Image formation from a concave mirror.

Computing locations and extent of images, except in the most trivial configurations or special cases, is a complex task. Even rays emanating from a point source and passing through an optical system generally fail to converge at a single image point, highlighting the care needed to establish image locations. We use three approaches to study image formation in a simple configuration, that of a point source following reflection from a spherical concave mirror. We calculate the caustic surfaces, compute cross sections of flux densities on image surfaces, and compare the results with experimentally generated light intensity fields. One of the two caustic surfaces is one dimensional while the other forms a surface. The latter undergoes a metamorphosis from a distorted cone to an open surface as the source is moved away from the axis. Cross sections of the caustic surfaces with an image plane are found to coincide with peaks in the flux density. Experimental studies validate these conclusions.

Imaging in reflecting spheres.

We study the formation of images in a reflective sphere in three configurations using caustics on the field of light rays. The optical wavefront emerging from a source point reaching a subject following passage through the optical system is, in general, a Gaussian surface with partial focus along the two principal directions of the Gaussian surface; i.e., there are two images of the source point, each with partial focus. As the source point moves, the images move on two surfaces, referred to as viewable surfaces. In our systems, one viewable surface consists of points with radial focus and the other consists of points with azimuthal focus. The problems we study are (1) imaging of a parallel beam of light, (2) imaging of the infinite viewed from a location outside the sphere, and (3) imaging of a planar object viewed through the point of its intersection with the radial line normal to the plane. We verify the existence of two images experimentally and show that the distance between them agrees with the computations.

Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination.

Accurate medical recordkeeping is a major challenge in many low-resource settings where well-maintained centralized databases do not exist, contributing to 1.5 million vaccine-preventable deaths annually. Here, we present an approach to encode medical history on a patient using the spatial distribution of biocompatible, near-infrared quantum dots (NIR QDs) in the dermis. QDs are invisible to the naked eye yet detectable when exposed to NIR light. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. The formulation showing the greatest resistance to photobleaching after simulated sunlight exposure (5-year equivalence) through pigmented human skin was encapsulated in microparticles for use in vivo. In parallel, microneedle geometry was optimized in silico and validated ex vivo using porcine and synthetic human skin. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.

A heat-stable microparticle platform for oral micronutrient delivery.

Micronutrient deficiencies affect up to 2 billion people and are the leading cause of cognitive and physical disorders in the developing world. Food fortification is effective in treating micronutrient deficiencies; however, its global implementation has been limited by technical challenges in maintaining micronutrient stability during cooking and storage. We hypothesized that polymer-based encapsulation could address this and facilitate micronutrient absorption. We identified poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate) (1:2:1) (BMC) as a material with proven safety, offering stability in boiling water, rapid dissolution in gastric acid, and the ability to encapsulate distinct micronutrients. We encapsulated 11 micronutrients (iron; iodine; zinc; and vitamins A, B2, niacin, biotin, folic acid, B12, C, and D) and co-encapsulated up to 4 micronutrients. Encapsulation improved micronutrient stability against heat, light, moisture, and oxidation. Rodent studies confirmed rapid micronutrient release in the stomach and intestinal absorption. Bioavailability of iron from microparticles, compared to free iron, was lower in an initial human study. An organotypic human intestinal model revealed that increased iron loading and decreased polymer content would improve absorption. Using process development approaches capable of kilogram-scale synthesis, we increased iron loading more than 30-fold. Scaled batches tested in a follow-up human study exhibited up to 89% relative iron bioavailability compared to free iron. Collectively, these studies describe a broad approach for clinical translation of a heat-stable ingestible micronutrient delivery platform with the potential to improve micronutrient deficiency in the developing world. These approaches could potentially be applied toward clinical translation of other materials, such as natural polymers, for encapsulation and oral delivery of micronutrients.

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals.

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

Multiplexed neural recording along a single optical fiber via optical reflectometry.

We introduce the design and theoretical analysis of a fiber-optic architecture for neural recording without contrast agents, which transduces neural electrical signals into a multiplexed optical readout. Our sensor design is inspired by electro-optic modulators, which modulate the refractive index of a waveguide by applying a voltage across an electro-optic core material. We estimate that this design would allow recording of the activities of individual neurons located at points along a 10-cm length of optical fiber with 40-µm axial resolution and sensitivity down to 100 µV using commercially available optical reflectometers as readout devices. Neural recording sites detect a potential difference against a reference and apply this potential to a capacitor. The waveguide serves as one of the plates of the capacitor, so charge accumulation across the capacitor results in an optical effect. A key concept of the design is that the sensitivity can be improved by increasing the capacitance. To maximize the capacitance, we utilize a microscopic layer of material with high relative permittivity. If suitable materials can be found­possessing high capacitance per unit area as well as favorable properties with respect to toxicity, optical attenuation, ohmic junctions, and surface capacitance­then such sensing fibers could, in principle, be scaled down to few-micron cross-sections for minimally invasive neural interfacing. We study these material requirements and propose potential material choices. Custom-designed multimaterial optical fibers, probed using a reflectometric readout, may, therefore, provide a powerful platform for neural sensing.

Global and Arctic climate engineering: numerical model studies.

We perform numerical simulations of the atmosphere, sea ice and upper ocean to examine possible effects of diminishing incoming solar radiation, insolation, on the climate system. We simulate both global and Arctic climate engineering in idealized scenarios in which insolation is diminished above the top of the atmosphere. We consider the Arctic scenarios because climate change is manifesting most strongly there. Our results indicate that, while such simple insolation modulation is unlikely to perfectly reverse the effects of greenhouse gas warming, over a broad range of measures considering both temperature and water, an engineered high CO2 climate can be made much more similar to the low CO2 climate than would be a high CO2 climate in the absence of such engineering. At high latitudes, there is less sunlight deflected per unit albedo change but climate system feedbacks operate more powerfully there. These two effects largely cancel each other, making the global mean temperature response per unit top-of-atmosphere albedo change relatively insensitive to latitude. Implementing insolation modulation appears to be feasible.

Determining selected quadratic coefficients in noncentrosymmetric crystals.

We present a systematic theoretical examination concerning the practical possibility of measuring components of the quadratic symmetry tensors for solid materials lacking inversion symmetry. We show that information concerning the quadratic effects in noncentrosymmetrical crystals can be obtained directly by methods that allow for the bypassing of the coexisting dominant linear effects. Here, we deal only with the particular case of the electro-optic effect; however, the results and conclusions are also valid for the elasto-optic effects.

Time-resolved optical transients in tetragonal BaTiO3.

We present and analyze the room temperature (T= 23.5 degrees C) time behavior of the transmitted intensities of polarized light passing through an unclamped (100)-type single crystal of barium titanate (BaTiO3) when subject to a time-dependent, externally applied electric field. To the authors' knowledge, this is the first reported observation and analysis of such time-resolved optical transients. According to a previous [J. Opt. Soc. Am. A 22, 377 (2005)] observation by the authors, this original optical technique can, in principle, be used on 18 out of 20 noncentrosymmetric crystal point groups where the first-order (Pockels) and second-order (Kerr) electrooptic effects coexist. Because of its nondestructive nature, this novel optical method would be a useful tool in other fields of condensed-matter physics in which time-behavior observation and characterization of certain physical parameters of crystals are important.

Method for measuring off-diagonal Kerr coefficients by using polarized light transmission.

We report a method for measuring the off-diagonal coefficients of the quadratic electro-optic (Kerr) tensor by using polarized light transmission. The method relies on designing an experimental configuration in which the linear electro-optic (Pockels) effect does not contribute to the data. Our method can be used to obtain off-diagonal Kerr coefficients for all but two of the 20 crystal point groups for which the Pockels effect and the Kerr effect coexist. Our theoretical model includes effects from transmission, multiple reflections, and electrostriction but neglects absorption in the crystal. To verify the method, we used it to measure the R12 and R13 Kerr coefficients for a (100)-type single crystal of ferroelectric barium titanate (BaTiO3) at room temperature (23.5 degrees). To our knowledge, this is the first time this method has been used and the first time these coefficients have been measured for the unclamped crystal in the tetragonal state. The mean values obtained with this method are R12 = -3.5+/-0.3 x 10(-17) m2/V2 and R13 = -8.0+/-0.7 x 10(-17) m2/V2.

Fraunhofer diffraction to determine the twin angle in single-crystal BaTiO3.

We present a new method for determining the electrically induced twin angle alpha of a (100) bulk single crystal of barium titanate (BaTiO3) using a nondestructive optical technique based on Fraunhofer diffraction. The technique required two steps that were performed simultaneously. First, we analyzed the diffracted light intensity captured with a line camera. Second, we measured the size of the diffracting element by analyzing images of crystal's surface taken with a CCD camera. The value obtained for the twin angle is 0.67 degrees +/- 0.05 degrees, which compares favorably with the theoretical value of 0.63 degrees.

Action from tunable periodic structures. II. Experimental observation of electric field-induced diffraction peaks.

As previously predicted [Appl. Opt. 40, 5583 (2001)], we have now observed electric field-induced diffraction peaks in transmission and reflection experiments by use of a LiNbO3 sample with interdigital planar electrodes that serve as a diffraction grating. The magnitudes of the new peaks in the reflection experiments are ten times larger than those in the transmission experiments. We interpret these effects in terms of a field-induced refractive-index change produced by the linear electro-optic effect. The positive and negative changes in the refractive index produce two diffraction gratings that are period doubled with respect to the original grating and that have a phase difference between them. The superposition of the diffracted light from these gratings is shown to account for the new peaks. From the relative magnitude of the new peak to that of the central peak, we estimate the refractive-index change to be 0.004.