A Fully Wireless and Batteryless Localization System With 50 Micrometre Motion Detection Capability and Adaptive Transmitter Power Control for Point-of-Care Biomedical Applications.

Localization has varied applications in biomedicine, such as wireless capsule endoscopy (WCE), detection of cancerous tissue, drug delivery, robotic surgeries, and brain mapping. Currently, most localization systems are battery-powered and suffer from issues regarding battery leakage and limited battery life, resulting in potential health hazards and inconveniences when using them for continuous health monitoring applications. This article proposes an entirely wireless and battery-less 2D localization system consisting of an integrated circuit (IC) that is wirelessly powered at a distance of 4 cm by a 40.68 MHz radio frequency (RF) power of only 2 W. The proposed localization system wirelessly transmits a locked sub-harmonic 13.56 MHz signal generated from the wirelessly received 40.68 MHz RF power signal, eliminating the need for a power-hungry oscillator. Additionally, the system, having a measurement latency of 11.3 ms, has also been verified to sense motion as small as 50 [Formula: see text] as well as measure the rate of motion up to 10 beats per minute, therefore extending its application to the detection of physiological motions such as diaphragm motion during breathing. The localizer has a small form factor of 17 mm × 12 mm × 0.2 mm and consumes an average power of 6 µW. Ex vivo measurements using the localizer inside the porcine intestine demonstrate a localization accuracy of less than 5 mm.

Design and Implementation of Multisite Stimulation System Using a Double-Tuned Transmitter Coil and Miniaturized Implants.

This letter presents a double-tuned dual input transmitter coil operating at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands for multisite biomedical applications. The proposed system removes the need for two separate coils, which reduces system size and unwanted couplings. The design and analysis of the double-tuned transmitter coil using a lumped element frequency trap are discussed in this letter. The transmitter achieves measured matching of -26.2 dB and -21.5 dB and isolation of -17.7 dB and -11.7dB at 13.56 MHz and 40.68 MHz, respectively. A 3 mm × 15 mm flexible coil is used as an implantable receiver. This letter shows synchronized multisite stimulation of two flexible implants at a distance of 2 cm while covered with 1 cm chicken breast.

Miniaturized Wirelessly Powered and Controlled Implants for Multisite Stimulation.

This paper presents a miniaturized implant with a diameter of only 14 mm, which houses a novel System on Chip (SoC) enabling two voltage level stimulation of up to 16 implants using a single Tx coil. Each implant can operate at a distance of 80 mm in the air through the inductive resonant link. The SoC consumes only 27 µW static power and enables two channels with stimulation amplitudes of 1.8 V and 3.3 V and timing resolution of 100 µs. The SoC is implemented in the standard 180 nm complementary metal oxide semiconductor (CMOS) technology and has an area of 0.75 mm × 1.6 mm. The SoC comprises an RF rectifier, low drop-out regulator (LDO), error detection block, clock data recovery, finite state machine (FSM), and output stage. Each implant has a PCB-defined passcode, which enables the individual addressability of the implants for synchronized therapies. The implantable device weighs only 80 mg and sizes 20.1 mm3. Tolerance of up to 70° to angular misalignment was measured at a distance of 50 mm. The efficacy of bilateral stimulation was further verified by implanting two devices on two sides of a pig's neck and performing bilateral vagus nerve stimulation (VNS), while monitoring the heart rate.

Vagus nerve stimulation using a miniaturized wirelessly powered stimulator in pigs.

Neuromodulation of peripheral nerves has been clinically used for a wide range of indications. Wireless and batteryless stimulators offer important capabilities such as no need for reoperation, and extended life compared to their wired counterparts. However, there are challenging trade-offs between the device size and its operating range, which can limit their use. This study aimed to examine the functionality of newly designed wirelessly powered and controlled implants in vagus nerve stimulation for pigs. The implant used near field inductive coupling at 13.56 MHz industrial, scientific, and medical band to harvest power from an external coil. The circular implant had a diameter of 13 mm and weighed 483 mg with cuff electrodes. The efficiency of the inductive link and robustness to distance and misalignment were optimized. As a result, the specific absorption rate was orders of magnitude lower than the safety limit, and the stimulation can be performed using only 0.1 W of external power. For the first time, wireless and batteryless VNS with more than 5 cm operation range was demonstrated in pigs. A total of 84 vagus nerve stimulations (10 s each) have been performed in three adult pigs. In a quantitative comparison of the effectiveness of VNS devices, the efficiency of systems on reducing heart rate was similar in both conventional (75%) and wireless (78.5%) systems. The pulse width and frequency of the stimulation were swept on both systems, and the response for physiological markers was drawn. The results were easily reproducible, and methods used in this study can serve as a basis for future wirelessly powered implants.

A 13.56-MHz -25-dBm-Sensitivity Inductive Power Receiver System-on-a-Chip With a Self-Adaptive Successive Approximation Resonance Compensation Front-End for Ultra-Low-Power Medical Implants.

Battery-less and ultra-low-power implantable medical devices (IMDs) with minimal invasiveness are the latest therapeutic paradigm. This work presents a 13.56-MHz inductive power receiver system-on-a-chip with an input sensitivity of -25.4 dBm (2.88 µW) and an efficiency of 46.4% while driving a light load of 30 µW. In particular, a real-time resonance compensation scheme is proposed to mitigate resonance variations commonly seen in IMDs due to different dielectric environments, loading conditions, and fabrication mismatches, etc. The power-receiving front-end incorporates a 6-bit capacitor bank that is periodically adjusted according to a successive-approximation-resonance-tuning (SART) algorithm. The compensation range is as much as 24 pF and it converges within 12 clock cycles and causes negligible power consumption overhead. The harvested voltage from 1.7 V to 3.3 V is digitized on-chip and transmitted via an ultra-wideband impulse radio (IR-UWB) back-telemetry for closed-loop regulation. The IC is fabricated in 180-nm CMOS process with an overall current dissipation of 750 nA. At a separation distance of 2 cm, the end-to-end power transfer efficiency reaches 16.1% while driving the 30-µW load, which is immune to artificially induced resonance capacitor offsets. The proposed system can be applied to various battery-less IMDs with the potential improvement of the power transfer efficiency on orders of magnitude.

Author Correction: Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers.

About 30% of patients with impaired cardiac function have ventricular dyssynchrony and seek cardiac resynchronization therapy (CRT). In this study, we demonstrate synchronized biventricular (BiV) pacing in a leadless fashion by implementing miniaturized and wirelessly powered pacemakers. With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The power consumption of these pacemakers is reduced to µW-level by a novel integrated circuit design, which considerably extends the maximum operating distance. Leadless BiV pacing is demonstrated for the first time in both open-chest and closed-chest porcine settings. The clinical outcomes associated with different interventricular delays are verified through electrophysiologic and hemodynamic responses. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2-3 orders of magnitude lower than the safety regulation limit. This work serves as a basis for future wirelessly powered leadless pacemakers that address various cardiac resynchronization challenges.

A UHF/UWB Hybrid RFID Tag With a 51-m Energy-Harvesting Sensitivity for Remote Vital-Sign Monitoring.

A novel ultra-high frequency (UHF)/ultra-wideband (UWB) hybrid RFID tag is reported for object-specific remote vital-sign monitoring application. The tag achieves a record energy-harvesting sensitivity at UHF band by codesigning a meander dipole antenna and a passive rectifier. The especially high quality-factor makes the frontend sensitive to near-field motions such as heartbeats and respiration in a wearable setting. The custom CMOS IC of approximately 1-µW power consumption builds around a low-power UWB transmitter and converts variations of the supply voltage to the impulse repetition rate. The tag consisting of the IC and UHF/UWB antennas requires no other discrete components and features a size of 4.2 cm × 2.9 cm and a weight of 0.93 g. A long-distance experiment verifies that the tag can be wirelessly powered up at 51 meters from a 4-W equivalent-isotropic-radiation-power (EIRP) UHF transmitter. Remote vital-sign monitoring is validated on a human subject, in which the UHF power source is placed 2 meters away from the subject with a power emission of less than 20 dBm. This work proposes a first-of-its-kind remote vital-sign monitoring scheme based on a noncontact wearable tag. The design of the far-field energy-harvesting frontend with a record sensitivity serves as a reference for future works on battery-free remote sensors.

Stretchable Transparent Wireless Charging Coil Fabricated by Negative Transfer Printing.

Wearable electronics, such as smartwatches, VR (virtual reality)/AR (augmented reality) smartglasses, and E-textiles, are an emerging technology platform that is reshaping the way people interact with the surrounding world. However, the power source of these devices can be a critical issue, causing short operational/standby times and frequent charging. Here, a stretchable transparent wireless charging coil fabricated by negative adhesive transfer printing (NATP) is demonstrated. The stretchable transparent conductor is based on the silver nanowire (AgNW)-polyurethane acrylate (PUA) composite with high conductivity and robustness under harsh mechanical treatment. A 10.6 ohm/sq thin film has a transmittance of 84% and is still conductive under a mechanical deformation up to 60% tensile strain. A maximum power of 59 mW (power transfer efficiency ∼24%) is transferred wirelessly. A green-light-emitting diode (LED) was wirelessly powered to illustratively demonstrate the functionality of the system. This work provides an alternative power solution which is compatible with the soft and flexible components of wearable devices.

An Integrated Germanium-Based THz Impulse Radiator with an Optical Waveguide Coupled Photoconductive Switch in Silicon.

This paper presents an integrated germanium (Ge)-based THz impulse radiator with an optical waveguide coupled photoconductive switch in a low-cost silicon-on-insulator (SOI) process. This process provides a Ge thin film, which is used as photoconductive material. To generate short THz impulses, N++ implant is added to the Ge thin film to reduce its photo-carrier lifetime to sub-picosecond for faster transient response. A bow-tie antenna is designed and connected to the photoconductive switch for radiation. To improve radiation efficiency, a silicon lens is attached to the substrate-side of the chip. This design features an optical-waveguide-enabled "horizontal" coupling mechanism between the optical excitation signal and the photoconductive switch. The THz emitter prototype works with 1550 nm femtosecond lasers. The radiated THz impulses achieve a full-width at half maximum (FWHM) of 1.14 ps and a bandwidth of 1.5 THz. The average radiated power is 0.337 µ W. Compared with conventional THz photoconductive antennas (PCAs), this design exhibits several advantages: First, it uses silicon-based technology, which reduces the fabrication cost; second, the excitation wavelength is 1550 nm, at which various low-cost laser sources operate; and third, in this design, the monolithic excitation mechanism between the excitation laser and the photoconductive switch enables on-chip programmable control of excitation signals for THz beam-steering.

A 430-MHz Wirelessly Powered Implantable Pulse Generator With Intensity/Rate Control and Sub-1 µA Quiescent Current Consumption.

This work presents a miniaturized µW-level implantable pulse generator (IPG) inductively powered at 430 MHz. Notches are intentionally applied to the incident power, which are replicated to precisely control the timing of the output pulses. Fabricated in a 180-nm CMOS process, the concise circuitry occupies a pad-included footprint of 850 µm × 450 µm and achieves a quiescent current consumption of 950 nA. To reduce the form factor, 401-457 MHz MedRadio-band is utilized to realize the induction link. The finalized assembly achieves one of the smallest dimensions (4.6 mm × 7.0 mm) for near-field IPGs with the Rx coil size of 4.5 mm × 3.6 mm. Codesign of the rectifier and Rx coil accommodates the possible resonant frequency drifts in biological tissues. In the benchtop measurement, a 430-MHz Tx coil is demonstrated to operate the IPG at 4.5 and 4 cm proximities in the air and through water, respectively. An in vivo experiment has been performed, in which the IPG was implanted on the hindlimb muscle belly of an anesthetized rat with the connective tissue and skin sutured. The electrical stimuli induced the isolated ankle flexion at specific strengths and rates, and the experiment complies with the specific absorption rate regulations. This work shows the potential for applications requiring stringent form factors and high sensitivities.

A Multi-site Heart Pacing Study Using Wirelessly Powered Leadless Pacemakers.

In this work, we report an energy-efficient switched capacitor based millimeter-scale pacemaker (5 mm ×7.5 mm) and a multi-receiver wireless energy transfer system operating at around 200 MHz, and use them in a proof-of-concept multi-site heart pacing study. Two pacemakers were placed on two beating Langendorff rodent heart models separately. By utilizing a single transmitter positioned 20-30 cm away, both Langendorff hearts captured the stimuli simultaneously and were electromechanically coupled. This study provides an insight for future energy-efficient and distributed cardiac pacemakers that can offer cardiac resynchronization therapies.

Leadless multisite pacing: A feasibility study using wireless power transfer based on Langendorff rodent heart models.

INTRODUCTION: Fifteen to thirty percent of patients with impaired cardiac function have ventricular dyssynchrony and warrant cardiac resynchronization therapy (CRT). While leadless pacemakers eliminate lead-related complications, their current form factor is limited to single-chamber pacing. In this study, we demonstrate the feasibility of multisite, simultaneous pacing using miniaturized pacing nodes powered through wireless power transfer (WPT). METHODS: A wireless energy transfer system was developed based on resonant coupling at approximately 200 MHz to power multiple pacing nodes. The pacing node comprises circuitry to efficiently convert the harvested energy to output stimuli. To validate the use of these pacing nodes, ex vivo studies were carried out on Langendorff rodent heart models (n = 4). To mimic biventricular pacing, two beating Langendorff rodent heart models, kept 10 cm apart, were paced using two distinct pacing nodes, each attached on the ventricular epicardial surface of a given heart. RESULTS: All ex vivo Langendorff heart models were successfully paced with a simple coil antenna at 2 to 3 cm from the pacing node. The coil was operated at 198 MHz and 0.3 W. Subsequently, simultaneous pacing of two Langendorff heart models 30 cm apart using an output power of 5 W was reliably demonstrated. CONCLUSION: WPT provides a feasible option for multisite, wireless cardiac pacing. While the current system remains limited in design, it offers support and a conceptual framework for future iterations and eventual clinical utility.

An Energy-Efficient Wirelessly Powered Millimeter-Scale Neurostimulator Implant Based on Systematic Codesign of an Inductive Loop Antenna and a Custom Rectifier.

In this work, a switched-capacitor-based stimulator circuit that enables efficient energy harvesting for neurostimulation applications is presented, followed by the discussion on the optimization of the inductive coupling front-end through a codesign approach. The stimulator salvages input energy and stores it in a storage capacitor, and, when the voltage reaches a threshold, releases the energy as an output stimulus. The dynamics of the circuit are automatically enabled by a positive feedback, eliminating any stimulation control circuit blocks. The IC is fabricated in a 180 nm CMOS process and achieves a quiescent current consumption of 1.8 µA. The inductive coupling front-end is optimized as a loaded resonator, in which the input impedance of the custom rectifier directly loads the inductive loop antenna. The loaded quality factor and the rectifier's efficiency determine the reception sensitivity of the stimulator, while a balance should be achieved for the robustness of the system against dielectric medium variations by increasing the reception bandwidth. The finalized stimulator adopts a 4.9 mm × 4.9 mm inductive loop antenna and achieves an overall assembly dimension of 5 mm × 7.5 mm. Operating at the resonant frequency of 198 MHz, the stimulator works at a 14 cm distance from the transmitter in the air. An animal experiment was performed, in which a fully implanted stimulator excited the sciatic nerve of a rat that consequently triggered the movement of the limb.

Tumor lysing genetically engineered T cells loaded with multi-modal imaging agents.

Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION-(64)Cu). This can now be potentially used for (64)Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR(+)SPION(pos) T cells effectively target in vitro CD19(+) lymphoma.

In-plane heterostructures of graphene and hexagonal boron nitride with controlled domain sizes.

Graphene and hexagonal boron nitride (h-BN) have similar crystal structures with a lattice constant difference of only 2%. However, graphene is a zero-bandgap semiconductor with remarkably high carrier mobility at room temperature, whereas an atomically thin layer of h-BN is a dielectric with a wide bandgap of ∼5.9 eV. Accordingly, if precise two-dimensional domains of graphene and h-BN can be seamlessly stitched together, hybrid atomic layers with interesting electronic applications could be created. Here, we show that planar graphene/h-BN heterostructures can be formed by growing graphene in lithographically patterned h-BN atomic layers. Our approach can create periodic arrangements of domains with size ranging from tens of nanometres to millimetres. The resulting graphene/h-BN atomic layers can be peeled off the growth substrate and transferred to various platforms including flexible substrates. We also show that the technique can be used to fabricate two-dimensional devices, such as a split closed-loop resonator that works as a bandpass filter.