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Whispering Gallery Mode (WGM) resonators demonstrate nearfield interactions that sensitively shift resonance frequencies with interaction lengths less than 200 nm. This range is ideal for observing the effect that double layers have on the motion of protein, virus, and artificial nanoparticles. In exploring the measurement possibilities we were immediately drawn to the opportunity for determining physical parameters that have not revealed themselves through microcavity experiments in the past. The first example of this general interest is the measurement of charge. Charge significantly influences the binding of virus and other nano-particles to microcavity bio-sensors, although surprisingly there have been no reports of the determination of either cavity charge density σw or nanoparticle charge qp using these sensors. In this paper we review our recent progress in experimentally demonstrating an approach for the determination of both. We use an opto-mechanical Whispering Gallery Mode (WGM) Carousel trap to extract the electrostatic interaction energy versus separation s between the cavity surface and an orbiting nanoparticle of know charge, from WGM frequency fluctuations induced by the particle. Next we fit this interaction energy to wall-colloid theory (first Debye-Hückel, and then Gouy-Chapman theory) and determine σw. This charge density on a just-prepared silica microsphere is far less than literature values. With this microcavity charge density in hand, a larger particle having unknown charge and orbiting the same microcavity has its charge measured from its associated electrostatic interaction energy. This charge is in agreement with independent measurements.
Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle–cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethyl-substituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine–silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33–45 nm. Surface charge of carboxymethyl-substituted dextran-coated nanoparticles ranged from −50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle–cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions.
We demonstrate a highly sensitive nanoparticle and virus detection method by using a thermal-stabilized reference interferometer in conjunction with an ultrahigh-Q microcavity. Sensitivity is sufficient to resolve shifts caused by binding of individual nanobeads in solution down to a record radius of 12.5 nm, a size approaching that of single protein molecules. A histogram of wavelength shift versus nanoparticle radius shows that particle size can be inferred from shift maxima. Additionally, the signal-to-noise ratio for detection of Influenza A virus is enhanced to 381 from the previously reported 31. The method does not use feedback stabilization of the probe laser. It is also observed that the conjunction of particle-induced backscatter and optical-path-induced shifts can be used to enhance detection signal-to-noise.
Due to double-layer forces a charged colloid suspended in an electrolyte is repelled from a like-charged planar wall. We demonstrate that and how a precise measurement of these double-layer forces acting on a colloid near a glass surface can be used to determine surface charge densities. The effective wallcolloid potentials are measured using the total internal reflection microscopy technique, and a whole series of such potentials, taken for various different salt concentrations, are then analysed in terms of a given theoretical interaction potential, where the surface charge densities are the only unknown parameters. We find reasonable values for the surface charge densities of silica and polystyrene spheres in water, and compare the proposed method with other more established techniques to measure surface charge densities on single particles.
Individual nanoparticles in aqueous solution are observed to be attracted to and orbit within the evanescent sensing ring of a Whispering Gallery Mode micro-sensor with only microwatts of driving power. This Carousel trap, caused by attractive optical gradient forces, interfacial interactions, and the circulating momentum flux, considerably enhances the rate of transport to the sensing region, thereby overcoming limitations posed by diffusion on such small area detectors. Resonance frequency fluctuations, caused by the radial Brownian motion of the nanoparticle, reveal the radial trapping potential and the nanoparticle size. Since the attractive forces draw particles to the highest evanescent intensity at the surface, binding steps are found to be uniform.
We report the label-free, real-time optical detection of Influenza A virus particles. Binding of single virions is observed from discrete changes in the resonance frequency/wavelength of a whispering-gallery mode excited in a microspherical cavity. We find that the magnitude of the discrete wavelength-shift signal can be sufficiently enhanced by reducing the microsphere size. A reactive sensing mechanism with inverse dependence on mode volume is confirmed in experiments with virus-sized polystyrene nanoparticles. By comparing the electromagnetic theory for this reactive effect with experiments, the size and mass ( approximately 5.2 x 10(-16) g) of a bound virion are determined directly from the optimal resonance shift.
Biosensors based on the shift of whispering-gallery modes in microspheres accompanying protein adsorption are described by use of a perturbation theory. For random spatial adsorption, theory predicts that the shift should be inversely proportional to microsphere radius R and proportional to protein surface density and excess polarizability. Measurements are found to be consistent with the theory, and the correspondence enables the average surface area occupied by a single protein to be estimated. These results are consistent with crystallographic data for bovine serum albumin. The theoretical shift for adsorption of a single protein is found to be extremely sensitive to the target region, with adsorption in the most sensitive region varying as 1/R(5/2). Specific parameters for single protein or virus particle detection are predicted.
The authors present an approach for specific and rapid unlabeled detection of a virus by using a microsphere-based whispering gallery mode sensor that transduces the interaction of a whole virus with an anchored antibody. They show theoretically that this sensor can detect a single virion below the mass of HIV. A micro-fluidic device is presented that enables the discrimination between viruses of similar size and shape.
Charge influences the binding of virus and other nano-particles to microcavity bio-sensors, although surprisingly there have been no reports of the determination of either cavity charge density σw or nanoparticle charge qp using these sensors. In this letter, we experimentally demonstrate an approach for the determination of both. We use an opto-mechanical Whispering Gallery Mode (WGM) Carousel trap to extract the electrostatic interaction energy versus separation s between the cavity surface and a nanoparticle from WGM frequency fluctuations induced by the orbiting particle. Next, we fit this interaction energy to linearized wall-colloid theory (Debye-Hückel theory) for a particle whose charge is known and determine σw. With this microcavity charge density in hand, a larger particle having unknown charge and orbiting the same microcavity has its charge measured from its associated electrostatic interaction energy. This charge is found to be smaller by 10% when compared to results from independent zeta potential measurements and outside of one standard deviation. However, non-linear Gouy-Chapman theory when applied to our measured data arrives at a charge that overlaps zeta potential measurements. Our method is non-destructive, enabling the same particle to be passed on for further characterization.
Interactions between whispering gallery modes (WGMs) and small nanoparticles are commonly modelled by treating the particle as a point dipole scatterer. This approach is assumed to be accurate as long as the nanoparticle radius, $a$, is small compared to the WGM wavelength $\lambda$. In this article, however, we show that the large field gradients associated with the evanescent decay of a WGM causes the dipole theory to significantly underestimate the interaction strength, and hence induced WGM resonance shift, even for particles as small as $a\sim \lambda/10$. To mitigate this issue we employ a renormalized Born approximation to more accurately determine nanoparticle induced resonance shifts and hence enable improved particle sizing. The domain of validity of this approximation is investigated and supporting experimental results are presented.
Measuring the charge of a nanoparticle is of great importance in many fields including optics, astronomy, biochemistry, atmospheric science, environmental engineering, and dusty plasma. Here, we propose to use a high-Q whispering-gallery-mode (WGM) optical microresonator to detect the surface and bulk charge of a dielectric nanoparticle. Because of the modification of nanoparticle conductivity induced by the surplus electrons, both the coupling strength between the nanoparticle and the WGM and the dissipation changes compared with the case of a neutral nanoparticle. The charge density can be inferred from the transmission spectrum of the WGM microresonator. By monitoring the mode splitting, the linewidth broadening or the resonance dip value of the transmission spectrum, surface (bulk) electron density as low as 0.007 nm−2 (0.001 nm−3) can be detected for nanoparticles with negative (positive) electron affinity. The high sensitivity is attributed to the ultranarrow resonance linewidth and small mode volume of the microresonator.
We have devised a simple means for determining the size of a nanoparticle in one binding event (i.e., real time) by utilizing two polar modes of a slightly eccentric Whispering Gallery Mode (WGM) spheroidal resonator. The ratio of shifts of these modes locates the absolute latitude angle at which a nano-particle binds. From this location, the size of the nanoparticle is calculated using the reactive sensing principle. Although our latitude-only micro-global positioning scheme is applied to nanoparticle sizing using slightly eccentric spheroids in aqueous solution, this approach can be applied to WGM micro-resonators having a variety of shapes. (C) 2014 AIP Publishing LLC.
The transfer of energy between neighboring molecules plays a pivotal role in nature. In photosynthesis, for example, a plant fuels its metabolism and growth with sunlight by taking advantage of a curious physical phenomenon that allows energy to hop from one chlorophyll molecule to another situated about a half a nonometer away. A couple of hundred chlorophyll molecules pass the energy they collect from the sum in this way to a single reaction center, the starting point for subsequent chemical reactions. Without this mechanism for transfering energy between molecules, photosynthesis would largely cease, and we would likely starve. About 15 years ago I began to wonder whether similar forms of energy transfer could influence photochemistry within aerosol particles. In particular, I wanted to know whether there are subtleties in the way energy is conveyed between molecules in an isolated droplet about 10 micrometers in diameter. To most physicists, the idea must have seemed crazy. After all, the range of the longest substantial exchange of this sort, as Nobelist Jean Perrin had discovered and Theodore Förster had described in quantummechanical terms decades ago, is only about 5 nonometers. The vessels I was proposing to use would be 2,000 times larger. So there was no obvious reason to expect that their tiny size would have any influence at all. Still, research elsewhere with similar microscopic particles hinted of interesting physical effects, and I urged one of my graduate students, Lorcan Folan, to investigate. Little did I know that the results we and other were soon to obtain would distinguish the lowly aerosol particle as a high-tech item. Such microscopic particles now stand poised to serve in a variety of ways, from lasers of exceptional efficiency to optical filters of unprecedented purity and chemical probes of tiny size-to name just few obvious applications.But before delving into how tiny spheres can provided such valuable functions, it is worthwhile to review how this rapidly evolving creature of 21st-century technology first arose from a primordial soup of basic research.
The present work studies a surface concentration of hydroxyl groups for a large number of amorphous silicas, viz., silica gels, aerosilogels, and porous glasses, differing in production conditions, surface area, and pore size distribution. It is shown that the surface density of OH groups (the silanol number) is a physicochemical constant for a fully hydroxylated surface and that the density as a function of temperature of vacuum treatment does not depend in a significant way on the type of silica.
The charge density of the particles in the commercial silica sol "Ludox" was determined as a function of the pH. A new technique was developed for this purpose, which allows the continuous measurement of the adsorption isotherm of the potential determining ion, without interference of a suspension effect. It was shown that the results obtained by means of this technique are consistent with certain theoretical expectations.
A review article is presented of the research results obtained by the author on the properties of amorphous silica surface. It has been shown that in any description of the surface silica the hydroxylation of the surface is of critical importance. An analysis was made of the processes of dehydration (the removal of physically adsorbed water), dehydroxylation (the removal of silanol groups from the silica surface), and rehydroxylation (the restoration of the hydroxyl covering). For each of these processes a probable mechanism is suggested. The results of experimental and theoretical studies permitted to construct the original model (Zhuravlev model-1 and model-2) for describing the surface chemistry of amorphous silica. The main advantage of this physico-chemical model lies in the possibility to determine the concentration and the distribution of different types of silanol and siloxane groups and to characterize the energetic heterogeneity of the silica surface as a function of the pretreatment temperature of SiO2 samples. The model makes it possible to determine the kind of the chemisorption of water (rapid, weakly activated or slow, strongly activated) under the restoration of the hydroxyl covering and also to assess of OH groups inside the SiO2 skeleton. The magnitude of the silanol number, that is, the number of OH groups per unit surface area, αOH, when the surface is hydroxylated to the maximum degree, is considered to be a physico-chemical constant. This constant has a numerical value: αOH,AVER=4.6 (least-squares method) and αOH,AVER=4.9 OH nm−2 (arithmetical mean) and is known in literature as the Kiselev–Zhuravlev constant. It has been established that adsorption and other surface properties per unit surface area of silica are identical (except for very fine pores). On the basis of data published in the literature, this model has been found to be useful in solving various applied and theoretical problems in the field of adsorption, catalysis, chromatography, chemical modification, etc. It has been shown that the Brunauer–Emmett–Teller (BET) method is the correct method and gives the opportunity to measure the real physical magnitude of the specific surface area, SKr (by using low temperature adsorption of krypton), for silicas and other oxide dispersed solids.
In the past few years optical ring resonators have emerged as a new sensing technology for highly sensitive detection of analytes in liquid or gas. This article introduces the ring resonator sensing principle, describes various ring resonator sensor designs, reviews the current state of the field, and presents an outlook of possible applications and related research and development directions.
To elucidate the effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles (NPs), rhodamine B (RhB) labeled carboxymethyl chitosan grafted NPs (RhB-CMCNP) and chitosan hydrochloride grafted NPs (RhB-CHNP) were developed as the model negatively and positively charged polymeric NPs, respectively. These NPs owned well defined particle sizes (150-500 nm) and Zeta potentials (-40 mV - +35 mV). FITC labeled protamine sulfate (FITC-PS) loaded RhB-CMCNP and camptothecin (CPT) loaded RhB-CHNP with high encapsulation efficiency were prepared. The fluorescence stability in plasma and towards I(-) was investigated, and the result indicated it was sufficient for qualitative and quantitative analysis. NPs with high surface charge and large particle size were phagocytized more efficiently by murine macrophage. Slight particle size and surface charge differences and different cell lines had significant implications in the cellular uptake of NPs, and various mechanisms were involved in the uptake process. In vivo biodistribution suggested that NPs with slight negative charges and particle size of 150 nm were tended to accumulate in tumor more efficiently. These results could serve as a guideline in the rational design of drug nanocarriers with maximized therapeutic efficacy and predictable in vivo properties, in which the control of particle size and surface charge was of significance.
Morphology-dependent resonances (MDR's) of solid microspheres are excited by using an optical fiber coupler. The narrowest measured MDR linewidths are limited by the excitation laser linewidth (<0.025 nm). Only MDR's, with an on-resonance to off-resonance intensity ratio of 10(4), contribute to scattering. The intensity of various resonance orders is understood by the localization principle and the recently developed generalized Lorentz-Mie theory. The microsphere fiber system has potential for becoming a building block in dispersive microphotonics. The basic physics underlying our approach may be considered a harbinger for the coupling of active photonic microstructures such as microdisk lasers.
An optical method is presented that allows simultaneous determination of the diffusion constant and electrophoretic mobility of individual charged particles with radius down to 0.2 mum. By this method the size dependency of the effective charges and zeta potentials of individual particles can be investigated, as well as interparticle interactions and Brownian motion in confined geometries. The diffusion constant and mobility are determined from the power spectrum of the particle speed in a sinusoidal electrical field. The accuracy of the method was tested on PMMA spheres of known size in water. Experiments have been carried out on charged pigment particles with low concentration in a nonaqueous medium containing a charging agent. The mobility is found to be independent of the particle size.
Whispering gallery mode single nanoparticle detection and sizing: the validity of the dipole approximation