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.
Anxiety disorders are estimated to be the most common mental illness in US affecting around 40 million people and related job stress is estimated to cost US industry up to $300 billion due to lower productivity and absenteeism. A personal diagnostic device which could help identify stressed individuals would therefore be a huge boost for workforce productivity. We are therefore developing a point of care diagnostic device that can be integrated with smartphones or tablets for the measurement of cortisol - a stress related salivary biomarker, which is known to be strongly involved in body's fight-or-flight response to a stressor (physical or mental). The device is based around a competitive lateral flow assay whose results can then be read and quantified through an accessory compatible with the smartphone. In this presentation, we report the development and results of such an assay and the integrated device. We then present the results of a study relating the diurnal patterns of cortisol levels and the alertness of an individual based on the circadian rhythm and sleep patterns of the individual. We hope to use the insight provided by combining the information provided by levels of stress related to chemical biomarkers of the individual with the physical biomarkers to lead to a better informed and optimized activity schedule for maximized work output.
Vitamin B12 deficiency is the leading cause of cognitive decline in the elderly and is associated with increased risks of several acute and chronic conditions including anemia. The deficiency is prevalent among the world population, most of whom are unaware of their condition due to the lack of a simple diagnostics system. Recent advancements in the smartphone-enabled mobile health can help address this problem by making the deficiency tests more accessible. Previously, our group has demonstrated the NutriPhone, a smartphone platform for the accurate quantification of vitamin D levels. The NutriPhone technology comprises of a disposable test strip that performs a colorimetric reaction upon collecting a sample, a reusable accessory that interfaces with the smartphone camera, and a smartphone app that stores the algorithm for analyzing the test-strip reaction. In this work, we show that the NutriPhone can be expanded to measure vitamin B12 concentrations by developing a lateral flow assay for B12 that is compatible with our NutriPhone system. Our novel vitamin B12 assay incorporates blood sample processing and key reagent storage on-chip, which advances it into a sample-in-answer-out format that is suitable for point-of-care diagnostic applications. In order to enable the detection of pM levels of vitamin B12 levels, silver amplification of the initial signal is used within the total assay time of less than 15 minutes. We demonstrate the effectiveness of our NutriPhone system by deploying it in a resource-limited clinical setting in India where it is used to test tens of participants for vitamin B12 deficiency.
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.
Chemical reactions are often described as a progression along a reaction coordinate. Waveguide evanescent fields
generate an electromagnetic force that spans tens of nanometers and have been used previously to trap protein
molecules. Applying this force along a reaction coordinate could radically alter the chemical reaction by modifying the
activation energy or biasing the reaction towards a specific pathway. Here, we show that the adsorption of proteins onto
carbon nanotubes can be controlled with opto-mechanical forces. An analytic model for the reaction was developed, the
predictions of which were explored by probing the energy barrier under various experimental conditions.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.