Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections.

PURPOSE: To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. DESIGN: Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). PARTICIPANTS: Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. METHODS: A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. MAIN OUTCOME MEASURES: We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. RESULTS: A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). CONCLUSIONS: Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.

A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene.

In search of the molecular identities of cold-sensing receptors, we carried out an unbiased genetic screen for cold-sensing mutants in C. elegans and isolated a mutant allele of glr-3 gene that encodes a kainate-type glutamate receptor. While glutamate receptors are best known to transmit chemical synaptic signals in the CNS, we show that GLR-3 senses cold in the peripheral sensory neuron ASER to trigger cold-avoidance behavior. GLR-3 transmits cold signals via G protein signaling independently of its glutamate-gated channel function, suggesting GLR-3 as a metabotropic cold receptor. The vertebrate GLR-3 homolog GluK2 from zebrafish, mouse, and human can all function as a cold receptor in heterologous systems. Mouse DRG sensory neurons express GluK2, and GluK2 knockdown in these neurons suppresses their sensitivity to cold but not cool temperatures. Our study identifies an evolutionarily conserved cold receptor, revealing that a central chemical receptor unexpectedly functions as a thermal receptor in the periphery.

High thermal conductivity in electrostatically engineered amorphous polymers.

High thermal conductivity is critical for many applications of polymers (for example, packaging of light-emitting diodes), in which heat must be dissipated efficiently to maintain the functionality and reliability of a system. Whereas uniaxially extended chain morphology has been shown to significantly enhance thermal conductivity in individual polymer chains and fibers, bulk polymers with coiled and entangled chains have low thermal conductivities (0.1 to 0.4 W m-1 K-1). We demonstrate that systematic ionization of a weak anionic polyelectrolyte, polyacrylic acid (PAA), resulting in extended and stiffened polymer chains with superior packing, can significantly enhance its thermal conductivity. Cross-plane thermal conductivity in spin-cast amorphous films steadily grows with PAA degree of ionization, reaching up to ~1.2 W m-1 K-1, which is on par with that of glass and about six times higher than that of most amorphous polymers, suggesting a new unexplored molecular engineering strategy to achieve high thermal conductivities in amorphous bulk polymers.

Thermal Conductance in Cross-linked Polymers: Effects of Non-Bonding Interactions.

Weak interchain interactions have been considered to be a bottleneck for heat transfer in polymers, while covalent bonds are believed to give a high thermal conductivity to polymer chains. For this reason, cross-linkers have been explored as a means to enhance polymer thermal conductivity; however, results have been inconsistent. Some studies show an enhancement in the thermal conductivity for polymers upon cross-linking, while others show the opposite trend. In this work we study the mechanisms of heat transfer in cross-linked polymers in order to understand the reasons for these discrepancies, in particular examining the relative contributions of covalent (referred to here as "bonding") and nonbonding (e.g., van der Waals and electrostatic) interactions. Our results indicate cross-linkers enhance thermal conductivity primarily when they are short in length and thereby bring polymer chains closer to each other, leading to increased interchain heat transfer by enhanced nonbonding interactions between the chains (nonbonding interactions being highly dependent on interchain distance). This suggests that enhanced nonbonding interactions, rather than thermal pathways through cross-linker covalent bonds, are the primary transport mechanism by which thermal conductivity is increased. We further illustrate this by showing that energy from THz acoustic waves travels significantly faster in polymers when nonbonding interactions are included versus when only covalent interactions are present. These results help to explain prior studies that measure differing trends in thermal conductivity for polymers upon cross-linking with various species.

High thermal conductivity in amorphous polymer blends by engineered interchain interactions.

Thermal conductivity is an important property for polymers, as it often affects product reliability (for example, electronics packaging), functionality (for example, thermal interface materials) and/or manufacturing cost. However, polymer thermal conductivities primarily fall within a relatively narrow range (0.1-0.5 W m(-1) K(-1)) and are largely unexplored. Here, we show that a blend of two polymers with high miscibility and appropriately chosen linker structure can yield a dense and homogeneously distributed thermal network. A sharp increase in cross-plane thermal conductivity is observed under these conditions, reaching over 1.5 W m(-1) K(-1) in typical spin-cast polymer blend films of nanoscale thickness, which is approximately an order of magnitude larger than that of other amorphous polymers.

Thermal and electrical transport in ultralow density single-walled carbon nanotube networks.

The thermal, electrical, and thermoelectric properties of aerogels of single-walled carbon nanotubes are characterized. Their ultralow density enables the transport properties of the junctions to be distinguished from those of the nanotubes themselves. Junction thermal and electrical conductances are found to be orders of magnitude larger than those found in typical dense SWCNT networks. In particular, the average junction thermal conductance is close to the theoretical maximum for a van der Waals bonded SWCNT junction.

Coherent control of GHz resonant modes by an integrated acoustic etalon.

By carefully tuning the thickness of a compliant thin film placed within an acoustic cavity, we achieve coherent control of the cavity's acoustic resonances, analogous to the operation of an optical etalon. This technique is demonstrated using a supported membrane oscillator in which multiple high-frequency harmonic resonances are simultaneously optoexcited by an ultrafast laser. Theoretical and computational methods are used to analyze the selective strengthening or suppression of these resonances by constructive or destructive interference.

High efficiency, broadband solar cell architectures based on arrays of volumetrically distributed narrowband photovoltaic fibers.

We propose a novel solar cell architecture consisting of multiple fiber-based photovoltaic (PV) cells. Each PV fiber element is designed to maximize the power conversion efficiency within a narrow band of the incident solar spectrum, while reflecting other spectral components through the use of optical microcavity effects and distributed Bragg reflector (DBR) coatings. Combining PV fibers with complementary absorption and reflection characteristics into volume-filling arrays enables spectrally tuned modules having an effective dispersion element intrinsic to the architecture, resulting in high external quantum efficiency over the incident spectrum. While this new reflective tandem architecture is not limited to one particular material system, here we apply the concept to organic PV (OPV) cells that use a metal-organic-metal-dielectric layer structure, and calculate the expected performance of such arrays. Using realistic material properties for organic absorbers, transport layers, metallic electrodes, and DBR coatings, 17% power conversion efficiency can be reached.

Surface plasmon mediated energy transfer of electrically-pumped excitons.

We report strong surface plasmon polariton mediated transfer of energy between molecular excitons across the metallic cathode of an electrically-pumped organic heterostructure. The donor molecular excitons at the organic heterojunction resonantly excite surface plasmon modes on both sides of the optically thick metal electrode, which evanescently couple to dye molecules near the electrode's exterior surface. Dye fluorescence in the capping layer on the exterior of the device shows a 6.5-fold increase in intensity due to this effect, far exceeding any enhancement attributable to Purcell or optical microcavity effects. Demonstration of this energy transfer mechanism for electrically-pumped excitons suggests new sensing and imaging applications with high signal to noise ratio and new routes for performance improvement in energy harvesting devices, plasmonic devices, and organic LEDs (including white light emission).

Localized current injection and submicron organic light-emitting device on a pyramidal atomic force microscopy tip.

An organic light-emitting device was fabricated on a commercial atomic force microscopy (AFM) probe having a pyramidal tip by a lithography-free vacuum thermal evaporation (VTE) process. The line-of-sight molecular transport characteristic of VTE results in controlled thickness variation across the nonplanar substrate, such that localized current injection occurs at the tip region. Furthermore, the high curvature of the AFM tip vertex concentrates the electric field, causing highly localized bipolar charge injection, accompanied by photon emission from a region less than a micrometer across. This light source exhibits a range of features potentially attractive for applications such as probe-based optical microscopy, nanoscale light sensing, and chemical detection.

Profiling the thermoelectric power of semiconductor junctions with nanometer resolution.

We have probed the local thermoelectric power of semiconductor nanostructures with the use of ultrahigh-vacuum scanning thermoelectric microscopy. When applied to a p-n junction, this method reveals that the thermoelectric power changes its sign abruptly within 2 nanometers across the junction. Because thermoelectric power correlates with electronic structure, we can profile with nanometer spatial resolution the thermoelectric power, band structures, and carrier concentrations of semiconductor junctions that constitute the building blocks of thermoelectric, electronic, and optoelectronic devices.