Integration of Microsphere Resonators with Bioassay Fluidics for Whispering Gallery Mode Imaging

PubMed Central

Kim, Daniel C.; Armendariz, Kevin P.

2013-01-01

Whispering gallery mode resonators are small, radially symmetric dielectrics that trap light through continuous total internal reflection. The resonant condition at which light is efficiently confined within the structure is linked with refractive index, which has led to the development of sensitive label-free sensing schemes based on whispering gallery mode resonators. One resonator design uses inexpensive high index glass microspheres that offer intrinsically superior optical characteristics, but have proven difficult to multiplex and integrate with the fluidics for sample delivery and fluid exchange necessary for assay development. Recently, we introduced a fluorescence imaging approach that enables large scale multiplexing with microsphere resonators, thus removing one obstacle for assay development. Here we report an approach for microsphere immobilization that overcomes limitations arising from their integration with fluidic delivery. The approach is an adaptation of a calcium-assisted glass bonding method originally developed for microfluidic glass chip fabrication. Microspheres bonded to glass using this technique are shown to be stable with respect to fluid flow and show no detectable loss in optical performance. Measured Q-factors, for example, remain unchanged following sphere bonding to the substrate. The stability of the immobilized resonators is further demonstrated by transferring lipid films onto the immobilized spheres using the Langmuir-Blodgett technique. Bilayers of DOPC doped with GM1 were transferred onto immobilized resonators to detect the binding of cholera toxin to GM1. Binding curves generated from shifts in the whispering gallery mode resonance result in a measured Kd of 1.5 × 10−11 with a limit of detection of 3.3 pM. These results are discussed in terms of future assay development using microsphere resonators. PMID:23615457

Real-time detection and analysis of Whispering gallery mode resonance in high-throughput flowing monodisperse microdroplets

NASA Astrophysics Data System (ADS)

El Abed, Abdel I.; Taly, Valérie

2013-11-01

We investigate light coupling into highly monodisperse liquid microdroplets, which are produced and manipulated at kHz rates in a microfluidic device. We show that such coupling leads to Whispering gallery mode resonances (WGMs) which are detected and analyzed versus time during the fast displacement of microdroplets into the microfluidic channel. Our results show that droplet-based microfluidics may be applied advantageously in the promising field of high-throughput label-free biosensing.

Nonlinear optical whispering gallery mode resonators

NASA Technical Reports Server (NTRS)

Ilchenko, Vladimir (Inventor); Matsko, Andrey B. (Inventor); Savchenkov, Anatoliy (Inventor); Maleki, Lutfollah (Inventor)

2005-01-01

Whispering gallery mode (WGM) optical resonators comprising nonlinear optical materials, where the nonlinear optical material of a WGM resonator includes a plurality of sectors within the optical resonator and nonlinear coefficients of two adjacent sectors are oppositely poled.

Optical apparatus for conversion of whispering-gallery modes into a free space gaussian like beam

DOEpatents

Stallard, Barry W.; Makowski, Michael A.; Byers, Jack A.

1992-01-01

An optical converter for efficient conversion of millimeter wavelength whispering-gallery gyrotron output into a linearly polarized, free-space Gaussian-like beam. The converter uses a mode-converting taper and three mirror optics. The first mirror has an azimuthal tilt to eliminate the k.sub..phi. component of the propagation vector of the gyrotron output beam. The second mirror has a twist reflector to linearly polarize the beam. The third mirror has a constant phase surface so the converter output is in phase.

Whispering gallery modes in a spherical microcavity with a photoluminescent shell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grudinkin, S. A., E-mail: grudink@gvg.ioffe.ru; Dontsov, A. A.; Feoktistov, N. A.

2015-10-15

Whispering-gallery mode spectra in optical microcavities based on spherical silica particles coated with a thin photoluminescent shell of hydrogenated amorphous silicon carbide are studied. The spectral positions of the whispering-gallery modes for spherical microcavities with a shell are calculated. The dependence of the spectral distance between the TE and TM modes on the shell thickness is examined.

Whispering Gallery Mode Thermometry

PubMed Central

Corbellini, Simone; Ramella, Chiara; Yu, Lili; Pirola, Marco; Fernicola, Vito

2016-01-01

This paper presents a state-of-the-art whispering gallery mode (WGM) thermometer system, which could replace platinum resistance thermometers currently used in many industrial applications, thus overcoming some of their well-known limitations and their potential for providing lower measurement uncertainty. The temperature-sensing element is a sapphire-crystal-based whispering gallery mode resonator with the main resonant modes between 10 GHz and 20 GHz. In particular, it was found that the WGM around 13.6 GHz maximizes measurement performance, affording sub-millikelvin resolution and temperature stability of better than 1 mK at 0 °C. The thermometer system was made portable and low-cost by developing an ad hoc interrogation system (hardware and software) able to achieve an accuracy in the order of a few parts in 109 in the determination of resonance frequencies. Herein we report the experimental assessment of the measurement stability, repeatability and resolution, and the calibration of the thermometer in the temperature range from −74 °C to 85 °C. The combined standard uncertainty for a single temperature calibration point is found to be within 5 mK (i.e., comparable with state-of-the-art for industrial thermometry), and is mainly due to the employed calibration setup. The uncertainty contribution of the WGM thermometer alone is within a millikelvin. PMID:27801868

Nonlinear optics and crystalline whispering gallery mode resonators

NASA Technical Reports Server (NTRS)

Matsko, Andrey; Savchenkov, Anatoliy; Ilchenko, Vladimir S.; Maleki, Lute

2004-01-01

We report on our recent results concerning fabrication of high-Q whispering gallery mode crystalline resonaors, and discuss some possible applications of lithium niobate WGM resonators in nonlinear optics and photonics.

Electro-pumped whispering gallery mode ZnO microlaser array

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, G. Y.; State Key Laboratory of Bioelectronics, School of Electronic Science and Engineering, Southeast University, Nanjing 210096; Li, J. T.

2015-01-12

By employing vapor-phase transport method, ZnO microrods are fabricated and directly assembled on p-GaN substrate to form a heterostructural microlaser array, which avoids of the relatively complicated etching process comparing previous work. Under applied forward bias, whispering gallery mode ZnO ultraviolet lasing is obtained from the as-fabricated heterostructural microlaser array. The device's electroluminescence originates from three distinct electron-hole recombination processes in the heterojunction interface, and whispering gallery mode ultraviolet lasing is obtained when the applied voltage is beyond the lasing threshold. This work may present a significant step towards future fabrication of a facile technique for micro/nanolasers.

Classification of antibiotics by neural network analysis of optical resonance data of whispering gallery modes in dielectric microspheres

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav; Ostendorf, Andreas

2012-04-01

A novel emerging technique for the label-free analysis of nanoparticles and biomolecules in liquid fluids using optical micro cavity resonance of whispering-gallery-type modes is being developed.A scheme based on polymer microspheres fixed by adhesive on the evanescence wave coupling element has been used. We demonstrated that the only spectral shift can't be used for identification of biological agents by developed approach. So neural network classifier for biological agents and micro/nano particles classification has been developed. The developed technique is the following. While tuning the laser wavelength images were recorded as avi-file. All sequences were broken into single frames and the location of the resonance was allocated in each frame. The image was filtered for noise reduction and integrated over two coordinates for evaluation of integrated energy of a measured signal. As input data normalized resonance shift of whispering-gallery modes and the relative efficiency of whispering-gallery modes excitation were used. Other parameters such as polarization of excited light, "center of gravity" of a resonance spectra etc. are also tested as input data for probabilistic neural network. After network designing and training we estimated the accuracy of classification. The classification of antibiotics such as penicillin and cephasolin have been performed with the accuracy of not less 97 %. Developed techniques can be used for lab-on-chip sensor based diagnostic tools as for identification of different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells and for dynamics of a delivery of medicines to bodies.

Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities

NASA Astrophysics Data System (ADS)

Zhu, Jiangang; Kaya Özdemir, Şahin; He, Lina; Chen, Da-Ren; Yang, Lan

2011-08-01

Detecting and characterizing single nanoparticles and airborne viruses are of paramount importance for disease control and diagnosis, for environmental monitoring, and for understanding size dependent properties of nanoparticles for developing innovative products. Although single particle and virus detection have been demonstrated in various platforms, single-shot size measurement of each detected particle has remained a significant challenge. Here, we present a nanoparticle size spectrometry scheme for label-free, real-time and continuous detection and sizing of single Influenza A virions, polystyrene and gold nanoparticles using split whispering-gallery-modes (WGMs) in an ultra-high-Q resonator. We show that the size of each particle and virion can be measured as they continuously bind to the resonator one-by-one, eliminating the need for ensemble measurements, stochastic analysis or imaging techniques employed in previous works. Moreover, we show that our scheme has the ability to identify the components of particle mixtures.

Adsorption detection for polylysine biomolecules based on high-Q silica capillary whispering gallery mode microresonator

NASA Astrophysics Data System (ADS)

Wu, Jixuan; Liu, Bo; Zhang, Hao; Song, Binbin

2017-11-01

A silica-capillary-based whispering gallery mode (WGM) microresonator has been proposed and experimentally demonstrated for the real-time monitoring of the polylysine adsorption process. The spectral characteristics of the WGM resonance dips with high quality factor and good wavelength selectivity have been investigated to evaluate the dynamic process for the binding of polylysine with a capillary surface. The WGM transmission spectrum shows a regular shift with increments of observation time, which could be exploited for the analysis of the polylysine adsorption process. The proposed WGM microresonator system possesses desirable qualities such as high sensitivity, fast response, label-free method, high detection resolution and compactness, which could find promising applications in histology and related bioengineering areas.

Interrelation of the effects caused by the rotation of the whispering gallery modes resonator

NASA Astrophysics Data System (ADS)

Dmitriyeva, Anna D.; Filatov, Yuri V.; Shalymov, Egor V.; Venediktov, Vladimir Yu.

2016-11-01

Optical whispering gallery modes resonators are characterized by unique properties: ultrahigh quality factor, small amount of the modes and small size. It allows to use them in compact high-precision measuring devices. In particular these resonators can be used in the composition of gyros. For today all researches, devoted to the application of the whispering gallery modes resonators in gyros, deals only with one of induced by the rotation effects (Sagnac effect or the influence of centrifugal forces on the resonator size). In this work we study the interrelation of the effects caused by the rotation of the whispering gallery modes resonator. Also in work we consider the possibility of joint application of both effects (the influence of centrifugal forces and Sagnac effect) for measuring angular velocity.

Three-dimensional whispering gallery modes in InGaAs nanoneedle lasers on silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tran, T.-T. D.; Chen, R.; Ng, K. W.

2014-09-15

As-grown InGaAs nanoneedle lasers, synthesized at complementary metal–oxide–semiconductor compatible temperatures on polycrystalline and crystalline silicon substrates, were studied in photoluminescence experiments. Radiation patterns of three-dimensional whispering gallery modes were observed upon optically pumping the needles above the lasing threshold. Using the radiation patterns as well as finite-difference-time-domain simulations and polarization measurements, all modal numbers of the three-dimensional whispering gallery modes could be identified.

Graded-Index "Whispering-Gallery" Optical Microresonators

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy; Maleki, Lute; Iltchenko, Vladimir; Matsko, Andrey

2006-01-01

Graded-index-of-refraction dielectric optical microresonators have been proposed as a superior alternative to prior dielectric optical microresonators, which include microspheres and microtori wherein electromagnetic waves propagate along circumferential paths in "whispering-gallery" modes. The design and method of fabrication of the proposed microresonators would afford improved performance by exploiting a combination of the propagation characteristics of the whisperinggallery modes and the effect of a graded index of refraction on the modes.

Optical filter having coupled whispering-gallery-mode resonators

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy (Inventor); Ilchenko, Vladimir (Inventor); Maleki, Lutfollah (Inventor); Handley, Timothy A. (Inventor)

2006-01-01

Optical filters having at least two coupled whispering-gallery-mode (WGM) optical resonators to produce a second order or higher order filter function with a desired spectral profile. At least one of the coupled WGM optical resonators may be tunable by a control signal to adjust the filtering function.

White-Light Whispering Gallery Mode Optical Resonator System and Method

NASA Technical Reports Server (NTRS)

Matsko, Andrey B. (Inventor); Savchenkov, Anatoliy A. (Inventor); Maleki, Lute (Inventor)

2009-01-01

An optical resonator system and method that includes a whispering-gallery mode (WGM) optical resonator that is capable of resonating across a broad, continuous swath of frequencies is provided. The optical resonator of the system is shaped to support at least one whispering gallery mode and includes a top surface, a bottom surface, a side wall, and a first curved transition region extending between the side wall and the top surface. The system further includes a coupler having a coupling surface which is arranged to face the transition region of the optical resonator and in the vicinity thereof such that an evanescent field emitted from the coupler is capable of being coupled into the optical resonator through the first curved transition region

Tunable Optical Filters Having Electro-optic Whispering-gallery-mode Resonators

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy (Inventor); Ilchenko, Vladimir (Inventor); Matsko, Andrey B. (Inventor); Maleki, Lutfollah (Inventor)

2006-01-01

Tunable optical filters using whispering-gallery-mode (WGM) optical resonators are described. The WGM optical resonator in a filter exhibits an electro-optical effect and hence is tunable by applying a control electrical signal.

Physics. Creating and probing electron whispering-gallery modes in graphene.

PubMed

Zhao, Yue; Wyrick, Jonathan; Natterer, Fabian D; Rodriguez-Nieva, Joaquin F; Lewandowski, Cyprian; Watanabe, Kenji; Taniguchi, Takashi; Levitov, Leonid S; Zhitenev, Nikolai B; Stroscio, Joseph A

2015-05-08

The design of high-finesse resonant cavities for electronic waves faces challenges due to short electron coherence lengths in solids. Complementing previous approaches to confine electronic waves by carefully positioned adatoms at clean metallic surfaces, we demonstrate an approach inspired by the peculiar acoustic phenomena in whispering galleries. Taking advantage of graphene's gate-tunable light-like carriers, we create whispering-gallery mode (WGM) resonators defined by circular pn junctions, induced by a scanning tunneling probe. We can tune the resonator size and the carrier concentration under the probe in a back-gated graphene device over a wide range. The WGM-type confinement and associated resonances are a new addition to the quantum electron-optics toolbox, paving the way to develop electronic lenses and resonators. Copyright © 2015, American Association for the Advancement of Science.

The comparison of the influence of centrifugal forces and the Sagnac effect on a rotating whispering gallery modes resonators

NASA Astrophysics Data System (ADS)

Filatov, Yuri V.; Shalymov, Egor V.; Venediktov, Vladimir Yu.; Dmitrieva, Anna D.

2016-10-01

The parameters of whispering gallery modes resonators can be significantly modified under the action of external factors, for instance, in the case of resonator movement. The effects, which take place in the moving resonators of whispering gallery modes, can be employed for measuring of the angular velocity. In this work we was compared the influence of centrifugal forces and the Sagnac effect on the eigenfrequencies (wavelengths) of whispering gallery modes resonators. Also work is devoted mutual relationships of the effects.

Reconfigurable Liquid Whispering Gallery Mode Microlasers

PubMed Central

Yang, Shancheng; Ta, Van Duong; Wang, Yue; Chen, Rui; He, Tingchao; Demir, Hilmi Volkan; Sun, Handong

2016-01-01

Engineering photonic devices from liquid has been emerging as a fascinating research avenue. Reconfigurably tuning liquid optical micro-devices are highly desirable but remain extremely challenging because of the fluidic nature. In this article we demonstrate an all-liquid tunable whispering gallery mode microlaser floating on a liquid surface fabricated by using inkjet print technique. We show that the cavity resonance of such liquid lasers could be reconfigurably manipulated by surface tension alteration originated from the tiny concentration change of the surfactant in the supporting liquid. As such, remarkable sensing of water-soluble organic compounds with a sensitivity of free spectral range as high as 19.85 THz / (mol · mL−1) and the detectivity limit around 5.56 × 10−3 mol · mL−1 is achieved. Our work provides not only a novel approach to effectively tuning a laser resonator but also new insight into potential applications in biological, chemical and environmental sensing. PMID:27256771

Nonlinear optics and crystalline whispering gallery mode resonators

NASA Technical Reports Server (NTRS)

Matsko, Andrey B.; Savchenkov, Anatoliy A.; Ilchenko, Vladimir S.; Maleki, Lute

2004-01-01

We report on our recent results concerning fabrication of high-Q whispering gallery mode (WGM) crystalline resonators, and discuss some possible applications of lithium niobate WGM resonators in nonlinear optics and photonics. In particular, we demonstrate experimentally a tunable third-order optical filter fabricated from the three metalized resonators; and report observation of parametric frequency dobuling in a WGM resonator made of periodically poled lithium niobate (PPLN).

Whispering gallery mode lithium niobate microresonators for photonics applications

NASA Astrophysics Data System (ADS)

Maleki, Lute; Savchenkov, Anatoliy A.; Ilchenko, Vladimir S.; Matsko, Andrey B.

2003-07-01

We review various photonics applications of whispering gallery mode (WGM) dielectric resonators and focus on the capability of generating trains of short optical pulses using WGM lithium niobate cavities. We introduce schemes of optical frequency comb generators, actively mode-locked lasers, and coupled opto-electronic oscillators where WGM cavities are utilized for the light amplification and modulation.

Real-Time Detection of Staphylococcus Aureus Using Whispering Gallery Mode Optical Microdisks

PubMed Central

Ghali, Hala; Chibli, Hicham; Nadeau, Jay L.; Bianucci, Pablo; Peter, Yves-Alain

2016-01-01

Whispering Gallery Mode (WGM) microresonators have recently been studied as a means to achieve real-time label-free detection of biological targets such as virus particles, specific DNA sequences, or proteins. Due to their high quality (Q) factors, WGM resonators can be highly sensitive. A biosensor also needs to be selective, requiring proper functionalization of its surface with the appropriate ligand that will attach the biomolecule of interest. In this paper, WGM microdisks are used as biosensors for detection of Staphylococcus aureus. The microdisks are functionalized with LysK, a phage protein specific for staphylococci at the genus level. A binding event on the surface shifts the resonance peak of the microdisk resonator towards longer wavelengths. This reactive shift can be used to estimate the surface density of bacteria that bind to the surface of the resonator. The limit of detection of a microdisk with a Q-factor around 104 is on the order of 5 pg/mL, corresponding to 20 cells. No binding of Escherichia coli to the resonators is seen, supporting the specificity of the functionalization scheme. PMID:27153099

Whispering gallery effect in relativistic optics

NASA Astrophysics Data System (ADS)

Abe, Y.; Law, K. F. F.; Korneev, Ph.; Fujioka, S.; Kojima, S.; Lee, S.-H.; Sakata, S.; Matsuo, K.; Oshima, A.; Morace, A.; Arikawa, Y.; Yogo, A.; Nakai, M.; Norimatsu, T.; d'Humières, E.; Santos, J. J.; Kondo, K.; Sunahara, A.; Gus'kov, S.; Tikhonchuk, V.

2018-03-01

relativistic laser pulse, confined in a cylindrical-like target, under specific conditions may perform multiple scattering along the internal target surface. This results in the confinement of the laser light, leading to a very efficient interaction. The demonstrated propagation of the laser pulse along the curved surface is just yet another example of the "whispering gallery" effect, although nonideal due to laser-plasma coupling. In the relativistic domain its important feature is a gradual intensity decrease, leading to changes in the interaction conditions. The proccess may pronounce itself in plenty of physical phenomena, including very efficient electron acceleration and generation of relativistic magnetized plasma structures.

Whispering gallery mode resonators based on radiation-sensitive materials

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy (Inventor); Maleki, Lutfollah (Inventor); Ilchenko, Vladimir (Inventor); Handley, Timothy A. (Inventor)

2005-01-01

Whispering gallery mode (WGM) optical resonators formed of radiation-sensitive materials to allow for permanent tuning of their resonance frequencies in a controlled manner. Two WGM resonators may be cascaded to form a composite filter to produce a second order filter function where at least one WGM resonator is formed a radiation-sensitive material to allow for proper control in the overlap of the two filter functions.

All-optical Photonic Oscillator with High-Q Whispering Gallery Mode Resonators

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy A.; Matsko, Andrey B.; Strekalov, Dmitry; Mohageg, Makan; Iltchenko, Vladimir S.; Maleki, Lute

2004-01-01

We demonstrated low threshold optical photonic hyper-parametric oscillator in a high-Q 10(exp 10) CaF2 whispering gallery mode resonator which generates stable 8.5 GHz signal. The oscillations result from the resonantly enhanced four wave mixing occurring due to Kerr nonlinearity of the material.

Sensitivity optimization in whispering gallery mode optical cylindrical biosensors

NASA Astrophysics Data System (ADS)

Khozeymeh, F.; Razaghi, M.

2018-01-01

Whispering-gallery-mode resonances propagated in cylindrical resonators have two angular and radial orders of l and i. In this work, the higher radial order whispering-gallery-mode resonances, (i = 1 - 4), at a fixed l are examined. The sensitivity of theses resonances is analysed as a function of the structural parameters of the cylindrical resonator like different radii and refractive index of composed material of the resonator. A practical application where cylindrical resonators are used for the measurement of glucose concentration in water is presented as a biosensor demonstrator. We calculate the wavelength shifts of the WG1-4, in several glucose/water solutions, with concentrations spanning from 0.0% to 9.0.% (weight/weight). Improved sensitivity can be achieved using multi-WGM cylindrical resonators with radius of R = 100 μm and resonator composed material of MgF 2 with refractive index of nc = 1.38. Also the effect of polarization on sensitivity is considered for all four WGMs. The best sensitivity of 83.07 nm/RIU for the fourth WGM with transverse magnetic polarization, is reported. These results propose optimized parameters aimed to fast designing of cylindrical resonators as optical biosensors, where both the sensitivity and the geometries can be optimized.

Coupler for coupling gyrotron whispering gallery mode RF into HE11 waveguide

DOEpatents

Neilson, Jeffrey M

2015-02-24

A cylindrical waveguide with a mode converter transforms a whispering gallery mode from a gyrotron cylindrical waveguide with a helical cut launch edge to a quasi-Gaussian beam suitable for conveyance through a corrugated waveguide. This quasi-Gaussian beam is radiated away from the waveguide using a spiral cut launch edge, which is in close proximity to a first mode converting reflector. The first mode converting reflector is coupled to a second mode converting reflector which provides an output free-space HE11 mode wave suitable for direct coupling into a corrugated waveguide. The radiated beam produced at the output of the second mode converting reflector is substantially circular.

GaN microwires as optical microcavities: whispering gallery modes Vs Fabry-Perot modes.

PubMed

Coulon, Pierre-Marie; Hugues, Maxime; Alloing, Blandine; Beraudo, Emmanuel; Leroux, Mathieu; Zuniga-Perez, Jesus

2012-08-13

GaN microwires grown by metalorganic vapour phase epitaxy and with radii typically on the order of 1-5 micrometers exhibit a number of resonances in their photoluminescence spectra. These resonances include whispering gallery modes and transverse Fabry-Perot modes. A detailed spectroscopic study by polarization-resolved microphotoluminescence, in combination with electron microscopy images, has enabled to differentiate both kinds of modes and determined their main spectral properties. Finally, the dispersion of the ordinary and extraordinary refractive indices of strain-free GaN in the visible-UV range has been obtained thanks to the numerical simulation of the observed modes.

Resonant Optical Circuits Based on Coupling Between Whispering Gallery Modes in Dielectric Microresonators

DTIC Science & Technology

2007-12-30

111111 (2006). 2. S.P. Ashili , V.N. Astratov, and E.C.H. Sykes, “The effects of inter-cavity separation on optical coupling in dielectric bispheres...chains of coupled spherical cavities,” Opt. Lett. 32, 409-411 (2007). 4. V.N. Astratov, and S.P. Ashili , “Percolation of light through whispering...Propagation via Whispering Gallery Modes in 3-D Networks of Coupled Spherical Cavities (Talk), V.N. Astratov, S.P. Ashili , and A.M. Kapitonov, in Frontiers in

Second-harmonic generation using tailored whispering gallery modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumeige, Yannick; Feron, Patrice

It has been shown that whispering gallery modes can be used to obtain a combination of modal and geometrical quasi-phase-matching in second-harmonic generation. This could be achieved in isotropic, nonferroelectric, strongly dispersive and highly nonlinear materials such as III-V semiconductors. Unfortunately the poor overlap between the second-harmonic field and second order nonlinear polarization limits the conversion efficiency. In this paper we show that by engineering the refractive index it is possible to increase field overlap and to enhance effective second order nonlinear polarization of semiconductor microdisks.

Method of fabricating a whispering gallery mode resonator

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy A. (Inventor); Matkso, Andrey B. (Inventor); Iltchenko, Vladimir S. (Inventor); Maleki, Lute (Inventor)

2011-01-01

A method of fabricating a whispering gallery mode resonator (WGMR) is provided. The WGMR can be fabricated from a particular material, annealed, and then polished. The WGMR can be repeatedly annealed and then polished. The repeated polishing of the WGMR can be carried out using an abrasive slurry. The abrasive slurry can have a predetermined, constant grain size. Each subsequent polishing of the WGMR can use an abrasive slurry having a grain size that is smaller than the grain size of the abrasive slurry of the previous polishing iteration.

Comparison of raised-microdisk whispering-gallery-mode characterization techniques.

PubMed

Redding, Brandon; Marchena, Elton; Creazzo, Tim; Shi, Shouyuan; Prather, Dennis W

2010-04-01

We compare the two prevailing raised-microdisk whispering-gallery-mode (WGM) characterization techniques, one based on coupling emission to a tapered fiber and the other based on collecting emission in the far field. We applied both techniques to study WGMs in Si nanocrystal raised microdisks and observed dramatically different behavior. We explain this difference in terms of the radiative bending loss on which the far-field collection technique relies and discuss the regimes of operation in which each technique is appropriate.

Direct electrical-to-optical conversion and light modulation in micro whispering-gallery-mode resonators

NASA Technical Reports Server (NTRS)

Maleki, Lute (Inventor); Levi, Anthony F. J. (Inventor)

2005-01-01

Techniques for directly converting an electrical signal into an optical signal by using a whispering gallery mode optical resonator formed of a dielectric material that allows for direct modulation of optical absorption by the electrical signal.

Active mode-locked lasers and other photonic devices using electro-optic whispering gallery mode resonators

NASA Technical Reports Server (NTRS)

Matsko, Andrey B. (Inventor); Ilchenko, Vladimir (Inventor); Savchenkov, Anatoliy (Inventor); Maleki, Lutfollah (Inventor)

2006-01-01

Techniques and devices using whispering gallery mode (WGM) optical resonators, where the optical materials of the WGM resonators exhibit an electro-optical effect to perform optical modulation. Examples of actively mode-locked lasers and other devices are described.

Dynamic Fano-like resonances in erbium-doped whispering-gallery-mode microresonators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei, Fuchuan; Department of Electrical and Systems Engineering, Washington University, St. Louis, Missouri 63130; Peng, Bo

2014-09-08

We report Fano-like asymmetric resonances modulated by optical gain in a whispering-gallery-mode resonator fabricated from erbium-doped silica. A time-dependent gain profile leads to dynamically varying sharp asymmetric resonances with features similar to Fano resonances. Depending on the scan speed of the frequency of the probe laser and the pump-probe power ratio, transmission spectra of the active microcavity exhibit a resonance dip, a resonance peak, or a Fano-like resonance.

Whispering gallery mode sensors

PubMed Central

Foreman, Matthew R.; Swaim, Jon D.; Vollmer, Frank

2015-01-01

We present a comprehensive overview of sensor technology exploiting optical whispering gallery mode (WGM) resonances. After a short introduction we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theoretical contributions to the modeling and analysis of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors by outlining efforts made to date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities to hybrid optomechanical sensors, which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resolution are beginning to emerge. We therefore summarize the techniques being pursued in this vein. Ultimately WGM sensors aim for real-world applications, such as measurements of force and temperature, or alternatively gas and biosensing. Each such application is thus reviewed in turn, and important achievements are discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a physical and biological context and consider how they may yet push the detection envelope further. PMID:26973759

Whispering-Gallery Mode Resonators for Detecting Cancer

PubMed Central

Pongruengkiat, Weeratouch; Pechprasarn, Suejit

2017-01-01

Optical resonators are sensors well known for their high sensitivity and fast response time. These sensors have a wide range of applications, including in the biomedical fields, and cancer detection is one such promising application. Sensor diagnosis currently has many limitations, such as being expensive, highly invasive, and time-consuming. New developments are welcomed to overcome these limitations. Optical resonators have high sensitivity, which enable medical testing to detect disease in the early stage. Herein, we describe the principle of whispering-gallery mode and ring optical resonators. We also add to the knowledge of cancer biomarker diagnosis, where we discuss the application of optical resonators for specific biomarkers. Lastly, we discuss advancements in optical resonators for detecting cancer in terms of their ability to detect small amounts of cancer biomarkers. PMID:28902169

Whispering-gallery nanocavity plasmon-enhanced Raman spectroscopy

PubMed Central

Zhang, Jing; Li, Jinxing; Tang, Shiwei; Fang, Yangfu; Wang, Jiao; Huang, Gaoshan; Liu, Ran; Zheng, Lirong; Cui, Xugao; Mei, Yongfeng

2015-01-01

The synergy effect in nature could enable fantastic improvement of functional properties and associated effects. The detection performance of surface-enhanced Raman scattering (SERS) can be highly strengthened under the cooperation with other factors. Here, greatly-enhanced SERS detection is realized based on rolled-up tubular nano-resonators decorated with silver nanoparticles. The synergy effect between whispering-gallery-mode (WGM) and surface plasmon leads to an extra enhancement at the order of 105 compared to non-resonant flat SERS substrates, which can be well tuned by altering the diameter of micron- and nanotubes and the excitation laser wavelengths. Such synchronous and coherent coupling between plasmonics and photonics could lead to new principle and design for various sub-wavelength optical devices, e.g. plasmonic waveguides and hyperbolic metamaterials. PMID:26443526

Whispering gallery mode photoemission from self-assembled poly-para-phenylenevinylene microspheres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kushida, Soh; Yamamoto, Yohei; Braam, Daniel

2015-12-31

Poly[2-methoxy-5-(3,7-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMOPPV) self-assembles to form well-defined spheres with several micrometers in diameter upon addition of a methanol vapor into a chloroform solution of MDMOPPV. The single sphere of MDMOPPV with 5.7 µm diameter exhibits whispering gallery mode (WGM) photoemission upon excitation with focused laser beam. The periodic emission lines are characterized by transverse electric and magnetic WGMs, and Q-factor reaches ∼345 at the highest.

Biosensing in a microelectrofluidic system using optical whispering-gallery mode spectroscopy

PubMed Central

Huang, Lei; Guo, Zhixiong

2011-01-01

Label-free detection of biomolecules using an optical whispering-gallery mode sensor in a microelectrofluidic channel is simulated. Negatively charged bovine serum albumin is considered as the model protein analyte. The analyte transport in aqueous solution is controlled by an externally applied electrical field. The finite element method is employed for solving the equations of the charged species transport, the Poisson equation of electric potential, the equations of conservation of momentum and energy, and the Helmholtz equations of electromagnetic waves. The adsorption process of the protein molecules on the microsensor head surface is monitored by the resonance frequency shifts. Frequency shift caused by temperature variation due to Joule heating is analyzed and found to be negligible. The induced shifts behave in a manner similar to Langmuir-like adsorption kinetics; but the time constant increases due to the presence of the external electrical field. A correlation of the frequency shift, the analyte feed concentration in the solution, and the applied voltage gradient is obtained, in which an excellent linear relationship between the frequency shift and the analyte concentration is revealed. The applied voltage gradient enhances significantly the analyte concentration in the vicinity of the sensor surface; thus, the sensor sensitivity which has a power function of the voltage gradient with exponent 2.85 in the controlled voltage range. Simulated detection of extremely low protein concentration to the pico-molar level is carried out. PMID:22662041

Microwave Photonics Systems Based on Whispering-gallery-mode Resonators

PubMed Central

Coillet, Aurélien; Henriet, Rémi; Phan Huy, Kien; Jacquot, Maxime; Furfaro, Luca; Balakireva, Irina; Larger, Laurent; Chembo, Yanne K.

2013-01-01

Microwave photonics systems rely fundamentally on the interaction between microwave and optical signals. These systems are extremely promising for various areas of technology and applied science, such as aerospace and communication engineering, sensing, metrology, nonlinear photonics, and quantum optics. In this article, we present the principal techniques used in our lab to build microwave photonics systems based on ultra-high Q whispering gallery mode resonators. First detailed in this article is the protocol for resonator polishing, which is based on a grind-and-polish technique close to the ones used to polish optical components such as lenses or telescope mirrors. Then, a white light interferometric profilometer measures surface roughness, which is a key parameter to characterize the quality of the polishing. In order to launch light in the resonator, a tapered silica fiber with diameter in the micrometer range is used. To reach such small diameters, we adopt the "flame-brushing" technique, using simultaneously computer-controlled motors to pull the fiber apart, and a blowtorch to heat the fiber area to be tapered. The resonator and the tapered fiber are later approached to one another to visualize the resonance signal of the whispering gallery modes using a wavelength-scanning laser. By increasing the optical power in the resonator, nonlinear phenomena are triggered until the formation of a Kerr optical frequency comb is observed with a spectrum made of equidistant spectral lines. These Kerr comb spectra have exceptional characteristics that are suitable for several applications in science and technology. We consider the application related to ultra-stable microwave frequency synthesis and demonstrate the generation of a Kerr comb with GHz intermodal frequency. PMID:23963358

Microwave photonics systems based on whispering-gallery-mode resonators.

PubMed

Coillet, Aurélien; Henriet, Rémi; Phan Huy, Kien; Jacquot, Maxime; Furfaro, Luca; Balakireva, Irina; Larger, Laurent; Chembo, Yanne K

2013-08-05

Microwave photonics systems rely fundamentally on the interaction between microwave and optical signals. These systems are extremely promising for various areas of technology and applied science, such as aerospace and communication engineering, sensing, metrology, nonlinear photonics, and quantum optics. In this article, we present the principal techniques used in our lab to build microwave photonics systems based on ultra-high Q whispering gallery mode resonators. First detailed in this article is the protocol for resonator polishing, which is based on a grind-and-polish technique close to the ones used to polish optical components such as lenses or telescope mirrors. Then, a white light interferometric profilometer measures surface roughness, which is a key parameter to characterize the quality of the polishing. In order to launch light in the resonator, a tapered silica fiber with diameter in the micrometer range is used. To reach such small diameters, we adopt the "flame-brushing" technique, using simultaneously computer-controlled motors to pull the fiber apart, and a blowtorch to heat the fiber area to be tapered. The resonator and the tapered fiber are later approached to one another to visualize the resonance signal of the whispering gallery modes using a wavelength-scanning laser. By increasing the optical power in the resonator, nonlinear phenomena are triggered until the formation of a Kerr optical frequency comb is observed with a spectrum made of equidistant spectral lines. These Kerr comb spectra have exceptional characteristics that are suitable for several applications in science and technology. We consider the application related to ultra-stable microwave frequency synthesis and demonstrate the generation of a Kerr comb with GHz intermodal frequency.

All-polymer whispering gallery mode sensor system.

PubMed

Petermann, Ann Britt; Varkentin, Arthur; Roth, Bernhard; Morgner, Uwe; Meinhardt-Wollweber, Merve

2016-03-21

Sensors based on whispering gallery modes have been extensively investigated with respect to their possible application as physical or biological sensors. Instead of using a single resonator, we use an all polymer resonator array as sensing element. A tunable narrowband laser is coupled into a PMMA plate serving as an optical wave guide. PMMA spheres are placed in the evanescent field on the surface of the plate. Due to small size variations, some spheres are in resonance at a given wavelength while others are not. We show that this device is well suited for the determination of an unknown wavelength or for temperature measurements. Moreover, we discuss several general aspects of the sensor concept such as the number and size of sensing elements which are necessary for a correct measurement result, or the maximum acceptable linewidth of the laser.

Whispering galleries and the control of artificial atoms.

PubMed

Forrester, Derek Michael; Kusmartsev, Feodor V

2016-04-28

Quantum computation using artificial-atoms, such as novel superconducting circuits, can be sensitively controlled by external electromagnetic fields. These fields and the self-fields attributable to the coupled artificial-atoms influence the amount of quantum correlation in the system. However, control elements that can operate without complete destruction of the entanglement of the quantum-bits are difficult to engineer. Here we investigate the possibility of using closely-spaced-linear arrays of metallic-elliptical discs as whispering gallery waveguides to control artificial-atoms. The discs confine and guide radiation through the array with small notches etched into their sides that act as scatterers. We focus on π-ring artificial-atoms, which can generate their own spontaneous fluxes. We find that the micro-discs of the waveguides can be excited by terahertz frequency fields to exhibit whispering-modes and that a quantum-phase-gate composed of π-rings can be operated under their influence. Furthermore, we gauge the level of entanglement through the concurrence measure and show that under certain magnetic conditions a series of entanglement sudden-deaths and revivals occur between the two qubits. This is important for understanding the stability and life-time of qubit operations using, for example, a phase gate in a hybrid of quantum technologies composed of control elements and artificial-atoms.

Whispering Gallery Mode Optomechanical Resonator

NASA Technical Reports Server (NTRS)

Aveline, David C.; Strekalov, Dmitry V.; Yu, Nan; Yee, Karl Y.

2012-01-01

Great progress has been made in both micromechanical resonators and micro-optical resonators over the past decade, and a new field has recently emerged combining these mechanical and optical systems. In such optomechanical systems, the two resonators are strongly coupled with one influencing the other, and their interaction can yield detectable optical signals that are highly sensitive to the mechanical motion. A particularly high-Q optical system is the whispering gallery mode (WGM) resonator, which has many applications ranging from stable oscillators to inertial sensor devices. There is, however, limited coupling between the optical mode and the resonator s external environment. In order to overcome this limitation, a novel type of optomechanical sensor has been developed, offering great potential for measurements of displacement, acceleration, and mass sensitivity. The proposed hybrid device combines the advantages of all-solid optical WGM resonators with high-quality micro-machined cantilevers. For direct access to the WGM inside the resonator, the idea is to radially cut precise gaps into the perimeter, fabricating a mechanical resonator within the WGM. Also, a strategy to reduce losses has been developed with optimized design of the cantilever geometry and positions of gap surfaces.

Ultra-high Q terahertz whispering-gallery modes in a silicon resonator

NASA Astrophysics Data System (ADS)

Vogt, Dominik Walter; Leonhardt, Rainer

2018-05-01

We report on the first experimental demonstration of terahertz (THz) whispering-gallery modes (WGMs) with an ultra-high quality factor of 1.5 × 104 at 0.62 THz. The WGMs are observed in a high resistivity float zone silicon spherical resonator coupled to a sub-wavelength silica waveguide. A detailed analysis of the coherent continuous wave THz spectroscopy measurements combined with a numerical model based on Mie-Debye-Aden-Kerker theory allows us to unambiguously identify the observed higher order radial THz WGMs.

Infrared light detection using a whispering-gallery-mode optical microcavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Jiangang, E-mail: jzhu@seas.wustl.edu, E-mail: ozdemir@seas.wustl.edu, E-mail: yang@seas.wustl.edu; Ozdemir, Sahin Kaya, E-mail: jzhu@seas.wustl.edu, E-mail: ozdemir@seas.wustl.edu, E-mail: yang@seas.wustl.edu; Yang, Lan, E-mail: jzhu@seas.wustl.edu, E-mail: ozdemir@seas.wustl.edu, E-mail: yang@seas.wustl.edu

2014-04-28

We demonstrate a thermal infrared (IR) detector based on an ultra-high-quality-factor (Q) whispering-gallery-mode (WGM) microtoroidal silica resonator and investigate its performance to detect IR radiation at 10 μm wavelength. The bandwidth and the sensitivity of the detector are dependent on the power of a probe laser and the detuning between the probe laser and the resonance frequency of the resonator. The microtoroid IR sensor achieved a noise-equivalent-power (NEP) of 7.46 nW, corresponding to an IR intensity of 0.095 mW/cm{sup 2}.

Biochemical component identification by plasmonic improved whispering gallery mode optical resonance based sensor

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Saetchnikov, Anton V.; Schweiger, Gustav; Ostendorf, Andreas

2014-05-01

Experimental data on detection and identification of variety of biochemical agents, such as proteins, microelements, antibiotic of different generation etc. in both single and multi component solutions under varied in wide range concentration analyzed on the light scattering parameters of whispering gallery mode optical resonance based sensor are represented. Multiplexing on parameters and components has been realized using developed fluidic sensor cell with fixed in adhesive layer dielectric microspheres and data processing. Biochemical component identification has been performed by developed network analysis techniques. Developed approach is demonstrated to be applicable both for single agent and for multi component biochemical analysis. Novel technique based on optical resonance on microring structures, plasmon resonance and identification tools has been developed. To improve a sensitivity of microring structures microspheres fixed by adhesive had been treated previously by gold nanoparticle solution. Another technique used thin film gold layers deposited on the substrate below adhesive. Both biomolecule and nanoparticle injections caused considerable changes of optical resonance spectra. Plasmonic gold layers under optimized thickness also improve parameters of optical resonance spectra. Biochemical component identification has been also performed by developed network analysis techniques both for single and for multi component solution. So advantages of plasmon enhancing optical microcavity resonance with multiparameter identification tools is used for development of a new platform for ultra sensitive label-free biomedical sensor.

Observation of defect-assisted enhanced visible whispering gallery modes in ytterbium-doped ZnO microsphere

NASA Astrophysics Data System (ADS)

Khanum, Rizwana; Moirangthem, Rakesh S.; Das, Nayan Mani

2017-06-01

Smooth surfaced and crystalline undoped and ytterbium doped zinc oxide (ZnO) microspheres having an approximate size of 3-5 μm were synthesized by hydrothermal process. Out of these microspheres, a single microparticle was chosen and engaged as a whispering gallery wave microresonator. The defect induced luminescence from an individual ZnO microsphere was investigated with micro-photoluminescence measurement in the spectral range of 565 to 740 nm under the excitation of a green laser having a centered wavelength at 532 nm. The defects-related emissions from a single ZnO microsphere show optical resonance peaks so-called "whispering gallery modes" (WGMs) which are confirmed with the theoretical calculation. Further, ZnO microspheres were chemically doped with the different molar percentages of Ytterbium (Yb), and enhancement in their emission properties was investigated. Our experimental results show that ZnO microspheres with 0.5 mol. % doping of Yb gives the strongest optical emission and has highest Q-factor which can be employed in the development of WGM based optical biosensor or laser.

Single-photon routing with whispering-gallery resonators

NASA Astrophysics Data System (ADS)

Huang, Jin-Song; Zhang, Jia-Hao; Wei, L. F.

2018-04-01

Quantum routing of single photons in a system with two waveguides coupled to two whispering-gallery resonators (WGRs) are investigated theoretically. Using a real-space full quantum theory, photonic scattering amplitudes along four ports of the waveguide network are analytically obtained. It is shown that, by adjusting the geometric and physical parameters of the two-WGR configuration, the quantum routing properties of single photons along the present waveguide network can be controlled effectively. The routing capability from input waveguide to another one can significantly exceed 0.5 near the resonance point of scattering spectra, which can be achieved with only one resonator. By properly designing the distance between two WGRs and the waveguide-WGR coupling strengths, the transfer rate between the waveguides can also reach certain sufficiently high values even in the non-resonance regime. Moreover, Fano-like resonances in the scattering spectra are designable. The proposed system may provide a potential application in controlling single-photon quantum routing.

Vertically-coupled Whispering Gallery Mode Resonator Optical Waveguide, and Methods

NASA Technical Reports Server (NTRS)

Matsko, Andrey B. (Inventor); Savchenkov, Anatolly A. (Inventor); Matleki, Lute (Inventor)

2007-01-01

A vertically-coupled whispering gallery mode (WGM) resonator optical waveguide, a method of reducing a group velocity of light, and a method of making a waveguide are provided. The vertically-coupled WGM waveguide comprises a cylindrical rod portion having a round cross-section and an outer surface. First and second ring-shaped resonators are formed on the outer surface of the cylindrical rod portion and are spaced from each other along a longitudinal direction of the cylindrical rod. The first and second ringshaped resonators are capable of being coupled to each other by way an evanescent field formed in an interior of the cylindrical rod portion.

Selective Coupling Enhances Harmonic Generation of Whispering-Gallery Modes

NASA Astrophysics Data System (ADS)

Trainor, Luke S.; Sedlmeir, Florian; Peuntinger, Christian; Schwefel, Harald G. L.

2018-02-01

We demonstrate second-harmonic generation (SHG) in an x -cut congruent lithium niobate (LN) whispering-gallery mode (WGM) resonator. First, we show theoretically that independent control of the coupling of the pump and signal modes is optimal for high conversion rates. A coupling scheme based on our earlier work [F. Sedlmeir et al., Phys. Rev. Applied 7, 024029 (2017), 10.1103/PhysRevApplied.7.024029] is then implemented experimentally to verify this improvement. Thereby, we are able to improve on the efficiency of SHG by more than an order of magnitude by selectively outcoupling using a LN prism, utilizing the birefringence of it and the resonator in kind. This method is also applicable to other nonlinear processes in WGM resonators.

Demonstration of versatile whispering-gallery micro-lasers for remote refractive index sensing.

PubMed

Wan, Lei; Chandrahalim, Hengky; Zhou, Jian; Li, Zhaohui; Chen, Cong; Cho, Sangha; Zhang, Hui; Mei, Ting; Tian, Huiping; Oki, Yuji; Nishimura, Naoya; Fan, Xudong; Guo, L Jay

2018-03-05

We developed chip-scale remote refractive index sensors based on Rhodamine 6G (R6G)-doped polymer micro-ring lasers. The chemical, temperature, and mechanical sturdiness of the fused-silica host guaranteed a flexible deployment of dye-doped polymers for refractive index sensing. The introduction of the dye as gain medium demonstrated the feasibility of remote sensing based on the free-space optics measurement setup. Compared to the R6G-doped TZ-001, the lasing behavior of R6G-doped SU-8 polymer micro-ring laser under an aqueous environment had a narrower spectrum linewidth, producing the minimum detectable refractive index change of 4 × 10 -4 RIU. The maximum bulk refractive index sensitivity (BRIS) of 75 nm/RIU was obtained for SU-8 laser-based refractive index sensors. The economical, rapid, and simple realization of polymeric micro-scale whispering-gallery-mode (WGM) laser-based refractive index sensors will further expand pathways of static and dynamic remote environmental, chemical, biological, and bio-chemical sensing.

Whispering-Gallery-Mode Resonances: A New Way to Accelerate Charged Particles

NASA Astrophysics Data System (ADS)

Żakowicz, Władysław

2005-09-01

Looking for future high energy accelerators we point at a very strong interaction between relativistic electrons and powerful electromagnetic fields existing in the vicinity of a dielectric cylinder in conditions of resonantly excited whispering gallery modes (WGM). A particular example of the WGM resonance, corresponding to angular index n=22, shows that the accelerating fields are almost 100 times stronger than these in the incident wave. That yields an acceleration rate of about 5GeV/m with the incident microwave radiation beam of the wavelength λ=1cm and a moderately high intensity of P=1MW/cm2.

Robust label-free biosensing using microdisk laser arrays with on-chip references.

PubMed

Wondimu, S F; Hippler, M; Hussal, C; Hofmann, A; Krämmer, S; Lahann, J; Kalt, H; Freude, W; Koos, C

2018-02-05

Whispering-gallery mode (WGM) microdisk lasers show great potential for highly sensitive label-free detection in large-scale sensor arrays. However, when used in practical applications under normal ambient conditions, these devices suffer from temperature fluctuations and photobleaching. Here we demonstrate that these challenges can be overcome by a novel referencing scheme that allows for simultaneous compensation of temperature drift and photobleaching. The technique relies on reference structures protected by locally dispensed passivation materials, and can be scaled to extended arrays of hundreds of devices. We prove the viability of the concept in a series of experiments, demonstrating robust and sensitive label-free detection over a wide range of constant or continuously varying temperatures. To the best of our knowledge, these measurements represent the first demonstration of biosensing in active WGM devices with simultaneous compensation of both photobleaching and temperature drift.

Classification of the micro and nanoparticles and biological agents by neural network analysis of the parameters of optical resonance of whispering gallery mode in dielectric microspheres

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav; Ostendorf, Andreas

2011-07-01

A novel technique for the label-free analysis of micro and nanoparticles including biomolecules using optical micro cavity resonance of whispering-gallery-type modes is being developed. Various schemes of the method using both standard and specially produced microspheres have been investigated to make further development for microbial application. It was demonstrated that optical resonance under optimal geometry could be detected under the laser power of less 1 microwatt. The sensitivity of developed schemes has been tested by monitoring the spectral shift of the whispering gallery modes. Water solutions of ethanol, ascorbic acid, blood phantoms including albumin and HCl, glucose, biotin, biomarker like C reactive protein so as bacteria and virus phantoms (gels of silica micro and nanoparticles) have been used. Structure of resonance spectra of the solutions was a specific subject of investigation. Probabilistic neural network classifier for biological agents and micro/nano particles classification has been developed. Several parameters of resonance spectra as spectral shift, broadening, diffuseness and others have been used as input parameters to develop a network classifier for micro and nanoparticles and biological agents in solution. Classification probability of approximately 98% for probes under investigation have been achieved. Developed approach have been demonstrated to be a promising technology platform for sensitive, lab-on-chip type sensor which can be used for development of diagnostic tools for different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells as well as in different experimental contexts e.g. proteomics, genomics, drug discovery, and membrane studies.

Whispering gallery modes in two-photon fluorescence from spherical DCM dye microresonators

NASA Astrophysics Data System (ADS)

Mamonov, Evgeniy A.; Maydykovskiy, Anton I.; Mitetelo, Nikolai V.; Venkatakrishnarao, Dasari; Chandrasekar, Rajadurai; Murzina, Tatyana V.

2018-03-01

Organic microstructures are well known for their resonator properties, which bring about whispering gallery mode (WGM) excitation. Here we report on experimental evidence of the WGM in the two-photon fluorescence (TPF) of DCM dye microspheres made using the self-assembly method. The WGM excitation accompanying the overall TPF in the spectral range from 530\\div640 nm demonstrated a quality factor of approximately 102 for spheres that were several microns in diameter. The power dependence of the TPF intensity proved the second order nature of the interaction process involved.

Modelling of rotation-induced frequency shifts in whispering gallery modes

NASA Astrophysics Data System (ADS)

Venediktov, V. Yu; Kukaev, A. S.; Filatov, Yu V.; Shalymov, E. V.

2018-02-01

We study the angular velocity sensors based on whispering gallery mode resonators. Rotation of such resonators gives rise to various effects that can cause a spectral shift of their modes. Optical methods allow this shift to be determined with high precision, which can be used practically to measure the angular velocity in inertial orientation and navigation systems. The basic principles of constructing the angular velocity sensors utilising these effects are considered, their advantages and drawbacks are indicated. We also study the interrelation between the effects and the possibility of their mutual influence on each other. Based on the analytical studies of the effects, we consider the possibility of their combined application for angular velocity measurements.

Active chiral control of GHz acoustic whispering-gallery modes

NASA Astrophysics Data System (ADS)

Mezil, Sylvain; Fujita, Kentaro; Otsuka, Paul H.; Tomoda, Motonobu; Clark, Matt; Wright, Oliver B.; Matsuda, Osamu

2017-10-01

We selectively generate chiral surface-acoustic whispering-gallery modes in the gigahertz range on a microscopic disk by means of an ultrafast time-domain technique incorporating a spatial light modulator. Active chiral control is achieved by making use of an optical pump spatial profile in the form of a semicircular arc, positioned on the sample to break the symmetry of clockwise- and counterclockwise-propagating modes. Spatiotemporal Fourier transforms of the interferometrically monitored two-dimensional acoustic fields measured to micron resolution allow individual chiral modes and their azimuthal mode order, both positive and negative, to be distinguished. In particular, for modes with 15-fold rotational symmetry, we demonstrate ultrafast chiral control of surface acoustic waves in a micro-acoustic system with picosecond temporal resolution. Applications include nondestructive testing and surface acoustic wave devices.

Cascaded Brillouin lasing in monolithic barium fluoride whispering gallery mode resonators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Guoping, E-mail: guoping.lin@femto-st.fr; Diallo, Souleymane; Saleh, Khaldoun

2014-12-08

We report the observation of stimulated Brillouin scattering and lasing at 1550 nm in barium fluoride (BaF{sub 2}) crystal. Brillouin lasing was achieved with ultra-high quality (Q) factor monolithic whispering gallery mode mm-size disk resonators. Overmoded resonators were specifically used to provide cavity resonances for both the pump and all Brillouin Stokes waves. Single and multiple Brillouin Stokes radiations with frequency shift ranging from 8.2 GHz up to 49 GHz have been generated through cascaded Brillouin lasing. BaF{sub 2} resonator-based Brillouin lasing can find potential applications for high-coherence lasers and microwave photonics.

Mode-splitting for refractive index sensing in fluorescent whispering gallery mode resonators with broken symmetry

NASA Astrophysics Data System (ADS)

Kang, Yvonne Q.; François, Alexandre; Riesen, Nicolas; Monro, Tanya M.

2018-02-01

Whispering Gallery Mode (WGM) biosensors have been widely exploited over the past decade, owing to their unprecedented detection limits and label free capability. WGM based sensing mechanisms, such as resonance frequency shift, linewidth broadening, and splitting of the two counter-propagating WGMs, have been extensively researched and applied for bio-chemical sensing. However, the mode-splitting of the originally degenerate WGMs from different equatorial planes on a fluorescent microsphere has not been fully investigated. In this work, we break the symmetry of the surrounding environment outside the microsphere by partially embedding the sphere into a high-refractive-index medium (i.e. glue), to lift the degeneracy of the modes from different WGM planes. The split-modes from multiple planes of the fluorescent microsphere are indiscriminately collected. It is found that the effective quality factor Q of the WGMs increases non-conventionally as the Refractive Index (RI) of the probing liquid increases up to the point where it is equal to that of the glue. This presents a new methodology for quantifying changes in the probing environment based on the Q spoiling of the resonances as determined by the RI difference between the environment and that of the reference glue. Furthermore, we find that this sensing platform opens the door to simple self-referenced sensing techniques based on the analysis of the spectral positions of subsets of the split modes.

High quality factor whispering gallery modes from self-assembled hexagonal GaN rods grown by metal-organic vapor phase epitaxy.

PubMed

Tessarek, C; Sarau, G; Kiometzis, M; Christiansen, S

2013-02-11

Self-assembled GaN rods were grown on sapphire by metal-organic vapor phase epitaxy using a simple two-step method that relies first on a nitridation step followed by GaN epitaxy. The mask-free rods formed without any additional catalyst. Most of the vertically aligned rods exhibit a regular hexagonal shape with sharp edges and smooth sidewall facets. Cathodo- and microphotoluminescence investigations were carried out on single GaN rods. Whispering gallery modes with quality factors greater than 4000 were measured demonstrating the high morphological and optical quality of the self-assembled GaN rods.

Combining Whispering-Gallery Mode Optical Biosensors with Microfluidics for Real-Time Detection of Protein Secretion from Living Cells in Complex Media.

PubMed

Chen, Ying-Jen; Schoeler, Ulrike; Huang, Chung-Hsuan Benjamin; Vollmer, Frank

2018-05-01

The noninvasive monitoring of protein secretion of cells responding to drug treatment is an effective and essential tool in latest drug development and for cytotoxicity assays. In this work, a surface functionalization method is demonstrated for specific detection of protein released from cells and a platform that integrates highly sensitive optical devices, called whispering-gallery mode biosensors, with precise microfluidics control to achieve label-free and real-time detection. Cell biomarker release is measured in real time and with nanomolar sensitivity. The surface functionalization method allows for antibodies to be immobilized on the surface for specific detection, while the microfluidics system enables detection in a continuous flow with a negligible compromise between sensitivity and flow control over stabilization and mixing. Cytochrome c detection is used to illustrate the merits of the system. Jurkat cells are treated with the toxin staurosporine to trigger cell apoptosis and cytochrome c released into the cell culture medium is monitored via the newly invented optical microfluidic platform. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly sensitive mode mapping of whispering-gallery modes by scanning thermocouple-probe microscopy.

PubMed

Klein, Angela E; Schmidt, Carsten; Liebsch, Mattes; Janunts, Norik; Dobynde, Mikhail; Tünnermann, Andreas; Pertsch, Thomas

2014-03-01

We propose a method for mapping optical near-fields with the help of a thermocouple scanning-probe microscope tip. As the tip scans the sample surface, its apex is heated by light absorption, generating a thermovoltage. The thermovoltage map represents the intensity distribution of light at the sample surface. The measurement technique has been employed to map optical whispering-gallery modes in fused silica microdisk resonators operating at near-infrared wavelengths. The method could potentially be employed for near-field imaging of a variety of systems in the near-infrared and visible spectral range.

Light scattering by magnons in whispering gallery mode cavities

NASA Astrophysics Data System (ADS)

Sharma, Sanchar; Blanter, Yaroslav M.; Bauer, Gerrit E. W.

2017-09-01

Brillouin light scattering is an established technique to study magnons, the elementary excitations of a magnet. Its efficiency can be enhanced by cavities that concentrate the light intensity. Here, we theoretically study inelastic scattering of photons by a magnetic sphere that supports optical whispering gallery modes in a plane normal to the magnetization. Magnons with low angular momenta scatter the light in the forward direction with a pronounced asymmetry in the Stokes and the anti-Stokes scattering strength, consistent with earlier studies. Magnons with large angular momenta constitute Damon-Eschbach modes which are shown to inelastically reflect light. The reflection spectrum contains either a Stokes or anti-Stokes peak, depending on the direction of the magnetization, a selection rule that can be explained by the chirality of the Damon-Eshbach magnons. The controllable energy transfer can be used to manage the thermodynamics of the magnet by light.

Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques

PubMed Central

Hammond, G. Denise; Vojta, Adam L.; Grant, Sheila A.; Hunt, Heather K.

2016-01-01

The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 106. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring. PMID:27314397

Controlled assembly of organic whispering-gallery-mode microlasers as highly sensitive chemical vapor sensors.

PubMed

Gao, Miaomiao; Wei, Cong; Lin, Xianqing; Liu, Yuan; Hu, Fengqin; Zhao, Yong Sheng

2017-03-09

We demonstrate the fabrication of organic high Q active whispering-gallery-mode (WGM) resonators from π-conjugated polymer by a controlled emulsion-solvent-evaporation method, which can simultaneously provide optical gain and act as an effective resonant cavity. By measuring the shift of their lasing modes on exposure to organic vapor, we successfully monitored the slight concentration variation in the chemical gas. These microlaser sensors demonstrated high detection sensitivity and good signal repeatability under continuous chemical gas treatments. The results offer an effective strategy to design miniaturized optical sensors.

Lithium Niobate Whispering Gallery Resonators: Applications and Fundamental Studies

NASA Astrophysics Data System (ADS)

Maleki, L.; Matsko, A. B.

Optical whispering gallery modes (WGMs) are closed circulating electromagnetic waves undergoing total internal reflection inside an axio-symmetric body of a transparent dielectric that forms a resonator. Radiative losses are negligible in these modes if the radius of the resonator exceeds several tens of wavelengths, and surface scattering losses can be made small with surface conditioning techniques. Thus, the quality factor (Q) in crystalline WGM resonators is limited by material losses that are, nevertheless, extremely small in optical materials. WGM resonators made of LiNbO3 have been successfully used in optics and microwave photonics. The resonators are characterized by narrow bandwidth, in the hundred kilohertz to gigahertz range. A proper choice of highly transparent and/or nonlinear resonator material, like lithium niobate, allows for realization of a number of high performance devices: tunable and multi-pole filters, resonant electro-optic modulators, photonic microwave receivers, opto-electronic microwave oscillators, and parametric frequency converters, among others.

Surface-Enhanced Raman Scattering Using Silica Whispering-Gallery Mode Resonators

NASA Technical Reports Server (NTRS)

Anderson, Mark S.

2013-01-01

The motivation of this work was to have robust spectroscopic sensors for sensitive detection and chemical analysis of organic and molecular compounds. The solution is to use silica sphere optical resonators to provide surface-enhanced spectroscopic signal. Whispering-gallery mode (WGM) resonators made from silica microspheres were used for surface-enhanced Raman scattering (SERS) without coupling to a plasmonic mechanism. Large Raman signal enhancement is observed by exclusively using 5.08-micron silica spheres with 785-nm laser excitation. The advantage of this non-plasmonic approach is that the active substrate is chemically inert silica, thermally stable, and relatively simple to fabricate. The Raman signal enhancement is broadly applicable to a wide range of molecular functional groups including aliphatic hydrocarbons, siloxanes, and esters. Applications include trace organic analysis, particularly for in situ planetary instruments that require robust sensors with consistent response.

High-Q BBO whispering gallery mode resonators

NASA Astrophysics Data System (ADS)

Lin, Guoping; Fürst, Josef U.; Strekalov, Dmitry V.; Grudinin, Ivan S.; Yu, Nan

2013-02-01

We report an investigation on optical whispering gallery mode (WGM) resonators made from non z-cut beta barium borate (BBO) crystals. We first fabricated high quality (Q) factor WGM resonators made of an angle-cut BBO crystal. Q factors of 1×108 level have been demonstrated at various wavelengths including UV. They led to new upper bounds for the absorption coefficients of BBO at 1560 nm, 980 nm and 370 nm. We observed only one set of ordinarily polarized WGMs with polarization rotating along the resonator circumference. We also fabricated xy-cut BBO WGM resonators, in which the optic axis is parallel to the resonator plane. In that case, two WGM families with different polarization exist, one with constant the other with oscillatory phase velocity. This enables a novel way of broadband phase matching in WGM resonators with cyclic gain. We experimentally demonstrated efficient second harmonic generation (SHG) to a wide harmonic wavelength range from 780 nm at near infrared to 317 nm in UV. It is also the first reported direct UV SHG in a high-Q WGM resonator. This work lays a foundation for further investigations of WGM properties of non-z cut birefringent resonators and their applications in nonlinear optics.

Highly efficient optical power transfer to whispering-gallery modes by use of a symmetrical dual-coupling configuration.

PubMed

Cai, M; Vahala, K

2000-02-15

We report that greater than 99.8% optical power transfer to whispering-gallery modes was achieved in fused-silica microspheres by use of a dual-tapered-fiber coupling method. The intrinsic cavity loss and the taper-to-sphere coupling coefficient are inferred from the experimental data. It is shown that the low intrinsic cavity loss and the symmetrical dual-coupling structure are crucial for obtaining the high coupling efficiency.

Exploring the Frequency Stability Limits of Whispering Gallery Mode Resonators for Metrological Applications

NASA Technical Reports Server (NTRS)

Chembo, Yanne K.; Baumgartel, Lukas; Grudinin, Ivan; Strekalov, Dmitry; Thompson, Robert; Yu, Nan

2012-01-01

Whispering gallery mode resonators are attracting increasing interest as promising frequency reference cavities. Unlike commonly used Fabry-Perot cavities, however, they are filled with a bulk medium whose properties have a significant impact on the stability of its resonance frequencies. In this context that has to be reduced to a minimum. On the other hand, a small monolithic resonator provides opportunity for better stability against vibration and acceleration. this feature is essential when the cavity operates in a non-laboratory environment. In this paper, we report a case study for a crystalline resonator, and discuss the a pathway towards the inhibition of vibration-and acceleration-induced frequency fluctuations.

Whispering gallery mode laser based on cholesteric liquid crystal microdroplets as temperature sensor

NASA Astrophysics Data System (ADS)

Zhao, Liyuan; Wang, Yan; Yuan, Yonggui; Liu, Yongjun; Liu, Shuangqiang; Sun, Weimin; Yang, Jun; Li, Hanyang

2017-11-01

We developed a tunable whispering gallery mode (WGM) microlaser based on dye-doped cholesteric liquid crystal (CLC) microdroplets with controllable size in an aqueous environment. An individual dye-doped CLC microdroplet confined at the tip of a microcapillary was optically pumped via a tapered optical fiber tip positioned within its vicinity. Numerical simulations and various spectral characteristics verify the WGM resonance of the lasing in microdroplets. Thermal tuning of the lasing modes is realized due to the thermo-optic effect of CLC. The proposed CLC microdroplet-based WGM resonator was applied as a temperature sensor and exhibited maximum temperature sensitivity up to 0.96 nm/°C.

Highly sensitive detection of nanoparticles with a self-referenced and self-heterodyned whispering-gallery Raman microlaser.

PubMed

Özdemir, Şahin Kaya; Zhu, Jiangang; Yang, Xu; Peng, Bo; Yilmaz, Huzeyfe; He, Lina; Monifi, Faraz; Huang, Steven He; Long, Gui Lu; Yang, Lan

2014-09-16

Optical whispering-gallery-mode resonators (WGMRs) have emerged as promising platforms for label-free detection of nano-objects. The ultimate sensitivity of WGMRs is determined by the strength of the light-matter interaction quantified by quality factor/mode volume, Q/V, and the resolution is determined by Q. To date, to improve sensitivity and precision of detection either WGMRs have been doped with rare-earth ions to compensate losses and increase Q or plasmonic resonances have been exploited for their superior field confinement and lower V. Here, we demonstrate, for the first time to our knowledge, enhanced detection of single-nanoparticle-induced mode splitting in a silica WGMR via Raman gain-assisted loss compensation and WGM Raman microlaser. In particular, the use of the Raman microlaser provides a dopant-free, self-referenced, and self-heterodyned scheme with a detection limit ultimately determined by the thermorefractive noise. Notably, we detected and counted individual nanoparticles with polarizabilities down to 3.82 × 10(-6) μm(3) by monitoring a heterodyne beatnote signal. This level of sensitivity is achieved without exploiting plasmonic effects, external references, or active stabilization and frequency locking. Single nanoparticles are detected one at a time; however, their characterization by size or polarizability requires ensemble measurements and statistical averaging. This dopant-free scheme retains the inherited biocompatibility of silica and could find widespread use for sensing in biological media. The Raman laser and operation band of the sensor can be tailored for the specific sensing environment and the properties of the targeted materials by changing the pump laser wavelength. This scheme also opens the possibility of using intrinsic Raman or parametric gain for loss compensation in other systems where dissipation hinders progress and limits applications.

Studies of geometrical profiling in fabricated tapered optical fibers using whispering gallery modes spectroscopy

NASA Astrophysics Data System (ADS)

Kavungal, Vishnu; Farrell, Gerald; Wu, Qiang; Kumar Mallik, Arun; Semenova, Yuliya

2018-03-01

This paper experimentally demonstrates a method for geometrical profiling of asymmetries in fabricated thin microfiber tapers with waist diameters ranging from ∼10 to ∼50 μm with submicron accuracy. The method is based on the analysis of whispering gallery mode resonances excited in cylindrical fiber resonators as a result of evanescent coupling of light propagating through the fiber taper. The submicron accuracy of the proposed method has been verified by SEM studies. The method can be applied as a quality control tool in fabrication of microfiber based devices and sensors or for fine-tuning of microfiber fabrication set-ups.

High-Q whispering-gallery mode sensor in liquids

NASA Astrophysics Data System (ADS)

Nadeau, Jay L.; Ilchenko, Vladimir S.; Kossakovski, Dmitri; Bearman, Gregory H.; Maleki, Lute

2002-06-01

Optical sensing of biomolecules on microfabricated glass surfaces requires surface coatings that minimize nonspecific binding while preserving the optical properties of the sensor. Microspheres with whispering-gallery (WG) modes can achieve quality factor (Q) levels many orders of magnitude greater than those of other WG-based microsensors: greater than 1010 in air, and greater than 109 in a variety of solvents, including methanol, H2O and phosphate buffered saline (PBS). The presence of dyes that absorb in the wavelength of the WG excitation in the evanescent zone can cause this Q value to drop by almost 3 orders of magnitude. Silanization of the surface with mercapto-terminal silanes is compatible with high Q (>109), but chemical cross-linking of streptavidin reduces the Q to 105-106 due to build-up of a thick, irregular layer of protein. However, linkage of biotin to the silane terminus preserves the Q at a ~2x107 and yields a reactive surface sensitive to avidin-containing ligands in a concentration-dependent manner. Improvements in the reliability of the surface chemistry show promise for construction of an ultrasensitive biosensor.

THz Pyro-Optical Detector Based on LiNbO3 Whispering Gallery Mode Microdisc Resonator

PubMed Central

Cosci, Alessandro; Cerminara, Matteo; Nunzi Conti, Gualtiero; Soria, Silvia; Righini, Giancarlo C.; Pelli, Stefano

2017-01-01

This study analyzes the capabilities of a LiNbO3 whispering gallery mode microdisc resonator as a potential bolometer detector in the THz range. The resonator is theoretically characterized in the stationary regime by its thermo-optic and thermal coefficients. Considering a Q-factor of 107, a minimum detectable power of 20 μW was evaluated, three orders of magnitude above its noise equivalent power. This value opens up the feasibility of exploiting LiNbO3 disc resonators as sensitive room-temperature detectors in the THz range. PMID:28134857

High-Q enhancement of attractive and repulsive optical forces between coupled whispering-gallery- mode resonators.

PubMed

Povinelli, Michelle; Johnson, Steven; Lonèar, Marko; Ibanescu, Mihai; Smythe, Elizabeth; Capasso, Federico; Joannopoulos, J

2005-10-03

We have calculated the optically-induced force between coupled high-Q whispering gallery modes of microsphere resonators. Attractive and repulsive forces are found, depending whether the bi-sphere mode is symmetric or antisymmetric. The magnitude of the force is linearly proportional to the total power in the spheres and consequently linearly enhanced by Q. Forces on the order of 100 nN are found for Q=108, large enough to cause displacements in the range of 1mum when the sphere is attached to a fiber stem with spring constant 0.004 N/m.

Self-assembled dye-doped polymer microspheres as whispering gallery mode lasers

NASA Astrophysics Data System (ADS)

Chen, Xiaogang; Sun, Hongyi; Yang, Hongqin; Wu, Xiang; Xie, Shusen

2016-10-01

Microlasers based on high-Q whispering-gallery-mode (WGM) resonances are promising low-threshold laser sources for bio-sensing and imaging applications. In this talk, we demonstrate a cost effective approach to obtain size-controllable polymer microspheres, which can be served as good WGM microcavities. By injecting SU-8 solution into low-refractiveindex UV polymer, self-assembled spherical droplet with smooth surface can be created inside the elastic medium and then solidified by UV exposure. The size of the microspheres can be tuned from several to hundreds of microns. WGM Lasing has been achieved by optically pumping the dye-doped microspheres with ns lasers. Experimental results show that the microsphere lasers have high quality factors and low lasing thresholds. The self-assembled dye-doped polymer microspheres would provide an excellent platform for the micro-laser sources in on-chip biosensing and imaging systems.

Possibility of measuring the Abraham force using whispering gallery modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brevik, I.; Ellingsen, S. A.

2010-06-15

Critical experimental tests of the time-dependent Abraham force in phenomenological electrodynamics are scarce. In this paper, we analyze the possibility of making use of intensity-modulated whispering gallery modes in a microresonator for this purpose. Systems of this kind appear attractive, as the strong concentration of electromagnetic fields near the rim of the resonator serves to enhance the Abraham torque exerted by the field. We analyze mainly spherical resonators, although as an introductory step we consider also the cylinder geometry. The orders of magnitude of the Abraham torques are estimated by inserting reasonable and common values for the various input parameters.more » As expected, the predicted torques turn out to be very small, although probably not beyond reach experimentally. Our main idea is essentially a generalization of the method used by G. B. Walker et al.[Can. J. Phys. 53, 2577 (1975)] for low-frequency fields, to the optical case.« less

Protein-based flexible whispering gallery mode resonators

NASA Astrophysics Data System (ADS)

Yilmaz, Huzeyfe; Pena-Francesch, Abdon; Xu, Linhua; Shreiner, Robert; Jung, Huihun; Huang, Steven H.; Özdemir, Sahin K.; Demirel, Melik C.; Yang, Lan

2016-02-01

The idea of creating photonics tools for sensing, imaging and material characterization has long been pursued and many achievements have been made. Approaching the level of solutions provided by nature however is hindered by routine choice of materials. To this end recent years have witnessed a great effort to engineer mechanically flexible photonic devices using polymer substrates. On the other hand, biodegradability and biocompatibility still remains to be incorporated. Hence biomimetics holds the key to overcome the limitations of traditional materials in photonics design. Natural proteins such as sucker ring teeth (SRT) and silk for instance have remarkable mechanical and optical properties that exceed the endeavors of most synthetic and natural polymers. Here we demonstrate for the first time, toroidal whispering gallery mode resonators (WGMR) fabricated entirely from protein structures such as SRT of Loligo vulgaris (European squid) and silk from Bombyx mori. We provide here complete optical and material characterization of proteinaceous WGMRs, revealing high quality factors in microscale and enhancement of Raman signatures by a microcavity. We also present a most simple application of a WGMR as a natural protein add-drop filter, made of SRT protein. Our work shows that with protein-based materials, optical, mechanical and thermal properties can be devised at the molecular level and it lays the groundwork for future eco-friendly, flexible photonics device design.

Nanoscale welding aerosol sensing based on whispering gallery modes in a cylindrical silica resonator.

PubMed

Lee, Aram; Mills, Thomas; Xu, Yong

2015-03-23

We report an experimental technique where one uses a standard silica fiber as a cylindrical whispering gallery mode (WGM) resonator to sense airborne nanoscale aerosols produced by electric arc welding. We find that the accumulation of aerosols on the resonator surface induces a measurable red-shift in resonance frequency, and establish an empirical relation that links the magnitude of resonance shift with the amount of aerosol deposition. The WGM quality factors, by contrast, do not decrease significantly, even for samples with a large percentage of surface area covered by aerosols. Our experimental results are discussed and compared with existing literature on WGM-based nanoparticle sensing.

Whispering gallery states of neutrons and anti-hydrogen atoms and their applications to fundamental and surface physics

NASA Astrophysics Data System (ADS)

Nesvizhevsky, Valery

2013-03-01

The `whispering gallery' effect has been known since ancient times for sound waves in air, later in water and more recently for a broad range of electromagnetic waves: radio, optics, Roentgen and so on. It is intensively used and explored due to its numerous crucial applications. It consists of wave localization near a curved reflecting surface and is expected for waves of various natures, for instance, for neutrons and (anti)atoms. For (anti)matter waves, it includes a new feature: a massive particle is settled in quantum states, with parameters depending on its mass. In this talk, we present the first observation of the quantum whispering-gallery effect for matter particles (cold neutrons) 1-2. This phenomenon provides an example of an exactly solvable problem analogous to the `quantum bouncer'; it is complementary to recently discovered gravitational quantum states of neutrons3. These two phenomena provide a direct demonstration of the weak equivalence principle for a massive particle in a quantum state. Deeply bound long-living states are weakly sensitive to surface potential; highly excited short-living states are very sensitive to the wall nuclear potential shape. Therefore, they are a promising tool for studying fundamental neutron-matter interactions, quantum neutron optics and surface physics effects. Analogous phenomena could be measured with atoms and anti-atoms 4-5.

Quantification of whispering gallery mode spectrum variability in application to sensing nanobiophotonics

NASA Astrophysics Data System (ADS)

Saetchnikov, Anton; Skakun, Victor; Saetchnikov, Vladimir; Tcherniavskaia, Elina; Ostendorf, Andreas

2017-10-01

An approach for the automated whispering gallery mode (WGM) signal decomposition and its parameter estimation is discussed. The algorithm is based on the peak picking and can be applied for the preprocessing of the raw signal acquired from the multiplied WGM-based biosensing chips. Quantitative estimations representing physically meaningful parameters of the external disturbing factors on the WGM spectral shape are the output values. Derived parameters can be directly applied to the further deep qualitative and quantitative interpretations of the sensed disturbing factors. The algorithm is tested on both simulated and experimental data taken from the bovine serum albumin biosensing task. The proposed solution is expected to be a useful contribution to the preprocessing phase of the complete data analysis engine and is expected to push the WGM technology toward the real-live sensing nanobiophotonics.

Optimal coupling to high-Q whispering gallery modes with a sub-wavelength metallic grating coupler

NASA Astrophysics Data System (ADS)

Zhou, Y.; Gu, B.; Yu, X.; Luan, F.

2015-03-01

Gold grating patterned on the end facet of an optical fiber is able to excite whispering gallery mode (WGM) in a silica microsphere. With a direct pathway of the metal reflection, the coupled WGM is able to superimpose and create an asymmetric Fano resonance. Since multiple resonances are present - the WGM, grating reflection, and a weak Fabry-Perot resonance along the diameter of the sphere - it is difficult to evaluate the power efficiency directly from the measured spectrum. Using temporal coupled-mode theory, a general model is constructed for the end-fire coupling from a grating to a WGM resonator.

Phase-Array Approach to Optical Whispering Gallery Modulators

NASA Technical Reports Server (NTRS)

Strekalov, Dmitry

2010-01-01

This technology leverages the well-defined orbital number of a whispering gallery modulator (WGM) to expand the range of applications for such resonators. This property rigidly connects the phase variation of the field in this mode with the azimuthal angle between the coupling locations. A WGM with orbital momentum L has exactly L instant nodes around the circumference of the WGM resonator supporting such a mode. Therefore, in two locations separated by the arc alpha, the phase difference of such a field will be equal to phi= alpha L. Coupling the field out of such locations, and into a balanced interferometer, once can observe a complete constructive or distractive interference (or have any situation in between) depending on the angle alpha. Similarly, a mode L + delta L will pick up the phase phi + alpha delta L. In all applications of a WGM resonator as a modulator, the orbital numbers for the carrier and sidebands are different, and their differences delta L are known (usually, but not necessarily, delta L = 1). Therefore, the choice of the angle alpha, and of the interferometer arms difference, allows one to control the relative phase between different modes and to perform the conversion, separation, and filtering tasks necessary.

Using Whispering-Gallery-Mode Resonators for Refractometry

NASA Technical Reports Server (NTRS)

Matsko, Andrey; Savchenkov, Anatoliy; Strekalov, Dmitry; Iltchenko, Vladimir; Maleki, Lute

2010-01-01

A method of determining the refractive and absorptive properties of optically transparent materials involves a combination of theoretical and experimental analysis of electromagnetic responses of whispering-gallery-mode (WGM) resonator disks made of those materials. The method was conceived especially for use in studying transparent photorefractive materials, for which purpose this method affords unprecedented levels of sensitivity and accuracy. The method is expected to be particularly useful for measuring temporally varying refractive and absorptive properties of photorefractive materials at infrared wavelengths. Still more particularly, the method is expected to be useful for measuring drifts in these properties that are so slow that, heretofore, the properties were assumed to be constant. The basic idea of the method is to attempt to infer values of the photorefractive properties of a material by seeking to match (1) theoretical predictions of the spectral responses (or selected features thereof) of a WGM of known dimensions made of the material with (2) the actual spectral responses (or selected features thereof). Spectral features that are useful for this purpose include resonance frequencies, free spectral ranges (differences between resonance frequencies of adjacently numbered modes), and resonance quality factors (Q values). The method has been demonstrated in several experiments, one of which was performed on a WGM resonator made from a disk of LiNbO3 doped with 5 percent of MgO. The free spectral range of the resonator was approximately equal to 3.42 GHz at wavelengths in the vicinity of 780 nm, the smallest full width at half maximum of a mode was approximately equal to 50 MHz, and the thickness of the resonator in the area of mode localization was 30 microns. In the experiment, laser power of 9 mW was coupled into the resonator with an efficiency of 75 percent, and the laser was scanned over a frequency band 9 GHz wide at a nominal wavelength of

The Role of Transport Phenomena in Whispering Gallery Mode Optical Biosensor Performance

NASA Astrophysics Data System (ADS)

Gamba, Jason

Whispering gallery mode (WGM) optical resonator sensors have emerged as promising tools for label-free detection of biomolecules in solution. These devices have even demonstrated single-molecule limits of detection in complex biological uids. This extraordinary sensitivity makes them ideal for low-concentration analytical and diagnostic measurements, but a great deal of work must be done toward understanding and optimizing their performance before they are capable of reliable quantitative measurents. The present work explores the physical processes behind this extreme sensitivity and how to best take advantage of them for practical applications of this technology. I begin by examining the nature of the interaction between the intense electromagnetic elds that build up in the optical biosensor and the biomolecules that bind to its surface. This work addresses the need for a coherent and thorough physical model that can be used to predict sensor behavior for a range of experimental parameters. While this knowledge will prove critical for the development of this technology, it has also shone a light on nonlinear thermo-optical and optical phenomena that these devices are uniquely suited to probing. The surprisingly rapid transient response of toroidal WGM biosensors despite sub-femtomolar analyte concentrations is also addressed. The development of asymmetric boundary layers around these devices under ow is revealed to enhance the capture rate of proteins from solution compared to the spherical sensors used previously. These lessons will guide the design of ow systems to minimize measurement time and consumption of precious sample, a key factor in any medically relevant assay. Finally, experimental results suggesting that WGM biosensors could be used to improve the quantitative detection of small-molecule biomarkers in exhaled breath condensate demonstrate how their exceptional sensitivity and transient response can enable the use of this noninvasive method to probe

Enhanced Raman scattering of single nanoparticles in a high-Q whispering-gallery microresonator

NASA Astrophysics Data System (ADS)

Liu, Rui-Shan; Jin, Wei-Liang; Yu, Xiao-Chong; Liu, Yong-Chun; Xiao, Yun-Feng

2015-04-01

We study Raman scattering of single nanoparticles coupled to a high-Q whispering-gallery microresonator. It is found that cavity resonances greatly enhance the Raman signal, and the enhancement factor is as high as 108. Unlike the noncavity case, the signal power exhibits a nonmonotonic dependence on particle size, and it reaches the maximum when the Rayleigh scattering loss and the cavity intrinsic loss are comparable. We further analyze how the Raman signal intensity is influenced by different parameters including cavity quality factors and taper-cavity coupling strength. The detection limit of observing single-nanoparticle Raman signal is discussed finally. As a potential application, this mechanism may provide an alternative way to detect specific biological targets without the need of precovered biorecognitions.

Bi-material crystalline whispering gallery mode microcavity structure for thermo-opto-mechanical stabilization

NASA Astrophysics Data System (ADS)

Itobe, Hiroki; Nakagawa, Yosuke; Mizumoto, Yuta; Kangawa, Hiroi; Kakinuma, Yasuhiro; Tanabe, Takasumi

2016-05-01

We fabricated a calcium fluoride (CaF2) whispering gallery mode (WGM) microcavity with a computer controlled ultra-precision cutting process. We observed a thermo-opto-mechanical (TOM) oscillation in the CaF2 WGM microcavity, which may influence the stability of the optical output when the cavity is employed for Kerr comb generation. We studied experimentally and numerically the mechanism of the TOM oscillation and showed that it is strongly dependent on cavity diameter. In addition, our numerical study suggests that a microcavity structure fabricated with a hybrid material (i.e. CaF2 and silicon), which is compatible with an ultra-high Q and high thermal conductivity, will allow us to reduce the TOM oscillation and stabilize the optical output.

Ringing phenomenon in coupled cavities: Application to modal coupling in whispering-gallery-mode resonators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trebaol, Stephane; Dumeige, Yannick; Feron, Patrice

We present a simple model to describe the transient response of two coupled resonators probed by a monochromatic wave whose frequency is rapidly swept across the resonances with respect to their characteristic photon lifetimes. The model is applied to analyze the dynamic behavior of the modal coupling between two degenerate resonances of the same cavity. In particular, this can be used to describe the coupling of counterpropagating whispering gallery modes (WGMs) by Rayleigh scattering. The theory is successfully compared to experiments carried out in silica microspheres. These results show that this ringdown technique can be extended to accurately measure linearmore » properties and frequency splittings of high-quality factor WGM microresonators.« less

All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers.

PubMed

Wienhold, T; Kraemmer, S; Wondimu, S F; Siegle, T; Bog, U; Weinzierl, U; Schmidt, S; Becker, H; Kalt, H; Mappes, T; Koeber, S; Koos, C

2015-09-21

We present an all-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers integrated into a microfluidic chip. The chip is entirely made from polymers, enabling the use of the devices as low-cost disposables. The microgoblet cavities feature quality factors exceeding 10(5) and are fabricated from poly(methyl methacrylate) (PMMA) using spin-coating, mask-based optical lithography, wet chemical etching, and thermal reflow. In contrast to silica-based microtoroid resonators, this approach replaces technically demanding vacuum-based dry etching and serial laser-based reflow techniques by solution-based processing and parallel thermal reflow. This enables scaling to large-area substrates, and hence significantly reduces device costs. Moreover, the resonators can be fabricated on arbitrary substrate materials, e.g., on transparent and flexible polymer foils. Doping the microgoblets with the organic dye pyrromethene 597 transforms the passive resonators into lasers. Devices have lasing thresholds below 0.6 nJ per pulse and can be efficiently pumped via free-space optics using a compact and low-cost green laser diode. We demonstrate that arrays of microgoblet lasers can be readily integrated into a state-of-the-art microfluidic chip replicated via injection moulding. In a proof-of-principle experiment, we show the viability of the lab-on-a-chip via refractometric sensing, demonstrating a bulk refractive index sensitivity (BRIS) of 10.56 nm per refractive index unit.

Gyrotron whispering gallery mode coupler with a mode conversion reflector for exciting a circular symmetric uniform phase RF beam in a corrugated waveguide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neilson, Jeffrey M.

A cylindrical waveguide with a mode converter transforms a whispering gallery mode from a gyrotron cylindrical waveguide with a helical cut launch edge to a quasi-Gaussian beam suitable for conveyance through a corrugated waveguide. This quasi-Gaussian beam is radiated away from the waveguide using a spiral cut launch edge, which is in close proximity to a first mode converting reflector. The first mode converting reflector is coupled to a second mode converting reflector which provides an output free-space HE11 mode wave suitable for direct coupling into a corrugated waveguide. The radiated beam produced at the output of the second modemore » converting reflector is substantially circular.« less

Mode conversion in a tapered fiber via a whispering gallery mode resonator and its application as add/drop filter.

PubMed

Huang, Ligang; Wang, Jie; Peng, Weihua; Zhang, Wending; Bo, Fang; Yu, Xuanyi; Gao, Feng; Chang, Pengfa; Song, Xiaobo; Zhang, Guoquan; Xu, Jingjun

2016-02-01

Based on the conversion between the fundamental mode (LP01) and the higher-order mode (LP11) in a tapered fiber via a whispering gallery mode resonator, an add/drop filter was proposed and demonstrated experimentally, in which the resonator only interacted with one tapered fiber, rather than two tapered fibers as in conventional configurations. The filter gains advantages of easy alignment and low scattering loss over the other filters based on tapered fiber and resonator, and will be useful in application.

Tunable liquid-crystal microshell-laser based on whispering-gallery modes and photonic band-gap mode lasing.

PubMed

Lu, Yuelan; Yang, Yue; Wang, Yan; Wang, Lei; Ma, Ji; Zhang, Lingli; Sun, Weimin; Liu, Yongjun

2018-02-05

The lasing behaviors of dye-doped cholesteric liquid crystal (DDCLC) microshells fabricated with silica-glass-microsphere coated DDCLCs were examined. Lasing characteristics were studied in a carrier medium with different refractive indices. The lasing in spherical cholesteric liquid crystals (CLCs) was attributed to two mechanisms, photonic band-gap (PBG) lasing and whispering-gallery modes (WGMs), which can independently exist by varying the chiral agent concentration and pumping energy. It was also found that DDCLC microshells can function as highly sensitive thermal sensors, with a temperature sensitivity of 0.982 nm °C -1 in PBG modes and 0.156 nm °C -1 in WGMs.

Label-free, single-object sensing with a microring resonator: FDTD simulation.

PubMed

Nguyen, Dan T; Norwood, Robert A

2013-01-14

Label-free, single-object sensing with a microring resonator is investigated numerically using the finite difference time-domain (FDTD) method. A pulse with ultra-wide bandwidth that spans over several resonant modes of the ring and of the sensing object is used for simulation, enabling a single-shot simulation of the microring sensing. The FDTD simulation not only can describe the circulation of the light in a whispering-gallery-mode (WGM) microring and multiple interactions between the light and the sensing object, but also other important factors of the sensing system, such as scattering and radiation losses. The FDTD results show that the simulation can yield a resonant shift of the WGM cavity modes. Furthermore, it can also extract eigenmodes of the sensing object, and therefore information from deep inside the object. The simulation method is not only suitable for a single object (single molecule, nano-, micro-scale particle) but can be extended to the problem of multiple objects as well.

Hybrid systems of AlInP microdisks and colloidal CdSe nanocrystals showing whispering-gallery modes at room temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strelow, Christian; Weising, Simon; Bonatz, Dennis

2014-09-01

We report on the realization of hybrid systems composed of passive optical microdisk resonators prepared from epitaxial layer systems and nanocrystal quantum emitters synthesized by colloidal chemistry. The AlInP disk material allows for the operation in the visible range, as probed by CdSe-based nanocrystals. Photoluminescence spectra at room temperature reveal sets of whispering-gallery modes consistent with finite-difference time-domain simulations. In the experiments, a special sample geometry renders it possible to detect resonant optical modes perpendicular to the disk plane.

Optically pumped whispering-gallery mode lasing from 2-μm GaN micro-disks pivoted on Si

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yiyun; Ma, Zetao; Zhang, Xuhui

2014-06-02

2-μm micro-disks containing InGaN/GaN quantum wells supported on a tiny Si nanotip are fabricated via microsphere lithography followed by dry and wet etch processes. The micro-disks are studied by photoluminescence at both room-temperature and 10 K. Optically pumped blue lasing at room-temperature is observed via whispering-gallery modes (WGMs) with a lasing threshold as low as 8.43 mJ/cm{sup 2}. Optical resonances in the micro-disks are studied through numerical computations and finite-difference time-domain simulations. The WGMs are further confirmed through the measured broadband transmission spectrum, whose transmission minima coincide well with predicted WGM frequencies.

Single Mode ZnO Whispering-Gallery Submicron Cavity and Graphene Improved Lasing Performance.

PubMed

Li, Jitao; Lin, Yi; Lu, Junfeng; Xu, Chunxiang; Wang, Yueyue; Shi, Zengliang; Dai, Jun

2015-07-28

Single-mode ultraviolet (UV) laser of ZnO is still in challenge so far, although it has been paid great attention along the past decades. In this work, single-mode lasing resonance was realized in a submicron-sized ZnO rod based on serially varying the dimension of the whispering-gallery mode (WGM) cavities. The lasing performance, such as the lasing quality factor (Q) and the lasing intensity, was remarkably improved by facilely covering monolayer graphene on the ZnO submicron-rod. The mode structure evolution from multimodes to single-mode was investigated systematically based on the total internal-wall reflection of the ZnO microcavities. Graphene-induced optical field confinement and lasing emission enhancement were revealed, indicating an energy coupling between graphene SP and ZnO exciton emission. This result demonstrated the response of graphene in the UV wavelength region and extended its potential applications besides many previous reports on the multifunctional graphene/semiconductor hybrid materials and devices in advanced electronics and optoelectronics areas.

Multiwavelength optical source at 12.5-GHz optical spacing based on a coupled optoelectronic oscillator with a whispering gallery mode resonator

NASA Astrophysics Data System (ADS)

Kossakovski, Dmitri; Solomatine, Iouri V.; Morozov, Nikolai; Ilchenko, Vladimir S.

2004-06-01

The evolution of optical networks calls for denser channel grids and increased number of channels. Additionally, there is a system architecture benefit to eliminate the banks of DFB lasers that act as light sources for individual channels, and use instead a single multi-wavelength source. We have demonstrated a compact multi-wavelength optical source (MWS) for 12.5 GHz DWDM. At least 16 channels are observed within 3 dB optical power bandwidth with optical spectrum contrast ratio exceeding 28 dB. The source is based on a coupled opto-electronic oscillator (COEO) with an optical whispering gallery mode (WGM) microresonator. Free spectral range of the resonator determines the spacing of the optical channels in the MWS. The spacing can be scaled up or down depending on design requirements. The resonator is robustly packaged and fiber pigtailed. In the RF domain the MWS acts as oscillator with operational frequency of 12.5 GHz.

A Fiber-Tip Label-Free Biological Sensing Platform: A Practical Approach toward In-Vivo Sensing

PubMed Central

François, Alexandre; Reynolds, Tess; Monro, Tanya M.

2015-01-01

The platform presented here was devised to address the unmet need for real time label-free in vivo sensing by bringing together a refractive index transduction mechanism based on Whispering Gallery Modes (WGM) in dye doped microspheres and Microstructured Optical Fibers. In addition to providing remote excitation and collection of the WGM signal, the fiber provides significant practical advantages such as an easy manipulation of the microresonator and the use of this sensor in a dip sensing architecture, alleviating the need for a complex microfluidic interface. Here, we present the first demonstration of the use of this approach for biological sensing and evaluate its limitation in a sensing configuration deprived of liquid flow which is most likely to occur in an in vivo setting. We also demonstrate the ability of this sensing platform to be operated above its lasing threshold, enabling enhanced device performance. PMID:25585104

Comparison of various excitation and detection schemes for dye-doped polymeric whispering gallery mode micro-lasers.

PubMed

Siegle, Tobias; Kellerer, Jonas; Bonenberger, Marielle; Krämmer, Sarah; Klusmann, Carolin; Müller, Marius; Kalt, Heinz

2018-02-05

We compare different excitation and collection configurations based on free-space optics and evanescently coupled tapered fibers for both lasing and fluorescence emission from dye-doped doped polymeric whispering gallery mode (WGM) micro-disk lasers. The focus of the comparison is on the lasing threshold and efficiency of light collection. With the aid of optical fibers, we localize the pump energy to the cavity-mode volume and reduce the necessary pump energy to achieve lasing by two orders of magnitude. When using fibers for detection, the collection efficiency is enhanced by four orders of magnitude compared to a free-space read-out perpendicular to the resonator plane. By enhancing the collection efficiency we are able to record a pronounced modulation of the dye fluorescence under continuous wave (cw) pumping conditions evoked by coupling to the WGMs. Alternatively to fibers as a collection tool, we present a read-out technique based on the detection of in-plane radiated light. We show that this method is especially beneficial in an aqueous environment as well as for size-reduced micro-lasers where radiation is strongly pronounced. Furthermore, we show that this technique allows for the assignment of transverse electric (TE) and transverse magnetic (TM) polarization to the observed fundamental modes in a water environment by performing polarization-dependent photoluminescence (PL) spectroscopy. We emphasize the importance of the polarization determination for sensing applications and verify expected differences in the bulk refractive index sensitivity for TE and TM WGMs experimentally.

Few-Mode Whispering-Gallery-Mode Resonators

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy; Strekalov, Dmitry; Matsko, Andrey; Iltchenko, Vladimir; Maleki, Lute

2006-01-01

Whispering-gallery-mode (WGM) optical resonators of a type now under development are designed to support few well-defined waveguide modes. In the simplest case, a resonator of this type would support one equatorial family of WGMs; in a more complex case, such a resonator would be made to support two, three, or some other specified finite number of modes. Such a resonator can be made of almost any transparent material commonly used in optics. The nature of the supported modes does not depend on which material is used, and the geometrical dispersion of this resonator is much smaller than that of a typical prior WGM resonator. Moreover, in principle, many such resonators could be fabricated as integral parts of a single chip. Basically, a resonator of this type consists of a rod, made of a suitable transparent material, from which protrudes a thin circumferential belt of the same material. The belt is integral with the rest of the rod (see figure) and acts as a circumferential waveguide. If the depth (d) and width (w) of the belt are made appropriately small, then the belt acts as though it were the core of a single-mode optical fiber: the belt and its adjacent supporting rod material support a single, circumferentially propagating mode or family of modes. It has been shown theoretically that the fiber-optic-like behavior of the belton- rod resonator structure can be summarized, in part, by the difference, Dn, between (1) an effective index of refraction of an imaginary fiber core and (2) the index of refraction (n) of the transparent rod/belt material. It has also been shown theoretically that for a given required value of Dn, the required depth of the belt can be estimated as d R Dn, where R is the radius of the rod. It must be emphasized that this estimated depth is independent of n and, hence, is independent of the choice of rod material. As in the cases of prior WGM resonators, input/output optical coupling involves utilization of evanescent fields. In the

Hyperparametric effects in a whispering-gallery mode rutile dielectric resonator at liquid helium temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nand, Nitin R.; Goryachev, Maxim; Floch, Jean-Michel le

2014-10-07

We report the first observation of low power drive level sensitivity, hyperparametric amplification, and single-mode hyperparametric oscillations in a dielectric rutile whispering-gallery mode resonator at 4.2 K. The latter gives rise to a comb of sidebands at 19.756 GHz. Whereas, most frequency combs in the literature have been observed in optical systems using an ensemble of equally spaced modes in microresonators or fibers, the present work represents generation of a frequency comb using only a single-mode. The experimental observations are explained by an additional 1/2 degree-of-freedom originating from an intrinsic material nonlinearity at optical frequencies, which affects the microwave propertiesmore » due to the extremely low loss of rutile. Using a model based on lumped circuits, we demonstrate that the resonance between the photonic and material 1/2 degree-of-freedom, is responsible for the hyperparametric energy transfer in the system.« less

Superpersistent currents and whispering gallery modes in relativistic quantum chaotic systems

PubMed Central

Xu, Hongya; Huang, Liang; Lai, Ying-Cheng; Grebogi, Celso

2015-01-01

Persistent currents (PCs), one of the most intriguing manifestations of the Aharonov-Bohm (AB) effect, are known to vanish for Schrödinger particles in the presence of random scatterings, e.g., due to classical chaos. But would this still be the case for Dirac fermions? Addressing this question is of significant value due to the tremendous recent interest in two-dimensional Dirac materials. We investigate relativistic quantum AB rings threaded by a magnetic flux and find that PCs are extremely robust. Even for highly asymmetric rings that host fully developed classical chaos, the amplitudes of PCs are of the same order of magnitude as those for integrable rings, henceforth the term superpersistent currents (SPCs). A striking finding is that the SPCs can be attributed to a robust type of relativistic quantum states, i.e., Dirac whispering gallery modes (WGMs) that carry large angular momenta and travel along the boundaries. We propose an experimental scheme using topological insulators to observe and characterize Dirac WGMs and SPCs, and speculate that these features can potentially be the base for a new class of relativistic qubit systems. Our discovery of WGMs in relativistic quantum systems is remarkable because, although WGMs are common in photonic systems, they are relatively rare in electronic systems. PMID:25758591

Superpersistent currents and whispering gallery modes in relativistic quantum chaotic systems.

PubMed

Xu, Hongya; Huang, Liang; Lai, Ying-Cheng; Grebogi, Celso

2015-03-11

Persistent currents (PCs), one of the most intriguing manifestations of the Aharonov-Bohm (AB) effect, are known to vanish for Schrödinger particles in the presence of random scatterings, e.g., due to classical chaos. But would this still be the case for Dirac fermions? Addressing this question is of significant value due to the tremendous recent interest in two-dimensional Dirac materials. We investigate relativistic quantum AB rings threaded by a magnetic flux and find that PCs are extremely robust. Even for highly asymmetric rings that host fully developed classical chaos, the amplitudes of PCs are of the same order of magnitude as those for integrable rings, henceforth the term superpersistent currents (SPCs). A striking finding is that the SPCs can be attributed to a robust type of relativistic quantum states, i.e., Dirac whispering gallery modes (WGMs) that carry large angular momenta and travel along the boundaries. We propose an experimental scheme using topological insulators to observe and characterize Dirac WGMs and SPCs, and speculate that these features can potentially be the base for a new class of relativistic qubit systems. Our discovery of WGMs in relativistic quantum systems is remarkable because, although WGMs are common in photonic systems, they are relatively rare in electronic systems.

Optothermal transport behavior in whispering gallery mode optical cavities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soltani, Soheil; Armani, Andrea M., E-mail: armani@usc.edu; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089

Over the past century, whispering gallery mode optical cavities have enabled numerous advances in science and engineering, such as discoveries in quantum mechanics and non-linear optics, as well as the development of optical gyroscopes and add drop filters. One reason for their widespread appeal is their ability to confine light for long periods of time, resulting in high circulating intensities. However, when sufficiently large amounts of optical power are coupled into these cavities, they begin to experience optothermal or photothermal behavior, in which the optical energy is converted into heat. Above the optothermal threshold, the resonance behavior is no longermore » solely defined by electromagnetics. Previous work has primarily focused on the role of the optothermal coefficient of the material in this instability. However, the physics of this optothermal behavior is significantly more complex. In the present work, we develop a predictive theory based on a generalizable analytical expression in combination with a geometry-specific COMSOL Multiphysics finite element method model. The simulation couples the optical and thermal physics components, accounting for geometry variations as well as the temporal and spatial profile of the optical field. To experimentally verify our theoretical model, the optothermal thresholds of a series of silica toroidal resonant cavities are characterized at different wavelengths (visible through near-infrared) and using different device geometries. The silica toroid offers a particularly rigorous case study for the developed optothermal model because of its complex geometrical structure which provides multiple thermal transport paths.« less

What is and what is not electromagnetically induced transparency in whispering-gallery microcavities.

PubMed

Peng, Bo; Özdemir, Sahin Kaya; Chen, Weijian; Nori, Franco; Yang, Lan

2014-10-24

There has been an increasing interest in all-optical analogues of electromagnetically induced transparency and Autler-Townes splitting. Despite the differences in their underlying physics, both electromagnetically induced transparency and Autler-Townes splitting are quantified by a transparency window in the absorption or transmission spectrum, which often leads to a confusion about its origin. While the transparency window in electromagnetically induced transparency is a result of Fano interference among different transition pathways, in Autler-Townes splitting it is the result of strong field-driven interactions leading to the splitting of energy levels. Being able to tell objectively whether an observed transparency window is because of electromagnetically induced transparency or Autler-Townes splitting is crucial for applications and for clarifying the physics involved. Here we demonstrate the pathways leading to electromagnetically induced transparency, Fano resonances and Autler-Townes splitting in coupled whispering-gallery-mode resonators. Moreover, we report the application of the Akaike Information Criterion discerning between all-optical analogues of electromagnetically induced transparency and Autler-Townes splitting and clarifying the transition between them.

Giant thermo-optical relaxation oscillations in millimeter-size whispering gallery mode disk resonators.

PubMed

Diallo, Souleymane; Lin, Guoping; Chembo, Yanne K

2015-08-15

In this Letter, we show that giant thermo-optical oscillations can be triggered in millimeter (mm)-size whispering gallery mode (WGM) disk resonators when they are pumped by a resonant continuous-wave laser. Our resonator is an ultrahigh-Q barium fluoride cavity that features a positive thermo-optic coefficient and a negative thermo-elastic coefficient. We demonstrate for the first time, to our knowledge, that the complex interplay between these two thermic coefficients and the intrinsic Kerr nonlinearity yields very sharp slow-fast relaxation oscillations with a slow timescale that can be exceptionally large, typically of the order of 1 s. We use a time-domain model to gain understanding into this instability, and we find that both the experimental and theoretical results are in excellent agreement. The understanding of these thermal effects is an essential requirement for every WGM-related application and our study demonstrates that even in the case of mm-size resonators, such effects can still be accurately analyzed using nonlinear time-domain models.

New spherical optical cavities with non-degenerated whispering gallery modes

NASA Astrophysics Data System (ADS)

Kumagai, Tsutaru; Palma, Giuseppe; Prudenzano, Francesco; Kishi, Tetsuo; Yano, Tetsuji

2017-02-01

New spherical resonators with internal defects are introduced to show anomalous whispering gallery modes (WGMs). The defect induces a symmetry breaking spherical cavity and splits the WGMs. A couple of defects, a hollow sphere (bubble), and a hollow ring, have been studied. The hollow sphere was fabricated and the splitting of WGM was observed. In this paper, this "non-degenerated WGMs (non-DWGMs) resonance" in a microsphere with hollow defect structure is reviewed based on our research. The resonance of WGMs in a sphere is identified by three integer parameters: the angular mode number, l, azimuthal mode number m, and radial mode number, n. The placement of the defect such as a hollow ring or single bubble is shown to break symmetry and resolve the degeneracy concerning m. This induces a variety of resonant wavelengths of the spherical cavity. A couple of simulations using the eigenmode and transient analyses propose how the placed defects affect the WGM resonance in the spherical cavity. For the sphere with a single bubble defect, the experimentally observed resonances in Nd-doped tellurite glass microsphere with a single bubble are clarified to be due to the splitting of resonance modes, i.e., the existence of "non-DWGMs" in the sphere. The defect bubble plays a role of opening the optically wide gate to introduce excitation light for Nd3+ pumping using non-DWGMs in the sphere efficiently.

Tapered optical fiber waveguide coupling to whispering gallery modes of liquid crystal microdroplet for thermal sensing application.

PubMed

Wang, Yan; Li, Hanyang; Zhao, Liyuan; Liu, Yongjun; Liu, Shuangqiang; Yang, Jun

2017-01-23

We demonstrate efficient coupling to the optical whispering gallery modes (WGMs) of nematic liquid crystal (NLC) microdroplets immersed in an immiscible aqueous environment. An individual NLC microdroplet, confined at the tip of a microcapillary, was coupled via a tapered optical fiber waveguide positioned correctly within its vicinity. Critical coupling of the taper-microdroplet system was facilitated by adjusting the gap between the taper and the microdroplet to change the overlap of the evanescent electromagnetic fields; efficient and controlled power transfer from the taper waveguide to the NLC microdroplet is indeed possible via the proposed technique. We also found that NLC microdroplets can function as highly sensitive thermal sensors: A maximum temperature sensitivity of 267.6 pm/°C and resolution of 7.5 × 10^-2 °C were achieved in a 78-μm-diameter NLC microdroplet.

Electrically tunable whispering gallery mode microresonator based on a grapefruit-microstructured optical fiber infiltrated with nematic liquid crystals.

PubMed

Yang, Chengkun; Zhang, Hao; Liu, Bo; Lin, Shiwei; Li, Yuetao; Liu, Haifeng

2017-08-01

An electrically tunable whispering gallery mode (WGM) microresonator based on an HF-etched microstructured optical fiber (MOF) infiltrated with nematic liquid crystals (NLCs) is proposed and experimentally demonstrated. Experimental results indicate that as the peak-to-peak voltage of the applied AC electric field increases from 160 to 220 V, WGM resonance peaks gradually move toward a shorter wavelength region by 0.527 nm with a wavelength sensitivity up to 0.01  nm/V for a TM1691 mode, and the Q-factor for each WGM resonance peak rapidly decreases with the increment of applied electric voltage. The proposed electrically controlled WGM tuning scheme shows a linear resonance wavelength shift with good spectral reversibility, which makes it a promising candidate to serve as an integrated functional photonic device in practical use and in related fundamental scientific studies.

Controlling slow and fast light and dynamic pulse-splitting with tunable optical gain in a whispering-gallery-mode microcavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asano, M.; Ikuta, R.; Imoto, N.

We report controllable manipulation of slow and fast light in a whispering-gallery-mode microtoroid resonator fabricated from Erbium (Er{sup 3+}) doped silica. We observe continuous transition of the coupling between the fiber-taper waveguide and the microresonator from undercoupling to critical coupling and then to overcoupling regimes by increasing the pump power even though the spatial distance between the resonator and the waveguide was kept fixed. This, in turn, enables switching from fast to slow light and vice versa just by increasing the optical gain. An enhancement of delay of two-fold over the passive silica resonator (no optical gain) was observed inmore » the slow light regime. Moreover, we show dynamic pulse splitting and its control in slow/fast light systems using optical gain.« less

Intensity fluctuations of erbium-doped whispering gallery mode lasers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Féron, Patrice; Ceppe, Jean-Baptiste; Dumeige, Yannick; Mortier, Michel S.

2017-02-01

Micro spherical resonators have attracted significant attention in recent years due to their interesting optical properties and the range of applications for which they can be used. Most of the publications dedicated to micro spherical Laser are devoted to lasing effects in different materials where the spectral properties of the emission depends on (i) the choice of dopant (e.g. Er3+, Yb3+, Tm3+) and (ii) the host matrix (e.g. silica, fluoride, phosphate or telluride glass) in which the dopant is embedded. Yet, the dynamics of theses Lasers are still to be studied. This paper shows experimental results on the amplitude fluctuations of a Whispering Gallery Mode Laser, also known as relative intensity noise (RIN). It gives information about the dynamics inside the cavity, such as photon lifetime, effective pumping rate and noise sources. We use as active medium Er3+ doped fluoride ZBLALiP glass and also industrial IOG-1 Yb3+- Er3+ co-doped phosphate glass. Theses glasses are well adapted to the development of micro spherical Laser operating in the infrared region, in particular with emission wavelengths falling respectively in the C-band and C+L band. We have observed that the RIN can provide insurance about the emission of the Laser. Moreover, we have shown that a single-mode emission comes with the presence of multiple harmonics of the relaxation frequency, which is the signature of a Laser with high noise levels. In this particular case, the second and higher orders of intensity fluctuations cannot be neglected any longer in the small-signal analysis.

Test of the FDTD accuracy in the analysis of the scattering resonances associated with high-Q whispering-gallery modes of a circular cylinder.

PubMed

Boriskin, Artem V; Boriskina, Svetlana V; Rolland, Anthony; Sauleau, Ronan; Nosich, Alexander I

2008-05-01

Our objective is the assessment of the accuracy of a conventional finite-difference time-domain (FDTD) code in the computation of the near- and far-field scattering characteristics of a circular dielectric cylinder. We excite the cylinder with an electric or magnetic line current and demonstrate the failure of the two-dimensional FDTD algorithm to accurately characterize the emission rate and the field patterns near high-Q whispering-gallery-mode resonances. This is proven by comparison with the exact series solutions. The computational errors in the emission rate are then studied at the resonances still detectable with FDTD, i.e., having Q-factors up to 10(3).

Percolation of light through whispering gallery modes in 3D lattices of coupled microspheres.

PubMed

Astratov, Vasily N; Ashili, Shashanka P

2007-12-10

Using techniques of flow-assisted self-assembly we synthesized three-dimensional (3D) lattices of dye-doped fluorescent (FL) 5 mum polystyrene spheres with 3% size dispersion with well controlled thickness from one monolayer up to 43 monolayers. In FL transmission spectra of such lattices we observed signatures of coupling between multiple spheres with nearly resonant whispering gallery modes (WGMs). These include (i) splitting of the WGM-related peaks with the magnitude 4.0-5.3 nm at the average wavelength 535 nm, (ii) pump dependence of FL transmission showing that the splitting is seen only above the threshold for lasing WGMs, and (iii) anomalously high transmission at the WGM peak wavelengths compared to the background for samples with thickness around 25 mum. We propose a qualitative interpretation of the observed WGM transport based on an analogy with percolation theory where the sites of the lattice (spheres) are connected with optical "bonds" which are present with probability depending on the spheres' size dispersion. We predict that the WGM percolation threshold should be achievable in close packed 3D lattices formed by cavities with ~10(3) quality factors of WGMs and with ~1% size dispersion. Such systems can be used for developing next generation of resonant sensors and arrayed-resonator light emitting devices.

Polarization characteristics of Whispering-Gallery-Mode fiber lasers based on evanescent-wave-coupled gain.

PubMed

Zhang, Yuan-Xian; Pu, Xiao-Yun; Feng, Li; Han, De-Yu; Ren, Yi-Tao

2013-05-20

The polarization characteristics of Whispering-Gallery-Mode (WGM) fiber lasers based on evanescent-wave-coupled gain are investigated. For the laser gain is excited by side-pumping scheme, it is found that the polarization property of lasing emission is simply dependent on the polarized states of the pump beams. The polarization property of lasing emission depends on the propagating situation of the pump beams in an optical fiber if the laser gain is excited by evanescent-wave pumping scheme, that is, if the pump beams within the fiber are meridional beams, the lasing emission is a transverse electric (TE) wave that forms a special radial polarization emission. However, if the pump beams within the fiber are skew beams, both transverse magnetic (TM) and TE waves exist simultaneously in lasing emission that forms a special axially and radially mixed polarization emission. Pumped by skew beams, the wave-number differences between TE and TM waves are also investigated quantitatively, the results demonstrate that the wave-number difference decreases with the increase of the fiber diameter and the refractive index (RI) of the cladding solution. The observed polarization characteristics have been well explained based on lasing radiation mechanism of WGM fiber laser of gain coupled by evanescent wave.

White-Light Whispering-Gallery-Mode Optical Resonators

NASA Technical Reports Server (NTRS)

Matsko, Andrey; Savchenkov, Anatoliy; Maleki, Lute

2006-01-01

Whispering-gallery-mode (WGM) optical resonators can be designed to exhibit continuous spectra over wide wavelength bands (in effect, white-light spectra), with ultrahigh values of the resonance quality factor (Q) that are nearly independent of frequency. White-light WGM resonators have potential as superior alternatives to (1) larger, conventional optical resonators in ring-down spectroscopy, and (2) optical-resonator/electro-optical-modulator structures used in coupling of microwave and optical signals in atomic clocks. In these and other potential applications, the use of white-light WGM resonators makes it possible to relax the requirement of high-frequency stability of lasers, thereby enabling the use of cheaper lasers. In designing a white-light WGM resonator, one exploits the fact that the density of the mode spectrum increases predictably with the thickness of the resonator disk. By making the resonator disk sufficiently thick, one can make the frequency differences between adjacent modes significantly less than the spectral width of a single mode, so that the spectral peaks of adjacent modes overlap, making the resonator spectrum essentially continuous. Moreover, inasmuch as the Q values of the various modes are determined primarily by surface Rayleigh scattering that does not depend on mode numbers, all the modes have nearly equal Q. By use of a proper coupling technique, one can ensure excitation of a majority of the modes. For an experimental demonstration of a white-light WGM resonator, a resonator disk 0.5-mm thick and 5 mm in diameter was made from CaF2. The shape of the resonator and the fiberoptic coupling arrangement were as shown in Figure 1. The resonator was excited with laser light having a wavelength of 1,320 nm and a spectral width of 4 kHz. The coupling efficiency exceeded 80 percent at any frequency to which the laser could be set in its tuning range, which was >100-GHz wide. The resonator response was characterized by means of ring

Biosensing operations based on whispering-gallery-mode optical cavities in single 1.0-µm diameter hexagonal GaN microdisks grown by radio-frequency plasma-assisted molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Kouno, Tetsuya; Sakai, Masaru; Kishino, Katsumi; Hara, Kazuhiko

2016-05-01

Biosensing operations based on a whispering-gallery-mode optical cavity in a single hexagonal GaN microdisk of approximately 1.0 µm diameter were demonstrated here. The sharp resonant peak in the photoluminescence spectrum obtained from the microdisk in aqueous sucrose solution redshifts with a change in sucrose concentration. The results indicate that an extremely small microdisk could be used as an optical transducer for sensing sugar, namely, as a biosensor. Furthermore, we investigate the relationship between the diameter of the microdisk and the sensitivity of the biosensor.

Study of NTA-Nickel (II) Motif Functionalization for Binding of Histidine-Tagged Proteins by a Whispering Gallery Mode Resonator

NASA Astrophysics Data System (ADS)

Khuong, Anne Chudolij

This work demonstrates the viability of the whispering gallery mode (WGM) photonic sensing method for use as a biosensor by demonstrating a surface immobilization strategy for histidine tagged biomolecules to the WGM sensor surface. The WGM resonator is a dielectric spherical microstructure that can sustain high-Q electromagnetic waves confined to the sphere by total internal reflection. Light circumnavigates the periphery of the WGM resonator and when the trapped light constructively superimposes onto itself on the round trip, a resonance condition is achieved. Because of minimal loss due to reflection, these modes can reach unusually high quality factors. When a change occurs in the evanescent field at the boundary of the resonator and surrounding environment, such as when a molecule binds to the resonator surface, a shift results in the resonance wavelength; this enables the WGM resonator to be used as a sensor. WGM optical biosensors offer a powerful alternative to conventional analytical techniques due to their high sensitivity, specificity and their ability to directly detect label-free events in real time. There has been considerable growth in this field over the last decade and potential applications to medical and biotechnological research are numerous; however, there are still obstacles limiting the widespread commercial use of these devices. The obstacle we address in this work relates to a general fundamental difficulty incorporating biomaterial into biosensors. We demonstrate a specific and controlled functionalization strategy intended for subsequent assimilation of biomolecules onto the WGM resonator surface. We have developed a general method which can be used to controllably immobilize recombinant proteins to WGM silica surfaces via their histidine tags. In the work presented herein we monitor by WGM, in real time, a two step functionalization strategy to incorporate an NTA-Ni2+ motif onto the surface of a WGM resonator. We estimated the

Bio-optical sensor for brain activity measurement based on whispering gallery modes

NASA Astrophysics Data System (ADS)

Ali, Amir R.; Massoud, Yasmin M.

2017-05-01

In this paper, a high-resolution bio-optical sensor is developed for brain activity measurement. The aim is to develop an optical sensor with enough sensitivity to detect small electric field perturbations caused by neuronal action potential. The sensing element is a polymeric dielectric micro-resonator fabricated in a spherical shape with a few hundred microns in diameter. They are made of optical quality polymers that are soft which make them mechanically compatible with tissue. The sensors are attached to or embedded in optical fibers which serve as input/output conduits for the sensors. Hundreds or even thousands of spheres can be attached to a single fiber to detect and transmit signals at different locations. The high quality factor for the optical resonator makes it significantly used in such bio-medical applications. The sensing phenomenon is based on whispering gallery modes (WGM) shifts of the optical sensor. To mimic the brain signals, the spherical resonator is immersed in a homogeneous electrical field that is created by applying potential difference across two metallic plates. One of the plates has a variable voltage while the volt on the other plate kept fixed. Any small perturbations of the potential difference (voltage) lead to change in the electric field intensity. In turn the sensor morphology will be affected due to the change in the electrostriction force acting on it causing change in its WGM. By tracking these WGM shift on the transmission spectrum, the induced potential difference (voltage change) could be measured. Results of a mathematical model simulation agree well with the preliminary experiments. Also, the results show that the brain activity could be measured using this principle.

Relationship between height and width of resonance peaks in a whispering gallery mode resonator immersed in water and sucrose solutions

NASA Astrophysics Data System (ADS)

Teraoka, Iwao; Yao, Haibei; Huiyi Luo, Natalie

2017-06-01

We employed a recently developed whispering gallery mode (WGM) dip sensor made of silica to obtain spectra for many resonance peaks in water and solutions of sucrose at different concentrations and thus having different refractive indices (RI). The apparent Q factor was estimated by fitting each peak profile in the busy resonance spectrum by a Lorentzian or a sum of Lorentzians. A plot of the Q factor as a function the peak height for all the peaks analyzed indicates a straight line with a negative slope as the upper limit, for each of water and the solutions. A coupling model for a resonator and a pair of fiber tapers to feed and pick up light, developed here, supports the presence of the upper limit. We also found that the round-trip attenuation of WGM was greater than the one estimated from light absorption by water, and the difference increased with the concentration of sucrose.

Laser-tuned whispering gallery modes in a solid-core microstructured optical fibre integrated with magnetic fluids

PubMed Central

Lin, Wei; Zhang, Hao; Liu, Bo; Song, Binbin; Li, Yuetao; Yang, Chengkun; Liu, Yange

2015-01-01

A laser-assisted tuning method of whispering gallery modes (WGMs) in a cylindrical microresonator based on magnetic-fluids-infiltrated microstructured optical fibres (MFIMOFs, where MF and MOF respectively refer to magnetic fluid and microstructured optical fibre) is proposed, experimentally demonstrated and theoretically analysed in detail. The MFIMOF is prepared by infiltrating the air-hole array of the MOF using capillary action effect. A fibre-coupling system is set up for the proposed MFIMOF-based microresonator to acquire an extinction ratio up to 25 dB and a Q-factor as large as 4.0 × 104. For the MF-infiltrated MOF, the light propagating in the fibre core region would rapidly spread out and would be absorbed by the MF-rod array cladding to induce significant thermal effect. This has been exploited to achieve a WGM resonance wavelength sensitivity of 0.034 nm/mW, which is ~20 times higher than it counterpart without MF infiltration. The wavelength response of the resonance dips exhibit linear power dependence, and owing to such desirable merits as ease of fabrication, high sensitivity and laser-assisted tunability, the proposed optical tuning approach of WGMs in the MFIMOF would find promising applications in the areas of optical filtering, sensing, and signal processing, as well as future all-optical networking systems. PMID:26632445

Whispering gallery mode resonators for frequency metrology applications

NASA Astrophysics Data System (ADS)

Baumgartel, Lukas

This dissertation describes an investigation into the use of whispering gallery mode (WGM) resonators for applications towards frequency reference and metrology. Laser stabilization and the measurement of optical frequencies have enabled myriad technologies of both academic and commercial interest. A technology which seems to span both motivations is optical atomic clocks. These devices are virtually unimaginable without the ultra stable lasers plus frequency measurement and down-conversion afforded by Fabry Perot (FP) cavities and model-locked laser combs, respectively. However, WGM resonators can potentially perform both of these tasks while having the distinct advantages of compactness and simplicity. This work represents progress towards understanding and mitigating the performance limitations of WGM cavities for such applications. A system for laser frequency stabilization to a the cavity via the Pound-Drever-Hall (PDH) method is described. While the laser lock itself is found to perform at the level of several parts in 1015, a variety of fundamental and technical mechanisms destabilize the WGM frequency itself. Owing to the relatively large thermal expansion coefficients in optical crystals, environmental temperature drifts set the stability limit at time scales greater than the thermal relaxation time of the crystal. Uncompensated, these drifts pull WGM frequencies about 3 orders of magnitude more than they would in an FP cavity. Thus, two temperature compensation schemes are developed. An active scheme measures and stabilizes the mode volume temperature to the level of several nK, reducing the effective temperature coefficient of the resonator to 1.7x10-7 K-1; simulations suggest that the value could eventually be as low as 3.5x10-8 K-1, on par with the aforementioned FP cavities. A second, passive scheme is also described, which employs a heterogeneous resonator structure that capitalizes on the thermo-mechanical properties of one material and the optical

Construction of high-dimensional universal quantum logic gates using a Λ system coupled with a whispering-gallery-mode microresonator.

PubMed

He, Ling Yan; Wang, Tie-Jun; Wang, Chuan

2016-07-11

High-dimensional quantum system provides a higher capacity of quantum channel, which exhibits potential applications in quantum information processing. However, high-dimensional universal quantum logic gates is difficult to achieve directly with only high-dimensional interaction between two quantum systems and requires a large number of two-dimensional gates to build even a small high-dimensional quantum circuits. In this paper, we propose a scheme to implement a general controlled-flip (CF) gate where the high-dimensional single photon serve as the target qudit and stationary qubits work as the control logic qudit, by employing a three-level Λ-type system coupled with a whispering-gallery-mode microresonator. In our scheme, the required number of interaction times between the photon and solid state system reduce greatly compared with the traditional method which decomposes the high-dimensional Hilbert space into 2-dimensional quantum space, and it is on a shorter temporal scale for the experimental realization. Moreover, we discuss the performance and feasibility of our hybrid CF gate, concluding that it can be easily extended to a 2n-dimensional case and it is feasible with current technology.

Light coupling into the Whispering Gallery Modes of a fiber array thin film solar cell for fixed partial Sun tracking

PubMed Central

Mariano, Marina; Rodríguez, Francisco J.; Romero-Gomez, Pablo; Kozyreff, Gregory; Martorell, Jordi

2014-01-01

We propose the use of whispering gallery mode coupling in a novel configuration based on implementing a thin film cell on the backside of an array of parallel fibers. We performed numerical calculations using the parameters of a thin film organic cell which demonstrate that light coupling becomes more effective as the angle for the incident light relative to the fiber array normal increases up to an optimal angle close to 55 deg. At this angle the power conversion efficiency of the fiber array solar cell we propose becomes 30% times larger than the one from an equivalent planar cell configuration. We demonstrate that the micro fiber array solar cell we propose may perform an effective partial tracking of the sun movement for over 100 degrees without any mechanical help. In addition, in the event that such fiber array cell would be installed with the adequate orientation on a vertical façade, an optimal photon-to-charge conversion would be reached for sunlight incident at 55 deg with respect to the horizon line, very close to the yearly average position for the sun at Latitude of 40 deg.

Low threshold lasing of bubble-containing glass microspheres by non-whispering gallery mode excitation over a wide wavelength range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumagai, Tsutaru, E-mail: kumagai.t.af@m.titech.ac.jp; Kishi, Tetsuo; Yano, Tetsuji

2015-03-21

Bubble-containing Nd{sup 3+}-doped tellurite glass microspheres were fabricated by localized laser heating technique to investigate their optical properties for use as microresonators. Fluorescence and excitation spectra measurements were performed by pumping with a tunable CW-Ti:Sapphire laser. The excitation spectra manifested several sharp peaks due to the conventional whispering gallery mode (WGM) when the pumping laser was irradiated to the edge part of the microsphere. However, when the excitation light was irradiated on the bubble position inside the microsphere, “non-WGM excitation” was induced, giving rise to numerous peaks at a broad wavelength range in the excitation spectra. Thus, efficient excitation wasmore » achieved over a wide wavelength range. Lasing threshold excited at the bubble position was much lower than that for the excitation at the edges of the microsphere. The lowest value of the laser threshold was 34 μW for a 4 μm sphere containing a 0.5 μm bubble. Efficiency of the excitation at the bubble position with broadband light was calculated to be 5 times higher than that for the edge of the microsphere. The bubble-containing microsphere enables efficient utilization of broadband light excitation from light-emitting diodes and solar light.« less

Development of optical micro resonance based sensor for detection and identification of microparticles and biological agents

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav

2009-05-01

A novel emerging technique for the label-free analysis of nanoparticles including biomolecules using optical micro cavity resonance of whispering-gallery-type modes is being developed. Schemes of such a method based on microsphere melted by laser on the tip of a standard single mode fiber optical cable with a laser and free microsphere matrix have been developed. Using a calibration principal of ultra high resolution spectroscopy based on such a scheme the method is being transformed to make further development for microbial application. The sensitivity of developed schemes has been tested to refractive index changes by monitoring the magnitude of the whispering gallery modes spectral shift. Water solutions of ethanol, glucose, vitamin C and biotin have been used. Some other schemes using similar principals: stand-alone, array and matrix microsphere resonators, liquid core optical ring resonators are also being under development. The influences of the gap in whispering-gallery modes on energy coupling, resonance quality and frequency have been investigated. An optimum gap for sensing applications has been defined at the half maximum energy coupling where both the Q factor and coupling efficiency are high and the resonance frequency is little affected by the gap variation. Developed schemes have been demonstrated to be a promising technology platform for sensitive, lab-on-chip type sensor which can be used for development of diagnostic tools for different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells as well as in different experimental contexts e.g. proteomics, genomics, drug discovery, and membrane studies.

Discovery of iron group impurity ion spin states in single crystal Y{sub 2}SiO{sub 5} with strong coupling to whispering gallery photons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goryachev, Maxim; Farr, Warrick G.; Carmo Carvalho, Natalia do

2015-06-08

Interaction of Whispering Gallery Modes (WGMs) with dilute spin ensembles in solids is an interesting paradigm of Hybrid Quantum Systems potentially beneficial for Quantum Signal Processing applications. Unexpected ion transitions are measured in single crystal Y{sub 2}SiO{sub 5} using WGM spectroscopy with large Zero Field Splittings at 14.7 GHz, 18.4 GHz, and 25.4 GHz, which also feature considerable anisotropy of the g-tensors as well as two inequivalent lattice sites, indicating spins from Iron Group Ion (IGI) impurities. The comparison of undoped and Rare-Earth doped crystals reveal that the IGIs are introduced during co-doping of Eu{sup 3+} or Er{sup 3+} with concentration at muchmore » lower levels of order 100 ppb. The strong coupling regime between an ensemble of IGI spins and WGM photons have been demonstrated at 18.4 GHz and near zero field. This approach together with useful optical properties of these ions opens avenues for “spins-in-solids” Quantum Electrodynamics.« less

Covariance Data File Formats for Whisper-1.0 & Whisper-1.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Forrest B.; Rising, Michael Evan

2017-01-09

Whisper is a statistical analysis package developed in 2014 to support nuclear criticality safety (NCS) validation. It uses the sensitivity profile data for an application as computed by MCNP6 along with covariance files for the nuclear data to determine a baseline upper-subcritical-limit (USL) for the application. Whisper version 1.0 was first developed and used at LANL in 2014. During 2015-2016, Whisper was updated to version 1.1 and is to be included with the upcoming release of MCNP6.2. This report describes the file formats used for the covariance data in both Whisper-1.0 and Whisper-1.1.

Less label, more free: approaches in label-free quantitative mass spectrometry.

PubMed

Neilson, Karlie A; Ali, Naveid A; Muralidharan, Sridevi; Mirzaei, Mehdi; Mariani, Michael; Assadourian, Gariné; Lee, Albert; van Sluyter, Steven C; Haynes, Paul A

2011-02-01

In this review we examine techniques, software, and statistical analyses used in label-free quantitative proteomics studies for area under the curve and spectral counting approaches. Recent advances in the field are discussed in an order that reflects a logical workflow design. Examples of studies that follow this design are presented to highlight the requirement for statistical assessment and further experiments to validate results from label-free quantitation. Limitations of label-free approaches are considered, label-free approaches are compared with labelling techniques, and forward-looking applications for label-free quantitative data are presented. We conclude that label-free quantitative proteomics is a reliable, versatile, and cost-effective alternative to labelled quantitation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implementation of single-photon quantum routing and decoupling using a nitrogen-vacancy center and a whispering-gallery-mode resonator-waveguide system.

PubMed

Cao, Cong; Duan, Yu-Wen; Chen, Xi; Zhang, Ru; Wang, Tie-Jun; Wang, Chuan

2017-07-24

Quantum router is a key element needed for the construction of future complex quantum networks. However, quantum routing with photons, and its inverse, quantum decoupling, are difficult to implement as photons do not interact, or interact very weakly in nonlinear media. In this paper, we investigate the possibility of implementing photonic quantum routing based on effects in cavity quantum electrodynamics, and present a scheme for single-photon quantum routing controlled by the other photon using a hybrid system consisting of a single nitrogen-vacancy (NV) center coupled with a whispering-gallery-mode resonator-waveguide structure. Different from the cases in which classical information is used to control the path of quantum signals, both the control and signal photons are quantum in our implementation. Compared with the probabilistic quantum routing protocols based on linear optics, our scheme is deterministic and also scalable to multiple photons. We also present a scheme for single-photon quantum decoupling from an initial state with polarization and spatial-mode encoding, which can implement an inverse operation to the quantum routing. We discuss the feasibility of our schemes by considering current or near-future techniques, and show that both the schemes can operate effectively in the bad-cavity regime. We believe that the schemes could be key building blocks for future complex quantum networks and large-scale quantum information processing.

Interfacing Whispering-Gallery Microresonators and Free Space Light With Cavity Enhanced Rayleigh Scattering

DTIC Science & Technology

2014-09-17

in deformed silica microspheres via free-space evanescent excitation. Optics Express 15, 16471–16477 (2007). 20. Peng, B. et al. Parity - time symmetric ...devices utilizing the concepts of parity - time symmetry20. Despite their great promises for photonic technologies, coupling light into and from WGMRs is...setup used in the experiments is depicted in Fig. 1b. It consists of a tunable external cavity laser and a fiber lens as the free-space light source

User Manual for Whisper-1.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Forrest B.; Rising, Michael Evan; Alwin, Jennifer Louise

2017-01-26

Whisper is a statistical analysis package developed in 2014 to support nuclear criticality safety (NCS) validation [1-3]. It uses the sensitivity profile data for an application as computed by MCNP6 [4-6] along with covariance files [7,8] for the nuclear data to determine a baseline upper-subcritical-limit (USL) for the application. Whisper version 1.0 was first developed and used at LANL in 2014 [3]. During 2015- 2016, Whisper was updated to version 1.1 and is to be included with the upcoming release of MCNP6.2. This document describes the user input and options for running whisper-1.1, including 2 perl utility scripts that simplifymore » ordinary NCS work, whisper_mcnp.pl and whisper_usl.pl. For many detailed references on the theory, applications, nuclear data & covariances, SQA, verification-validation, adjointbased methods for sensitivity-uncertainty analysis, and more – see the Whisper – NCS Validation section of the MCNP Reference Collection at mcnp.lanl.gov. There are currently over 50 Whisper reference documents available.« less

On the dispersion management of fluorite whispering-gallery mode resonators for Kerr optical frequency comb generation in the telecom and mid-infrared range.

PubMed

Lin, Guoping; Chembo, Yanne K

2015-01-26

Optical whispering gallery mode (WGM) resonators have been very attracting platforms for versatile Kerr frequency comb generations. We report a systematic study on the material dispersion of various optical materials that are capable of supporting quality factors above 10⁹. Using an analytical approximation of WGM resonant frequencies in disk resonators, we investigate the effect of the geometry and transverse mode order on the total group-velocity dispersion (GVD). We demonstrate that the major radii and the radial mode indices play an important role in tailoring the GVD of WGM resonators. In particular, our study shows that in WGM disk-resonators, the polar families of modes have very similar GVD, while the radial families of modes feature dispersion values that can differ by up to several orders of magnitude. The effect of these giant dispersion shifts are experimentally evidenced in Kerr comb generation with magnesium fluoride. From a more general perspective, this critical feature enables to push the zero-dispersion wavelength of fluorite crystals towards the mid-infrared (mid-IR) range, thereby allowing for efficient Kerr comb generation in that spectral range. We show that barium fluoride is the most interesting crystal in this regard, due to its zero dispersion wavelength (ZDW) at 1.93 μm and an optimal dispersion profile in the mid-IR regime. We expect our results to facilitate the design of different platforms for Kerr frequency comb generations in both telecommunication and mid-IR spectral ranges.

Production and perception of whispered vowels

NASA Astrophysics Data System (ADS)

Kiefte, Michael

2005-09-01

Information normally associated with pitch, such as intonation, can still be conveyed in whispered speech despite the absence of voicing. For example, it is possible to whisper the question ``You are going today?'' without any syntactic information to distinguish this sentence from a simple declarative. It has been shown that pitch change in whispered speech is correlated with the simultaneous raising or lowering of several formants [e.g., M. Kiefte, J. Acoust. Soc. Am. 116, 2546 (2004)]. However, spectral peak frequencies associated with formants have been identified as important correlates to vowel identity. Spectral peak frequencies may serve two roles in the perception of whispered speech: to indicate both vowel identity and intended pitch. Data will be presented to examine the relative importance of several acoustic properties including spectral peak frequencies and spectral shape parameters in both the production and perception of whispered vowels. Speakers were asked to phonate and whisper vowels at three different pitches across a range of roughly a musical fifth. It will be shown that relative spectral change is preserved within vowels across intended pitches in whispered speech. In addition, several models of vowel identification by listeners will be presented. [Work supported by SSHRC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zubov, F. I.; Kryzhanovskaya, N. V.; Moiseev, E. I.

The spectral, threshold, and power characteristics of a microdisk laser 31 μm in diameter with an active region based on InAs/InGaAs quantum dots, operating in the continuous-wave (cw) mode at room temperature are studied. The minimum threshold current density is 0.58 kA/cm{sup 2}, the subthreshold linewidth of the whispering-gallery mode is 50 pm at a wavelength lying in the range of 1.26–1.27 μm. The total power emitted into free space reaches ~0.1 mW in the cw mode, whereas the radiation power of the whispering-gallery modes is ~2.8%.

Whispering - The hidden side of auditory communication.

PubMed

Frühholz, Sascha; Trost, Wiebke; Grandjean, Didier

2016-11-15

Whispering is a unique expression mode that is specific to auditory communication. Individuals switch their vocalization mode to whispering especially when affected by inner emotions in certain social contexts, such as in intimate relationships or intimidating social interactions. Although this context-dependent whispering is adaptive, whispered voices are acoustically far less rich than phonated voices and thus impose higher hearing and neural auditory decoding demands for recognizing their socio-affective value by listeners. The neural dynamics underlying this recognition especially from whispered voices are largely unknown. Here we show that whispered voices in humans are considerably impoverished as quantified by an entropy measure of spectral acoustic information, and this missing information needs large-scale neural compensation in terms of auditory and cognitive processing. Notably, recognizing the socio-affective information from voices was slightly more difficult from whispered voices, probably based on missing tonal information. While phonated voices elicited extended activity in auditory regions for decoding of relevant tonal and time information and the valence of voices, whispered voices elicited activity in a complex auditory-frontal brain network. Our data suggest that a large-scale multidirectional brain network compensates for the impoverished sound quality of socially meaningful environmental signals to support their accurate recognition and valence attribution. Copyright © 2016 Elsevier Inc. All rights reserved.

Release Notes for Whisper-1.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Forrest B.; Rising, Michael Evan; Alwin, Jennifer Louise

Whisper is a statistical analysis package developed in 2014 to support nuclear criticality safety (NCS) validation [1-3]. It uses the sensitivity profile data for an application as computed by MCNP6 [4-6] along with covariance files [7,8] for the nuclear data to determine a baseline upper-subcritical-limit (USL) for the application. Whisper version 1.0 was first developed and used at LANL in 2014 [3]. During 2015-2016, Whisper was updated to version 1.1 [9] and is to be included with the upcoming release of MCNP6.2. This document describes the Whisper-1.1 package that will be included with the MCNP6.2 release during 2017. Specific detailsmore » are provided on the computer systems supported, the software quality assurance (SQA) procedures, installation, and testing. This document does not address other important topics, such as the importance of sensitivity-uncertainty (SU) methods to NCS validation, the theory underlying SU methodology, tutorials on the usage of MCNP-Whisper, practical approaches to using SU methodology to support and extend traditional validation, etc. There are over 50 documents included with Whisper-1.1 and available in the MCNP Reference Collection on the MCNP website (mcnp.lanl.gov) that address all of those topics and more. In this document, however, a complete bibliography of relevant MCNP-Whisper references is provided.« less

Design and Development of Nanostructured Surfaces for Enhanced Optical Sensing

NASA Astrophysics Data System (ADS)

Santiago Cordoba, Miguel A.

At smaller size regimes, materials' physicochemical properties change with respect to bulk analogs. In the case of metal nanoparticles like gold or silver, specific wavelengths of light can induce a coherent oscillation of their conduction electrons, generating an optical field confined to the nanoparticle surface. This phenomenon is termed surface plasmon, and has been used as an enhancing mechanism in optical sensing, allowing the detection of foreign materials at small concentrations. The goal of this dissertation is to develop nanostructured materials relying on surface plasmons that can be combined with different optical sensing platforms in order to enhance current detection limits. Initially, we focus on the development of surfactant free, stimuli responsive nanoparticle thin films, which undergo an active release when exposed to a stimulus such as a change in pH. These nanoparticle thin films provide faster analyte particle transport and direct electronic coupling with the analyte molecule, all without attenuating the evanescent wave from the optical transducer to the particle. These stimuli responsive nanostructured substrates are tested within a surface enhanced Raman platform for the detection of biomolecular probes at sub-nanomolar concentrations and microL sample sizes. Furthermore, the developed nanosubstrates can be patterned, providing a versatile nanoparticle thin film for multiplexing analysis, offering a substantial advantage over conventional surface based nanoparticle detection methods. Our results encouraged further optimization of light-matter interactions in optical detection platforms. It is for that reason that this dissertation evolves towards confined optical systems. Particularly, whispering gallery microcavities confine electromagnetic waves - at high volumes - at the boundary of a dielectric resonator. In this dissertation, we examined the sensitivity of whispering gallery modes combining optical microcavities with plasmonic

Cool Cosmology: ``WHISPER" better than ``BANG"

NASA Astrophysics Data System (ADS)

Carr, Paul

2007-10-01

Cosmologist Fred Hoyle coined ``big bang'' as a term of derision for Belgian priest George Lemaitre's prediction that the universe had originated from the expansion of a ``primeval atom'' in space-time. Hoyle referred to Lamaitre's hypothesis sarcastically as ``this big bang idea'' during a program broadcast on March 28, 1949 on the BBC. Hoyle's continuous creation or steady state theory can not explain the microwave background radiation or cosmic whisper discovered by Penzias and Wilson in 1964. The expansion and subsequent cooling of Lemaitre's hot ``primeval atom'' explains the whisper. ``Big bang'' makes no physical sense, as there was no matter (or space) to carry the sound that Hoyle's term implies. The ``big bang'' is a conjecture. New discoveries may be able to predict the observed ``whispering cosmos'' as well as dark matter and the nature of dark energy. The ``whispering universe'' is cooler cosmology than the big bang. Reference: Carr, Paul H. 2006. ``From the 'Music of the Spheres' to the 'Whispering Cosmos.' '' Chapter 3 of Beauty in Science and Spirit. Beech River Books. Center Ossipee, NH, http://www.MirrorOfNature.org.

Field results from Whisper® stethoscope studies.

PubMed

Noffsinger, Tom; Brattain, Kurt; Quakenbush, Greg; Taylor, Garrett

2014-12-01

One area where the feedlot industry has been historically weak is the area of BRD "case definition" or diagnosis. Numerous studies demonstrate a weak correlation between lung lesions at harvest and treatment history. This poor track record is due in part to lack of specific chute side diagnostic tools. To analyze the effectiveness of current diagnostic tools (temperature, manual lung scores, and Whisper® lung scores), two data sets were collected. The first evaluated the correlation between rectal temperature, manual lung scores, and case fatality rate in feedlot cattle pulled for BRD. The second evaluated the relative accuracy of Whisper® scores and rectal temperature. Fever was defined as a rectal temperature of 104.5° F or greater. Manual lung scores better correlated with case fatality rate than fever. When fever and Whisper® scores were compared, a Whisper® score of 1 or less better predicted survival than a temperature of less than 104.5° F. The combination of no fever and Whisper® score of 1 or less best predicted survival. The determination of Whisper® score along with rectal temperature in cattle identified with signs of acute BRD can improve case definition, improve risk assessment, and allow more targeted use of antibiotics.

Advancements in robust algorithm formulation for speaker identification of whispered speech

NASA Astrophysics Data System (ADS)

Fan, Xing

Whispered speech is an alternative speech production mode from neutral speech, which is used by talkers intentionally in natural conversational scenarios to protect privacy and to avoid certain content from being overheard/made public. Due to the profound differences between whispered and neutral speech in production mechanism and the absence of whispered adaptation data, the performance of speaker identification systems trained with neutral speech degrades significantly. This dissertation therefore focuses on developing a robust closed-set speaker recognition system for whispered speech by using no or limited whispered adaptation data from non-target speakers. This dissertation proposes the concept of "High''/"Low'' performance whispered data for the purpose of speaker identification. A variety of acoustic properties are identified that contribute to the quality of whispered data. An acoustic analysis is also conducted to compare the phoneme/speaker dependency of the differences between whispered and neutral data in the feature domain. The observations from those acoustic analysis are new in this area and also serve as a guidance for developing robust speaker identification systems for whispered speech. This dissertation further proposes two systems for speaker identification of whispered speech. One system focuses on front-end processing. A two-dimensional feature space is proposed to search for "Low''-quality performance based whispered utterances and separate feature mapping functions are applied to vowels and consonants respectively in order to retain the speaker's information shared between whispered and neutral speech. The other system focuses on speech-mode-independent model training. The proposed method generates pseudo whispered features from neutral features by using the statistical information contained in a whispered Universal Background model (UBM) trained from extra collected whispered data from non-target speakers. Four modeling methods are proposed

Nanophotonics for Lab-on-Chip Applications

NASA Astrophysics Data System (ADS)

Seitz, Peter

Optical methods are the preferred measurement techniques for biosensors and lab-on-chip applications. Their key properties are sensitivity, selectivity and robustness. To simplify the systems and their operation, it is desirable to employ label-free optical methods, requiring the functionalization of interfaces. Evanescent electromagnetic waves are probing the optical proper ties near the interfaces, a few 100 nm deep into the sample fluid. The sensitivity of these measurements can be improved with optical micro-resonators, in particular whispering gallery mode devices. Q factors as high as 2x108 have been achieved in practice. The resulting narrow-linewidth resonances and an unexpected thermo-optic effect make it possible to detect single biomolecules using a label-free biosensor principle. Future generations of biosensors and labs-on-chip for point-of-care and high-troughput screening applications will require large numbers of parallel measurement channels, necessitating optical micro-resonators in array format produced very cost-effectively.

Fabrication et caracterisation de cavites organiques a modes de galerie

NASA Astrophysics Data System (ADS)

Amrane, Tassadit

The aim of this master project is to combine the high quality factor of whispering gallery optical microcavities with the high photoluminescence efficiency of conjugated polymers. These polymer-cavity composite systems have a great potential for studying the interaction of light and matter in the strong coupling regime. In particular, this system would offer a great opportunity to create a Bose-Einstein condensate of polaritons, the quasi-particles made from a strong interaction between excitons and photons. Organic semiconductors, with their large delocalized excitons, coupled to good whispering gallery cavities with high quality factors and small volumes are an ideal system for this purpose. Two approaches toward this end were explored: in the first approach a pre-existing dielectric whispering gallery cavity was coated with a thin film of conjugated polymer, while in the second one the whispering gallery cavity was fabricated directly with the organic semi-conductor. For testing the first approach, a silica microsphere was dip-coated with copolymer, and the interaction between the whispering gallery modes in the microcavity and the copolymer was studied using photoluminescence spectroscopy. The well-defined resonances obtained at the emission wavelength of the organic material confirm the effective coupling between the photoluminescence and the modes of the cavity. In the second approach, we developed a process to fabricate microdisk cavities with the copolymer. The difficulty in this approach lies in the sensitivity of the organic semiconductor to the microfabrication process. It is critical to avoid dissolving or otherwise altering it during the photolithographic steps. For this purpose a protective polymer, parylene-C, is deposited on the top of the copolymer. This protective polymer was chosen to be transparent at the absorption and emission wavelengths of the copolymer and inert in the solvents used during the different steps of microfabrication. The

Tunable Filter Made From Three Coupled WGM Resonators

NASA Technical Reports Server (NTRS)

Savchenkov, Anatoliy; Iltchenko, Vladimir; Maleki, Lute; Matsko, Andrey

2006-01-01

A tunable third-order band-pass optical filter has been constructed as an assembly of three coupled, tunable, whispering-gallery-mode resonators similar to the one described in Whispering-Gallery-Mode Tunable Narrow-Band-Pass Filter (NPO-30896), NASA Tech Briefs, Vol. 28, No. 4 (April 2004), page 5a. This filter offers a combination of four characteristics that are desirable for potential applications in photonics: (1) wide real-time tunability accompanied by a high-order filter function, (2) narrowness of the passband, (3) relatively low loss between input and output coupling optical fibers, and (4) a sparse spectrum. In contrast, prior tunable band-pass optical filters have exhibited, at most, two of these four characteristics. As described in several prior NASA Tech Briefs articles, a whispering-gallery-mode (WGM) resonator is a spheroidal, disklike, or toroidal body made of a highly transparent material. It is so named because it is designed to exploit whispering-gallery electromagnetic modes, which are waveguide modes that propagate circumferentially and are concentrated in a narrow toroidal region centered on the equatorial plane and located near the outermost edge. Figure 1 depicts the optical layout of the present filter comprising an assembly of three coupled, tunable WGM resonators. Each WGM resonator is made from a disk of Z-cut LiNbO3 of 3.3-mm diameter and 50-m thickness. The perimeter of the disk is polished and rounded to a radius of curvature of 40 microns. The free spectral range of each WGM resonator is about 13.3 GHz. Gold coats on the flat faces of the disk serve as electrodes for exploiting the electro-optical effect in LiNbO3 for tuning. There is no metal coat on the rounded perimeter region, where the whispering-gallery modes propagate. Light is coupled from an input optical fiber into the whispering-gallery-modes of the first WGM resonator by means of a diamond prism. Another diamond prism is used to couple light from the whispering-gallery

Scaffold-free, label-free and nozzle-free biofabrication technology using magnetic levitational assembly.

PubMed

Parfenov, Vladislav A; Koudan, Elizaveta V; Bulanova, Elena A; Karalkin, Pavel A; Pereira, Frederico DAS; Norkin, Nikita E; Knyazeva, Alisa D; Gryadunova, Anna A; Petrov, Oleg F; Vasiliev, M M; Myasnikov, Maxim; Chernikov, Valery P; Kasyanov, Vladimir A; Marchenkov, Artem Yu; Brakke, Kenneth A; Khesuani, Yusef D; Demirci, Utkan; Mironov, Vladimir A

2018-05-31

Tissue spheroids have been proposed as building blocks in 3D biofabrication. Conventional magnetic force-driven 2D patterning of tissue spheroids requires prior cell labeling by magnetic nanoparticles, meanwhile a label-free approach for 3D magnetic levitational assembly has been introduced. Here we present first-time report on rapid assembly of 3D tissue construct using scaffold-free, nozzle-free and label-free magnetic levitation of tissue spheroids. Chondrospheres of standard size, shape and capable to fusion have been biofabricated from primary sheep chondrocytes using non-adhesive technology. Label-free magnetic levitation was performed using a prototype device equipped with permanent magnets in presence of gadolinium (Gd3+) in culture media, which enables magnetic levitation. Mathematical modeling and computer simulations were used for prediction of magnetic field and kinetics of tissue spheroids assembly into 3D tissue constructs. First, we used polystyrene beads to simulate the assembly of tissue spheroids and to determine the optimal settings for magnetic levitation in presence of Gd3+. Second, we proved the ability of chondrospheres to assemble rapidly into 3D tissue construct in the permanent magnetic field in the presence of Gd3+. Thus, scaffold- and label-free magnetic levitation of tissue spheroids is a promising approach for rapid 3D biofabrication and attractive alternative to label-based magnetic force-driven tissue engineering. . © 2018 IOP Publishing Ltd.

78 FR 47154 - Food Labeling; Gluten-Free Labeling of Foods

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-05

...The Food and Drug Administration (FDA or we) is issuing a final rule to define the term ``gluten-free'' for voluntary use in the labeling of foods. The final rule defines the term ``gluten-free'' to mean that the food bearing the claim does not contain an ingredient that is a gluten-containing grain (e.g., spelt wheat); an ingredient that is derived from a gluten-containing grain and that has not been processed to remove gluten (e.g., wheat flour); or an ingredient that is derived from a gluten-containing grain and that has been processed to remove gluten (e.g., wheat starch), if the use of that ingredient results in the presence of 20 parts per million (ppm) or more gluten in the food (i.e., 20 milligrams (mg) or more gluten per kilogram (kg) of food); or inherently does not contain gluten; and that any unavoidable presence of gluten in the food is below 20 ppm gluten (i.e., below 20 mg gluten per kg of food). A food that bears the claim ``no gluten,'' ``free of gluten,'' or ``without gluten'' in its labeling and fails to meet the requirements for a ``gluten-free'' claim will be deemed to be misbranded. In addition, a food whose labeling includes the term ``wheat'' in the ingredient list or in a separate ``Contains wheat'' statement as required by a section of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) and also bears the claim ``gluten-free'' will be deemed to be misbranded unless its labeling also bears additional language clarifying that the wheat has been processed to allow the food to meet FDA requirements for a ``gluten-free'' claim. Establishing a definition of the term ``gluten-free'' and uniform conditions for its use in food labeling will help ensure that individuals with celiac disease are not misled and are provided with truthful and accurate information with respect to foods so labeled. We are issuing the final rule under the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA).

Whispering--a single-subject study of glottal configuration and aerodynamics.

PubMed

Sundberg, Johan; Scherer, Ronald; Hess, Markus; Müller, Frank

2010-09-01

Whisper productions were produced by a single adult male subject over a wide range of subglottal pressures, glottal areas, and glottal flows. Dimensional measurements were made of these three variables, including glottal perimeter. Subglottal pressure was directly obtained by a pressure transducer in a tracheal catheter, and wide-band flow with a pneumotach mask. Four types of whispers were used-hyperfunctional, hypofunctional, neutral, and postphonation-in addition to three levels of loudness (soft, medium, loud). Sequences of the /pae/ syllable were used. Video recordings of the larynx were made. The glottis was outlined by hand with extrapolation for unseen parts, and area and perimeter were obtained through image analysis software. The whisper tokens resulted in the following wide ranges: subglottal pressure: 1.3-17 cm H2O; glottal flow: 0.9-1.71 L/s; glottal area: 0.065-1.76 m2; and glottal perimeter: 1.09-6.55 cm. Hyperfunctional whisper tended to have higher subglottal pressures and lower areas and flows than hypofunctional whisper, with neutral and postphonation whisper values in between. An important finding is that glottal flow changed more for small changes of area when the area was already small, and did not create much flow change when area was changed for already larger areas; that is, whisper is "more sensitive" to airflow changes for smaller glottal areas. A general equation for whisper aerodynamics was obtained, namely, P (subglottal pressure [cm H2O])=C X F (glottal flow [cm(3)/s]), where C = 0.052 x A(4) - 0.1913 x A(3) + 0.2577 x A(2) - 0.1523 x A+0.0388, where A is the glottal area (cm(2)). Another general equation for nondimensional terms (pressure coefficient vs Reynolds number) also is offered. Implications for whisper flow resistance and aerodynamic power are given. These results give insight into whisper aerodynamics and offer equations relevant to speech synthesis. Copyright © 2010 The Voice Foundation. Published by Mosby, Inc. All

Significance of parametric spectral ratio methods in detection and recognition of whispered speech

NASA Astrophysics Data System (ADS)

Mathur, Arpit; Reddy, Shankar M.; Hegde, Rajesh M.

2012-12-01

In this article the significance of a new parametric spectral ratio method that can be used to detect whispered speech segments within normally phonated speech is described. Adaptation methods based on the maximum likelihood linear regression (MLLR) are then used to realize a mismatched train-test style speech recognition system. This proposed parametric spectral ratio method computes a ratio spectrum of the linear prediction (LP) and the minimum variance distortion-less response (MVDR) methods. The smoothed ratio spectrum is then used to detect whispered segments of speech within neutral speech segments effectively. The proposed LP-MVDR ratio method exhibits robustness at different SNRs as indicated by the whisper diarization experiments conducted on the CHAINS and the cell phone whispered speech corpus. The proposed method also performs reasonably better than the conventional methods for whisper detection. In order to integrate the proposed whisper detection method into a conventional speech recognition engine with minimal changes, adaptation methods based on the MLLR are used herein. The hidden Markov models corresponding to neutral mode speech are adapted to the whispered mode speech data in the whispered regions as detected by the proposed ratio method. The performance of this method is first evaluated on whispered speech data from the CHAINS corpus. The second set of experiments are conducted on the cell phone corpus of whispered speech. This corpus is collected using a set up that is used commercially for handling public transactions. The proposed whisper speech recognition system exhibits reasonably better performance when compared to several conventional methods. The results shown indicate the possibility of a whispered speech recognition system for cell phone based transactions.

Segregation of Whispered Speech Interleaved with Noise or Speech Maskers

DTIC Science & Technology

2011-08-01

range over which the talker can be heard. Whispered speech is produced by modulating the flow of air through partially open vocal folds. Because the...source of excitation is turbulent air flow , the acoustic characteristics of whispered speech differs from voiced speech [1, 2]. Despite the acoustic...signals provided by cochlear implants. Two studies investigated the segregation of simultaneously presented whispered vowels [7, 8] in a standard

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MedlinePlus

... R S T U V W X Y Z Image Gallery Share: The Image Gallery contains high-quality digital photographs available from ... Select a category below to view additional thumbnail images. Images are available for direct download in 2 ...

Whisper-like behavior in a non-human primate.

PubMed

Morrison, Rachel; Reiss, Diana

2013-01-01

In humans, whispering has evolved as a counteractive strategy against eavesdropping. Some evidence for whisper-like behavior exists in a few other species, but has not been reported in non-human primates. We discovered the first evidence of whisper-like behavior in a non-human primate, the cotton-top tamarin (Saguinus oedipus), in the course of investigating their use of human-directed mobbing calls. We exposed a family of captive cotton-top tamarins to a supervisor who previously elicited a strong mobbing response. Simultaneous audio-video recordings documented the animals' behavioral and vocal responses in the supervisor's presence and absence. Rather than exhibiting a mobbing response and producing loud human-directed mobbing calls, the tamarins exhibited other anti-predator behaviors and produced low amplitude vocalizations that initially eluded our detection. A post-hoc analysis of the data was conducted to test a new hypothesis-the tamarins were reducing the amplitude of their vocalizations in the context of exposure to a potential threat. Consistent with whisper-like behavior, the amplitude of the tamarins' vocalizations was significantly reduced only in the presence of the supervisor. Due to its subtle properties, this phenomenon may have eluded detection in this species. Increasing evidence of whisper-like behavior in non-human species suggests that such low amplitude signaling may represent a convergence in a communication strategy amongst highly social and cooperative species. © 2013 Wiley Periodicals, Inc.

Speaker-Sex Discrimination for Voiced and Whispered Vowels at Short Durations.

PubMed

Smith, David R R

2016-01-01

Whispered vowels, produced with no vocal fold vibration, lack the periodic temporal fine structure which in voiced vowels underlies the perceptual attribute of pitch (a salient auditory cue to speaker sex). Voiced vowels possess no temporal fine structure at very short durations (below two glottal cycles). The prediction was that speaker-sex discrimination performance for whispered and voiced vowels would be similar for very short durations but, as stimulus duration increases, voiced vowel performance would improve relative to whispered vowel performance as pitch information becomes available. This pattern of results was shown for women's but not for men's voices. A whispered vowel needs to have a duration three times longer than a voiced vowel before listeners can reliably tell whether it's spoken by a man or woman (∼30 ms vs. ∼10 ms). Listeners were half as sensitive to information about speaker-sex when it is carried by whispered compared with voiced vowels.

Speaker-Sex Discrimination for Voiced and Whispered Vowels at Short Durations

PubMed Central

2016-01-01

Whispered vowels, produced with no vocal fold vibration, lack the periodic temporal fine structure which in voiced vowels underlies the perceptual attribute of pitch (a salient auditory cue to speaker sex). Voiced vowels possess no temporal fine structure at very short durations (below two glottal cycles). The prediction was that speaker-sex discrimination performance for whispered and voiced vowels would be similar for very short durations but, as stimulus duration increases, voiced vowel performance would improve relative to whispered vowel performance as pitch information becomes available. This pattern of results was shown for women’s but not for men’s voices. A whispered vowel needs to have a duration three times longer than a voiced vowel before listeners can reliably tell whether it’s spoken by a man or woman (∼30 ms vs. ∼10 ms). Listeners were half as sensitive to information about speaker-sex when it is carried by whispered compared with voiced vowels. PMID:27757218

The Child Whisperer: Effective Parenting Strategies Adapted from "The Dog Whisperer"

ERIC Educational Resources Information Center

McKinney, Cliff; Durr, Brandi

2013-01-01

Behavior modification with children has been popularized through television shows such as "Super Nanny" and "Nanny 911". The popularity of these shows may be related to the demand parents have for improving their children's behavior. Interestingly, an approach adopted by "The Dog Whisperer" may prove effective when used with children. The purpose…

Lecture Notes on Criticality Safety Validation Using MCNP & Whisper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Forrest B.; Rising, Michael Evan; Alwin, Jennifer Louise

Training classes for nuclear criticality safety, MCNP documentation. The need for, and problems surrounding, validation of computer codes and data area considered first. Then some background for MCNP & Whisper is given--best practices for Monte Carlo criticality calculations, neutron spectra, S(α,β) thermal neutron scattering data, nuclear data sensitivities, covariance data, and correlation coefficients. Whisper is computational software designed to assist the nuclear criticality safety analyst with validation studies with the Monte Carlo radiation transport package MCNP. Whisper's methodology (benchmark selection – C k's, weights; extreme value theory – bias, bias uncertainty; MOS for nuclear data uncertainty – GLLS) and usagemore » are discussed.« less

Progress of new label-free techniques for biosensors: a review.

PubMed

Sang, Shengbo; Wang, Yajun; Feng, Qiliang; Wei, Ye; Ji, Jianlong; Zhang, Wendong

2016-01-01

The detection techniques used in biosensors can be broadly classified into label-based and label-free. Label-based detection relies on the specific properties of labels for detecting a particular target. In contrast, label-free detection is suitable for the target molecules that are not labeled or the screening of analytes which are not easy to tag. Also, more types of label-free biosensors have emerged with developments in biotechnology. The latest developed techniques in label-free biosensors, such as field-effect transistors-based biosensors including carbon nanotube field-effect transistor biosensors, graphene field-effect transistor biosensors and silicon nanowire field-effect transistor biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress-based biosensors and other type of biosensors based on the nanotechnology are discussed. The sensing principles, configurations, sensing performance, applications, advantages and restriction of different label-free based biosensors are considered and discussed in this review. Most concepts included in this survey could certainly be applied to the development of this kind of biosensor in the future.

Cavity QED implementation of non-adiabatic holonomies for universal quantum gates in decoherence-free subspaces with nitrogen-vacancy centers.

PubMed

Zhou, Jian; Yu, Wei-Can; Gao, Yu-Mei; Xue, Zheng-Yuan

2015-06-01

A cavity QED implementation of the non-adiabatic holonomic quantum computation in decoherence-free subspaces is proposed with nitrogen-vacancy centers coupled commonly to the whispering-gallery mode of a microsphere cavity, where a universal set of quantum gates can be realized on the qubits. In our implementation, with the assistant of the appropriate driving fields, the quantum evolution is insensitive to the cavity field state, which is only virtually excited. The implemented non-adiabatic holonomies, utilizing optical transitions in the Λ type of three-level configuration of the nitrogen-vacancy centers, can be used to construct a universal set of quantum gates on the encoded logical qubits. Therefore, our scheme opens up the possibility of realizing universal holonomic quantum computation with cavity assisted interaction on solid-state spins characterized by long coherence times.

Performance limitations of label-free sensors in molecular diagnosis using complex samples

NASA Astrophysics Data System (ADS)

Varma, Manoj

2016-03-01

Label-free biosensors promised a paradigm involving direct detection of biomarkers from complex samples such as serum without requiring multistep sample processing typical of labelled methods such as ELISA or immunofluorescence assays. Label-free sensors have witnessed decades of development with a veritable zoo of techniques available today exploiting a multitude of physical effects. It is appropriate now to critically assess whether label-free technologies have succeeded in delivering their promise with respect to diagnostic applications, particularly, ambitious goals such as early cancer detection using serum biomarkers, which require low limits of detection (LoD). Comparison of nearly 120 limits of detection (LoD) values reported by labelled and label-free sensing approaches over a wide range of detection techniques and target molecules in serum revealed that labeled techniques achieve 2-3 orders of magnitude better LoDs. Data from experiments where labelled and label-free assays were performed simultaneously using the same assay parameters also confirm that the LoD achieved by labelled techniques is 2 to 3 orders of magnitude better than that by label-free techniques. Furthermore, label-free techniques required significant signal amplification, for e.g. using nanoparticle conjugated secondary antibodies, to achieve LoDs comparable to labelled methods substantially deviating from the original "direct detection" paradigm. This finding has important implications on the practical limits of applying label-free detection methods for molecular diagnosis.

On the Problem of Filtration to an Imperfect Gallery in a Pressureless Bed

NASA Astrophysics Data System (ADS)

Bereslavskii, É. N.; Dudina, L. M.

2018-01-01

The problem of plane steady-state filtration in a pressureless bed to an imperfect gallery in the presence of evaporation from the flow free surface is considered. To study such type of flow, a mixed boundary-value problem of the theory of analytical functions is formulated and solved with application of the Polubarinova-Kochina method. Based on the model suggested, an algorithm for computing the discharge of the gallery and the ordinate of free surface emergence to the impermeable screen is developed. A detailed hydrodynamic analysis of the influence of all physical parameters of the model on the desired filtration characteristics is given.

Label-free functional nucleic acid sensors for detecting target agents

DOEpatents

Lu, Yi; Xiang, Yu

2015-01-13

A general methodology to design label-free fluorescent functional nucleic acid sensors using a vacant site approach and an abasic site approach is described. In one example, a method for designing label-free fluorescent functional nucleic acid sensors (e.g., those that include a DNAzyme, aptamer or aptazyme) that have a tunable dynamic range through the introduction of an abasic site (e.g., dSpacer) or a vacant site into the functional nucleic acids. Also provided is a general method for designing label-free fluorescent aptamer sensors based on the regulation of malachite green (MG) fluorescence. A general method for designing label-free fluorescent catalytic and molecular beacons (CAMBs) is also provided. The methods demonstrated here can be used to design many other label-free fluorescent sensors to detect a wide range of analytes. Sensors and methods of using the disclosed sensors are also provided.

Gluten-Free Labeling of Foods

MedlinePlus

... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Guidance & Regulation Guidance Documents & Regulatory Information by Topic Allergens Gluten-Free Labeling of Foods Share Tweet Linkedin Pin it More sharing options ...

Excitonic lasing of strain-free InP(As) quantum dots in AlInAs microdisk

NASA Astrophysics Data System (ADS)

Lebedev, D. V.; Kulagina, M. M.; Troshkov, S. I.; Vlasov, A. S.; Davydov, V. Y.; Smirnov, A. N.; Bogdanov, A. A.; Merz, J. L.; Kapaldo, J.; Gocalinska, A.; Juska, G.; Moroni, S. T.; Pelucchi, E.; Barettin, D.; Rouvimov, S.; Mintairov, A. M.

2017-03-01

Formation, emission, and lasing properties of strain-free InP(As)/AlInAs quantum dots (QDs) embedded in AlInAs microdisk (MD) cavity were investigated using transmission electron microscopy and photoluminescence (PL) techniques. In MD structures, the QDs have the nano-pan-cake shape with the height of ˜2 nm, the lateral size of 20-50 nm, and the density of ˜5 × 109 cm-2. Their emission observed at ˜940 nm revealed strong temperature quenching, which points to exciton decomposition. It also showed unexpected type-I character, indicating In-As intermixing as confirmed by band structure calculations. We observed lasing of InP(As) QD excitons into whispering gallery modes in MD having the diameter of ˜3.2 μm and providing a free spectral range of ˜27 nm and quality factors up to Q˜13 000. Threshold of ˜50 W/cm2 and spontaneous emission coupling coefficient of ˜0.2 were measured for this MD-QD system.

freeQuant: A Mass Spectrometry Label-Free Quantification Software Tool for Complex Proteome Analysis.

PubMed

Deng, Ning; Li, Zhenye; Pan, Chao; Duan, Huilong

2015-01-01

Study of complex proteome brings forward higher request for the quantification method using mass spectrometry technology. In this paper, we present a mass spectrometry label-free quantification tool for complex proteomes, called freeQuant, which integrated quantification with functional analysis effectively. freeQuant consists of two well-integrated modules: label-free quantification and functional analysis with biomedical knowledge. freeQuant supports label-free quantitative analysis which makes full use of tandem mass spectrometry (MS/MS) spectral count, protein sequence length, shared peptides, and ion intensity. It adopts spectral count for quantitative analysis and builds a new method for shared peptides to accurately evaluate abundance of isoforms. For proteins with low abundance, MS/MS total ion count coupled with spectral count is included to ensure accurate protein quantification. Furthermore, freeQuant supports the large-scale functional annotations for complex proteomes. Mitochondrial proteomes from the mouse heart, the mouse liver, and the human heart were used to evaluate the usability and performance of freeQuant. The evaluation showed that the quantitative algorithms implemented in freeQuant can improve accuracy of quantification with better dynamic range.

Final Report Advanced Quasioptical Launcher System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeffrey Neilson

2010-04-30

This program developed an analytical design tool for designing antenna and mirror systems to convert whispering gallery RF modes to Gaussian or HE11 modes. Whispering gallery modes are generated by gyrotrons used for electron cyclotron heating of fusion plasmas in tokamaks. These modes cannot be easily transmitted and must be converted to free space or waveguide modes compatible with transmission line systems.This program improved the capability of SURF3D/LOT, which was initially developed in a previous SBIR program. This suite of codes revolutionized quasi-optical launcher design, and this code, or equivalent codes, are now used worldwide. This program added functionality tomore » SURF3D/LOT to allow creating of more compact launcher and mirror systems and provide direct coupling to corrugated waveguide within the vacuum envelope of the gyrotron. Analysis was also extended to include full-wave analysis of mirror transmission line systems. The code includes a graphical user interface and is available for advanced design of launcher systems.« less

Physical Investigations of Small Particles: (I) Aerosol Particle Charging and Flux Enhancement and (II) Whispering Gallery Mode Sensing

NASA Astrophysics Data System (ADS)

Lopez-Yglesias, Xerxes

of the molecule and the electromagnetic interaction between the molecule and particle, especially for the neutral particle case, are completely ignored, or, as is often the case for a permanent dipole vapor species, strongly underestimated. Comparing our model to these classical models we determine an "enhancement factor" to characterize how important the addition of these physical parameters and processes is to the understanding of particle nucleation and growth. Part II: Whispering gallery mode (WGM) optical biosensors are capable of extraordinarily sensitive specific and non-specific detection of species suspended in a gas or fluid. Recent experimental results suggest that these devices may attain single-molecule sensitivity to protein solutions in the form of stepwise shifts in their resonance wavelength, lambdaR, but present sensor models predict much smaller steps than were reported. This study examines the physical interaction between a WGM sensor and a molecule adsorbed to its surface, exploring assumptions made in previous efforts to model WGM sensor behavior, and describing computational schemes that model the experiments for which single protein sensitivity was reported. The resulting model is used to simulate sensor performance, within constraints imposed by the limited material property data. On this basis, we conclude that nonlinear optical effects would be needed to attain the reported sensitivity, and that, in the experiments for which extreme sensitivity was reported, a bound protein experiences optical energy fluxes too high for such effects to be ignored.

Label-free probing of genes by time-domain terahertz sensing.

PubMed

Haring Bolivar, P; Brucherseifer, M; Nagel, M; Kurz, H; Bosserhoff, A; Büttner, R

2002-11-07

A label-free sensing approach for the label-free characterization of genetic material with terahertz (THz) electromagnetic waves is presented. Time-resolved THz analysis of polynucleotides demonstrates a strong dependence of the complex refractive index of DNA molecules in the THz frequency range on their hybridization state. By monitoring THz signals one can thus infer the binding state (hybridized or denatured) of oligo- and polynucleotides, enabling the label-free determination the genetic composition of unknown DNA sequences. A broadband experimental proof-of-principle in a freespace analytic configuration, as well as a higher-sensitivity approach using integrated THz sensors reaching femtomol detection levels and demonstrating the capability to detect single-base mutations, are presented. The potential application for next generation high-throughput label-free genetic analytic systems is discussed.

Using label-free screening technology to improve efficiency in drug discovery.

PubMed

Halai, Reena; Cooper, Matthew A

2012-02-01

Screening assays have traditionally utilized reporter labels to quantify biological responses relevant to the disease state of interest. However, there are limitations associated with the use of labels that may be overcome with temporal measurements possible with label-free. This review comprises general and system-specific information from literature searches using PubMed, published books and the authors' personal experience. This review highlights the label-free approaches in the context of various applications. The authors also note technical issues relevant to the development of label-free assays and their application to HTS. The limitations associated with the use of transfected cell lines and the use of label-based assays are gradually being realized. As such, greater emphasis is being placed on label-free biophysical techniques using native cell lines. The introduction of 96- and 384-well plate label-free systems is helping to broker a wider acceptance of these approaches in high-throughput screening. However, potential users of the technologies remain skeptical, primarily because the physical basis of the signals generated, and their contextual relevance to cell biology and signal transduction, has not been fully elucidated. Until this is done, these new technology platforms are more likely to complement, rather than replace, traditional screening platforms.

Emerging applications of label-free optical biosensors

NASA Astrophysics Data System (ADS)

Zanchetta, Giuliano; Lanfranco, Roberta; Giavazzi, Fabio; Bellini, Tommaso; Buscaglia, Marco

2017-01-01

Innovative technical solutions to realize optical biosensors with improved performance are continuously proposed. Progress in material fabrication enables developing novel substrates with enhanced optical responses. At the same time, the increased spectrum of available biomolecular tools, ranging from highly specific receptors to engineered bioconjugated polymers, facilitates the preparation of sensing surfaces with controlled functionality. What remains often unclear is to which extent this continuous innovation provides effective breakthroughs for specific applications. In this review, we address this challenging question for the class of label-free optical biosensors, which can provide a direct signal upon molecular binding without using secondary probes. Label-free biosensors have become a consolidated approach for the characterization and screening of molecular interactions in research laboratories. However, in the last decade, several examples of other applications with high potential impact have been proposed. We review the recent advances in label-free optical biosensing technology by focusing on the potential competitive advantage provided in selected emerging applications, grouped on the basis of the target type. In particular, direct and real-time detection allows the development of simpler, compact, and rapid analytical methods for different kinds of targets, from proteins to DNA and viruses. The lack of secondary interactions facilitates the binding of small-molecule targets and minimizes the perturbation in single-molecule detection. Moreover, the intrinsic versatility of label-free sensing makes it an ideal platform to be integrated with biomolecular machinery with innovative functionality, as in case of the molecular tools provided by DNA nanotechnology.

MoMLA: From Panel to Gallery

ERIC Educational Resources Information Center

Vitanza, Victor, Ed.; Kuhn, Virginia, Ed.

2013-01-01

The work presented here in this "Panel to Gallery" was originally produced and assembled for the 2012 Modern Language Association Conference in Seattle, Washington. Similar to "From Gallery to Webtext", the event Victor curated for the 2006 College Composition and Communication Conference, this "Panel to Gallery" event at MLA set aside the…

Landslide Caused Damages in a Gallery

NASA Astrophysics Data System (ADS)

Poisel, R.; Mair am Tinkhof, K.; Preh, A.

2016-06-01

On October 5th, 2010, cracks were found in a gallery 1.8 m high and 1.4 m wide. The gallery is 100 years old, runs parallel to a valley flank and was excavated in a tectonically strongly stressed, weathered and slightly dipping sandwich of clayey shales, sandstones and marls. The cracks in the roof as well as in the invert ran parallel to the axis of the gallery. Monitoring showed that crack widths were increasing 1.5 mm per year, sidewall distances were increasing 3.5 mm per year, whereas the height of the gallery was decreasing 2.5 mm per year. After eliminating several possible causes of cracking, a landslide producing the damages had to be taken into consideration. Monitoring of the valley flank surface as well as inclinometer readings revealed that a landslide was occurring, loading the gallery lining. Most probably the landslide had been reactivated by excessive rainfall in 2009 as well as by works for the renewal of a weir in the valley bottom. As stabilization of the slope was not an option for several reasons, it was decided to replace the gallery by a new one deeper inside the slope, which will be ready for operation in 2017. Thus the old gallery has to be kept in operation till then and it was decided to reinforce the old gallery by a heavily reinforced shotcrete lining 10 cm thick. As slope displacements went on, cracks in the shotcrete lining developed with a completely different pattern: in the section where the gallery lies completely in the landslide shear zone no cracks formed until now due to heavy reinforcement, whereas in the transition sections stable ground-landslide and landslide-stable ground diagonal tension cracks in the roof due to shear by the landslide developed. Numerical models showed that cracking and spalling of the shotcrete lining would occur only after some centimetres of additional displacements of the slope, which hopefully will not occur before 2017.

Label-free high-throughput imaging flow cytometry

NASA Astrophysics Data System (ADS)

Mahjoubfar, A.; Chen, C.; Niazi, K. R.; Rabizadeh, S.; Jalali, B.

2014-03-01

Flow cytometry is an optical method for studying cells based on their individual physical and chemical characteristics. It is widely used in clinical diagnosis, medical research, and biotechnology for analysis of blood cells and other cells in suspension. Conventional flow cytometers aim a laser beam at a stream of cells and measure the elastic scattering of light at forward and side angles. They also perform single-point measurements of fluorescent emissions from labeled cells. However, many reagents used in cell labeling reduce cellular viability or change the behavior of the target cells through the activation of undesired cellular processes or inhibition of normal cellular activity. Therefore, labeled cells are not completely representative of their unaltered form nor are they fully reliable for downstream studies. To remove the requirement of cell labeling in flow cytometry, while still meeting the classification sensitivity and specificity goals, measurement of additional biophysical parameters is essential. Here, we introduce an interferometric imaging flow cytometer based on the world's fastest continuous-time camera. Our system simultaneously measures cellular size, scattering, and protein concentration as supplementary biophysical parameters for label-free cell classification. It exploits the wide bandwidth of ultrafast laser pulses to perform blur-free quantitative phase and intensity imaging at flow speeds as high as 10 meters per second and achieves nanometer-scale optical path length resolution for precise measurements of cellular protein concentration.

Novel image processing method study for a label-free optical biosensor

NASA Astrophysics Data System (ADS)

Yang, Chenhao; Wei, Li'an; Yang, Rusong; Feng, Ying

2015-10-01

Optical biosensor is generally divided into labeled type and label-free type, the former mainly contains fluorescence labeled method and radioactive-labeled method, while fluorescence-labeled method is more mature in the application. The mainly image processing methods of fluorescent-labeled biosensor includes smooth filtering, artificial gridding and constant thresholding. Since some fluorescent molecules may influence the biological reaction, label-free methods have been the main developing direction of optical biosensors nowadays. The using of wider field of view and larger angle of incidence light path which could effectively improve the sensitivity of the label-free biosensor also brought more difficulties in image processing, comparing with the fluorescent-labeled biosensor. Otsu's method is widely applied in machine vision, etc, which choose the threshold to minimize the intraclass variance of the thresholded black and white pixels. It's capacity-constrained with the asymmetrical distribution of images as a global threshold segmentation. In order to solve the irregularity of light intensity on the transducer, we improved the algorithm. In this paper, we present a new image processing algorithm based on a reflectance modulation biosensor platform, which mainly comprises the design of sliding normalization algorithm for image rectification and utilizing the improved otsu's method for image segmentation, in order to implement automatic recognition of target areas. Finally we used adaptive gridding method extracting the target parameters for analysis. Those methods could improve the efficiency of image processing, reduce human intervention, enhance the reliability of experiments and laid the foundation for the realization of high throughput of label-free optical biosensors.

Deep Learning in Label-free Cell Classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individualmore » cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. In conclusion, this system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.« less

Deep Learning in Label-free Cell Classification

PubMed Central

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia; Blaby, Ian K.; Huang, Allen; Niazi, Kayvan Reza; Jalali, Bahram

2016-01-01

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individual cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. This system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells. PMID:26975219

Deep Learning in Label-free Cell Classification

DOE PAGES

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia; ...

2016-03-15

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individualmore » cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. In conclusion, this system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.« less

Deep Learning in Label-free Cell Classification

NASA Astrophysics Data System (ADS)

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia; Blaby, Ian K.; Huang, Allen; Niazi, Kayvan Reza; Jalali, Bahram

2016-03-01

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individual cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. This system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.

Hereditary whispering dysphonia.

PubMed Central

Parker, N

1985-01-01

An Australian family group is described where at least twenty members have inherited torsion dystonia and two siblings with an affected mother have similar clinical manifestations, but have also the biochemical and pathological changes found in Wilson's disease. Whispering dysphonia was the commonest presenting symptom, and a diagnosis of hysteria was invariably made if the family history was not known. This group emphasises the enormously varied ways in which torsion dystonia may be manifested in one family, and raises the possibility of a disturbance in copper transport in diseases of the basal ganglia other than Wilson's disease. Images PMID:3156966

Label-free resistive-pulse cytometry.

PubMed

Chapman, M R; Sohn, L L

2011-01-01

Numerous methods have recently been developed to characterize cells for size, shape, and specific cell-surface markers. Most of these methods rely upon exogenous labeling of the cells and are better suited for large cell populations (>10,000). Here, we review a label-free method of characterizing and screening cells based on the Coulter-counter technique of particle sizing: an individual cell transiting a microchannel (or "pore") causes a downward pulse in the measured DC current across that "pore". Pulse magnitude corresponds to the cell size, pulse width to the transit time needed for the cell to pass through the pore, and pulse shape to how the cell traverses across the pore (i.e., rolling or tumbling). When the pore is functionalized with an antibody that is specific to a surface-epitope of interest, label-free screening of a specific marker is possible, as transient binding between the two results in longer time duration than when the pore is unfunctionalized or functionalized with a nonspecific antibody. While this method cannot currently compete with traditional technology in terms of throughput, there are a number of applications for which this technology is better suited than current commercial cytometry systems. Applications include the rapid and nondestructive analysis of small cell populations (<100), which is not possible with current technology, and a platform for providing true point-of-care clinical diagnostics, due to the simplicity of the device, low manufacturing costs, and ease of use. Copyright © 2011 Elsevier Inc. All rights reserved.

Study and development of label-free optical biosensors for biomedical applications

NASA Astrophysics Data System (ADS)

Choi, Charles J.

For the majority of assays currently performed, fluorescent or colorimetric chemical labels are commonly attached to the molecules under study so that they may be readily visualized. The methods of using labels to track biomolecular binding events are very sensitive and effective, and are employed as standardized assay protocol across research labs worldwide. However, using labels induces experimental uncertainties due to the effect of the label on molecular conformation, active binding sites, or inability to find an appropriate label that functions equivalently for all molecules in an experiment. Therefore, the ability to perform highly sensitive biochemical detection without the use of fluorescent labels would further simplify assay protocols and would provide quantitative kinetic data, while removing experimental artifacts from fluorescent quenching, shelf-life, and background fluorescence phenomena. In view of the advantages mentioned above, the study and development of optical label-free sensor technologies have been undertaken here. In general, label-free photonic crystal (PC) biosensors and metal nanodome array surface-enhanced Raman scattering (SERS) substrates, both of which are fabricated by nanoreplica molding process, have been used as the method to attack the problem. Chapter 1 shows the work on PC label-free biosensor incorporated microfluidic network for bioassay performance enhancement and kinetic reaction rate constant determination. Chapter 2 describes the work on theoretical and experimental comparison of label-free biosensing in microplate, microfluidic, and spot-based affinity capture assays. Chapter 3 shows the work on integration of PC biosensor with actuate-to-open valve microfluidic chip for pL-volume combinatorial mixing and screening application. In Chapter 4, the development and characterization of SERS nanodome array is shown. Lastly, Chapter 5 describes SERS nanodome sensor incorporated tubing for point-of-care monitoring of

Nanoscale Label-free Bioprobes to Detect Intracellular Proteins in Single Living Cells

PubMed Central

Hong, Wooyoung; Liang, Feng; Schaak, Diane; Loncar, Marko; Quan, Qimin

2014-01-01

Fluorescent labeling techniques have been widely used in live cell studies; however, the labeling processes can be laborious and challenging for use in non-transfectable cells, and labels can interfere with protein functions. While label-free biosensors have been realized by nanofabrication, a method to track intracellular protein dynamics in real-time, in situ and in living cells has not been found. Here we present the first demonstration of label-free detection of intracellular p53 protein dynamics through a nanoscale surface plasmon-polariton fiber-tip-probe (FTP). PMID:25154394

Intravital imaging by simultaneous label-free autofluorescence-multiharmonic microscopy.

PubMed

You, Sixian; Tu, Haohua; Chaney, Eric J; Sun, Yi; Zhao, Youbo; Bower, Andrew J; Liu, Yuan-Zhi; Marjanovic, Marina; Sinha, Saurabh; Pu, Yang; Boppart, Stephen A

2018-05-29

Intravital microscopy (IVM) emerged and matured as a powerful tool for elucidating pathways in biological processes. Although label-free multiphoton IVM is attractive for its non-perturbative nature, its wide application has been hindered, mostly due to the limited contrast of each imaging modality and the challenge to integrate them. Here we introduce simultaneous label-free autofluorescence-multiharmonic (SLAM) microscopy, a single-excitation source nonlinear imaging platform that uses a custom-designed excitation window at 1110 nm and shaped ultrafast pulses at 10 MHz to enable fast (2-orders-of-magnitude improvement), simultaneous, and efficient acquisition of autofluorescence (FAD and NADH) and second/third harmonic generation from a wide array of cellular and extracellular components (e.g., tumor cells, immune cells, vesicles, and vessels) in living tissue using only 14 mW for extended time-lapse investigations. Our work demonstrates the versatility and efficiency of SLAM microscopy for tracking cellular events in vivo, and is a major enabling advance in label-free IVM.

Label-free photoacoustic nanoscopy

PubMed Central

Danielli, Amos; Maslov, Konstantin; Garcia-Uribe, Alejandro; Winkler, Amy M.; Li, Chiye; Wang, Lidai; Chen, Yun; Dorn, Gerald W.; Wang, Lihong V.

2014-01-01

Abstract. Super-resolution microscopy techniques—capable of overcoming the diffraction limit of light—have opened new opportunities to explore subcellular structures and dynamics not resolvable in conventional far-field microscopy. However, relying on staining with exogenous fluorescent markers, these techniques can sometimes introduce undesired artifacts to the image, mainly due to large tagging agent sizes and insufficient or variable labeling densities. By contrast, the use of endogenous pigments allows imaging of the intrinsic structures of biological samples with unaltered molecular constituents. Here, we report label-free photoacoustic (PA) nanoscopy, which is exquisitely sensitive to optical absorption, with an 88 nm resolution. At each scanning position, multiple PA signals are successively excited with increasing laser pulse energy. Because of optical saturation or nonlinear thermal expansion, the PA amplitude depends on the nonlinear incident optical fluence. The high-order dependence, quantified by polynomial fitting, provides super-resolution imaging with optical sectioning. PA nanoscopy is capable of super-resolution imaging of either fluorescent or nonfluorescent molecules. PMID:25104412

Systematic Comparison of Label-Free, Metabolic Labeling, and Isobaric Chemical Labeling for Quantitative Proteomics on LTQ Orbitrap Velos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhou; Adams, Rachel M; Chourey, Karuna

2012-01-01

A variety of quantitative proteomics methods have been developed, including label-free, metabolic labeling, and isobaric chemical labeling using iTRAQ or TMT. Here, these methods were compared in terms of the depth of proteome coverage, quantification accuracy, precision, and reproducibility using a high-performance hybrid mass spectrometer, LTQ Orbitrap Velos. Our results show that (1) the spectral counting method provides the deepest proteome coverage for identification, but its quantification performance is worse than labeling-based approaches, especially the quantification reproducibility; (2) metabolic labeling and isobaric chemical labeling are capable of accurate, precise, and reproducible quantification and provide deep proteome coverage for quantification. Isobaricmore » chemical labeling surpasses metabolic labeling in terms of quantification precision and reproducibility; (3) iTRAQ and TMT perform similarly in all aspects compared in the current study using a CID-HCD dual scan configuration. Based on the unique advantages of each method, we provide guidance for selection of the appropriate method for a quantitative proteomics study.« less

GLCF: Gallery

Science.gov Websites

UMD Land Cover Classification Product External Galleries * ASTER at JPL * AVHRR at JHU * Earth Observatory at NASA * Landsat 7 at USGS * MODIS at NASA * Visible Earth at NASA e-link 4321 Hartwick Building

Brillouin Light Scattering by Magnetic Quasivortices in Cavity Optomagnonics

NASA Astrophysics Data System (ADS)

Osada, A.; Gloppe, A.; Hisatomi, R.; Noguchi, A.; Yamazaki, R.; Nomura, M.; Nakamura, Y.; Usami, K.

2018-03-01

A ferromagnetic sphere can support optical vortices in the form of whispering gallery modes and magnetic quasivortices in the form of magnetostatic modes with nontrivial spin textures. These vortices can be characterized by their orbital angular momenta. We experimentally investigate Brillouin scattering of photons in the whispering gallery modes by magnons in the magnetostatic modes, zeroing in on the exchange of the orbital angular momenta between the optical vortices and magnetic quasivortices. We find that the conservation of the orbital angular momentum results in different nonreciprocal behavior in the Brillouin light scattering. New avenues for chiral optics and optospintronics can be opened up by taking the orbital angular momenta as a new degree of freedom for cavity optomagnonics.

Chaos-assisted broadband momentum transformation in optical microresonators

NASA Astrophysics Data System (ADS)

Jiang, Xuefeng; Shao, Linbo; Zhang, Shu-Xin; Yi, Xu; Wiersig, Jan; Wang, Li; Gong, Qihuang; Lončar, Marko; Yang, Lan; Xiao, Yun-Feng

2017-10-01

The law of momentum conservation rules out many desired processes in optical microresonators. We report broadband momentum transformations of light in asymmetric whispering gallery microresonators. Assisted by chaotic motions, broadband light can travel between optical modes with different angular momenta within a few picoseconds. Efficient coupling from visible to near-infrared bands is demonstrated between a nanowaveguide and whispering gallery modes with quality factors exceeding 10 million. The broadband momentum transformation enhances the device conversion efficiency of the third-harmonic generation by greater than three orders of magnitude over the conventional evanescent-wave coupling. The observed broadband and fast momentum transformation could promote applications such as multicolor lasers, broadband memories, and multiwavelength optical networks.

Label-Free Aptasensors for the Detection of Mycotoxins

PubMed Central

Rhouati, Amina; Catanante, Gaelle; Nunes, Gilvanda; Hayat, Akhtar; Marty, Jean-Louis

2016-01-01

Various methodologies have been reported in the literature for the qualitative and quantitative monitoring of mycotoxins in food and feed samples. Based on their enhanced specificity, selectivity and versatility, bio-affinity assays have inspired many researchers to develop sensors by exploring bio-recognition phenomena. However, a significant problem in the fabrication of these devices is that most of the biomolecules do not generate an easily measurable signal upon binding to the target analytes, and signal-generating labels are required to perform the measurements. In this context, aptamers have been emerged as a potential and attractive bio-recognition element to design label-free aptasensors for various target analytes. Contrary to other bioreceptor-based approaches, the aptamer-based assays rely on antigen binding-induced conformational changes or oligomerization states rather than binding-assisted changes in adsorbed mass or charge. This review will focus on current designs in label-free conformational switchable design strategies, with a particular focus on applications in the detection of mycotoxins. PMID:27999353

Developments in label-free microfluidic methods for single-cell analysis and sorting.

PubMed

Carey, Thomas R; Cotner, Kristen L; Li, Brian; Sohn, Lydia L

2018-04-24

Advancements in microfluidic technologies have led to the development of many new tools for both the characterization and sorting of single cells without the need for exogenous labels. Label-free microfluidics reduce the preparation time, reagents needed, and cost of conventional methods based on fluorescent or magnetic labels. Furthermore, these devices enable analysis of cell properties such as mechanical phenotype and dielectric parameters that cannot be characterized with traditional labels. Some of the most promising technologies for current and future development toward label-free, single-cell analysis and sorting include electronic sensors such as Coulter counters and electrical impedance cytometry; deformation analysis using optical traps and deformation cytometry; hydrodynamic sorting such as deterministic lateral displacement, inertial focusing, and microvortex trapping; and acoustic sorting using traveling or standing surface acoustic waves. These label-free microfluidic methods have been used to screen, sort, and analyze cells for a wide range of biomedical and clinical applications, including cell cycle monitoring, rapid complete blood counts, cancer diagnosis, metastatic progression monitoring, HIV and parasite detection, circulating tumor cell isolation, and point-of-care diagnostics. Because of the versatility of label-free methods for characterization and sorting, the low-cost nature of microfluidics, and the rapid prototyping capabilities of modern microfabrication, we expect this class of technology to continue to be an area of high research interest going forward. New developments in this field will contribute to the ongoing paradigm shift in cell analysis and sorting technologies toward label-free microfluidic devices, enabling new capabilities in biomedical research tools as well as clinical diagnostics. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices. © 2018 Wiley Periodicals, Inc.

Escherichia coli cell-free protein synthesis and isotope labeling of mammalian proteins.

PubMed

Terada, Takaho; Yokoyama, Shigeyuki

2015-01-01

This chapter describes the cell-free protein synthesis method, using an Escherichia coli cell extract. This is a cost-effective method for milligram-scale protein production and is particularly useful for the production of mammalian proteins, protein complexes, and membrane proteins that are difficult to synthesize by recombinant expression methods, using E. coli and eukaryotic cells. By adjusting the conditions of the cell-free method, zinc-binding proteins, disulfide-bonded proteins, ligand-bound proteins, etc., may also be produced. Stable isotope labeling of proteins can be accomplished by the cell-free method, simply by using stable isotope-labeled amino acid(s) in the cell-free reaction. Moreover, the cell-free protein synthesis method facilitates the avoidance of stable isotope scrambling and dilution over the recombinant expression methods and is therefore advantageous for amino acid-selective stable isotope labeling. Site-specific stable isotope labeling is also possible with a tRNA molecule specific to the UAG codon. By the cell-free protein synthesis method, coupled transcription-translation is performed from a plasmid vector or a PCR-amplified DNA fragment encoding the protein. A milligram quantity of protein can be produced with a milliliter-scale reaction solution in the dialysis mode. More than a thousand solution structures have been determined by NMR spectroscopy for uniformly labeled samples of human and mouse functional domain proteins, produced by the cell-free method. Here, we describe the practical aspects of mammalian protein production by the cell-free method for NMR spectroscopy. © 2015 Elsevier Inc. All rights reserved.

Labeling of indocyanine green with carrier-free iodine-123

DOEpatents

Ansari, Azizullah N.; Lambrecht, Richard M.; Redvanly, Carol S.; Wolf, Alfred P.

1976-01-01

The method of labeling indocyanine green (ICG) with carrier-free iodine-123 comprising the steps of condensing xenon-123 on crystals of ICG followed by permitting decay of the .sup.123 Xe a sufficient length of time to produce .sup.123 I-electronically excited ions and atoms which subsequently label ICG.

Heritage Gallery

NASA Technical Reports Server (NTRS)

2002-01-01

Marshall Space Flight Center's (MSFC's) building 4200 hosts a new spaceflight history museum referred to as the Heritage Gallery, allowing employees and visitors alike to have the opportunity to experience history first hand. On display are many models of launch vehicles and spacecraft that have made the center famous. It features a full-scale mockup of the lunar roving vehicle, three built-in multimedia displays, a large theater screen, and two glass cases that house memorabilia such as personal items belonging to Wernher von Braun, MSFC's first Center Director. The new Heritage Gallery features the accomplishments of several past and present members of the Marshall team. Attending the ribbon cutting ceremony are: (left to right) Gerhard Reisig; Cort Durocher, executive director of the American Institute of Aeronautics and Astronautics; Ernst Stuhlinger; Konrad Darnenburg; Werner Dahm; Walter Jacobi; and host of event, Center Director Art Stephenson.

Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

NASA Astrophysics Data System (ADS)

Chirvi, Sajal

Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi

Tailoring of the free spectral range and geometrical cavity dispersion of a microsphere by a coating layer.

PubMed

Ristić, Davor; Mazzola, Maurizio; Chiappini, Andrea; Rasoloniaina, Alphonse; Féron, Patrice; Ramponi, Roberta; Righini, Giancarlo C; Cibiel, Gilles; Ivanda, Mile; Ferrari, Maurizio

2014-09-01

The modal dispersion of a whispering gallery mode (WGM) resonator is a very important parameter for use in all nonlinear optics applications. In order to tailor the WGM modal dispersion of a microsphere, we have coated a silica microsphere with a high-refractive-index coating in order to study its effect on the WGM modal dispersion. We used Er(3+) ions as a probe for a modal dispersion assessment. We found that, by varying the coating thickness, the geometrical cavity dispersion can be used to shift overall modal dispersion in a very wide range in both the normal and anomalous dispersion regime.

Label and label-free based surface-enhanced Raman scattering for pathogen bacteria detection: A review.

PubMed

Liu, Yu; Zhou, Haibo; Hu, Ziwei; Yu, Guangxia; Yang, Danting; Zhao, Jinshun

2017-08-15

Rapid, accurate detection of pathogen bacteria is a highly topical research area for the sake of food safety and public health. Surface-enhanced Raman scattering (SERS) is being considered as a powerful and attractive technique for pathogen bacteria detection, due to its sensitivity, high speed, comparatively low cost, multiplexing ability and portability. This contribution aims to give a comprehensive overview of SERS as a technique for rapid detection of pathogen bacteria based on label and label-free strategies. A brief tutorial on SERS is given first of all. Then we summarize the recent trends and developments of label and label-free based SERS applied to detection of pathogen bacteria, including the relatively complete interpretation of SERS spectra. In addition, multifunctional SERS platforms for pathogen bacteria in matrix are discussed as well. Furthermore, an outlook of the work done and a perspective on the future directions of SERS as a reliable tool for real-time pathogen bacteria detection are given. Copyright © 2017 Elsevier B.V. All rights reserved.

The WHISPER Relaxation Sounder and the CLUSTER Active Archive

NASA Astrophysics Data System (ADS)

Trotignon, J. G.; Décréau, P. M. E.; Rauch, J. L.; Vallières, X.; Rochel, A.; Kougblénou, S.; Lointier, G.; Facskó, G.; Canu, P.; Darrouzet, F.; Masson, A.

The Waves of HIgh frequency and Sounder for Probing of Electron density by Relaxation (WHISPER) instrument is part of the Wave Experiment Consortium (WEC) of the CLUSTER mission. With the help of the long double sphere antennae of the Electric Field and Wave (EFW) instrument and the Digital Wave Processor (DWP), it delivers active (sounding) and natural (transmitter off) electric field spectra, respectively from 4 to 82 kHz, and from 2 to 80 kHz. These frequency ranges have been chosen to include the electron plasma frequency, which is closely related to the total electron density, in most of the regions encountered by the CLUSTER spacecraft. Presented here is an overview of the WHISPER data products available in the CLUSTER Active Archive (CAA). The instrument and its performance are first recalled. The way the WHISPER products are obtained is then described, with particular attention being paid to the density determination. Both sounding and natural measurements are commonly used in this process, which depends on the ambient plasma regime. This is illustrated using drawings similar to the Bryant plots commonly used in the CLUSTER master science plan. These give a clear overview of typical density values and the parts of the orbits where they are obtained. More information on the applied software or on the quality/reliability of the density determination can also be highlighted.

A Method for Label-Free, Differential Top-Down Proteomics.

PubMed

Ntai, Ioanna; Toby, Timothy K; LeDuc, Richard D; Kelleher, Neil L

2016-01-01

Biomarker discovery in the translational research has heavily relied on labeled and label-free quantitative bottom-up proteomics. Here, we describe a new approach to biomarker studies that utilizes high-throughput top-down proteomics and is the first to offer whole protein characterization and relative quantitation within the same experiment. Using yeast as a model, we report procedures for a label-free approach to quantify the relative abundance of intact proteins ranging from 0 to 30 kDa in two different states. In this chapter, we describe the integrated methodology for the large-scale profiling and quantitation of the intact proteome by liquid chromatography-mass spectrometry (LC-MS) without the need for metabolic or chemical labeling. This recent advance for quantitative top-down proteomics is best implemented with a robust and highly controlled sample preparation workflow before data acquisition on a high-resolution mass spectrometer, and the application of a hierarchical linear statistical model to account for the multiple levels of variance contained in quantitative proteomic comparisons of samples for basic and clinical research.

Guards, Galleries, Fortresses, and the Octoplex

ERIC Educational Resources Information Center

Michael, T. S.

2011-01-01

The art gallery problem asks for the maximum number of stationary guards required to protect the interior of a polygonal art gallery with "n" walls. This article explores solutions to this problem and several of its variants. In addition, some unsolved problems involving the guarding of geometric objects are presented.

Parity-Time-Symmetric Whispering-Gallery Microcavities

DTIC Science & Technology

2014-04-06

Stone, A. D. PT - symmetry breaking and laser -absorber modes in optical scattering systems. Phys. Rev. Lett. 106, 093902 (2011). 31. Liang, G. Q. & Chong...see that only when the PT - symmetry is broken, the field is localized in the active resonator and thus the signal at the output port of the fiber ...peaks. Fig.S9. Localization of the optical field in the active resonator in the broken- PT symmetry phase. Fiber taper waveguide with ports 1 and

Recognizing Whispered Speech Produced by an Individual with Surgically Reconstructed Larynx Using Articulatory Movement Data

PubMed Central

Cao, Beiming; Kim, Myungjong; Mau, Ted; Wang, Jun

2017-01-01

Individuals with larynx (vocal folds) impaired have problems in controlling their glottal vibration, producing whispered speech with extreme hoarseness. Standard automatic speech recognition using only acoustic cues is typically ineffective for whispered speech because the corresponding spectral characteristics are distorted. Articulatory cues such as the tongue and lip motion may help in recognizing whispered speech since articulatory motion patterns are generally not affected. In this paper, we investigated whispered speech recognition for patients with reconstructed larynx using articulatory movement data. A data set with both acoustic and articulatory motion data was collected from a patient with surgically reconstructed larynx using an electromagnetic articulograph. Two speech recognition systems, Gaussian mixture model-hidden Markov model (GMM-HMM) and deep neural network-HMM (DNN-HMM), were used in the experiments. Experimental results showed adding either tongue or lip motion data to acoustic features such as mel-frequency cepstral coefficient (MFCC) significantly reduced the phone error rates on both speech recognition systems. Adding both tongue and lip data achieved the best performance. PMID:29423453

Plutonium Critical Mass Curve Comparison to Mass at Upper Subcritical Limit (USL) Using Whisper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alwin, Jennifer Louise; Zhang, Ning

Whisper is computational software designed to assist the nuclear criticality safety analyst with validation studies with the MCNP ® Monte Carlo radiation transport package. Standard approaches to validation rely on the selection of benchmarks based upon expert judgment. Whisper uses sensitivity/uncertainty (S/U) methods to select relevant benchmarks to a particular application or set of applications being analyzed. Using these benchmarks, Whisper computes a calculational margin. Whisper attempts to quantify the margin of subcriticality (MOS) from errors in software and uncertainties in nuclear data. The combination of the Whisper-derived calculational margin and MOS comprise the baseline upper subcritical limit (USL), tomore » which an additional margin may be applied by the nuclear criticality safety analyst as appropriate to ensure subcriticality. A series of critical mass curves for plutonium, similar to those found in Figure 31 of LA-10860-MS, have been generated using MCNP6.1.1 and the iterative parameter study software, WORM_Solver. The baseline USL for each of the data points of the curves was then computed using Whisper 1.1. The USL was then used to determine the equivalent mass for plutonium metal-water system. ANSI/ANS-8.1 states that it is acceptable to use handbook data, such as the data directly from the LA-10860-MS, as it is already considered validated (Section 4.3 4) “Use of subcritical limit data provided in ANSI/ANS standards or accepted reference publications does not require further validation.”). This paper attempts to take a novel approach to visualize traditional critical mass curves and allows comparison with the amount of mass for which the k eff is equal to the USL (calculational margin + margin of subcriticality). However, the intent is to plot the critical mass data along with USL, not to suggest that already accepted handbook data should have new and more rigorous requirements for validation.« less

Label-free electrical detection using carbon nanotube-based biosensors.

PubMed

Maehashi, Kenzo; Matsumoto, Kazuhiko

2009-01-01

Label-free detections of biomolecules have attracted great attention in a lot of life science fields such as genomics, clinical diagnosis and practical pharmacy. In this article, we reviewed amperometric and potentiometric biosensors based on carbon nanotubes (CNTs). In amperometric detections, CNT-modified electrodes were used as working electrodes to significantly enhance electroactive surface area. In contrast, the potentiometric biosensors were based on aptamer-modified CNT field-effect transistors (CNTFETs). Since aptamers are artificial oligonucleotides and thus are smaller than the Debye length, proteins can be detected with high sensitivity. In this review, we discussed on the technology, characteristics and developments for commercialization in label-free CNT-based biosensors.

Label-free optical resonant sensors for biochemical applications

NASA Astrophysics Data System (ADS)

Ciminelli, Caterina; Campanella, Clarissa Martina; Dell'Olio, Francesco; Campanella, Carlo Edoardo; Armenise, Mario Nicola

2013-03-01

For a number of years, the scientific community has been paying growing attention to the monitoring and enhancement of public health and the quality of life through the detection of all dangerous agents for the human body, including gases, proteins, virus, and bacterial agents. When these agents are detected through label-free biochemical sensors, the molecules are not modified structurally or functionally by adding fluorescent or radioactive dyes. This work focuses on label-free optical ring resonator-based configurations suited for bio-chemical sensing, highlighting their physical aspects and specific applications. Resonant wavelength shift and the modal splitting occurring when the analyte interacts with microresonant structures are the two major physical aspects analyzed in this paper. Competitive optical platforms proposed in the literature are also illustrated together with their properties and performance.

Real-time label-free biosensing with integrated planar waveguide ring resonators

NASA Astrophysics Data System (ADS)

Sohlström, Hans; Gylfason, Kristinn B.; Hill, Daniel

2010-05-01

We review the use of planar integrated optical waveguide ring resonators for label free bio-sensing and present recent results from two European biosensor collaborations: SABIO and InTopSens. Planar waveguide ring resonators are attractive for label-free biosensing due to their small footprint, high Q-factors, and compatibility with on-chip optics and microfluidics. This enables integrated sensor arrays for compact labs-on-chip. One application of label-free sensor arrays is for point-of-care medical diagnostics. Bringing such powerful tools to the single medical practitioner is an important step towards personalized medicine, but requires addressing a number of issues: improving limit of detection, managing the influence of temperature, parallelization of the measurement for higher throughput and on-chip referencing, efficient light-coupling strategies to simplify alignment, and packaging of the optical chip and integration with microfluidics. From the SABIO project we report refractive index measurement and label-free biosensing in an 8-channel slotwaveguide ring resonator sensor array, within a compact cartridge with integrated microfluidics. The sensors show a volume sensing detection limit of 5 x 10-6 RIU and a surface sensing detection limit of 0.9 pg/mm2. From the InTopSens project we report early results on silicon-on-insulator racetrack resonators.

Hybrid label-free multiphoton and optoacoustic microscopy (MPOM)

NASA Astrophysics Data System (ADS)

Soliman, Dominik; Tserevelakis, George J.; Omar, Murad; Ntziachristos, Vasilis

2015-07-01

Many biological applications require a simultaneous observation of different anatomical features. However, unless potentially harmful staining of the specimens is employed, individual microscopy techniques do generally not provide multi-contrast capabilities. We present a hybrid microscope integrating optoacoustic microscopy and multiphoton microscopy, including second-harmonic generation, into a single device. This combined multiphoton and optoacoustic microscope (MPOM) offers visualization of a broad range of structures by employing different contrast mechanisms and at the same time enables pure label-free imaging of biological systems. We investigate the relative performance of the two microscopy modalities and demonstrate their multi-contrast abilities through the label-free imaging of a zebrafish larva ex vivo, simultaneously visualizing muscles and pigments. This hybrid microscopy application bears great potential for developmental biology studies, enabling more comprehensive information to be obtained from biological specimens without the necessity of staining.

High-throughput screening based on label-free detection of small molecule microarrays

NASA Astrophysics Data System (ADS)

Zhu, Chenggang; Fei, Yiyan; Zhu, Xiangdong

2017-02-01

Based on small-molecule microarrays (SMMs) and oblique-incidence reflectivity difference (OI-RD) scanner, we have developed a novel high-throughput drug preliminary screening platform based on label-free monitoring of direct interactions between target proteins and immobilized small molecules. The screening platform is especially attractive for screening compounds against targets of unknown function and/or structure that are not compatible with functional assay development. In this screening platform, OI-RD scanner serves as a label-free detection instrument which is able to monitor about 15,000 biomolecular interactions in a single experiment without the need to label any biomolecule. Besides, SMMs serves as a novel format for high-throughput screening by immobilization of tens of thousands of different compounds on a single phenyl-isocyanate functionalized glass slide. Based on the high-throughput screening platform, we sequentially screened five target proteins (purified target proteins or cell lysate containing target protein) in high-throughput and label-free mode. We found hits for respective target protein and the inhibition effects for some hits were confirmed by following functional assays. Compared to traditional high-throughput screening assay, the novel high-throughput screening platform has many advantages, including minimal sample consumption, minimal distortion of interactions through label-free detection, multi-target screening analysis, which has a great potential to be a complementary screening platform in the field of drug discovery.

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

DOE PAGES

Lu, Fa-Ke; Basu, Srinjan; Igras, Vivien; ...

2015-08-31

Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based onmore » changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Moreover, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. In conclusion, our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time.« less

Label-free DNA imaging in vivo with stimulated Raman scattering microscopy

PubMed Central

Lu, Fa-Ke; Basu, Srinjan; Igras, Vivien; Hoang, Mai P.; Ji, Minbiao; Fu, Dan; Holtom, Gary R.; Neel, Victor A.; Freudiger, Christian W.; Fisher, David E.; Xie, X. Sunney

2015-01-01

Label-free DNA imaging is highly desirable in biology and medicine to perform live imaging without affecting cell function and to obtain instant histological tissue examination during surgical procedures. Here we show a label-free DNA imaging method with stimulated Raman scattering (SRS) microscopy for visualization of the cell nuclei in live animals and intact fresh human tissues with subcellular resolution. Relying on the distinct Raman spectral features of the carbon-hydrogen bonds in DNA, the distribution of DNA is retrieved from the strong background of proteins and lipids by linear decomposition of SRS images at three optimally selected Raman shifts. Based on changes on DNA condensation in the nucleus, we were able to capture chromosome dynamics during cell division both in vitro and in vivo. We tracked mouse skin cell proliferation, induced by drug treatment, through in vivo counting of the mitotic rate. Furthermore, we demonstrated a label-free histology method for human skin cancer diagnosis that provides comparable results to other conventional tissue staining methods such as H&E. Our approach exhibits higher sensitivity than SRS imaging of DNA in the fingerprint spectral region. Compared with spontaneous Raman imaging of DNA, our approach is three orders of magnitude faster, allowing both chromatin dynamic studies and label-free optical histology in real time. PMID:26324899

Label-free and live cell imaging by interferometric scattering microscopy.

PubMed

Park, Jin-Sung; Lee, Il-Buem; Moon, Hyeon-Min; Joo, Jong-Hyeon; Kim, Kyoung-Hoon; Hong, Seok-Cheol; Cho, Minhaeng

2018-03-14

Despite recent remarkable advances in microscopic techniques, it still remains very challenging to directly observe the complex structure of cytoplasmic organelles in live cells without a fluorescent label. Here we report label-free and live-cell imaging of mammalian cell, Escherischia coli , and yeast, using interferometric scattering microscopy, which reveals the underlying structures of a variety of cytoplasmic organelles as well as the underside structure of the cells. The contact areas of the cells attached onto a glass substrate, e.g. , focal adhesions and filopodia, are clearly discernible. We also found a variety of fringe-like features in the cytoplasmic area, which may reflect the folded structures of cytoplasmic organelles. We thus anticipate that the label-free interferometric scattering microscopy can be used as a powerful tool to shed interferometric light on in vivo structures and dynamics of various intracellular phenomena.

A multicenter study benchmarks software tools for label-free proteome quantification.

PubMed

Navarro, Pedro; Kuharev, Jörg; Gillet, Ludovic C; Bernhardt, Oliver M; MacLean, Brendan; Röst, Hannes L; Tate, Stephen A; Tsou, Chih-Chiang; Reiter, Lukas; Distler, Ute; Rosenberger, George; Perez-Riverol, Yasset; Nesvizhskii, Alexey I; Aebersold, Ruedi; Tenzer, Stefan

2016-11-01

Consistent and accurate quantification of proteins by mass spectrometry (MS)-based proteomics depends on the performance of instruments, acquisition methods and data analysis software. In collaboration with the software developers, we evaluated OpenSWATH, SWATH 2.0, Skyline, Spectronaut and DIA-Umpire, five of the most widely used software methods for processing data from sequential window acquisition of all theoretical fragment-ion spectra (SWATH)-MS, which uses data-independent acquisition (DIA) for label-free protein quantification. We analyzed high-complexity test data sets from hybrid proteome samples of defined quantitative composition acquired on two different MS instruments using different SWATH isolation-window setups. For consistent evaluation, we developed LFQbench, an R package, to calculate metrics of precision and accuracy in label-free quantitative MS and report the identification performance, robustness and specificity of each software tool. Our reference data sets enabled developers to improve their software tools. After optimization, all tools provided highly convergent identification and reliable quantification performance, underscoring their robustness for label-free quantitative proteomics.

OAM-labeled free-space optical flow routing.

PubMed

Gao, Shecheng; Lei, Ting; Li, Yangjin; Yuan, Yangsheng; Xie, Zhenwei; Li, Zhaohui; Yuan, Xiaocong

2016-09-19

Space-division multiplexing allows unprecedented scaling of bandwidth density for optical communication. Routing spatial channels among transmission ports is critical for future scalable optical network, however, there is still no characteristic parameter to label the overlapped optical carriers. Here we propose a free-space optical flow routing (OFR) scheme by using optical orbital angular moment (OAM) states to label optical flows and simultaneously steer each flow according to their OAM states. With an OAM multiplexer and a reconfigurable OAM demultiplexer, massive individual optical flows can be routed to the demanded optical ports. In the routing process, the OAM beams act as data carriers at the same time their topological charges act as each carrier's labels. Using this scheme, we experimentally demonstrate switching, multicasting and filtering network functions by simultaneously steer 10 input optical flows on demand to 10 output ports. The demonstration of data-carrying OFR with nonreturn-to-zero signals shows that this process enables synchronous processing of massive spatial channels and flexible optical network.

Label-free nano-biosensing on the road to tuberculosis detection.

PubMed

Golichenari, Behrouz; Velonia, Kelly; Nosrati, Rahim; Nezami, Alireza; Farokhi-Fard, Aref; Abnous, Khalil; Behravan, Javad; Tsatsakis, Aristidis M

2018-08-15

Tuberculosis, an ailment caused by the bacterium Mycobacterium tuberculosis (Mtb) complex, is one of the catastrophic transmittable diseases that affect human. Reports published by WHO indicate that in 2017 about 6.3 million people progressed to TB and 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. Common diagnostics like the traditional PPD test and antibody-assisted assays suffer the lack of sensitivity, long processing time and cumbersome post-test proceedings. These shortcomings restrict their use and encourage innovations in TB diagnostics. In recent years, the biosensor concept opened up new horizons in sensitive and fast detection of the disease, reducing the interval time between sampling and diagnostic result. Among new diagnostics, label-free nano-biosensors are highly promising for sensitive and accessible detection of tuberculosis. Various specific label-free nano-biosensors have been recently reported detecting the whole cell of M. tuberculosis, mycobacterial proteins and IFN-γ as crucial markers in early diagnosis of TB. This article provides a focused overview on nanomaterial-based label-free biosensors for tuberculosis detection. Copyright © 2018 Elsevier B.V. All rights reserved.

Label free detection of phospholipids by infrared absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ahmed, Tahsin; Foster, Erick; Vigil, Genevieve; Khan, Aamir A.; Bohn, Paul; Howard, Scott S.

2014-08-01

We present our study on compact, label-free dissolved lipid sensing by combining capillary electrophoresis separation in a PDMS microfluidic chip online with mid-infrared (MIR) absorption spectroscopy for biomarker detection. On-chip capillary electrophoresis is used to separate the biomarkers without introducing any extrinsic contrast agent, which reduces both cost and complexity. The label free biomarker detection could be done by interrogating separated biomarkers in the channel by MIR absorption spectroscopy. Phospholipids biomarkers of degenerative neurological, kidney, and bone diseases are detectable using this label free technique. These phospholipids exhibit strong absorption resonances in the MIR and are present in biofluids including urine, blood plasma, and cerebrospinal fluid. MIR spectroscopy of a 12-carbon chain phosphatidic acid (PA) (1,2-dilauroyl-snglycero- 3-phosphate (sodium salt)) dissolved in N-methylformamide, exhibits a strong amide peak near wavenumber 1660 cm-1 (wavelength 6 μm), arising from the phosphate headgroup vibrations within a low-loss window of the solvent. PA has a similar structure to many important phospholipids molecules like phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and phosphatidylserine (PS), making it an ideal molecule for initial proof-of-concept studies. This newly proposed detection technique can lead us to minimal sample preparation and is capable of identifying several biomarkers from the same sample simultaneously.

Label-free isolation of circulating tumor cells in microfluidic devices: Current research and perspectives.

PubMed

Cima, Igor; Wen Yee, Chay; Iliescu, Florina S; Phyo, Wai Min; Lim, Kiat Hon; Iliescu, Ciprian; Tan, Min Han

2013-01-01

This review will cover the recent advances in label-free approaches to isolate and manipulate circulating tumor cells (CTCs). In essence, label-free approaches do not rely on antibodies or biological markers for labeling the cells of interest, but enrich them using the differential physical properties intrinsic to cancer and blood cells. We will discuss technologies that isolate cells based on their biomechanical and electrical properties. Label-free approaches to analyze CTCs have been recently invoked as a valid alternative to "marker-based" techniques, because classical epithelial and tumor markers are lost on some CTC populations and there is no comprehensive phenotypic definition for CTCs. We will highlight the advantages and drawbacks of these technologies and the status on their implementation in the clinics.

A comparative analysis of whispered and normally phonated speech using an LPC-10 vocoder

NASA Astrophysics Data System (ADS)

Wilson, J. B.; Mosko, J. D.

1985-12-01

The determination of the performance of an LPC-10 vocoder in the processing of adult male and female whispered and normally phonated connected speech was the focus of this study. The LPC-10 vocoder's analysis of whispered speech compared quite favorably with similar studies which used sound spectrographic processing techniques. Shifting from phonated speech to whispered speech caused a substantial increase in the phonomic formant frequencies and formant bandwidths for both male and female speakers. The data from this study showed no evidence that the LPC-10 vocoder's ability to process voices with pitch extremes and quality extremes was limited in any significant manner. A comparison of the unprocessed natural vowel waveforms and qualities with the synthesized vowel waveforms and qualities revealed almost imperceptible differences. An LPC-10 vocoder's ability to process linguistic and dialectical suprasegmental features such as intonation, rate and stress at low bit rates should be a critical issue of concern for future research.

Microchannel DNA Sequencing by End-Labelled Free Solution Electrophoresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barron, A.

2005-09-29

The further development of End-Labeled Free-Solution Electrophoresis will greatly simplify DNA separation and sequencing on microfluidic devices. The development and optimization of drag-tags is critical to the success of this research.

Exhibition Spaces/Galleries.

ERIC Educational Resources Information Center

American School & University, 2003

2003-01-01

Presents educational exhibition space/galleries considered outstanding in a competition, which judged the most outstanding learning environments at educational institutions nationwide. Jurors spent two days reviewing projects, highlighting concepts and ideas that made them exceptional. For each citation, the article offers information on the firm,…

Detecting single DNA molecule interactions with optical microcavities (Presentation Recording)

NASA Astrophysics Data System (ADS)

Vollmer, Frank

2015-09-01

as the detection of less than 1 kDa intercalating small molecules[1]. [1] M. D. Baaske, M. R. Foreman, and F. Vollmer, "Single molecule nucleic acid interactions monitored on a label-free microcavity biosensing platform," Nature Nanotechnology, vol. 9, pp. 933-939, 2014. [2] Y. Wu, D. Y. Zhang, P. Yin, and F. Vollmer, "Ultraspecific and Highly Sensitive Nucleic Acid Detection by Integrating a DNA Catalytic Network with a Label-Free Microcavity," Small, vol. 10, pp. 2067-2076, 2014. [3] M. R. Foreman, W.-L. Jin, and F. Vollmer, "Optimizing Detection Limits in Whispering Gallery Mode Biosensing," Optics Express, vol. 22, pp. 5491-5511, 2014. [4] M. A. Santiago-Cordoba, S. V. Boriskina, F. Vollmer, and M. C. Demirel, "Nanoparticle-based protein detection by optical shift of a resonant microcavity," Applied Physics Letters, vol. 99, Aug 2011. [5] M. R. Foreman and F. Vollmer, "Theory of resonance shifts of whispering gallery modes by arbitrary plasmonic nanoparticles," New Journal of Physics, vol. 15, p. 083006, Aug 2013. [6] M. R. Foreman and F. Vollmer "Level repulsion in hybrid photonic-plasmonic microresonators for enhanced biodetection" Phys. Rev. A 88, 023831 (2013).

Plasmonic improvement of microcavity biomedical sensor spectroscopic characteristics

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Saetchnikov, Anton V.; Schweiger, Gustav; Ostendorf, Andreas; Ghadiri, Reza

2014-03-01

New opportunity to improve a sensetivity of a label-free biomolecule detection in sensing systems based on microcavity evanescent wave optical sensors has been recently found and is being under intensive development. Novel technique based on combination of optical resonance on microring structures with plasmon resonance. Recently developed tools based on neural network data processing can realize real-time identification of biological agents. So combining advantages of plasmon enhancing optical microcavity resonance with identification tools can give a new platform for ulta sensitive label-free biomedical sensor. Our developed technique used standard glass and polymer microspheres as sensetive elements. They are fixed in the solution flow by adhesive layer on the surface being in the field of evanescence wave. Sensitive layer have been treated by gold nanoparticel (GN) solution. Another technique used thin film gold layers deposited on the substrate below adhesive. The light from a tuneable diode laser is coupled into the microsphere through a prism and was sharply focussed on the single microsphere. Images were recorded by CMOS camera. Normalized by free spectral range resonance shift of whispering gallery mode (WGM) and a relative efficiency of their excitation were used as input data for biomolecule classification. Both biomolecules and NP injection was obtained caused WGM spectra modification. But after NP treatment spectral shift and intensity of WGM resonances in biomolecule solutions increased. WGM resonances in microspheres fixed on substrate with gold layer with optimized layer thickness in biomolecule solutions also had higher intensity and spectra modification then without gold layer.

Optical spectrum measurement of a cell-adhered microcavity for the cell-cycle analysis applications

NASA Astrophysics Data System (ADS)

Saito, Ryusuke; Terakawa, Mitsuhiro; Tanabe, Takasumi

2015-03-01

We build a setup and demonstrate successful measurement of the transmittance spectrum of a whispering gallery mode silica optical microcavity in which NIH 3T3 cells adhered on the top surface to achieve real-time and label-free measurement of the cell cycle. Label-free measurement is expected to prevent the cells to exhibit secondary effect. We build a system that enables the control of the gap distance between the microcavity and the tapered fiber, both of which are placed in the cell culture medium. The optimization of the tapered fiber diameter is the key to measure the spectrum of a microcavity in liquid. A swept wavelength laser light at a wavelength of 766 to 780 nm is used for the measurement. The cavity exhibit a Q of 1 . 0 ×106 in air, where the value is 1 . 0 ×105 in the medium and drops to 3 . 1 ×104 after the cell-adhesion. Still the Q of the microcavity is sufficiently high to detect the change at the cavity surface. Indeed we observe slight spectrum shift toward a longer wavelength, which we believe is due to the adherence of NIH 3T3 cells on the silica microcavity.The successful measurement of the transmittance spectrum of a microcavity in cell culture medium is the first step to realize the analysis of the cell-cycle based on microcavity system.

Soilcrust Photo Gallery

Science.gov Websites

Soil Crust Home Crust 101 Advanced Gallery References CCERS Site Links updated: January 30, 2008 images representative of Biological Soil Crusts on the Colorado Plateau. TIF downloads are available for 1 - Open spaces covered by biological soil crusts, a highly specialized community of cyanobacteria

19. MAIN MEETING ROOM LOOKING SOUTH FROM GALLERY. Note coved ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. MAIN MEETING ROOM LOOKING SOUTH FROM GALLERY. Note coved extension of gallery, erected when offices were built on gallery for the use of the Friends Service Committee in 1936. Note also the short stair balusters resulting from the wide modesty stair stringer provided for the women's side. - Twelfth Street Meeting House, 20 South Twelfth Street, Philadelphia, Philadelphia County, PA

Fungus symbionts colonizing the galleries of the ambrosia beetle Platypus quercivorus.

PubMed

Endoh, Rikiya; Suzuki, Motofumi; Okada, Gen; Takeuchi, Yuko; Futai, Kazuyoshi

2011-07-01

Isolations were made to determine the fungal symbionts colonizing Platypus quercivorus beetle galleries of dead or dying Quercus laurifolia, Castanopsis cuspidata, Quercus serrata, Quercus crispula, and Quercus robur. For these studies, logs from oak wilt-killed trees were collected from Kyoto Prefecture, Japan. Fungi were isolated from the: (1) entrances of beetle galleries, (2) vertical galleries, (3) lateral galleries, and (4) the larval cradle of P. quercivorus in each host tree. Among the fungus colonies which appeared on YM agar plates, 1,219 were isolated as the representative isolates for fungus species inhabiting in the galleries based on their cultural characteristics. The validity of the visual classification of the fungus colonies was checked and if necessary properly corrected using microsatellite-primed PCR fingerprints. The nucleotide sequence of the D1/D2 region of the large subunit nuclear rRNA gene detected 38 fungus species (104 strains) of which three species, i.e., Candida sp. 3, Candida kashinagacola (both yeasts), and the filamentous fungus Raffaelea quercivora were isolated from all the tree species. The two yeasts were most prevalent in the interior of galleries, regardless of host tree species, suggesting their close association with the beetle. A culture-independent method, terminal restriction fragment length polymorphism (T-RFLP) analysis was also used to characterize the fungus flora of beetle galleries. T-RFLP patterns showed that yeast species belonging to the genus Ambrosiozyma frequently occurred on the gallery walls along with the two Candida species. Ours is the first report showing the specific fungi inhabiting the galleries of a platypodid ambrosia beetle.

Chaos-assisted broadband momentum transformation in optical microresonators.

PubMed

Jiang, Xuefeng; Shao, Linbo; Zhang, Shu-Xin; Yi, Xu; Wiersig, Jan; Wang, Li; Gong, Qihuang; Lončar, Marko; Yang, Lan; Xiao, Yun-Feng

2017-10-20

The law of momentum conservation rules out many desired processes in optical microresonators. We report broadband momentum transformations of light in asymmetric whispering gallery microresonators. Assisted by chaotic motions, broadband light can travel between optical modes with different angular momenta within a few picoseconds. Efficient coupling from visible to near-infrared bands is demonstrated between a nanowaveguide and whispering gallery modes with quality factors exceeding 10 million. The broadband momentum transformation enhances the device conversion efficiency of the third-harmonic generation by greater than three orders of magnitude over the conventional evanescent-wave coupling. The observed broadband and fast momentum transformation could promote applications such as multicolor lasers, broadband memories, and multiwavelength optical networks. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Experiences from full-scale rockfall testing of protection gallery

NASA Astrophysics Data System (ADS)

Volkwein, Axel; Fergg, Daniel; Hess, Reto; Schellenberg, Kristian

2017-04-01

Vertical drop tests have been performed at the Swiss Oberalppass road. The planned deconstruction of two avalanche protection galleries enabled a precedent evaluation of one gallery (Parde 1} regarding its capacity against rockfall. The background for this evaluation was also to evaluate an existing model for predicting the protection capacity of a rockfall gallery. Based on this model existing galleries can be evaluated whether their residual capacity is sufficient or if it is necessary to strengthen the structureaccording to the current guidelines. This contribution focusses the conduction of the experiments and the experiences obtained from. The presentation gives details on experimental setup, impact characterization, gallery performance, weather implications, data retrieval and data analysis.According to the limited time span for testing and the resources available, a compact testing series has been setup. Three fields of the gallery were tested with drop weights of 800, 1600 and 3200 kg falling from up to 25 m height. The blocks were lifted by a mobil crane. The concrete roof is supported by columns on the valley side and on the mountainside simply supported on the retention wall. The roof slabspans approximately 6x5 m with a thickness of about 0.60 m and is covered by a soil cushion, which has been unified to 0.40 m thickness previous to the test. Additional wooden columns have been installed at the roof's valleyside to avoid a failure of the concrete columns and to favorize a failure of the roof itself due to bending or punching. The measurements performed consist of high speed video records, accelerations within the impactors and on the bottom surface of the gallery roof.

Automated selected reaction monitoring software for accurate label-free protein quantification.

PubMed

Teleman, Johan; Karlsson, Christofer; Waldemarson, Sofia; Hansson, Karin; James, Peter; Malmström, Johan; Levander, Fredrik

2012-07-06

Selected reaction monitoring (SRM) is a mass spectrometry method with documented ability to quantify proteins accurately and reproducibly using labeled reference peptides. However, the use of labeled reference peptides becomes impractical if large numbers of peptides are targeted and when high flexibility is desired when selecting peptides. We have developed a label-free quantitative SRM workflow that relies on a new automated algorithm, Anubis, for accurate peak detection. Anubis efficiently removes interfering signals from contaminating peptides to estimate the true signal of the targeted peptides. We evaluated the algorithm on a published multisite data set and achieved results in line with manual data analysis. In complex peptide mixtures from whole proteome digests of Streptococcus pyogenes we achieved a technical variability across the entire proteome abundance range of 6.5-19.2%, which was considerably below the total variation across biological samples. Our results show that the label-free SRM workflow with automated data analysis is feasible for large-scale biological studies, opening up new possibilities for quantitative proteomics and systems biology.

Label-free measurements on cell apoptosis using a terahertz metamaterial-based biosensor

NASA Astrophysics Data System (ADS)

Zhang, Caihong; Liang, Lanju; Ding, Liang; Jin, Biaobing; Hou, Yayi; Li, Chun; Jiang, Ling; Liu, Weiwei; Hu, Wei; Lu, Yanqing; Kang, Lin; Xu, Weiwei; Chen, Jian; Wu, Peiheng

2016-06-01

Label-free, real-time, and in-situ measurement on cell apoptosis is highly desirable in cell biology. We propose here a design of terahertz (THz) metamaterial-based biosensor for meeting this requirement. This metamaterial consists of a planar array of five concentric subwavelength gold ring resonators on a 10 μm-thick polyimide substrate, which can sense the change of dielectric environment above the metamaterial. We employ this sensor to an oral cancer cell (SCC4) with and without cisplatin, a chemotherapy drug for cancer treatment, and find a linear relation between cell apoptosis measured by Flow Cytometry and the relative change of resonant frequencies of the metamaterial measured by THz time-domain spectroscopy. This implies that we can determine the cell apoptosis in a label-free manner. We believe that this metamaterial-based biosensor can be developed into a cheap, label-free, real-time, and in-situ detection tool, which is of significant impact on the study of cell biology.

Label-Free Alignment of Nonmagnetic Particles in a Small Uniform Magnetic Field.

PubMed

Wang, Zhaomeng; Wang, Ying; Wu, Rui Ge; Wang, Z P; Ramanujan, R V

2018-01-01

Label-free manipulation of biological entities can minimize damage, increase viability and improve efficiency of subsequent analysis. Understanding the mechanism of interaction between magnetic and nonmagnetic particles in an inverse ferrofluid can provide a mechanism of label-free manipulation of such entities in a uniform magnetic field. The magnetic force, induced by relative magnetic susceptibility difference between nonmagnetic particles and surrounding magnetic particles as well as particle-particle interaction were studied. Label-free alignment of nonmagnetic particles can be achieved by higher magnetic field strength (Ba), smaller particle spacing (R), larger particle size (rp1), and higher relative magnetic permeability difference between particle and the surrounding fluid (Rμr). Rμr can be used to predict the direction of the magnetic force between both magnetic and nonmagnetic particles. A sandwich structure, containing alternate layers of magnetic and nonmagnetic particle chains, was studied. This work can be used for manipulation of nonmagnetic particles in lab-on-a-chip applications.

Pompton Lakes Photo Gallery

EPA Pesticide Factsheets

This gallery provides representative photographs of the soil removal and dredging operations within the Pompton Lake Study Area (PLSA) performed starting in 2016 through the present. It will be periodically updated in conjunction with the progress of the

Coral Reefs: A Gallery Program, Grades 7-12.

ERIC Educational Resources Information Center

National Aquarium in Baltimore, MD. Dept. of Education.

Gallery classes at the National Aquarium in Baltimore give the opportunity to study specific aquarium exhibits which demonstrate entire natural habitats. The coral reef gallery class features the gigantic western Atlantic coral reef (325,000 gallons) with over 1,000 fish. The exhibit simulates a typical Caribbean coral reef and nearby sandy…

High-Q Microsphere Cavity for Laser Stabilization and Optoelectronic Microwave

NASA Technical Reports Server (NTRS)

Ilchenko, V.; Yao, X.; Maleki, L.

1999-01-01

With submillimeter size and optical Q up to 10(sup 10), microspheres with whispering-gallery (WG) modes are attractive new component for fiber-optics/photonics applications and a potential core in ultra-compact high-spectral-purity optical and microwave oscillators.

A novel label-free cell-based assay technology using biolayer interferometry.

PubMed

Verzijl, D; Riedl, T; Parren, P W H I; Gerritsen, A F

2017-01-15

Biolayer interferometry (BLI) is a well-established optical label-free technique to study biomolecular interactions. Here we describe for the first time a cell-based BLI (cBLI) application that allows label-free real-time monitoring of signal transduction in living cells. Human A431 epidermoid carcinoma cells were captured onto collagen-coated biosensors and serum-starved, followed by exposure to agonistic compounds targeting various receptors, while recording the cBLI signal. Stimulation of the epidermal growth factor receptor (EGFR) with EGF, the β 2 -adrenoceptor with dopamine, or the hepatocyte growth factor receptor (HGFR/c-MET) with an agonistic antibody resulted in distinct cBLI signal patterns. We show that the mechanism underlying the observed changes in cBLI signal is mediated by rearrangement of the actin cytoskeleton, a process referred to as dynamic mass redistribution (DMR). A panel of ligand-binding blocking and non-blocking anti-EGFR antibodies was used to demonstrate that this novel BLI application can be efficiently used as a label-free cellular assay for compound screening and characterization. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Circular free-electron laser

DOEpatents

Brau, Charles A.; Kurnit, Norman A.; Cooper, Richard K.

1984-01-01

A high efficiency, free electron laser utilizing a circular relativistic electron beam accelerator and a circular whispering mode optical waveguide for guiding optical energy in a circular path in the circular relativistic electron beam accelerator such that the circular relativistic electron beam and the optical energy are spatially contiguous in a resonant condition for free electron laser operation. Both a betatron and synchrotron are disclosed for use in the present invention. A free electron laser wiggler is disposed around the circular relativistic electron beam accelerator for generating a periodic magnetic field to transform energy from the circular relativistic electron beam to optical energy.

Thermal Properties of Whispering Gallery Mode Resonators

DTIC Science & Technology

2014-12-22

in a vacuum chamber, to lower the noise floor and increase the SNR. To study the frequency response of the IR detector , we varied the modulation...performance at a fixed IR modulation (chopping) frequency. Finally, we estimated the noise equivalent power (NEP) of our IR detector . Note that the...the thennal relaxation time of the resonator to estimate the response time of the resonator based infrared (IR) detector . We found that, depending on

Polarization Dependent Whispering Gallery Modes in Microspheres

NASA Technical Reports Server (NTRS)

Adamovsky, Grigory (Inventor); Wrbanek, Susan Y. (Inventor)

2016-01-01

A tunable resonant system is provided and includes a microsphere that receives an incident portion of a light beam generated via a light source, the light beam having a fundamental mode, a waveguide medium that transmits the light beam from the light source to the microsphere, and a polarizer disposed in a path of the waveguide between the light source and the microsphere. The incident portion of the light beam creates a fundamental resonance inside the microsphere. A change in a normalized frequency of the wavelength creates a secondary mode in the waveguide and the secondary mode creates a secondary resonance inside the microsphere.

Screening of hearing in elderly people: assessment of accuracy and reproducibility of the whispered voice test.

PubMed

Labanca, Ludimila; Guimarães, Fernando Sales; Costa-Guarisco, Letícia Pimenta; Couto, Erica de Araújo Brandão; Gonçalves, Denise Utsch

2017-11-01

Given the high prevalence of presbycusis and its detrimental effect on quality of life, screening tests can be useful tools for detecting hearing loss in primary care settings. This study therefore aimed to determine the accuracy and reproducibility of the whispered voice test as a screening method for detecting hearing impairment in older people. This cross-sectional study was carried out with 210 older adults aged between 60 and 97 years who underwent the whispered voice test employing ten different phrases and using audiometry as a reference test. Sensitivity, specificity and positive and negative predictive values were calculated and accuracy was measured by calculating the area under the ROC curve. The test was repeated on 20% of the ears by a second examiner to assess inter-examiner reproducibility (IER). The words and phrases that showed the highest area under the curve (AUC) and IER values were: "shoe" (AUC = 0.918; IER = 0.877), "window" (AUC = 0.917; IER = 0.869), "it looks like it's going to rain" (AUC = 0.911; IER = 0.810), and "the bus is late" (AUC = 0.900; IER = 0.810), demonstrating that the whispered voice test is a useful screening tool for detecting hearing loss among older people. It is proposed that these words and phrases should be incorporated into the whispered voice test protocol.

Label-free SERS in biological and biomedical applications: Recent progress, current challenges and opportunities

NASA Astrophysics Data System (ADS)

Zheng, Xiao-Shan; Jahn, Izabella Jolan; Weber, Karina; Cialla-May, Dana; Popp, Jürgen

2018-05-01

To achieve an insightful look within biomolecular processes on the cellular level, the development of diseases as well as the reliable detection of metabolites and pathogens, a modern analytical tool is needed that is highly sensitive, molecular-specific and exhibits fast detection. Surface-enhanced Raman spectroscopy (SERS) is known to meet these requirements and, within this review article, the recent progress of label-free SERS in biological and biomedical applications is summarized and discussed. This includes the detection of biomolecules such as metabolites, nucleic acids and proteins. Further, the characterization and identification of microorganisms has been achieved by label-free SERS-based approaches. Eukaryotic cells can be characterized by SERS in order to gain information about the outer cell wall or to detect intracellular molecules and metabolites. The potential of SERS for medically relevant detection schemes is emphasized by the label-free detection of tissue, the investigation of body fluids as well as applications for therapeutic and illicit drug monitoring. The review article is concluded with an evaluation of the recent progress and current challenges in order to highlight the direction of label-free SERS in the future.

The Tell-Tale Data: Virtual Whispering and Final Student Grades

ERIC Educational Resources Information Center

Cook, Susan; Germann, Clark

2010-01-01

Online classroom management issues pose new problems for the online instructor and pose seductive communicative options for students. This exploratory group of studies examined Blackboard/WEBCT[TM] data as collected for the course designer of an online course as possible indicators of "whispering" or backchanneling between students with…

A label-free fluorescent aptamer sensor based on regulation of malachite green fluorescence

PubMed Central

Xu, Weichen; Lu, Yi

2009-01-01

We report a label-free fluorescent aptamer sensor for adenosine based on the regulation of malachite green (MG) fluorescence, with comparable sensitivity and selectivity to other labeled adenosine aptamer-based sensors. The sensor consists of free MG, an aptamer strand containing an adenosine aptamer next to an MG aptamer, and a bridging strand that partially hybridizes to the aptamer strand. Such a hybridization prevents MG from binding to MG aptamer, resulting in low fluorescence of MG in the absence of adenosine. Addition of adenosine causes the adenosine aptamer to bind adenosine, weakening the hybridization of the aptamer strand with the bridging strand, making it possible for MG to bind to the aptamer strand and exhibits high fluorescence intensity. Since this design is based purely on nucleic acid hybridization, it can be generally applied to other aptamers for the label-free detection of a broad range of analytes. PMID:20017558

A multi-center study benchmarks software tools for label-free proteome quantification

PubMed Central

Gillet, Ludovic C; Bernhardt, Oliver M.; MacLean, Brendan; Röst, Hannes L.; Tate, Stephen A.; Tsou, Chih-Chiang; Reiter, Lukas; Distler, Ute; Rosenberger, George; Perez-Riverol, Yasset; Nesvizhskii, Alexey I.; Aebersold, Ruedi; Tenzer, Stefan

2016-01-01

The consistent and accurate quantification of proteins by mass spectrometry (MS)-based proteomics depends on the performance of instruments, acquisition methods and data analysis software. In collaboration with the software developers, we evaluated OpenSWATH, SWATH2.0, Skyline, Spectronaut and DIA-Umpire, five of the most widely used software methods for processing data from SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra), a method that uses data-independent acquisition (DIA) for label-free protein quantification. We analyzed high-complexity test datasets from hybrid proteome samples of defined quantitative composition acquired on two different MS instruments using different SWATH isolation windows setups. For consistent evaluation we developed LFQbench, an R-package to calculate metrics of precision and accuracy in label-free quantitative MS, and report the identification performance, robustness and specificity of each software tool. Our reference datasets enabled developers to improve their software tools. After optimization, all tools provided highly convergent identification and reliable quantification performance, underscoring their robustness for label-free quantitative proteomics. PMID:27701404

Label-free imaging of cellular malformation using high resolution photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Chen, Zhongjiang; Li, Bingbing; Yang, Sihua

2014-09-01

A label-free high resolution photoacoustic microscopy (PAM) system for imaging cellular malformation is presented. The carbon fibers were used to testify the lateral resolution of the PAM. Currently, the lateral resolution is better than 2.7 μm. The human normal red blood cells (RBCs) were used to prove the imaging capability of the system, and a single red blood cell was mapped with high contrast. Moreover, the iron deficiency anemia RBCs were clearly distinguished from the cell morphology by using the PAM. The experimental results demonstrate that the photoacoustic microscopy system can accomplish label-free photoacoustic imaging and that it has clinical potential for use in the detection of erythrocytes and blood vessels malformation.

A dual marker label free electrochemical assay for Flavivirus dengue diagnosis.

PubMed

Santos, Adriano; Bueno, Paulo R; Davis, Jason J

2018-02-15

Dengue is a RNA viral illness of the genus Flavivirus which can cause, depending on the pervasiveness of the infection, hemorrhagic dengue fever or dengue shock syndrome. Herein we present an electrochemical label free approach enabling the rapid sensitive quantification of NS1 and IgG (supporting an ability to distinguish primary and secondary infections). Using a bifunctional SAM containing PEG moieties and a tethered redox thiol, both markers are detectable across clinically relevant levels by label free impedance derived redox capacitance. A subsequent frequency specific immittance function approach enables assaying (within seconds) with no impairment of analytical quality (linearity, sensitivity and variance). Copyright © 2017 Elsevier B.V. All rights reserved.

Specific labeling of zinc finger proteins using noncanonical amino acids and copper-free click chemistry.

PubMed

Kim, Younghoon; Kim, Sung Hoon; Ferracane, Dean; Katzenellenbogen, John A; Schroeder, Charles M

2012-09-19

Zinc finger proteins (ZFPs) play a key role in transcriptional regulation and serve as invaluable tools for gene modification and genetic engineering. Development of efficient strategies for labeling metalloproteins such as ZFPs is essential for understanding and controlling biological processes. In this work, we engineered ZFPs containing cysteine-histidine (Cys2-His2) motifs by metabolic incorporation of the unnatural amino acid azidohomoalanine (AHA), followed by specific protein labeling via click chemistry. We show that cyclooctyne promoted [3 + 2] dipolar cycloaddition with azides, known as copper-free click chemistry, provides rapid and specific labeling of ZFPs at high yields as determined by mass spectrometry analysis. We observe that the DNA-binding activity of ZFPs labeled by conventional copper-mediated click chemistry was completely abolished, whereas ZFPs labeled by copper-free click chemistry retain their sequence-specific DNA-binding activity under native conditions, as determined by electrophoretic mobility shift assays, protein microarrays, and kinetic binding assays based on Förster resonance energy transfer (FRET). Our work provides a general framework to label metalloproteins such as ZFPs by metabolic incorporation of unnatural amino acids followed by copper-free click chemistry.

Comparing model-based and model-free analysis methods for QUASAR arterial spin labeling perfusion quantification.

PubMed

Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J

2013-05-01

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Copyright © 2012 Wiley Periodicals, Inc.

Mobile, Multi-modal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia

DTIC Science & Technology

2015-10-01

eyes and image choroidal vessels/capillaries using CARS intravital microscopy Subtask 3: Measure oxy-hemoglobin levels in PBI test and control eyes...AWARD NUMBER: W81XWH-14-1-0537 TITLE: Mobile, Multi-modal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia...4. TITLE AND SUBTITLE Mobile, Multimodal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia 5a. CONTRACT NUMBER W81XWH

Label-free, real-time interaction and adsorption analysis 1: surface plasmon resonance.

PubMed

Fee, Conan J

2013-01-01

A key requirement for the development of proteins for use in nanotechnology is an understanding of how individual proteins bind to other molecules as they assemble into larger structures. The introduction of labels to enable the detection of biomolecules brings the inherent risk that the labels themselves will influence the nature of biomolecular interactions. Thus, there is a need for label-free interaction and adsorption analysis. In this and the following chapter, two biosensor techniques are reviewed: surface plasmon resonance (SPR) and the quartz crystal microbalance (QCM). Both allow real-time analysis of biomolecular interactions and both are label-free. The first of these, SPR, is an optical technique that is highly sensitive to the changes in refractive index that occur with protein (or other molecule) accumulation near an illuminated gold surface. Unlike QCM ( Chapter 18 ) SPR is not affected by the water that may be associated with the adsorbed layer nor by conformational changes in the adsorbed species. SPR thus provides unique information about the interaction of a protein with its binding partners.

Optical pumping in a whispering mode optical waveguide

DOEpatents

Kurnit, Norman A.

1984-01-01

A device and method for optical pumping in a whispering mode optical waveguide. Both a helical ribbon and cylinder are disclosed which incorporate an additional curvature for confining the beam to increase intensity. An optical pumping medium is disposed in the optical path of the beam as it propagates along the waveguide. Optical pumping is enhanced by the high intensities of the beam and long interaction pathlengths which are achieved in a small volume.

PSEA-Quant: a protein set enrichment analysis on label-free and label-based protein quantification data.

PubMed

Lavallée-Adam, Mathieu; Rauniyar, Navin; McClatchy, Daniel B; Yates, John R

2014-12-05

The majority of large-scale proteomics quantification methods yield long lists of quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches are required to analyze such intricate quantitative proteomics data sets. We propose a statistical approach to computationally identify protein sets (e.g., Gene Ontology (GO) terms) that are significantly enriched with abundant proteins with reproducible quantification measurements across a set of replicates. To this end, we developed PSEA-Quant, a protein set enrichment analysis algorithm for label-free and label-based protein quantification data sets. It offers an alternative approach to classic GO analyses, models protein annotation biases, and allows the analysis of samples originating from a single condition, unlike analogous approaches such as GSEA and PSEA. We demonstrate that PSEA-Quant produces results complementary to GO analyses. We also show that PSEA-Quant provides valuable information about the biological processes involved in cystic fibrosis using label-free protein quantification of a cell line expressing a CFTR mutant. Finally, PSEA-Quant highlights the differences in the mechanisms taking place in the human, rat, and mouse brain frontal cortices based on tandem mass tag quantification. Our approach, which is available online, will thus improve the analysis of proteomics quantification data sets by providing meaningful biological insights.

PSEA-Quant: A Protein Set Enrichment Analysis on Label-Free and Label-Based Protein Quantification Data

PubMed Central

2015-01-01

The majority of large-scale proteomics quantification methods yield long lists of quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches are required to analyze such intricate quantitative proteomics data sets. We propose a statistical approach to computationally identify protein sets (e.g., Gene Ontology (GO) terms) that are significantly enriched with abundant proteins with reproducible quantification measurements across a set of replicates. To this end, we developed PSEA-Quant, a protein set enrichment analysis algorithm for label-free and label-based protein quantification data sets. It offers an alternative approach to classic GO analyses, models protein annotation biases, and allows the analysis of samples originating from a single condition, unlike analogous approaches such as GSEA and PSEA. We demonstrate that PSEA-Quant produces results complementary to GO analyses. We also show that PSEA-Quant provides valuable information about the biological processes involved in cystic fibrosis using label-free protein quantification of a cell line expressing a CFTR mutant. Finally, PSEA-Quant highlights the differences in the mechanisms taking place in the human, rat, and mouse brain frontal cortices based on tandem mass tag quantification. Our approach, which is available online, will thus improve the analysis of proteomics quantification data sets by providing meaningful biological insights. PMID:25177766

Optical micro-bubble resonators as promising biosensors

NASA Astrophysics Data System (ADS)

Giannetti, A.; Barucci, A.; Berneschi, S.; Cosci, A.; Cosi, F.; Farnesi, D.; Nunzi Conti, G.; Pelli, S.; Soria, S.; Tombelli, S.; Trono, C.; Righini, G. C.; Baldini, F.

2015-05-01

Recently, optical micro-bubble resonators (OMBRs) have gained an increasing interest in many fields of photonics thanks to their particular properties. These hollow microstructures can be suitable for the realization of label - free optical biosensors by combining the whispering gallery mode (WGM) resonator properties with the intrinsic capability of integrated microfluidics. In fact, the WGMs are morphology-dependent modes: any change on the OMBR inner surface (due to chemical and/or biochemical binding) causes a shift of the resonance position and reduces the Q factor value of the cavity. By measuring this shift, it is possible to obtain information on the concentration of the analyte to be detected. A crucial step for the development of an OMBR-based biosensor is constituted by the functionalization of its inner surface. In this work we report on the development of a physical and chemical process able to guarantee a good homogeneity of the deposed bio-layer and, contemporary, to preserve a high quality factor Q of the cavity. The OMBR capability of working as bioassay was proved by different optical techniques, such as the real time measurement of the resonance broadening after each functionalization step and fluorescence microscopy.

Science Outreach through Art: A Journal Article Cover Gallery

ERIC Educational Resources Information Center

McCullough, Ian

2015-01-01

Research faculty journal covers were used to create a gallery in the Science & Technology branch library at the University of Akron. The selection, presentation, and promotion process is shared along with copyright considerations and a review of galleries used for library outreach. The event and display was a great success attracting faculty…

Label-Free Bioanalyte Detection from Nanometer to Micrometer Dimensions-Molecular Imprinting and QCMs †.

PubMed

Mujahid, Adnan; Mustafa, Ghulam; Dickert, Franz L

2018-06-01

Modern diagnostic tools and immunoassay protocols urges direct analyte recognition based on its intrinsic behavior without using any labeling indicator. This not only improves the detection reliability, but also reduces sample preparation time and complexity involved during labeling step. Label-free biosensor devices are capable of monitoring analyte physiochemical properties such as binding sensitivity and selectivity, affinity constants and other dynamics of molecular recognition. The interface of a typical biosensor could range from natural antibodies to synthetic receptors for example molecular imprinted polymers (MIPs). The foremost advantages of using MIPs are their high binding selectivity comparable to natural antibodies, straightforward synthesis in short time, high thermal/chemical stability and compatibility with different transducers. Quartz crystal microbalance (QCM) resonators are leading acoustic devices that are extensively used for mass-sensitive measurements. Highlight features of QCM devices include low cost fabrication, room temperature operation, and most importantly ability to monitor extremely low mass shifts, thus potentially a universal transducer. The combination of MIPs with quartz QCM has turned out as a prominent sensing system for label-free recognition of diverse bioanalytes. In this article, we shall encompass the potential applications of MIP-QCM sensors exclusively label-free recognition of bacteria and virus species as representative micro and nanosized bioanalytes.

Skin protection by sunscreens is improved by explicit labeling and providing free sunscreen.

PubMed

Nicol, Isabelle; Gaudy, Caroline; Gouvernet, Joanny; Richard, Marie A; Grob, Jean J

2007-01-01

Whatever the improvement in the protection spectrum of sunscreens (SCs), actual skin protection mainly depends on the way they are used, especially on the quantity applied. This prospective randomized study assessed how much sun protection factor (SPF) labeling, which is hardly understandable by a layman, and high cost account for misuse of SCs. In three beach resorts in France, 364 individuals were blindly randomized during their holidays to three arms (1) free SCs intervention (FS) = four types of SCs with their usual SPF label (60B-A, 20B-A, 12B-A, 6B-3A) at free disposal; (2) same free SCs with an explicit labeling (FNL), including sunburn protection, likely protection against long-term effects of UV, and possibility to get a tan; and (3) no intervention (NI). As compared to FS, FNL increased the quantity of SCs applied, mainly in the minority of people who were not "tan-seekers", reduced sunburns particularly in sun-sensitive individuals (25.6 vs 58.3%, P=0.005), and induced a shift in the level of SCs chosen. Free delivery SCs were associated with a more systematic application of SCs in case of exposure, and a decreased sunburn occurrence, without increase of exposure. These results suggest that a labeling more explicit for the public would result in a better protection in SC users and that cost could be a limiting factor to use SC as often as necessary.

Label-enhanced surface plasmon resonance applied to label-free interaction analysis of small molecules and fragments.

PubMed

Eng, Lars; Nygren-Babol, Linnéa; Hanning, Anders

2016-10-01

Surface plasmon resonance (SPR) is a well-established method for studying interactions between small molecules and biomolecules. In particular, SPR is being increasingly applied within fragment-based drug discovery; however, within this application area, the limited sensitivity of SPR may constitute a problem. This problem can be circumvented by the use of label-enhanced SPR that shows a 100-fold higher sensitivity as compared with conventional SPR. Truly label-free interaction data for small molecules can be obtained by applying label-enhanced SPR in a surface competition assay format. The enhanced sensitivity is accompanied by an increased specificity and inertness toward disturbances (e.g., bulk refractive index disturbances). Label-enhanced SPR can be used for fragment screening in a competitive assay format; the competitive format has the added advantage of confirming the specificity of the molecular interaction. In addition, label-enhanced SPR extends the accessible kinetic regime of SPR to the analysis of very fast fragment binding kinetics. In this article, we demonstrate the working principles and benchmark the performance of label-enhanced SPR in a model system-the interaction between carbonic anhydrase II and a number of small-molecule sulfonamide-based inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Ohio Appalachian residents' views on smoke-free laws and cigarette warning labels.

PubMed

Reiter, Paul L; Wewers, Mary E; Paskett, Electra D; Klein, Elizabeth G; Katz, Mira L

2012-01-01

Smoke-free laws and the addition of graphic warning labels to cigarette packages represent public health policies that can potentially reduce smoking and smoking-related disease. The attitudes and beliefs relating to these policies were examined among residents of Ohio Appalachia, a mostly rural region with high smoking prevalence among its residents. Focus groups were conducted with participants from Ohio Appalachia during the summer of 2007. Groups included healthcare providers (n=37), community leaders (n=31), parents (n=19), and young adult women aged 18-26 years (n=27). Most participants were female (94%), non-Hispanic White (94%), and married (65%). Participants believed that most non-smokers supported Ohio's enforced statewide comprehensive smoke-free law that began in 2007, while some smokers opposed the law due to a perceived infringement of their rights. They also reported that most residents and local businesses were abiding by and enforcing the law. Participants supported the addition of graphic warning labels to cigarette packages in the USA. They believed that such warning labels could help deter adolescents and adult non-smokers from smoking initiation, particularly if the negative aesthetic effects of smoking were emphasized. However, they felt the labels would be less effective among current smokers and older individuals living in their communities. Participants generally held positive views about both the smoke-free law and the addition of graphic warning labels to cigarette packages in the USA. These tobacco-related public health policies are promising strategies for potentially reducing smoking and its associated diseases among residents living in Appalachia. Additional research is needed to further examine support for these policies among more diverse Appalachian populations.

Nanoplasmonic biochips for rapid label-free detection of imidacloprid pesticides with a smartphone.

PubMed

Lee, Kuang-Li; You, Meng-Lin; Tsai, Chia-Hsin; Lin, En-Hung; Hsieh, Shu-Yi; Ho, Ming-Hsun; Hsu, Ju-Chun; Wei, Pei-Kuen

2016-01-15

The widespread and intensive use of neonicotinoid insecticides induces negative cascading effects on ecosystems. It is desirable to develop a portable sensitive sensing platform for on-site screening of high-risk pesticides. We combined an indirect competitive immunoassay, highly sensitive surface plasmon resonance (SPR) biochip and a simple portable imaging setup for label-free detection of imidacloprid pesticides. The SPR biochip consists of several capped nanoslit arrays with different periods which form a spectral image on the chip. The qualitative and semiquantitative analyses of pesticides can be directly observed from the spot shift on the chip. The precise semiquantitative analyses can be further completed by using image processing in a smartphone. We demonstrate simultaneous detection of four different concentrations of imidacloprid pesticides. The visual detection limit is about 1ppb, which is well below the maximum residue concentration permitted by law (20ppb). Compared to the one-step strip assay, the proposed chip is capable of performing semiquantitative analyses and multiple detection. Compared to the enzyme-linked immunosorbent assay, our method is label-free and requires simple washing steps and short reaction time. In addition, the label-free chip has a comparable sensitivity but wider working range than those labeling techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

Raman scattering in a whispering mode optical waveguide

DOEpatents

Kurnit, Norman A.

1982-01-01

A device and method for Raman scattering in a whispering mode optical waveguide. Both a helical ribbon and cylinder are disclosed which incorporate an additional curvature .rho. p for confining the beam to increase intensity. A Raman scattering medium is disposed in the optical path of the beam as it propagates along the waveguide. Raman scattering is enhanced by the high intensities of the beam and long interaction path lengths which are achieved in a small volume.

Optical pumping in a whispering-mode optical waveguide

DOEpatents

Kurnit, N.A.

1981-08-11

A device and method for optical pumping in a whispering mode optical waveguide are described. Both a helical ribbon and cylinder are disclosed which incorporate an additional curvature for confining the beam to increase intensity. An optical pumping medium is disposed in the optical path of the beam as it propagates along the waveguide. Optical pumping is enhanced by the high intensities of the beam and long interaction path lengths which are achieved in a small volume.

Label-Free Raman Imaging to Monitor Breast Tumor Signatures

NASA Astrophysics Data System (ADS)

Ciubuc, John

Methods built on Raman spectroscopy have shown major potential in describing and discriminating between malignant and benign specimens. Accurate, real-time medical diagnosis benefits in substantial improvements through this vibrational optical method. Not only is acquisition of data possible in milliseconds and analysis in minutes, Raman allows concurrent detection and monitoring of all biological components. Besides validating a significant Raman signature distinction between non-tumorigenic (MCF-10A) and tumorigenic (MCF-7) breast epithelial cells, this study reveals a label-free method to assess overexpression of epidermal growth factor receptors (EGFR) in tumor cells. EGFR overexpression sires Raman features associated with phosphorylated threonine and serine, and modifications of DNA/RNA characteristics. Investigations by gel electrophoresis reveal EGF induction of phosphorylated Akt, agreeing with the Raman results. The analysis presented is a vital step toward Raman-based evaluation of EGF receptors in breast cancer cells. With the goal of clinically applying Raman-guided methods for diagnosis of breast tumors, the current results lay the basis for proving label-free optical alternatives in making prognosis of the disease.

19. Historic American Building Survey Crocker Art Gallery Collection Copy ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. Historic American Building Survey Crocker Art Gallery Collection Copy from N. P. Goodell, Architect C1879 NORTHWEST CORNER (EAST ELEVATION?) OF 3RD & P ST. (property of Mrs. E. B. Crocker) - Crocker Art Gallery, 216 O Street, Sacramento, Sacramento County, CA

View north of west gallery of inside machine shop 36; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View north of west gallery of inside machine shop 36; the gallery housed turret, engine and toolroom lathes, small milling machines and drill presses used for machining small parts. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

Self-injection locked blue laser

NASA Astrophysics Data System (ADS)

Donvalkar, Prathamesh S.; Savchenkov, Anatoliy; Matsko, Andrey

2018-04-01

We demonstrate a 446.5 nm GaN semiconductor laser with sub-MHz linewidth. The linewidth reduction is achieved by locking the laser to a magnesium fluoride whispering gallery mode resonator characterized with 109 quality factor. Self-injection locking ensures single longitudinal mode operation of the laser.

21 CFR 101.91 - Gluten-free labeling of food.

Code of Federal Regulations, 2014 CFR

2014-04-01

... that has not been processed to remove gluten (e.g., wheat flour); or (3) An ingredient that is derived... is below 20 ppm gluten (i.e., below 20 mg gluten per kg of food). (b) Requirements. (1) A food that... Nutrient Content Claims nor Health Claims § 101.91 Gluten-free labeling of food. (a) Definitions. (1) The...

A Near-Infrared Spectroscopy Study on Cortical Hemodynamic Responses to Normal and Whispered Speech in 3- to 7-Year-Old Children

ERIC Educational Resources Information Center

Remijn, Gerard B.; Kikuchi, Mitsuru; Yoshimura, Yuko; Shitamichi, Kiyomi; Ueno, Sanae; Tsubokawa, Tsunehisa; Kojima, Haruyuki; Higashida, Haruhiro; Minabe, Yoshio

2017-01-01

Purpose: The purpose of this study was to assess cortical hemodynamic response patterns in 3- to 7-year-old children listening to two speech modes: normally vocalized and whispered speech. Understanding whispered speech requires processing of the relatively weak, noisy signal, as well as the cognitive ability to understand the speaker's reason for…

Patterns of free amino acids in German convenience food products: marked mismatch between label information and composition.

PubMed

Hermanussen, M; Gonder, U; Jakobs, C; Stegemann, D; Hoffmann, G

2010-01-01

Free amino acids affect food palatability. As information on amino acids in frequently purchased pre-packaged food is virtually absent, we analyzed free amino acid patterns of 17 frequently purchased ready-to-serve convenience food products, and compared them with the information obtained from the respective food labels. Quantitative amino acid analysis was performed using ion-exchange chromatography. gamma-Aminobutyric acid (GABA) concentrations were verified using a stable isotope dilution gas chromatography/mass spectrometry (GC-MS) method. The patterns of free amino acids were compared with information obtained from food labels. An obvious mismatch between free amino acid patterns and food label information was detected. Even on considering that tomatoes and cereal proteins are naturally rich in glutamate, the concentrations of free glutamate outranged the natural concentration of this amino acid in several products, and strongly suggested artificial enrichment. Free glutamate was found to be elevated even in dishes that explicitly state 'no glutamate added'. Arginine was markedly elevated in lentils. Free cysteine was generally low, possibly reflecting thermal destruction of this amino acid during food processing. The meat and brain-specific dipeptide carnosine (CARN) was present in most meat-containing products. Some products did not contain detectable amounts of CARN in spite of meat content being claimed on the food labels. We detected GABA at concentrations that contribute significantly to the taste sensation. This investigation highlights a marked mismatch between food label information and food composition.

Analysis of nonreciprocal noise based on mode splitting in a high-Q optical microresonator

NASA Astrophysics Data System (ADS)

Yang, Zhaohua; Xiao, Yarong; Huo, Jiayan; Shao, Hui

2018-01-01

The whispering gallery mode optical microresonator offers a high quality factor, which enables it to act as the core component of a high sensitivity resonator optic gyro; however, nonreciprocal noise limits its precision. Considering the Sagnac effect, i.e. mode splitting in high-quality optical micro-resonators, we derive the explicit expression for the angular velocity versus the splitting amount, and verify the sensing mechanism by simulation using finite element method. Remarkably, the accuracy of the angular velocity measurement in the whispering gallery mode optical microresonator with a quality factor of 108 is 106 °/s. We obtain the optimal coupling position of the novel angular velocity sensing system by detecting the output transmittance spectra of different vertical coupling distances and axial coupling positions. In addition, the reason for the nonreciprocal phenomenon is determined by theoretical analysis of the evanescent distribution of a tapered fiber. These results will provide an effective method and a theoretical basis for suppression of the nonreciprocal noise.

Intracellular microlasers

NASA Astrophysics Data System (ADS)

Humar, Matjaž; Hyun Yun, Seok

2015-09-01

Optical microresonators, which confine light within a small cavity, are widely exploited for various applications ranging from the realization of lasers and nonlinear devices to biochemical and optomechanical sensing. Here we use microresonators and suitable optical gain materials inside biological cells to demonstrate various optical functions in vitro including lasing. We explore two distinct types of microresonator—soft and hard—that support whispering-gallery modes. Soft droplets formed by injecting oil or using natural lipid droplets support intracellular laser action. The laser spectra from oil-droplet microlasers can chart cytoplasmic internal stress (˜500 pN μm-2) and its dynamic fluctuations at a sensitivity of 20 pN μm-2 (20 Pa). In a second form, whispering-gallery modes within phagocytized polystyrene beads of different sizes enable individual tagging of thousands of cells easily and, in principle, a much larger number by multiplexing with different dyes.

Engineered biomarkers for leprosy diagnosis using labeled and label-free analysis.

PubMed

de Santana, Juliana F; da Silva, Mariângela R B; Picheth, Guilherme F; Yamanaka, Isabel B; Fogaça, Rafaela L; Thomaz-Soccol, Vanete; Machado-de-Avila, Ricardo A; Chávez-Olórtegui, Carlos; Sierakowski, Maria Rita; de Freitas, Rilton Alves; Alvarenga, Larissa M; de Moura, Juliana

2018-09-01

The biotechnological evolution towards the development of antigens to detect leprosy has been progressing. However, the identification of leprosy in paucibacillary patients, based solely on the antigen-antibody interaction still remains a challenge. The complexity of clinical manifestations requires innovative approaches to improve the sensitivity of assays to detect leprosy before the onset of symptoms, thus avoiding disabilities and contributing, indirectly, to reduce transmission. In this study, the strategies employed for early leprosy diagnosis were: i. using a phage-displayed mimotope (APDDPAWQNIFNLRR) which mimics an immunodominant sequence (PPNDPAWQRNDPILQ) of an antigen of Mycobacterium leprae known as Ag85B; ii. engineering the mimotope by adding a C-terminal flexible spacer (SGSG-C); iii. conjugating the mimotope to a carrier protein to provide better exposure to antibodies; iv. amplifying the signal using biotin-streptavidin detection system in an ELISA; and v. coating the optimized mimotope on a quartz crystal microbalance (QCM) sensor for label-free biosensing. The ELISA sensitivity increased up to 91.7% irrespective of the immunological profile of the 132 patients assayed. By using comparative modeling, the M. tuberculosis Ag85B was employed as a template to ascertain which features make the mimotope a good antigen in terms of its specificity. For the first time, a sensitive QCM-based immunosensor to detect anti M. leprae antibodies in human serum was used. M. leprae antibodies could also be detected in the sera of paucibacillary patients; thus, the use of a mimotope-derived synthetic peptide as bait for antibodies in a novel analytical label-free immunoassay for leprosy diagnosis exhibits great potential. Copyright © 2018 Elsevier B.V. All rights reserved.

Specific Labeling of Zinc Finger Proteins using Non-canonical Amino Acids and Copper-free Click Chemistry

PubMed Central

Kim, Younghoon; Kim, Sung Hoon; Ferracane, Dean; Katzenellenbogen, John A.

2012-01-01

Zinc finger proteins (ZFPs) play a key role in transcriptional regulation and serve as invaluable tools for gene modification and genetic engineering. Development of efficient strategies for labeling metalloproteins such as ZFPs is essential for understanding and controlling biological processes. In this work, we engineered ZFPs containing cysteine-histidine (Cys2-His2) motifs by metabolic incorporation of the unnatural amino acid azidohomoalanine (AHA), followed by specific protein labeling via click chemistry. We show that cyclooctyne promoted [3 + 2] dipolar cycloaddition with azides, known as copper-free click chemistry, provides rapid and specific labeling of ZFPs at high yields as determined by mass spectrometry analysis. We observe that the DNA-binding activity of ZFPs labeled by conventional copper-mediated click chemistry was completely abolished, whereas ZFPs labeled by copper-free click chemistry retain their sequence-specific DNA-binding activity under native conditions, as determined by electrophoretic mobility shift assays, protein microarrays and kinetic binding assays based on Förster resonance energy transfer (FRET). Our work provides a general framework to label metalloproteins such as ZFPs by metabolic incorporation of unnatural amino acids followed by copper-free click chemistry. PMID:22871171

Benchmarking quantitative label-free LC-MS data processing workflows using a complex spiked proteomic standard dataset.

PubMed

Ramus, Claire; Hovasse, Agnès; Marcellin, Marlène; Hesse, Anne-Marie; Mouton-Barbosa, Emmanuelle; Bouyssié, David; Vaca, Sebastian; Carapito, Christine; Chaoui, Karima; Bruley, Christophe; Garin, Jérôme; Cianférani, Sarah; Ferro, Myriam; Van Dorssaeler, Alain; Burlet-Schiltz, Odile; Schaeffer, Christine; Couté, Yohann; Gonzalez de Peredo, Anne

2016-01-30

Proteomic workflows based on nanoLC-MS/MS data-dependent-acquisition analysis have progressed tremendously in recent years. High-resolution and fast sequencing instruments have enabled the use of label-free quantitative methods, based either on spectral counting or on MS signal analysis, which appear as an attractive way to analyze differential protein expression in complex biological samples. However, the computational processing of the data for label-free quantification still remains a challenge. Here, we used a proteomic standard composed of an equimolar mixture of 48 human proteins (Sigma UPS1) spiked at different concentrations into a background of yeast cell lysate to benchmark several label-free quantitative workflows, involving different software packages developed in recent years. This experimental design allowed to finely assess their performances in terms of sensitivity and false discovery rate, by measuring the number of true and false-positive (respectively UPS1 or yeast background proteins found as differential). The spiked standard dataset has been deposited to the ProteomeXchange repository with the identifier PXD001819 and can be used to benchmark other label-free workflows, adjust software parameter settings, improve algorithms for extraction of the quantitative metrics from raw MS data, or evaluate downstream statistical methods. Bioinformatic pipelines for label-free quantitative analysis must be objectively evaluated in their ability to detect variant proteins with good sensitivity and low false discovery rate in large-scale proteomic studies. This can be done through the use of complex spiked samples, for which the "ground truth" of variant proteins is known, allowing a statistical evaluation of the performances of the data processing workflow. We provide here such a controlled standard dataset and used it to evaluate the performances of several label-free bioinformatics tools (including MaxQuant, Skyline, MFPaQ, IRMa-hEIDI and Scaffold) in

Plasmonic biosensor for label-free G-quadruplexes detection

NASA Astrophysics Data System (ADS)

Qiu, Suyan; Zhao, Fusheng; Santos, Greggy M.; Shih, Wei-Chuan

2016-03-01

G-quadruplex, readily formed by the G-rich sequence, potentially distributes in over 40 % of all human genes, such as the telomeric DNA with the G-rich sequence found at the end of the chromosome. The G-quadruplex structure is supposed to possess a diverse set of critical functions in the mammalian genome for transcriptional regulation, DNA replication and genome stability. However, most of the currently available methods for G-quadruplex identification are restricted to fluorescence techniques susceptible to poor sensitivity. It is essential to propose methods with higher sensitivity to specifically recognize the G-quadruplexes. In this study, we demonstrate a label-free plasmonic biosensor for G-quadruplex detection by relying on the advantages of nanoporous gold (NPG) disks that provide high-density plasmonic hot spots, suitable for molecular recognition capability without the requirement for labeling processes.

Label-free detection of DNA hybridization using carbon nanotube network field-effect transistors

NASA Astrophysics Data System (ADS)

Star, Alexander; Tu, Eugene; Niemann, Joseph; Gabriel, Jean-Christophe P.; Joiner, C. Steve; Valcke, Christian

2006-01-01

We report carbon nanotube network field-effect transistors (NTNFETs) that function as selective detectors of DNA immobilization and hybridization. NTNFETs with immobilized synthetic oligonucleotides have been shown to specifically recognize target DNA sequences, including H63D single-nucleotide polymorphism (SNP) discrimination in the HFE gene, responsible for hereditary hemochromatosis. The electronic responses of NTNFETs upon single-stranded DNA immobilization and subsequent DNA hybridization events were confirmed by using fluorescence-labeled oligonucleotides and then were further explored for label-free DNA detection at picomolar to micromolar concentrations. We have also observed a strong effect of DNA counterions on the electronic response, thus suggesting a charge-based mechanism of DNA detection using NTNFET devices. Implementation of label-free electronic detection assays using NTNFETs constitutes an important step toward low-cost, low-complexity, highly sensitive and accurate molecular diagnostics. hemochromatosis | SNP | biosensor

Dynamic and label-free high-throughput detection of biomolecular interactions based on phase-shift interferometry

NASA Astrophysics Data System (ADS)

Li, Qiang; Huang, Guoliang; Gan, Wupeng; Chen, Shengyi

2009-08-01

Biomolecular interactions can be detected by many established technologies such as fluorescence imaging, surface plasmon resonance (SPR)[1-4], interferometry and radioactive labeling of the analyte. In this study, we have designed and constructed a label-free, real-time sensing platform and its operating imaging instrument that detects interactions using optical phase differences from the accumulation of biological material on solid substrates. This system allows us to monitor biomolecular interactions in real time and quantify concentration changes during micro-mixing processes by measuring the changes of the optical path length (OPD). This simple interferometric technology monitors the optical phase difference resulting from accumulated biomolecular mass. A label-free protein chip that forms a 4×4 probe array was designed and fabricated using a commercial microarray robot spotter on solid substrates. Two positive control probe lines of BSA (Bovine Serum Albumin) and two experimental human IgG and goat IgG was used. The binding of multiple protein targets was performed and continuously detected by using this label-free and real-time sensing platform.

Optofluidic ring resonator sensor for sensitive label-free detection of breast cancer antigen CA15-3 in human serum

NASA Astrophysics Data System (ADS)

Zhu, Hongying; Dale, Paul S.; Fan, Xudong

2009-05-01

Breast cancer is the most frequently diagnosed malignancy in women worldwide. Because of its great impact on society, a lot of research funding has been used to develop novel detection tools for aiding breast cancer diagnosis and prognosis. In this work, we demonstrated a simple, fast, and sensitive detection of circulating breast cancer biomarker CA15-3 with opto-fluidic ring resonator (OFRR) sensors. The OFRR sensor employs a thin-walled capillary with wall thickness less than 4 μm. The circular cross section of the capillary forms the optical ring resonator, in which the light circulates in the form of whispering gallery modes (WGMs). The capillary wall is thin enough that the evanescent field of the WGM extends into the capillary core and responds to refractive index changes in the capillary core or close to its interior surface. The WGM spectral position will change when the biomolecules bind to the surface, yielding quantitative and kinetic information about the biomolecule interaction. Here, the direct immunoassay method was employed for the detection of CA15-3 antigen without any signal amplification steps. The sensor performance in both PBS buffer and human serum were investigated, respectively. The experimental detection limit was 5 units/mL in PBS buffer and 30 units/mL for CA15-3 spiked in serum, both of which satisfied clinical diagnosis requirements. The potential use of the OFRR as the point-of-care device for breast cancer detection was tested by measuring the CA15-3 level in blood samples collected from stage IV breast cancer patients and the results were compared with standard clinical test.

Highly stable porous silicon-carbon composites as label-free optical biosensors.

PubMed

Tsang, Chun Kwan; Kelly, Timothy L; Sailor, Michael J; Li, Yang Yang

2012-12-21

A stable, label-free optical biosensor based on a porous silicon-carbon (pSi-C) composite is demonstrated. The material is prepared by electrochemical anodization of crystalline Si in an HF-containing electrolyte to generate a porous Si template, followed by infiltration of poly(furfuryl) alcohol (PFA) and subsequent carbonization to generate the pSi-C composite as an optically smooth thin film. The pSi-C sensor is significantly more stable toward aqueous buffer solutions (pH 7.4 or 12) compared to thermally oxidized (in air, 800 °C), hydrosilylated (with undecylenic acid), or hydrocarbonized (with acetylene, 700 °C) porous Si samples prepared and tested under similar conditions. Aqueous stability of the pSi-C sensor is comparable to related optical biosensors based on porous TiO(2) or porous Al(2)O(3). Label-free optical interferometric biosensing with the pSi-C composite is demonstrated by detection of rabbit IgG on a protein-A-modified chip and confirmed with control experiments using chicken IgG (which shows no affinity for protein A). The pSi-C sensor binds significantly more of the protein A capture probe than porous TiO(2) or porous Al(2)O(3), and the sensitivity of the protein-A-modified pSi-C sensor to rabbit IgG is found to be ~2× greater than label-free optical biosensors constructed from these other two materials.

In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles

PubMed Central

2015-01-01

Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticles and radio-isotopes are two major concerns for this approach. Here, we present a chelator-free zirconium-89 (89Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (−Si–O–) from two types of silica nanoparticles investigated. This work reports 89Zr-labeled MSN with a detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, 89Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future. PMID:26213260

In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles.

PubMed

Chen, Feng; Goel, Shreya; Valdovinos, Hector F; Luo, Haiming; Hernandez, Reinier; Barnhart, Todd E; Cai, Weibo

2015-08-25

Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticles and radio-isotopes are two major concerns for this approach. Here, we present a chelator-free zirconium-89 ((89)Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (-Si-O(-)) from two types of silica nanoparticles investigated. This work reports (89)Zr-labeled MSN with a detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, (89)Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future.

A gallery approach for off-angle iris recognition

NASA Astrophysics Data System (ADS)

Karakaya, Mahmut; Yoldash, Rashiduddin; Boehnen, Christopher

2015-05-01

It has been proven that hamming distance score between frontal and off-angle iris images of same eye differs in iris recognition system. The distinction of hamming distance score is caused by many factors such as image acquisition angle, occlusion, pupil dilation, and limbus effect. In this paper, we first study the effect of the angle variations between iris plane and the image acquisition systems. We present how hamming distance changes for different off-angle iris images even if they are coming from the same iris. We observe that increment in acquisition angle of compared iris images causes the increment in hamming distance. Second, we propose a new technique in off-angle iris recognition system that includes creating a gallery of different off-angle iris images (such as, 0, 10, 20, 30, 40, and 50 degrees) and comparing each probe image with these gallery images. We will show the accuracy of the gallery approach for off-angle iris recognition.

Label-free and substrate-free potentiometric aptasensing using polycation-sensitive membrane electrodes.

PubMed

Ding, Jiawang; Chen, Yan; Wang, Xuewei; Qin, Wei

2012-02-21

A potentiometric label-free and substrate-free (LFSF) aptasensing strategy which eliminates the labeling, separation, and immobilization steps is described in this paper. An aptamer binds specifically to a target molecule via reaction incubation, which could induce a change in the aptamer conformation from a random coil-like configuration to a rigid folded structure. Such a target binding-induced aptamer conformational change effectively prevents the aptamer from electrostatically interacting with the protamine binding domain. This could either shift the response curve for the potentiometric titration of the aptamer with protamine as monitored by a conventional polycation-sensitive membrane electrode or change the current-dependent potential detected by a protamine-conditioned polycation-sensitive electrode with the pulsed current-driven ion fluxes of protamine across the polymeric membrane. Using adenosine triphosphate (ATP) as a model analyte, the proposed concept offers potentiometric detection of ATP down to the submicromolar concentration range and has been applied to the determination of ATP in HeLa cells. In contrast to the current LFSF aptasensors based on optical detection, the proposed strategy allows the LFSF biosensing of aptamer/target binding events in a homogeneous solution via electrochemical transduction. It is anticipated that the proposed strategy will lay a foundation for development of potentiometric sensors for LFSF aptasensing of a variety of analytes where target binding-induced conformational changes such as the formation of folded structures and the opening of DNA hairpin loops are involved.

Label-free optical biosensing with slot-waveguides.

PubMed

Barrios, Carlos A; Bañuls, María José; González-Pedro, Victoria; Gylfason, Kristinn B; Sánchez, Benito; Griol, Amadeu; Maquieira, A; Sohlström, H; Holgado, M; Casquel, R

2008-04-01

We demonstrate label-free molecule detection by using an integrated biosensor based on a Si(3)N(4)/SiO(2) slot-waveguide microring resonator. Bovine serum albumin (BSA) and anti-BSA molecular binding events on the sensor surface are monitored through the measurement of resonant wavelength shifts with varying biomolecule concentrations. The biosensor exhibited sensitivities of 1.8 and 3.2 nm/(ng/mm(2)) for the detection of anti-BSA and BSA, respectively. The estimated detection limits are 28 and 16 pg/mm(2) for anti-BSA and BSA, respectively, limited by wavelength resolution.

The Authors Gallery: A Meaningful Integration of Technology and Writing

ERIC Educational Resources Information Center

Martin, Deb

2008-01-01

In this article, the author first explains what an authors gallery is and suggests additional uses and modifications. Next, readers are taken through a day-by-day description of creating the gallery while having the theory behind this pedagogical choice explained. The step-by-step discussion is supported with student examples and concepts drawn…

The Habitable Zone Gallery and its Applications

NASA Astrophysics Data System (ADS)

Gelino, Dawn M.; Kane, S. R.

2012-05-01

The Habitable Zone Gallery (www.hzgallery.org) is a service to the exoplanet community which provides Habitable Zone (HZ) information for each of the exoplanetary systems with known planetary orbital parameters. The service includes a sortable table, a plot with the period and eccentricity of each of the planets with respect to their time spent in the HZ, a gallery of known systems which plot the orbits and the location of the HZ with respect to those orbits, and orbital movies. Here we discuss various educational and scientific applications of the site such as target selection, exploring planets with eccentric orbits, and investigating habitability.

Advantages and application of label-free detection assays in drug screening.

PubMed

Cunningham, Brian T; Laing, Lance G

2008-08-01

Adoption is accelerating for a new family of label-free optical biosensors incorporated into standard format microplates owing to their ability to enable highly sensitive detection of small molecules, proteins and cells for high-throughput drug discovery applications. Label-free approaches are displacing other detection technologies owing to their ability to provide simple assay procedures for hit finding/validation, accessing difficult target classes, screening the interaction of cells with drugs and analyzing the affinity of small molecule inhibitors to target proteins. This review describes several new drug discovery applications that are under development for microplate-based photonic crystal optical biosensors and the key issues that will drive adoption of the technology. Microplate-based optical biosensors are enabling a variety of cell-based assays, inhibition assays, protein-protein binding assays and protein-small molecule binding assays to be performed with high-throughput and high sensitivity.

Mass spectrometry–based relative quantification of proteins in precatalytic and catalytically active spliceosomes by metabolic labeling (SILAC), chemical labeling (iTRAQ), and label-free spectral count

PubMed Central

Schmidt, Carla; Grønborg, Mads; Deckert, Jochen; Bessonov, Sergey; Conrad, Thomas; Lührmann, Reinhard; Urlaub, Henning

2014-01-01

The spliceosome undergoes major changes in protein and RNA composition during pre-mRNA splicing. Knowing the proteins—and their respective quantities—at each spliceosomal assembly stage is critical for understanding the molecular mechanisms and regulation of splicing. Here, we applied three independent mass spectrometry (MS)–based approaches for quantification of these proteins: (1) metabolic labeling by SILAC, (2) chemical labeling by iTRAQ, and (3) label-free spectral count for quantification of the protein composition of the human spliceosomal precatalytic B and catalytic C complexes. In total we were able to quantify 157 proteins by at least two of the three approaches. Our quantification shows that only a very small subset of spliceosomal proteins (the U5 and U2 Sm proteins, a subset of U5 snRNP-specific proteins, and the U2 snRNP-specific proteins U2A′ and U2B′′) remains unaltered upon transition from the B to the C complex. The MS-based quantification approaches classify the majority of proteins as dynamically associated specifically with the B or the C complex. In terms of experimental procedure and the methodical aspect of this work, we show that metabolically labeled spliceosomes are functionally active in terms of their assembly and splicing kinetics and can be utilized for quantitative studies. Moreover, we obtain consistent quantification results from all three methods, including the relatively straightforward and inexpensive label-free spectral count technique. PMID:24448447

Label-free detection of real-time DNA amplification using a nanofluidic diffraction grating

NASA Astrophysics Data System (ADS)

Yasui, Takao; Ogawa, Kensuke; Kaji, Noritada; Nilsson, Mats; Ajiri, Taiga; Tokeshi, Manabu; Horiike, Yasuhiro; Baba, Yoshinobu

2016-08-01

Quantitative DNA amplification using fluorescence labeling has played an important role in the recent, rapid progress of basic medical and molecular biological research. Here we report a label-free detection of real-time DNA amplification using a nanofluidic diffraction grating. Our detection system observed intensity changes during DNA amplification of diffracted light derived from the passage of a laser beam through nanochannels embedded in a microchannel. Numerical simulations revealed that the diffracted light intensity change in the nanofluidic diffraction grating was attributed to the change of refractive index. We showed the first case reported to date for label-free detection of real-time DNA amplification, such as specific DNA sequences from tubercle bacilli (TB) and human papillomavirus (HPV). Since our developed system allows quantification of the initial concentration of amplified DNA molecules ranging from 1 fM to 1 pM, we expect that it will offer a new strategy for developing fundamental techniques of medical applications.

Label-free biosensing of Salmonella enterica serovars at single-cell level

USDA-ARS?s Scientific Manuscript database

Nanotechnology has greatly facilitated the development of label-free biosensors. The atomic force microscopy (AFM) has been used to study the molecular mechanism of the reactions for protein and aptamers. The surface plasmon resonance (SPR) have been used in fast detection of various pathogenic bact...

Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope

PubMed Central

Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

2015-01-01

Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications. PMID:26525841

Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope.

PubMed

Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

2015-11-03

Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications.

Dynamic nano-imaging of label-free living cells using electron beam excitation-assisted optical microscope

NASA Astrophysics Data System (ADS)

Fukuta, Masahiro; Kanamori, Satoshi; Furukawa, Taichi; Nawa, Yasunori; Inami, Wataru; Lin, Sheng; Kawata, Yoshimasa; Terakawa, Susumu

2015-11-01

Optical microscopes are effective tools for cellular function analysis because biological cells can be observed non-destructively and non-invasively in the living state in either water or atmosphere condition. Label-free optical imaging technique such as phase-contrast microscopy has been analysed many cellular functions, and it is essential technology for bioscience field. However, the diffraction limit of light makes it is difficult to image nano-structures in a label-free living cell, for example the endoplasmic reticulum, the Golgi body and the localization of proteins. Here we demonstrate the dynamic imaging of a label-free cell with high spatial resolution by using an electron beam excitation-assisted optical (EXA) microscope. We observed the dynamic movement of the nucleus and nano-scale granules in living cells with better than 100 nm spatial resolution and a signal-to-noise ratio (SNR) around 10. Our results contribute to the development of cellular function analysis and open up new bioscience applications.

Implementation of Arithmetic and Nonarithmetic Functions on a Label-free and DNA-based Platform

NASA Astrophysics Data System (ADS)

Wang, Kun; He, Mengqi; Wang, Jin; He, Ronghuan; Wang, Jianhua

2016-10-01

A series of complex logic gates were constructed based on graphene oxide and DNA-templated silver nanoclusters to perform both arithmetic and nonarithmetic functions. For the purpose of satisfying the requirements of progressive computational complexity and cost-effectiveness, a label-free and universal platform was developed by integration of various functions, including half adder, half subtractor, multiplexer and demultiplexer. The label-free system avoided laborious modification of biomolecules. The designed DNA-based logic gates can be implemented with readout of near-infrared fluorescence, and exhibit great potential applications in the field of bioimaging as well as disease diagnosis.

Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

NASA Astrophysics Data System (ADS)

Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

2011-07-01

We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

Label-free surface plasmon sensing towards cancer diagnostics

NASA Astrophysics Data System (ADS)

Sankaranarayanan, Goutham

The main objective of this thesis is to develop a conventional, home-built SPR bio-sensor to demonstrate bio-sensing applications. This emphasizes the understanding of basic concepts of Surface Plasmon Resonance and various interrogation techniques. Intensity Modulation was opted to perform the label-free SPR bio-sensing experiments due to its cost-efficient and compact setup. Later, label-free surface plasmon sensing was carried out to study and understand the bio-molecular interactions between (1). BSA and Anti BSA molecules and (2). Exosome/Liposome on thin metal (Au) films. Exosomes are cell-derived vesicles present in bodily fluids like blood, saliva, urine, epididymal fluid containing miRNAs, RNA, proteins, etc., at stable quantities during normal health conditions. The exosomes comprise varied constituents based on their cell origin from where they are secreted and is specific to that particular origin. However an exacerbated release is observed during tumor or cancer conditions. This increased level of exosomes present in the sample, can be detected using the SPR bio-sensor demonstrated in this thesis and effective thickness of adsorption on Au surface can be estimated. Also, chemically synthesized liposome particles were studied to determine if they can generate an equivalent sensor response to that of exosomes to consider them as an alternate. Finally a 10ppb Mercury (Hg) sensing was performed as part of Environment Monitoring application and results have been tabulated and compared.

Label-free density difference amplification-based cell sorting.

PubMed

Song, Jihwan; Song, Minsun; Kang, Taewook; Kim, Dongchoul; Lee, Luke P

2014-11-01

The selective cell separation is a critical step in fundamental life sciences, translational medicine, biotechnology, and energy harvesting. Conventional cell separation methods are fluorescent activated cell sorting and magnetic-activated cell sorting based on fluorescent probes and magnetic particles on cell surfaces. Label-free cell separation methods such as Raman-activated cell sorting, electro-physiologically activated cell sorting, dielectric-activated cell sorting, or inertial microfluidic cell sorting are, however, limited when separating cells of the same kind or cells with similar sizes and dielectric properties, as well as similar electrophysiological phenotypes. Here we report a label-free density difference amplification-based cell sorting (dDACS) without using any external optical, magnetic, electrical forces, or fluidic activations. The conceptual microfluidic design consists of an inlet, hydraulic jump cavity, and multiple outlets. Incoming particles experience gravity, buoyancy, and drag forces in the separation chamber. The height and distance that each particle can reach in the chamber are different and depend on its density, thus allowing for the separation of particles into multiple outlets. The separation behavior of the particles, based on the ratio of the channel heights of the inlet and chamber and Reynolds number has been systematically studied. Numerical simulation reveals that the difference between the heights of only lighter particles with densities close to that of water increases with increasing the ratio of the channel heights, while decreasing Reynolds number can amplify the difference in the heights between the particles considered irrespective of their densities.

Label-free imaging and spectroscopy for early detection of cervical cancer.

PubMed

Jing, Yueyue; Wang, Yulan; Wang, Xinyi; Song, Chuan; Ma, Jiong; Xie, Yonghui; Fei, Yiyan; Zhang, Qinghua; Mi, Lan

2018-05-01

The label-free imaging and spectroscopy method was studied on cervical unstained tissue sections obtained from 36 patients. The native fluorescence spectra of tissues are analyzed by the optical redox ratio (ORR), which is defined as fluorescence intensity ratio between NADH and FAD, and indicates the metabolism change with the cancer development. The ORRs of normal tissues are consistently higher than those of precancer or cancerous tissues. A criterion line of ORR at 5.0 can be used to discriminate cervical precancer/cancer from normal tissues. The sensitivity and specificity of the native fluorescence spectroscopy method for cervical cancer diagnosis are determined as 100% and 91%. Moreover, the native fluorescence spectroscopy study is much more sensitive on the healthy region of cervical precancer/cancer patients compared with the traditional clinical staining method. The results suggest label-free imaging and spectroscopy is a fast, highly sensitive and specific method on the detection of cervical cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A free-air system for long-term stable carbon isotope labeling of adult forest trees

EPA Science Inventory

Stable carbon (C) isotopes, in particular employed in labeling experiments, are an ideal tool to broaden our understanding of C dynamics in trees and forest ecosystems. Here, we present a free-air exposure system, named isoFACE, designed for long-term stable C isotope labeling in...

The Art Gallery/La Galeria de Arte: An Exhibition of Transformation.

ERIC Educational Resources Information Center

Biagi, Juliet

2001-01-01

Describes the development of an art gallery within an urban elementary school, examining its impact on diverse students and their social interactions at school and home. The gallery had a positive impact on students (improved self-esteem, motivation, and appreciation of others); the school (transformation of the physical space and appreciation of…

A Resonator for Low-Threshold Frequency Conversion

NASA Technical Reports Server (NTRS)

Iltchenko, Vladimir; Matsko, Andrey; Savchenkov, Anatoliy; Maleki, Lute

2004-01-01

A proposed toroidal or disklike dielectric optical resonator (dielectric optical cavity) would be made of an optically nonlinear material and would be optimized for use in parametric frequency conversion by imposition of a spatially periodic permanent electric polarization. The poling (see figure) would suppress dispersions caused by both the material and the geometry of the optical cavity, thereby effecting quasi-matching of the phases of high-resonance-quality (high-Q) whispering-gallery electromagnetic modes. The quasi-phase-matching of the modes would serve to maximize the interactions among them. Such a resonator might be a prototype of a family of compact, efficient nonlinear devices for operation over a broad range of optical wavelengths. A little background information is prerequisite to a meaningful description of this proposal: (1) Described in several prior NASA Tech Briefs articles, the whispering-gallery modes in a component of spheroidal, disklike, or toroidal shape are waveguide modes that propagate circumferentially and are concentrated in a narrow toroidal region centered on the equatorial plane and located near the outermost edge. (2) For the sake of completeness, it must be stated that even though optical resonators of the type considered here are solid dielectric objects and light is confined within them by total internal reflection at dielectric interfaces without need for mirrors, such components are sometimes traditionally called cavities because their effects upon the light propagating within them are similar to those of true cavities bounded by mirrors. (3) For a given set of electromagnetic modes interacting with each other in an optically nonlinear material (e.g., modes associated with the frequencies involved in a frequency-conversion scheme), the threshold power for oscillation depends on the mode volumes and the mode-overlap integral. (4) Whispering-gallery modes are attractive in nonlinear optics because they maximize the effects of

Influence of musical training on understanding voiced and whispered speech in noise.

PubMed

Ruggles, Dorea R; Freyman, Richard L; Oxenham, Andrew J

2014-01-01

This study tested the hypothesis that the previously reported advantage of musicians over non-musicians in understanding speech in noise arises from more efficient or robust coding of periodic voiced speech, particularly in fluctuating backgrounds. Speech intelligibility was measured in listeners with extensive musical training, and in those with very little musical training or experience, using normal (voiced) or whispered (unvoiced) grammatically correct nonsense sentences in noise that was spectrally shaped to match the long-term spectrum of the speech, and was either continuous or gated with a 16-Hz square wave. Performance was also measured in clinical speech-in-noise tests and in pitch discrimination. Musicians exhibited enhanced pitch discrimination, as expected. However, no systematic or statistically significant advantage for musicians over non-musicians was found in understanding either voiced or whispered sentences in either continuous or gated noise. Musicians also showed no statistically significant advantage in the clinical speech-in-noise tests. Overall, the results provide no evidence for a significant difference between young adult musicians and non-musicians in their ability to understand speech in noise.

Semi-Supervised Sparse Representation Based Classification for Face Recognition With Insufficient Labeled Samples

NASA Astrophysics Data System (ADS)

Gao, Yuan; Ma, Jiayi; Yuille, Alan L.

2017-05-01

This paper addresses the problem of face recognition when there is only few, or even only a single, labeled examples of the face that we wish to recognize. Moreover, these examples are typically corrupted by nuisance variables, both linear (i.e., additive nuisance variables such as bad lighting, wearing of glasses) and non-linear (i.e., non-additive pixel-wise nuisance variables such as expression changes). The small number of labeled examples means that it is hard to remove these nuisance variables between the training and testing faces to obtain good recognition performance. To address the problem we propose a method called Semi-Supervised Sparse Representation based Classification (S$^3$RC). This is based on recent work on sparsity where faces are represented in terms of two dictionaries: a gallery dictionary consisting of one or more examples of each person, and a variation dictionary representing linear nuisance variables (e.g., different lighting conditions, different glasses). The main idea is that (i) we use the variation dictionary to characterize the linear nuisance variables via the sparsity framework, then (ii) prototype face images are estimated as a gallery dictionary via a Gaussian Mixture Model (GMM), with mixed labeled and unlabeled samples in a semi-supervised manner, to deal with the non-linear nuisance variations between labeled and unlabeled samples. We have done experiments with insufficient labeled samples, even when there is only a single labeled sample per person. Our results on the AR, Multi-PIE, CAS-PEAL, and LFW databases demonstrate that the proposed method is able to deliver significantly improved performance over existing methods.

Label-free electrochemical genosensor based on mesoporous silica thin film.

PubMed

Saadaoui, Maroua; Fernández, Iñigo; Luna, Gema; Díez, Paula; Campuzano, Susana; Raouafi, Noureddine; Sánchez, Alfredo; Pingarrón, José M; Villalonga, Reynaldo

2016-10-01

A novel label-free electrochemical strategy for nucleic acid detection was developed by using gold electrodes coated with mesoporous silica thin films as sensing interface. The biosensing approach relies on the covalent attachment of a capture DNA probe on the surface of the silica nanopores and further hybridization with its complementary target oligonucleotide sequence, causing a diffusion hindering of an Fe(CN)6 (3-/4-) electrochemical probe through the nanochannels of the mesoporous film. This DNA-mesoporous silica thin film-modified electrodes allowed sensitive (91.7 A/M) and rapid (45 min) detection of low nanomolar levels of synthetic target DNA (25 fmol) and were successfully employed to quantify the endogenous content of Escherichia coli 16S ribosomal RNA (rRNA) directly in raw bacterial lysate samples without isolation or purification steps. Moreover, the 1-month stability demonstrated by these biosensing devices enables their advanced preparation and storage, as desired for practical real-life applications. Graphical abstract Mesoporous silica thin films as scaffolds for the development of novel label-free electrochemical genosensors to perform selective, sensitive and rapid detection of target oligonucleotide sequences. Application towards E. coli determination.

Label-free multiphoton microscopy reveals altered tissue architecture in hippocampal sclerosis.

PubMed

Uckermann, Ortrud; Galli, Roberta; Leupold, Susann; Coras, Roland; Meinhardt, Matthias; Hallmeyer-Elgner, Susanne; Mayer, Thomas; Storch, Alexander; Schackert, Gabriele; Koch, Edmund; Blümcke, Ingmar; Steiner, Gerald; Kirsch, Matthias

2017-01-01

The properties and structure of tissue can be visualized without labeling or preparation by multiphoton microscopy combining coherent anti-Stokes Raman scattering (CARS), addressing lipid content, second harmonic generation (SHG) showing collagen, and two-photon excited fluorescence (TPEF) of endogenous fluorophores. We compared samples of sclerotic and nonsclerotic human hippocampus to detect pathologic changes in the brain of patients with pharmacoresistant temporomesial epilepsy (n = 15). Multiphoton microscopy of cryosections and bulk tissue revealed hippocampal layering and micromorphologic details in accordance with reference histology: CARS displayed white and gray matter layering and allowed the assessment of axonal myelin. SHG visualized blood vessels based on adventitial collagen. In addition, corpora amylacea (CoA) were found to be SHG-active. Pyramidal cell bodies were characterized by intense cytoplasmic endogenous TPEF. Furthermore, diffuse TPEF around blood vessels was observed that co-localized with positive albumin immunohistochemistry and might indicate degeneration-associated vascular leakage. We present a label-free and fast optical approach that analyzes pathologic aspects of HS. Hippocampal layering, loss of pyramidal cells, and presence of CoA indicative of sclerosis are visualized. Label-free multiphoton microscopy has the potential to extend the histopathologic armamentarium for ex vivo assessment of changes of the hippocampal formation on fresh tissue and prospectively in vivo. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Theorizing How Art Gallery Interventions Impact People With Dementia and Their Caregivers.

PubMed

Camic, Paul M; Baker, Erin L; Tischler, Victoria

2016-12-01

Dementia refers to a variety of diseases that are characterized by cognitive difficulties and an overall decline in daily living skills. Psychologically informed arts and health programs may be particularly beneficial ways of improving the lives of people with dementia and their caregivers. This study sought to better understand how programs at contemporary and traditional art galleries might play a role in the lives of people with dementia. Participants included 12 people with mild-to-moderate dementia, their 12 caregivers and 4 gallery facilitators. Those with dementia and their caregivers were engaged in art viewing followed by art making over an 8-week period. Data, collected through postintervention interviews with participants, field notes and extensive written communication between the facilitators and research team, were analyzed using grounded theory methodology to theorize how gallery-based interventions affect people with dementia and those who care for them. The emerging theory has four primary components: the art gallery is seen as being a physically valued place that provides intellectual stimulation and offers opportunities for social inclusion that can change how dementia is perceived. These components coalesced to create positive emotional and relational effects for those with dementia and caregivers. The resulting theory has potential implications for the use of gallery-based programs in dementia care within public health, healthcare, and museum/art gallery policy and practice. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Label-free imaging and temporal signature in phenotypic cellular assays: a new approach to high-content screening.

PubMed

Martin, Julio

2010-09-01

Some drug targets are not amenable to screening because of the lack of a practical or validated biological assay. Likewise, some screening assays may not be predictive of compound activity in a more disease-relevant scenario, or assay development may demand excessive allocation of resources (i.e., time, money or personnel) with limited knowledge of the actual tractability of the target. Label-free methodologies, implemented in microtiter plate format, may help address these issues and complement, simplify, or facilitate assays. Label-free biosensors, based on grating resonance or electrical impedance, are versatile platforms for detecting phenotypic changes in both engineered and native cells. Their non-invasive nature allows for the kinetic monitoring of multiple real-time cellular responses to external stimuli, as well as for the use of successive pharmacological challenges. The temporal signature recorded for a particular stimulus is characteristic of the cell type and the signaling pathway activated upon binding of a ligand to its receptor. Cellular label-free technology is an important technical advance in the study of functional pharmacological selectivity. Described in this overview are some of the hurdles encountered in modern drug discovery and the ways in which label-free technologies can be used to overcome these obstacles.

Durability of visitable concrete sewer gallery under the effect of domestic wastewater

NASA Astrophysics Data System (ADS)

Salhi, Aimed; Kriker, Abdelouahed; Tioua, Tahar; Abimiloud, Youcef; Barluenga, Gonzalo

2016-07-01

The durability of concrete structures for the disposal of wastewater depends on their behavior when faced to different aggressions such as mechanics, chemical and biological, causing a deterioration often cementing matrix. The deterioration of recent evacuations wastewater infrastructure, made of reinforced concrete less than 15 years ago, has become an important concern. The aim of this study was to investigate the degradation and the factors responsible for the deterioration of the concrete visitable gallery of sewage from the town of Touggourt (south-east of Algeria). Thus, samples from different parts of the gallery were extracted and unaltered samples were selected as a reference. A degraded sample exposed to H2S gas and another sample of the gallery submerged into wastewater were analyzed to characterize the internal and external damage to the gallery as well as the chemical and mineralogical changes. These tests were complemented by a physical and mechanical characterization of the samples. The experimental results showed the strong anisotropy of both internal and external damage.

EIT in resonator chains: similarities and differences with atomic media

NASA Technical Reports Server (NTRS)

Matsko, A. B.; Maleki, L.; Savchenkov, A. A.; Ilchenko, V. S.

2004-01-01

We theoretically study a parallel configuration of two interacting whispering gallery mode optical resonators and show a narrow-band modal structure as a basis for a widely tunable delay line. For the optimum coupling configuration the system can possess an unusually narrow spectral feature with a much narrower bandwidth than the loaded bandwidth of each individual resonator.

High bandwidth on-chip capacitive tuning of microtoroid resonators

NASA Astrophysics Data System (ADS)

Baker, Christopher G.; Bekker, Christiaan; McAuslan, David L.; Sheridan, Eoin; Bowen, Warwick P.

2016-09-01

We report on the design, fabrication and characterization of silica microtoroid based cavity opto-electromechanical systems (COEMS). Electrodes patterned onto the microtoroid resonators allow for rapid capacitive tuning of the optical whispering gallery mode resonances while maintaining their ultrahigh quality factor, enabling applications such as efficient radio to optical frequency conversion, optical routing and switching applications.

Road to Silicon Microsphere Fabrication and Mode Coupling

DTIC Science & Technology

2014-07-01

from optical fiber onto a microsphere in whispering gallery mode (courtesy of B. Butkus, Biophotonics International [2...Butkus, Biophotonics International [5]). 2 BACKGROUND SILICON MICROSPHERE FABRICATION METHODS Processes for forming spherical structures exist in...Sensitive DNA Detection.” October 2003. Biophotonics International. http://www.rowland.org/rjf/vollmer/images/biophotonics.pdf [6] James E. McDonald

Polymer dual ring resonators for label-free optical biosensing using microfluidics.

PubMed

Salleh, Muhammad H M; Glidle, Andrew; Sorel, Marc; Reboud, Julien; Cooper, Jonathan M

2013-04-18

We demonstrate a polymer resonator microfluidic biosensor that overcomes the complex manufacturing procedures required to fabricate traditional devices. In this new format, we show that a gapless light coupling photonic configuration, fabricated in SU8 polymer, can achieve high sensitivity, label-free chemical sensing in solution and high sensitivity biological sensing, at visible wavelengths.

Affinity Versus Label-Free Isolation of Circulating Tumor Cells: Who Wins?

PubMed

Murlidhar, Vasudha; Rivera-Báez, Lianette; Nagrath, Sunitha

2016-09-01

The study of circulating tumor cells (CTCs) has been made possible by many technological advances in their isolation. Their isolation has seen many fronts, but each technology brings forth a new set of challenges to overcome. Microfluidics has been a key player in the capture of CTCs and their downstream analysis, with the aim of shedding light into their clinical application in cancer and metastasis. Researchers have taken diverging paths to isolate such cells from blood, ranging from affinity-based isolation targeting surface antigens expressed on CTCs, to label-free isolation taking advantage of the size differences between CTCs and other blood cells. For both major groups, many microfluidic technologies have reported high sensitivity and specificity for capturing CTCs. However, the question remains as to the superiority among these two isolation techniques, specifically to identify different CTC populations. This review highlights the key aspects of affinity and label-free microfluidic CTC technologies, and discusses which of these two would be the highest benefactor for the study of CTCs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo label-free photoacoustic microscopy of the anterior segment of the mouse eye

NASA Astrophysics Data System (ADS)

Rao, Bin; Hu, Song; Li, Li; Maslov, Konstantin; Wang, Lihong V.

2010-02-01

Both iris fluorescein angiography (IFA) and indocyanine green angiography (ICGA) provide ophthalmologists imaging tools in studying the microvasculature structure and hemodynamics of the anterior segment of the eye in normal and diseased status. However, a non-invasive, endogenous imaging modality is preferable for the monitoring of hemodynamics of the iris microvasculature. We investigated the in vivo, label-free ocular anterior segment imaging with photo-acoustic microscopy (PAM) in mouse eyes. We demonstrated the unique advantage of endogenous contrast that is not available in both IFA and ICGA. The laser radiation was maintained within the ANSI laser safety limit. The in vivo, label-free nature of our imaging technology has the potential for ophthalmic applications.

Connecting Universal Design for Learning with Gallery Tours in Art Museum Education

ERIC Educational Resources Information Center

Neach, Lauren

2017-01-01

My research study titled, "Connecting Universal Design for Learning with Gallery Tours in Art Museum Education," establishes a relationship between gallery tours in art museum education and the principles of UDL, (CAST, 2011). Through this study I will address contemporary theories on art museum education, volunteer guide training, and…

A 100K well screen for a muscarinic receptor using the Epic label-free system--a reflection on the benefits of the label-free approach to screening seven-transmembrane receptors.

PubMed

Dodgson, K; Gedge, L; Murray, D C; Coldwell, M

2009-01-01

Seven-transmembrane receptors (7TMRs) are a family of proteins of great interest as therapeutic targets because of their abundance on the cell surface, diverse effects in modulating cell behavior and success as a key class of drugs. We have evaluated the Epic label-free system for the purpose of identifying antagonists of the muscarinic M3 receptor. We compared the data generated from the label-free technology with data for the same compounds in a calcium flux assay. We have shown that this technology can be used for high throughput screening (HTS) of 7TMRs and as an orthogonal approach to enable rapid evaluation of HTS outputs. A number of compounds have been identified which were not found in a functional HTS measuring the output from a single pathway, which may offer new approaches to inhibiting responses through this receptor.

Live Imaging of Cellular Internalization of Single Colloidal Particle by Combined Label-Free and Fluorescence Total Internal Reflection Microscopy.

PubMed

Byrne, Gerard D; Vllasaliu, Driton; Falcone, Franco H; Somekh, Michael G; Stolnik, Snjezana

2015-11-02

In this work we utilize the combination of label-free total internal reflection microscopy and total internal reflectance fluorescence (TIRM/TIRF) microscopy to achieve a simultaneous, live imaging of single, label-free colloidal particle endocytosis by individual cells. The TIRM arm of the microscope enables label free imaging of the colloid and cell membrane features, while the TIRF arm images the dynamics of fluorescent-labeled clathrin (protein involved in endocytosis via clathrin pathway), expressed in transfected 3T3 fibroblasts cells. Using a model polymeric colloid and cells with a fluorescently tagged clathrin endocytosis pathway, we demonstrate that wide field TIRM/TIRF coimaging enables live visualization of the process of colloidal particle interaction with the labeled cell structure, which is valuable for discerning the membrane events and route of colloid internalization by the cell. We further show that 500 nm in diameter model polystyrene colloid associates with clathrin, prior to and during its cellular internalization. This association is not apparent with larger, 1 μm in diameter colloids, indicating an upper particle size limit for clathrin-mediated endocytosis.

Functionalized nanopipettes: toward label-free, single cell biosensors.

PubMed

Actis, Paolo; Mak, Andy C; Pourmand, Nader

2010-08-01

Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms.

Functionalized nanopipettes: toward label-free, single cell biosensors

PubMed Central

Actis, Paolo; Mak, Andy C.

2010-01-01

Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms. PMID:20730113

Portrait Gallery Illuminates--Grant's Triumphs, Failures.

ERIC Educational Resources Information Center

Lambert, Robert G., Jr.

The 100th anniversary of Ulysses S. Grant's death was observed on July 23, 1985. The Smithsonian National Portrait Gallery featured an exhibit of Grant portraiture, which covered his life, from its humble beginnings to military and political triumphs and to failures and disappointment. The exhibit included pictures, artifacts, and momentos from…

Label-free and non-contact optical biosensing of glucose with quantum dots.

PubMed

Khan, Saara A; Smith, Gennifer T; Seo, Felix; Ellerbee, Audrey K

2015-02-15

We present a label-free, optical sensor for biomedical applications based on changes in the visible photoluminescence (PL) of quantum dots in a thin polymer film. Using glucose as the target molecule, the screening of UV excitation due to pre-absorption by the product of an enzymatic assay leads to quenching of the PL of quantum dots (QDs) in a non-contact scheme. The irradiance changes in QD PL indicate quantitatively the level of glucose present. The non-contact nature of the assay prevents surface degradation of the QDs, which yields an efficient, waste-free, cost-effective, portable, and sustainable biosensor with attractive market features. The limit of detection of the demonstrated biosensor is ~3.5 µm, which is competitive with existing contact-based bioassays. In addition, the biosensor operates over the entire clinically relevant range of glucose concentrations of biological fluids including urine and whole blood. The comparable results achieved across a range of cost-affordable detectors, including a spectrophotometer, portable spectrometer, and iPhone camera, suggest that label-free and visible quantification of glucose with QD films can be applied to low-cost, point-of-care biomedical sensing as well as scientific applications in the laboratory for characterizing glucose or other analytes. Copyright © 2014 Elsevier B.V. All rights reserved.

Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging

NASA Astrophysics Data System (ADS)

Shi, Sixiang; Fliss, Brianne C.; Gu, Zi; Zhu, Yian; Hong, Hao; Valdovinos, Hector F.; Hernandez, Reinier; Goel, Shreya; Luo, Haiming; Chen, Feng; Barnhart, Todd E.; Nickles, Robert J.; Xu, Zhi Ping; Cai, Weibo

2015-11-01

Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation 64Cu2+ and trivalent cation 44Sc3+ were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation 89Zr4+ could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with 64Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.

Second-harmonic generation in AlGaAs microdisks in the telecom range.

PubMed

Mariani, S; Andronico, A; Lemaître, A; Favero, I; Ducci, S; Leo, G

2014-05-15

We report on second-harmonic generation in whispering-gallery-mode AlGaAs microcavities suspended on a GaAs pedestal. Frequency doubling of a 1.58 μm pump is observed with 7×10(-4)   W(-1) conversion efficiency. This device can be integrated in a monolithic photonic chip for classical and quantum applications in the telecom band.

Label-free optical biosensors based on aptamer-functionalized porous silicon scaffolds.

PubMed

Urmann, Katharina; Walter, Johanna-Gabriela; Scheper, Thomas; Segal, Ester

2015-02-03

A proof-of-concept for a label-free and reagentless optical biosensing platform based on nanostructured porous silicon (PSi) and aptamers is presented in this work. Aptamers are oligonucleotides (single-stranded DNA or RNA) that can bind their targets with high affinity and specificity, making them excellent recognition elements for biosensor design. Here we describe the fabrication and characterization of aptamer-conjugated PSi biosensors, where a previously characterized his-tag binding aptamer (6H7) is used as model system. Exposure of the aptamer-functionalized PSi to the target proteins as well as to complex fluids (i.e., bacteria lysates containing target proteins) results in robust and well-defined changes in the PSi optical interference spectrum, ascribed to specific aptamer-protein binding events occurring within the nanoscale pores, monitored in real time. The biosensors show exceptional stability and can be easily regenerated by a short rinsing step for multiple biosensing analyses. This proof-of-concept study demonstrates the possibility of designing highly stable and specific label-free optical PSi biosensors, employing aptamers as capture probes, holding immense potential for application in detection of a broad range of targets, in a simple yet reliable manner.

Electrochemical lectin based biosensors as a label-free tool in glycomics

PubMed Central

Bertók, Tomáš; Katrlík, Jaroslav; Gemeiner, Peter; Tkac, Jan

2016-01-01

Glycans and other saccharide moieties attached to proteins and lipids, or present on the surface of a cell, are actively involved in numerous physiological or pathological processes. Their structural flexibility (that is based on the formation of various kinds of linkages between saccharides) is making glycans superb “identity cards”. In fact, glycans can form more “words” or “codes” (i.e., unique sequences) from the same number of “letters” (building blocks) than DNA or proteins. Glycans are physicochemically similar and it is not a trivial task to identify their sequence, or - even more challenging - to link a given glycan to a particular physiological or pathological process. Lectins can recognise differences in glycan compositions even in their bound state and therefore are most useful tools in the task to decipher the “glycocode”. Thus, lectin-based biosensors working in a label-free mode can effectively complement the current weaponry of analytical tools in glycomics. This review gives an introduction into the area of glycomics and then focuses on the design, analytical performance, and practical utility of lectin-based electrochemical label-free biosensors for the detection of isolated glycoproteins or intact cells. PMID:27239071

Multiplex and label-free screening of foodborne pathogens using surface plasmon resonance imaging

USDA-ARS?s Scientific Manuscript database

In order to protect outbreaks caused by foodborne pathogens, more rapid and efficient methods are needed for pathogen screening from food samples. Surface plasmon resonance imaging (SPRi) is an emerging optical technique, which allows for label-free screening of multiple targets simultaneously with ...

Label free imaging of cell-substrate contacts by holographic total internal reflection microscopy.

PubMed

Mandracchia, Biagio; Gennari, Oriella; Marchesano, Valentina; Paturzo, Melania; Ferraro, Pietro

2017-09-01

The study of cell adhesion contacts is pivotal to understand cell mechanics and interaction at substrates or chemical and physical stimuli. We designed and built a HoloTIR microscope for label-free quantitative phase imaging of total internal reflection. Here we show for the first time that HoloTIR is a good choice for label-free study of focal contacts and of cell/substrate interaction as its sensitivity is enhanced in comparison with standard TIR microscopy. Finally, the simplicity of implementation and relative low cost, due to the requirement of less optical components, make HoloTIR a reasonable alternative, or even an addition, to TIRF microscopy for mapping cell/substratum topography. As a proof of concept, we studied the formation of focal contacts of fibroblasts on three substrates with different levels of affinity for cell adhesion. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Label-free chemical imaging of live Euglena gracilis by high-speed SRS spectral microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wakisaka, Yoshifumi; Suzuki, Yuta; Tokunaga, Kyoya; Hirose, Misa; Domon, Ryota; Akaho, Rina; Kuroshima, Mai; Tsumura, Norimichi; Shimobaba, Tomoyoshi; Iwata, Osamu; Suzuki, Kengo; Nakashima, Ayaka; Goda, Keisuke; Ozeki, Yasuyuki

2016-03-01

Microbes, especially microalgae, have recently been of great interest for developing novel biofuels, drugs, and biomaterials. Imaging-based screening of live cells can provide high selectivity and is attractive for efficient bio-production from microalgae. Although conventional cellular screening techniques use cell labeling, labeling of microbes is still under development and can interfere with their cellular functions. Furthermore, since live microbes move and change their shapes rapidly, a high-speed imaging technique is required to suppress motion artifacts. Stimulated Raman scattering (SRS) microscopy allows for label-free and high-speed spectral imaging, which helps us visualize chemical components inside biological cells and tissues. Here we demonstrate high-speed SRS imaging, with temporal resolution of 0.14 seconds, of intracellular distributions of lipid, polysaccharide, and chlorophyll concentrations in rapidly moving Euglena gracilis, a unicellular phytoflagellate. Furthermore, we show that our method allows us to analyze the amount of chemical components inside each living cell. Our results indicate that SRS imaging may be applied to label-free screening of living microbes based on chemical information.

Label-free and amplified quantitation of proteins in complex mixtures using diffractive optics technology.

PubMed

Cleverley, Steve; Chen, Irene; Houle, Jean-François

2010-01-15

Immunoaffinity approaches remain invaluable tools for characterization and quantitation of biopolymers. Their application in separation science is often limited due to the challenges of immunoassay development. Typical end-point immunoassays require time consuming and labor-intensive approaches for optimization. Real-time label-free analysis using diffractive optics technology (dot) helps guide a very effective iterative process for rapid immunoassay development. Both label-free and amplified approaches can be used throughout feasibility testing and ultimately in the final assay, providing a robust platform for biopolymer analysis over a very broad dynamic range. We demonstrate the use of dot in rapidly developing assays for quantitating (1) human IgG in complex media, (2) a fusion protein in production media and (3) protein A contamination in purified immunoglobulin preparations. 2009 Elsevier B.V. All rights reserved.

Controlled viable release of selectively captured label-free cells in microchannels.

PubMed

Gurkan, Umut Atakan; Anand, Tarini; Tas, Huseyin; Elkan, David; Akay, Altug; Keles, Hasan Onur; Demirci, Utkan

2011-12-07

Selective capture of cells from bodily fluids in microchannels has broadly transformed medicine enabling circulating tumor cell isolation, rapid CD4(+) cell counting for HIV monitoring, and diagnosis of infectious diseases. Although cell capture methods have been demonstrated in microfluidic systems, the release of captured cells remains a significant challenge. Viable retrieval of captured label-free cells in microchannels will enable a new era in biological sciences by allowing cultivation and post-processing. The significant challenge in release comes from the fact that the cells adhere strongly to the microchannel surface, especially when immuno-based immobilization methods are used. Even though fluid shear and enzymes have been used to detach captured cells in microchannels, these methods are known to harm cells and affect cellular characteristics. This paper describes a new technology to release the selectively captured label-free cells in microchannels without the use of fluid shear or enzymes. We have successfully released the captured CD4(+) cells (3.6% of the mononuclear blood cells) from blood in microfluidic channels with high specificity (89% ± 8%), viability (94% ± 4%), and release efficiency (59% ± 4%). We have further validated our system by specifically capturing and controllably releasing the CD34(+) stem cells from whole blood, which were quantified to be 19 cells per million blood cells in the blood samples used in this study. Our results also indicated that both CD4(+) and CD34(+) cells released from the microchannels were healthy and amenable for in vitro culture. Manual flow based microfluidic method utilizes inexpensive, easy to fabricate microchannels allowing selective label-free cell capture and release in less than 10 minutes, which can also be used at the point-of-care. The presented technology can be used to isolate and purify a broad spectrum of cells from mixed populations offering widespread applications in applied biological

The Empirical Spectator and Gallery Education

ERIC Educational Resources Information Center

Fulkova, Marie; Straker, Alison; Jaros, Milan

2004-01-01

This paper examines the onto-epistemic status and understanding of contemporary material culture and of visual art, particularly in the context of gallery education. It does so through a case study of the response of 15 year-old school students in the Czech Republic and in England to a recent photographic exhibition, I.N.R.I., created by artists…

Multiplex surface plasmon resonance imaging platform for label-free detection of foodborne pathogens

USDA-ARS?s Scientific Manuscript database

Salmonellae are among the leading causes of foodborne outbreaks in the United States, and more rapid and efficient detection methods are needed. Surface plasmon resonance imaging (SPRi) is an emerging optical technique, which allows for rapid and label-free screening of multiple targets simultaneous...

Surface plasmon resonance imaging for label-free detection of foodborne pathogens and toxins

USDA-ARS?s Scientific Manuscript database

More rapid and efficient detection methods for foodborne pathogenic bacteria and toxins are needed to address the long assay time and limitations in multiplex capacity. Surface plasmon resonance imaging (SPRi) is an emerging optical technique, which allows for rapid and label-free screening of multi...

Recognizing different tissues in human fetal femur cartilage by label-free Raman microspectroscopy

NASA Astrophysics Data System (ADS)

Kunstar, Aliz; Leijten, Jeroen; van Leuveren, Stefan; Hilderink, Janneke; Otto, Cees; van Blitterswijk, Clemens A.; Karperien, Marcel; van Apeldoorn, Aart A.

2012-11-01

Traditionally, the composition of bone and cartilage is determined by standard histological methods. We used Raman microscopy, which provides a molecular "fingerprint" of the investigated sample, to detect differences between the zones in human fetal femur cartilage without the need for additional staining or labeling. Raman area scans were made from the (pre)articular cartilage, resting, proliferative, and hypertrophic zones of growth plate and endochondral bone within human fetal femora. Multivariate data analysis was performed on Raman spectral datasets to construct cluster images with corresponding cluster averages. Cluster analysis resulted in detection of individual chondrocyte spectra that could be separated from cartilage extracellular matrix (ECM) spectra and was verified by comparing cluster images with intensity-based Raman images for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific dendrograms were created using Ward's clustering method, and principal component analysis (PCA) was performed with the separated and averaged Raman spectra of cells and ECM of all measured zones. Overall (dis)similarities between measured zones were effectively visualized on the dendrograms and main spectral differences were revealed by PCA allowing for label-free detection of individual cartilaginous zones and for label-free evaluation of proper cartilaginous matrix formation for future tissue engineering and clinical purposes.

A label-free impedimetric DNA sensing chip integrated with AC electroosmotic stirring.

PubMed

Wu, Ching-Chou; Yang, Dong-Jie

2013-05-15

AC electroosmosis (ACEO) flow and label-free electrochemical impedance spectroscopy are employed to increase the hybridization rate and specifically detect target DNA (tDNA) concentrations. A low-ionic-strength solution, 6.1μS/cm 1mM Tris (pH 9.3), was used to produce ACEO and proved the feasibility of hybridization. Adequate voltage parameters for the simultaneous ACEO driving and DNA hybridization in the 1mM Tris solution were 1.5 Vpp and 200Hz. Moreover, an electrode set with a 1:4 ring width-to-disk diameter ratio exhibited a larger ACEO velocity above the disk electrode surface to improve collecting efficiency. The ACEO-integrated DNA sensing chips could reach 90% saturation hybridization within 117s. The linear range and detection limit of the sensors was 10aM-10pM and 10aM, respectively. The label-free impedimetric DNA sensing chips with integrated ACEO stirring can perform rapid hybridization and highly-sensitive detections to specifically measure tDNA concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

Label-free optical imaging of lymphatic vessels within tissue beds in vivo

PubMed Central

Yousefi, Siavash; Zhi, Zhongwei; Wang, Ruikang K.

2015-01-01

Lymphatic vessels are a part of circulatory system in vertebrates that maintain tissue fluid homeostasis and drain excess fluid and large cells that cannot easily find their way back into venous system. Due to the lack of non-invasive monitoring tools, lymphatic vessels are known as forgotten circulation. However, lymphatic system plays an important role in diseases such as cancer and inflammatory conditions. In this paper, we start to briefly review the current existing methods for imaging lymphatic vessels, mostly involving dye/targeting cell injection. We then show the capability of optical coherence tomography (OCT) for label-free non-invasive in vivo imaging of lymph vessels and nodes. One of the advantages of using OCT over other imaging modalities is its ability to assess label-free blood flow perfusion that can be simultaneously observed along with lymphatic vessels for imaging the microcirculatory system within tissue beds. Imaging the microcirculatory system including blood and lymphatic vessels can be utilized for imaging and better understanding pathologic mechanisms and treatment technique development in some critical diseases such as inflammation, malignant cancer angiogenesis and metastasis. PMID:25642129

Whisper: Tracing the Spatiotemporal Process of Information Diffusion in Real Time.

PubMed

Cao, Nan; Lin, Yu-Ru; Sun, Xiaohua; Lazer, D; Liu, Shixia; Qu, Huamin

2012-12-01

When and where is an idea dispersed? Social media, like Twitter, has been increasingly used for exchanging information, opinions and emotions about events that are happening across the world. Here we propose a novel visualization design, "Whisper", for tracing the process of information diffusion in social media in real time. Our design highlights three major characteristics of diffusion processes in social media: the temporal trend, social-spatial extent, and community response of a topic of interest. Such social, spatiotemporal processes are conveyed based on a sunflower metaphor whose seeds are often dispersed far away. In Whisper, we summarize the collective responses of communities on a given topic based on how tweets were retweeted by groups of users, through representing the sentiments extracted from the tweets, and tracing the pathways of retweets on a spatial hierarchical layout. We use an efficient flux line-drawing algorithm to trace multiple pathways so the temporal and spatial patterns can be identified even for a bursty event. A focused diffusion series highlights key roles such as opinion leaders in the diffusion process. We demonstrate how our design facilitates the understanding of when and where a piece of information is dispersed and what are the social responses of the crowd, for large-scale events including political campaigns and natural disasters. Initial feedback from domain experts suggests promising use for today's information consumption and dispersion in the wild.

Label-free cell separation and sorting in microfluidic systems

PubMed Central

Gossett, Daniel R.; Weaver, Westbrook M.; Mach, Albert J.; Hur, Soojung Claire; Tse, Henry Tat Kwong; Lee, Wonhee; Amini, Hamed

2010-01-01

Cell separation and sorting are essential steps in cell biology research and in many diagnostic and therapeutic methods. Recently, there has been interest in methods which avoid the use of biochemical labels; numerous intrinsic biomarkers have been explored to identify cells including size, electrical polarizability, and hydrodynamic properties. This review highlights microfluidic techniques used for label-free discrimination and fractionation of cell populations. Microfluidic systems have been adopted to precisely handle single cells and interface with other tools for biochemical analysis. We analyzed many of these techniques, detailing their mode of separation, while concentrating on recent developments and evaluating their prospects for application. Furthermore, this was done from a perspective where inertial effects are considered important and general performance metrics were proposed which would ease comparison of reported technologies. Lastly, we assess the current state of these technologies and suggest directions which may make them more accessible. Figure A wide range of microfluidic technologies have been developed to separate and sort cells by taking advantage of differences in their intrinsic biophysical properties PMID:20419490

Cell-free measurements of brightness of fluorescently labeled antibodies

PubMed Central

Zhou, Haiying; Tourkakis, George; Shi, Dennis; Kim, David M.; Zhang, Hairong; Du, Tommy; Eades, William C.; Berezin, Mikhail Y.

2017-01-01

Validation of imaging contrast agents, such as fluorescently labeled imaging antibodies, has been recognized as a critical challenge in clinical and preclinical studies. As the number of applications for imaging antibodies grows, these materials are increasingly being subjected to careful scrutiny. Antibody fluorescent brightness is one of the key parameters that is of critical importance. Direct measurements of the brightness with common spectroscopy methods are challenging, because the fluorescent properties of the imaging antibodies are highly sensitive to the methods of conjugation, degree of labeling, and contamination with free dyes. Traditional methods rely on cell-based assays that lack reproducibility and accuracy. In this manuscript, we present a novel and general approach for measuring the brightness using antibody-avid polystyrene beads and flow cytometry. As compared to a cell-based method, the described technique is rapid, quantitative, and highly reproducible. The proposed method requires less than ten microgram of sample and is applicable for optimizing synthetic conjugation procedures, testing commercial imaging antibodies, and performing high-throughput validation of conjugation procedures. PMID:28150730

Polarization Dependent Coupling of Whispering Gallery Modes in Microspheres

NASA Technical Reports Server (NTRS)

Adamovsky, G.; Wrbanek, S.; Floyd, B.; Crotty, M.

2010-01-01

Two sets of resonances in glass microspheres attached to a standard communication-grade single-mode optical fiber have been observed. It has been found that the strength of the resonances depends strongly on the polarization of the coupled light. Furthermore, the position of the resonances in the wavelength domain depends on the polarization of light in the optical fiber with maximum magnitudes shifted by approximately 45 .

Passivated aluminum nanohole arrays for label-free biosensing applications.

PubMed

Canalejas-Tejero, Víctor; Herranz, Sonia; Bellingham, Alyssa; Moreno-Bondi, María Cruz; Barrios, Carlos Angulo

2014-01-22

We report the fabrication and performance of a surface plasmon resonance aluminum nanohole array refractometric biosensor. An aluminum surface passivation treatment based on oxygen plasma is developed in order to circumvent the undesired effects of oxidation and corrosion usually found in aluminum-based biosensors. Immersion tests in deionized water and device simulations are used to evaluate the effectiveness of the passivation process. A label-free bioassay based on biotin analysis through biotin-functionalized dextran-lipase conjugates immobilized on the biosensor-passivated surface in aqueous media is performed as a proof of concept to demonstrate the suitability of these nanostructured aluminum films for biosensing.

On the Determination of Uncertainty and Limit of Detection in Label-Free Biosensors.

PubMed

Lavín, Álvaro; Vicente, Jesús de; Holgado, Miguel; Laguna, María F; Casquel, Rafael; Santamaría, Beatriz; Maigler, María Victoria; Hernández, Ana L; Ramírez, Yolanda

2018-06-26

A significant amount of noteworthy articles reviewing different label-free biosensors are being published in the last years. Most of the times, the comparison among the different biosensors is limited by the procedure used of calculating the limit of detection and the measurement uncertainty. This article clarifies and establishes a simple procedure to determine the calibration function and the uncertainty of the concentration measured at any point of the measuring interval of a generic label-free biosensor. The value of the limit of detection arises naturally from this model as the limit at which uncertainty tends when the concentration tends to zero. The need to provide additional information, such as the measurement interval and its linearity, among others, on the analytical systems and biosensor in addition to the detection limit is pointed out. Finally, the model is applied to curves that are typically obtained in immunoassays and a discussion is made on the application validity of the model and its limitations.

Real-time dual-loop electric current measurement for label-free nanofluidic preconcentration chip.

PubMed

Chung, Pei-Shan; Fan, Yu-Jui; Sheen, Horn-Jiunn; Tian, Wei-Cheng

2015-01-07

An electrokinetic trapping (EKT)-based nanofluidic preconcentration device with the capability of label-free monitoring trapped biomolecules through real-time dual-loop electric current measurement was demonstrated. Universal current-voltage (I-V) curves of EKT-based preconcentration devices, consisting of two microchannels connected by ion-selective channels, are presented for functional validation and optimal operation; universal onset current curves indicating the appearance of the EKT mechanism serve as a confirmation of the concentrating action. The EKT mechanism and the dissimilarity in the current curves related to the volume flow rate (Q), diffusion coefficient (D), and diffusion layer (DL) thickness were explained by a control volume model with a five-stage preconcentration process. Different behaviors of the trapped molecular plug were categorized based on four modes associated with different degrees of electroosmotic instability (EOI). A label-free approach to preconcentrating (bio)molecules and monitoring the multibehavior molecular plug was demonstrated through real-time electric current monitoring, rather than through the use of microscope images.

Topological Galleries: A High Level User Interface for Topology Controlled Volume Rendering

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacCarthy, Brian; Carr, Hamish; Weber, Gunther H.

2011-06-30

Existing topological interfaces to volume rendering are limited by their reliance on sophisticated knowledge of topology by the user. We extend previous work by describing topological galleries, an interface for novice users that is based on the design galleries approach. We report three contributions: an interface based on hierarchical thumbnail galleries to display the containment relationships between topologically identifiable features, the use of the pruning hierarchy instead of branch decomposition for contour tree simplification, and drag-and-drop transfer function assignment for individual components. Initial results suggest that this approach suffers from limitations due to rapid drop-off of feature size in themore » pruning hierarchy. We explore these limitations by providing statistics of feature size as function of depth in the pruning hierarchy of the contour tree.« less

The Cosmology Gallery: Unity through diversity in a vast and awe-inspiring universe.

NASA Astrophysics Data System (ADS)

Goldsmith, John

2011-06-01

Scientists, artists, religious and cultural leaders have come together to create the Cosmology Gallery at the Gravity Discovery Centre (GDC) located 70 km north of Perth, Western Australia. The Cosmology Gallery exhibitions include the multicultural cosmology artworks, Celestial Visions astronomical photography exhibition and the Timeline of the Universe. The multicultural cosmology artworks are new artworks inspired by Australian Indigenous, Christian, Buddhist, Islamic, Hindu, scientific and technological perspectives of the universe. The Celestial Visions exhibition features astronomical events above famous landmarks, including Stonehenge and the Pyramids. The AUD 400,000+ project was funded by Lotterywest, Western Australia and the Cosmology Gallery was officially opened in July 2008 by the Premier of Western Australia.

Relation between clinical mature and immature lymphocyte cells in human peripheral blood and their spatial label free scattering patterns

NASA Astrophysics Data System (ADS)

Zhang, Lu; Zhao, Xin; Zhang, Zhenxi; Zhao, Hong; Chen, Wei; Yuan, Li

2016-07-01

A single living cell's light scattering pattern (LSP) in the horizontal plane, which has been denoted as the cell's "2D fingerprint," may provide a powerful label-free detection tool in clinical applications. We have recently studied the LSP in spatial scattering planes, denoted as the cell's "3D fingerprint," for mature and immature lymphocyte cells in human peripheral blood. The effects of membrane size, morphology, and the existence of the nucleus on the spatial LSP are discussed. In order to distinguish clinical label-free mature and immature lymphocytes, the special features of the spatial LSP are studied by statistical method in both the spatial and frequency domains. Spatial LSP provides rich information on the cell's morphology and contents, which can distinguish mature from immature lymphocyte cells and hence ultimately it may be a useful label-free technique for clinical leukemia diagnosis.

Traveling in the Snite Museum: A Gallery Game for Families and Young Children.

ERIC Educational Resources Information Center

Matthias, Diana C. J.; Grey, Richard

This game, designed for use in the Snite Museum of Art, Knott Beckman Gallery, Indiana, focuses on some of the different types of travel depicted in gallery paintings from 16th and 17th century Europe. The questions, with multiple choice answers, encourage viewers to find details of every day life, and to consider whether their meaning is…

Teaching Students to Teach: A Case Study from the Yale University Art Gallery

ERIC Educational Resources Information Center

Manekin, Elizabeth; Williams, Elizabeth

2015-01-01

The way the Yale University Art Gallery engages students and the adult public has shifted profoundly over time, a change reflected in the evolution of the museum's signature Gallery Guide program. Founded in 1998 as an organic, experimental way to better engage Yale students to give lecture-based tours, it is now a structured, well-articulated…

Doppler Fourier Domain Optical Coherence Tomography for Label-Free Tissue Angiography

NASA Astrophysics Data System (ADS)

Leitgeb, Rainer A.; Szkulmowski, Maciej; Blatter, Cedric; Wojtkowski, Maciej

Information about tissue perfusion and the vascular structure is certainly most important for assessment of tissue state or personal health and the diagnosis of any pathological conditions. It is therefore of key medical interest to have tools available for both quantitative blood flow assessment as well as qualitative vascular imaging. The strength of optical techniques is the unprecedented level of detail even for small capillary structures or microaneurysms and the possibility to combine different techniques for additional tissue spectroscopy giving insight into tissue metabolism. There is an immediate diagnostic and pharmacological demand for high-resolution, label-free, tissue angiography and flow assessment that in addition allow for precise depth gating of flow information. The most promising candidate is Doppler optical coherence tomography (DOCT) being noncontact, label free, and without employing hazardous radiation. DOCT provides fully quantitative volumetric information about blood flow together with the vascular and structural anatomy. Besides flow quantification, analysis of OCT signal fluctuations allows to contrast moving scatterers in tissue such as red blood cells from static tissue. This allows for non-invasive optical angiography and yields high resolution even for smallest capillaries. Because of the huge potential of DOCT and lable-free optical angiography for diagnosis, the last years saw a rapid increase of publications in this field with many different approaches. The present chapter gives an overview over existing Doppler OCT approaches and angiography techniques. It furthermore discusses limitations and noise issues, and gives examples for angiography in the eye and the skin.

Fiber optic label-free biophotonic diagnostic tool for cardiovascular disease

NASA Astrophysics Data System (ADS)

Rius, Cristina; Ackermann, Tobias N.; Dorado, Beatriz; Muñoz-Berbel, Xavier; Andrés, Vicente; Llobera, Andreu

2015-06-01

A label-free compact method for performing photonic characterization of "healthy" versus "diseased" arteries has been developed. It permits the detection of atherosclerotic lesion in living mouse arteries. Using this prototype, we observed that the spectral response (photonic fingerprint, PIN) obtained from aortas of wild-type mice differs from the response of ApoE-KO mice fed with high-fat diet (an atheroprone mouse model). Benchmark of the results against gold standard was performed by staining the aortas with Oil-Red-O to visualize atherosclerotic plaques.

Printable Silicon Nanomembranes for Solar-Powered, Bi-Directional Phased-Array-Antenna Communication System on Flexible Substrates

DTIC Science & Technology

2013-04-01

Identification (RFID), Large Area Flexible Displays, Electronic Paper, Bio - Sensors , Large Area Conformal and Flexible Antennas, Smart and Interactive Textiles...Lepeshkin, R. W. Boyd, C. Chase, and J. E. Fajardo, “An environmental sensor based on an integrated optical whispering gallery mode disk resonator ...Ubiquitous Sensor Networks (USN), Vehicle Clickers Readers, Real Time Locating Systems, Lighting, Photovoltaics etc. FA9550-11-C-0014 STTR Phase II

Chemotaxis of cancer cells in three-dimensional environment monitored label-free by quantitative phase digital holographic microscopy

NASA Astrophysics Data System (ADS)

Kemper, Björn; Schnekenburger, Jürgen; Ketelhut, Steffi

2017-02-01

We investigated the capabilities of digital holographic microscopy (DHM) for label-free quantification of the response of living single cells to chemical stimuli in 3D assays. Fibro sarcoma cells were observed in a collagen matrix inside 3D chemotaxis chambers with a Mach-Zehnder interferometer-based DHM setup. From the obtained series of quantitative phase images, the migration trajectories of single cells were retrieved by automated cell tracking and subsequently analyzed for maximum migration distance and motility. Our results demonstrate DHM as a highly reliable and efficient tool for label-free quantification of chemotaxis in 2D and 3D environments.

Whole-organ atlas imaged by label-free high-resolution photoacoustic microscopy assisted by a microtome

NASA Astrophysics Data System (ADS)

Wong, Terence T. W.; Zhang, Ruiying; Hsu, Hsun-Chia; Maslov, Konstantin I.; Shi, Junhui; Chen, Ruimin; Shung, K. Kirk; Zhou, Qifa; Wang, Lihong V.

2018-02-01

In biomedical imaging, all optical techniques face a fundamental trade-off between spatial resolution and tissue penetration. Therefore, obtaining an organelle-level resolution image of a whole organ has remained a challenging and yet appealing scientific pursuit. Over the past decade, optical microscopy assisted by mechanical sectioning or chemical clearing of tissue has been demonstrated as a powerful technique to overcome this dilemma, one of particular use in imaging the neural network. However, this type of techniques needs lengthy special preparation of the tissue specimen, which hinders broad application in life sciences. Here, we propose a new label-free three-dimensional imaging technique, named microtomy-assisted photoacoustic microscopy (mPAM), for potentially imaging all biomolecules with 100% endogenous natural staining in whole organs with high fidelity. We demonstrate the first label-free mPAM, using UV light for label-free histology-like imaging, in whole organs (e.g., mouse brains), most of them formalin-fixed and paraffin- or agarose-embedded for minimal morphological deformation. Furthermore, mPAM with dual wavelength illuminations is also employed to image a mouse brain slice, demonstrating the potential for imaging of multiple biomolecules without staining. With visible light illumination, mPAM also shows its deep tissue imaging capability, which enables less slicing and hence reduces sectioning artifacts. mPAM could potentially provide a new insight for understanding complex biological organs.

Practice First: Flipped Training for Gallery Educators

ERIC Educational Resources Information Center

Palamara, Andrew

2017-01-01

In recent years, museum educators have urgently explored more dynamic ways to train gallery educators, paid or volunteer, that account for different types of learning styles and teaching practices. This article demonstrates how utilizing a flipped learning model, with online webinars as the basic instructional content, can foster individual and…

Gallery productivity, emergence, and flight activity of the redbay ambrosia beetle (Coleoptera: Curculionidae: Scolytinae)

Treesearch

M. Lake Maner; James Hanula; S. Kristine Braman

2013-01-01

Flight and emergence of the redbay ambrosia beetle, Xyleborus glabratus Eichhoff, were monitored from March 2011 through August 2012 using Lindgren funnel traps baited with manuka oil and emergence traps attached over individual beetle galleries on infested redbay (Persea borbonia (L.) Sprengel) trees. Of the 432 gallery entrances...

Label-free SERS detection of Salmonella Typhimurium on DNA aptamer modified AgNR substrates

USDA-ARS?s Scientific Manuscript database

A straightforward label-free method based on aptamer binding and surface enhanced Raman specstroscopy (SERS) has been developed for the detection of Salmonella Typhimurium, an important foodborne pathogen that causes gastroenteritis in both humans and animals. Surface of the SERS-active silver nanor...

Optical Microfibre Based Photonic Components and Their Applications in Label-Free Biosensing

PubMed Central

Wang, Pengfei; Bo, Lin; Semenova, Yuliya; Farrell, Gerald; Brambilla, Gilberto

2015-01-01

Optical microfibre photonic components offer a variety of enabling properties, including large evanescent fields, flexibility, configurability, high confinement, robustness and compactness. These unique features have been exploited in a range of applications such as telecommunication, sensing, optical manipulation and high Q resonators. Optical microfibre biosensors, as a class of fibre optic biosensors which rely on small geometries to expose the evanescent field to interact with samples, have been widely investigated. Due to their unique properties, such as fast response, functionalization, strong confinement, configurability, flexibility, compact size, low cost, robustness, ease of miniaturization, large evanescent field and label-free operation, optical microfibres based biosensors seem a promising alternative to traditional immunological methods for biomolecule measurements. Unlabeled DNA and protein targets can be detected by monitoring the changes of various optical transduction mechanisms, such as refractive index, absorption and surface plasmon resonance, since a target molecule is capable of binding to an immobilized optical microfibre. In this review, we critically summarize accomplishments of past optical microfibre label-free biosensors, identify areas for future research and provide a detailed account of the studies conducted to date for biomolecules detection using optical microfibres. PMID:26287252

Optical Microfibre Based Photonic Components and Their Applications in Label-Free Biosensing.

PubMed

Wang, Pengfei; Bo, Lin; Semenova, Yuliya; Farrell, Gerald; Brambilla, Gilberto

2015-07-22

Optical microfibre photonic components offer a variety of enabling properties, including large evanescent fields, flexibility, configurability, high confinement, robustness and compactness. These unique features have been exploited in a range of applications such as telecommunication, sensing, optical manipulation and high Q resonators. Optical microfibre biosensors, as a class of fibre optic biosensors which rely on small geometries to expose the evanescent field to interact with samples, have been widely investigated. Due to their unique properties, such as fast response, functionalization, strong confinement, configurability, flexibility, compact size, low cost, robustness, ease of miniaturization, large evanescent field and label-free operation, optical microfibres based biosensors seem a promising alternative to traditional immunological methods for biomolecule measurements. Unlabeled DNA and protein targets can be detected by monitoring the changes of various optical transduction mechanisms, such as refractive index, absorption and surface plasmon resonance, since a target molecule is capable of binding to an immobilized optical microfibre. In this review, we critically summarize accomplishments of past optical microfibre label-free biosensors, identify areas for future research and provide a detailed account of the studies conducted to date for biomolecules detection using optical microfibres.

Surface Plasmon Resonance Label-Free Monitoring of Antibody Antigen Interactions in Real Time

ERIC Educational Resources Information Center

Kausaite, Asta; van Dijk, Martijn; Castrop, Jan; Ramanaviciene, Almira; Baltrus, John P.; Acaite, Juzefa; Ramanavicius, Arunas

2007-01-01

Detection of biologically active compounds is one of the most important topics in molecular biology and biochemistry. One of the most promising detection methods is based on the application of surface plasmon resonance for label-free detection of biologically active compounds. This method allows one to monitor binding events in real time without…

Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.

PubMed

Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika; Yki-Järvinen, Hannele; Ikonen, Elina

2016-01-01

Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0-4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading.

Quantitative label-free multimodality nonlinear optical imaging for in situ differentiation of cancerous lesions

NASA Astrophysics Data System (ADS)

Xu, Xiaoyun; Li, Xiaoyan; Cheng, Jie; Liu, Zhengfan; Thrall, Michael J.; Wang, Xi; Wang, Zhiyong; Wong, Stephen T. C.

2013-03-01

The development of real-time, label-free imaging techniques has recently attracted research interest for in situ differentiation of cancerous lesions from normal tissues. Molecule-specific intrinsic contrast can arise from label-free imaging techniques such as Coherent Anti-Stokes Raman Scattering (CARS), Two-Photon Excited AutoFluorescence (TPEAF), and Second Harmonic Generation (SHG), which, in combination, would hold the promise of a powerful label-free tool for cancer diagnosis. Among cancer-related deaths, lung carcinoma is the leading cause for both sexes. Although early treatment can increase the survival rate dramatically, lesion detection and precise diagnosis at an early stage is unusual due to its asymptomatic nature and limitations of current diagnostic techniques that make screening difficult. We investigated the potential of using multimodality nonlinear optical microscopy that incorporates CARS, TPEAF, and SHG techniques for differentiation of lung cancer from normal tissue. Cancerous and non-cancerous lung tissue samples from patients were imaged using CARS, TPEAF, and SHG techniques for comparison. These images showed good pathology correlation with hematoxylin and eosin (H and E) stained sections from the same tissue samples. Ongoing work includes imaging at various penetration depths to show three-dimensional morphologies of tumor cell nuclei using CARS, elastin using TPEAF, and collagen using SHG and developing classification algorithms for quantitative feature extraction to enable lung cancer diagnosis. Our results indicate that via real-time morphology analyses, a multimodality nonlinear optical imaging platform potentially offers a powerful minimally-invasive way to differentiate cancer lesions from surrounding non-tumor tissues in vivo for clinical applications.

Development of a label-free immunosensor system for detecting plasma cortisol levels in fish.

PubMed

Wu, Haiyun; Ohnuki, Hitoshi; Hibi, Kyoko; Ren, Huifeng; Endo, Hideaki

2016-02-01

Fishes display a wide variation in their physiological responses to stress, which is clearly evident in the plasma corticosteroid changes, chiefly cortisol levels in fish. In the present study, we describe a novel label-free immunosensor for detecting plasma cortisol levels. The method is based on immunologic reactions and amperometric measurement using cyclic voltammetry. For the immobilization of the antibody on the surface of sensing electrode, we used a self-assembled monolayer of thiol-containing compounds. Using this electrode, we detect the CV signal change caused by the generation of antigen-antibody complex. The immunosensor showed a response to cortisol levels, and the anodic peak value linearly decreased with a correlation coefficient of 0.990 in diluted plasma. The specificity of the label-free immunosensor system was investigated using other steroid hormones, such as 17α, 20β-dihydroxy-4-pregnen-3-one, progesterone, estriol, estradiol, and testosterone. The specific detection of cortisol was suggested by a minimal change from -0.32 to 0.51 μA in the anodic peak value of the other steroid hormones. The sensor system was used to determine the plasma cortisol levels in Nile tilapia (Oreochromis niloticus), and the results were compared with those of the same samples determined using the conventional method (ELISA). A good correlation was obtained between values determined using both methods (correlation coefficient 0.993). These findings suggest that the proposed label-free immunosensor could be useful for rapid and convenient analysis of cortisol levels in fish plasma samples.

Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy.

PubMed

Verma, Anil K; Gatti, Simona; Galeazzi, Tiziana; Monachesi, Chiara; Padella, Lucia; Baldo, Giada Del; Annibali, Roberta; Lionetti, Elena; Catassi, Carlo

2017-02-07

A strict and lifelong gluten-free diet is the only treatment of celiac disease. Gluten contamination has been frequently reported in nominally gluten-free products. The aim of this study was to test the level of gluten contamination in gluten-free products currently available in the Italian market. A total of 200 commercially available gluten-free products (including both naturally and certified gluten-free products) were randomly collected from different Italian supermarkets. The gluten content was determined by the R5 ELISA Kit approved by EU regulations. Gluten level was lower than 10 part per million (ppm) in 173 products (86.5%), between 10 and 20 ppm in 9 (4.5%), and higher than 20 ppm in 18 (9%), respectively. In contaminated foodstuff (gluten > 20 ppm) the amount of gluten was almost exclusively in the range of a very low gluten content. Contaminated products most commonly belonged to oats-, buckwheat-, and lentils-based items. Certified and higher cost gluten-free products were less commonly contaminated by gluten. Gluten contamination in either naturally or labeled gluten-free products marketed in Italy is nowadays uncommon and usually mild on a quantitative basis. A program of systematic sampling of gluten-free food is needed to promptly disclose at-risk products.

Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy

PubMed Central

Verma, Anil K.; Gatti, Simona; Galeazzi, Tiziana; Monachesi, Chiara; Padella, Lucia; Baldo, Giada Del; Annibali, Roberta; Lionetti, Elena; Catassi, Carlo

2017-01-01

Background: A strict and lifelong gluten-free diet is the only treatment of celiac disease. Gluten contamination has been frequently reported in nominally gluten-free products. The aim of this study was to test the level of gluten contamination in gluten-free products currently available in the Italian market. Method: A total of 200 commercially available gluten-free products (including both naturally and certified gluten-free products) were randomly collected from different Italian supermarkets. The gluten content was determined by the R5 ELISA Kit approved by EU regulations. Results: Gluten level was lower than 10 part per million (ppm) in 173 products (86.5%), between 10 and 20 ppm in 9 (4.5%), and higher than 20 ppm in 18 (9%), respectively. In contaminated foodstuff (gluten > 20 ppm) the amount of gluten was almost exclusively in the range of a very low gluten content. Contaminated products most commonly belonged to oats-, buckwheat-, and lentils-based items. Certified and higher cost gluten-free products were less commonly contaminated by gluten. Conclusion: Gluten contamination in either naturally or labeled gluten-free products marketed in Italy is nowadays uncommon and usually mild on a quantitative basis. A program of systematic sampling of gluten-free food is needed to promptly disclose at-risk products. PMID:28178205

Mega-pixel PQR laser chips for interconnect, display ITS, and biocell-tweezers OEIC

NASA Astrophysics Data System (ADS)

Kwon, O'Dae; Yoon, J. H.; Kim, D. K.; Kim, Y. C.; Lee, S. E.; Kim, S. S.

2008-02-01

We describe a photonic quantum ring (PQR) laser device of three dimensional toroidal whispering gallery cavity. We have succeeded in fabricating the first genuine mega-pixel laser chips via regular semiconductor technology. This has been realized since the present injection laser emitting surface-normal dominant 3D whispering gallery modes (WGMs) can be operated CW with extremely low operating currents (μA-nA per pixel), together with the lasing temperature stabilities well above 140 deg C with minimal redshifts, which solves the well-known integration problems facing the conventional VCSEL. Such properties unusual for quantum well lasers become usual because the active region, involving vertically confining DBR structure in addition to the 2D concave WGM geometry, induces a 'photonic quantum ring (PQR)-like' carrier distribution through a photonic quantum corral effect. A few applications of such mega-pixel PQR chips are explained as follows: (A) Next-generation 3D semiconductor technologies demand a strategy on the inter-chip and intra-chip optical interconnect schemes with a key to the high-density emitter array. (B) Due to mounting traffic problems and fatalities ITS technology today is looking for a revolutionary change in the technology. We will thus outline how 'SLEEP-ITS' can emerge with the PQR's position-sensing capability. (C) We describe a recent PQR 'hole' laser of convex WGM: Mega-pixel PQR 'hole' laser chips are even easier to fabricate than PQR 'mesa' lasers. Genuine Laguerre-Gaussian (LG) beam patterns of PQR holes are very promising for biocell manipulations like sorting mouse myeloid leukemia (M1s) cells. (D) Energy saving and 3D speckle-free POR laser can outdo LEDs in view of red GaAs and blue GaN devices fabricated recently.

Label-free fluorescent aptasensor for potassium ion using structure-switching aptamers and berberine

NASA Astrophysics Data System (ADS)

Guo, Yanqing; Chen, Yanxia; Wei, Yanli; Li, Huanhuan; Dong, Chuan

2015-02-01

A simple, rapid and label-free fluorescent aptasensor was fabricated for the detection of potassium ion (K+ ion) in aqueous solution using K+ ion-stabilized single stranded DNA (ssDNA) with G-rich sequence as the recognition element and a fluorescent dye, berberine, as the fluorescence probe. In the presence of K+ ion, the G-rich ssDNA is promoted to form the aptamer-target complex with a G-quadruplex conformation, and berberine binding to the G-quadruplex structure results in the enhancement of its fluorescence. The fluorescence intensity of the sensing system displayed a calibration response for K+ ion in the range of 0-1600 μM with a detection limit of 31 nM (S/N = 3) and a relative standard deviation (RSD) of 0.45%. This label-free fluorescence aptasensor is conveniently and effectively applicable for analysis of K+ ion in blood serum samples with the recovery range of 81.7-105.3%. The assay for detection of potassium ion is easy, economical, robust, and stable in rough conditions.

Species composition, community and population dynamics of two gallery forests from the Brazilian Cerrado domain

PubMed Central

Almado, Roosevelt P; Miazaki, Angela S; Diniz, Écio S; Moreira, Luis C B; Meira-Neto, João A.A.

2016-01-01

Abstract Background To understand the impacts of global changes on future community compositions, knowledge of community dynamics is of crucial importance. To improve our knowledge of community composition, biomass stock and maintenance of gallery forests in the Brazilian Cerrado, we provide two datasets from the 0.5 ha Corrego Fazendinha Gallery Forest Dynamics Plot and the Corrego Fundo Gallery Forest Dynamics Plot situated in the Bom Despacho region, Minas Gerais, Southeastern Brazil. New information We report diameter at breast height, basal area and height measurements of 3417 trees and treelets identified during three censuses in both areas. PMID:27660529

Hairpin assembly circuit-based fluorescence cooperative amplification strategy for enzyme-free and label-free detection of small molecule.

PubMed

Feng, Chunjing; Zhu, Jing; Sun, Jiewei; Jiang, Wei; Wang, Lei

2015-10-01

Here, we developed an enzyme-free, label-free, and sensitive fluorescence cooperative amplification strategy based on a hairpin assembly circuit which coupled catalytic hairpin assembly (CHA) with hybridization chain reaction (HCR) for small molecule adenosine. A double-strand DNA probe with aptamer-catalysis strand (Apt-C) and inhibit strand (Inh) was designed for adenosine recognition and signal transduction which was named as Apt-C/Inh. Hairpins H1 and H2 were employed for constructing the CHA, and hairpins H3 and H4 for the HCR. Through the binding of adenosine and the Apt-C, the Inh was released from the Apt-C/Inh. Then the free Apt-C initiated the CHA through successively opening H1 and H2, generating H1/H2 complex and recyclable Apt-C. Next, the released Apt-C entered another CHA cycle, and the H1/H2 complex further initiated the HCR of H3 and H4 which induced the formation of the concatemers of H3/H4 complex. Such a process brought the two ends of hairpins H3 into close proximity, yielding numerous integrated G-quadruplexes which were initially sequestered in the stem and two terminals of H3. Finally, N-methyl mesoporphyrin IX (NMM) was added to generate an enhanced fluorescence signal. In the proposed strategy, driven only by the energy from hybridization, one target could trigger multiple HCR events via CHA-based target-cycle, leading to a remarkable enzyme-free amplification for adenosine. The detection limit could achieve as low as 9.7 × 10(-7) mol L(-1). Furthermore, G-quadruplexes were applied to construct label-free hairpin assembly circuit, which made it more simple and cost-effective. The satisfactory recoveries were obtained when detecting adenosine in spiked human serum and urine samples, demonstrating the feasibility of this detection strategy in biological samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Photo Gallery from the Los Angeles River Watershed (California)

EPA Pesticide Factsheets

Photo gallery of the Los Angeles River Watershed area of the Urban Waters Federal Partnership (UWFP) reconnects urban communities with their waterways by improving coordination among federal agencies and collaborating with community-led efforts.

Ultrasensitive Sensing Material Based on Opal Photonic Crystal for Label-Free Monitoring of Transferrin.

PubMed

Wu, Enqi; Peng, Yuan; Zhang, Xihao; Bai, Jialei; Song, Yanqiu; He, Houluo; Fan, Longxing; Qu, Xiaochen; Gao, Zhixian; Liu, Ying; Ning, Baoan

2017-02-22

A new opal photonic crystal (PC) sensing material, allowing label-free detection of transferrin (TRF), is proposed in the current study. This photonic crystal was prepared via a vertical convective self-assembly method with monodisperse microspheres polymerized by methyl methacrylate (MMA) and 3-acrylamidophenylboronic acid (AAPBA). FTIR, TG, and DLS were used to characterize the components and particle size of the monodisperse microspheres. SEM was used to observe the morphology of the PC. The diffraction peak intensity decreases as the TRF concentration increase. This was due to the combination of TRF to the boronic acid group of the photonic crystal. After condition optimization, a standard curve was obtained and the linear range of TRF concentration was from 2 × 10 -3 ng/mL to 200 ng/mL. Measurement of TRF concentration in simulated urine sample was also investigated using the sensing material. The results indicated that the PC provided a cheap, label-free, and easy-to-use alternative for TRF determination in clinical diagnostics.

Label-free and high-sensitive detection for genetic point mutation based on hyperspectral interferometry

NASA Astrophysics Data System (ADS)

Fu, Rongxin; Li, Qi; Zhang, Junqi; Wang, Ruliang; Lin, Xue; Xue, Ning; Su, Ya; Jiang, Kai; Huang, Guoliang

2016-10-01

Label free point mutation detection is particularly momentous in the area of biomedical research and clinical diagnosis since gene mutations naturally occur and bring about highly fatal diseases. In this paper, a label free and high sensitive approach is proposed for point mutation detection based on hyperspectral interferometry. A hybridization strategy is designed to discriminate a single-base substitution with sequence-specific DNA ligase. Double-strand structures will take place only if added oligonucleotides are perfectly paired to the probe sequence. The proposed approach takes full use of the inherent conformation of double-strand DNA molecules on the substrate and a spectrum analysis method is established to point out the sub-nanoscale thickness variation, which benefits to high sensitive mutation detection. The limit of detection reach 4pg/mm2 according to the experimental result. A lung cancer gene point mutation was demonstrated, proving the high selectivity and multiplex analysis capability of the proposed biosensor.

Nanophotonic label-free biosensors for environmental monitoring.

PubMed

Chocarro-Ruiz, Blanca; Fernández-Gavela, Adrián; Herranz, Sonia; Lechuga, Laura M

2017-06-01

The field of environmental monitoring has experienced a substantial progress in the last years but still the on-site control of contaminants is an elusive problem. In addition, the growing number of pollutant sources is accompanied by an increasing need of having efficient early warning systems. Several years ago biosensor devices emerged as promising environmental monitoring tools, but their level of miniaturization and their fully operation outside the laboratory prevented their use on-site. In the last period, nanophotonic biosensors based on evanescent sensing have emerged as an outstanding choice for portable point-of-care diagnosis thanks to their capability, among others, of miniaturization, multiplexing, label-free detection and integration in lab-on-chip platforms. This review covers the most relevant nanophotonic biosensors which have been proposed (including interferometric waveguides, grating-couplers, microcavity resonators, photonic crystals and localized surface plasmon resonance sensors) and their recent application for environmental surveillance. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Portable Art Gallery: Fostering Student Ownership and Meaningful Artmaking through Exhibiting Student Artwork

ERIC Educational Resources Information Center

Gillespie, Jethro

2014-01-01

This article describes how High School Visual Arts Teacher Jethro Gillespie built a portable art gallery for his students--essentially an 8-foot cube made from plywood and lightweight boards that can be assembled with bolts and taken apart in sections. The ceiling pieces of the gallery have track lights, the interior walls have been painted gray,…

Label-free quantitative cell division monitoring of endothelial cells by digital holographic microscopy

NASA Astrophysics Data System (ADS)

Kemper, Björn; Bauwens, Andreas; Vollmer, Angelika; Ketelhut, Steffi; Langehanenberg, Patrik; Müthing, Johannes; Karch, Helge; von Bally, Gert

2010-05-01

Digital holographic microscopy (DHM) enables quantitative multifocus phase contrast imaging for nondestructive technical inspection and live cell analysis. Time-lapse investigations on human brain microvascular endothelial cells demonstrate the use of DHM for label-free dynamic quantitative monitoring of cell division of mother cells into daughter cells. Cytokinetic DHM analysis provides future applications in toxicology and cancer research.

The Phosphates of Pleistocene-Holocene Sediments of the Eastern Gallery of Denisova Cave

NASA Astrophysics Data System (ADS)

Shunkov, M. V.; Kulik, N. A.; Kozlikin, M. B.; Sokol, E. V.; Miroshnichenko, L. V.; Ulianov, V. A.

2018-01-01

Authigenic phosphate mineralization was first studied on the territory of Russia on the basis of the Holocene and Pleistocene deposits of Denisova Cave. The formation of phosphates in the eastern gallery is related to biodegradation of the horizons of guano of insectivorous bats, which inhabited the cave in the absence man. The results confirmed the archaeological record of the Holocene and the upper part of Pleistocene sequences of the eastern gallery.

Label-Free Raman Imaging to Monitor Breast Tumor Signatures.

PubMed

Manciu, Felicia S; Ciubuc, John D; Parra, Karla; Manciu, Marian; Bennet, Kevin E; Valenzuela, Paloma; Sundin, Emma M; Durrer, William G; Reza, Luis; Francia, Giulio

2017-08-01

Although not yet ready for clinical application, methods based on Raman spectroscopy have shown significant potential in identifying, characterizing, and discriminating between noncancerous and cancerous specimens. Real-time and accurate medical diagnosis achievable through this vibrational optical method largely benefits from improvements in current technological and software capabilities. Not only is the acquisition of spectral information now possible in milliseconds and analysis of hundreds of thousands of data points achieved in minutes, but Raman spectroscopy also allows simultaneous detection and monitoring of several biological components. Besides demonstrating a significant Raman signature distinction between nontumorigenic (MCF-10A) and tumorigenic (MCF-7) breast epithelial cells, our study demonstrates that Raman can be used as a label-free method to evaluate epidermal growth factor activity in tumor cells. Comparative Raman profiles and images of specimens in the presence or absence of epidermal growth factor show important differences in regions attributed to lipid, protein, and nucleic acid vibrations. The occurrence, which is dependent on the presence of epidermal growth factor, of new Raman features associated with the appearance of phosphothreonine and phosphoserine residues reflects a signal transduction from the membrane to the nucleus, with concomitant modification of DNA/RNA structural characteristics. Parallel Western blotting analysis reveals an epidermal growth factor induction of phosphorylated Akt protein, corroborating the Raman results. The analysis presented in this work is an important step toward Raman-based evaluation of biological activity of epidermal growth factor receptors on the surfaces of breast cancer cells. With the ultimate future goal of clinically implementing Raman-guided techniques for the diagnosis of breast tumors (e.g., with regard to specific receptor activity), the current results just lay the foundation for

Label-free imaging to study phenotypic behavioural traits of cells in complex co-cultures

NASA Astrophysics Data System (ADS)

Suman, Rakesh; Smith, Gabrielle; Hazel, Kathryn E. A.; Kasprowicz, Richard; Coles, Mark; O'Toole, Peter; Chawla, Sangeeta

2016-02-01

Time-lapse imaging is a fundamental tool for studying cellular behaviours, however studies of primary cells in complex co-culture environments often requires fluorescent labelling and significant light exposure that can perturb their natural function over time. Here, we describe ptychographic phase imaging that permits prolonged label-free time-lapse imaging of microglia in the presence of neurons and astrocytes, which better resembles in vivo microenvironments. We demonstrate the use of ptychography as an assay to study the phenotypic behaviour of microglial cells in primary neuronal co-cultures through the addition of cyclosporine A, a potent immune-modulator.

Surface plasmon resonance label-free monitoring of antibody antigen interactions in real time

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kausaite, A.; van Dijk, M.; Castrop, J.

2007-01-01

Detection of biologically active compounds is one of the most important topics in molecular biology and biochemistry. One of the most promising detection methods is based on the application of surface plasmon resonance for label-free detection of biologically active compounds. This method allows one to monitor binding events in real time without labeling. The system can therefore be used to determine both affinity and rate constants for interactions between various types of molecules. Here, we describe the application of a surface plasmon resonance biosensor for label-free investigation of the interaction between an immobilized antigen bovine serum albumin (BSA) and antibodymore » rabbit anti-cow albumin IgG1 (anti-BSA). The formation of a self-assembled monolayer (SAM) over a gold surface is introduced into this laboratory training protocol as an effective immobilization method, which is very promising in biosensing systems based on detection of affinity interactions. In the next step, covalent attachment via artificially formed amide bonds is applied for the immobilization of proteins on the formed SAM surface. These experiments provide suitable experience for postgraduate students to help them understand immobilization of biologically active materials via SAMs, fundamentals of surface plasmon resonance biosensor applications, and determination of non-covalent biomolecular interactions. The experiment is designed for master and/or Ph.D. students. In some particular cases, this protocol might be adoptable for bachelor students that already have completed an extended biochemistry program that included a background in immunology.« less

Large area, label-free imaging of extracellular matrix using telecentricity

NASA Astrophysics Data System (ADS)

Visbal Onufrak, Michelle A.; Konger, Raymond L.; Kim, Young L.

2017-02-01

Subtle alterations in stromal tissue structures and organizations within the extracellular matrix (ECM) have been observed in several types of tissue abnormalities, including early skin cancer and wounds. Current microscopic imaging methods often lack the ability to accurately determine the extent of malignancy over a large area, due to their limited field of view. In this research we focus on the development of simple mesoscopic (i.e. between microscopic and macroscopic) biomedical imaging device for non-invasive assessment of ECM alterations over a large, heterogeneous area. In our technology development, a telecentric lens, commonly used in machine vision systems but rarely used in biomedical imaging, serves as a key platform to visualize alterations in tissue microenvironments in a label-free manner over a clinically relevant area. In general, telecentric imaging represents a simple, alternative method for reducing unwanted scattering or diffuse light caused by the highly anisotropic scattering properties of biological tissue. In particular, under telecentric imaging the light intensity backscattered from biological tissue is mainly sensitive to the scattering anisotropy factor, possibly associated with the ECM. We demonstrate the inherent advantages of combining telecentric lens systems with hyperspectral imaging for providing optical information of tissue scattering in biological tissue of murine models, as well as light absorption of hemoglobin in blood vessel tissue phantoms. Thus, we envision that telecentric imaging could potentially serve for simple site-specific, tissue-based assessment of stromal alterations over a clinically relevant field of view in a label-free manner, for studying diseases associated with disruption of homeostasis in ECM.

Exact Tuning of High-Q Optical Microresonators by Use of UV

NASA Technical Reports Server (NTRS)

Savchankov, Anaotliy; Maleki, Lute; Iltchenko, Vladimir; Handley, Timothy

2006-01-01

In one of several alternative approaches to the design and fabrication of a "whispering-gallery" optical microresonator of high resonance quality (high Q), the index of refraction of the resonator material and, hence, the resonance frequencies. In this approach, a microresonator structure is prepared by forming it from an ultraviolet-sensitive material. Then the structure is subjected to controlled exposure to UV light while its resonance frequencies are monitored.

Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study

PubMed Central

Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika

2016-01-01

Background and Aims Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. Methods We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0–4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. Results We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. Conclusions This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading. PMID:26808140

LFQuant: a label-free fast quantitative analysis tool for high-resolution LC-MS/MS proteomics data.

PubMed

Zhang, Wei; Zhang, Jiyang; Xu, Changming; Li, Ning; Liu, Hui; Ma, Jie; Zhu, Yunping; Xie, Hongwei

2012-12-01

Database searching based methods for label-free quantification aim to reconstruct the peptide extracted ion chromatogram based on the identification information, which can limit the search space and thus make the data processing much faster. The random effect of the MS/MS sampling can be remedied by cross-assignment among different runs. Here, we present a new label-free fast quantitative analysis tool, LFQuant, for high-resolution LC-MS/MS proteomics data based on database searching. It is designed to accept raw data in two common formats (mzXML and Thermo RAW), and database search results from mainstream tools (MASCOT, SEQUEST, and X!Tandem), as input data. LFQuant can handle large-scale label-free data with fractionation such as SDS-PAGE and 2D LC. It is easy to use and provides handy user interfaces for data loading, parameter setting, quantitative analysis, and quantitative data visualization. LFQuant was compared with two common quantification software packages, MaxQuant and IDEAL-Q, on the replication data set and the UPS1 standard data set. The results show that LFQuant performs better than them in terms of both precision and accuracy, and consumes significantly less processing time. LFQuant is freely available under the GNU General Public License v3.0 at http://sourceforge.net/projects/lfquant/. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Label-free optical imaging of nonfluorescent molecules by stimulated radiation.

PubMed

Min, Wei

2011-12-01

Imaging contrasts other than fluorescence are highly desirable for label-free detection and interrogation of nonfluorescent molecular species inside live cells, tissues, and organisms. The recently developed stimulated Raman scattering (SRS) and stimulated emission microscopy techniques provide sensitive and specific contrast mechanisms for nonfluorescent species, by employing the light amplification aspect of stimulated radiation. Compared to their spontaneous counterparts, stimulated radiation can enhance the imaging performance significantly, making the previously 'dark' molecules observable. Here we review and summarize the underlying principles of this emerging class of molecular imaging techniques. Copyright © 2011 Elsevier Ltd. All rights reserved.

Label-free super-resolution with coherent nonlinear structured-illumination microscopy

NASA Astrophysics Data System (ADS)

Huttunen, Mikko J.; Abbas, Aazad; Upham, Jeremy; Boyd, Robert W.

2017-08-01

Structured-illumination microscopy enables up to a two-fold lateral resolution improvement by spatially modulating the intensity profile of the illumination beam. We propose a novel way to generalize the concept of structured illumination to nonlinear widefield modalities by spatially modulating, instead of field intensities, the phase of the incident field while interferometrically measuring the complex-valued scattered field. We numerically demonstrate that for second-order and third-order processes an almost four- and six-fold increase in lateral resolution is achievable, respectively. This procedure overcomes the conventional Abbe diffraction limit and provides new possibilities for label-free super-resolution microscopy.

Optical micro resonance based sensor schemes for detection and identification of nano particles and biological agents in situ

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav; Ostendorf, Andreas

2010-05-01

A novel emerging technique for the label-free analysis of nano particles including biomolecules using optical micro cavity resonance is being developed. Various schemes based on a mechanically fixed microspheres as well as microspheres melted by laser on the tip of a standard single mode fiber have been investigated to make further development for microbial application. Water solutions of ethanol, HCl, glucose, vitamin C and biotin have been used to test refractive index changes by monitoring the magnitude of the whispering gallery modes spectral shift. Particular efforts were made for effective fixing of the micro spheres in the water flow, an optimal geometry for micro resonance observation and material of microsphere the most appropriate for microbial application. Optical resonance in free micro spheres from PMMA fixed in micro channels produced by photolithography has been observed under the laser power of less then 1 microwatt. Resonance shifts of C reactive protein water solutions as well as albumin solutions in pure water and with HCl modelling blood have been investigated. Introducing controlled amount of glass gel nano particles into sensor microsphere surrounding were accompanied by both correlative resonance shift (400 nm in diameter) and total reconstruct of resonance spectra (57 nm in diameter). Developed schemes have been demonstrated to be a promising technology platform for sensitive, lab-on-chip type sensor of diagnostic tools for different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells as well as in different experimental contexts e.g. proteomics, genomics, drug discovery, and membrane studies.

Label-free Quantitative Protein Profiling of vastus lateralis Muscle During Human Aging*

PubMed Central

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe

2014-01-01

Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers. PMID:24217021

Label-free quantitative protein profiling of vastus lateralis muscle during human aging.

PubMed

Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe

2014-01-01

Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers.

High-throughput quantification of the levels and labeling abundance of free amino acids by liquid chromatography tandem mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cocuron, Jean-Christophe; Tsogtbaatar, Enkhtuul; Alonso, Ana P.

Accurate assessment of mass isotopomer distributions (MIDs) of intracellular metabolites, such as free amino acids (AAs), is crucial for quantifying in vivo fluxes. To date, the majority of studies that measured AA MIDs have relied on the analysis of proteinogenic rather than free AAs by: i) GC–MS, which involved cumbersome process of derivatization, or ii) NMR, which requires large quantities of biological sample. In this work, the development and validation of a high-throughput LC–MS/MS method allowing the quantification of the levels and labeling of free AAs is described. Sensitivity in the order of the femtomol was achieved using multiple reactionmore » monitoring mode (MRM). The MIDs of all free AAs were assessed without the need of derivatization, and were validated (except for Trp) on a mixture of unlabeled AA standards. Finally, this method was applied to the determination of the 13C-labeling abundance in free AAs extracted from maize embryos cultured with 13C-glutamine or 13C-glucose. Although Cys was below the limit of detection in these biological samples, the MIDs of a total of 18 free AAs were successfully determined. Due to the increased application of tandem mass spectrometry for 13C-Metabolic Flux Analysis, this novel method will enable the assessment of more complete and accurate labeling information of intracellular AAs, and therefore a better definition of the fluxes.« less

High-throughput quantification of the levels and labeling abundance of free amino acids by liquid chromatography tandem mass spectrometry

DOE PAGES

Cocuron, Jean-Christophe; Tsogtbaatar, Enkhtuul; Alonso, Ana P.

2017-02-16

Accurate assessment of mass isotopomer distributions (MIDs) of intracellular metabolites, such as free amino acids (AAs), is crucial for quantifying in vivo fluxes. To date, the majority of studies that measured AA MIDs have relied on the analysis of proteinogenic rather than free AAs by: i) GC–MS, which involved cumbersome process of derivatization, or ii) NMR, which requires large quantities of biological sample. In this work, the development and validation of a high-throughput LC–MS/MS method allowing the quantification of the levels and labeling of free AAs is described. Sensitivity in the order of the femtomol was achieved using multiple reactionmore » monitoring mode (MRM). The MIDs of all free AAs were assessed without the need of derivatization, and were validated (except for Trp) on a mixture of unlabeled AA standards. Finally, this method was applied to the determination of the 13C-labeling abundance in free AAs extracted from maize embryos cultured with 13C-glutamine or 13C-glucose. Although Cys was below the limit of detection in these biological samples, the MIDs of a total of 18 free AAs were successfully determined. Due to the increased application of tandem mass spectrometry for 13C-Metabolic Flux Analysis, this novel method will enable the assessment of more complete and accurate labeling information of intracellular AAs, and therefore a better definition of the fluxes.« less

Differentiating intratumoral melanocytes from Langerhans cells in nonmelanocytic pigmented skin tumors in vivo by label-free third-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Weng, Wei-Hung; Liao, Yi-Hua; Tsai, Ming-Rung; Wei, Ming-Liang; Huang, Hsin-Yi; Sun, Chi-Kuang

2016-07-01

Morphology and distribution of melanocytes are critical imaging information for the diagnosis of melanocytic lesions. However, how to image intratumoral melanocytes noninvasively in pigmented skin tumors is seldom investigated. Third-harmonic generation (THG) is shown to be enhanced by melanin, whereas high accuracy has been demonstrated using THG microscopy for in vivo differential diagnosis of nonmelanocytic pigmented skin tumors. It is thus desirable to investigate if label-free THG microscopy was capable to in vivo identify intratumoral melanocytes. In this study, histopathological correlations of label-free THG images with the immunohistochemical images stained with human melanoma black (HMB)-45 and cluster of differentiation 1a (CD1a) were made. The correlation results indicated that the intratumoral THG-bright dendritic-cell-like signals were endogenously derived from melanocytes rather than Langerhans cells (LCs). The consistency between THG-bright dendritic-cell-like signals and HMB-45 melanocyte staining showed a kappa coefficient of 0.807, 84.6% sensitivity, and 95% specificity. In contrast, a kappa coefficient of -0.37, 21.7% sensitivity, and 30% specificity were noted between the THG-bright dendritic-cell-like signals and CD1a staining for LCs. Our study indicates the capability of noninvasive label-free THG microscopy to differentiate intratumoral melanocytes from LCs, which is not feasible in previous in vivo label-free clinical-imaging modalities.

Shooting Gallery Attendance among IDUs in Tijuana and Ciudad Juarez, Mexico: Correlates, Prevention Opportunities, and the Role of the Environment

PubMed Central

Philbin, Morgan; Pollini, Robin A.; Ramos, Rebecca; Lozada, Remedios; Brouwer, Kimberly C.; Ramos, Maria Elena; Firestone-Cruz, Michelle; Case, Patricia; Strathdee, Steffanie A.

2009-01-01

We identified factors associated with shooting gallery attendance among injection drug users (IDUs) in two Mexico–US border cities. IDUs in Tijuana (n = 222) and Ciudad Juarez (n = 205), Mexico, who were ≥18 years and injected illicit drugs in the last month were recruited using respondent-driven sampling (RDS). An interviewer-administered survey collected sociodemographic and behavioral data. Logistic regression was used to examine correlates of shooting gallery attendance in each of the two cities. Homelessness and being arrested for syringe possession—both structural level factors—were associated with shooting gallery use in both cities. In Ciudad Juarez, younger age and having overdosed were also associated with shooting gallery use. Our study highlights the need for structural interventions that mitigate homelessness among IDUs and facilitate changes in law enforcement practices associated with shooting gallery use. Harm reduction interventions based within shooting galleries should also be considered to prevent transmission of blood-borne pathogens among IDUs. PMID:18369723

Label-Free QCM Immunosensor for the Detection of Ochratoxin A

PubMed Central

Ertekin, Özlem; Laguna, Duygu Ercan; Özen, Fehime Şeyma; Öztürk, Zafer Ziya; Öztürk, Selma

2018-01-01

Ochratoxin A (OTA) is a potent mycotoxin that poses a risk in food and feed moieties and subject to worldwide regulation. Laboratory-based analytical methods are traditionally employed for reliable OTA quantification, but these methods cannot provide rapid and on-site analysis, where biosensors fill this gap. In this study a label-free quartz crystal microbalance (QCM)-based immunosensor for the detection of OTA, which is one of the most important small molecule contaminants, was developed by direct immobilization of OTA to amine-bearing sensor surfaces using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-Hydroxysuccinimide (NHS) chemistry. The protein-free sensor surface enabled regeneration of sensor surface with 50 mM NaOH and 1% SDS up to 13 times without loss of performance, which would disrupt a protein-containing sensor surface. We developed a QCM immunosensor using the developed sensor surface with a 17.2–200 ng/mL detection range which can be used for on-site detection of feedstuffs. PMID:29641432

Label-Free QCM Immunosensor for the Detection of Ochratoxin A.

PubMed

Pirinçci, Şerife Şeyda; Ertekin, Özlem; Laguna, Duygu Ercan; Özen, Fehime Şeyma; Öztürk, Zafer Ziya; Öztürk, Selma

2018-04-11

Ochratoxin A (OTA) is a potent mycotoxin that poses a risk in food and feed moieties and subject to worldwide regulation. Laboratory-based analytical methods are traditionally employed for reliable OTA quantification, but these methods cannot provide rapid and on-site analysis, where biosensors fill this gap. In this study a label-free quartz crystal microbalance (QCM)-based immunosensor for the detection of OTA, which is one of the most important small molecule contaminants, was developed by direct immobilization of OTA to amine-bearing sensor surfaces using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-Hydroxysuccinimide (NHS) chemistry. The protein-free sensor surface enabled regeneration of sensor surface with 50 mM NaOH and 1% SDS up to 13 times without loss of performance, which would disrupt a protein-containing sensor surface. We developed a QCM immunosensor using the developed sensor surface with a 17.2-200 ng/mL detection range which can be used for on-site detection of feedstuffs.

10. VIEW WITHIN THE EAST OPERATING GALLERY OF WORK STATION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. VIEW WITHIN THE EAST OPERATING GALLERY OF WORK STATION WITH MANIPULATOR ARMS. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Intra-operative label-free multimodal multiphoton imaging of breast cancer margins and microenvironment (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, Yi; You, Sixian; Tu, Haohua; Spillman, Darold R.; Marjanovic, Marina; Chaney, Eric J.; Liu, George Z.; Ray, Partha S.; Higham, Anna; Boppart, Stephen A.

2017-02-01

Label-free multi-photon imaging has been a powerful tool for studying tissue microstructures and biochemical distributions, particularly for investigating tumors and their microenvironments. However, it remains challenging for traditional bench-top multi-photon microscope systems to conduct ex vivo tumor tissue imaging in the operating room due to their bulky setups and laser sources. In this study, we designed, built, and clinically demonstrated a portable multi-modal nonlinear label-free microscope system that combined four modalities, including two- and three- photon fluorescence for studying the distributions of FAD and NADH, and second and third harmonic generation, respectively, for collagen fiber structures and the distribution of micro-vesicles found in tumors and the microenvironment. Optical realignments and switching between modalities were motorized for more rapid and efficient imaging and for a light-tight enclosure, reducing ambient light noise to only 5% within the brightly lit operating room. Using up to 20 mW of laser power after a 20x objective, this system can acquire multi-modal sets of images over 600 μm × 600 μm at an acquisition rate of 60 seconds using galvo-mirror scanning. This portable microscope system was demonstrated in the operating room for imaging fresh, resected, unstained breast tissue specimens, and for assessing tumor margins and the tumor microenvironment. This real-time label-free nonlinear imaging system has the potential to uniquely characterize breast cancer margins and the microenvironment of tumors to intraoperatively identify structural, functional, and molecular changes that could indicate the aggressiveness of the tumor.

Label-free cell-cycle analysis by high-throughput quantitative phase time-stretch imaging flow cytometry

NASA Astrophysics Data System (ADS)

Mok, Aaron T. Y.; Lee, Kelvin C. M.; Wong, Kenneth K. Y.; Tsia, Kevin K.

2018-02-01

Biophysical properties of cells could complement and correlate biochemical markers to characterize a multitude of cellular states. Changes in cell size, dry mass and subcellular morphology, for instance, are relevant to cell-cycle progression which is prevalently evaluated by DNA-targeted fluorescence measurements. Quantitative-phase microscopy (QPM) is among the effective biophysical phenotyping tools that can quantify cell sizes and sub-cellular dry mass density distribution of single cells at high spatial resolution. However, limited camera frame rate and thus imaging throughput makes QPM incompatible with high-throughput flow cytometry - a gold standard in multiparametric cell-based assay. Here we present a high-throughput approach for label-free analysis of cell cycle based on quantitative-phase time-stretch imaging flow cytometry at a throughput of > 10,000 cells/s. Our time-stretch QPM system enables sub-cellular resolution even at high speed, allowing us to extract a multitude (at least 24) of single-cell biophysical phenotypes (from both amplitude and phase images). Those phenotypes can be combined to track cell-cycle progression based on a t-distributed stochastic neighbor embedding (t-SNE) algorithm. Using multivariate analysis of variance (MANOVA) discriminant analysis, cell-cycle phases can also be predicted label-free with high accuracy at >90% in G1 and G2 phase, and >80% in S phase. We anticipate that high throughput label-free cell cycle characterization could open new approaches for large-scale single-cell analysis, bringing new mechanistic insights into complex biological processes including diseases pathogenesis.

Label-Free Detection of Insulin and Glucagon within Human Islets of Langerhans Using Raman Spectroscopy

PubMed Central

Hilderink, Janneke; Otto, Cees; Slump, Cees; Lenferink, Aufried; Engelse, Marten; van Blitterswijk, Clemens; de Koning, Eelco; Karperien, Marcel; van Apeldoorn, Aart

2013-01-01

Intrahepatic transplantation of donor islets of Langerhans is a promising therapy for patients with type 1 diabetes. It is of critical importance to accurately monitor islet quality before transplantation, which is currently done by standard histological methods that are performed off-line and require extensive sample preparation. As an alternative, we propose Raman spectroscopy which is a non-destructive and label-free technique that allows continuous real-time monitoring of the tissue to study biological changes as they occur. By performing Raman spectroscopic measurements on purified insulin and glucagon, we showed that the 520 cm-1 band assigned to disulfide bridges in insulin, and the 1552 cm-1 band assigned to tryptophan in glucagon are mutually exclusive and could therefore be used as indirect markers for the label-free distinction between both hormones. High-resolution hyperspectral Raman imaging for these bands showed the distribution of disulfide bridges and tryptophan at sub-micrometer scale, which correlated with the location of insulin and glucagon as revealed by conventional immunohistochemistry. As a measure for this correlation, quantitative analysis was performed comparing the Raman images with the fluorescence images, resulting in Dice coefficients (ranging between 0 and 1) of 0.36 for insulin and 0.19 for glucagon. Although the use of separate microscope systems with different spatial resolution and the use of indirect Raman markers cause some image mismatch, our findings indicate that Raman bands for disulfide bridges and tryptophan can be used as distinctive markers for the label-free detection of insulin and glucagon in human islets of Langerhans. PMID:24167603

5. JL photographer, summer 1978. View in filteration gallery looking ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. JL photographer, summer 1978. View in filteration gallery looking to filter pits. - Division Avenue Pumping Station & Filtration Plant, West 45th Street and Division Avenue, Cleveland, Cuyahoga County, OH

Cavity optomechanics in a levitated helium drop

NASA Astrophysics Data System (ADS)

Childress, L.; Schmidt, M. P.; Kashkanova, A. D.; Brown, C. D.; Harris, G. I.; Aiello, A.; Marquardt, F.; Harris, J. G. E.

2017-12-01

We describe a proposal for a type of optomechanical system based on a drop of liquid helium that is magnetically levitated in vacuum. In the proposed device, the drop would serve three roles: its optical whispering-gallery modes would provide the optical cavity, its surface vibrations would constitute the mechanical element, and evaporation of He atoms from its surface would provide continuous refrigeration. We analyze the feasibility of such a system in light of previous experimental demonstrations of its essential components: magnetic levitation of mm-scale and cm-scale drops of liquid He , evaporative cooling of He droplets in vacuum, and coupling to high-quality optical whispering-gallery modes in a wide range of liquids. We find that the combination of these features could result in a device that approaches the single-photon strong-coupling regime, due to the high optical quality factors attainable at low temperatures. Moreover, the system offers a unique opportunity to use optical techniques to study the motion of a superfluid that is freely levitating in vacuum (in the case of 4He). Alternatively, for a normal fluid drop of 3He, we propose to exploit the coupling between the drop's rotations and vibrations to perform quantum nondemolition measurements of angular momentum.

Resonant coupling into hybrid 3D micro-resonator devices on organic/biomolecular film/glass photonic structures

NASA Astrophysics Data System (ADS)

Bêche, Bruno; Potel, Arnaud; Barbe, Jérémy; Vié, Véronique; Zyss, Joseph; Godet, Christian; Huby, Nolwenn; Pluchon, David; Gaviot, Etienne

2010-01-01

We have designed and realized an integrated photonic family of micro-resonators (MR) on multilayer SU8/lipidic film/glass materials. Such a family involves hybrid 3D-MR structures composed of spherical glass-MR arranged upon organic pair-SU8-waveguides, an efficient coupling being ensured with a Langmuir-Blodgett Dipalmitoylphosphatidylcholine (DPPC-lipid from Avanti Polar ®) film whose thickness is ranging from 12 to 48 nm. We have characterized such add/drop filters, respectively, in intensity and spectral measurements, and experimentally achieved an evanescent resonant-photonic-coupling between the 3D-MR and the 4-ports structure through the DPPC-gap. Spectral resonances have been measured for 4-whispering gallery-modes (WGM) into such 3D-structures, respectively, characterized with a 0.97 nm free spectral range (FSR) and a high quality Q-factor up to 4.10 4.

Museums and art galleries as partners for public health interventions.

PubMed

Camic, Paul M; Chatterjee, Helen J

2013-01-01

The majority of public health programmes are based in schools, places of employment and in community settings. Likewise, nearly all health-care interventions occur in clinics and hospitals. An underdeveloped area for public health-related planning that carries international implications is the cultural heritage sector, and specifically museums and art galleries. This paper presents a rationale for the use of museums and art galleries as sites for public health interventions and health promotion programmes through discussing the social role of these organisations in the health and well-being of the communities they serve. Recent research from several countries is reviewed and integrated into a proposed framework for future collaboration between cultural heritage, health-care and university sectors to further advance research, policy development and evidence-based practice.

Label-free as-grown double wall carbon nanotubes bundles for Salmonella typhimurium immunoassay.

PubMed

Punbusayakul, Niramol; Talapatra, Saikat; Ajayan, Pulickel M; Surareungchai, Werasak

2013-01-01

A label-free immunosensor from as-grown double wall carbon nanotubes (DW) bundles was developed for detecting Salmonella typhimurium. The immunosensor was fabricated by using the as-grown DW bundles as an electrode material with an anti-Salmonella impregnated on the surface. The immunosensor was electrochemically characterized by cyclic voltammetry. The working potential (100, 200, 300 and 400 mV vs. Ag/AgCl) and the anti-Salmonella concentration (10, 25, 50, 75, and 100 μg/mL) at the electrode were subsequently optimized. Then, chronoamperometry was used with the optimum potential of 100 mV vs. Ag/AgCl) and the optimum impregnated anti-Salmonella of 10 μg/mL to detect S. typhimurium cells (0-10(9) CFU/mL). The DW immunosensor exhibited a detection range of 10(2) to 10(7) CFU/mL for the bacteria with a limit of detection of 8.9 CFU/mL according to the IUPAC recommendation. The electrode also showed specificity to S. typhimurium but no current response to Escherichia coli. These findings suggest that the use of a label-free DW immunosensor is promising for detecting S. typhimurium.

Uncovering stem-cell heterogeneity in the microniche with label-free microfluidics

NASA Astrophysics Data System (ADS)

Sohn, Lydia L.

2013-03-01

Better suited for large number of cells from bulk tissue, traditional cell-screening techniques, such as fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS), cannot easily screen stem or progenitor cells from minute populations found in their physiological niches. Furthermore, they rely upon irreversible antibody binding, potentially altering cell properties, including gene expression and regenerative capacity. We have developed a label-free, single-cell analysis microfluidic platform capable of quantifying cell-surface marker expression of functional organ stem cells directly isolated from their micro-anatomical niche. With this platform, we have screened single quiescent muscle stem (satellite) cells derived from single myofibers, and we have uncovered an important heterogeneity in the surface-marker expression of these cells. By sorting the screened cells with our microfluidic device, we have determined what this heterogeneity means in terms of muscle stem-cell functionality. For instance, we show that the levels of beta1-integrin can predict the differentiation capacity of quiescent satellite cells, and in contrast to recent literature, that some CXCR4 + cells are not myogenic. Our results provide the first direct demonstration of a microniche-specific variation in gene expression in stem cells of the same lineage. Overall, our label-free, single-cell analysis and cell-sorting platform could be extended to other systems involving rare-cell subsets. This work was funded by the W. M. Keck Foundation, NIH, and California Institute of Regenerative Medicine

A compact and portable optofluidic device for detection of liquid properties and label-free sensing

NASA Astrophysics Data System (ADS)

Lahoz, F.; Martín, I. R.; Walo, D.; Gil-Rostra, J.; Yubero, F.; Gonzalez-Elipe, A. R.

2017-06-01

Optofluidic lasers have been widely investigated over the last few years mainly because they can be easily integrated in sensor devices. However, high power pulse lasers are required as excitation sources, which, in practice, limit the portability of the system. Trying to overcome some of these limitations, in this paper we propose the combined use of a small CW laser with a Fabry-Perot optofluidic planar microcavity showing high sensitivity and versatility for detection of liquid properties and label-free sensing. Firstly, a fluorescein solution in ethanol is used to demonstrate the high performances of the FP microcavity as a temperature sensor both in the laser (high pump power above laser threshold) and in the fluorescence (low pump power) regimes. A shift in the wavelength of the resonant cavity modes is used to detect changes in the temperature and our results show that high sensitivities could be already obtained using cheap and portable CW diode lasers. In the second part of the paper, the demonstration of this portable device for label-free sensing is illustrated under low CW pumping. The wavelength positions of the optofluidic resonant modes are used to detect glucose concentrations in water solutions using a protein labelled with a fluorescent dye as the active medium.

Asymmetric split-ring resonator-based biosensor for detection of label-free stress biomarkers

NASA Astrophysics Data System (ADS)

Lee, Hee-Jo; Lee, Jung-Hyun; Choi, Suji; Jang, Ik-Soon; Choi, Jong-Soon; Jung, Hyo-Il

2013-07-01

In this paper, an asymmetric split-ring resonator, metamaterial element, is presented as a biosensing transducer for detection of highly sensitive and label-free stress biomarkers. In particular, the two biomarkers, cortisol and α-amylase, are used for evaluating the sensitivity of the proposed biosensor. In case of cortisol detection, the competitive reaction between cortisol-bovine serum albumin and free cortisol is employed, while alpha-amylase is directly detected by its antigen-antibody reaction. From the experimental results, we find that the limit of detection and sensitivity of the proposed sensing device are about 1 ng/ml and 1.155 MHz/ng ml-1, respectively.

High-contrast grating resonators for label-free detection of disease biomarkers

PubMed Central

Sun, Tianbo; Kan, Shu; Marriott, Gerard; Chang-Hasnain, Connie

2016-01-01

A label-free optical biosensor is described that employs a silicon-based high-contrast grating (HCG) resonator with a spectral linewidth of ~500 pm that is sensitive to ligand-induced changes in surface properties. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100 pg/ml within 4 mins, which is faster, and as sensitive as current enzyme-linked immuno-assays for cTnI. PMID:27265624

High-contrast grating resonators for label-free detection of disease biomarkers

NASA Astrophysics Data System (ADS)

Sun, Tianbo; Kan, Shu; Marriott, Gerard; Chang-Hasnain, Connie

2016-06-01

A label-free optical biosensor is described that employs a silicon-based high-contrast grating (HCG) resonator with a spectral linewidth of ~500 pm that is sensitive to ligand-induced changes in surface properties. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100 pg/ml within 4 mins, which is faster, and as sensitive as current enzyme-linked immuno-assays for cTnI.

Engaging Families in the Galleries Using Design Thinking

ERIC Educational Resources Information Center

Larson, Lucy

2017-01-01

The Palo Alto Art Center sought a solution to the challenge that loyal family audiences, visiting weekly for art studio classes, rarely visit the contemporary art exhibition galleries. This article relates the experience of using the human-centered design process, often called Design Thinking, as the methodology to create a solution for family…

14. VIEW IN THE WEST OPERATING GALLERY OF POSTMORTEM CELL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. VIEW IN THE WEST OPERATING GALLERY OF POST-MORTEM CELL WORK STATION AND MANIPULATOR ARMS. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Label-free proteome of water buffalo (Bubalus bubalis) seminal plasma.

PubMed

Brito, Mayara F; Auler, Patrícia A; Tavares, Guilherme C; Rezende, Cristiana P; Almeida, Gabriel M F; Pereira, Felipe L; Leal, Carlos A G; Moura, Arlindo de Alencar; Figueiredo, Henrique C P; Henry, Marc

2018-06-11

The study aimed to describe the Bubalus bubalis seminal plasma proteome using a label-free shotgun UDMS E approach. A total of 859 nonredundant proteins were identified across five biological replicates with stringent identification. Proteins specifically related to sperm maturation and protection, capacitation, fertilization and metabolic activity were detected in the buffalo seminal fluid. In conclusion, we provide a comprehensive proteomic profile of buffalo seminal plasma, which establishes a foundation for further studies designed to understand regulation of sperm function and discovery of novel biomarkers for fertility. MS data are available in the ProteomeXchange with identifier PXD003728. © 2018 Blackwell Verlag GmbH.

Label-free Raman observation of cytochrome c dynamics during apoptosis

PubMed Central

Okada, Masaya; Smith, Nicholas Isaac; Palonpon, Almar Flotildes; Endo, Hiromi; Kawata, Satoshi; Sodeoka, Mikiko; Fujita, Katsumasa

2012-01-01

We performed label-free observation of molecular dynamics in apoptotic cells by Raman microscopy. Dynamic changes in cytochrome c distribution at the Raman band of 750 cm-1 were observed after adding an apoptosis inducer to the cells. The comparison of mitochondria fluorescence images and Raman images of cytochrome c confirmed that changes in cytochrome c distribution can be distinguished as release of cytochrome c from mitochondria. Our observation also revealed that the redox state of cytochrome c was maintained during the release from the mitochondria. Monitoring mitochondrial membrane potential with JC-1 dye confirmed that the observed cytochrome c release was associated with apoptosis. PMID:22184220

Low-cost Engineering of Laser Rods and Slabs with Liquid Phase Epitaxy

DTIC Science & Technology

2011-09-01

SUPPLEMENTARY NOTES 14. ABSTRACT We investigated the use of a liquid phase epitaxial ( LPE ) coating to improve the performance of a rod or slab laser. A...single crystal erbium-doped yttrium aluminum garnet (Er:YAG) rod coated with undoped YAG, and an uncoated sample were procured, then compared on the...the whispering gallery modes, which otherwise would deplete the gain in ~50% of the rod volume. We also investigated LPE growth on a ceramic sample

Label-free amino acid detection based on nanocomposites of graphene oxide hybridized with gold nanoparticles.

PubMed

Zhang, Qian; Zhang, Diming; Lu, Yanli; Xu, Gang; Yao, Yao; Li, Shuang; Liu, Qingjun

2016-03-15

Nanocomposites of graphene oxide and gold nanoparticles (GO/GNPs) were synthesized for label-free detections of amino acids. Interactions between the composites and amino acids were investigated by both naked-eye observation and optical absorption spectroscopy. The GO/GNPs composites displayed apparent color changes and absorption spectra changes in presences of amino acids including glutamate, aspartate, and cysteine. The interaction mechanisms of the composites and amino acids were discussed and explored with sulfhydryl groups and non-α-carboxylic groups on the amino acids. Sensing properties of the composites were tested, while pure gold particles were used as the control. The results suggested that the GO/GNPs composites had better linearity and stability in dose-dependent responses to the amino acids than those of the particles, especially in detections for acidic amino acids. Therefore, the nanocomposites platform can provide a convenient and efficient approach for label-free optical detections of important molecules such as amino acids. Copyright © 2015 Elsevier B.V. All rights reserved.

What Can The Habitable Zone Gallery Do for You?

NASA Astrophysics Data System (ADS)

Gelino, Dawn M.; Kane, Stephen R.

2014-06-01

The Habitable Zone Gallery (www.hzgallery.org) has been online since August 2011 as a service to the exoplanet community to provide Habitable Zone (HZ) information for each of the exoplanetary systems with known planetary orbital parameters. The service includes a sortable table, a plot with the period and eccentricity of each of the planets with respect to their time spent in the HZ, a gallery of known systems which plots the orbits and the location of the HZ with respect to those orbits, and orbital movies. Recently, we have added new features including: implementation of both conservative and optimistic HZs, more user-friendly table and movies, movies for circumbinary planets, and a count of planets whose orbits lie entirely within the system’s HZ. Here we discuss various educational and scientific applications of the site such as target selection, exploring planets with eccentric or circumbinary orbits, and investigating habitability.

What Can the Habitable Zone Gallery Do For You?

NASA Astrophysics Data System (ADS)

Gelino, Dawn M.; Kane, Stephen

2015-12-01

The Habitable Zone Gallery (www.hzgallery.org) came online in August 2011 as a service to the exoplanet community that provides Habitable Zone (HZ) information for each of the exoplanetary systems with known planetary orbital parameters. The service includes a sortable table, a plot with the period and eccentricity of each of the planets with respect to their time spent in the HZ, a gallery of known systems which plot the orbits and the location of the HZ with respect to those orbits, and orbital movies. Recently, we have added new features including: implementation of both conservative and optimistic HZs, more user-friendly table and movies, movies for circumbinary planets, and a count of planets whose orbits lie entirely within the system's HZ. Here we discuss various educational and scientific applications of the site such as target selection, exploring planets with eccentric or circumbinary orbits, and investigating habitability.

What Can The Habitable Zone Gallery Do For You?

NASA Astrophysics Data System (ADS)

Gelino, D.

2014-04-01

The Habitable Zone Gallery (www.hzgallery.org) came online in August 2011 as a service to the exoplanet community that provides Habitable Zone (HZ) information for each of the exoplanetary systems with known planetary orbital parameters. The service includes a sortable table, a plot with the period and eccentricity of each of the planets with respect to their time spent in the HZ, a gallery of known systems which plot the orbits and the location of the HZ with respect to those orbits, and orbital movies. Recently, we have added new features including: implementation of both conservative and optimistic HZs, more user-friendly table and movies, movies for circumbinary planets, and a count of planets whose orbits lie entirely within the system's HZ. Here we discuss various educational and scientific applications of the site such as target selection, exploring planets with eccentric or circumbinary orbits, and investigating habitability.

HoloMonitor M4: holographic imaging cytometer for real-time kinetic label-free live-cell analysis of adherent cells

NASA Astrophysics Data System (ADS)

Sebesta, Mikael; Egelberg, Peter J.; Langberg, Anders; Lindskov, Jens-Henrik; Alm, Kersti; Janicke, Birgit

2016-03-01

Live-cell imaging enables studying dynamic cellular processes that cannot be visualized in fixed-cell assays. An increasing number of scientists in academia and the pharmaceutical industry are choosing live-cell analysis over or in addition to traditional fixed-cell assays. We have developed a time-lapse label-free imaging cytometer HoloMonitorM4. HoloMonitor M4 assists researchers to overcome inherent disadvantages of fluorescent analysis, specifically effects of chemical labels or genetic modifications which can alter cellular behavior. Additionally, label-free analysis is simple and eliminates the costs associated with staining procedures. The underlying technology principle is based on digital off-axis holography. While multiple alternatives exist for this type of analysis, we prioritized our developments to achieve the following: a) All-inclusive system - hardware and sophisticated cytometric analysis software; b) Ease of use enabling utilization of instrumentation by expert- and entrylevel researchers alike; c) Validated quantitative assay end-points tracked over time such as optical path length shift, optical volume and multiple derived imaging parameters; d) Reliable digital autofocus; e) Robust long-term operation in the incubator environment; f) High throughput and walk-away capability; and finally g) Data management suitable for single- and multi-user networks. We provide examples of HoloMonitor applications of label-free cell viability measurements and monitoring of cell cycle phase distribution.

Flexible Label-Free Quantitative Assay for Antibodies to Influenza Virus Hemagglutinins ▿

PubMed Central

Carney, Paul J.; Lipatov, Aleksandr S.; Monto, Arnold S.; Donis, Ruben O.; Stevens, James

2010-01-01

During the initial pandemic influenza H1N1 virus outbreak, assays such as hemagglutination inhibition and microneutralization provided important information on the relative protection afforded by the population's cross-reactivity from prior infections and immunizations with seasonal vaccines. However, these assays continue to be limited in that they are difficult to automate for high throughput, such as in pandemic situations, as well as to standardize between labs. Thus, new technologies are being sought to improve standardization, reliability, and throughput by using chemically defined reagents rather than whole cells and virions. We now report the use of a cell-free and label-free flu antibody biosensor assay (f-AbBA) for influenza research and diagnostics that utilizes recombinant hemagglutinin (HA) in conjunction with label-free biolayer interferometry technology to measure biomolecular interactions between the HA and specific anti-HA antibodies or sialylated ligands. We evaluated f-AbBA to determine anti-HA antibody binding activity in serum or plasma to assess vaccine-induced humoral responses. This assay can reveal the impact of antigenic difference on antibody binding to HA and also measure binding to different subtypes of HA. We also show that the biosensor assay can measure the ability of HA to bind a model sialylated receptor-like ligand. f-AbBA could be used in global surveillance laboratories since preliminary tests on desiccated HA probes showed no loss of activity after >2 months in storage at room temperature, indicating that the same reagent lots could be used in different laboratories to minimize interlaboratory assay fluctuation. Future development of such reagents and similar technologies may offer a robust platform for future influenza surveillance activities. PMID:20660137

Hybrid integrated label-free chemical and biological sensors.

PubMed

Mehrabani, Simin; Maker, Ashley J; Armani, Andrea M

2014-03-26

Label-free sensors based on electrical, mechanical and optical transduction methods have potential applications in numerous areas of society, ranging from healthcare to environmental monitoring. Initial research in the field focused on the development and optimization of various sensor platforms fabricated from a single material system, such as fiber-based optical sensors and silicon nanowire-based electrical sensors. However, more recent research efforts have explored designing sensors fabricated from multiple materials. For example, synthetic materials and/or biomaterials can also be added to the sensor to improve its response toward analytes of interest. By leveraging the properties of the different material systems, these hybrid sensing devices can have significantly improved performance over their single-material counterparts (better sensitivity, specificity, signal to noise, and/or detection limits). This review will briefly discuss some of the methods for creating these multi-material sensor platforms and the advances enabled by this design approach.

16. VIEW OF FIRST FLOOR EAST OPERATING GALLERY. NOTE THE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. VIEW OF FIRST FLOOR EAST OPERATING GALLERY. NOTE THE SERIES OF MANIPULATOR ARMS ALONG THE LEFT WALL. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Label-free NIR reflectance imaging as a complimentary tool for two-photon fluorescence microscopy: multimodal investigation of stroke (Conference Presentation)

NASA Astrophysics Data System (ADS)

Allegra Mascaro, Anna Letizia; Costantini, Irene; Margoni, Emilia; Iannello, Giulio; Bria, Alessandro; Sacconi, Leonardo; Pavone, Francesco S.

2016-03-01

Two-photon imaging combined with targeted fluorescent indicators is extensively used for visualizing critical features of brain functionality and structural plasticity. Back-scattered photons from the NIR laser provide complimentary information without introducing any exogenous labelling. Here, we describe a versatile approach that, by collecting the reflected NIR light, provides structural details on the myelinated axons and blood vessels in the brain, both in fixed samples and in live animals. Indeed, by combining NIR reflectance and two-photon imaging of a slice of hippocampus from Thy1-GFPm mice, we show the presence of randomly oriented axons intermingled with sparsely fluorescent neuronal processes. The back-scattered photons guide the contextualization of the fluorescence structure within brain atlas thanks to the recognition of characteristic hippocampal structures. Label-free detection of axonal elongations over the layer 2/3 of mouse cortex under a cranial window was also possible in live brain. Finally, blood flow could be measured in vivo, thus validating label free NIR reflectance as a tool for monitoring hemodynamic fluctuations. The prospective versatility of this label-free technique complimentary to two-photon fluorescence microscopy is demonstrated in a mouse model of photothrombotic stroke in which the axonal degeneration and blood flow remodeling can be investigated simultaneously.

Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis.

PubMed

Dai, Peng; Wang, Qin; Wang, Weihua; Jing, Ruirui; Wang, Wei; Wang, Fengqin; Azadzoi, Kazem M; Yang, Jing-Hua; Yan, Zhen

2016-01-21

Gastric cancer (GC) has significant morbidity and mortality worldwide and especially in China. Its molecular pathogenesis has not been thoroughly elaborated. The acknowledged biomarkers for diagnosis, prognosis, recurrence monitoring and treatment are lacking. Proteins from matched pairs of human GC and adjacent tissues were analyzed by a coupled label-free Mass Spectrometry (MS) approach, followed by functional annotation with software analysis. Nano-LC-MS/MS, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry were used to validate dysregulated proteins. One hundred forty-six dysregulated proteins with more than twofold expressions were quantified, 22 of which were first reported to be relevant with GC. Most of them were involved in cancers and gastrointestinal disease. The expression of a panel of four upregulated nucleic acid binding proteins, heterogeneous nuclear ribonucleoprotein hnRNPA2B1, hnRNPD, hnRNPL and Y-box binding protein 1 (YBX-1) were validated by Nano-LC-MS/MS, qRT-PCR, western blot and immunohistochemistry assays in ten GC patients' tissues. They were located in the keynotes of a predicted interaction network and might play important roles in abnormal cell growth. The label-free quantitative proteomic approach provides a deeper understanding and novel insight into GC-related molecular changes and possible mechanisms. It also provides some potential biomarkers for clinical diagnosis.

Combining Raman spectroscopy and digital holographic microscopy for label-free classification of human immune cells (Conference Presentation)

NASA Astrophysics Data System (ADS)

McReynolds, Naomi; Cooke, Fiona G. M.; Chen, Mingzhou; Powis, Simon J.; Dholakia, Kishan

2017-02-01

Moving towards label-free techniques for cell identification is essential for many clinical and research applications. Raman spectroscopy and digital holographic microscopy (DHM) are both label-free, non-destructive optical techniques capable of providing complimentary information. We demonstrate a multi-modal system which may simultaneously take Raman spectra and DHM images to provide both a molecular and a morphological description of our sample. In this study we use Raman spectroscopy and DHM to discriminate between three immune cell populations CD4+ T cells, B cells, and monocytes, which together comprise key functional immune cell subsets in immune responses to invading pathogens. Various parameters that may be used to describe the phase images are also examined such as pixel value histograms or texture analysis. Using our system it is possible to consider each technique individually or in combination. Principal component analysis is used on the data set to discriminate between cell types and leave-one-out cross-validation is used to estimate the efficiency of our method. Raman spectroscopy provides specific chemical information but requires relatively long acquisition times, combining this with a faster modality such as DHM could help achieve faster throughput rates. The combination of these two complimentary optical techniques provides a wealth of information for cell characterisation which is a step towards achieving label free technology for the identification of human immune cells.

Label-free image-based detection of drug resistance with optofluidic time-stretch microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kobayashi, Hirofumi; Lei, Cheng; Mao, Ailin; Jiang, Yiyue; Guo, Baoshan; Ozeki, Yasuyuki; Goda, Keisuke

2017-02-01

Acquired drug resistance is a fundamental predicament in cancer therapy. Early detection of drug-resistant cancer cells during or after treatment is expected to benefit patients from unnecessary drug administration and thus play a significant role in the development of a therapeutic strategy. However, the development of an effective method of detecting drug-resistant cancer cells is still in its infancy due to their complex mechanism in drug resistance. To address this problem, we propose and experimentally demonstrate label-free image-based drug resistance detection with optofluidic time-stretch microscopy using leukemia cells (K562 and K562/ADM). By adding adriamycin (ADM) to both K562 and K562/ADM (ADM-resistant K562 cells) cells, both types of cells express unique morphological changes, which are subsequently captured by an optofluidic time-stretch microscope. These unique morphological changes are extracted as image features and are subjected to supervised machine learning for cell classification. We hereby have successfully differentiated K562 and K562/ADM solely with label-free images, which suggests that our technique is capable of detecting drug-resistant cancer cells. Our optofluidic time-stretch microscope consists of a time-stretch microscope with a high spatial resolution of 780 nm at a 1D frame rate of 75 MHz and a microfluidic device that focuses and orders cells. We compare various machine learning algorithms as well as various concentrations of ADM for cell classification. Owing to its unprecedented versatility of using label-free image and its independency from specific molecules, our technique holds great promise for detecting drug resistance of cancer cells for which its underlying mechanism is still unknown or chemical probes are still unavailable.

Label-free in vivo flow cytometry in zebrafish using two-photon autofluorescence imaging.

PubMed

Zeng, Yan; Xu, Jin; Li, Dong; Li, Li; Wen, Zilong; Qu, Jianan Y

2012-07-01

We demonstrate a label-free in vivo flow cytometry in zebrafish blood vessels based on two-photon excited autofluorescence imaging. The major discovery in this work is the strong autofluorescence emission from the plasma in zebrafish blood. The plasma autofluorescence provides excellent contrast for visualizing blood vessels and counting blood cells. In addition, the cellular nicotinamide adenine dinucleotide autofluorescence enables in vivo imaging and counting of white blood cells (neutrophils).

Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart tissue reveals immediate mitochondrial impairment after ionising radiation.

PubMed

Azimzadeh, Omid; Scherthan, Harry; Yentrapalli, Ramesh; Barjaktarovic, Zarko; Ueffing, Marius; Conrad, Marcus; Neff, Frauke; Calzada-Wack, Julia; Aubele, Michaela; Buske, Christian; Atkinson, Michael J; Hauck, Stefanie M; Tapio, Soile

2012-04-18

Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics. However, quantitative proteome analysis of FFPE tissue is hampered by the lack of an efficient labelling method. The usage of conventional protein labelling on FFPE tissue has turned out to be inefficient. Classical labelling targets lysine residues that are blocked by the formalin treatment. The aim of this study was to establish a quantitative proteomics analysis of FFPE tissue by combining the label-free approach with optimised protein extraction and separation conditions. As a model system we used FFPE heart tissue of control and exposed C57BL/6 mice after total body irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated proteins (p≤0.05) in irradiated hearts 24h after the exposure. The proteomics data were further evaluated and validated by bioinformatics and immunoblotting investigation. In good agreement with our previous results using fresh-frozen tissue, the analysis indicated radiation-induced alterations in three main biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism. The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives. Copyright © 2012 Elsevier B.V. All rights reserved.

Label-Free, LC-MS-Based Assays to Quantitate Small-Molecule Antagonist Binding to the Mammalian BLT1 Receptor.

PubMed

Chen, Xun; Stout, Steven; Mueller, Uwe; Boykow, George; Visconti, Richard; Siliphaivanh, Phieng; Spencer, Kerrie; Presland, Jeremy; Kavana, Michael; Basso, Andrea D; McLaren, David G; Myers, Robert W

2017-08-01

We have developed and validated label-free, liquid chromatography-mass spectrometry (LC-MS)-based equilibrium direct and competition binding assays to quantitate small-molecule antagonist binding to recombinant human and mouse BLT1 receptors expressed in HEK 293 cell membranes. Procedurally, these binding assays involve (1) equilibration of the BLT1 receptor and probe ligand, with or without a competitor; (2) vacuum filtration through cationic glass fiber filters to separate receptor-bound from free probe ligand; and (3) LC-MS analysis in selected reaction monitoring mode for bound probe ligand quantitation. Two novel, optimized probe ligands, compounds 1 and 2, were identified by screening 20 unlabeled BLT1 antagonists for direct binding. Saturation direct binding studies confirmed the high affinity, and dissociation studies established the rapid binding kinetics of probe ligands 1 and 2. Competition binding assays were established using both probe ligands, and the affinities of structurally diverse BLT1 antagonists were measured. Both binding assay formats can be executed with high specificity and sensitivity and moderate throughput (96-well plate format) using these approaches. This highly versatile, label-free method for studying ligand binding to membrane-associated receptors should find broad application as an alternative to traditional methods using labeled ligands.

Label-free SnO2 nanowire FET biosensor for protein detection

NASA Astrophysics Data System (ADS)

Jakob, Markus H.; Dong, Bo; Gutsch, Sebastian; Chatelle, Claire; Krishnaraja, Abinaya; Weber, Wilfried; Zacharias, Margit

2017-06-01

Novel tin oxide field-effect-transistors (SnO2 NW-FET) for pH and protein detection applicable in the healthcare sector are reported. With a SnO2 NW-FET the proof-of-concept of a bio-sensing device is demonstrated using the carrier transport control of the FET channel by a (bio-) liquid modulated gate. Ultra-thin Al2O3 fabricated by a low temperature atomic layer deposition (ALD) process represents a sensitive layer to H+ ions safeguarding the nanowire at the same time. Successful pH sensitivity is demonstrated for pH ranging from 3 to 10. For protein detection, the SnO2 NW-FET is functionalized with a receptor molecule which specifically interacts with the protein of interest to be detected. The feasibility of this approach is demonstrated via the detection of a biotinylated protein using a NW-FET functionalized with streptavidin. An immediate label-free electronic read-out of the signal is shown. The well-established Enzyme-Linked Immunosorbent Assay (ELISA) method is used to determine the optimal experimental procedure which would enable molecular binding events to occur while being compatible with a final label-free electronic read-out on a NW-FET. Integration of the bottom-up fabricated SnO2 NW-FET pH- and biosensor into a microfluidic system (lab-on-a-chip) allows the automated analysis of small volumes in the 400 μl range as would be desired in portable on-site point-of-care (POC) devices for medical diagnosis.

Determining the Composition and Stability of Protein Complexes Using an Integrated Label-Free and Stable Isotope Labeling Strategy

PubMed Central

Greco, Todd M.; Guise, Amanda J.; Cristea, Ileana M.

2016-01-01

In biological systems, proteins catalyze the fundamental reactions that underlie all cellular functions, including metabolic processes and cell survival and death pathways. These biochemical reactions are rarely accomplished alone. Rather, they involve a concerted effect from many proteins that may operate in a directed signaling pathway and/or may physically associate in a complex to achieve a specific enzymatic activity. Therefore, defining the composition and regulation of protein complexes is critical for understanding cellular functions. In this chapter, we describe an approach that uses quantitative mass spectrometry (MS) to assess the specificity and the relative stability of protein interactions. Isolation of protein complexes from mammalian cells is performed by rapid immunoaffinity purification, and followed by in-solution digestion and high-resolution mass spectrometry analysis. We employ complementary quantitative MS workflows to assess the specificity of protein interactions using label-free MS and statistical analysis, and the relative stability of the interactions using a metabolic labeling technique. For each candidate protein interaction, scores from the two workflows can be correlated to minimize nonspecific background and profile protein complex composition and relative stability. PMID:26867737

Fully integrated graphene electronic biosensor for label-free detection of lead (II) ion based on G-quadruplex structure-switching.

PubMed

Li, Yijun; Wang, Cheng; Zhu, Yibo; Zhou, Xiaohong; Xiang, Yu; He, Miao; Zeng, Siyu

2017-03-15

This work presents a fully integrated graphene field-effect transistor (GFET) biosensor for the label-free detection of lead ions (Pb 2+ ) in aqueous-media, which first implements the G-quadruplex structure-switching biosensing principle in graphene nanoelectronics. We experimentally illustrate the biomolecular interplay that G-rich DNA single-strands with one-end confined on graphene surface can specifically interact with Pb 2+ ions and switch into G-quadruplex structures. Since the structure-switching of electrically charged DNA strands can disrupt the charge distribution in the vicinity of graphene surface, the carrier equilibrium in graphene sheet might be altered, and manifested by the conductivity variation of GFET. The experimental data and theoretical analysis show that our devices are capable of the label-free and specific quantification of Pb 2+ with a detection limit down to 163.7ng/L. These results first verify the signaling principle competency of G-quadruplex structure-switching in graphene electronic biosensors. Combining with the advantages of the compact device structure and convenient electrical signal, a label-free GFET biosensor for Pb 2+ monitoring is enabled with promising application potential. Copyright © 2016 Elsevier B.V. All rights reserved.

An aggregated perylene-based broad-spectrum, efficient and label-free quencher for multiplexed fluorescent bioassays.

PubMed

Liu, Tao; Hu, Rong; Lv, Yi-Fan; Wu, Yuan; Liang, Hao; Huan, Shuang-Yan; Zhang, Xiao-Bing; Tan, Weihong; Yu, Ru-Qin

2014-08-15

Fluorescent sensing systems based on the quenching of fluorophores have found wide applications in bioassays. An efficient quencher will endow the sensing system a high sensitivity. The frequently used quenchers are based on organic molecules or nanomaterials, which usually need tedious synthesizing and modifying steps, and exhibit different quenching efficiencies to different fluorophores. In this work, we for the first time report that aggregated perylene derivative can serve as a broad-spectrum and label-free quencher that is able to efficiently quench a variety of fluorophores, such as green, red and far red dyes labeled on DNA. By choosing nucleases as model biomolecules, such a broad-spectrum quencher was then employed to construct a multiplexed bioassay platform through a label-free manner. Due to the high quenching efficiency of the aggregated perylene, the proposed platform could detect nuclease with high sensitivity, with a detection limit of 0.03U/mL for EcoRV, and 0.05U/mL for EcoRI. The perylene quencher does not affect the activity of nuclease, which makes it possible to design post-addition type bioassay platform. Moreover, the proposed platform allows simultaneous and multicolor analysis of nucleases in homogeneous solution, demonstrating its value of potential application in rapid screening of multiple bio-targets. Copyright © 2014 Elsevier B.V. All rights reserved.

15. GENERAL INTERIOR VIEW LOOKING EAST TOWARDS GALLERY AND FRONT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. GENERAL INTERIOR VIEW LOOKING EAST TOWARDS GALLERY AND FRONT ENTRY (NOTE DOORWAY TO BELL TOWER AT TOP AND CONFESSIONAL BOOTHS TO LEFT REAR) - Sacred Heart Church at Whitemarsh, 16101 Annapolis Road, Bowie, Prince George's County, MD

Label-free Raman spectroscopy for accessing intracellular anticancer drug release on gold nanoparticles.

PubMed

Ock, Kwang-Su; Ganbold, Erdene Ochir; Park, Jin; Cho, Keunchang; Joo, Sang-Woo; Lee, So Yeong

2012-06-21

We investigated glutathione (GSH)-induced purine or pyrimidine anticancer drug release on gold nanoparticle (AuNP) surfaces by means of label-free Raman spectroscopy. GSH-triggered releases of 6-thioguanine (6TG), gemcitabine (GEM), acycloguanosine (ACY), and fadrozole (FAD) were examined in a comparative way by means of surface-enhanced Raman scattering (SERS). The GSH-induced dissociation constant of GEM (or ACY/FAD) from AuNPs was estimated to be larger by more than 38 times than that of 6TG from the kinetic relationship. Tripeptide control experiments were presented to check the turn-off Raman signalling mechanism. Dark-field microscopy (DFM) and transmission electron microscopy (TEM) indicated the intracellular AuNP loads. After their cellular uptake, GEM, ACY, and FAD would not show SERS intensities as strong as 6TG. This may be due to easier release of GEM, ACY, and FAD than 6TG by intracellular reducing species including GSH. We observed fairly strong SERS signals of GEM and 6TG in cell culture media solution. Our CCK-8 cytotoxicity assay data support that 6TG-AuNPs did not exhibit a substantial decrease in cell viability presumably due to strong binding. Label-free confocal Raman spectroscopy can be utilized as an effective tool to access intracellular anticancer drug release.

A gallery of HCMM images

NASA Technical Reports Server (NTRS)

1982-01-01

A gallery of what might be called the ""Best of HCMM'' imagery is presented. These 100 images, consisting mainly of Day-VIS, Day-IR, and Night-IR scenes plus a few thermal inertia images, were selected from the collection accrued in the Missions Utilization Office (Code 902) at the Goddard Space Flight Center. They were selected because of both their pictorial quality and their information or interest content. Nearly all the images are the computer processed and contrast stretched products routinely produced by the image processing facility at GSFC. Several LANDSAT images, special HCMM images made by HCMM investigators, and maps round out the input.

Hybrid Integrated Label-Free Chemical and Biological Sensors

PubMed Central

Mehrabani, Simin; Maker, Ashley J.; Armani, Andrea M.

2014-01-01

Label-free sensors based on electrical, mechanical and optical transduction methods have potential applications in numerous areas of society, ranging from healthcare to environmental monitoring. Initial research in the field focused on the development and optimization of various sensor platforms fabricated from a single material system, such as fiber-based optical sensors and silicon nanowire-based electrical sensors. However, more recent research efforts have explored designing sensors fabricated from multiple materials. For example, synthetic materials and/or biomaterials can also be added to the sensor to improve its response toward analytes of interest. By leveraging the properties of the different material systems, these hybrid sensing devices can have significantly improved performance over their single-material counterparts (better sensitivity, specificity, signal to noise, and/or detection limits). This review will briefly discuss some of the methods for creating these multi-material sensor platforms and the advances enabled by this design approach. PMID:24675757

To label or not to label: applications of quantitative proteomics in neuroscience research.

PubMed

Filiou, Michaela D; Martins-de-Souza, Daniel; Guest, Paul C; Bahn, Sabine; Turck, Christoph W

2012-02-01

Proteomics has provided researchers with a sophisticated toolbox of labeling-based and label-free quantitative methods. These are now being applied in neuroscience research where they have already contributed to the elucidation of fundamental mechanisms and the discovery of candidate biomarkers. In this review, we evaluate and compare labeling-based and label-free quantitative proteomic techniques for applications in neuroscience research. We discuss the considerations required for the analysis of brain and central nervous system specimens, the experimental design of quantitative proteomic workflows as well as the feasibility, advantages, and disadvantages of the available techniques for neuroscience-oriented questions. Furthermore, we assess the use of labeled standards as internal controls for comparative studies in humans and review applications of labeling-based and label-free mass spectrometry approaches in relevant model organisms and human subjects. Providing a comprehensive guide of feasible and meaningful quantitative proteomic methodologies for neuroscience research is crucial not only for overcoming current limitations but also for gaining useful insights into brain function and translating proteomics from bench to bedside. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nest-Gallery Development and Caste Composition of Isolated Foraging Groups of the Drywood Termite, Incisitermes minor (Isoptera: Kalotermitidae)

PubMed Central

Himmi, S. Khoirul; Yoshimura, Tsuyoshi; Yanase, Yoshiyuki; Oya, Masao; Torigoe, Toshiyuki; Akada, Masanori; Imadzu, Setsuo

2016-01-01

An X-ray computed-tomographic examination of nest-gallery development from timbers naturally infested by foraging groups of Incisitermes minor colonies was conducted. This study documents the colonization process of I. minor to new timbers and how the isolated groups maintain their nest-gallery system. The results suggested that development of a nest-gallery within a suitable wood item is not random, but shows selection for softer substrate and other adaptations to the different timber environments. Stigmergic coordinations were expressed in dynamic changes of the nest-gallery system; indicated by fortification behavior in sealing and re-opening a tunnel approaching the outer edge of the timber, and accumulating fecal pellets in particular chambers located beneath the timber surface. The study also examines the caste composition of isolated groups to discover how I. minor sustains colonies with and without primary reproductives. PMID:27455332

Separable Bilayer Microfiltration Device for Label-Free Enrichment of Viable Circulating Tumor Cells.

PubMed

Hao, Sijie; Nisic, Merisa; He, Hongzhang; Tai, Yu-Chong; Zheng, Si-Yang

2017-01-01

Analysis of rare circulating tumor cells enriched from metastatic cancer patients yields critical information on disease progression, therapy response, and the mechanism of cancer metastasis. Here we describe in detail a label-free enrichment process of circulating tumor cells based on its unique physical properties (size and deformability). Viable circulating tumor cells can be successfully enriched and analyzed, or easily released for further characterization due to the novel separable two-layer design.

Self-reference and random sampling approach for label-free identification of DNA composition using plasmonic nanomaterials.

PubMed

Freeman, Lindsay M; Pang, Lin; Fainman, Yeshaiahu

2018-05-09

The analysis of DNA has led to revolutionary advancements in the fields of medical diagnostics, genomics, prenatal screening, and forensic science, with the global DNA testing market expected to reach revenues of USD 10.04 billion per year by 2020. However, the current methods for DNA analysis remain dependent on the necessity for fluorophores or conjugated proteins, leading to high costs associated with consumable materials and manual labor. Here, we demonstrate a potential label-free DNA composition detection method using surface-enhanced Raman spectroscopy (SERS) in which we identify the composition of cytosine and adenine within single strands of DNA. This approach depends on the fact that there is one phosphate backbone per nucleotide, which we use as a reference to compensate for systematic measurement variations. We utilize plasmonic nanomaterials with random Raman sampling to perform label-free detection of the nucleotide composition within DNA strands, generating a calibration curve from standard samples of DNA and demonstrating the capability of resolving the nucleotide composition. The work represents an innovative way for detection of the DNA composition within DNA strands without the necessity of attached labels, offering a highly sensitive and reproducible method that factors in random sampling to minimize error.

Free-Labeling Facial Expressions and Emotional Situations in Children Aged 3-7 Years: Developmental Trajectory and a Face Inferiority Effect

ERIC Educational Resources Information Center

Wang, Zhenhong; Lü, Wei; Zhang, Hui; Surina, Alyssa

2014-01-01

Chinese children (N = 185, aged 3-7 years) were assessed on their abilities to freely label facial expressions and emotional situations. Results indicated that the overall accuracy of free-labeling facial expressions increased relatively quickly in children aged 3-5 years, but slowed down in children aged 5-7 years. In contrast, the overall…

Stabilizing gas bearing in free piston machines

NASA Technical Reports Server (NTRS)

Dhar, Manmohan (Inventor)

1992-01-01

In a free piston engine, to reduce dynamic loads on the reciprocating elements caused by a time varying pressure gradient across the gas bearing and close clearance seals provided therein, drain galleries are incorporated at the ends of the gas bearings to isolate the same, and circumferentially spaced grooves are incorporated in the close clearance seal region.

Stabilizing Gas Bearings In Free-Piston Machines

NASA Technical Reports Server (NTRS)

Dhar, Manmohan

1995-01-01

Gas bearings and clearance seals between pistons and cylinders in free-piston machines designed to reduce undesired dynamic forces and torques on pistons, gas bearings, and cylinders. Circumferential grooves and drain galleries added to piston or cylinder in improved design. Provides stabilization without significant reduction in length of seal, or significant increase in leakage and consequent reduction of efficiency.

Enhancement of fluorescence using nanoplasmonic and photonic structures

NASA Astrophysics Data System (ADS)

Arya, Akash; Tagore, Amit K.; Dantham, Venkata R.

2018-05-01

Two different nanoplasmonic structures have been synthesized using wet-chemistry method and demonstrated the enhancement of fluorescence of dye molecules. The difficulties associated with the plasmonic enhancement of fluorescence are discussed and to overcome these, an efficient approach has been proposed to enhance the fluorescence of a few molecules with the help of a high quality factor photonic microstructure (whispering gallery mode microresonator). The fabrication details of microresonators and experimental arrangement for enhancing the fluorescence are reported here.

Old tree with new shoots: silver nanoparticles for label-free and colorimetric mercury ions detection

NASA Astrophysics Data System (ADS)

Gao, Shuyan; Jia, Xiaoxia; Chen, Yanli

2013-01-01

Mercury in the environment from global mercury emissions as well as various forms of contamination poses severe threats to both human health and the environment. Long-term exposure to high levels of Hg-based toxins results in serious and irreversible damage of the central nervous system and other organs. Therefore, the development of effective sensing systems for mercury detection becomes an increasing demand. In this article, a yogurt-mediated silver nanostructure is reported to be unprecedentedly used in the naked-eye and label-free detection of mercury. The method relies on the redox reaction resulting from the electrode potential difference between Ag+/Ag (0.7996 V) and Hg2+/Hg2 2+ (0.920 V) that makes colorless Hg2+ ions which oxidize colored silver nanoparticle (AgNP) to colorless Ag+. The labor-intensive modification of AgNPs and expensive labeling are avoided, and the traditional AuNPs are substituted by AgNPs in this Hg2+ ions sensing platform, which makes it facile, low-cost, and particularly useful for home, clinic, or field applications as well as resource-limited conditions. This sensing system achieves a detection limit as low as 10 nM, lower than the toxicity level of Hg2+ ions in drinking water (30 nM) defined by World Health Organization, and exhibits excellent selectivity, largely free from the matrix effect of the real water samples. This visual label-free Hg2+ ions sensing motif shows great promise for sensing Hg2+ ions in terms of sensitivity, selectivity, cost, and maneuverability. It is also a good example for the organic combination of green chemistry and functional materials, which may trigger interest in furthering biosystems for environmental science applications.

Label-free biodetection using a smartphone.

PubMed

Gallegos, Dustin; Long, Kenneth D; Yu, Hojeong; Clark, Peter P; Lin, Yixiao; George, Sherine; Nath, Pabitra; Cunningham, Brian T

2013-06-07

Utilizing its integrated camera as a spectrometer, we demonstrate the use of a smartphone as the detection instrument for a label-free photonic crystal biosensor. A custom-designed cradle holds the smartphone in fixed alignment with optical components, allowing for accurate and repeatable measurements of shifts in the resonant wavelength of the sensor. Externally provided broadband light incident upon an entrance pinhole is subsequently collimated and linearly polarized before passing through the biosensor, which resonantly reflects only a narrow band of wavelengths. A diffraction grating spreads the remaining wavelengths over the camera's pixels to display a high resolution transmission spectrum. The photonic crystal biosensor is fabricated on a plastic substrate and attached to a standard glass microscope slide that can easily be removed and replaced within the optical path. A custom software app was developed to convert the camera images into the photonic crystal transmission spectrum in the visible wavelength range, including curve-fitting analysis that computes the photonic crystal resonant wavelength with 0.009 nm accuracy. We demonstrate the functionality of the system through detection of an immobilized protein monolayer, and selective detection of concentration-dependent antibody binding to a functionalized photonic crystal. We envision the capability for an inexpensive, handheld biosensor instrument with web connectivity to enable point-of-care sensing in environments that have not been practical previously.

13. VIEW OF EAST OPERATING GALLERY ALONG THE POSTMORTEM CELLS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. VIEW OF EAST OPERATING GALLERY ALONG THE POST-MORTEM CELLS. A NUMBER OF MANIPULATOR ARMS COVERED WITH PLASTIC ARE ON THE LEFT WALL. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Development of cadmium-free quantum dot for intracellular labelling through electroporation or lipid-calcium-phosphate

NASA Astrophysics Data System (ADS)

Liu, Ying-Feng; Hung, Wei-Ling; Hou, Tzh-Yin; Huang, Hsiu-Ying; Lin, Cheng-An J.

2016-04-01

Traditional fluorescent labelling techniques has severe photo-bleaching problem such as organic dyes and fluorescent protein. Quantum dots made up of traditional semiconductor (CdSe/ZnS) material has sort of biological toxicity. This research has developed novel Cd-free quantum dots divided into semiconductor (Indium phosphide, InP) and noble metal (Gold). Former has lower toxicity compared to traditional quantum dots. Latter consisting of gold (III) chloride (AuCl3) and toluene utilizes sonochemical preparation and different stimulus to regulate fluorescent wavelength. Amphoteric macromolecule surface technology and ligand Exchange in self-Assembled are involved to develop hydrophilic nanomaterials which can regulate the number of grafts per molecule of surface functional groups. Calcium phosphate (CaP) nanoparticle (NP) with an asymmetric lipid bilayer coating technology developed for intracellular delivery and labelling has synthesized Cd-free quantum dots possessing high brightness and multi-fluorescence successfully. Then, polymer coating and ligand exchange transfer to water-soluble materials to produce liposome nanomaterials as fluorescent probes and enhancing medical applications of nanotechnology.

A highly-sensitive label-free biosensor based on two dimensional photonic crystals with negative refraction

NASA Astrophysics Data System (ADS)

Malmir, Narges; Fasihi, Kiazand

2017-11-01

In this work, we present a novel high-sensitive optical label-free biosensor based on a two-dimensional photonic crystal (2D PC). The suggested structure is composed of a negative refraction structure in a hexagonal lattice PC, along with a positive refraction structure which is arranged in a square lattice PC. The frequency shift of the transmission peak is measured respect to the changes of refractive indices of the studied materials (the blood plasma, water, dry air and normal air). The studied materials are filled into a W1 line-defect waveguide which is located in the PC structure with positive refraction (the microfluidic nanochannel). Our numerical simulations, which are based on finite-difference time-domain (FDTD) method, show that in the proposed structure, a sensitivity about 1100 nm/RIU and a transmission efficiency more than 75% can be achieved. With this design, to the best of our knowledge, the obtained sensitivity and the transmission efficiency are one of the highest values in the reported PC label-free biosensors.

Label-Free Detection of Bacillus anthracis Spore Uptake in Macrophage Cells Using Analytical Optical Force Measurements.

PubMed

Hebert, Colin G; Hart, Sean; Leski, Tomasz A; Terray, Alex; Lu, Qin

2017-10-03

Understanding the interaction between macrophage cells and Bacillus anthracis spores is of significant importance with respect to both anthrax disease progression, spore detection for biodefense, as well as understanding cell clearance in general. While most detection systems rely on specific molecules, such as nucleic acids or proteins and fluorescent labels to identify the target(s) of interest, label-free methods probe changes in intrinsic properties, such as size, refractive index, and morphology, for correlation with a particular biological event. Optical chromatography is a label free technique that uses the balance between optical and fluidic drag forces within a microfluidic channel to determine the optical force on cells or particles. Here we show an increase in the optical force experienced by RAW264.7 macrophage cells upon the uptake of both microparticles and B. anthracis Sterne 34F2 spores. In the case of spores, the exposure was detected in as little as 1 h without the use of antibodies or fluorescent labels of any kind. An increase in the optical force was also seen in macrophage cells treated with cytochalasin D, both with and without a subsequent exposure to spores, indicating that a portion of the increase in the optical force arises independent of phagocytosis. These results demonstrate the capability of optical chromatography to detect subtle biological differences in a rapid and sensitive manner and suggest future potential in a range of applications, including the detection of biological threat agents for biodefense and pathogens for the prevention of sepsis and other diseases.

Quantum Cascade Laser-Based Infrared Microscopy for Label-Free and Automated Cancer Classification in Tissue Sections.

PubMed

Kuepper, Claus; Kallenbach-Thieltges, Angela; Juette, Hendrik; Tannapfel, Andrea; Großerueschkamp, Frederik; Gerwert, Klaus

2018-05-16

A feasibility study using a quantum cascade laser-based infrared microscope for the rapid and label-free classification of colorectal cancer tissues is presented. Infrared imaging is a reliable, robust, automated, and operator-independent tissue classification method that has been used for differential classification of tissue thin sections identifying tumorous regions. However, long acquisition time by the so far used FT-IR-based microscopes hampered the clinical translation of this technique. Here, the used quantum cascade laser-based microscope provides now infrared images for precise tissue classification within few minutes. We analyzed 110 patients with UICC-Stage II and III colorectal cancer, showing 96% sensitivity and 100% specificity of this label-free method as compared to histopathology, the gold standard in routine clinical diagnostics. The main hurdle for the clinical translation of IR-Imaging is overcome now by the short acquisition time for high quality diagnostic images, which is in the same time range as frozen sections by pathologists.

Comparative study of label and label-free techniques using shotgun proteomics for relative protein quantification.

PubMed

Sjödin, Marcus O D; Wetterhall, Magnus; Kultima, Kim; Artemenko, Konstantin

2013-06-01

The analytical performance of three different strategies, iTRAQ (isobaric tag for relative and absolute quantification), dimethyl labeling (DML) and label free (LF) for relative protein quantification using shotgun proteomics have been evaluated. The methods have been explored using samples containing (i) Bovine proteins in known ratios and (ii) Bovine proteins in known ratios spiked into Escherichia coli. The latter case mimics the actual conditions in a typical biological sample with a few differentially expressed proteins and a bulk of proteins with unchanged ratios. Additionally, the evaluation was performed on both QStar and LTQ-FTICR mass spectrometers. LF LTQ-FTICR was found to have the highest proteome coverage while the highest accuracy based on the artificially regulated proteins was found for DML LTQ-FTICR (54%). A varying linearity (k: 0.55-1.16, r(2): 0.61-0.96) was shown for all methods within selected dynamic ranges. All methods were found to consistently underestimate Bovine protein ratios when matrix proteins were added. However, LF LTQ-FTICR was more tolerant toward a compression effect. A single peptide was demonstrated to be sufficient for a reliable quantification using iTRAQ. A ranking system utilizing several parameters important for quantitative proteomics demonstrated that the overall performance of the five different methods was; DML LTQ-FTICR>iTRAQ QStar>LF LTQ-FTICR>DML QStar>LF QStar. Copyright © 2013 Elsevier B.V. All rights reserved.

Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-04-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

Label-Free Quantitation of Ribosomal Proteins from Bacillus subtilis for Antibiotic Research.

PubMed

Schäkermann, Sina; Prochnow, Pascal; Bandow, Julia E

2017-01-01

Current research is focusing on ribosome heterogeneity as a response to changing environmental conditions and stresses, such as antibiotic stress. Altered stoichiometry and composition of ribosomal proteins as well as association of additional protein factors are mechanisms for shaping the protein expression profile or hibernating ribosomes. Here, we present a method for the isolation of ribosomes to analyze antibiotic-induced changes in the composition of ribosomes in Bacillus subtilis or other bacteria. Ribosomes and associated proteins are isolated by ultracentrifugation and proteins are identified and quantified using label-free mass spectrometry.

Testing Lorentz and C P T invariance with ultracold neutrons

NASA Astrophysics Data System (ADS)

Martín-Ruiz, A.; Escobar, C. A.

2018-05-01

In this paper we investigate, within the standard model extension framework, the influence of Lorentz- and C P T -violating terms on gravitational quantum states of ultracold neutrons. Using a semiclassical wave packet, we derive the effective nonrelativistic Hamiltonian which describes the neutrons vertical motion by averaging the contributions from the perpendicular coordinates to the free falling axis. We compute the physical implications of the Lorentz- and C P T -violating terms on the spectra. The comparison of our results with those obtained in the GRANIT experiment leads to an upper bound for the symmetries-violation cμν n coefficients. We find that ultracold neutrons are sensitive to the ain and ein coefficients, which thus far are unbounded by experiments in the neutron sector. We propose two additional problems involving ultracold neutrons which could be relevant for improving our current bounds; namely, gravity-resonance spectroscopy and neutron whispering gallery wave.

Label-free optical detection of action potential in mammalian neurons (Conference Presentation)

NASA Astrophysics Data System (ADS)

Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra K.; Davé, Digant P.

2017-02-01

Electrophysiology techniques are the gold standard in neuroscience for studying functionality of a single neuron to a complex neuronal network. However, electrophysiology techniques are not flawless, they are invasive nature, procedures are cumbersome to implement with limited capability of being used as a high-throughput recording system. Also, long term studies of neuronal functionality with aid of electrophysiology is not feasible. Non-invasive stimulation and detection of neuronal electrical activity has been a long standing goal in neuroscience. Introduction of optogenetics has ushered in the era of non-invasive optical stimulation of neurons, which is revolutionizing neuroscience research. Optical detection of neuronal activity that is comparable to electro-physiology is still elusive. A number of optical techniques have been reported recording of neuronal electrical activity but none is capable of reliably measuring action potential spikes that is comparable to electro-physiology. Optical detection of action potential with voltage sensitive fluorescent reporters are potential alternatives to electrophysiology techniques. The heavily rely on secondary reporters, which are often toxic in nature with background fluorescence, with slow response and low SNR making them far from ideal. The detection of one shot (without averaging)-single action potential in a true label-free way has been elusive so far. In this report, we demonstrate the optical detection of single neuronal spike in a cultured mammalian neuronal network without using any exogenous labels. To the best of our knowledge, this is the first demonstration of label free optical detection of single action potentials in a mammalian neuronal network, which was achieved using a high-speed phase sensitive interferometer. We have carried out stimulation and inhibition of neuronal firing using Glutamate and Tetrodotoxin respectively to demonstrate the different outcome (stimulation and inhibition) revealed in

8. MAIN INLET FROM FILTER GALLERY AND CANAL INTO HINDS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. MAIN INLET FROM FILTER GALLERY AND CANAL INTO HINDS PLANT. VIEW LOOKING DUE WEST OF HINDS COMPLEX IN BACKGROUND OF SAND FILTERS. - Hinds Pump Plant, East of Joshua Tree National Monument, 5 miles north of Route 10, Hayfield, Riverside County, CA

71. (Credit JTL) Pipe gallery looking south in basement underneath ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

71. (Credit JTL) Pipe gallery looking south in basement underneath 1910-11 and 1924 filter wing extensions. Note bottoms of converted New York horizontal pressure filters in right background. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

Coupling compositional liquid gas Darcy and free gas flows at porous and free-flow domains interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Masson, R., E-mail: roland.masson@unice.fr; Team COFFEE INRIA Sophia Antipolis Méditerranée; Trenty, L., E-mail: laurent.trenty@andra.fr

This paper proposes an efficient splitting algorithm to solve coupled liquid gas Darcy and free gas flows at the interface between a porous medium and a free-flow domain. This model is compared to the reduced model introduced in [6] using a 1D approximation of the gas free flow. For that purpose, the gas molar fraction diffusive flux at the interface in the free-flow domain is approximated by a two point flux approximation based on a low-frequency diagonal approximation of a Steklov–Poincaré type operator. The splitting algorithm and the reduced model are applied in particular to the modelling of the massmore » exchanges at the interface between the storage and the ventilation galleries in radioactive waste deposits.« less

Real-time label-free quantitative fluorescence microscopy-based detection of ATP using a tunable fluorescent nano-aptasensor platform

NASA Astrophysics Data System (ADS)

Shrivastava, Sajal; Sohn, Il-Yung; Son, Young-Min; Lee, Won-Il; Lee, Nae-Eung

2015-11-01

Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules.Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (r

A Comparative Analysis of Computational Approaches to Relative Protein Quantification Using Peptide Peak Intensities in Label-free LC-MS Proteomics Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matzke, Melissa M.; Brown, Joseph N.; Gritsenko, Marina A.

2013-02-01

Liquid chromatography coupled with mass spectrometry (LC-MS) is widely used to identify and quantify peptides in complex biological samples. In particular, label-free shotgun proteomics is highly effective for the identification of peptides and subsequently obtaining a global protein profile of a sample. As a result, this approach is widely used for discovery studies. Typically, the objective of these discovery studies is to identify proteins that are affected by some condition of interest (e.g. disease, exposure). However, for complex biological samples, label-free LC-MS proteomics experiments measure peptides and do not directly yield protein quantities. Thus, protein quantification must be inferred frommore » one or more measured peptides. In recent years, many computational approaches to relative protein quantification of label-free LC-MS data have been published. In this review, we examine the most commonly employed quantification approaches to relative protein abundance from peak intensity values, evaluate their individual merits, and discuss challenges in the use of the various computational approaches.« less

In situ label-free imaging of hemicellulose in plant cell walls using stimulated Raman scattering microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, Yining; Yarbrough, John M.; Mittal, Ashutosh

Plant hemicellulose (largely xylan) is an excellent feedstock for renewable energy production and second only to cellulose in abundance. Beyond a source of fermentable sugars, xylan constitutes a critical polymer in the plant cell wall, where its precise role in wall assembly, maturation, and deconstruction remains primarily hypothetical. Effective detection of xylan, particularly by in situ imaging of xylan in the presence of other biopolymers, would provide critical information for tackling the challenges of understanding the assembly and enhancing the liberation of xylan from plant materials. Raman-based imaging techniques, especially the highly sensitive stimulated Raman scattering (SRS) microscopy, have provenmore » to be valuable tools for label-free imaging. However, due to the complex nature of plant materials, especially those same chemical groups shared between xylan and cellulose, the utility of specific Raman vibrational modes that are unique to xylan have been debated. Here, we report a novel approach based on combining spectroscopic analysis and chemical/enzymatic xylan removal from corn stover cell walls, to make progress in meeting this analytical challenge. We have identified several Raman peaks associated with xylan content in cell walls for label-free in situ imaging xylan in plant cell wall. We demonstrated that xylan can be resolved from cellulose and lignin in situ using enzymatic digestion and label-free SRS microscopy in both 2D and 3D. As a result, we believe that this novel approach can be used to map xylan in plant cell walls and that this ability will enhance our understanding of the role played by xylan in cell wall biosynthesis and deconstruction.« less

In situ label-free imaging of hemicellulose in plant cell walls using stimulated Raman scattering microscopy

DOE PAGES

Zeng, Yining; Yarbrough, John M.; Mittal, Ashutosh; ...

2016-11-22

Plant hemicellulose (largely xylan) is an excellent feedstock for renewable energy production and second only to cellulose in abundance. Beyond a source of fermentable sugars, xylan constitutes a critical polymer in the plant cell wall, where its precise role in wall assembly, maturation, and deconstruction remains primarily hypothetical. Effective detection of xylan, particularly by in situ imaging of xylan in the presence of other biopolymers, would provide critical information for tackling the challenges of understanding the assembly and enhancing the liberation of xylan from plant materials. Raman-based imaging techniques, especially the highly sensitive stimulated Raman scattering (SRS) microscopy, have provenmore » to be valuable tools for label-free imaging. However, due to the complex nature of plant materials, especially those same chemical groups shared between xylan and cellulose, the utility of specific Raman vibrational modes that are unique to xylan have been debated. Here, we report a novel approach based on combining spectroscopic analysis and chemical/enzymatic xylan removal from corn stover cell walls, to make progress in meeting this analytical challenge. We have identified several Raman peaks associated with xylan content in cell walls for label-free in situ imaging xylan in plant cell wall. We demonstrated that xylan can be resolved from cellulose and lignin in situ using enzymatic digestion and label-free SRS microscopy in both 2D and 3D. As a result, we believe that this novel approach can be used to map xylan in plant cell walls and that this ability will enhance our understanding of the role played by xylan in cell wall biosynthesis and deconstruction.« less

Microfluidic and Label-Free Multi-Immunosensors Based on Carbon Nanotube Microelectrodes

NASA Astrophysics Data System (ADS)

Tsujita, Yuichi; Maehashi, Kenzo; Matsumoto, Kazuhiko; Chikae, Miyuki; Takamura, Yuzuru; Tamiya, Eiichi

2009-06-01

We fabricated microfluidic and label-free multi-immunosensors by the integration of carbon nanotube (CNT)-arrayed electrodes and microchannels with pneumatic micropumps made of poly(dimethylsiloxane). In the microfluidic systems, four kinds of sample solutions were transported from each liquid inlet to microchannels using six pneumatic micropumps. As a result, two kinds of antibodies were immobilized onto different CNT electrodes using the microfluidic systems. Next, two kinds of cancer markers, prostate specific antigen and human chorionic gonadotropin in phosphate buffer solution, were simultaneously detected by differential pulse voltammetry. Therefore, microfludic multi-immunosensors based on CNT electrodes and pneumatic micropumps are useful for the development of multiplex hand-held biosensors.

Label-free logic modules and two-layer cascade based on stem-loop probes containing a G-quadruplex domain.

PubMed

Guo, Yahui; Cheng, Junjie; Wang, Jine; Zhou, Xiaodong; Hu, Jiming; Pei, Renjun

2014-09-01

A simple, versatile, and label-free DNA computing strategy was designed by using toehold-mediated strand displacement and stem-loop probes. A full set of logic gates (YES, NOT, OR, NAND, AND, INHIBIT, NOR, XOR, XNOR) and a two-layer logic cascade were constructed. The probes contain a G-quadruplex domain, which was blocked or unfolded through inputs initiating strand displacement and the obviously distinguishable light-up fluorescent signal of G-quadruplex/NMM complex was used as the output readout. The inputs are the disease-specific nucleotide sequences with potential for clinic diagnosis. The developed versatile computing system based on our label-free and modular strategy might be adapted in multi-target diagnosis through DNA hybridization and aptamer-target interaction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging

PubMed Central

2014-01-01

The molecular mechanisms underlying skeletal muscle aging and associated sarcopenia have been linked to an altered oxidative status of redox-sensitive proteins. Reactive oxygen and reactive nitrogen species (ROS/RNS) generated by contracting skeletal muscle are necessary for optimal protein function, signaling, and adaptation. To investigate the redox proteome of aging gastrocnemius muscles from adult and old male mice, we developed a label-free quantitative proteomic approach that includes a differential cysteine labeling step. The approach allows simultaneous identification of up- and downregulated proteins between samples in addition to the identification and relative quantification of the reversible oxidation state of susceptible redox cysteine residues. Results from muscles of adult and old mice indicate significant changes in the content of chaperone, glucose metabolism, and cytoskeletal regulatory proteins, including Protein DJ-1, cAMP-dependent protein kinase type II, 78 kDa glucose regulated protein, and a reduction in the number of redox-responsive proteins identified in muscle of old mice. Results demonstrate skeletal muscle aging causes a reduction in redox-sensitive proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response. Data is available via ProteomeXchange with identifier PXD001054. PMID:25181601

Label-free in situ imaging of oil body dynamics and chemistry in germination

PubMed Central

Waschatko, Gustav; Billecke, Nils; Schwendy, Sascha; Jaurich, Henriette; Bonn, Mischa; Vilgis, Thomas A.

2016-01-01

Plant oleosomes are uniquely emulsified lipid reservoirs that serve as the primary energy source during seed germination. These oil bodies undergo significant changes regarding their size, composition and structure during normal seedling development; however, a detailed characterization of these oil body dynamics, which critically affect oil body extractability and nutritional value, has remained challenging because of a limited ability to monitor oil body location and composition during germination in situ. Here, we demonstrate via in situ, label-free imaging that oil bodies are highly dynamic intracellular organelles that are morphologically and biochemically remodelled extensively during germination. Label-free, coherent Raman microscopy (CRM) combined with bulk biochemical measurements revealed the temporal and spatial regulation of oil bodies in native soya bean cotyledons during the first eight days of germination. Oil bodies undergo a cycle of growth and shrinkage that is paralleled by lipid and protein compositional changes. Specifically, the total protein concentration associated with oil bodies increases in the first phase of germination and subsequently decreases. Lipids contained within the oil bodies change in saturation and chain length during germination. Our results show that CRM is a well-suited platform to monitor in situ lipid dynamics and local chemistry and that oil bodies are actively remodelled during germination. This underscores the dynamic role of lipid reservoirs in plant development. PMID:27798279

An Old-Growth Definition for Western Hardwood Gallery Forests

Treesearch

Kelly Kindscher; Jenny Holah

1998-01-01

Western hardwood gallery forests are found across an extremely large, diverse geographical area that encompasses the Great Plains in the United States and Canada. Remnant forests of this type still exist in the "Prairie Peninsula," which historically projected an eastern finger into Ohio. The forests are restricted to floodplains of major rivers and are in...

Flexible Microsphere-Embedded Film for Microsphere-Enhanced Raman Spectroscopy.

PubMed

Xing, Cheng; Yan, Yinzhou; Feng, Chao; Xu, Jiayu; Dong, Peng; Guan, Wei; Zeng, Yong; Zhao, Yan; Jiang, Yijian

2017-09-27

Dielectric microspheres with extraordinary microscale optical properties, such as photonic nanojets, optical whispering-gallery modes (WGMs), and directional antennas, have drawn interest in many research fields. Microsphere-enhanced Raman spectroscopy (MERS) is an alternative approach for enhanced Raman detection by dielectric microstructures. Unfortunately, fabrication of microsphere monolayer arrays is the major challenge of MERS for practical applications on various specimen surfaces. Here we report a microsphere-embedded film (MF) by immersing a highly refractive microsphere monolayer array in the poly(dimethylsiloxane) (PDMS) film as a flexible MERS sensing platform for one- to three-dimensional (1D to 3D) specimen surfaces. The directional antennas and wave-guided whispering-gallery modes (WG-WGMs) contribute to the majority of Raman enhancement by the MFs. Moreover, the MF can be coupled with surface-enhanced Raman spectroscopy (SERS) to provide an extra >10-fold enhancement. The limit of detection is therefore improved for sensing of crystal violet (CV) and Sudan I molecules in aqueous solutions at concentrations down to 10 -7 M. A hybrid dual-layer microsphere enhancer, constructed by depositing a MF onto a microsphere monolayer array, is also demonstrated, wherein the WG-WGMs become dominant and boost the enhancement ratio >50-fold. The present work opens up new opportunities for design of cost-effective and flexible MERS sensing platforms as individual or associated techniques toward practical applications in ultrasensitive Raman detection.

Label-free detection of HIV-1 infected cells via integration of optical tweezers and photoluminescence spectroscopy

NASA Astrophysics Data System (ADS)

Lugongolo, Masixole Yvonne; Ombinda-Lemboumba, Saturnin; Noto, Luyanda Lunga; Maaza, Malik; Mthunzi-Kufa, Patience

2018-02-01

The human immunodeficiency virus-1 (HIV-1) is currently detected using conventional qualitative and quantitative tests to determine the presence or absence of HIV in blood samples. However, the approach of these tests detects the presence of either viral antibodies or viral RNA that require labelling which may be costly, sophisticated and time consuming. A label-free approach of detecting the presence of HIV is therefore desirable. Of note optical tweezers can be coupled with other technologies including spectroscopy, which also investigates light-matter interactions. For example, coupling of optical tweezers with luminescence spectroscopy techniques has emerged as a powerful tool in biology for micro-manipulation, detection and analysis of individual cells. Integration of optical techniques has enabled studying biological particles in a label-free manner, whilst detecting functional groups and other essential molecules within mixed populations of cells. In the current study, an optical trapping system coupled to luminescence spectroscopy was utilised to detect the presence of HIV infection in TZM-bl cells in vitro. This was performed by infecting TZM-bl cells with the ZM53 HIV-1 pseudovirus, and incubating them for 48 hours prior analysis. The differences between infected and uninfected cells were thereafter displayed as shown by the spectrographs obtained. Combination of these two techniques has a potential in the field of infectious disease diagnostics.

Commissioning and Performance Analysis of WhisperGen Stirling Engine

NASA Astrophysics Data System (ADS)

Pradip, Prashant Kaliram

Stirling engine based cogeneration systems have potential to reduce energy consumption and greenhouse gas emission, due to their high cogeneration efficiency and emission control due to steady external combustion. To date, most studies on this unit have focused on performance based on both experimentation and computer models, and lack experimental data for diversified operating ranges. This thesis starts with the commissioning of a WhisperGen Stirling engine with components and instrumentation to evaluate power and thermal performance of the system. Next, a parametric study on primary engine variables, including air, diesel, and coolant flowrate and temperature were carried out to further understand their effect on engine power and efficiency. Then, this trend was validated with the thermodynamic model developed for the energy analysis of a Stirling cycle. Finally, the energy balance of the Stirling engine was compared without and with heat recovery from the engine block and the combustion chamber exhaust.

Beyond Art Waitressing: Meaningful Engagement in Interactive Art Galleries

ERIC Educational Resources Information Center

Kothe, Elsa Lenz

2012-01-01

The metaphor of "art waitressing" is a valuable tool for educators who seek guidance in enacting many of the new roles in museums, particularly the role of facilitator in an open-ended interactive gallery. Though this metaphor provides a valuable model for engaging visitors, the question quickly arises of how educators can go beyond "serving" an…

Label-Free Pyrophosphate Recognition with Functionalized Asymmetric Nanopores.

PubMed

Ali, Mubarak; Ahmed, Ishtiaq; Ramirez, Patricio; Nasir, Saima; Niemeyer, Christof M; Mafe, Salvador; Ensinger, Wolfgang

2016-04-01

The label-free detection of pyrophosphate (PPi) anions with a nanofluidic sensing device based on asymmetric nanopores is demonstrated. The pore surface is functionalized with zinc complexes based on two di(2-picolyl)amine [bis(DPA)] moieties using carbodiimide coupling chemistry. The complexation of zinc (Zn(2+) ) ion is achieved by exposing the modified pore to a solution of zinc chloride to form bis(Zn(2+) -DPA) complexes. The chemical functionalization is demonstrated by recording the changes in the observed current-voltage (I-V) curves before and after pore modification. The bis(Zn(2+) -DPA) complexes on the pore walls serve as recognition sites for pyrophosphate anion. The experimental results show that the proposed nanofluidic sensor has the ability to sense picomolar concentrations of PPi anion in the surrounding environment. On the contrary, it does not respond to other phosphate anions, including monohydrogen phosphate, dihydrogen phosphate, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate. The experimental results are described theoretically by using a model based on the Poisson-Nernst-Planck equations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

40. CONSTRUCTION OF GALLERY NO. 3, SHOWING INCLINED PLANE USED ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

40. CONSTRUCTION OF GALLERY NO. 3, SHOWING INCLINED PLANE USED TO TRANSPORT MATERIALS, ALSO SPOIL FROM TUNNEL INTERIOR. POWDER HOUSE AND TOOL SHED VISIBLE TO RIGHT OF BASE INCLINE - Zion-Mount Carmel Highway, Tunnel, Two miles east of Zion Canyon Scenic Drive, Springdale, Washington County, UT

Compact 3D printed module for fluorescence and label-free imaging using evanescent excitation

NASA Astrophysics Data System (ADS)

Pandey, Vikas; Gupta, Shalini; Elangovan, Ravikrishnan

2018-01-01

Total internal reflection fluorescence (TIRF) microscopy is widely used for selective excitation and high-resolution imaging of fluorophores, and more recently label-free nanosized objects, with high vertical confinement near a liquid-solid interface. Traditionally, high numerical aperture objectives (>1.4) are used to simultaneously generate evanescent waves and collect fluorescence emission signals which limits their use to small area imaging (<0.1 mm2). Objective-based TIRFs are also expensive as they require dichroic mirrors and efficient notch filters to prevent specular reflection within the objective lenses. We have developed a compact 3D module called cTIRF that can generate evanescent waves in microscope glass slides via a planar waveguide illumination. The module can be attached as a fixture to any existing optical microscope, converting it into a TIRF and enabling high signal-to-noise ratio (SNR) fluorescence imaging using any magnification objective. As the incidence optics is perpendicular to the detector, label-free evanescent scattering-based imaging of submicron objects can also be performed without using emission filters. SNR is significantly enhanced in this case as compared to cTIRF alone, as seen through our model experiments performed on latex beads and mammalian cells. Extreme flexibility and the low cost of our approach makes it scalable for limited resource settings.

Nanostructured plasmonic interferometers for ultrasensitive label-free biosensing

NASA Astrophysics Data System (ADS)

Gao, Yongkang

Optical biosensors that utilize surface plasmon resonance (SPR) technique to analyze the biomolecular interactions have been extensively explored in the last two decades and have become the gold standard for label-free biosensing. These powerful sensing tools allow fast, highly-sensitive monitoring of the interaction between biomolecules in real time, without the need for laborious fluorescent labeling, and have found widely ranging applications from biomedical diagnostics and drug discovery, to environmental sensing and food safety monitoring. However, the prism-coupling SPR geometry is complex and bulky, and has severely limited the integration of this technique into low-cost portable biomedical devices for point-of-care diagnostics and personal healthcare applications. Also, the complex prism-coupling scheme prevents the use of high numerical aperture (NA) optics to increase the spatial resolution for multi-channel, high-throughput detection in SPR imaging mode. This dissertation is focused on the design and fabrication of a promising new class of nanopatterned interferometric SPR sensors that integrate the strengths of miniaturized nanoplasmonic architectures with sensitive optical interferometry techniques to achieve bold advances in SPR biosensing. The nanosensor chips developed provide superior sensing performance comparable to conventional SPR systems, but employing a far simpler collinear optical transmission geometry, which largely facilitates system integration, miniaturization, and low-cost production. Moreover, the fabricated nanostructure-based SPR sensors feature a very small sensor footprint, allowing massive multiplexing on a chip for high-throughput detection. The successful transformation of SPR technique from bulky prism-coupling setup into this low-cost compact plasmonic platform would have a far-reaching impact on point-of-care diagnostic tools and also lead to advances in high-throughput sensing applications in proteomics, immunology, drug

Novel label-free biosensing technology for monitoring of aqueous solutions (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kehl, Florian; Bielecki, Robert; Follonier, Stephane; Dorokhin, Denis

2016-03-01

Waste water, drinking water and other industrial water sources are more and more/increasingly polluted with a large variety of contaminants, such as pesticides or residuals of pharmaceuticals. These compounds can impact human and animal organisms and lead to serious health issues. Today, in order to analyze the presence and quantity of the abovementioned micropollutants, samples are typically sent to specialized centralized laboratories and their processing may take up to several days. In order to meet the demand for continuous and consistent monitoring of aqueous solutions we propose a novel label-free technology system comprising proprietary chip and reader device designs. The core of the system is constituted by a planar-grated-waveguide (PGW) chip. Label-free biosensors, based on PGWs are sensitive to effective refractive index changes caused by the adsorption of biomolecules (micropollutants) onto the sensor surface or due to refractive index changes of the bulk solution. The presented reader device operates with a novel readout concept based on a scanning MEMS mirror for the angular interrogation of input grating couplers at a high repetition rate. The reader has fully integrated optics, electronics and fluidics and at the same time consumes limited energy (portable, field use ready). In the recent experiments, the effectiveness of the technology has been demonstrated with various liquids and bioassays showing (i) an excellent refractometric sensitivity with a limit of detection towards effective refractive index changes of ▵neff < 2 x 10-7, and (ii) the capability to perform affinity measurements for large (<150 kDa) and small (<250 Da) molecules.

Label-free in vitro prostate cancer cell detection via photonic-crystal biosensor

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFei; Sagredo, Ismael; Bustamante, Gilbert; Sun, Lu-Zhe; Ye, Jing Yong

2018-02-01

Prostate-specific antigen (PSA) biomarker assays are the current clinical method for mass screening of prostate cancer. However, high false-positive rates are often reported due to PSA's low specificity, leading to an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we demonstrated the feasibility of using cellular refractive indices (RI) as a unique contrast parameter to accomplish label-free detection of prostate cancer cells via variance testing, but were unable to determine if a specific cell was cancerous or noncancerous. In this paper, we report the use of our Photonic-Crystal biosensor in a Total-Internal-Reflection (PC-TIR) configuration to construct a label-free imaging system, which allows for the detection of individual prostate cancer cells utilizing cellular RI as the only contrast parameter. Noncancerous prostate (BPH-1) cells and prostate cancer (PC-3) cells were mixed at varied ratios and measured concurrently. Additionally, we isolated and induced PC-3 cells to undergo epithelial-mesenchymal transition (EMT) by exposing these cells to soluble factors such as TGF-β1. The biophysical characteristics of the cellular RI were quantified extensively in comparison to non-induced PC-3 cells as well as BPH-1 cells. EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. Our study shows promising clinical potential in utilizing the PC-TIR biosensor imaging system to not only detect prostate cancer cells, but also evaluate prostate cancer progression.

The relationship between resonance scattering and the formation of an acoustojet under the interaction of ultrasound with a dielectric sphere immersed in water

NASA Astrophysics Data System (ADS)

Minin, I. V.; Minin, O. V.; Tseplyaev, I. S.

2017-08-01

We demonstrated for the first time the influence of the main parameters of dielectric spherical cavity, immersed in water, to transformation of whispering gallery mode into acoustojet (acoustic jets) by interaction of acoustic plane wave scatterer. It has been shown that the relative speed of sound in the material, the relative density of the material and the radius of particle significantly affect the condition for the formation of WGM resonance. However, the "more sensitive" parameter is the relative speed of sound.

Generation of Kerr combs centered at 4.5 μm in crystalline microresonators pumped with quantum-cascade lasers.

PubMed

Savchenkov, Anatoliy A; Ilchenko, Vladimir S; Di Teodoro, Fabio; Belden, Paul M; Lotshaw, William T; Matsko, Andrey B; Maleki, Lute

2015-08-01

We report on the generation of mid-infrared Kerr frequency combs in high-finesse CaF2 and MgF2 whispering-gallery-mode resonators pumped with continuous-wave room-temperature quantum cascade lasers. The combs were centered at 4.5 μm, the longest wavelength to date. A frequency comb wider than one half of an octave was demonstrated when approximately 20 mW of pump power was coupled to an MgF2 resonator characterized with quality factor exceeding 10(8).

Ligand-free palladium-mediated site-specific protein labeling inside gram-negative bacterial pathogens.

PubMed

Li, Jie; Lin, Shixian; Wang, Jie; Jia, Shang; Yang, Maiyun; Hao, Ziyang; Zhang, Xiaoyu; Chen, Peng R

2013-05-15

Palladium, a key transition metal in advancing modern organic synthesis, mediates diverse chemical conversions including many carbon-carbon bond formation reactions between organic compounds. However, expanding palladium chemistry for conjugation of biomolecules such as proteins, particularly within their native cellular context, is still in its infancy. Here we report the site-specific protein labeling inside pathogenic Gram-negative bacterial cells via a ligand-free palladium-mediated cross-coupling reaction. Two rationally designed pyrrolysine analogues bearing an aliphatic alkyne or an iodophenyl handle were first encoded in different enteric bacteria, which offered two facial handles for palladium-mediated Sonogashira coupling reaction on proteins within these pathogens. A GFP-based bioorthogonal reaction screening system was then developed, allowing evaluation of both the efficiency and the biocompatibilty of various palladium reagents in promoting protein-small molecule conjugation. The identified simple compound-Pd(NO3)2 exhibited high efficiency and biocompatibility for site-specific labeling of proteins in vitro and inside living E. coli cells. This Pd-mediated protein coupling method was further utilized to label and visualize a Type-III Secretion (T3S) toxin-OspF in Shigella cells. Our strategy may be generally applicable for imaging and tracking various virulence proteins within Gram-negative bacterial pathogens.

Label-Free 3D Visualization of Cellular and Tissue Structures in Intact Muscle with Second and Third Harmonic Generation Microscopy

PubMed Central

Rehberg, Markus; Krombach, Fritz; Pohl, Ulrich; Dietzel, Steffen

2011-01-01

Second and Third Harmonic Generation (SHG and THG) microscopy is based on optical effects which are induced by specific inherent physical properties of a specimen. As a multi-photon laser scanning approach which is not based on fluorescence it combines the advantages of a label-free technique with restriction of signal generation to the focal plane, thus allowing high resolution 3D reconstruction of image volumes without out-of-focus background several hundred micrometers deep into the tissue. While in mammalian soft tissues SHG is mostly restricted to collagen fibers and striated muscle myosin, THG is induced at a large variety of structures, since it is generated at interfaces such as refraction index changes within the focal volume of the excitation laser. Besides, colorants such as hemoglobin can cause resonance enhancement, leading to intense THG signals. We applied SHG and THG microscopy to murine (Mus musculus) muscles, an established model system for physiological research, to investigate their potential for label-free tissue imaging. In addition to collagen fibers and muscle fiber substructure, THG allowed us to visualize blood vessel walls and erythrocytes as well as white blood cells adhering to vessel walls, residing in or moving through the extravascular tissue. Moreover peripheral nerve fibers could be clearly identified. Structure down to the nuclear chromatin distribution was visualized in 3D and with more detail than obtainable by bright field microscopy. To our knowledge, most of these objects have not been visualized previously by THG or any label-free 3D approach. THG allows label-free microscopy with inherent optical sectioning and therefore may offer similar improvements compared to bright field microscopy as does confocal laser scanning microscopy compared to conventional fluorescence microscopy. PMID:22140560

Highly Reproducible Label Free Quantitative Proteomic Analysis of RNA Polymerase Complexes*

PubMed Central

Mosley, Amber L.; Sardiu, Mihaela E.; Pattenden, Samantha G.; Workman, Jerry L.; Florens, Laurence; Washburn, Michael P.

2011-01-01

The use of quantitative proteomics methods to study protein complexes has the potential to provide in-depth information on the abundance of different protein components as well as their modification state in various cellular conditions. To interrogate protein complex quantitation using shotgun proteomic methods, we have focused on the analysis of protein complexes using label-free multidimensional protein identification technology and studied the reproducibility of biological replicates. For these studies, we focused on three highly related and essential multi-protein enzymes, RNA polymerase I, II, and III from Saccharomyces cerevisiae. We found that label-free quantitation using spectral counting is highly reproducible at the protein and peptide level when analyzing RNA polymerase I, II, and III. In addition, we show that peptide sampling does not follow a random sampling model, and we show the need for advanced computational models to predict peptide detection probabilities. In order to address these issues, we used the APEX protocol to model the expected peptide detectability based on whole cell lysate acquired using the same multidimensional protein identification technology analysis used for the protein complexes. Neither method was able to predict the peptide sampling levels that we observed using replicate multidimensional protein identification technology analyses. In addition to the analysis of the RNA polymerase complexes, our analysis provides quantitative information about several RNAP associated proteins including the RNAPII elongation factor complexes DSIF and TFIIF. Our data shows that DSIF and TFIIF are the most highly enriched RNAP accessory factors in Rpb3-TAP purifications and demonstrate our ability to measure low level associated protein abundance across biological replicates. In addition, our quantitative data supports a model in which DSIF and TFIIF interact with RNAPII in a dynamic fashion in agreement with previously published reports. PMID