We provide a detailed study of the light-graphene interactions by investigating the optical absorption in the SLG, the density of optical states at the location of the SLG, and the extraction efficiency of the SERS signal of the SLG. Our numerical calculations of both the excitation field and the emission rate enhancements support the experimental results. We find that the enhancement is due to the increase in the confinement of electromagnetic fields on the location of the SLG that results in enhanced light absorption in the graphene at the excitation wavelength. We also find that water droplets increase the density of optical radiative states at the location of the SLG, leading to enhanced spontaneous emission rate of graphene at its Raman emission wavelengths.We numerically design and experimentally test a SERS-active substrate for enhancing the SERS signal of a single layer of graphene (SLG) in water. The SLG is placed on top of an array of silver-covered nanoholes in a polymer and is covered with water. Here we report a large enhancement of up to 2 × 10 The Raman signal of molecules is strongly enhanced when they are adsorbed on the surface of metallic nanostructures, which exhibit local surface plasmon resonances. This SERS effect originates in the giant enhancement of the local electromagnetic field at the pump laser wavelength23 and of the local density of optical states (LDOS) at the Raman emission wavelengths26 in hotspots, due to surface plasmon resonances of the metallic nanostructures to which the target molecules are adsorbed34. Owing to its ultra-high sensitivity, SERS has shown promise as a powerful tool for chemical identification with applications in biochemistry, food sciences, environmental studies and forensics35. In many of these applications, such as in detection of pollutants in sea-water and in measurement of blood glucose17, SERS is measured in water.Since its discovery in 1974 surface enhanced Raman spectroscopy (SERS)2-bonded carbon atoms, and the easiness of its integration with plasmonic nanostructures has made graphene a useful probe for investigating the optical response of such nanostructures44. Graphene itself has also been used as a planar SERS substrate for other target molecules48. In addition, using graphene is useful for overcoming some of the problems associated with conventional SERS substrates, such as the photochemical reaction of molecules in direct contact with metallic nanostructures, and the continuum spectral background originated from fluorescence49.The two-dimensional (2D) nature of graphene with a single atomic layer of sp5 in the SERS signal of the SLG on the patterned plasmonic nanostructure for a 532 nm excitation laser wavelength, when the SLG is covered with water. We provide a detailed study of the light-graphene interactions by investigating the optical absorption in the SLG, the density of optical states at the location of the SLG, and the extraction efficiency of the SERS signal of the SLG. The origin of the additional enhancement when water is placed on the graphene monolayer is that water leads to a red shift in the surface plasmon resonance, so that the excitation wavelength approximately matches the resonance wavelength of the structure50. We find that water droplets increase the confinement of electromagnetic fields on the location of the SLG that results in enhanced light absorption in the graphene at the excitation wavelength. We also find that water droplets increase the density of optical radiative states at the location of the SLG, leading to enhanced spontaneous emission rate of graphene at its Raman emission wavelengths.In this paper, we numerically design and experimentally test a SERS-active substrate for enhancing the SERS signal of a single layer of graphene (SLG) in water. The SLG is placed on top of an array of silver-covered nanoholes in a polymer and is covered with water. The SLG experiences an enhanced optical overlap with the local fields at the surface of the SERS substrate. Here we report a large enhancement of up to 2 × 1039. The periodicity of the square lattice of nanoholes and the cup depth h are chosen to be 350 nm and 500 nm, respectively -grown graphene layer was wet transferred onto the plasmonic nanohole array in which Titanium (Ti) and silver (Ag) layers are 9 nm and 90 nm in thickness, respectively Fig.  and Rama43. If this difference in areas is taken into account, the enhancement in the SERS signal of graphene is calculated to be ~2 × 105 for the plasmonic nanohole array covered with water (see Supplementary Information).Figure 54:γ is the SERS signal enhancement. The excitation rate enhancement Γexc is defined as the enhancement in the light absorption in the SLG on the plasmonic nanohole array substrate covered with either air or water at the pump laser wavelength, compared with the absorption in the SLG on glass substrate, that is:Pabs)g, (Pabs)a and (Pabs)w are the absorbed electromagnetic power in the SLG on glass substrate, in the SLG on plasmonic nanohole array substrate covered with air, and in the SLG on plasmonic nanohole array substrate covered with water, respectively. Here to elucidate the effect of water on the intensity of the SERS signal of the SLG when placed on the plasmonic nanohole substrate, we also investigate the optical response of the SLG when it is placed on the plasmonic nanohole array substrate and covered with air. The emission efficiency enhancement Γem is defined as the enhancement in the spontaneous emission rate of the SLG on plasmonic nanohole array substrate covered with either air or water at its Raman emission wavelengths, compared with the spontaneous emission rate of the SLG on glass substrate:γsp)g, (γsp)a and (γsp)w are the spontaneous emission rate of the SLG on glass substrate, on the plasmonic nanohole array substrate covered with air, and on the plasmonic nanohole array substrate covered with water droplets, respectively.In this sample the SERS signal of the SLG is enhanced through two physical processes of excitation rate enhancement and emission efficiency enhancement as follows55:σ(ω) is the surface conductivity of SLG, |E|2 is the intensity of the local electric field on the surface of the SLG, and S corresponds to the area of the SLG in one unit cell of the nanostructure. Absorption in the SLG is proportional to the local electric field intensity. To investigate changes in the absorption in the SLG due to addition of water droplets, we calculated the intensity of the local electric field on the surface of the nanohole array using full-wave 3D FDTD simulations. Figure z) direction at the interface between the nanohole array and the SLG , and its effect on electric field intensity is negligible due to its small thickness. For ease in comparison, graphs are normalized to the electric field intensity at the silver-air interface. The silver-water field profile shows ~4.3 times enhancement on resonance in the local electric field at the surface of the SLG compared to the silver-air profile. This leads to stronger peak intensity of the averaged local field on the SLG covered with water at 544 nm compared to the peak intensity of the averaged local field on the SLG covered with air at 441 nm  by a factor of ~5 compared to the glass substrate  and 620 nm (484 THz), respectively, for 532 nm excitation pump laser wavelength. When the SLG is on the plasmonic nanohole array covered with air, these emissions are mostly coupled to non-radiative states trapped in the nanostructure  is the LDOS. Based on equation  which is given by58:c is the speed of light in free space, z = 2 nm for nanostructure covered either air or water compared to the averaged LDOS on the surface of glass substrate in the wavelength range of interest (λ = 500 nm–650 nm). At 581 and 620 nm, corresponding to the G and 2D Raman emission peaks of the SLG, respectively, the averaged LDOS on the surface of the nanostructure is increased ~2 times compared to the averaged LDOS on the surface of a glass substrate. The averaged LDOS also increases ~3 times when the substrate is covered with water compared to a glass substrate. Thus, for this sample we conclude that γ ≈ 10 and γ ≈ 60 for the plasmonic nanohole array substrate covered with air and water, respectively, compared to the glass substrate.The intensified confinement in the electromagnetic field due to addition of water droplets results in increased LDOS at the surface of the SLG. To investigate the effect of water droplets on LDOS, we calculated the band diagram of the plasmonic nanohole array nanostructure covered with air and water, shown in Fig. ure Fig. . These ture Fig. . From Fi581 nm 51 THz and z > 0 in Fig. z direction to the total emitted power from an electric dipole emitter placed on the surface of the nanostructure. The location and polarization of the electric dipole emitter was varied as in the LDOS calculation (see Supplementary Information). Figure γtot)a ≈ 15 when compared to the SLG on glass substrate. In addition, the total enhancement of the intensity of the SERS signal of the SLG when placed on the plasmonic nanohole array and covered with water is (γtot)w ≈ 120. The addition of water droplets not only traps light on the location of the SLG leading to enhancement of both absorption and density of optical states, but also increases the extraction efficiency of the SERS signal of graphene.A critical parameter in collecting the Raman re-radiation of a sample is the extraction efficiency, which is calculated as the ratio of the radiated power from an emitter which can be extracted at the detector, to the total emitted power by the emitter. Here we investigate the effect of addition of water on the sample on the extraction efficiency of the SERS signal of the SLG. In the experimental setup the detector is located above the sample (γtot)a ≈ 10 and (γtot)w ≈ 100. It should be noted that the area over which the Raman spectra is measured is comparable with the excitation wavelength. However, the Raman enhancement in the graphene is mostly attributed to the plasmonic resonances  on the surface of the nanohole array which are typically on the order of few nanometers43. If this difference in the excitation area and the size of hotspots on the sample are taken into account the actual enhancement factor achieved is up to 2 × 105 (see Supplementary Information).These numeric calculations are in good agreement with the experiments in which we measured (5) from graphene on a SERS substrate consisting of a plasmonic nanohole array and covered with water. The enhancement is due to the increase in the confinement of electromagnetic fields on the location of the SLG that results in enhanced light absorption in the graphene at the excitation wavelength. Water droplets also increase the density of optical radiative states at the location of the SLG, leading to enhanced spontaneous emission rate of graphene at its Raman emission wavelengths. We believe the proposed sample can be used in biomedical and environmental applications that require SERS measurements in water.We numerically designed and experimentally tested a SERS substrate to enhance the Raman signal of a monolayer of graphene in water. We showed a large enhancement of Raman signal . The measured 2D band of the graphene sample had a symmetric Lorentzian shape with a full width at half maximum of ~39 cm−1 which corresponds to a single layer of graphene. In addition, the measured drop in the transmission spectra when the graphene sample was placed on top of the glass substrate was ~2.3% which again corresponds to a single layer of graphene. Finally, the high 2D to G peak intensity ratio for the graphene sample measured on several different regions using a 633 nm laser also corresponds to a single layer of graphene.Graphene layers were CVD-grown on both sides of a Cu substrate. A protective PMMA layer was deposited on one side and the unprotected graphene and Cu were etched by O−1.Renishaw PL/Raman micro-spectroscope system was used for Raman signal measurements. 532 nm Nd:YAG laser was used as the excitation light source. 50× long working distance objective lens was used to focus/collect incident light and Raman signal onto/from the surface of the graphene-metallic device. The range of measured wavenumbers was from 200 to 3000 cm59. Graphene was simulated as a 2D object based on its surface conductivity. The surface conductivity was tuned to give 2.3% light absorption in a single graphene layer suspended in air in the visible and NIR wavelength ranges60. In the absorption and field calculations periodic boundary conditions were used along the x and y directions, and perfectly matched layer (PML)61 was used along the z direction. The structure was excited by a broadband x-polarized plane wave. In band diagram calculations, Bloch boundary conditions were used along x and y61. An electric dipole emitter was used for Green’s function calculations, from which the local density of optical states and spontaneous emission rate were derived. A large nanohole array substrate (9 × 9 unit cells) was used with PML boundary conditions along all boundaries for the Green’s function calculations (see Supplementary Information for more details).A commercial package  was used to simulate absorption, field enhancement, band diagram, LDOS and extraction efficiency. A fine mesh size of 1 nm was used throughout the simulation domain. The dielectric permittivity of silver was taken from CRC dataSupplementary Information


In the limit of strong waveguide confinement and depending on the velocity of the cloud, three main regimes are observed corresponding (1) to the absence of reflection, (2) to partial reflection and (3) to full reflection into the second waveguide. In view of the application to atom interferometry, the condition to split the cloud into mainly two equally-populated fragments is only met in the highest velocity regime, where the fraction of reflected and transmitted atoms can be controlled by tuning the lattice height. A diagnostic of the momentum distribution shows that a quasi-Bragg splitter with the occupation of mainly two momentum states is achieved in this regime. This behaviour can be understood by considering the band structure associated with the potential in the crossing region and agrees with numerical simulations of the atomic dynamics.We perform an experimental and theoretical study of a novel distributed quasi-Bragg splitter for cold atoms propagating in crossed optical waveguides. The atoms are guided by horizontal red-detuned laser beams which cross with an angle of roughly 90°. The lattice formed by the interference between the two waveguides is used as a quasi-Bragg splitter to  A major goal in the field of atom optics is the realization of coherent atomic circuits. There is indeed a strong interest towards the potential technological application of these systems as guided atom interferometers4, and also as analogs of electronic circuits with enhanced control on the carrier particles, an emerging field known as Atomtronics6. For all these applications, it is of primary importance to develop appropriate techniques to control the dynamics of the atoms in the waveguides, starting from the basic building block of any circuit and interferometer: the beam splitter. Coherent beam splitters have been realized for Bose-Einstein condensates (BECs) trapped in double-well potentials7, guided in linear optical waveguides8, and in Y-shaped waveguides with a small opening angle10. However an integrated splitter able to continuously separate a guided atomic cloud and to spatially deflect it by a large and arbitrary angle has not been realized yet.Since the first realization of ultracold matter waves, the strong analogy with optics has boosted a number of seminal achievements and has driven novel technological progress11. In the domain of optical waveguides, a controlled reflection of the light is commonly achieved by employing distributed Bragg reflectors which serve as optical filters, couplers and optical (de)multiplexers. An analogous version for matter waves propagating in a single linear waveguide has been recently realized12.Here we consider a system where the atoms are confined in horizontal waveguides realized by means of red-detuned laser beams. The simple intersection of two such waveguides has shown not to lead to a good beam splitter as the atoms exit all the four available channels following chaotic dynamicsquasi-Bragg we refer to an intermediate regime between the Bragg and the so-called channeling regime, where the diffraction pattern is still similar to the one generated by a Bragg diffraction14. We propose to realize the periodic potential required for such a reflector by allowing the two crossing waveguides to interfere, thus generating an inhomogeneous optical lattice in the spatial region where they overlap, as shown in Fig. θ. This minimal scheme thus allows a controlled reflection of the atoms into one specific direction of the crossing waveguide and could work for any angle θ, as the orientation of the lattice is naturally correlated with the alignment of the two waveguides. The proposed splitter could be used for Michelson as well as for Mach-Zehnder interferometry where a large deflection of the atomic beams can be exploited to design circuits with large enclosed areas for high-sensitivity measurements. In the latter case, the mirrors and the recombiner can be in principle realized with the same design of the splitter, provided four linear waveguides are properly intersected. We note that the recombination of two split clouds confined in waveguides can be done, without re-passing through the same path, either by bending the waveguides or by using straight waveguides and mirrors, similarly to optical interferometers. As bent optical dipole traps are not easy to realize9, our technique can provide a simpler solution for the generation of controlled atomic circuits with laser beams. Moreover, splitting and recombining the atoms in two momentum states provides an easier readout with respect to the Y-splitters, where the states to be read are external states of the radial trap realized by the waveguide. Our technique would ideally suit applications in optical waveguides realized by integrated or miniaturized optical elements. Atoms both in the BEC regime or in the thermal regime can be used, provided the momentum spread of the cloud is smaller than the recoil velocity which corresponds to a temperature much lower than 140 nK for our experimental parameters.In this paper we study both theoretically and experimentally a novel all-optical splitter for propagating matter waves which combines for the first time these two features: a crossing guide configuration with a distributed quasi-Bragg reflector, where by θ is α is the atomic polarizability, E0 the amplitude of the light field and the normalized intensity I in the assumption of kR = 2π/λ the wave number of the light, w0 the beams’ waist and θ/2 and we work in the reference frame set by the lattice. The potential in the rotated basis {x′, y′} can be simply written asd being the lattice spacing. In the intersection region, the potential U is the sum of two terms: a trapping potential, Ut is the trap depth of the single waveguide. Given U0 and A are slowly varying compared to cos (qR(θ)y′).We first theoretically study the proposed matterwave reflector in the simplified assumption of a two-dimensional (2D) system with no interparticle interactions, which is experimentally justified in the case of low atomic density. In the following we consider the motion of the atoms limited to a horizontal plane, as correction due to the gravitational sag is negligible in the considered range of parameters. The potential that results from the intersection between two identical Gaussian beams crossing near the two waists at an angle mentclass2pt{minimmentclass2pt{minimκ. The solutions of the Mathieu equations have the form κ indicates that the wavefunction is evanescent. For particle energies lying within a band gap, the transmission by the lattice is exponentially suppressed and reflection takes place. The inhomogeneity of the lattice amplitude has the effect of projecting in real space the band gap structure, giving rise to reflective barriers for the atoms called spatial gaps. The presence of an external confining potential, in addition, determines the spatial distribution of these gaps within the intersection region of the two crossing beams, where the lattice is formed. In particular, this is responsible for the lowest energy band gaps to appear at the external edge of the intersection region, the exact number of these side gaps depending on the depth of the trap.We thus study the local band gap structure produced by the potential entclass1pt{minimax axis as shown in Fig. θ = 90° has been also chosen, in the first instance, to avoid the coupling of the axial and radial degrees of freedom in the waveguides which takes place when an atomic cloud propagates in the intersection region of two non-interfering crossing beams, as shown in ref. ε, we plot in Fig. κ at the crossing region versus the velocity of the incoming particle to obtain a 1D map of the spatial regions where the atoms can undergo a reflection. For a given trap depth Ut, the location of these regions depends on the atom velocity and on the lattice amplitude. The atoms with an initial velocity lower than the recoil velocity vR are mainly deflected by the first spatial band gap opening at a distance larger than the beam waist w0 from the center of the intersection, starting from very low lattice amplitudes Fig. κ and a smaller spatial width of the gap, which means a reduced probability of reflection, are associated with the higher order band gaps for a certain lattice strength. However, by tuning these parameters, it should be possible to control both the amount of reflected atoms and the position where reflection takes place, including the center of the crossing region as shown in Fig. N × vR = N × ħkR/m, these values are also independent of the crossing angle θ.A full map of the spatial gaps in two dimensions is rather complex as it relies onto the details of the atomic dynamics in the crossing region. In the following we thus restrict this analysis to just one dimension by considering an atomic wavepacket propagating towards the intersection of the beams along the entclass1pt{minimaR for typical parameters of our splitter. The velocity spread fundamentally limits the efficiency of a Bragg splitter16. In our case, due to the spatial inhomogeneity, the distribution of the initial velocities also determines the extension of the region where the atoms are reflected. A velocity spread much smaller than the recoil velocity vR is thus necessary for mode-matching of the reflected cloud to the radial trap of the second waveguide. For our experimental parameters this implies that the temperature of the atomic cloud should be much lower than 140 nK, which indicates that a Bose-Einstein condensate is the ideal atomic source to be used with the splitter.In order to get a more analytical insight on the shape of the spatial gaps, it is instructive to extend the perturbative approach of ref. 87Rb atoms, external potential equal to U and in absence of interparticle interactions. The results obtained with the two different approaches are consistent. While the spatial band gaps calculated within the Mathieu equation approach provide a general understanding of the interaction of the atoms with the inhomogeneous lattice, the solution of the time-dependent Schroedinger equation reveals all the details of the complex two-dimensional dynamics that the atoms undergo in the crossing region.Finally, we complement the theoretical description provided by the Mathieu equation approach with the simulation of the atomic dynamics. This is done by numerically solving the time-dependent Schroedinger equation for a BEC in 2D with the split-step Fourier method. The calculations are performed for 4 Rb atoms and we release it in a linear waveguide (WG1) by rapidly switching off the beams of the crossed dipole trap where the BEC is initially produced. The atoms can thus propagate in the harmonic trap formed by WG1, which has an axial frequency ωax = 2π × 2.4 Hz and a radial frequency ωrad = 2π × 190 Hz. A second similar waveguide (WG2) is aligned orthogonally to WG1 at a distance δ from the position where the BEC is generated and in such a way that the two waveguides intersect at their minimum waist position, see Methods for more details on the experimental apparatus. Both the waveguides are created by linearly polarized laser beams with waist w0 ≃ 20 μm and wavelength λ = 1064 nm. Each waveguide produces at the intersection region a trapping potential Ut ~ 25ER. Once the atoms are released in WG1 they naturally move towards the minimum of this trap, which coincides with the position of the minimum waist, thus acquiring a maximum velocity v ≃ ωaxδ immediately before the intersection between WG1 and WG2. The measured velocity spread δv = ±0.2 vR, where vR = 4.3 mm/s is the recoil velocity, is mainly due to the interaction energy of the atoms converting into kinetic energy as they are released from the initial trap. Being derived from the same laser, WG1 and WG2 can interfere at their crossing, thus forming an optical lattice whose height can be set by tuning the relative polarization between the two beams. By changing the distance δ we can control the velocity of the atomic cloud center of mass at the lattice position, while maintaining the same atomic density after a fixed expansion time of 100 ms, avoiding effects due to the interactions. The maximum velocity we can achieve in this way is roughly 4.7 vR corresponding to a distance δ ~ 1 mm equal to the Rayleigh length of the WG1 Gaussian beam.We prepare a spinor BEC of 7 × 101 ≃ vR, the atoms are blocked at the external edge of the intersection region for very low lattice amplitudes and we do not observe any macroscopic reflection into WG2, see Figs w0 from the center of the crossing, the precise position depending on the initial velocity of the wavepacket. At this point, they have not acquired sufficient kinetic energy to leave WG1 and they remain confined in the combined trap formed by the lattice and the trapping potential of the waveguides. Only very few atoms, see Fig. We study the dynamics of the atomic wavepacket when passing through the crossing region with different velocities and for different lattice heights. In our measurements we can identify three main regimes, in the limit of strong confinement 1 < v ≤ v2 ≃ 3vR, we observe a substantial reflection into WG2. Indeed, while a fraction of the atoms are still reflected in both directions of WG2 for intermediate lattice amplitudes, the cloud is more consistently deflected into one single exit port of WG2 for increasing lattice strengths. At low lattice strength, the atoms are broadly diffused from the center of the intersection region, whereas for higher lattice height they are reflected out of the center of WG2, and acquire an oscillation along the radial direction when later propagating in WG2 see Fig. w0, as derived from the solution of the Mathieu equation. Even if this results in a higher probability of reflection into WG2, at this distance however the atoms cannot yet directly enter WG2 once reflected by the band gaps, see Fig. cascade of multiple reflections by several spatial gaps opening in the xy-plane for increasing atomic velocities. Additionally, the fraction of atoms reflected into WG2 (in a single port) is always below 50%, see Figs single lattice site, estimated analytically by using a similar barrier shape17, occurs only for relatively high lattice amplitudes in this range of velocities, see Methods. Neither the observed reflection into WG2 or the blocking of the atoms at the edge of the crossing region can be explained with reflection by a single barrier. They are thus due to the periodic potential and, more specifically, to the action of spatial gaps of different order.For intermediate velocity v2 an increasingly larger fraction of the atoms are reflected into WG2, to the point where an almost complete reflection can be achieved , the second option turns out to be possible only by reducing the radial size of the waveguides. In Fig. R, with beam waist of 5 μm), we have numerically found a non-zero probability of occupation of several excited states. The reflection process is indeed taking place on time-scales which are comparable to those set by the radial frequency of the waveguides and the transfer of the atoms from WG1 to WG2 results in a non-adiabatic process. For reducing these effects, a possibility consists in decreasing the angle of intersection between the waveguides  with a coherence preserving quasi-adiabatic approach. Even though this may be difficult to achieve in free space experiments where the waveguides are realized by single Gaussian beams, it is experimentally feasible when state-of-the-art all optical waveguides in planar chip configurations are employed19.We have presented the realization of the first distributed quasi-Bragg splitter for ultracold atoms confined in crossed optical waveguides which is able to split the atoms with a large angle of roughly 90° and overall efficiency of 80%. A splitter for atom interferometry should ideally lead to the occupation of two momentum states with no further excitation produced. For a pulsed quasi-Bragg splitter with a Gaussian envelope in time, the population in the scattering orders other than those allowed by the Bragg condition can be very small when the pulse has a smooth envelope function even out of the Bragg regime87Rb Bose-Einstein condensates in an all optical way. We use a crossed dipole trap realized by a recirculating single laser beam with 1064 nm wavelength, 18 W initial power and 65 μm waist at the position of the atoms. After a first passage through the cell, the beam is reflected back with orthogonal polarization and refocussed to the atomic cloud in such a way to form an angle of 25° with respect to the incoming direction of propagation. In order to evaporatively cool the sample, the power of the trap beam is decreased with an exponential ramp of 8 s duration. For the measurements presented here, we prepare the BEC in the combined trap realized by the superposition of the crossed dipole trap and a waveguide (WG1) which acts as a dimple. This allows us to prepare the initial condensate in the radial ground state of WG1. The waveguide is created by means of a linearly polarized laser beam with λ = 1064 nm, power 15.5 mW and minimum waist of 22 μm. To avoid cross interference between the WG1 and the dipole trap, the first beam is shifted in frequency by 80 MHz with respect to the second one. The WG1 beam is focussed at a distance δ from the center of the dipole trap where the BEC is formed. Another almost identical waveguide (WG2), with waist 24 μm, power 17 mW and same frequency as WG1, is aligned with focal position coinciding with WG1 and forming with it an angle of roughly 90°, see Fig. In our experiment we produce N4) or reflected into the second channel of WG2 (N2). A different onset of the blockage of the atoms before the crossing region is also observed (N1), likely following the onset of the quantum reflection from the single barriers of the inhomogeneous lattice.A complete analysis of the way in which the atoms redistribute among the different channels of the distributed quasi-Bragg splitter, as a function of the lattice height, helps to highlight the mechanisms which determine the dynamics in the different velocity regimes. Figure


Early‐stage prostate cancer is widely treated by iodine‐125 (I‐125) seed implantation. While quality assurance methods are in place to assure consistency in I‐125 seed source strength, current methods involve the breaking of the sterilization package, raising issues concerning sterility and time limitations. The purpose of this study was to develop a method of characterizing the total source strength of I‐125 seeds within a cartridge that has been sealed within a sterilization package and to evaluate the probability of detecting an out‐of‐calibration seed (aberrant seed). We defined a protocol to determine the ability of a well‐type ionization chamber to detect aberrant I‐125 seeds within a cartridge sealed in the sterilization package. A novel jig for a well‐type ionization chamber was designed to accommodate the sterilization package. One seed was chosen randomly from two cartridges containing five or 15 seeds (0.544 U source strength) and was exchanged with aberrant seeds of six different source strengths. The source strength was measured at each position within the cartridge. The results indicated that the response of the well chamber was sensitive to changes in the aberrant seed position within the cartridge and the source strength of the aberrant seed. The correlation coefficient between single seed and batch assay results was high (0.998). A novel jig and a measurement method using a well ionization chamber were developed, which allowed for a batch assay characterization of the total source strength of I‐125 seeds within a cartridge sealed within sterilization package. This method is simple, time‐saving, and offers greater practical application.PACS number: D6.20.Dk The OncoSeed model 6711  is the type of therapeutic I‐125 seed used by most Japanese institutions and is delivered in a sterile convenient blister pack (SCBP). Currently used only in Japan, this form of SCBP, which contains a preloaded five‐seed or 15‐seed cartridge, was jointly developed by two companies  as an improvement on the conventional sterile convenient Tyvek pack (SCTP)  with respect to prevention of seed loss from the cartridge and damage to the sterilization package.Iodine‐125 (I‐125) permanent implant brachytherapy is a widely used modality in the treatment of prostate cancer.–5 BeThe American Association of Physicists in Medicine (AAPM) Task Group 64 recommended that institutional medical physicists perform seed calibration on at least 10% of the seeds in all shipments to satisfy the need for an independent assay of a random sample.7(–) This method can assess the source strength of various seeds with one measurement, but the operators must return the seeds to the cartridge after the assay. The cartridge approach can assess the source strength using an imaging plate or a well ionization chamber, with the seeds still in the cartridge.(–) Although the cartridge approach can effectively assess the source strength while preserving sterilization, it requires the sterile inserts to be deployed in the operating room relatively close to the time of implant and, hence, poses the risk of seeds being lost and inserts being contaminated. These disadvantages have encouraged the development of a new method of characterizing the total actual source strength of I‐125 seeds within a cartridge sealed in an SCBP and of evaluating the probability of detecting aberrant seeds. The purpose of this study was to develop a method that achieves these goals in a time‐efficient manner without encountering the disadvantages of the other methods of measurement currently in use.However, there are several downsides to the evaluation of individual seeds. It is extremely time‐consuming, involves exposing hospital personnel to frequent doses of radiation, and poses a challenge regarding the resterilization procedure. To meet these challenges, several batch assay methods have been developed, among which the two main approaches are the source holder approach and the cartridge approach. In the source holder approach, several seeds are removed from the cartridge and loaded in a source holder to allow the measurement of their source strength, typically using a well ionization chamber.–10 Tk=2). The common single‐seed assay was used to confirm the manufacturer's claims that the source strength among seeds varied by less than 5%  calibration standard for the OncoSeed model 6711 was obtained from the Japan Radioisotope Association  were evaluated to determine the correlation between the single‐seed and batch assays, with the correlation for the five‐seed and 15‐seed cartridges being evaluated separately. The result of the single‐seed assay was determined from the mean value of 15 seeds measured three times, while that of the batch assay was determined from the mean value of one batch measured three times. In the batch assay, after measurement of a 15‐seed cartridge, ten seeds were pushed out from the cartridge, a five‐seed cartridge was measured, and the seeds were exchanged and arranged randomly for every measurement.To investigate the impact of inclusion of an aberrant seed in the SCBP, one seed was chosen at random from two cartridges containing five or 15 seeds and exchanged. A seed with source strength of 0.544 U was used as the reference seed, and six seeds with different source strengths (source strength: 0.395 (73% of the 0.544 U), 0.367 (68%), 0.336 (62%), 0.310 (57%), 0.285 (52%), and 0 (0%) U) were used as the aberrant seeds. The position of each aberrant seed was interchanged at every possible position within the cartridge, and the source strength was measured at each position. The change in position of the aberrant seed was achieved by refilling the top of a cartridge seed pushed out from under a cartridge. Similarly, one seed was randomly selected from the reference seeds for measurement of its source strength when the position was changed.To evaluate the clinical relevance of the proposed methodology, the batch assay method was used for source strength measurements at our facility. Measurements of 15 cartridges containing five seeds and 69 cartridges containing 15 seeds were made on a weekly basis on the same day. In our facility, the nominal manufacturer's source strength of 0.460 U is always used.Figure U±0.010 and 0.144 U±0.012, respectively.The reproducibility of measurements for each seed was found to be 1.1% (range: 0.1% to 3.8%). The reproducibility of measurements in the five‐seed cartridge and in the 15‐seed cartridge was found to be 1.2% and 0.2%, respectively. Analysis of the correlation between the number of seeds and the mean source strength yielded a correlation coefficient of 0.999 for a third‐order polynomial fit Fig. . The ave−0.1% to 1.6%). In contrast, the 15‐seed cartridge was found to be 0% (range: −2.6% to 1.5%).The measured source strength for various single seeds is plotted in Fig. −1.2% (range: −0.7% to 1.8%) and −0.3% (range: 0% to 0.6%), respectively. Figures Figure −2.9% to 2.0%) and −0.6% (range: −2.1% to 2.7%), respectively.The predicted source strength from the batch assay of the five‐seed and 15‐seed cartridges, as calculated using the formula of the approximated curve, was found to be 1.60 U and 4.27 U, respectively. Figure  demonstrated that in an assay using a shielded 15‐seed cartridge, the probability of detecting a missing or extra seed  is higher than for a single‐seed assay, or 10% of the seeds in a shipment.In this study, a novel jig and a measurement method using a well ionization chamber were developed. This allowed for a batch assay characterization of the total source strength of I‐125 seeds within a cartridge sealed within an SCBP. To the best of our knowledge, this study is the first to describe the use of a batch assay to measure the source strength of I‐125 seeds with an SCBP. The method can be performed simply and quickly. However, to quantify the performance of the cartridge inspection schemes, Brame et al.12 dem None of the cases investigated in this study exceeded the 3% deviation from the reference value that is generally tolerated, using our batch assay on an intact SCBP , so the difference from the normal value could exceed 5% even in normal cases, and even an abnormal reading may still be within the acceptable range. The AAPM TG138 indicates that in the calibration of a well ionization chamber by the University of Wisconsin Accredited Dosimetry Calibration Laboratory (ADCL), the propagation of best practice uncertainty is 2.56%. In other words, if the calibration uncertainty of a well ionization chamber becomes small, the reliability of this quality assurance method will improve.The AAPM Low Energy Brachytherapy Source Calibration Working Group recommends that institutional medical physicists determine a source strength against which the measured source strength is evaluated when performing a batch assay. If a difference of more than 3% is found between the measured source strength of each cartridge and the reference value, the Working Group recommends the discrepancy be investigated. If a difference of more than 5% is found, consulting the manufacturer to resolve the difference is recommended.14 NonCBP Fig. . HoweverFigure Figure In this study, seeds of a higher activity than the standardized source strength were not used as aberrant seeds. However, Figs.  recommended the use of a five‐seed batch assay method with a plastic spacing holder and a well ionization chamber. Their study revealed that when exchanging a live seed with a dead seed, the measured source strength decreased by 20% with respect to the theoretical source strength. As shown in Figs. Among the authors who have investigated different batch assay techniques, Lee et al.8 reco proposed the use of an imaging‐plate dosimetry system, in which they found a 0.999 correlation between the linear response of the source strength for a 15‐seed cartridge and the overall source strength. Use of this method can allow for the simultaneous characterization of 100% of seeds in a sterile environment, but requires that sterile inserts be deployed in the operating room relatively close to the time of the implant.Furutani et al.11 proThe results of the study by Furutani and colleagues indicate that the method most likely to detect aberrant seeds in a time‐efficient manner is one in which every cartridge in a shipment is measured, as does the method used in this study. Specifically, the method used in our study does not need to be performed in the operating room, poses no time limitations, and does not require resterilization. However, use of this method may pose a time penalty when the cartridge well chamber reading is out of the acceptance range, as the cartridge must be opened and the seeds individually assayed if this is the case. Despite this, our method offers additional advantages including the decreased probability of seed loss and minimization of personal exposure to radiation.We developed a novel jig for exclusive use with SCBP and carried out batch assays of source strength by using a well ionization chamber. This method is practical for all institutions needing to assay OncoSeed model 6711 seeds contained in an SCBP.This study was partly supported by a Grant‐in‐Aid for Cancer Research from the Ministry of Health, Labour and Welfare of the Government of Japan (21‐8‐2).


The increasing complexity of Radiation Oncology equipment and treatment techniques have led to increased demands on the work load of the medical physicist. Regular testing needs to be as efficient as possible. Generally, the QA tests, as recommended by the AAPM Task Group 40 for medical LINACs, can be grouped into two categories: dosimetry and mechanical checks. A new QA device has been developed that facilitates many of the daily and monthly mechanical QA checks. Its efficiency and speed is achieved through a set of QA tools that are mounted on a single platform, which is designed to fit into the accessory mount of the medical LINAC. Named Mini‐GARD (MG), it verifies the accuracy of the digital readouts for gantry angles, collimator angles, and field sizes. It also tests crosshair position, the optical distance indicator (ODI), and patient setup laser alignment. It uses two calibrated digital levels for the gantry and collimator angle verification, an electronic tape measure for ODI verification, and a calibrated transparent projection scale for the remaining tests. This paper evaluates the stability and accuracy of the device in clinical tests over a period of a year. Results show that the MG is reliable and capable of measuring gantry and collimator angle constancy to PACS number(s): 87.56.Fc It is of fundamental importance to test and verify the geometric and mechanical accuracy of every medical LINAC on a regular basis.The MG achieves increased efficiency through a setup of a single fixed platform from which all measurements are made, thus eliminating the extra time and uncertainty associated with the use of multiple independent measurement devices. The purpose of this paper is to describe the designed uses of the MG, and to determine its accuracy and reproducibility in the clinical environment over the period of a year.23−cm thick) aluminum support plate that fits into the accessory mount of the medical LINAC and has a 17×17cm2 aperture in the center. Mounted on this plate are two calibratable electronic digital goniometers for measurement of the gantry and collimator angles, a tape measure with an electronic digital readout for ODI verification, and a precision projection scale for light field size and laser alignment verifications . The tape measure is mounted on an arm that is locked outside the aperture in the base plate when not in use and swings into the central axis of the beam line for measurement of the MSD as shown in Figs. The average measured MSD from 40 measurements taken on ten different days spanning a period of a year for an SSD of 100 cm was 25.74 cm with a standard deviation of only 0.05 cm. All measurements made had a MSD reading that varied between 25.8 cm and 25.7 cm. The results of the SSD's measured with the MG are shown in Table ±0.025 cm.For the MG initialization of the precision projection scale, a conventional, independent method must be used to assure that the projected crosshair shadow on the LINAC is properly centered. The MG is then configured by adjusting the position of the acetates so that the crosshair on the acetate coincides with the projection of the LINAC's crosshair. The ability to use the MG to verify the LINAC's crosshair is dependent on the reproducibility of the MG within the accessory tray and the sag of the accessory mount on the LINAC. We tested the variation of the MG's crosshair projection position within our LINACs by recording the projected position of the MG's crosshair at an SSD of 100 cm for numerous insertions of the MG into the accessory tray. All distances were measured with a calibrated ruler that had 0.05‐cm scale. On a single day the reproducibility of the cross hair center was determined to be better than 5×5,10×10,15×15, and 20×20cm2 and tick marks spaced 0.1 cm apart along the crosshairs at a SSD of 100 cm. The actual collimator light field size can then be easily measured by observing the shadow of the collimators against the scale. We verified the size of the field outlines on the acetate, as well as their projected sizes at 100‐cm SSD. The acetate scale dimensions were measured in order to verify the accuracy of the field size templates; the projections at 100 cm SSD were measured in order to assess their readability.The medical LINAC's light field sizes are measured and its digital readouts verified by comparing its collimated light field with the calibrated projection scale from the MG acetate. The MG is designed such that its scale projects field sizes of ±0.025 cm. The errors in the field sizes on the acetate projected to a SSD of 100 cm were ±0.04 cm. Measurements made of the actual projection at a SSD of 100 cm showed similar errors of ±0.05 cm, which is slightly higher because of the artifacts from the light bulb size and light transmission through the transparent material of the MG.The field sizes measured on the acetate are shown in Table The laser alignment tests are performed with the gantry precisely rotated to the inverted vertical position for the overhead laser and the two horizontal positions for the right and left‐side transverse lasers. The laser alignment constancy is evaluated by observing the position of the laser lines on the coordinate system marked on the acetate of the MG. The initial baseline position of the laser on the acetate is established with the laser aligned using conventional methodologies, and with the gantry set to 0°, 90°, and 270° using the MG goniometers. The verification of the laser position is tested by measuring the laser's displacement from these initial calibrated positions.d is the apparent displacement of the laser from the initial calibration position, Δθ is the error in the gantry position, and A is the distance from the isocenter to the accessory tray. For our LINAC A=34.6 cm. From the gantry goniometer results in Table Because the position of the lasers' projected cross on the MG acetate are dependent on the angular position of the gantry, any deviation of the gantry angle will cause errors in the position of the lasers' projections on the MG acetate. This error is given by ±1°. However, over the course of a year the error was not randomly scattered about an average, but drifted over time. This drift reached a maximum error of 0.3° after three months. Because of this drift, we suggest that the goniometers be recalibrated after three‐six months.The above experiments show that once calibrated a single MG device is well suited for daily and monthly QA tests on an individual LINAC. The average deviation of the gantry and collimator tests with the MG was 0.12° from the reference angle and is within the TG‐40 suggested tolerance of (±0.2 cm). Its SSD readings were stable and reproducible to within ±0.05 cm over a 12 month period with an accuracy of ±0.06 cm.The 1‐mm precision of the MG's electronic tape measure is within the limits required for the TG‐40 suggested ODI verification tolerance ±2 mm tolerance suggested by TG‐40. Its reproducibility, however, is dependent on the slack within the LINAC's accessory tray, so the variance of the MG's crosshairs should be determined for an individual machine.The reproducibility of the MG's positioning of the field size and crosshair are also within the ±0.2 cm, but the larger errors in the gantry angle could produce incorrect results.The small uncertainty of the gantry angle, determined by the MG, may lead to inadequate precision in the verification of the patient positioning lasers. The average and maximum gantry goniometer angle errors of 0.12° and 0.4° results in errors in the angular position of the laser on the acetate of 0.08 cm and 0.24 cm, respectively. Thus, on average the uncertainty caused by the gantry angle error would be acceptable for the TG‐40 suggested tolerance of The Mini‐GARD is an alternative QA device for measuring the geometric parameters associated with standard daily and monthly QA protocols. We have quantitatively tested its accuracy and determined that it is well suited for most of its purposed uses. The uncertainties in the gantry angle, collimator angle, and ODI verification are well within the tolerances needed for daily and monthly protocols. The crosshairs and field size verification are also within acceptable tolerances for most LINACs, but should be verified before use. The usefulness of the laser alignment test depends on the tolerances established at each institution and should be carefully evaluated.


We explored whether positioning patients in a 25° back-up sniffing position improved glottic views and ease of intubation.In the first part of the study, patients were intubated in the standard supine sniffing position. In the second part, the back of the operating table was raised 25° from the horizontal by flexion of the torso at the hips while maintaining the sniffing position. The best view obtained during laryngoscopy was assessed using the Cormack and Lehane classification and Percentage of Glottic Opening (POGO) score. The number of attempts at both laryngoscopy and tracheal intubation, together with the use of ancillary equipment and manoeuvres were recorded. The ease of intubation was indirectly assessed by recording the time interval between beginning of laryngoscopy and insertion of the tracheal tube.p = 0.004). The time from beginning of laryngoscopy to insertion of the tracheal tube was 14 % shorter  in the back-up position. There was no significant difference in glottic views.Seven hundred eighty one unselected surgical patients scheduled for non-emergency surgery were included. In the back-up position, ancillary laryngeal manoeuvres, which included cricoid pressure, backwards upwards rightward pressure and external laryngeal manipulation, were required less frequently  contains supplementary material, which is available to authorized users. The horizontal supine sniffing position has traditionally been considered the optimal head position for direct laryngoscopy and is preferred by most anaesthetists. Although contentious , neck flThe back-up position achieved by flexion of the torso at the hips was described by Chevalier Jackson almost a century ago ; such a In clinical practice, the back-up position has been successfully used in obese patients , 8 and sTherefore the aim of this study was to test whether a 25° back-up position improves laryngeal views and makes intubation easier compared to the standard horizontal position.The study outline was reviewed by North Wales Research Ethics Committee of the Betsi Cadwaladr University Health Board who deemed that the observation of routine established anaesthetic techniques should not be classified as research and therefore further consideration by the Ethics Committee and individual patient consent was not required . The project was registered with the Health Board’s Research and Development Department.The study had two parts. Part 1 was an observational period of standard practice to ascertain the distribution of glottic views and ease of intubation with the patient in the horizontal sniffing position. Part 2 was identical except that the patients had their anaesthesia induced and tracheas intubated in a 25° back-up position achieved by flexion of the operating table at the hips.Patients less than 18 years old,Patients recognised to have difficult airways where an alternative method of intubation (e.g. fibre optic) was the method of choice,Patients undergoing emergency surgery where patient positioning and data collection might cause delay (e.g. exsanguinating patients) or where the supine position is not optimal (e.g. brisk bleeding into the upper airway),Patients requiring rapid sequence induction of anaesthesia.Adult patients who required intubation as part of their routine anaesthesia were studied. However, the following groups of patients were excluded:all patients were in the standard sniffing position with a head ring or non-compressible pillow so that a line from the sternal notch to external auditory meatus was horizontal.in Part 2 only, the back of the operating table was raised 25° from the horizontal Fig.  while madirect laryngoscopy was performed using an adult Macintosh blade (size 3 or 4) after suppression of all twitches on a train-of-four monitor.The data collection form  and manoeuvres  were recorded but applied at the intubating anaesthetist’s discretion. The time between the beginning of laryngoscopy and detection of CO2 on the end-tidal CO2 monitor after the successful placement of the tracheal tube was recorded by either the intubating anaesthetist or other members of the anaesthetic team.Patient demographics  and drugs used at induction were recorded. The best view obtained during laryngoscopy was assessed using the Cormack and Lehane classification  and PercDescriptive statistics for normally distributed data are presented as means and standard deviations (SD) while skewed data is summarised as medians and interquartile ranges (IQR). Mann–Whitney U tests were used to explore differences in non-normally distributed data while Chi-squared tests or Chi-squared tests for trend explored difference in frequencies. Assuming an incidence of Cormack and Lehane Grade I views to be 95 % and that a 4 % increase in these views can be achieved by a 25° back-up position, 325 patients in both parts would be required to have a power of 0.8 and an alpha error of 0.05. Statistical analysis was performed using Minitab (version 15). A p value of less than 0.05 was considered significant.The study enrolled a total of 781 unselected patients (374 in Part 1 and 407 in Part 2) between December 2011 and November 2014 representing an average enrolment rate of 22 patients per month. Sixty-eight members of the Anaesthetic Department recorded data on glottic views; experience varied from consultant anaesthetists with over 20 years experience to trainees with just over 1 year. There was no significant difference between numbers of training versus senior grades contributing to either part of the study (Table p < 0.001). The distribution of anaesthetic agents was similar in both groups except that atracurium was more frequently used in the second phase . There were no reports of difficulty with mask ventilation in any patients.The demographic details of the patients are summarised in Table p = 0.025). In the back-up position, ancillary laryngeal manoeuvres  were required less frequently .With regard to intubation, 90.5 % patients in both parts of the study were intubated successfully at the first direct laryngoscopy and first attempt at intubation Table . The usep = 0.001). In the second part of the study, the time from the beginning of laryngoscopy to tube insertion was significantly shorter for both training and senior grades  (Table Overall, the time from beginning of laryngoscopy to insertion of the tracheal tube was significantly shorter when performed by senior grades as opposed to trainees (median time 24 versus 28 s, There was no significant difference in glottic views when assessed by the Cormack and Lehane Grades Table  or POGO The main findings of this study are that the need for ancillary manoeuvres and the time taken for intubation are reduced when the patients are 25° back-up. The back-up position does not appear to improve glottic views in an unselected surgical population who were not anticipated to have difficult airways. Ninety-three percent of views obtained were classified as Cormack and Lehane Grades I or II; the median POGO score was 80.The 25° back-up position was chosen as this incline was used by Lee and others  suggesteOur study attempted to help clarify whether the back-up position made intubation easier for the anaesthetist. Moving the operating table into the backup position is a simple inexpensive manoeuvre which may enable the line of sight fall more quickly upon the glottis. In Part 2, the combination of the sniffing and back-up position was not recorded as interfering with the insertion of the laryngoscope blade or decreasing the effectiveness of cricoid pressure or other laryngeal manoeuvres. A disadvantage of the back-up position is that lowering the operating table may not be sufficient to satisfactorily align the patient’s head at the level of a short anaesthetist’s sternum; a footstool may be required.The shorter time taken for intubation when the patients are 25° back-up is relatively modest at 4 s. Both training and senior grades completed intubation faster in the back-up position and the difference although not significant was larger for the senior anaesthetists (Table Although intubation was faster, we failed to find improved Cormack and Lehane grades or higher POGO scores in the back-up position. There are several possible explanations for this. A simple non-interventional change such as altering the patient’s position might be expected to make relatively modest improvements to glottic view compared to more sophisticated aids such as advanced laryngoscopes. The back-up position improves the view most successfully when intubation is anticipated to be difficult, for example in obstetric or bariatric surgery; its impact when the patients’ airways are likely to be normal may well be less. Cormack and Lehane Grades I and II views and views with a POGO score above the median of 80 are satisfactory for successful intubation. If the back-up position produces only small improvements in glottic view during routine clinical practice where difficulties are unanticipated, a much larger study would be required. The present study was underpowered to detect small differences.Figure The pragmatic observational design of the study inevitably leads to a number of weaknesses. One of the most important was the number of anaesthetists contributing to the data. Although a total of 68 personnel contributed, the majority did not enrol more than 10 patients. This will have increased the inter-observer variability and may have been responsible for some misclassification. However, the ratio of training to permanent anaesthetic staff was similar in both parts of the study. Other weaknesses in the methodology include the inevitable unblinded nature of the study and the selection of patients. Unfortunately due to the relatively small number of recording laryngoscopes within the Department, independent verification of the glottic view was not possible. Adult Macintosh blades remain the most commonly used at Glan Clwyd Hospital. Although regularly encouraged, the decision to enrol patients was left to the individual anaesthetist; the number of patients who could have been enrolled but were not studied is unknown. Such variability combined with a lower incidence of Grade I views actually found rather than assumed in the original power calculation underpowered the study with regard to improvements in glottis views.While randomised controlled trials are the gold standard for scientific investigation, the efficacy of such trials tends to decline when applied outside the original trial conditions because of the vagaries inevitably encountered in routine clinical practice, such as different operators and unselected surgical patients. The present study was deliberately designed to observe the effect of a simple non-interventional change in routine clinical practice. Despite its weaknesses, the present study’s results may be robust when suggesting that intubation is easier and quicker in the back-up position. Even though more nasal intubations and facio-maxillary procedures were included in the second phase, intubation time was shorter.Patients predicted to have difficult airways were excluded from this study and so intubation was anticipated as ‘routine’. Recognising our inter-observer variability, our distribution of the Cormack and Lehane grades do not reflect the glottic views reported by Williams. There seems to have been a progressive decline in the completeness of glottis views over time Table . In 2005In conclusion, this study has confirmed that when used at a departmental level, the 25° back-up position reduced the need for laryngeal manipulation and the time taken for intubation. The study was underpowered to determine whether or not glottic views were improved. In an unselected surgical population, the distribution of glottic views seems to be changing over time with less complete views becoming more frequent.


Mucociliary clearance is the main self-clearing system of the nasal cavity and paranasal sinuses.This is a very important means of non specific defence against continuous organic and inorganic contamination conveyed by air. It works by trapping particles and microorganisms in the mucus and then by transporting the mucous film to the pharynx where it is eliminated with a cough or swallowed. Its congenital or acquired abnormalities are involved in the occurrence of widespread infectious and often severe nose and paranasal sinuses diseases; generally concerning the rhinopharyngealtubal district.Restoring mucociliary clearance of the nasal epithelium when altered thus represents a key therapeutic tool against rhinosinus chronic diseases.This study evaluates the clinical efficacy of the inhalation of a natural compound  in chronic vasomotor rhinitis.The study involved 79 patients suffering from chronic vasomotor rhinitis presenting an increased mucociliary clearance time. Patients were randomized into 2 groups: a first group of 49 subjects and a second group of 30 subjects.The first group was treated with a nasal spray  (2 sprays per nostril twice a day) for 30 days.The second group was treated with a nasal spray containing isotonic solution in the same way and for the same period of the first group.Nasal Mucociliary transport time was measured in the patients of both groups before treatment, after 15 days of treatment, and at the end of the 30 days treatment.The study shows how one of the treatments carried out determines a major objective reduction of the mucociliary clearance time in the patients under examination, using the method which involves the use of an insoluble coloured tracer (vegetable carbon), bringing the values back within normal range. At the end of the study we objectivated an increase in the rate of mucociliary transport in 97.9% percentage of patients we enrolled.This study shows the effectiveness of treatment with natural extracts with nasal mucosa restoring function in the treatment of chronic vasomotor rhinitis, a nasal inflammatory disease characterized by morphological and functional alteration of the normal nasal mucosa. The mucosa of the nose and paranasal sinuses is formed by a respiratory cylindrical motile epithelium, completely analogous to the one of the trachea and bronchi.Among the cells with cilia which, with their undulating movement, sweep nasal secretions from the outside towards the inside, there are numerous serummucous glands that produce nasal mucus, which has the function of retaining the dust particles inhaled and releasing moisture and heat to the breathed in air.Nasal mucus is rich in glycoproteins and contains numerous molecules  which contribute to a joint specific and nonspecific defence of the nasal epithelium. Its rheological properties influence the smooth operation of that function called mucociliary clearance.This clearance particularly takes advantage of the mucociliary transport (MCT) system which allows all secretions to be pushed by the ciliated cells towards the back of the nasal passages to then descend into the pharynx.The absence or deficiency of this self-clearing system of the nasal cavity and paranasal sinuses can constitute evidence or be the consequence of many diseases.The present study was conducted to evaluate the clinical efficacy of nasal inhalation of a medical device  in selected patients with chronic vasomotor rhinitis, a nasal pathology which is characterised by an increased mucociliary transport time.Narivent® is a natural compound with antioedema and anti-inflammatory osmotic properties mainly consisting of Mannitol, Glycerol and Dipotassium Glycyrrhizate.The treatment effectiveness was evaluated following objective methods, with the measurement of nasal MCT speed before, during and after treatment.During the recruitment and follow up visits, samples of nasal mucosa cells were taken by scraping, subsequently examined by optical microscope.The study involved 79 subjects suffering from chronic vasomotor rhinitis with increased mucociliary clearance time from a minimum of 24 min to over 30 min, between the ages of 16 and 61 years, of both genders. The subjects were randomised into two groups of 49 (first group) and 30 (second group) subjects.The main recruitment criterion was the presence of chronic vasomotor rhinitis not associated with nasal polyposis but associated with a deficiency of mucociliary clearance. No other drugs were allowed during the treatment and in the 30 days before the beginning of the study.The study was conducted by administering two sprays per nostril twice a day for 30 days the drugAt the time of the recruitment visit, all personal data and clinical history were collected and ENT examination with a fiberoptic examination of the nasal cavity and mucociliary transport test .All patients recruited in the study were previously informed and gave their consent to participate in this study.Patients with rhinosinus pathologies often exhibit a decreased mucociliary clearance, evaluated as an increase in the mucociliary transport time, expressed in minutes.The MCT time is calculated in our clinic by placing a tracking powder  to the head of the inferior turbinate ; throughNormally, the tracer is found in the pharynx after about 10–15 min , but theThe MCT time is calculated for each patient as the average of the values obtained in both nasal cavities.Nasal scraping was carried out at the same time as the MCT test in 12 cases.nasal scraping. After having the patient blown his/her nose in order to eliminate any excess secretions, the top layer of the mucous membrane at the level of the middle third of the inferior turbinate was removed bilaterally. An appropriate plastic curette was used. A sample was collected both from the right and from the left nostril for each patient.In this study, the collection of cytology specimens was performed noninvasively, by The cellular material was then transferred and laid, swiping it as uniformly as possible, on a slide.We used the May Grunwald Giemsa rapid staining procedure (quick stain).The test was carried out as follows: after drying the smear at room temperature, the slide is immersed 5 times for 1 s in the three solutions, one after the other, washing it under running water.With this staining procedure the nuclei became purple, cytoplasmic filaments pink, eosinophil granules orange.Examination was carried out with a Nikon optical microscope at 100× magnification.Each slide was evaluated dividing it into 6 equal fields in order to count the amount of each cell type per microscopic field. A comparison between the cells amount before and after treatment was then carried on.A clinical study in vivo was carried out making on a comparison between pre and after treatment phase with a mid therapy course assessment, based on objective clinical criteria.The statistical significance of the results was assessed by a one way ANOVA analysis and two tailed T-Test.The analysis of the results was conducted by analysing only those subjects who had completed the treatment and had carried out the recruitment and control visits.The condensed data collected in this study are listed in Table The analysis of the results is shown in Table In both groups of patients included in this study the average mucociliary transport time (MCT) detected during/before treatment was around 28 min. (28.8 min. in the first group and 28 min. in the second group) with a minimum value of 24 min.31 out of the 49 cases included in the first group of study (63.3%) and 11 out of the 30 subjects included in the second group (36.7%) had a blocked MCT (> 30 min.).At the end of the treatment no adverse reactions were reported.In the first group the results were the following.A MCT mean time of 19.2 min. with a minimum value of 8 min. was found at the first follow up exam, performed after 15 days of continuous therapy, thus a mean decrease of 9.6 min. representing a 33.3% decrease from the starting value. The percentage of responder patients was equal to 85.7%. In 75.5% of the examined cases we witnessed a normalisation of the MCT time. In 5 cases, MCT time remained blocked.The results of the final follow up exam, carried out after 30 days, at the end of therapy, show an average MCT time of 15.3 min. with a minimum value of 10 min., a final average decrease of 13.4 min. representing a 46.7% decrease from the starting value and of 20% compared with the previous follow up. The percentage of patients where there was an increase in the rate of mucociliary clearance was 97.9%. Only in one case we observed persisted in having a MCT time > 30 min.Therefore, the treatment was successful in 97.9% of cases, bringing the MCT time within the threshold of normality in 48 out of 49 cases. Almost all patients answering to a simple questionnaire referred a favourable opinion on the treatment and reported an improvement in their nasal symptoms and especially on nasal obstruction almost accordingly with the MCT time improvement.At the end of the observation period there was only one non responder patient documented.p <0.00001).The data analysis performed using the ANOVA method was statistically significant .The data analysis performed using the ANOVA method was statistically significant  result in an improvement in the symptoms and quality of life, but not in a significant decrease in mucociliary transport time , 4.A 2008 systematic review published in the Cochrane Library analysed more than 2000 articles, including 64 clinical trials, on the efficacy of nasal washes to treat the symptoms of chronic rhinosinusitis. The conclusions highlighted that the use of hypertonic saline solution promotes mucociliary clearance, but there is no evidence of a greater effectiveness compared with the isotonic solution or with other agents in relieving rhinosinusitis symptoms .In this regard, a trial on human nasal mucosa models carried out by Kim and colleagues shows that given the lack of a direct correlation between ciliary movement frequency in vitro and mucociliary clearance in vivo and the presence of contradictory results in the literature on the effects of irrigation with various concentrations of saline solutions on ciliary activity, the most important factors which determine mucociliary clearance are the quantity and the rheological properties of the secreted mucus .This study also states that "the isotonic saline solution is the most physiologic irrigation solution in terms of cell morphology and mucin secretion from airway epithelial cells". Washes of distilled water or hypotonic solutions, in fact, harm the integrity of the cell junctions creating disruptions in the mucosal barrier, promoting the secretion of large amounts of mucus and decreasing the total number of ciliated cells, while the action in vitro of hypertonic saline solutions promotes the secretion of mucins, albeit without damaging the nasal mucosa significantly from a morphological point of view.The optical microscope analysis of the nasal mucosa samples obtained from 12 subject by scraping highlights the normalization of the after treatment nasal cytology Fig. -2b.Fig. The therapy cycle was well tolerated, with no side effects reported by patients.p <0.05).This study allows underlining how the administration of the medical device under consideration improves an important nasal functionality parameter, such as mucociliary clearance is and should be regarded. In addition, it shows that this improvement is statistically significant in comparison with the improvement achieved in the second group  during an inflammatory process and on the inhibiting action of glycyrrhetinic acid on it –14.HMGB1 is a non histonic nuclear protein that is primarly expressed in the nucleus of normal nasal mucosa cells. Higher extracellular levels and lower nuclear levels of HMGB1 are normally found in chronic inflammatory conditions .It has been recently observed that HMGB1 extracellular release is related to the nuclear concentration of Sirt 6, a protein member of Sirtuines family, NAD+ dependent class III histone deacetylases closely correlated to inflammatory conditions –17.Sirt 6 is found in the nucleus of normal nasal mucosa cells. It promotes epithelialization of nasal mucosa. A depletion of this protein induces a dramatic translocation of HMGB1 from nucleus to cytoplasm and leads to the suppression of the number of human nasal epithelial cell cilia . It has This study shows the effectiveness of a natural extract in the treatment of chronic vasomotor rhinitis. Glycyrrhetinic acid is a specific medical compound that may be isolated from the licorice plant that binds selectively to HMGB1 protein released extracellularly and so inhibits its cytokine activities through a scavenger mechanism on the protein accumulation , 15. Gly


The reflection of light from moving boundaries is of interest both fundamentally and for applications in frequency conversion, but typically requires high pump power. By using a dispersion-engineered silicon photonic crystal waveguide, we are able to achieve a propagating free carrier front with only a moderate on-chip peak power of 6 W in a 6 ps-long pump pulse. We employ an intraband indirect photonic transition of a co-propagating probe, whereby the probe practically escapes from the front in the forward direction. This forward reflection has up to 35% efficiency and it is accompanied by a strong frequency upshift, which significantly exceeds that expected from the refractive index change and which is a function of group velocity, waveguide dispersion and pump power. Pump, probe and shifted probe all are around 1.5 µm wavelength which opens new possibilities for “on-chip” frequency manipulation and all-optical switching in optical telecommunications. Here the authors present an experimental demonstration of a free carrier front induced intraband indirect photonic transition and show how the waveguide dispersion can be exploited to decrease the required free carrier concentration for substantial reflection via an indirect intraband transition. Nonrelativistic plasma mirrors driven by lasers have been also used to improve the temporal contrast of ultraintense pulses with reflectivities up to 70% in the fundamental wavelength of 800 nm at free carrier (FC) density of the order of 1021 cm−36. Blue shifts of several nanometres were observed in these experiments due to Doppler reflection from plasma expanding with sound velocity7. Ionization fronts are a more versatile route to achieving moving mirrors since lower pump power densities are necessary. In this case, only the boundary of FC plasma is moving and not the electrons themselves in vacuum. This approach is well known for frequency conversion in free space at microwave frequencies8. More recently, the effect has been extended to terahertz light by generating the plasma front in a silicon wafer with the FC concentration of 1020 cm−310. For the plasma to act as a metallic reflector, the plasma density N must be high enough for the effective plasma frequency 9. For a wavelength of 800 nm, for example, this corresponds to a carrier density of 1.7 × 1021 cm−3, while 1550 nm requires 0.46 × 1021 cm−3.Reflection of electromagnetic waves from moving boundaries has been of interest for many years due to their potential for frequency conversion. Doppler effects occurring in the case of moving mirrors13 by using slow light PhC waveguides17 facilitates the generation of FCs by two photon absorption (TPA) using picojoule pulses. Furthermore, slow light PhC waveguides allow for tailoring the photonic bands with regions of different group velocities and dispersion19. This way, an ionization front can be generated by a pump moving with a group velocity that is different to the group velocity of the probe21. The transmission of light through the ionization front can then be described as an indirect photonic transition, whereby the wave vector and frequency of an optical probe are simultaneously altered upon a transition between two modes of a photonic structure23. Recently, the reflection from a counter propagating front in a slow light waveguide was theoretically proposed assuming a FC concentration of the order of 1019 cm−3, a level that cannot be generated by TPA in silicon24.We now translate this exciting physics into guided wave optics and show how the waveguide dispersion can be exploited to substantially decrease required FC concentration for substantial reflection via an indirect intraband transition. Photonic crystal (PhC) waveguides, fabricated on silicon, are an appealing platform due to their compatibility with on-chip integration and their inherent flexibility in dispersion design. First, the ability to dramatically enhance nonlinear effects17 cm−3. We investigate the reflectivity via the interaction of a continuous wave (CW) probe wave co-propagating with the plasma front inside a 400 µm-long slow light waveguide. Only a portion of the CW probe is interacting with the front and experiences indirect transition. To explain the transition, we split the CW probe into wave packets of finite duration and follow their trajectories in time and space. Some of the wave packets initially propagating slower than the plasma front, are bounced and accelerated, finally escaping from the front in forward direction. The forward reflection of the probe wave packets (i.e. the “bouncing”) is accompanied by a frequency upshift. In this respect, the effect is similar to the optical analogue of event horizons induced by Kerr nonlinearity27. We also conduct our experiments using a CW probe light, as it simplifies the experimental verification of the frequency shift and reflection efficiency. A narrow CW spectrum facilitates spectral separation between the probe and shifted probe wavelengths. The portion of CW light interacting with the front can be determined from the group velocities of the pump and probe and the length of the slow light waveguide. This way the energy at the shifted frequency can be directly compared to the energy in this portion of CW light resulting in the conversion efficiency. The experimental results are confirmed by numerical simulations.Here, we optimize the indirect transition for the co-propagating scheme and adjust the group velocity of the pump that generates FC plasma. We manage to achieve the case when light stays in the same band of the unaltered waveguide and thus undergoes an indirect intraband transition. As a result, we demonstrate a forward reflectivity of 35% from the plasma front. The plasma front is generated by the TPA of a 6 ps-long pump pulse with an on-chip peak power of 6.2 W and an induced FC density of 7 × 10We also show that the FC plasma front is asymmetric in its reflection properties. It will accelerate and bounce a slow probe wave packet propagating in front of it, yet it will transmit a fast probe wave packet approaching from behind.20. When a probe wave packet is launched into the waveguide, the changes of its wave vector and frequency that are induced by the interaction with the co-propagating front are determined by the dispersion curve of the system, the propagation velocity of the front and the initial position of the probe wave vector and frequency in the band20.After injection of the pump pulse into the PhC waveguide, the pulse modifies the optical properties of the waveguide by generating FCs via TPA. In the switched zone, the refractive index of silicon, 20, phase evolution integrals24 or from the Doppler equation25. Subsequently, by utilizing the flexibility in dispersion designs, a variety of indirect transitions can be envisaged by changing the intersection points of phase continuity line with the bands of the PhC before and after the front. We are interested in the particular situation when the phase continuity line does not cut through the band of the perturbed PhC and thus there is no states behind the front that can be excited.Here, we are interested in the particular situation where the probe wave packet ahead of the front cannot find states on the band of the switched PhC behind the front. Thus, the state of the probe wave, after interacting with the moving front, must remain in the initial band, which means that an intraband transition takes place. This intraband transition manifests itself as a forward reflection from the front. The basic concept to induce this transition is schematically shown in Fig. The intraband transition can be achieved by setting the pump pulses at the knee of the solid band at the frequency where group velocity corresponds to the slope of the phase continuity line, as illustrated in Fig. However, implementing the configuration shown in Fig. 19. However, slow light PhC waveguides can also be engineered to obtain a dispersion relation with equal group velocities at three different frequencies19. This engineered waveguide can be used to excite pump pulses with the required group velocity at a frequency distant from the initial and final frequencies of the probe. A similar dispersion relation was used in refs. 28 using a chirped PhC waveguide; however, due to both stronger dispersion and short length (200 µm) of the waveguide it is too challenging to induce an intraband transition in such a structure. It should be noted that both publications are focused on different effect to that discussed here and intraband transitions and reflection from the front were not investigated. The chirp in the structure further complicates the interpretation of the results obtained in refs.28.Normally, slow light waveguides are optimized to obtain large bandwidth with constant low group velocity20, , i.e. when 17 cm−3 and a refractive index change of approximately –3 × 10−3 at the input of the slow light waveguide  in ref. 20.Figure z-coordinate range of the waveguide where the refractive index has been switched already (switched zone). As the time evolves to the right the switched zone dimension extends to positive z-coordinate values. Eventually, the waveguide is completely switched. As the FC lifetime in silicon PhC waveguides is in the order of 100 ps29, we neglect recombination in the time frame of the front propagation. The graded reddish area indicates the fact that the time function of the FC concentration employs a finite steepness. The two horizontal dotted lines represent the spatial width of the index front. The gradual profile of the front can be explained as follows. The FC generation rate via TPA is proportional to local pump power squared η of the CW probe wave power that enters the front and is frequency converted is:L and the second term relates to the CW probe wave that entered the waveguide when the front has just partly evolved for a fraction of its rise time −3 and this value corresponds to a 100% conversion efficiency. From the measurements shown in Fig. −4. The ratio of this transformed probe power fraction to the maximally transformable probe power fraction of 1 × 10−3 equals 35% and marks the actual efficiency of the intraband transition due to reflection at the propagating plasma fronts. While the amount of transformed probe power caused by interband transitions with final velocity slower than the front is estimated to be approximately 5%. The missing 60% could be attributed to the absorption of the probe wave packets by FCs during their interaction with the plasma front, as is shown in the simulations below.As we use a CW probe, only a small fraction of the total probe light can be converted within the finite length of PhC waveguide. The fraction −3. Figure Next, we simulate the FC front and CW probe wave packets interaction inside the Here we show the trajectories of only four wave packets for clarity. Solid black lines represent those wave packets that undergo complete transitions, while the dashed lines depict the wave packets which only undergo incomplete transitions. We can see clearly that after interaction with the front some wave packets are accelerated by the front and bounced in the forward direction (solid lines) and some other wave packets still have velocities smaller than the front (dashed lines). In addition, we can observe that some wave packets starting initially inside the front are accelerated but do not have the enough time to leave the front.−1 for FC concentration of 7 × 1017 cm−3, corresponding to refractive index change of ≈−3 × 10−335, and for a slow-down factor of 10 present in the waveguides considered12. In case of a sharper front, the time spent by the wave packets inside the front For the spectral evaluation we have launched 120 equally spaced wave packets with starting time in the interval It should be also mentioned that since a CW probe was used here to determine the reflection efficiency, only 0.1% of CW wave was converted. All power of the CW probe at times between the pump pulses adds to the average detected power, thus lowering the “apparent” conversion efficiency while the “effective” conversion efficiency of the probe wave packets participating in the conversion process remains at 35% for 6 ps pump pulses. For probe pulses or pulse trains that have durations equal to the interaction time with FC front we expect the conversion efficiency to approach 100%.36. In addition, for switching in WDM systems, the pump can be positioned outside of the signal frequency window, such that pump has no frequency components at the signal frequency. In comparison, the FWM approach requires the pump frequency always to lie between signal frequency and shifted frequency thus additional measures would be required to filter the pump out of the signal window and spectral cross-talk between the high power pump and the signal is difficult to avoid. The third advantage is the fact that to change the frequency shift neither power nor frequency of the pump has to be adjusted. The different frequency shifts can be achieved with the same pump in waveguides with different dispersion. These advantages make the intraband optical transitions a viable option for all optical signals routing in WDM networks37.We would like to discuss here briefly the advantages of the frequency shift induced by the FC front in comparison to idler generation in the FWM configuration. First, the time span of the probe wave shifted to new frequency is not limited by pulse duration as in FWM but depends on both the group velocity differences between the pump and the probe and on the interaction length. Thus, with a FC front we can envisage to shift large portions of probe, for example, a packet of binary optical signal information. For example, if we assume a 1 mm-long slow light waveguide and a group index difference between the pump and the probe of 30, then the time span of the converted probe will be 100 ps. For a wavelength-division-multiplexing (WDM) system 0.8 nm wavelength shift would be sufficient to switch between two channels. In this case smaller pump power can be used as in this experiment and thus TPA induced pump depletion can be avoided. This value is much larger than what can normally be achieved in a FWM process, which is limited by the picosecond, or shorter, pump pulse durations. Recently, FWM has been demonstrated in a silicon PhC waveguides using a CW light for both pump and probe waves; however, the conversion efficiency is in the order of ≈−30 dBIn conclusion, we have experimentally demonstrated a 35% optical-wave reflection and −3.4 nm wavelength shift by interaction with a FC plasma front generated, confined and propagating inside a 400 µm-long dispersion engineered silicon slow light PhC waveguide. The front was generated by TPA of 6 ps-long pump pulse with a peak power of 6.2 W. The forward reflection of the probe wave packets co-propagating with the plasma front are accompanied by a frequency upshift. The presented reflection becomes possible due to a novel indirect intraband optical transition in a slow light waveguide. Under these special conditions the incident light does not find states beyond the front and has to reflect from it. The effect presented here is based on the fascinating dispersion properties of carefully engineered silicon slow light PhC waveguides which allow to control the speed of the plasma front with respect to the group velocity of the probe wave packets. We show also that the FC plasma front is asymmetric in its reflection properties. It will accelerate and reflect a slow probe wave packets propagating in front of it and will transmit a fast probe wave packets initially behind it. Due to the fact that the pump, probe and shifted probe are all at 1.5 µm wavelength, the presented effect opens new possibilities for frequency manipulation and all optical switching in optical telecommunication.38. The occurrence of an intraband indirect transition in our waveguide can be verified by recording the optical spectra of the output probe light with and without pump pulses present and as function of the pump pulse power.The optical measurement proceeds by launching 6 ps-long pump pulses derived from 100 MHz repetition rate mode locked fibre laser into a 396 µm-long slow light silicon PhC waveguide at a centre wavelength of 1539 nm with a group index of In our simulations, we focus on the part of the incident probe light that interacts with the front and ignore both the unperturbed input CW probe light, as well as the components that are slightly down shifted in frequency due to slow FC decay after the front propagation. We assume that we can split the CW probe into wave packets and track their trajectory and frequency shift. At the end of the waveguide we calculate the energy of the shifted probe by adding up the energy of the shifted wave packets. This approach neglects the spectral width of the wave packet and interference effects between the wave packets and thus represents a ray optics approximation.−1 at FC concentration of 7 × 1017 cm−335, taking a slow-down factor of 10 into account. Also, we consider an exponential decay of the front refractive index change during propagation inside the waveguide due to scattering and TPA and FC absorption with decay constant corresponding to 8 dB decay in 400 µm waveguide. We start with a defined frequency of the wave packet and calculate its wavenumber and group velocity at the input in accordance to its position in respect to the front. In a small time step a wave packet propagates a small distance according to its group velocity. Being inside the front the wave packet accumulates a frequency shift according to Eq. (In our simulation we use a front with a linear slope. We took into account the FC absorption of the probe scaling linearly with FC concentration. The absorption coefficient is 30 cmThe data that support the findings of this study are available from the corresponding author upon request.Supplementary InformationPeer Review File