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.

Optimal bilayer composites for temperature-tracking wireless electronics.

Modern silicone-based epidermal electronics engineered for body temperature sensing represent a pivotal development in the quest for advancing preventive medicine and enhancing post-surgical monitoring. While these compact and highly flexible electronics empower real-time monitoring in dynamic environments, a noteworthy limitation is the challenge in regulating the infiltration or obstruction of heat from the external environment into the surface layers of these electronics. The study presents a cost-effective temperature sensing solution by embedding wireless electronics in a multi-layered elastomeric composite to meet the dual needs of enhanced thermal insulation for encapsulation in contact with air and improved thermal conductivity for the substrate in contact with the skin. The encapsulating composite benefits from the inclusion of hollow silica microspheres, which reduce the thermal conductivity by 40%, while non-spherical aluminum nitride enhances the thermal conductivity of the substrate by 370%. The addition of particles to the respective composites inevitably leads to an increase in modulus. Two composite elements are engineered to coexist while maintaining a matching low modulus of 3.4 MPa and a stretchability exceeding 30%, all without compromising the optimized thermal properties. Consecutive thermal, electrical, and mechanical characterization confirms the sensor's capacity for precise body temperature monitoring during a single day's lifespan, while also assessing the influence of behavioral factors on body temperature.

Highly Reliable 3D Channel Memory and Its Application in a Neuromorphic Sensory System for Hand Gesture Recognition.

Brain-inspired neuromorphic computing systems, based on a crossbar array of two-terminal multilevel resistive random-access memory (RRAM), have attracted attention as promising technologies for processing large amounts of unstructured data. However, the low reliability and inferior conductance tunability of RRAM, caused by uncontrollable metal filament formation in the uneven switching medium, result in lower accuracy compared to the software neural network (SW-NN). In this work, we present a highly reliable CoOx-based multilevel RRAM with an optimized crystal size and density in the switching medium, providing a three-dimensional (3D) grain boundary (GB) network. This design enhances the reliability of the RRAM by improving the cycle-to-cycle endurance and device-to-device stability of the I-V characteristics with minimal variation. Furthermore, the designed 3D GB-channel RRAM (3D GB-RRAM) exhibits excellent conductance tunability, demonstrating high symmetricity (624), low nonlinearity (ßLTP/ßLTD ∼ 0.20/0.39), and a large dynamic range (Gmax/Gmin ∼ 31.1). The cyclic stability of long-term potentiation and depression also exceeds 100 cycles (105 voltage pulses), and the relative standard deviation of Gmax/Gmin is only 2.9%. Leveraging these superior reliability and performance attributes, we propose a neuromorphic sensory system for finger motion tracking and hand gesture recognition as a potential elemental technology for the metaverse. This system consists of a stretchable double-layered photoacoustic strain sensor and a crossbar array neural network. We perform training and recognition tasks on ultrasonic patterns associated with finger motion and hand gestures, attaining a recognition accuracy of 97.9% and 97.4%, comparable to that of SW-NN (99.8% and 98.7%).

Implantable, Bioresorbable Radio Frequency Resonant Circuits for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes.

Fluorescent-based biodegradable microneedle sensor array for tether-free continuous glucose monitoring with smartphone application.

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

Ultrathin Crystalline Silicon Nano and Micro Membranes with High Areal Density for Low-Cost Flexible Electronics.

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

A battery-less wireless implant for the continuous monitoring of vascular pressure, flow rate and temperature.

Devices for monitoring blood haemodynamics can guide the perioperative management of patients with cardiovascular disease. Current technologies for this purpose are constrained by wired connections to external electronics, and wireless alternatives are restricted to monitoring of either blood pressure or blood flow. Here we report the design aspects and performance parameters of an integrated wireless sensor capable of implantation in the heart or in a blood vessel for simultaneous measurements of pressure, flow rate and temperature in real time. The sensor is controlled via long-range communication through a subcutaneously implanted and wirelessly powered Bluetooth Low Energy system-on-a-chip. The device can be delivered via a minimally invasive transcatheter procedure or it can be mounted on a passive medical device such as a stent, as we show for the case of the pulmonary artery in a pig model and the aorta and left ventricle in a sheep model, where the device performs comparably to clinical tools for monitoring of blood flow and pressure. Battery-less and wireless devices such as these that integrate capabilities for flow, pressure and temperature sensing offer the potential for continuous monitoring of blood haemodynamics in patients.

Wireless and battery-free technologies for neuroengineering.

Tethered and battery-powered devices that interface with neural tissues can restrict natural motions and prevent social interactions in animal models, thereby limiting the utility of these devices in behavioural neuroscience research. In this Review Article, we discuss recent progress in the development of miniaturized and ultralightweight devices as neuroengineering platforms that are wireless, battery-free and fully implantable, with capabilities that match or exceed those of wired or battery-powered alternatives. Such classes of advanced neural interfaces with optical, electrical or fluidic functionality can also combine recording and stimulation modalities for closed-loop applications in basic studies or in the practical treatment of abnormal physiological processes.

Vertical Gate-All-Around Device Architecture to Improve the Device Performance for Sub-5-nm Technology.

In this work, we propose a vertical gate-all-around device architecture (GAA-FinFET) with the aim of simultaneously improving device performance as well as addressing the short channel effect (SCE). The GAA-FinFET was built using the technology computer-aided design (TCAD) simulation tool, and then, its electrical characteristics were quantitatively evaluated. The electrical characteristics of the GAA-FinFET were compared to those of conventional FinFET and nano-sheet FET (NSFET) at 7 nm or 5 nm nodes. When comparing the GAA-FinFET against the FinFET, it achieved not only better SCE characteristics, but also higher on-state drive current due to its gate-all-around device structure. This helps to improve the ratio of effective drive current to off-state leakage current (i.e., Ieff/Ioff) by ~30%, resulting in an improvement in DC device performance by ~10%. When comparing the GAA-FinFET against the NSFET, it exhibited SCE characteristics that were comparable or superior thanks to its improved sub-channel leakage suppression. It turned out that the proposed GAA-FinFET (compared to conventional FinFET at the 7 nm or 5 nm nodes, or even beyond) is an attractive option for improving device performance in terms of SCE and series resistance. Furthermore, it is expected that the device structure of GAA-FinFET is very similar to that of conventional FinFET, resulting in further improvement to its electrical characteristics as a result of its gate-all-around device structure without significant modification with respect to the processing steps for conventional FinFET.

Micro-ultrasonic Assessment of Early Stage Clot Formation and Whole Blood Coagulation Using an All-Optical Ultrasound Transducer and Adaptive Signal Processing Algorithm.

Abnormal formation of solid thrombus inside a blood vessel can cause thrombotic morbidity and mortality. This necessitates early stage diagnosis, which requires quantitative assessment with a small volume, for effective therapy with low risk to unwanted development of various diseases. We propose a micro-ultrasonic diagnosis using an all-optical ultrasound-based spectral sensing (AOUSS) technique for sensitive and quantitative characterization of early stage and whole blood coagulation. The AOUSS technique detects and analyzes minute viscoelastic variations of blood at a micro-ultrasonic spot (<100 µm) defined by laser-generated focused ultrasound (LGFU). This utilizes (1) a uniquely designed optical transducer configuration for frequency-spectral matching and wideband operation (6 dB widths: 7-32 MHz and d.c. ∼ 46 MHz, respectively) and (2) an empirical mode decomposition (EMD)-based signal process particularly adapted to nonstationary LGFU signals backscattered from the spot. An EMD-derived spectral analysis enables one to assess viscoelastic variations during the initiation of fibrin formation, which occurs at a very early stage of blood coagulation (1 min) with high sensitivity (frequency transition per storage modulus increment = 8.81 MHz/MPa). Our results exhibit strong agreement with those obtained by conventional rheometry (Pearson's R > 0.95), which are also confirmed by optical microscopy. The micro-ultrasonic and high-sensitivity detection of AOUSS poses a potential clinical significance, serving as a screening modality to diagnose early stage clot formation (e.g., as an indicator for hypercoagulation of blood) and stages of blood-to-clot transition to check a potential risk for development into thrombotic diseases.

Strain-Dependent Photoacoustic Characteristics of Free-Standing Carbon-Nanocomposite Transmitters.

In this paper we demonstrate strain-dependent photoacoustic (PA) characteristics of free-standing nanocomposite transmitters that are made of carbon nanotubes (CNT) and candle soot nanoparticles (CSNP) with an elastomeric polymer matrix. We analyzed and compared PA output performances of these transmitters which are prepared first on glass substrates and then in a delaminated free-standing form for strain-dependent characterization. This confirms that the nanocomposite transmitters with lower concentration of nanoparticles exhibit more flexible and stretchable property in terms of Young's modulus in a range of 4.08-10.57 kPa. Then, a dynamic endurance test was performed revealing that both types of transmitters are reliable with pressure amplitude variation as low as 8-15% over 100-800 stretching cycles for a strain level of 5-28% with dynamic endurance in range of 0.28-2.8%. Then, after 2000 cycles, the transmitters showed pressure amplitude variation of 6-29% (dynamic endurance range of 0.21-1.03%) at a fixed strain level of 28%. This suggests that the free-standing nanocomposite transmitters can be used as a strain sensor under a variety of environments providing robustness under repeated stretching cycles.

Experimental Demonstration of a Stacked Hybrid Optoacoustic-Piezoelectric Transducer for Localized Heating and Enhanced Cavitation.

Laser-generated focused ultrasound (LGFU) is an emerging modality for cavitation-based therapy. However, focal pressure amplitudes by LGFU alone to achieve pulsed cavitation are often lacking as a treatment depth increases. This requires a higher pressure from a transmitter surface and more laser energies that even approach to a damage threshold of transmitter. To mitigate the requirement for LGFU-induced cavitation, we propose LGFU configurations with a locally heated focal zone using an additional high-intensity focused ultrasound (HIFU) transmitter. After confirming heat-induced cavitation enhancement using two separate transmitters, we then developed a stacked hybrid optoacoustic-piezoelectric transmitter, which is a unique configuration made by coating an optoacoustic layer directly onto a piezoelectric substrate. This shared curvature design has great practical advantage without requiring the complex alignment of two focal zones. Moreover, this enabled the amplification of cavitation bubble density by 18.5-fold compared to the LGFU operation alone. Finally, the feasibility of tissue fragmentation was confirmed through a tissue-mimicking gel, using the combination of LGFU and HIFU (not via a stacked structure). We expect that the stacked transmitter can be effectively used for stronger and faster tissue fragmentation than the LGFU transmitter alone.

Vital signal sensing and manipulation of a microscale organ with a multifunctional soft gripper.

Soft grippers that incorporate functional materials are important in the development of mechanically compliant and multifunctional interfaces for both sensing and stimulating soft objects and organisms. In particular, the capability for firm and delicate grasping of soft cells and organs without mechanical damage is essential to identify the condition of and monitor meaningful biosignals from objects. Here, we report a millimeter-scale soft gripper based on a shape memory polymer that enables manipulating a heavy object (payload-to-weight ratio up to 6400) and grasping organisms at the micro/milliscale. The silver nanowires and crack-based strain sensor embedded in this soft gripper enable simultaneous measurement of the temperature and pressure on grasped objects and offer temperature and mechanical stimuli for the grasped object. We validate our miniaturized soft gripper by demonstrating that it can grasp a snail egg while simultaneously applying a moderate temperature stimulation to induce hatching process and monitor the heart rate of a newborn snail. The results present the potential for widespread utility of soft grippers in the area of biomedical engineering, especially in the development of conditional or closed-loop interfacing with microscale biotissues and organisms.

Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents.

Implantable deep brain stimulation (DBS) systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic pain. However, long-term efficacy of DBS is limited, and chronic neuroplastic changes and associated therapeutic mechanisms are not well understood. Fundamental and mechanistic investigation, typically accomplished in small animal models, is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise insight. To overcome these challenges, we demonstrate a fully implantable, wireless, battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real time. The devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance, surface-engineered platinum electrodes. The devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid dissemination. Efficacy of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days.

Three-dimensional electronic microfliers inspired by wind-dispersed seeds.

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.

Battery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.

Variable-focus optoacoustic lens with wide dynamic range and long focal length by using a flexible polymer nano-composite membrane.

We demonstrate a variable-focus optoacoustic lens (VFOL) by pneumatically controlling a flexible polymer nano-composite membrane, which can produce laser-generated focused ultrasound (LGFU) with a high peak amplitude (>30 MPa) and a tight focal dimension (several hundred µm) over a wide dynamic range of focus variation (>20 mm) together with a long focal length up to 60 mm, each of which is widest and longest among optoacoustic lenses developed so far. Two different designs in lens dimension have been fabricated and characterized: VFOL-L with a 40-mm diameter and VFOL-S with 10 mm. VFOL-L exhibits a wide dynamic range of focal length variation from 38.52 to 60.39 mm with a center frequency near ~ 10 MHz, which is proper for practical long-range applications with several-cm depth. In comparison, VFOL-S covers a focal variation range from 6.75 to 11.1 mm with ~ 14 MHz, producing a relatively higher-pressure amplitude, which allows the inception of acoustic cavitation at an impedance-mismatched boundary. The nano-composite membrane of VFOL is actuated from a planar to deeply curved shape by externally injecting liquid into the VFOL, resulting in a focal gain up to 255 and a positive peak pressure of > 30 MPa in the VFOL-L case. The minimum-geometrical f-number as low as 0.963 is achieved at the shortest focal length (38.52 mm) with 6-dB lateral and axial spot dimensions of 304 µm and 2.86 mm, respectively. We expect that the proposed VFOL-based LGFU with a high peak pressure, a wide dynamic axial range, and a tight focal dimension are suitably applied for depth-dependent characterization of tissues and shockwave treatment, taking advantages of optoacoustic pulses as input with inherent broadband high-frequency characteristics.

Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue.

Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young's modulus of skin and of other soft tissues at depths of approximately 1-8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders.