Batteryless implantable device with built-in mechanical clock for automated and precisely timed drug administration.

Adherence to medication plays a crucial role in the effective management of chronic diseases. However, patients often miss their scheduled drug administrations, resulting in suboptimal disease control. Therefore, we propose an implantable device enabled with automated and precisely timed drug administration. Our device incorporates a built-in mechanical clock movement to utilize a clockwork mechanism, i.e., a periodic turn of the hour axis, enabling automatic drug infusion at precise 12-h intervals. The actuation principle relies on the sophisticated design of the device, where the rotational movement of the hour axis is converted into potential mechanical energy and is abruptly released at the exact moment for drug administration. The clock movement can be charged either automatically by mechanical agitations or manually by winding the crown, while the device remains implanted, thereby enabling the device to be used permanently without the need for batteries. When tested using metoprolol, an antihypertensive drug, in a spontaneously hypertensive animal model, the implanted device can deliver drug automatically at precise 12-h intervals without the need for further attention, leading to similarly effective blood pressure control and ultimately, prevention of ventricular hypertrophy as compared with scheduled drug administrations. These findings suggest that our device is a promising alternative to conventional methods for complex drug administration.

Low-threshold 2†µm InAs/InP quantum dash lasers enabled by punctuated growth.

2 µm photonics and optoelectronics is promising for potential applications such as optical communications, LiDAR, and chemical sensing. While the research on 2 µm detectors is on the rise, the development of InP-based 2 µm gain materials with 0D nanostructures is rather stalled. Here, we demonstrate low-threshold, continuous wave lasing at 2 µm wavelength from InAs quantum dash/InP lasers enabled by punctuated growth of the quantum structure. We demonstrate low threshold current densities from the 7.1 µm width ridge-waveguide lasers, with values of 657, 1183, and 1944 A/cm2 under short pulse wave (SPW), quasi-continuous wave (QCW), and continuous wave operation. The lasers also exhibited good thermal stability, with a characteristic temperature T0 of 43 K under SPW mode. The lasing spectra is centered at 1.97 µm, coinciding with the ground-state emission observed from photoluminescence studies. We believe that the InAs quantum dash/InP lasers emitting near 2 µm will be a key enabling technology for 2 µm communication and sensing.

High-sensitivity waveguide-integrated bolometer based on free-carrier absorption for Si photonic sensors.

Conventional photon detectors necessarily face critical challenges regarding strong wavelength-selective response and narrow spectral bandwidth, which are undesirable for spectroscopic applications requiring a wide spectral range. With this perspective, herein, we overcome these challenges through a free-carrier absorption-based waveguide-integrated bolometer for infrared spectroscopic sensors on a silicon-on-insulator (SOI) platform featuring a spectrally flat response at near-infrared (NIR) range (1520-1620 nm). An in-depth thermal analysis was conducted with a systematic investigation of geometry dependence on the detectors. We achieved great performances: temperature coefficient of resistance (TCR) of -3.786%/K and sensitivity of -26.75%/mW with a low wavelength dependency, which are record-high values among reported waveguide bolometers so far, to our knowledge. In addition, a clear on-off response with the rise/fall time of 24.2/29.2 µs and a 3-dB roll-off frequency of ∼22 kHz were obtained, sufficient for a wide range of sensing applications. Together with the possibility of expanding an operation range to the mid-infrared (MIR) band, as well as simplicity in the detector architecture, our work here presents a novel strategy for integrated photodetectors covering NIR to MIR at room temperature for the development of the future silicon photonic sensors with ultrawide spectral bandwidth.

Flexible GaAs photodetector arrays hetero-epitaxially grown on GaP/Si for a low-cost III-V wearable photonics platform.

We demonstrate flexible GaAs photodetector arrays that were hetero-epitaxially grown on a Si wafer for a new cost-effective and reliable wearable optoelectronics platform. A high crystalline quality GaAs layer was transferred onto a flexible foreign substrate and excellent retention of device performance was demonstrated by measuring the optical responsivities and dark currents. Optical simulation proves that the metal stacks used for wafer bonding serve as a back-reflector and enhance GaAs photodetector responsivity via a resonant-cavity effect. Device durability was also tested by bending 1000 times and no performance degradation was observed. This work paves a way for a cost-effective and flexible III-V optoelectronics technology with high durability.

Accepting telemedicine in a circulatory medicine ward in major hospitals in South Korea: patients' and health professionals' perception of real-time electrocardiogram monitoring.

BACKGROUND: South Korean government is currently in progress of expanding the coverage of telemedicine projects as part of an attempt to vitalize service industry, but is facing fierce opposition from KMA. Practice of telemedicine requires sufficient discussions among related parties. Although the participation of medical specialists is important, agreement from the public is essential. METHODS: Three main tertiary care centers in Seoul were selected for data collection. A total of 224 patients (patients n = 180, patient guardian n = 44) and medical professionals (n = 41) were selected using simple random sampling. Mixed method of quantitative survey and qualitative semi-interview was used. RESULTS: This study analyzed patients' and medical professionals' perception about the application of telemedicine in cardiology ward in tertiary care centers to provide baseline data when developing and applying telemedicine services. Results implied high need for encouraging telemedicine projects in order to appeal needs among population by providing experience (p < 0.001) and knowledge (p < 0.001). Other results showed that the need for electrocardiography monitoring was high among not only in remote areas but also in areas close to the capital. 64.52% of all participants thought that telemedicine was needed, and 73.21% of participants were willing to use telemedicine service if provided. Semi-interviews revealed that participants expected more cost and time saving services through remote treatment, by not having to visit long distance hospitals frequently. CONCLUSIONS: Research results oppose Korean Medical Association's opinion that the population is against enforcing telemedicine related laws. The findings in this study reflect an up-to-date perception of telemedicine among patients and medical professionals in a tertiary care centers' cardiology ward. Moreover, the study provides a baseline that is needed in order to overcome past failures and to successfully implement telemedicine in South Korea.

Reduction of GaAs Buffer Thickness and Its Impact on Epitaxially Integrated III-V Quantum Dot Lasers on a Si Substrate.

Monolithic integration of III-V quantum dot (QD) lasers onto a Si substrate is a scalable and reliable approach for obtaining highly efficient light sources for Si photonics. Recently, a combination of optimized GaAs buffers and QD gain materials resulted in monolithically integrated butt-coupled lasers on Si. However, the use of thick GaAs buffers up to 3 µm not only hinders accurate vertical alignment to the Si optical waveguide but also imposes considerable growth costs and time constraints. Here, for the first time, we demonstrate InAs QD lasers epitaxially grown on a 700 nm thick GaAs/Si template, which is approximately four times thinner than the conventional III-V buffers on Si. The optimized 700 nm GaAs buffer yields a remarkably smooth surface and low threading dislocation density of 4 × 108 cm-2, which is sufficient for QD laser growth. The InAs QD lasers fabricated on these ultrathin templates still lase at room temperature with a threshold current density of 661 A/cm2 and a characteristic temperature of 50 K. We believe that these results are important for the monolithically integrated III-V QD lasers for Si photonics applications.

Fe-Porphyrin Cross-Linked Hydrogel for Reactive Oxygen Species Scavenging and Oxygen Generation in Diabetic Wounds.

Healing chronic diabetic wounds is challenging because of excessive reactive oxygen species (ROS) and hypoxia in the wound microenvironment. To address this issue, we propose a hydrogel wound dressing composed of polyethylene glycol (PEG) cross-linked with a biomimetic catalase, Fe-containing porphyrin (FeP) (i.e., FeP hydrogel). The immobilized FeP can serve as a catalyst for both ROS scavenging and O2 generation. The properties of the hydrogels were optimized by varying the composition ratios of the two constituent materials based on their mechanical properties and catalytic activity. Our in vitro cell experiments revealed that the FeP-80 hydrogel enhanced the proliferation and migration of keratinocytes and dermal fibroblasts and promoted the expression of angiogenic growth factors in keratinocytes. When tested with an in vivo diabetic chronic wound model, the FeP-80 hydrogel promoted wound healing by facilitating re-epithelialization, promoting angiogenesis, and suppressing inflammation, compared with other control groups.

In Situ Hydrogel with Immobilized Mn-Porphyrin for Reactive Oxygen Species Scavenging, Oxygen Generation, and Risedronate Delivery in Bone Defect Treatment.

We propose a hydrogel immobilized with manganese porphyrin (MnP), a biomimetic superoxide dismutase (SOD), and catalase (CAT) to modulate reactive oxygen species (ROS) and hypoxia that impede the repair of large bone defects. Our hydrogel synthesis involved thiolated chitosan and polyethylene glycol-maleimide conjugated with MnPs (MnP-PEG-MAL), which enabled in situ gelation via a click reaction. Through optimization, a hydrogel with mechanical properties and catalytic effects favorable for bone repair was selected. Additionally, the hydrogel was incorporated with risedronate to induce synergistic effects of ROS scavenging, O2 generation, and sustained drug release. In vitro studies demonstrated enhanced proliferation and differentiation of MG-63 cells and suppressed proliferation and differentiation of RAW 264.7 cells in ROS-rich environments. In vivo evaluation of a calvarial bone defect model revealed that this multifunctional hydrogel facilitated significant bone regeneration. Therefore, the hydrogel proposed in this study is a promising strategy for addressing complex wound environments and promoting effective bone healing.

Metal-organic framework for biomimetic nitric oxide generation and anticancer drug delivery.

The potential therapeutic implications of nitric oxide (NO) have drawn a great deal of interest for reversing multidrug resistance (MDR) in cancer; however, previous strategies utilized unstable or toxic NO donors often oxidized by the excessive addition of reactive oxygen species, leading to unexpected side effects. Therefore, this study proposed a metal-organic framework (MOF), Porous coordination network (PCN)-223-Fe, to be loaded with a biocompatible NO donor, L-arginine (L-arg; i.e., PCN-223-Fe/L-arg). This specific MOF possesses a ligand of Fe-porphyrin, a biomimetic catalyst. Thus, with PCN-223-Fe/L-arg, L-arg was released in a sustained manner, which generated NO by a catalytic reaction between L-arg and Fe-porphyrin in PCN-223-Fe. Through this biomimetic process, PCN-223-Fe/L-arg could generate sufficient NO to reverse MDR at the expense of hydrogen peroxide already present and highly expressed in cancer environments. For treatment of MDR cancer, this study also proposed PCN-223-Fe loaded with an anticancer drug, irinotecan (CPT-11; i.e., PCN-223-Fe/CPT-11), to be formulated together with PCN-223-Fe/L-arg. Owing to the synergistic effect of reversed MDR by NO generation and sustained release of CPT-11, this combined formulation exhibited a higher anticancer effect on MDR cancer cells (MCF-7/ADR). When intratumorally injected in vivo, coadministration of PCN-223-Fe/L-arg and PCN-223-Fe/CPT-11 greatly suppressed tumor growth in nude mice bearing MDR tumors.

Fe-containing metal-organic framework with D-penicillamine for cancer-specific hydrogen peroxide generation and enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) is based on the production of cytotoxic reactive oxygen species, such as hydroxyl radicals (•OH). Thus, CDT can be advantageous when it is cancer-specific, in terms of efficacy and safety. Therefore, we propose NH2-MIL-101(Fe), a Fe-containing metal-organic framework (MOF), as a carrier of Cu (copper)-chelating agent, d-penicillamine (d-pen; i.e., the NH2-MIL-101(Fe)/d-pen), as well as a catalyst with Fe-metal clusters for Fenton reaction. NH2-MIL-101(Fe)/d-pen in the form of nanoparticles was efficiently taken into cancer cells and released d-pen in a sustained manner. The released d-pen chelated Cu that is highly expressed in cancer environments and this produces extra H2O2, which is then decomposed by Fe in NH2-MIL-101(Fe) to generate •OH. Therefore, the cytotoxicity of NH2-MIL-101(Fe)/d-pen was observed in cancer cells, not in normal cells. We also suggest a formulation of NH2-MIL-101(Fe)/d-pen combined with NH2-MIL-101(Fe) loaded with the chemotherapeutic drug, irinotecan (CPT-11; NH2-MIL-101(Fe)/CPT-11). When intratumorally injected into tumor-bearing mice in vivo, this combined formulation exhibited the most prominent anticancer effects among all tested formulations, owing to the synergistic effect of CDT and chemotherapy.

Implantable device actuated by manual button clicks for noninvasive self-drug administration.

Self-injectable therapy has several advantages in the treatment of metabolic disorders. However, frequent injections with needles impair patient compliance and medication adherence. Therefore, we develop a fully implantable device capable of on-demand administration of self-injection drugs via noninvasive manual button clicks on the outer skin. The device is designed to infuse the drug only at the moment of click actuation, which allows for an accurate and reproducible drug infusion, and also prevents unwanted drug leakage. Using a mechanical means of drug infusion, this implantable device does not contain any electronic compartments or batteries, making it compact, and semi-permanent. When tested in animals, the device can achieve subcutaneous injection-like pharmacokinetic and pharmacodynamic effects for self-injection drugs such as exenatide, insulin, and glucagon.

Demonstration of programmable light intensity of a micro-LED with a Hf-based ferroelectric ITZO TFT for Mura-free displays.

We demonstrate the programmable light intensity of a micro-LED by compensating threshold voltage variability of thin-film transistors (TFTs) by introducing a non-volatile programmable ferroelectric material, HfZrO2 (HZO) into the gate stack of the TFT. We fabricated an amorphous ITZO TFT, ferroelectric TFTs (FeTFTs), and micro-LEDs and verified the feasibility of our proposed current-driving active matrix circuit. Importantly, we successfully present the programmed multi-level lighting of the micro-LED, utilizing partial polarization switching in the a-ITZO FeTFT. We expect that this approach will be highly promising for the next-generation display technology, replacing complicated threshold voltage compensation circuits with a simple a-ITZO FeTFT.

Microneedles coated with composites of phenylboronic acid-containing polymer and carbon nanotubes for glucose measurements in interstitial fluids.

A microneedle (MN) sensor coated with a sensing composite material was proposed for measuring glucose concentrations in interstitial fluid (ISF). The sensing composite material was prepared by blending a polymer containing glucose-responsive phenylboronic acid (PBA) moieties (i.e., polystyrene-block-poly(acrylic acid-co-acrylamidophenylboronic acid)) with conductive carbon nanotubes (CNTs). The polymer exhibited reversible swelling behavior in response to glucose concentrations, which influenced the distribution of the embedded CNTs, resulting in sensitive variations in electrical percolation, even when coated onto a confined surface of the MN in the sensor. We varied the ratio of PBA moieties and the loading amount of CNTs in the sensing composite material of the MN sensor and tested them in vitro using an ISF-mimicking gel with physiological glucose concentrations to determine the optimal sensitivity conditions. When tested in animal models with varying blood glucose concentrations, the MN sensor coated with the selected sensing material exhibited a strong correlation between the measured electrical currents and blood glucose concentrations, showing accuracy comparable to that of a glucometer in clinical use.

Implantable device with magnetically rotating disk for needle-free administrations of emergency drug.

Prompt administration of first-aid drugs can save lives during medical emergencies such as anaphylaxis and hypoglycemia. However, this is often performed by needle self-injection, which is not easy for patients under emergency conditions. Therefore, we propose an implantable device capable of on-demand administration of first-aid drugs (i.e., the implantable device with a magnetically rotating disk [iMRD]), such as epinephrine and glucagon, via a noninvasive simple application of the magnet from the outside skin (i.e., the external magnet). The iMRD contained a disk embedded with a magnet, as well as multiple drug reservoirs that were sealed with a membrane, which was designed to rotate at a precise angle only when the external magnet was applied. During this rotation, the membrane on a designated single-drug reservoir was aligned and torn to expose the drug to the outside. When implanted in living animals, the iMRD, actuated by an external magnet, delivers epinephrine and glucagon, similar to conventional subcutaneous needle injections.

Chromophoric cerium oxide nanoparticle-loaded sucking disk-type strip sensor for optical measurement of glucose in tear fluid.

BACKGROUND: Noninvasive monitoring of tear glucose levels can be convenient for patients to manage their diabetes mellitus. However, there are issues with monitoring tear glucose levels, such as the invasiveness of some methods, the miniaturization, inaccuracy, or the high cost of wearable devices. To overcome the issues, we newly designed a sucking disk-type (SD) strip biosensor that can quickly suck tear fluid and contains cerium oxide nanoparticle (CNP) that causes a unique color change according to the glucose level of the tear without complicated electronic components. METHODS: The SD strip biosensor composed of three distinct parts (tip, channel, and reaction chamber) was designed to contain the sensing paper, onto which tear fluid can be collected and delivered. The sensing paper treated with CNP/APTS (aminopropyltriethoxysilane) /GOx (glucose oxidase) was characterized. Then we carried out the reliability of the SD strip biosensor in the diabetic rabbit animals. We quantitatively analyzed the color values of the SD strip biosensor through the colorimetric analysis algorithm. RESULTS: We contacted the inferior palpebral conjunctiva (IPC) of a diabetic rabbit eye using an SD strip biosensor to collect tears without eye irritation and successfully verified the performance and quantitative efficacy of the sensor. An image processing algorithm that can optimize measurement accuracy is developed for accurate color change measurement of SD strip biosensors. The validation tests show a good correlation between glucose concentrations measured in the tear and blood. CONCLUSION: Our findings demonstrate that the CNP-embedded SD strip biosensor and the associated image processing can simply monitor tear glucose to manage diabetes mellitus.

Energy-Efficient III-V Tunnel FET-Based Synaptic Device with Enhanced Charge Trapping Ability Utilizing Both Hot Hole and Hot Electron Injections for Analog Neuromorphic Computing.

A charge trap device based on field-effect transistors (FET) is a promising candidate for artificial synapses because of its high reliability and mature fabrication technology. However, conventional MOSFET-based charge trap synapses require a strong stimulus for synaptic update because of their inefficient hot-carrier injection into the charge trapping layer, consequently causing a slow speed operation and large power consumption. Here, we propose a highly efficient charge trap synapse using III-V materials-based tunnel field-effect transistor (TFET). Our synaptic TFETs present superior subthreshold swing and improved charge trapping ability utilizing both carriers as charge trapping sources: hot holes created by impact ionization in the narrow bandgap InGaAs after being provided from the p+-source, and band-to-band tunneling hot electrons (BBHEs) generated at the abrupt p+n junctions in the TFETs. Thanks to these advances, our devices achieved outstanding efficiency in synaptic characteristics with a 5750 times faster synaptic update speed and 51 times lower sub-fJ/um2 energy consumption per single synaptic update in comparison to the MOSFET-based synapse. An artificial neural network (ANN) simulation also confirmed a high recognition accuracy of handwritten digits up to ∼90% in a multilayer perceptron neural network based on our synaptic devices.

Microchannel-embedded implantable device with fibrosis suppression for prolonged controlled drug delivery.

For the prolonged, controlled delivery of systemic drugs, we propose an implantable drug-delivery chip (DDC) embedded with pairs of a microchannel and drug-reservoir serving as a drug diffusion barrier and depot, respectively. We pursued a DDC for dual drugs: a main-purpose drug, diclofenac (DF), for systemic exposure, and an antifibrotic drug, tranilast (TR), for local delivery. Thus, the problematic fibrotic tissue formation around the implanted device could be diminished, thereby less hindrance in systemic exposure of DF released from the DDC. First, we separately prepared DDCs for DF or TR delivery, and sought to find a proper microchannel length for a rapid onset and sustained pattern of drug release, as well as the required drug dose. Then, two distinct DDCs for DF and TR delivery, respectively, were assembled to produce a Dual_DDC for the concurrent delivery of DF and TR. When the Dual_DDC was implanted in living rats, the DF concentration in blood plasma did not drop significantly in the later periods after implantation relative to that in the early periods before fibrotic tissue formation. When the Dual_DDC was implanted without TR, there was a significant decrease in the blood plasma DF concentration as the time elapsed after implantation. Biopsied tissues around the Dual_DDC exhibited a significant decrease in the fibrotic capsule thickness and collagen density relative to the Dual_DDC without TR, owing to the effect of the local, sustained release of the TR.

Magnetically actuating implantable pump for the on-demand and needle-free administration of human growth hormone.

A bolus of human growth hormone (hGH) is often prescribed for the treatment of growth hormone deficiency, which requires frequent injections in current clinical settings. This painful needle-involved delivery often results in poor patient compliance, leading to low medication adherence and poor clinical outcomes. Therefore, we propose a magnetically actuating implantable pump (MAP) that can infuse an accurate dose of hGH only at the time of non-invasive magnet application from the skin. The MAP herein could reproducibly infuse 20.6 ±â€¯0.9 µg hGH per actuation without any leak at times without actuation. The infused amount increased proportionally with an increase in the number of actuations. When the MAP was implanted and actuated with a magnet in animals with growth hormone deficiency for 21 days, the profiles of plasma hGH concentration and insulin-like growth factor (IGF)-1, as well as changes in body weight, were similar to those observed in animals treated with conventional subcutaneous hGH injections. Therefore, we anticipate that the MAP fabricated in this study can be a non-invasive alternative to administer hGH without repeated and frequent needle injections.

Enhanced Photoluminescence of 1.3 µm InAs Quantum Dots Grown on Ultrathin GaAs Buffer/Si Templates by Suppressing Interfacial Defect Emission.

We report on the photoluminescence enhancement of 1.3 µm InAs quantum dots (QDs) epitaxially grown on an ultrathin 250 nm GaAs buffer on a Si substrate. Decreasing the GaAs buffer thickness from 1000 to 250 nm was found to not only increase the coalesced QD density from 6.5 × 108 to 1.9 × 109 cm-2 but also decrease the QD photoluminescence emission intensity dramatically. Inserting an Al0.4Ga0.6As potential barrier layer maintained strong photoluminescence from the QDs by effectively suppressing carrier leakage to the GaAs/Si interfacial region even when the GaAs buffer was thinned to 250 nm. We then fabricated a light-emitting diode using the ultrathin 250 nm GaAs buffer on Si and confirmed strong electroluminescence peaking at 1.28 µm without interfacial defect emission at room temperature. We believe that this work is promising for monolithically integrated evanescent Si lasers using InAs/GaAs QDs.

Heterogeneously-Integrated Optical Phase Shifters for Next-Generation Modulators and Switches on a Silicon Photonics Platform: A Review.

The realization of a silicon optical phase shifter marked a cornerstone for the development of silicon photonics, and it is expected that optical interconnects based on the technology relax the explosive datacom growth in data centers. High-performance silicon optical modulators and switches, integrated into a chip, play a very important role in optical transceivers, encoding electrical signals onto the light at high speed and routing the optical signals, respectively. The development of the devices is continuously required to meet the ever-increasing data traffic at higher performance and lower cost. Therefore, heterogeneous integration is one of the highly promising approaches, expected to enable high modulation efficiency, low loss, low power consumption, small device footprint, etc. Therefore, we review heterogeneously integrated optical modulators and switches for the next-generation silicon photonic platform.