarly, CYP 1A2 and 2E1 activity dropped 42% and 24% in rejecting samples, respectively. Competitive reverse transcriptase polymerase chain reaction (RT-PCR) showed a fivefold upregulation of interferon gamma (IFN-gamma) gene expression. Inducible, but not constitutive NO-synthase gene expression was upregulated fivefold in samples from rejecting patients suggesting a local induction of NO in response to immune events. Our data show a marked impairment of CYP enzyme activity during allograft rejection which is presumably secondary to an increased intragraft production of proinflammatory cytokines and NO.

CCR4-deficient Mice Show Prolonged Graft Survival in a Chronic Cardiac Transplant Rejection Model

Chronic graft rejection mediated by cellular immune responses still poses a serious clinical problem in transplant surgery. Chemokines coordinate the recruitment of leukocytes in inflammatory and immune responses. Their precise functions in the rejection of allografts are still ill defined. This study investigates the role of chemokine receptor 4 (CCR4) in acute and chronic cardiac allograft rejection in mice. Allogeneic hearts were transplanted into CCR4 deficient (CCR4(-/-)) and control recipients. Reverse transcription-PCR showed transcription of macrophage-derived chemokine and thymus and activation-regulated chemokine, the cognate chemokine ligands of CCR4, within the graft. Compared to wild-type controls, acute allograft rejection in CCR4(-/-) recipients was only slightly prolonged. In contrast, in a gallium nitrate chronic cardiac allograft rejection model, cardiac graft survival was significantly prolonged in CCR4(-/-) recipients. A relative increase in the percentage of graft infiltrating CD8(+) T cells in CCR4(-/-) recipients was observed 30 days after transplantation and was accompanied by a decrease in CD4(+) T cells. Moreover, the percentage of NK1.1(+)CD3(+) graft-infiltrating cells was significantly reduced on day 5 and day 30 post transplantation. These findings indicate that CCR4 is involved in the recruitment of NK1.1(+)CD3(+) cells into cardiac allografts and clearly establish an important and novel role for CCR4 in chronic graft rejection.

Impact of Interleukin-12, Oxidative Burst, and INOS on the Survival of Murine Fecal Peritonitis

Abdominal sepsis due to secondary fecal peritonitis following anastomosis insufficiency is a rare but life threatening complication of colorectal surgery. The induction of IFN-gamma by IL-12 is believed to play a key role in sepsis as it promotes antibacterial effector mechanisms such as oxidative burst or nitric oxide induction. The impact of gene deficiency for IL-12 (IL-12p40 KO), oxidative burst (p47(phox) KO), or NO induction (iNOS KO) on the outcome of fecal peritonitis was characterized using the murine Colon Ascendens Stent Peritonitis model (CASP). In the IL-12p40 KO model, 3 and 12 h after surgery, serum cytokine levels of IL-1beta, TNF, IL-18, and IL-10 were analyzed. Expression of IL-1beta, IL-10, IP-10, and MIP-1alpha was measured in lung and liver by RNAse Protection Assay. IL-12p40 and iNOS-deficient mice exhibited a significantly higher susceptibility to CASP as compared to the controls, whereas no significant difference was observed in p47(phox) KO mice. Absence of IL-12 resulted in delayed expression of proinflammatory cytokines and chemokines in both the liver and the lung, and was associated with significant reduction of IL-1beta levels in the serum 12 h after CASP. IL-12 and iNOS possess protective functions in fecal murine peritonitis. Surprisingly, no significant contribution of oxidative burst to the immune response was observed. Overall, these findings suggest that IL-12 deficiency causes a profound delay of the immune response after polymicrobial challenge resulting in significantly increased susceptibility in the CASP model.

The Vagal Nerve As a Link Between the Nervous and Immune System in the Instance of Polymicrobial Sepsis

The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the "cholinergic inflammatory pathway." Through stimulation of the acetylcholine receptors located upon the macrophages, the "unspecific" immune system can be directly influenced.

Terahertz Surface Plasmon-polariton Propagation and Focusing on Periodically Corrugated Metal Wires

In this Letter, we show how the dispersion relation of surface plasmon polaritons (SPPs) propagating along a perfectly conducting wire can be tailored by corrugating its surface with a periodic array of radial grooves. In this way, highly localized SPPs can be sustained in the terahertz region of the electromagnetic spectrum. Importantly, the propagation characteristics of these spoof SPPs can be controlled by the surface geometry, opening the way to important applications such as energy concentration on cylindrical wires and superfocusing using conical structures.

Plasmonic Field Enhancement and SERS in the Effective Mode Volume Picture

The controlled creation of nanometric electromagnetic field confinement via surface plasmon polariton excitations in metal/insulator/metal heterostructures is described via the concept of an effective electromagnetic mode volume Veff. Extensively used for the description of dielectric microcavities, its extension to plasmonics provides a convenient figure of merit and allows comparisons with dielectric counterparts. Using a one-dimensional analytical model and three-dimensional finite-difference time-domain simulations, it is shown that plasmonic cavities with nanometric dielectric gaps indeed allow for physical as well as effective mode volumes well below the diffraction limit in the gap material, despite significant energy penetration into the metal. In this picture, matter-plasmon interactions can be quantified in terms of quality factor Q and Veff, enabling a resonant cavity description of surface enhanced Raman scattering.

Cytochrome P450 Activity Mirrors Nitric Oxide Levels in Postoperative Sepsis: Predictive Indicators of Lethal Outcome

The development of liver failure significantly influences prognosis during the course of major septic complications. Although the underlying cause for septic liver failure is still unclear, research using animal models has demonstrated that an increased nitric oxide (NO) synthesis compromises detoxification processes in the liver.

Colon Ascendens Stent Peritonitis--a Model of Sepsis Adopted to the Rat: Physiological, Microcirculatory and Laboratory Changes

The colon ascendens stent peritonitis (CASP) procedure creates an intestinal leakage of feces, resulting in diffuse peritonitis and polymicrobial sepsis. Mouse models of CASP have been used to study sepsis experimentally. The aim of the present study was to establish CASP sepsis in rats and to provide basic functional characteristics of this model. In analogy to the mouse model, 3 degrees of severity of CASP sepsis, 2 sublethal and 1 lethal, were established depending on the stent diameter. Radio-telemetric recordings in a sublethal model showed that the nonsurvivors remained hemodynamically stable until approximately 1 h before death, when heart rate and blood pressure fell rapidly. Intestinal microcirculatory changes were analyzed 3, 6, 12, and 18 h after CASP surgery using intravital microscopy in a sublethal model. After 18 h, the numbers of the leukocytes firmly adhering to the endothelium and of the ones temporarily interacting were significantly increased. The levels of IL-6 and IL-1beta increased continuously during the CASP experiments while remaining unchanged in the sham group. TNF-alpha and IL-10 levels of CASP animals reached a maximum after 12 h. In conclusion, a rat model of CASP sepsis has been established and characterized with regard to alterations in cardiovascular and microcirculatory function as well as plasma cytokine levels. In experimental settings where genetically engineered animals are not required, it will facilitate detailed examination of dynamic changes in integrated organ function during the course of sepsis and the investigation of treatment strategies.

Sepsis Affects Cardiac Expression of Multidrug Resistance Protein 5 (MRP5, ABCC5), an ABC-type CGMP Export Pump

One of the clinical characteristics associated with septic shock is heart failure. Several lines of evidence indicate that functional consequences of heart failure in septic shock are linked to the activated NO-cyclic guanosine monophosphate (NO-cGMP) pathway. We have previously shown that the high-affinity cGMP export transporter, multidrug resistance protein 5 (MRP5), is expressed in the heart, which modulates intracellular concentrations and, hence, the effects of cGMP. Thus, modified expression of cardiac MRP5 in septic shock can alter cGMP concentrations and contribute to the development of heart failure. We therefore investigated MRP5 expression in the heart using two established murine models of septic shock (intraperitoneal LPS injection and surgical implantation of a stent into the ascending colon, resulting in a multibacterial peritonitis [CASP, colon ascendens stent peritonitis] in C57BL/6N mice, respectively; n = 38). Cardiac MRP5 was assessed by quantitative polymerase chain reaction and immunofluorescence. The protein was localized in the endothelial wall, smooth muscle, and cardiac myocytes. MRP5 mRNA expression was significantly reduced compared with controls both in the LPS (31.9 +/- 16.8 x 10(-4) vs. 54.1 +/- 14.8 x 10(-4), P = 0.025) and CASP model (18.3 +/- 9.4 x 10(-4) vs. 42.8 +/- 12.1 x 10(-4), P = 0.009; MRP5/glyceraldehyde 3-phosphate dehydrogenase copy numbers, respectively). In parallel, IL-6 plasma levels were significantly increased in both models. Incubation of cultured murine cardiomyocytes (HL1) with 5 ng/mL IL-6 resulted in decreased expression of MRP5 (54% of control), as did incubation of the cells with serum from septic mice (LPS serum, 22% of control; CASP serum, 11% of control). In conclusion, cardiac expression of the cGMP export transporter MRP5 is decreased in two murine models of septic shock, most likely by a transcriptional mechanism. Reduced cGMP export as a consequence of decreased MRP5 expression can attenuate heart failure in sepsis.

Seasonal Variations in Inflammatory Responses to Sepsis and Stress in Mice

In this study, we analyzed seasonal variations of immunoreactivity using a model of septic shock and a model of immunosuppression induced by chronic stress in mice.

Metallic Mode Confinement in Microstructured Fibres

We report the first long, uniform, optical fibers in which visible light is guided in a single mode by metallic reflection. We describe the fabrication, experiment and characterization of these metallic optical fibers and compare them with theoretical calculations.

Detrimental Role of CC Chemokine Receptor 4 in Murine Polymicrobial Sepsis

CC chemokine receptor 4 (CCR4) and its two ligands, CCL17 and CCL22, are critically involved in different immune processes. In models of lipopolysaccharide-induced shock, CCR4-deficient (CCR4(-/-)) mice showed improved survival rates associated with attenuated proinflammatory cytokine release. Using CCR4(-/-) mice with a C57BL/6 background, this study describes for the first time the role of CCR4 in a murine model of polymicrobial abdominal sepsis, the colon ascendens stent peritonitis (CASP). CASP-induced sepsis led to a massive downregulation of CCR4 in lymphoid and nonlymphoid tissues, whereas the expression of CCL17 and CCL22 was independent of the presence of CCR4. After CASP, CCR4(-/-) animals showed a strongly enhanced bacterial clearance in several organs but not in the peritoneal lavage fluid and the blood. In addition, significantly reduced levels of proinflammatory cytokines/chemokines were measured in organ supernatants as well as in the sera of CCR4(-/-) mice. CCR4 deficiency consequently resulted in an attenuated severity of systemic sepsis and a strongly improved survival rate after CASP or CASP with intervention. Thus, our data provide clear evidence that CCR4 plays a strictly detrimental role in the course of polymicrobial sepsis.

Symmetry Breaking in Plasmonic Nanocavities: Subradiant LSPR Sensing and a Tunable Fano Resonance

A metallic nanostructure consisting of a disk inside a thin ring supports superradiant and very narrow subradiant modes. Symmetry breaking in this structure enables a coupling between plasmon modes of differing multipolar order, resulting in a tunable Fano resonance. The LSPR sensitivities of the subradiant and Fano resonances are predicted to be among the largest yet for individual nanostructures.

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

Resident tissue macrophages exert important functions during severe systemic infection and contribute to changes in local as well as systemic immune responses. Alveolar macrophages (AM) play a crucial role in airway diseases and in the defense against microorganisms invading the body via the bronchopulmonary tract. It has been postulated that AM are involved in the development of acute local disorders as a consequence of extrapulmonary stimuli like pancreatitis, peritonitis, or trauma.

Plasmonics: The Benefits of Darkness

Electron Energy-loss Spectroscopy (EELS) of Surface Plasmons in Single Silver Nanoparticles and Dimers: Influence of Beam Damage and Mapping of Dark Modes

We demonstrate the use of a scanning transmission electron microscope (STEM) equipped with a monochromator and an electron energy loss (EEL) spectrometer as a powerful tool to study localized surface plasmons in metallic nanoparticles. We find that plasmon modes can be influenced by changes in nanostructure geometry and electron beam damage and show that it is possible to delineate the two effects through optimization of specimen preparation techniques and acquisition parameters. The results from the experimental mapping of bright and dark plasmon energies are in excellent agreement with the results from theoretical modeling.

Broadband Spoof Plasmons and Subwavelength Electromagnetic Energy Confinement on Ultrathin Metafilms

A complementary split ring resonator (CSRR)-based metallic layer is proposed as a route to mimic surface plasmon polaritons. A numerical analysis of the textured surface is carried out and compared to previous prominent topologies such as metal mesh, slit array, hole array, and Sievenpiper mushroom surfaces, which are studied as well from a transmission line perspective. These well-documented geometries suffer from a narrowband response, alongside, in most cases, metal thickness constraint (usually of the order of lambda/4) and non-subwavelength modal size as a result of the large dimensions of the unit cell (one dimensions is at least of the order of lambda/2). All of these limitations are overcome by the proposed CSRR-based surface. Besides, a planar waveguide is proposed as a proof of the potential of this CSRR-based metallic layer for spoof surface plasmon polariton guiding. Fundamental aspects aside, the structure under study is easy to manufacture by simple PCB techniques and it is expected to provide good performance within the frequency band from GHz to THz.

Fano Resonances in Individual Coherent Plasmonic Nanocavities

We observe the appearance of Fano resonances in the optical response of plasmonic nanocavities due to the coherent coupling between their superradiant and subradiant plasmon modes. Two reduced-symmetry nanostructures probed via confocal spectroscopy, a dolmen-style slab arrangement and a ring/disk dimer, clearly exhibit the strong polarization and geometry dependence expected for this behavior at the individual nanostructure level, confirmed by full-field electrodynamic analysis of each structure. In each case, multiple Fano resonances occur as structure size is increased.

Tunability of Subradiant Dipolar and Fano-type Plasmon Resonances in Metallic Ring/disk Cavities: Implications for Nanoscale Optical Sensing

Plasmonic nanocavities consisting of the concentric arrangement of a disk and a ring sustain both subradiant and superradiant dipolar plasmon modes with large associated field enhancements and high refractive index sensitivities. In structures with broken symmetry, additionally a highly tunable Fano interference feature appears, which can be explained with a simple analytical harmonic oscillator model. The spectral tunability of these resonances from the visible to the mid-infrared is investigated, highlighting a potential for applications in surface enhanced spectroscopies.

Single-particle Plasmon Resonance Spectroscopy of Phase Transition in Vanadium Dioxide

We demonstrate thermally controlled plasmon resonance modulation of single gold nanoparticles on vanadium dioxide thin films by performing dark-field spectroscopy measurements at different temperatures. The plasmon resonance of the nanoparticles exhibits a significant blueshift in the visible range when the vanadium dioxide film undergoes its insulator-to-metal phase transition around 67 °C. More importantly, the resonance shift shows a clear hysteresis, mirroring the behavior of the vanadium dioxide film. At a fixed wavelength, the scattering intensity of Au particles also shows a hysteretic behavior decorated with an overshoot before (after) the insulator-metal (metal-insulator) phase transition of the vanadium dioxide film, suggesting that the nanoparticle is probing local variations in the phase transition.

Interaction Between Plasmonic Nanoparticles Revisited with Transformation Optics

The interaction between plasmonic nanoparticles is investigated by means of transformation optics. The optical response of a dimer can be decomposed as a sum of modes whose resonances redshift when the nanoparticles approach each other. The extinction and scattering cross sections as well as the field enhancement induced by the dimer are derived analytically taking into account radiation damping. Interestingly, some invisibility dips occur in the scattering spectrum and originate from a destructive interference between each surface plasmon mode.

Geometry Dependence of Surface Plasmon Polariton Lifetimes in Nanohole Arrays

We study surface plasmon polariton lifetimes in two-dimensional arrays of blind holes on gold surfaces. The lifetimes are determined from the line widths of the resonant dips appearing in the specular reflection spectra. We find a strong dependence of lifetimes on the resonant wavelength and the hole geometry. Through both experiments and numerical simulations, we analyze the validity of the Rayleigh approximation and also explore the range of wavelengths and geometric parameters where it fails. Finally, we show that, within the range of geometries and wavelengths considered in our experiments, the behavior of surface plasmon polariton lifetimes can be understood as resulting from the interplay between the intrinsic metal absorption and the scattering of surface waves by single isolated holes.

Experimental Realization of Subradiant, Superradiant, and Fano Resonances in Ring/disk Plasmonic Nanocavities

Subradiant and superradiant plasmon modes in concentric ring/disk nanocavities are experimentally observed. The subradiance is obtained through an overall reduction of the total dipole moment of the hybridized mode due to antisymmetric coupling of the dipole moments of the parent plasmons. Multiple Fano resonances appear within the superradiant continuum when structural symmetry is broken via a nanometric displacement of the disk, due to coupling with higher order ring modes. Both subradiant modes and Fano resonances exhibit substantial reductions in line width compared to the parent plasmon resonances, opening up possibilities in optical and near IR sensing via plasmon line shape design.

Scattering Efficiency and Near Field Enhancement of Active Semiconductor Plasmonic Antennas at Terahertz Frequencies

Terahertz plasmonic resonances in semiconductor (indium antimonide, InSb) dimer antennas are investigated theoretically. The antennas are formed by two rods separated by a small gap. We demonstrate that, with an appropriate choice of the shape and dimension of the semiconductor antennas, it is possible to obtain large electromagnetic field enhancement inside the gap. Unlike metallic antennas, the enhancement around the semiconductor plasmonics antenna can be easily adjusted by varying the concentration of free carriers, which can be achieved by optical or thermal excitation of carriers or electrical carrier injection. Such active plasmonic antennas are interesting structures for THz applications such as modulators and sensors.

Kupffer Cell Depletion Reduces Hepatic Inflammation and Apoptosis but Decreases Survival in Abdominal Sepsis

During abdominal sepsis, the activation of hepatic Kupffer cells (KC) and its consequences are of central interest. This study evaluates the impact of selective KC depletion on hepatic microcirculation, cytokine release, and systemic alterations in the colon ascendens stent peritonitis (CASP), a model of polymicrobial abdominal sepsis.

Quantum Smoluchowski Equation: a Systematic Study

The strong-friction regime at low temperatures is analyzed systematically starting from the formally exact path-integral expression for the reduced dynamics. This quantum Smoluchowski regime allows for a type of semiclassical treatment in the inverse friction strength so that higher-order quantum corrections to the original quantum Smoluchowski equation [J. Ankerhold, P. Pechukas, and H. Grabert, Phys. Rev. Lett. 87, 086802 (2001); J. Ankerhold and H. Grabert, Phys. Rev. Lett. 101, 119903 (2008)] can be derived. Drift and diffusion coefficients are determined by the equilibrium distribution in position and are directly related to the corresponding action of extremal paths and fluctuations around them. It is shown that the inclusion of higher-order corrections reproduces the quantum enhancement above crossover for the decay rate out of a metastable well exactly.

Enhanced Surface Plasmon Resonance on a Smooth Silver Film with a Seed Growth Layer

This paper reports an effective method to enhance the surface plasmon resonance (SPR) on Ag films by using a thin Ni seed layer assisted deposition. Ag films with a thickness of about 50 nm were deposited by electron beam evaporation above an ultrathin Ni seed layer of approximately 2 nm on both silicon and quartz substrates. The root-mean-square (rms) surface roughness and the correlation length have been reduced from >4 nm and 28 nm for a pure Ag film to approximately 1.3 and 19 nm for Ag/Ni films, respectively. Both experimental and simulation results show that the Ag/Ni films exhibit an enhanced SPR over the pure Ag film with a narrower full width at half-maximum. Ag films with a Ge seed layer have also been prepared under the same conditions. The surface roughness can be reduced to less than 0.7 nm, but narrowing of the SPR curve is not observed due to increased absorptive damping in the Ge seed layer. Our results show that Ni acts as a roughness-diminishing growth layer for the Ag film while at the same time maintaining and enhancing the plasmonic properties of the combined structures. This points toward its use for low-loss plasmonic devices and optical metamaterials applications.

Plasmonic Light-harvesting Devices over the Whole Visible Spectrum

On the basis of conformal transformation, a general strategy is proposed to design plasmonic nanostructures capable of an efficient harvesting of light over a broadband spectrum. The surface plasmon modes propagate toward the singularity of these structures where the group velocity vanishes and energy accumulates. A considerable field enhancement and confinement is thus expected. Radiation losses are also investigated when the structure dimension becomes comparable to the wavelength.

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Improves the Innate Immune Response and Enhances Survival in Murine Polymicrobial Sepsis

To investigate the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in postoperative polymicrobial abdominal sepsis.Sepsis is the leading cause of death among critically ill surgical patients. TRAIL is commonly known as an apoptosis-inducing agent in cancer cells. It also plays an important role in the regulation of inflammatory reactions. The role of TRAIL in polymicrobial sepsis is still unclear.

The Fano Resonance in Plasmonic Nanostructures and Metamaterials

Since its discovery, the asymmetric Fano resonance has been a characteristic feature of interacting quantum systems. The shape of this resonance is distinctively different from that of conventional symmetric resonance curves. Recently, the Fano resonance has been found in plasmonic nanoparticles, photonic crystals, and electromagnetic metamaterials. The steep dispersion of the Fano resonance profile promises applications in sensors, lasing, switching, and nonlinear and slow-light devices.

Low-temperature Quantum Fluctuations in Overdamped Ratchets

At low temperatures and strong friction the time evolution of the density distribution in position follows a quantum Smoluchowski equation. Recently, also higher-order contributions of quantum fluctuations to drift and diffusion coefficients have been systematically derived. As a nontrivial situation to reveal the impact of subleading quantum corrections and to demonstrate convergence properties of the perturbation series, directed transport in ratchets is studied. It is shown that the perturbation series typically has a nonmonotonous behavior. Depending on symmetry properties higher-order contributions may even compensate current reversals induced by leading quantum fluctuations. This analysis demonstrates how to consistently treat the dynamics of overdamped quantum systems at low temperatures also in numerical applications.

Controlling Light Localization and Light-matter Interactions with Nanoplasmonics

Nanoplasmonics is the emerging research field that studies light-matter interactions mediated by resonant excitations of surface plasmons in metallic nanostructures. It allows the manipulation of the flow of light and its interaction with matter at the nanoscale (10(-9) m). One of the most promising characteristics of plasmonic resonances is that they occur at frequencies corresponding to typical electronic excitations in matter. This leads to the appearance of strong interactions between localized surface plasmons and light emitters (such as molecules, dyes, or quantum dots) placed in the vicinity of metals. Recent advances in nanofabrication and the development of novel concepts in theoretical nanophotonics have opened the way to the design of structures aimed to reduce the lifetime and enhance the decay rate and quantum efficiency of available emitters. In this article, some of the most relevant experimental and theoretical achievements accomplished over the last several years are presented and analyzed.

Implantation of Alloplastic Material Increases Survival of Mice Subsequently Exposed to Polymicrobial Sepsis

Major surgery can modulate the immune system and by this the clinical course of following complications. Effects of minor surgical treatments on the immune system and septic complications are poorly understood.

Platelet Factor 4 Binds to Bacteria, [corrected] Inducing Antibodies Cross-reacting with the Major Antigen in Heparin-induced Thrombocytopenia

A clinically important adverse drug reaction, heparin-induced thrombocytopenia (HIT), is induced by antibodies specific for complexes of the chemokine platelet factor 4 (PF4) and the polyanion heparin. Even heparin-naive patients can generate anti-PF4/heparin IgG as early as day 4 of heparin treatment, suggesting preimmunization by antigens mimicking PF4/heparin complexes. These antibodies probably result from bacterial infections, as (1) PF4 bound charge-dependently to various bacteria, (2) human heparin-induced anti-PF4/heparin antibodies cross-reacted with PF4-coated Staphylococcus aureus and Escherichia coli, and (3) mice developed anti-PF4/heparin antibodies during polymicrobial sepsis without heparin application. Thus, after binding to bacteria, the endogenous protein PF4 induces antibodies with specificity for PF4/polyanion complexes. These can target a large variety of PF4-coated bacteria and enhance bacterial phagocytosis in vitro. The same antigenic epitopes are expressed when pharmacologic heparin binds to platelets augmenting formation of PF4 complexes. Boosting of preformed B cells by PF4/heparin complexes could explain the early occurrence of IgG antibodies in HIT. We also found a continuous, rather than dichotomous, distribution of anti-PF4/heparin IgM and IgG serum concentrations in a cross-sectional population study (n = 4029), indicating frequent preimmunization to modified PF4. PF4 may have a role in bacterial defense, and HIT is probably a misdirected antibacterial host defense mechanism.

Structure of Plasmonic Aerogel and the Breakdown of the Effective Medium Approximation

A method for making aerogel doped with gold nanoparticles (GNPs) produces a composite material with a well-defined localized surface plasmon resonance peak at 520 nm. The width of the extinction feature indicates the GNPs are well dispersed in the aerogel, making it suited to optical study. A simple effective medium approximation cannot explain the peak extinction wavelengths. The plasmonic field extends on a scale where aerogel cannot be considered isotropic, so a new model is required: a 5 nm glass coating on the GNPs models the extinction spectrum of the composite material, with air (aerogel), methanol (alcogel), or toluene filling the pores.

High-resolution Mapping of Electron-beam-excited Plasmon Modes in Lithographically Defined Gold Nanostructures

We demonstrate the use of high-resolution electron beam lithography to fabricate complex nanocavities with nanometric spatial and positional control. The plasmon modes of these nanostructures are then mapped using electron energy-loss spectroscopy in a scanning transmission electron microsope. This powerful combination of patterning and plasmon mapping provides direct experimental verification to theoretical predictions of plasmon hybridization theory in complex metal nanostructures and allows the determination of the full mode spectrum of such cavities.

Plasmonic Hybridization Between Nanowires and a Metallic Surface: a Transformation Optics Approach

The interaction between metallic nanowires and a metal substrate is investigated by means of transformation optics. This plasmonic system is of particular interest for single molecule detection or nanolasers. By mapping such a plasmonic device onto a metal-insulator-metal infinite structure, its optical response can be fully derived analytically. In this article, the absorption cross-section of a nanowire placed close to a metallic surface is derived within and beyond the quasi-static limit. The system is shown to support several modes characterized by a different angular momentum and whose resonance red-shifts when the nanoparticle approaches the metal substrate. These resonances give rise to a drastic field enhancement (>10(2)) within the narrow gap separating the nanoparticle from the metal surface. The case of a nanowire dimer is also investigated and is closely related to the previous configuration. More physical insights are provided especially with respect to the invisibility dips appearing in the radiative spectrum. Numerical simulations have also been performed to confirm our analytical predictions and determine their range of validity.

Plasmonic Nanoantennas: Fundamentals and Their Use in Controlling the Radiative Properties of Nanoemitters

Fano Resonances in Nanoscale Plasmonic Systems: a Parameter-free Modeling Approach

The interaction between plasmonic resonances, sharp modes, and light in nanoscale plasmonic systems often leads to Fano interference effects. This occurs because the plasmonic excitations are usually spectrally broad and the characteristic narrow asymmetric Fano line-shape results upon interaction with spectrally sharper modes. By considering the plasmonic resonance in the Fano model, as opposed to previous flat continuum approaches, here we show that a simple and exact expression for the line-shape can be found. This allows the role of the width and energy of the plasmonic resonance to be properly understood. As examples, we show how Fano resonances measured on an array of gold nanoantennas covered with PMMA, as well as the hybridization of dark with bright plasmons in nanocavities, are well reproduced with a simple exact formula and without any fitting parameters.

Bridging Electromagnetic and Carrier Transport Calculations for Three-dimensional Modelling of Plasmonic Solar Cells

We report three-dimensional modelling of plasmonic solar cells in which electromagnetic simulation is directly linked to carrier transport calculations. To date, descriptions of plasmonic solar cells have only involved electromagnetic modelling without realistic assumptions about carrier transport, and we found that this leads to considerable discrepancies in behaviour particularly for devices based on materials with low carrier mobility. Enhanced light absorption and improved electronic response arising from plasmonic nanoparticle arrays on the solar cell surface are observed, in good agreement with previous experiments. The complete three-dimensional modelling provides a means to design plasmonic solar cells accurately with a thorough understanding of the plasmonic interaction with a photovoltaic device.

An Oxidative Coupling Route to Macrocyclic Thiophenes and Its Application in the Synthesis of a Donor/acceptor Hybrid Molecule

A route towards phenylene-bithiophene macrocycles via oxidative thiophene coupling under pseudo-high dilution conditions is reported. This method is applied to the synthesis of a shape-persistent thiophene macrocycle with extraannularly attached perylenebisimide moieties that forms supramolecular aggregates at the solid/liquid interface.

Photoinduced Charge Separation in an Organic Donor-acceptor Hybrid Molecule

Photoinduced charge separation in blends of organic materials of different electronic affinity and in organic donor-acceptor hybrids is a process of increasing importance for biological and artificial energy conversion and photovoltaics. Organic polymer solar cells are composed of an electron donor and an electron acceptor between which an electron transfer occurs after excitation by sunlight. Charge separation results in the formation of donor cation radicals and acceptor anion radicals. Here, we present our studies on a donor-acceptor hybrid molecule composed of a phenylene-bithiophene macrocycle used as a donor and a perylene bisimide acceptor. Using continuous wave EPR and modern pulsed EPR methodology in combination with light excitation, intermolecular as well as intramolecular charge separation has been observed. Light-induced charge separation observed upon selective excitation of either one of the chromophores indicates that both LUMO-based and HOMO-based electron transfer from donor to acceptor takes place. These experimental findings are corroborated by DFT calculations in which the HOMO of the donor-acceptor hybrid molecule is found at the phenylene-bithiophene macrocycle and the LUMO at the perylene bisimide.

Three-dimensionally Isotropic Negative Refractive Index Materials from Block Copolymer Self-assembled Chiral Gyroid Networks

Plasmonic Sinks for the Selective Removal of Long-lived States

The use of plasmonic nanostructures for the removal of unwanted long-lived states is investigated. We show that the total decay rate of such a state can be increased by up to 4 orders of magnitude, as compared to its intrinsic radiative decay rate, while leaving other neighboring optical transitions unaffected. For the specific case of molecular triplet excited states, we show that the use of a "plasmonic sink" has the potential to reduce photobleaching and ground-state depletion by at least 2 orders of magnitude. We consider, in addition, the impact of such structures on the performance of organic semiconductor lasers and show that, under realistic device conditions, plasmonic sinks have the capacity to increase the achievable laser repetition rate by a factor equal to the triplet decay rate enhancement. We conclude by studying the effect of exciton diffusion on the triplet density in the presence of metallic nanoparticles.

Plasmonic Interaction Between Overlapping Nanowires

The plasmonic interaction between overlapping nanowires with and without structure singularities is studied analytically and numerically. A conformal transformation approach is adopted to predict analytically the optical response of overlapping nanowires in the quasi-static limit. Surface plasmon excitations are shown to exhibit a lower bound cutoff frequency, which blue-shifts when the overlap distance increases. Between this cutoff and the surface plasmon frequencies, overlapping nanowires are capable of a strong and broad-band harvesting of light. This band gap feature is shown to be robust to radiative losses and to the bluntness of the structure singularities. Hence, the light harvesting performance of overlapping nanowires would not be damaged by nanofabrication imperfections. These remarkable features might be beneficial to the realization of plasmonic band gap filters.

Optically Induced Interaction of Magnetic Moments in Hybrid Metamaterials

We propose a novel type of hybrid metal-dielectric structures composed of silicon nanoparticles and split-ring resonators for advanced control of optically induced magnetic response. We reveal that a hybrid "metamolecule" may exhibit a strong distance-dependent magnetic interaction that may flip the magnetization orientation and support "antiferromagnetic" ordering in a hybrid metamaterial created by a periodic lattice of such metamolecules. The propagation of magnetization waves in the hybrid structures opens new ways for manipulating artificial "antiferromagnetic" ordering at high frequencies.

Revealing Plasmonic Gap Modes in Particle-on-Film Systems Using Dark-Field Spectroscopy

Polarization-controlled excitation of plasmonic modes in nanometric Au particle-on-film gaps is investigated experimentally using single-particle dark-field spectroscopy. Two distinct geometries are explored: nanospheres on top of and inserted in a thin gold film. Numerical simulations reveal that the three resonances arising in the scattering spectra measured for particles on top of a film originate from highly confined gap modes at the interface. These modes feature different azimuthal characteristics, which are consistent with recent theoretical transformation optics studies. On the other hand, the scattering maxima of embedded particles are linked to dipolar modes having different orientations and damping rates. Finally, the radiation properties of the particle-film gap modes are studied through the mapping of the scattered power within different solid angle ranges.

Role of Defects in the Phase Transition of VO(2) Nanoparticles Probed by Plasmon Resonance Spectroscopy

Defects are known to affect nanoscale phase transitions, but their specific role in the metal-to-insulator transition in VO(2) has remained elusive. By combining plasmon resonance nanospectroscopy with density functional calculations, we correlate decreased phase-transition energy with oxygen vacancies created by strain at grain boundaries. By measuring the degree of metallization in the lithographically defined VO(2) nanoparticles, we find that hysteresis width narrows with increasing size, thus illustrating the potential for domain boundary engineering in phase-changing nanostructures.

Plasmonic Systems Unveiled by Fano Resonances

We show in detail how a derivation of Fano theory can serve as a new paradigm to study, understand, and control the interaction of nano-objects with light. Examples include a plasmonic crystal, a dolmen-type structure sustaining dark and bright plasmon modes, and a nanoshell heptamer. On the basis of only three coupling factors, a straightforward analytical formula is obtained, only assuming a plasmonic resonance for the continuum, and retaining the nonclassical character of the original formalism. It allows one to predict, reproduce, or decompose Fano interferences solely in terms of the physical properties of the uncoupled nanostructures when available, without the need of additional fitting parameters.

Nanoplasmonics: Classical Down to the Nanometer Scale

We push the fabrication limit of gold nanostructures to the exciting sub-nanometer regime, in which light-matter interactions have been anticipated to be strongly affected by the quantum nature of electrons in metals. Doing so allows us to (1) evaluate the validity of classical electrodynamics to describe plasmonic effects at this length scale and (2) witness the gradual (instead of sudden) evolution of plasmon modes when two gold nanoprisms are brought into contact. Using electron energy-loss spectroscopy and transmission electron microscope imaging, we investigated nanoprisms separated by gaps of only 0.5 nm and connected by conductive bridges as narrow as 3 nm. Good agreement of our experimental results with electromagnetic calculations and LC circuit models evidence the gradual evolution of the plasmonic resonances toward the quantum coupling regime. We demonstrate that down to the nanometer length scales investigated classical electrodynamics still holds, and a full quantum description of electrodynamics phenomena in such systems might be required only when smaller gaps of a few angstroms are considered. Our results show also the gradual onset of the charge-transfer plasmon mode and the evolution of the dipolar bright mode into a 3λ/2 mode as one literally bridges the gap between two gold nanoprisms.

Broadband Light Harvesting Nanostructures Robust to Edge Bluntness

Metallic structures with sharp corners harvest the energy of incident light through plasmonic resonances, concentrating it in the corners and greatly increasing the local energy density. Despite its wide array of applications, this effect is normally strongly dependent on how sharp the corners are, presenting problems for fabrication. In this Letter, an analytical approach is proposed, based on transformation optics, to investigate a general class of plasmonic nanostructures with blunt edges or corners. Comprehensive discussions are provided on how the geometry affects the local field enhancement as well as the frequency and energy of each plasmonic resonance. Remarkably, our results evidence the possibility of designing broadband light harvesting devices with an absorption property insensitive to the geometry bluntness.

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