Electrical programmable multilevel nonvolatile photonic random-access memory.

Photonic Random-Access Memories (P-RAM) are an essential component for the on-chip non-von Neumann photonic computing by eliminating optoelectronic conversion losses in data links. Emerging Phase-Change Materials (PCMs) have been showed multilevel memory capability, but demonstrations still yield relatively high optical loss and require cumbersome WRITE-ERASE approaches increasing power consumption and system package challenges. Here we demonstrate a multistate electrically programmed low-loss nonvolatile photonic memory based on a broadband transparent phase-change material (Ge2Sb2Se5, GSSe) with ultralow absorption in the amorphous state. A zero-static-power and electrically programmed multi-bit P-RAM is demonstrated on a silicon-on-insulator platform, featuring efficient amplitude modulation up to 0.2 dB/µm and an ultralow insertion loss of total 0.12 dB for a 4-bit memory showing a 100× improved signal to loss ratio compared to other phase-change-materials based photonic memories. We further optimize the positioning of dual microheaters validating performance tradeoffs. Experimentally we demonstrate a half-a-million cyclability test showcasing the robust approach of this material and device. Low-loss photonic retention-of-state adds a key feature for photonic functional and programmable circuits impacting many applications including neural networks, LiDAR, and sensors for example.

Interstitial Photothermal Therapy Generates Durable Treatment Responses in Neuroblastoma.

Photothermal therapy (PTT) represents a promising modality for tumor control typically using infrared light-responsive nanoparticles illuminated by a wavelength-matched external laser. However, due to the constraints of light penetration, PTT is generally restricted to superficially accessible tumors. With the goal of extending the benefits of PTT to all tumor settings, interstitial PTT (I-PTT) is evaluated by the photothermal activation of intratumorally administered Prussian blue nanoparticles with a laser fiber positioned interstitially within the tumor. This interstitial fiber, which is fitted with a terminal diffuser, distributes light within the tumor microenvironment from the "inside-out" as compared to from the "outside-in" traditionally observed during superficially administered PTT (S-PTT). I-PTT improves the heating efficiency and heat distribution within a target treatment area compared to S-PTT. Additionally, I-PTT generates increased cytotoxicity and thermal damage at equivalent thermal doses, and elicits immunogenic cell death at lower thermal doses in targeted neuroblastoma tumor cells compared to S-PTT. In vivo, I-PTT induces significantly higher long-term tumor regression, lower rates of tumor recurrence, and improved long-term survival in multiple syngeneic murine models of neuroblastoma. This study highlights the significantly enhanced therapeutic benefit of I-PTT compared to traditional S-PTT as a promising treatment modality for solid tumors.

Mimicking Native Heart Tissue Physiology and Pathology in Silk Fibroin Constructs through a Perfusion-Based Dynamic Mechanical Stimulation Microdevice.

In vitro cardiomyocyte (CM) maturation is an imperative step to replicate native heart tissue-like structures as cardiac tissue grafts or as drug screening platforms. CMs are known to interpret biophysical cues such as stiffness, topography, external mechanical stimulation or dynamic perfusion load through mechanotransduction and change their behavior, organization, and maturation. In this regard, a silk-based cardiac tissue (CT) coupled with a dynamic perfusion-based mechanical stimulation platform (DMM) for achieving maturation and functionality in vitro is tried to be delivered. Silk fibroin (SF) is used to fabricate lamellar scaffolds to provide native tissue-like anisotropic architecture and is found to be nonimmunogenic and biocompatible allowing cardiomyocyte attachment and growth in vitro. Further, the scaffolds display excellent mechanical properties by their ability to undergo cyclic compressions without any deformation when places in the DMM. Gradient compression strains (5% to 20%), mimicking the native physiological and pathological conditions, are applied to the cardiomyocyte culture seeded on lamellar silk scaffolds in the DMM. A strain-dependent difference in cardiomyocyte maturation, gene expression, sarcomere elongation, and extracellular matrix formation is observed. These silk-based CTs matured in the DMM can open up several avenues toward the development of host-specific grafts and in vitro models for drug screening.

Quantifying Information via Shannon Entropy in Spatially Structured Optical Beams.

While information is ubiquitously generated, shared, and analyzed in a modern-day life, there is still some controversy around the ways to assess the amount and quality of information inside a noisy optical channel. A number of theoretical approaches based on, e.g., conditional Shannon entropy and Fisher information have been developed, along with some experimental validations. Some of these approaches are limited to a certain alphabet, while others tend to fall short when considering optical beams with a nontrivial structure, such as Hermite-Gauss, Laguerre-Gauss, and other modes with a nontrivial structure. Here, we propose a new definition of the classical Shannon information via the Wigner distribution function, while respecting the Heisenberg inequality. Following this definition, we calculate the amount of information in Gaussian, Hermite-Gaussian, and Laguerre-Gaussian laser modes in juxtaposition and experimentally validate it by reconstruction of the Wigner distribution function from the intensity distribution of structured laser beams. We experimentally demonstrate the technique that allows to infer field structure of the laser beams in singular optics to assess the amount of contained information. Given the generality, this approach of defining information via analyzing the beam complexity is applicable to laser modes of any topology that can be described by well-behaved functions. Classical Shannon information, defined in this way, is detached from a particular alphabet, i.e., communication scheme, and scales with the structural complexity of the system. Such a synergy between the Wigner distribution function encompassing the information in both real and reciprocal space and information being a measure of disorder can contribute into future coherent detection algorithms and remote sensing.

Symmetry perception with spiking neural networks.

Mirror symmetry is an abundant feature in both nature and technology. Its successful detection is critical for perception procedures based on visual stimuli and requires organizational processes. Neuromorphic computing, utilizing brain-mimicked networks, could be a technology-solution providing such perceptual organization functionality, and furthermore has made tremendous advances in computing efficiency by applying a spiking model of information. Spiking models inherently maximize efficiency in noisy environments by placing the energy of the signal in a minimal time. However, many neuromorphic computing models ignore time delay between nodes, choosing instead to approximate connections between neurons as instantaneous weighting. With this assumption, many complex time interactions of spiking neurons are lost. Here, we show that the coincidence detection property of a spiking-based feed-forward neural network enables mirror symmetry. Testing this algorithm exemplary on geospatial satellite image data sets reveals how symmetry density enables automated recognition of man-made structures over vegetation. We further demonstrate that the addition of noise improves feature detectability of an image through coincidence point generation. The ability to obtain mirror symmetry from spiking neural networks can be a powerful tool for applications in image-based rendering, computer graphics, robotics, photo interpretation, image retrieval, video analysis and annotation, multi-media and may help accelerating the brain-machine interconnection. More importantly it enables a technology pathway in bridging the gap between the low-level incoming sensor stimuli and high-level interpretation of these inputs as recognized objects and scenes in the world.

Heterogeneously integrated ITO plasmonic Mach-Zehnder interferometric modulator on SOI.

Densely integrated active photonics is key for next generation on-chip networks for addressing both footprint and energy budget concerns. However, the weak light-matter interaction in traditional active Silicon optoelectronics mandates rather sizable device lengths. The ideal active material choice should avail high index modulation while being easily integrated into Silicon photonics platforms. Indium tin oxide (ITO) offers such functionalities and has shown promising modulation capacity recently. Interestingly, the nanometer-thin unity-strong index modulation of ITO synergistically combines the high group-index in hybrid plasmonic with nanoscale optical modes. Following this design paradigm, here, we demonstrate a spectrally broadband, GHz-fast Mach-Zehnder interferometric modulator, exhibiting a high efficiency signified by a miniscule VπL of 95 V µm, deploying a one-micrometer compact electrostatically tunable plasmonic phase-shifter, based on heterogeneously integrated ITO thin films into silicon photonics. Furthermore we show, that this device paradigm enables spectrally broadband operation across the entire telecommunication near infrared C-band. Such sub-wavelength short efficient and fast modulators monolithically integrated into Silicon platform open up new possibilities for high-density photonic circuitry, which is critical for high interconnect density of photonic neural networks or applications in GHz-fast optical phased-arrays, for example.

Exploiting Unique Alignment of Cobalt Ferrite Nanoparticles, Mild Hyperthermia, and Controlled Intrinsic Cobalt Toxicity for Cancer Therapy.

Nanoparticle-based magnetic hyperthermia is a well-known thermal therapy platform studied to treat solid tumors, but its use for monotherapy is limited due to incomplete tumor eradication at hyperthermia temperature (45 °C). It is often combined with chemotherapy for obtaining a more effective therapeutic outcome. Cubic-shaped cobalt ferrite nanoparticles (Co-Fe NCs) serve as magnetic hyperthermia agents and as a cytotoxic agent due to the known cobalt ion toxicity, allowing the achievement of both heat and cytotoxic effects from a single platform. In addition to this advantage, Co-Fe NCs have the unique ability to form growing chains under an alternating magnetic field (AMF). This unique chain formation, along with the mild hyperthermia and intrinsic cobalt toxicity, leads to complete tumor regression and improved overall survival in an in vivo murine xenograft model, all under clinically approved AMF conditions. Numerical calculations identify magnetic anisotropy as the main Co-Fe NCs' feature to generate such chain formations. This novel combination therapy can improve the effects of magnetic hyperthermia, inaugurating investigation of mechanical behaviors of nanoparticles under AMF, as a new avenue for cancer therapy.

Biodegradable and Insoluble Cellulose Photonic Crystals and Metasurfaces.

The replacement of plastic with eco-friendly and biodegradable materials is one of the most stringent environmental challenges. In this respect, cellulose stands out as a biodegradable polymer. However, a significant challenge is to obtain biodegradable materials for high-end photonics that are robust in humid environments. Here, we demonstrate the fabrication of high-quality micro- and nanoscale photonic and plasmonic structures via replica molding using pure cellulose and a blended version with nonedible agro-wastes. Both materials are biodegradable in soil and seawater according to the ISO 17556 standard. The pure cellulose films are transparent in the vis-NIR spectrum, having a refractive index similar to glass. The microstructured photonic crystals show high-quality diffractive properties that are maintained under extended exposure to water. Nanostructuring the cellulose transforms it to a biodegradable metasurface manifesting bright structural colors. A subsequent deposition of Ag endowed the metasurface with plasmonic properties used to produce plasmonic colors and for surface-enhanced Raman scattering.

CLEAR: A Holistic Figure-of-Merit for Post- and Predicting Electronic and Photonic-based Compute-system Evolution.

Continuing demands for increased computing efficiency and communication bandwidth have pushed the current semiconductor technology to its limit. This led to novel technologies with the potential to outperform conventional electronic solutions such as photonic pre-processors or accelerators, electronic-photonic hybrid circuits, and neural networks. However, the efforts made to describe and predict the performance evolution of compute-performance fall short to accurately predict and thereby explain the actually observed development pace with time; that is all proposed metrics eventually deviate from their development trajectory after several years from when they were originally proposed. This discrepancy demands a figure-of-merit that includes a holistic set of driving forces of the compute-system evolution. Here we introduce the Capability-to-Latency-Energy-Amount-Resistance (CLEAR) metric encompassing synchronizing speed, energy efficiency, physical machine size scaling, and economic cost. We show that CLEAR is the only metric to accurately describe the historical compute-system development. We find that even across different technology options CLEAR matches the observed (post-diction) constant rate-of-growth, and also fits proposed future compute-system (prediction). Therefore, we propose CLEAR to serve as a guide to quantitatively predict required compute-system demands at a given time in the future.

Nanoparticle-Based Hybrid Scaffolds for Deciphering the Role of Multimodal Cues in Cardiac Tissue Engineering.

Myocardial microenvironment plays a decisive role in guiding the function and fate of cardiomyocytes, and engineering this extracellular niche holds great promise for cardiac tissue regeneration. Platforms utilizing hybrid hydrogels containing various types of conductive nanoparticles have been a critical tool for constructing engineered cardiac tissues with outstanding mechanical integrity and improved electrophysiological properties. However, there has been no attempt to directly compare the efficacy of these hybrid hydrogels and decipher the mechanisms behind how these platforms differentially regulate cardiomyocyte behavior. Here, we employed gelatin methacryloyl (GelMA) hydrogels containing three different types of carbon-based nanoparticles: carbon nanotubes (CNTs), graphene oxide (GO), and reduced GO (rGO), to investigate the influence of these hybrid scaffolds on the structural organization and functionality of cardiomyocytes. Using immunofluorescent staining for assessing cellular organization and proliferation, we showed that electrically conductive scaffolds (CNT- and rGO-GelMA compared to relatively nonconductive GO-GelMA) played a significant role in promoting desirable morphology of cardiomyocytes and elevated the expression of functional cardiac markers, while maintaining their viability. Electrophysiological analysis revealed that these engineered cardiac tissues showed distinct cardiomyocyte phenotypes and different levels of maturity based on the substrate (CNT-GelMA: ventricular-like, GO-GelMA: atrial-like, and rGO-GelMA: ventricular/atrial mixed phenotypes). Through analysis of gene-expression patterns, we uncovered that the engineered cardiac tissues matured on CNT-GelMA and native cardiac tissues showed comparable expression levels of maturation markers. Furthermore, we demonstrated that engineered cardiac tissues matured on CNT-GelMA have increased functionality through integrin-mediated mechanotransduction (via YAP/TAZ) in contrast to cardiomyocytes cultured on rGO-GelMA.

Towards integrated metatronics: a holistic approach on precise optical and electrical properties of Indium Tin Oxide.

The class of transparent conductive oxides includes the material indium tin oxide (ITO) and has become a widely used material of modern every-day life such as in touch screens of smart phones and watches, but also used as an optically transparent low electrically-resistive contract in the photovoltaics industry. More recently ITO has shown epsilon-near-zero (ENZ) behavior in the telecommunication frequency band enabling both strong index modulation and other optically-exotic applications such as metatronics. However, the ability to precisely obtain targeted electrical and optical material properties in ITO is still challenging due to complex intrinsic effects in ITO and as such no integrated metatronic platform has been demonstrated to-date. Here we deliver an extensive and accurate description process parameter of RF-sputtering, showing a holistic control of the quality of ITO thin films in the visible and particularly near-infrared spectral region. We are able to custom-engineer the ENZ point across the telecommunication band by explicitly controlling the sputtering process conditions. Exploiting this control, we design a functional sub-wavelength-scale filter based on lumped circuit-elements, towards the realization of integrated metatronic devices and circuits.

Planar Aperiodic Arrays as Metasurfaces for Optical Near-Field Patterning.

Plasmonic metasurfaces have spawned the field of flat optics using nanostructured planar metallic or dielectric surfaces that can replace bulky optical elements and enhance the capabilities of traditional far-field optics. Furthermore, the potential of flat optics can go far beyond far-field modulation and can be exploited for functionality in the near-field itself. Here, we design metasurfaces based on aperiodic arrays of plasmonic Au nanostructures for tailoring the optical near-field in the visible and near-infrared spectral range. The basic element of the arrays is a rhomboid that is modulated in size, orientation, and position to achieve the desired functionality of the micron-size metasurface structure. Using two-photon-photoluminescence as a tool to probe the near-field profiles in the plane of the metasurfaces, we demonstrate the molding of light into different near-field intensity patterns and active pattern control via the far-field illumination. Finite element method simulations reveal that the near-field modulation occurs via a combination of the plasmonic resonances of the rhomboids and field enhancement in the nanoscale gaps in between the elements. This approach enables optical elements that can switch the near-field distribution across the metasurface via wavelength and polarization of the incident far-field light and provides pathways for light matter interaction in integrated devices.

Giant-Shell CdSe/CdS Nanocrystals: Exciton Coupling to Shell Phonons Investigated by Resonant Raman Spectroscopy.

The interaction between excitons and phonons in semiconductor nanocrystals plays a crucial role in the exciton energy spectrum and dynamics, and thus in their optical properties. We investigate the exciton-phonon coupling in giant-shell CdSe/CdS core-shell nanocrystals via resonant Raman spectroscopy. The Huang-Rhys parameter is evaluated by the intensity ratio of the longitudinal-optical (LO) phonon of CdS with its first multiscattering (2LO) replica. We used four different excitation wavelengths in the range from the onset of the CdS shell absorption to well above the CdS shell band edge to get insight into resonance effects of the CdS LO phonon with high-energy excitonic transitions. The isotropic spherical giant-shell nanocrystals show consistently stronger exciton-phonon coupling as compared to the anisotropic rod-shaped dot-in-rod (DiR) architecture, and the 2LO/LO intensity ratio decreases for excitation wavelengths approaching the CdS band edge. The strong exciton-phonon coupling in the spherical giant-shell nanocrystals can be related to the delocalization of the electronic wave functions. Furthermore, we observe the radial breathing modes of the GS nanocrystals and their overtones by ultralow frequency Raman spectroscopy with nonresonant excitation, using laser energies well below the band gap of the heteronanocrystals, and highlight the differences between higher-order optical and acoustic phonon modes.

Effects of graphene defects on gas sensing properties towards NO2 detection.

The crystal structure of graphene flakes is expected to significantly affect their sensing properties. Here we report an experimental investigation on the crystalline structure of graphene aimed at exploring the effects on the gas sensing properties. The morphology of graphene, prepared via Chemical Vapor Deposition (CVD), Liquid Phase Exfoliation (LPE) and Mechanical Exfoliation (ME), is inspected through Raman spectroscopy, Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). CVD and LPE-graphene structures are found to be more defective with respect to ME-graphene. The defects are due to the jagged morphology of the films rather than originating from intrinsic disorder. The flatness of ME-graphene flakes, instead, explains the absence of defects. Chemiresistors based on the three different graphene preparation methods are subsequently exposed to NO2 in the concentration range 0.1-1.5 ppm (parts per million). The device performance is demonstrated to be strongly and unambiguously affected by the material structure: the less defective the material is, the higher the response rate is. In terms of signal variation, at 1.5 ppm, for instance, ME-graphene shows the highest value (5%) among the three materials. This study, comparing simultaneously graphene and sensors prepared via different routes, provides the first experimental evidence of the role played by the graphene level of defectiveness in the interaction with analytes. Moreover, these findings can pave the path for tailoring the sensor behavior as a function of graphene morphology.

Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model.

Organ-on-a-chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. HGPS targets primarily vascular cells, which reside in mechanically active tissues. Here, a progeria-on-a-chip model is developed and the effects of biomechanical strain are examined in the context of vascular aging and disease. Physiological strain induces a contractile phenotype in primary smooth muscle cells (SMCs), while a pathological strain induces a hypertensive phenotype similar to that of angiotensin II treatment. Interestingly, SMCs derived from human induced pluripotent stem cells of HGPS donors (HGPS iPS-SMCs), but not from healthy donors, show an exacerbated inflammatory response to strain. In particular, increased levels of inflammation markers as well as DNA damage are observed. Pharmacological intervention reverses the strain-induced damage by shifting gene expression profile away from inflammation. The progeria-on-a-chip is a relevant platform to study biomechanics in vascular biology, particularly in the setting of vascular disease and aging, while simultaneously facilitating the discovery of new drugs and/or therapeutic targets.

Confined Acoustic Phonons in Colloidal Nanorod Heterostructures Investigated by Nonresonant Raman Spectroscopy and Finite Elements Simulations.

Lattice vibrational modes in cadmium chalcogenide nanocrystals (NCs) have a strong impact on the carrier dynamics of excitons in such confined systems and on the optical properties of these nanomaterials. A prominent material for light emitting applications are CdSe/CdS core-shell dot-in-rods. Here we present a detailed investigation of the acoustic phonon modes in such dot-in-rods by nonresonant Raman spectroscopy with laser excitation energy lower than their bandgap. With high signal-to-noise ratio in the frequency range from 5-50 cm-1, we reveal distinct Raman bands that can be related to confined extensional and radial-breathing modes (RBM). Comparison of the experimental results with finite elements simulation and analytical analysis gives detailed insight into the localized nature of the acoustic vibration modes and their resonant frequencies. In particular, the RBM of dot-in-rods cannot be understood by an oscillation of a CdSe sphere embedded in a CdS rod matrix. Instead, the dot-in-rod architecture leads to a reduction of the sound velocity in the core region of the rod, which results in a redshift of the rod RBM frequency and localization of the phonon induced strain in vicinity of the core where optical transitions occur. Such localized effects potentially can be exploited as a tool to tune exciton-phonon coupling in nanocrystal heterostructures.

A liver-on-a-chip platform with bioprinted hepatic spheroids.

The inadequacy of animal models in correctly predicting drug and biothreat agent toxicity in humans has resulted in a pressing need for in vitro models that can recreate the in vivo scenario. One of the most important organs in the assessment of drug toxicity is liver. Here, we report the development of a liver-on-a-chip platform for long-term culture of three-dimensional (3D) human HepG2/C3A spheroids for drug toxicity assessment. The bioreactor design allowed for in situ monitoring of the culture environment by enabling direct access to the hepatic construct during the experiment without compromising the platform operation. The engineered bioreactor could be interfaced with a bioprinter to fabricate 3D hepatic constructs of spheroids encapsulated within photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. The engineered hepatic construct remained functional during the 30 days culture period as assessed by monitoring the secretion rates of albumin, alpha-1 antitrypsin, transferrin, and ceruloplasmin, as well as immunostaining for the hepatocyte markers, cytokeratin 18, MRP2 bile canalicular protein and tight junction protein ZO-1. Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.

Highly Elastic and Conductive Human-Based Protein Hybrid Hydrogels.

A highly elastic hybrid hydrogel of methacryloyl-substituted recombinant human tropoelastin (MeTro) and graphene oxide (GO) nanoparticles are developed. The synergistic effect of these two materials significantly enhances both ultimate strain (250%), reversible rotation (9700°), and the fracture energy (38.8 ± 0.8 J m(-2) ) in the hybrid network. Furthermore, improved electrical signal propagation and subsequent contraction of the muscles connected by hybrid hydrogels are observed in ex vivo tests.

Aligned carbon nanotube-based flexible gel substrates for engineering bio-hybrid tissue actuators.

Muscle-based biohybrid actuators have generated significant interest as the future of biorobotics but so far they move without having much control over their actuation behavior. Integration of microelectrodes into the backbone of these systems may enable guidance during their motion and allow precise control over these actuators with specific activation patterns. Here, we addressed this challenge by developing aligned CNT forest microelectrode arrays and incorporated them into scaffolds for stimulating the cells. Aligned CNTs were successfully embedded into flexible and biocompatible hydrogel exhibiting excellent anisotropic electrical conductivity. Bioactuators were then engineered by culturing cardiomyocytes on the CNT microelectrode-integrated hydrogel constructs. The resulting cardiac tissue showed homogeneous cell organization with improved cell-to-cell coupling and maturation, which was directly related to the contractile force of muscle tissue. This centimeter-scale bioactuator has excellent mechanical integrity, embedded microelectrodes and is capable of spontaneous actuation behavior. Furthermore, we demonstrated that a biohybrid machine can be controlled by an external electrical field provided by the integrated CNT microelectrode arrays. In addition, due to the anisotropic electrical conductivity of the electrodes provided from aligned CNTs, significantly different excitation thresholds were observed in different configurations such as the ones in parallel vs. perpendicular direction to the CNT alignment.

Analysis of MWCNT/epoxy composites at microwave frequency: reproducibility investigation.

A wide-band microwave characterization of nanocomposites based on commercial multiwalled carbon nanotubes (MWCNTs) and epoxy resin is presented. The sample preparation method is discussed in detail. Field emission scanning electron microscopy is used for morphological sample analysis of nanocomposites and MWCNTs. The complex permittivity is measured in a wide frequency band (3 to 18 GHz) using a commercial dielectric probe (Agilent 85070D) and a network analyzer (E8361A). A statistical analysis based on one-way analysis of variance (ANOVA) technique is performed. The aim of this statistical analysis is to investigate the influence of concentration of nanoparticles inside the polymer matrix on the complex permittivity. This can be significantly different in nanocomposites even if the samples have similar electrical properties.