Perry Schein

Nanophotonic detection of freely interacting molecules on a single influenza virus

Biomolecular interactions, such as antibody-antigen binding, are fundamental to many biological processes. At present, most techniques for analyzing these interactions require immobilizing one or both of the interacting molecules on an assay plate or a sensor surface. This is convenient experimentally but can constrain the natural binding affinity and capacity of the molecules, resulting in data that can deviate from the natural free-solution behavior. Here we demonstrate a label-free method for analyzing free-solution interactions between a single influenza virus and specific antibodies at the single particle level using near-field optical trapping and light-scattering techniques. We determine the number of specific antibodies binding to an optically trapped influenza virus by analyzing the change of the Brownian fluctuations of the virus. We develop an analytical model that determines the increased size of the virus resulting from antibodies binding to the virus membrane with uncertainty of ±1–2 nm. We present stoichiometric results of 26 ± 4 (6.8 ± 1.1 attogram) anti-influenza antibodies binding to an H1N1 influenza virus. Our technique can be applied to a wide range of molecular interactions because the nanophotonic tweezer can handle molecules from tens to thousands of nanometers in diameter.

Nanophotonic Force Microscopy: Characterizing Particle–Surface Interactions Using Near-Field Photonics

Direct measurements of particle-surface interactions are important for characterizing the stability and behavior of colloidal and nanoparticle suspensions. Current techniques are limited in their ability to measure pico-Newton scale interaction forces on submicrometer particles due to signal detection limits and thermal noise. Here we present a new technique for making measurements in this regime, which we refer to as nanophotonic force microscopy. Using a photonic crystal resonator, we generate a strongly localized region of exponentially decaying, near-field light that allows us to confine small particles close to a surface. From the statistical distribution of the light intensity scattered by the particle we are able to map out the potential well of the trap and directly quantify the repulsive force between the nanoparticle and the surface. As shown in this Letter, our technique is not limited by thermal noise, and therefore, we are able to resolve interaction forces smaller than 1 pN on dielectric particles as small as 100 nm in diameter.

Near-Field Light Scattering Techniques for Measuring Nanoparticle-Surface Interaction Energies and Forces

Nanoparticles are quickly becoming commonplace in many commercial and industrial products, ranging from cosmetics to pharmaceuticals to medical diagnostics. Predicting the stability of the engineered nanoparticles within these products a priori remains an important and difficult challenge. Here, we describe our techniques for measuring the mechanical interactions between nanoparticles and surfaces using near-field light scattering. Particle-surface interfacial forces are measured by optically “pushing” a particle against a reference surface and observing its motion using scattered near-field light. Unlike atomic force microscopy, this technique is not limited by the thermal noise, but instead takes advantage of it. The integrated waveguide and microfluidic architecture allow for high-throughput measurements of about 1000 particles/h. We characterize the reproducibility of and experimental uncertainty in the measurements made using the NanoTweezer surface instrument. We report surface interaction studies on gold nanoparticles with 50 nm diameters, smaller than previously reported in the literature using similar techniques.

Nutrilyzer: A Mobile System for Characterizing Liquid Food with Photoacoustic Effect

In this paper, we propose Nutrilyzer, a novel mobile sensing system for characterizing the nutrients and detecting adulterants in liquid food with the photoacoustic effect. By listening to the sound of the intensity modulated light or electromagnetic wave with different wavelengths, our mobile photoacoustic sensing system captures unique spectra produced by the transmitted and scattered light while passing through various liquid food. As different liquid foods with different chemical compositions yield uniquely different spectral signatures, Nutrilyzers signal processing and machine learning algorithm learn to map the photoacoustic signature to various liquid food characteristics including nutrients and adulterants. We evaluated Nutrilyzer for milk nutrient prediction (i.e., milk protein) and milk adulterant detection. We have also explored Nutrilyzer for alcohol concentration prediction. The Nutrilyzer mobile system consists of an array of 16 LEDs in ultraviolet, visible and near-infrared region, two piezoelectric sensors and an ARM microcontroller unit, which are designed and fabricated in a printed circuit board and a 3D printed photoacoustic housing.

Simultaneous Characterization of Nanoparticle Size and Particle-Surface Interactions with Three-Dimensional Nanophotonic Force Microscopy

The behavior of a nanoparticle in solution depends strongly on the particles physical and chemical characteristics, most notably the particle size and the surface properties. Accurately characterizing these properties is critical for quality control in a wide variety of industries. To understand a complex and polydisperse nanoparticle suspension, however, ensemble averaging is not sufficient, and there is a great need for direct measurements of size and surface properties at the individual nanoparticle level. In this work, we present an analysis technique for simultaneous characterization of particle-surface interactions and size using near-field light scattering and verify it using Brownian-dynamics simulations. Using a nanophotonic waveguide, single particles can be stably held near the waveguides surface by strongly localized optical forces. By tracking the dynamic 3D motion of the particle under the influence of these forces using an optical microscope, it is possible to extract the particle-surface interaction forces, as well as to estimate the size and refractive index of the nanoparticle. Because of the strong light-scattering signal, this method is viable for high-throughput characterization of particles as small as 100 nm in only a few seconds each.

Dynamics of an optically confined nanoparticle diffusing normal to a surface.

Here we measure the hindered diffusion of an optically confined nanoparticle in the direction normal to a surface, and we use this to determine the particle-surface interaction profile in terms of the absolute height. These studies are performed using the evanescent field of an optically excited single-mode silicon nitride waveguide, where the particle is confined in a height-dependent potential energy well generated from the balance of optical gradient and surface forces. Using a high-speed cmos camera, we demonstrate the ability to capture the short time-scale diffusion dominated motion for 800-nm-diam polystyrene particles, with measurement times of only a few seconds per particle. Using established theory, we show how this information can be used to estimate the equilibrium separation of the particle from the surface. As this measurement can be made simultaneously with equilibrium statistical mechanical measurements of the particle-surface interaction energy landscape, we demonstrate the ability to determine these in terms of the absolute rather than relative separation height. This enables the comparison of potential energy landscapes of particle-surface interactions measured under different experimental conditions, enhancing the utility of this technique.

Measurement of nanoparticle size, suspension polydispersity, and stability using near-field optical trapping and light scattering (Conference Presentation)

Nanoparticles are becoming ubiquitous in applications including diagnostic assays, drug delivery and therapeutics. However, there remain challenges in the quality control of these products. Here we present methods for the orthogonal measurement of these parameters by tracking the motion of the nanoparticle in all three special dimensions as it interacts with an optical waveguide. These simultaneous measurements from a single particle basis address some of the gaps left by current measurement technologies such as nanoparticle tracking analysis, ζ-potential measurements, and absorption spectroscopy. As nanoparticles suspended in a microfluidic channel interact with the evanescent field of an optical waveguide, they experience forces and resulting motion in three dimensions: along the propagation axis of the waveguide (x-direction) they are propelled by the optical forces, parallel to the plane of the waveguide and perpendicular to the optical propagation axis (y-direction) they experience an optical gradient force generated from the waveguide mode profile which confines them in a harmonic potential well, and normal to the surface of the waveguide they experience an exponential downward optical force balanced by the surface interactions that confines the particle in an asymmetric well. Building on our Nanophotonic Force Microscopy technique, in this talk we will explain how to simultaneously use the motion in the y-direction to estimate the size of the particle, the comparative velocity in the x-direction to measure the polydispersity of a particle population, and the motion in the z-direction to measure the potential energy landscape of the interaction, providing insight into the colloidal stability.

Optofluidic reactors for reverse combustion photocatalytic production of hydrocarbons (Conference Presentation)

In combustion, hydrocarbon fuels are burned with oxygen to release energy, carbon dioxide and water vapor. Here, we introduce a photocatalytic reactor for reversing this process, when carbon dioxide and water are combined and using optical and thermal energy from the sun hydrocarbons are produced and oxygen is released. This allows for the sustainable production of hydrocarbon products from non-fossil sources, allowing for the development of “green” hydrocarbon products. Our reactors take the form of modular cells of 10 x 10 x 10 cm scale where light is delivered to nanostructured catalysts through the evanescent field around dielectric slab waveguides. The light distribution is optimized through the use of engineered scattering sites to enhance field uniformity. This is combined with integrated fluidic architecture to deliver a stream rich in water and carbon dioxide (such as exhaust from a natural gas burning plant) to the nanostructured catalyst particles in a narrow channel. Exhaust streams rich in oxygen and hydrocarbon products are collected at the outlet of the reactor cell. The cell is heated using solar thermal energy and temperatures of up to 200°C are achieved, enhancing reaction efficiency. Hydrocarbon products produced include methanol as well as other potentially useful molecules for fuel production or precursors to the manufacture of plastics. These reactors can be coupled to solar collectors to take advantage of the sun as a free source of heat and light, and the modular nature of the cells enables scaling to larger deployments.

An integrated platform for assessing biologics(Conference Presentation)

Protein therapeutics are a rapidly growing portion of the pharmaceuticals market and have many significant advantages over traditional small molecule drugs. As this market expands, however, critical regulatory and quality control issues remain, most notably the problem of protein aggregation. Individual target proteins often aggregate into larger masses which trigger an immune response in the body, which can reduce the efficacy of the drug for its intended purpose, or cause serious anaphylactic side-effects. Although detecting and minimizing aggregate formation is critical to ensure an effective product, aggregation dynamics are often highly complicated and there is little hope of reliable prediction and prevention from first principles. This problem is compounded for aggregates in the subvisible range of 100 nm to 10 micrometers where traditional techniques for detecting aggregates have significant limitations. Here, we present an integrated optofluidic platform for detecting nanoscale protein aggregates and characterizing interactions between these aggregates and a reference surface. By delivering light to a solution of proteins with an optical waveguide, scattered light from individual protein aggregates can be detected and analyzed to determine the force profile between each particle and the waveguide surface. Unlike existing methods which only determine size or charge, our label-free screening technique can directly measure the surface interaction forces between single aggregates and the glass substrate. This direct measurement capability may allow for better empirical predictions of the stability of protein aggregates during drug manufacturing and storage.

Direct measurement of nanoparticle interactions using near-field photonics(Conference Presentation)

Nanoparticle suspensions are used in numerous biomedical applications ranging from sensing and diagnostics to in vivo therapeutic agents and drug delivery mechanisms. One key challenge in developing these technologies is engineering particles that remain stable in the presence of physiological salt concentrations and different pH regimes encountered in applications. Here, we show an approach for high-throughput characterization of nanoparticle stability by directly measuring the interaction energy profiles between nanoparticles and surfaces. As nanoparticles are trapped and propelled along an optical waveguide, they scatter light. Our technique takes advantage of the confined Brownian motion exhibited by the particles as they fluctuate about the equilibrium position between the optical and particle-surface interaction forces. In this way, unlike colloidal probe atomic force microscopy, this technique is capable of making measurements that are not limited by thermal noise, and capable of mapping interaction energy profiles on the sub-kT scale, driven by sub-pN forces. We demonstrate direct measurement of the interactions between protein-coated gold nanoparticles with 50 nm diameters and surfaces in a variety of experimental conditions including changes in specific ions present, overall ionic strength and pH, giving insight into the dynamics of these biologically relevant systems at the nanoscale. These direct measurements on particles with sub-100 nm diameters offer new insights into suspension stability missed by indirect measurements such as absorbance spectroscopy, zeta-potential, and dynamic light scattering, and allow for the detailed study of sub-populations in a heterogeneous sample. Additionally, the sub-pN force resolution makes this a suitable platform for fundamental biophysical studies.