Analysis of Self-Assembled Low- and High-Molecular-Weight Poly-L-Lysine-Ce6 Conjugate-Based Nanoparticles.

In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Ultrafast (∼0.6 s), Robust, and Highly Linear Hydrogen Detection up to 10% Using Fully Suspended Pure Pd Nanowire.

The high explosiveness of hydrogen gas in the air necessitates prompt detection in settings where hydrogen is used. For this reason, hydrogen sensors are required to offer rapid detection and possess superior sensing characteristics in terms of measurement range, linearity, selectivity, lifetime, and environment insensitivity according to the publicized protocol. However, previous approaches have only partially achieved the standardized requirements and have been limited in their capability to develop reliable materials for spatially accessible systems. Here, an electrical hydrogen sensor with an ultrafast response (∼0.6 s) satisfying all demands for hydrogen detection is demonstrated. Tailoring structural engineering based on the reaction kinetics of hydrogen and palladium, an optimized heating architecture that thermally activates fully suspended palladium (Pd) nanowires at a uniform temperature is designed. The developed Pd nanostructure, at a designated temperature distribution, rapidly reacts with hydrogen, enabling a hysteresis-free response from 0.1% to 10% and durable characteristics in mechanical shock and repetitive operation (>10,000 cycles). Moreover, the device selectively detects hydrogen without performance degradation in humid or carbon-based interfering gas circumstances. Finally, to verify spatial accessibility, the wireless hydrogen detection system has been demonstrated, detecting and reporting hydrogen leakage in real-time within just 1 s.

Development of Shape Prediction Model of Microlens Fabricated via Diffuser-Assisted Photolithography.

The fabrication of microlens arrays (MLAs) using diffuser-assisted photolithography (DPL) has garnered substantial recent interest owing to the exceptional capabilities of DPL in adjusting the size and shape, achieving high fill factors, enhancing productivity, and ensuring excellent reproducibility. The inherent unpredictability of light interactions within the diffuser poses challenges in accurately forecasting the final shape and dimensions of microlenses in the DPL process. Herein, we introduce a comprehensive theoretical model to forecast microlens shapes in response to varying exposure doses within a DPL framework. We establish a robust MLA fabrication method aligned with conventional DPL techniques to enable precise shape modulation. By calibrating the exposure doses meticulously, we generate diverse MLA configurations, each with a distinct shape and size. Subsequently, by utilizing the experimentally acquired data encompassing parameters such as height, radius of curvature, and angles, we develop highly precise theoretical prediction models, achieving R-squared values exceeding 95%. The subsequent validation of our model encompasses the accurate prediction of microlens shapes under specific exposure doses. The verification results exhibit average error rates of approximately 2.328%, 7.45%, and 3.16% for the height, radius of curvature, and contact angle models, respectively, all of which were well below the 10% threshold.

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic-DEVD-Doxorubicin Conjugate for Targeted Cancer Therapy.

In the development of new drugs, typical polymer- or macromolecule-based nanocarriers suffer from manufacturing process complexity, unwanted systematic toxicity, and low loading capacity. However, carrier-free nanomedicines have made outstanding progress in drug delivery and pharmacokinetics, demonstrating most of the advantages associated with nanoparticles when applied in targeted anticancer therapy. Here, to overcome the problems of nanocarriers and conventional cytotoxic drugs, we developed a novel, carrier-free, self-assembled prodrug consisting of a hydrophobic palmitic (16-carbon chain n-hexadecane chain) moiety and hydrophilic group (or moiety) which is included in a caspase-3-specific cleavable peptide (Asp-Glu-Val-Asp, DEVD) and a cytotoxic drug (doxorubicin, DOX). The amphiphilic conjugate, the palmitic-DEVD-DOX, has the ability to self-assemble into nanoparticles in saline without the need for any carriers or nanoformulations. Additionally, the inclusion of doxorubicin is in its prodrug form and the apoptosis-specific DEVD peptide lead to the reduced side effects of doxorubicin in normal tissue. Furthermore, the carrier-free palmitic-DEVD-DOX nanoparticles could passively accumulate in the tumor tissues of tumor-bearing mice due to an enhanced permeation and retention (EPR) effect. As a result, the palmitic-DEVD-DOX conjugate showed an enhanced therapeutic effect compared with the unmodified DEVD-DOX conjugate. Therefore, this carrier-free palmitic-DEVD-DOX prodrug has great therapeutic potential to treat solid tumors, overcoming the problems of conventional chemotherapy and nanoparticles.

High-speed, scanned laser structuring of multi-layered eco/bioresorbable materials for advanced electronic systems.

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.

Micro-/Nano-Structured Biodegradable Pressure Sensors for Biomedical Applications.

The interest in biodegradable pressure sensors in the biomedical field is growing because of their temporary existence in wearable and implantable applications without any biocompatibility issues. In contrast to the limited sensing performance and biocompatibility of initially developed biodegradable pressure sensors, device performances and functionalities have drastically improved owing to the recent developments in micro-/nano-technologies including device structures and materials. Thus, there is greater possibility of their use in diagnosis and healthcare applications. This review article summarizes the recent advances in micro-/nano-structured biodegradable pressure sensor devices. In particular, we focus on the considerable improvement in performance and functionality at the device-level that has been achieved by adapting the geometrical design parameters in the micro- and nano-meter range. First, the material choices and sensing mechanisms available for fabricating micro-/nano-structured biodegradable pressure sensor devices are discussed. Then, this is followed by a historical development in the biodegradable pressure sensors. In particular, we highlight not only the fabrication methods and performances of the sensor device, but also their biocompatibility. Finally, we intoduce the recent examples of the micro/nano-structured biodegradable pressure sensor for biomedical applications.

Soft, bioresorbable coolers for reversible conduction block of peripheral nerves.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

Wireless and Linear Hydrogen Detection up to 4% with High Sensitivity through Phase-Transition-Inhibited Pd Nanowires.

Palladium (Pd) has been drawing increasing attention as a hydrogen (H2) detecting material due to its highly selective sensitivity to H2. However, at H2 concentrations above 2%, Pd undergoes an inevitable phase transition, causing undesirable electrical and mechanical alterations. In particular, nonlinear gas response (ΔR/R0) that accompanies phase transition has been a great bottleneck for detecting H2 in high concentrations, which is especially important as there is a risk of explosion over 4% H2. Here, we propose a phase-transition-inhibited Pd nanowire H2 sensor that can detect up to 4% H2 with high linearity and high sensitivity. Based on the calculation of the change in free energy, we designed Pd nanowires that are highly adhered to the substrate to withstand the stress that leads to phase transition. We theoretically optimized the Pd nanowire dimensions using a finite element method simulation and then experimentally fabricated the proposed sensor by exploiting a developed nanofabrication method. The proposed sensor exhibits a high sensing linearity (98.9%) with high and stable sensitivity (ΔR/R0/[H2] = 875%·bar-1) over a full range of H2 concentrations (0.1-4%). Using the fabricated Pd sensors, we have successfully demonstrated a wireless sensor module that can detect H2 with high linearity, notifying real-time H2 leakage through remote communication. Overall, our work suggests a nanostructuring strategy for detecting H2 with a phase-transition-inhibited pure Pd H2 sensor with rigorous scientific exploration.

Aligned CuO nanowire array for a high performance visible light photodetector.

Recently, copper oxide (CuO) has drawn much attention as a promising material in visible light photodetection with its advantages in ease of nanofabrication. CuO allows a variety of nanostructures to be explored to enhance the optoelectrical performance such as photogenerated carriers scattering and bandgap engineering. However, previous researches neglect in-depth analysis of CuO's light interaction effects, restrictively using random orientation such as randomly arranged nanowires, single nanowires, and dispersed nanoparticles. Here, we demonstrate an ultra-high performance CuO visible light photodetector utilizing perfectly-aligned nanowire array structures. CuO nanowires with 300 nm-width critical dimension suppressed carrier transport in the dark state and enhanced the conversion of photons to carriers; additionally, the aligned arrangement of the nanowires with designed geometry improved the light absorption by means of the constructive interference effect. The proposed nanostructures provide advantages in terms of dark current, photocurrent, and response time, showing unprecedentedly high (state-of-the-art) optoelectronic performance, including high values of sensitivity (S = 172.21%), photo-responsivity (R = 16.03 A/W, λ = 535 nm), photo-detectivity (D* = 7.78 × 1011 Jones), rise/decay time (τr/τd = 0.31 s/1.21 s).

Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

Integration of Gold Nanoparticle-Carbon Nanotube Composite for Enhanced Contact Lifetime of Microelectromechanical Switches with Very Low Contact Resistance.

Electrical circuits require ideal switches with low power consumption for future electronic applications. However, transistors, the most developed electrical switches available currently, have certain fundamental limitations such as increased leakage current and limited subthreshold swing. To overcome these limitations, micromechanical switches have been extensively studied; however, it is challenging to develop micromechanical switches with high endurance and low contact resistance. This study demonstrates highly reliable microelectromechanical switches using nanocomposites. Nanocomposites consisting of gold nanoparticles (Au NPs) and carbon nanotubes (CNTs) are coated on contact electrodes as contact surfaces through a scalable and solution-based fabrication process. While deformable CNTs in the nanocomposite increase the effective contact area under mechanical loads, highly conductive Au NPs provide current paths with low contact resistance between CNTs. Given these advantages, the switches exhibit robust switching operations over 5 × 106 cycles under hot-switching conditions in air. The switches also show low contact resistance without subthreshold region, an extremely small leakage current, and a high on/off ratio.

Bioresorbable Metals for Biomedical Applications: From Mechanical Components to Electronic Devices.

Bioresorbable metals and metal alloys are of growing interest for myriad uses in temporary biomedical implants. Examples range from structural elements as stents, screws, and scaffolds to electronic components as sensors, electrical stimulators, and programmable fluidics. The associated physical forms span mechanically machined bulk parts to lithographically patterned conductive traces, across a diversity of metals and alloys based on magnesium, zinc, iron, tungsten, and others. The result is a rich set of opportunities in healthcare materials science and engineering. This review article summarizes recent advances in this area, starting with an historical perspective followed by a discussion of materials options, considerations in biocompatibility, and device applications. Highlights are in system level bioresorbable electronic platforms that support functions as diagnostics and therapeutics in the context of specific, temporary clinical needs. A concluding section highlights challenges and emerging research directions.

Chemo-Mechanically Operating Palladium-Polymer Nanograting Film for a Self-Powered H2 Gas Sensor.

This study proposes a reliable and self-powered hydrogen (H2) gas sensor composed of a chemo-mechanically operating nanostructured film and photovoltaic cell. Specifically, the nanostructured film has a configuration in which an asymmetrically coated palladium (Pd) film is coated on a periodic polyurethane acrylate (PUA) nanograting. The asymmetric Pd nanostructures, optimized by a finite element method simulation, swell upon reacting with H2 and thereby bend the PUA nanograting, changing the amount of transmitted light and the current output of the photovoltaic cell. Since the degree of warping is determined by the concentration of H2 gas, a wide concentration range of H2 (0.1-4.0%) can be detected by measuring the self-generated electrical current of the photovoltaic cell without external power. The normalized output current changes are ∼1.5%, ∼2.8%, ∼3.5%, ∼5.0%, ∼21.5%, and 25.3% when the concentrations of H2 gas are 0.1%, 0.5%, 1.0%, 1.6%, 2%, and 4%, respectively. Moreover, because Pd is highly chemically reactive to H2 and also because there is no electrical current applied through Pd, the proposed sensor can avoid device failure due to the breakage of the Pd sensing material, resulting in high reliability, and can show high selectivity against various gases such as carbon monoxide, hydrogen sulfide, nitrogen dioxide, and water vapor. Finally, using only ambient visible light, the sensor was modularized to produce an alarm in the presence of H2 gas, verifying a potential always-on H2 gas monitoring application.

Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities.

Soft microfluidic systems that capture, store, and perform biomarker analysis of microliter volumes of sweat, in situ, as it emerges from the surface of the skin, represent an emerging class of wearable technology with powerful capabilities that complement those of traditional biophysical sensing devices. Recent work establishes applications in the real-time characterization of sweat dynamics and sweat chemistry in the context of sports performance and healthcare diagnostics. This paper presents a collection of advances in biochemical sensors and microfluidic designs that support multimodal operation in the monitoring of physiological signatures directly correlated to physical and mental stresses. These wireless, battery-free, skin-interfaced devices combine lateral flow immunoassays for cortisol, fluorometric assays for glucose and ascorbic acid (vitamin C), and digital tracking of skin galvanic responses. Systematic benchtop evaluations and field studies on human subjects highlight the key features of this platform for the continuous, noninvasive monitoring of biochemical and biophysical correlates of the stress state.

Bioresorbable, Wireless, Passive Sensors as Temporary Implants for Monitoring Regional Body Temperature.

Measurements of regional internal body temperatures can yield important information in the diagnosis of immune response-related anomalies, for precisely managing the effects of hyperthermia and hypothermia therapies and monitoring other transient body processes such as those associated with wound healing. Current approaches rely on permanent implants that require extraction surgeries after the measurements are no longer needed. Emerging classes of bioresorbable sensors eliminate the requirements for extraction, but their use of percutaneous wires for data acquisition leads to risks for infection at the suture site. As an alternative, a battery-free, wireless implantable device is reported here, which is constructed entirely with bioresorbable materials for monitoring regional internal body temperatures over clinically relevant timeframes. Ultimately, these devices disappear completely in the body through natural processes. In vivo demonstrations indicate stable operation as subcutaneous and intracranial implants in rat models for up to 4 days. Potential applications include monitoring of healing cascades associated with surgical wounds, recovery processes following internal injuries, and the progression of thermal therapies for various conditions.

Geometrically Structured Nanomaterials for Nanosensors, NEMS, and Nanosieves.

Recently, geometrically structured nanomaterials have received great attention due to their unique physical and chemical properties, which originate from the geometric variation in such materials. Indeed, the use of various geometrically structured nanomaterials has been actively reported in enhanced-performance devices in a wide range of applications. Recent significant progress in the development of geometrically structured nanomaterials and associated devices is summarized. First, a brief introduction of advanced nanofabrication methods that enable the fabrication of various geometrically structured nanomaterials is given, and then the performance enhancements achieved in devices utilizing these nanomaterials, namely, i) physical and gas nanosensors, ii) nanoelectromechanical devices, and iii) nanosieves are described. For the device applications, a systematic summary of their structures, working mechanisms, fabrication methods, and output performance is provided. Particular focus is given to how device performance can be enhanced through the geometric structures of the nanomaterials. Finally, perspectives on the development of novel nanomaterial structures and associated devices are presented.

Stress-engineered palladium nanowires for wide range (0.1%-3.9%) of H2 detection with high durability.

Pd nanowire-based H2 sensors have attracted significant attention because of their superior sensing performance. However, when exposed to H2 concentrations of more than 2%, Pd experiences volume expansion over 10%, resulting in a significant amount of mechanical stress. Thus, exposure to such high H2 concentrations causes physical destruction of Pd nanowires, such as breaks and peel-offs, leading to severe difficulty in the reliable detection of H2 over a wide concentration range. Here, we proposed a structural approach to resolve this issue by introducing a partially anchored Pd nanowire (PA-PdNW) structure. In this configuration, most of the structure was air-suspended, leaving a small portion anchored to the substrate. Air-suspension enabled PA-PdNW to expand freely, thus relieving the mechanical stress; therefore, the Pd nanowires could withstand numerous exposures to high H2 concentrations. To demonstrate the PA-PdNW structure, we developed a nano-fabrication method based on conventional semiconductor processes and successfully manufactured H2 sensor devices with uniform, perfectly aligned PA-PdNW arrays stably air-suspended with designed gaps from the substrate. The fabricated sensors achieved reliable detection of H2 in the 0.1%-3.9% concentration range with a significant resistance change. In addition, compared with fully anchored Pd nanowire (FA-PdNW) sensors, the PA-PdNW sensors showed superior durability, and the nanowires retained their initial structures even after 300 exposures to high H2 concentrations. Furthermore, it was confirmed that the PA-PdNW sensor can stably operate even in extremely humid environments at 85% relative humidity.

High Lithium Ion Transport Through rGO-Wrapped LiNi0.6Co0.2Mn0.2O2 Cathode Material for High-Rate Capable Lithium Ion Batteries.

In this work, we show an effective ultrasonication-assisted self-assembly method under surfactant solution for a high-rate capable rGO-wrapped LiNi0.6Co0.2Mn0.2O2 (Ni-rich cathode material) composite. Ultrasonication indicates the pulverization of the aggregated bulk material into primary nanoparticles, which is effectively beneficial for synthesizing a homogeneous wrapped composite with rGO. The cathode composite demonstrates a high initial capacity of 196.5 mAh/g and a stable capacity retention of 83% after 100 cycles at a current density of 20 mA/g. The high-rate capability shows 195 and 140 mAh/g at a current density of 50 and 500 mA/g, respectively. The high-rate capable performance is attributed to the rapid lithium ion diffusivity, which is confirmed by calculating the transformation kinetics of the lithium ion by galvanostatic intermittent titration technique (GITT) measurement. The lithium ion diffusion rate (D Li) of the rGO-wrapped LiNi0.6Co0.2Mn0.2O2 composite is ca. 20 times higher than that of lithium metal plating on anode during the charge procedure, and this is demonstrated by the high interconnection of LiNi0.6Co0.2Mn0.2O2 and conductive rGO sheets in the composite. The unique transformation kinetics of the cathode composite presented in this study is an unprecedented verification example of a high-rate capable Ni-rich cathode material wrapped by highly conductive rGO sheets.

High-Performance Copper Oxide Visible-Light Photodetector via Grain-Structure Model.

Recently, copper oxide (CuO)-based visible-light photodetectors have attracted great interest due to their narrow bandgap (1.2 eV), low cost, and ease of fabrication. However, there has been insufficient theoretical analysis and study of CuO-based photodetectors, resulting in inferior performance in terms of responsivity, detectivity, and response speed. This work develops a method to enhance the performance of CuO photodetectors by engineering a grain structure based on a newly-developed theoretical model. In the developed theoretical grain-structure model, the grain size and the connections between grains are considered because they can strongly affect the optoelectronic characteristics of CuO photodetectors. Based upon the proposed model, the engineered CuO device achieves enhanced optoelectronic performance. The engineered device shows high responsivity of 15.3 A/W and detectivity of 1.08 × 1011 Jones, which are 18 and 50 times better than those of the unoptimized device, and also shows fast rising and decaying response speeds of 0.682 s and 1.77 s, respectively. In addition, the proposed method is suitable for the mass-production of performance-enhanced, reliable photodetectors. By using a conventional semiconductor fabrication process, a photodetector-array is demonstrated on a 4-inch wafer. The fabricated devices show uniform, high, and stable optoelectronic performance for a month.