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.
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.
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.
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.
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