A Wirelessly Powered Scattered Neural Recording Wearable System.

This paper introduces a wirelessly powered scattered neural recording wearable system that can facilitate continuous, untethered, and long-term electroencephalogram (EEG) recording. The proposed system, including 32 standalone EEG recording devices and a central controller, is incorporated in a wearable form factor. The standalone devices are sparsely distributed on the scalp, allowing for flexible placement and varying quantities to provide extensive spatial coverage and scalability. Each standalone device featuring a low-power EEG recording application-specific integrated circuit (ASIC) wirelessly receives power through a 60 MHz inductive link. The low-power ASIC design (84.6 µW) ensures sufficient wireless power reception through a small receiver (Rx) coil. The 60 MHz inductive link also serves as the data carrier for wireless communication between standalone devices and the central controller, eliminating the need for additional data antennas. All these efforts contribute to the miniaturization of standalone devices with dimensions of 12×12×5 mm3, enhancing device wearability. The central controller applies the pulse width modulation (PWM) scheme on the 60 MHz carrier, transmitting user commands at 4 Mbps to EEG recording ASICs. The ASIC employs a novel synchronized PWM demodulator to extract user commands, operating signal digitization and data transmission. The analog frontend (AFE) amplifies the EEG signal with a gain of 45 dB and applies band-pass filtering from 0.03 Hz to 400 Hz, with an input-referred noise (IRN) of 3.62 µVRMS. The amplified EEG signal is then digitized by a 10-bit successive approximation register (SAR) analog-to-digital converter (ADC) with a peak signal-to-noise and distortion ratio (SNDR) of 55.4 dB. The resulting EEG data is transmitted to an external software-defined radio (SDR) Rx through load-shift-keying (LSK) backscatter at 3.75 Mbps. The system's functionality is fully evaluated in human experiments.

E-Tattoos: Toward Functional but Imperceptible Interfacing with Human Skin.

The human body continuously emits physiological and psychological information from head to toe. Wearable electronics capable of noninvasively and accurately digitizing this information without compromising user comfort or mobility have the potential to revolutionize telemedicine, mobile health, and both human-machine or human-metaverse interactions. However, state-of-the-art wearable electronics face limitations regarding wearability and functionality due to the mechanical incompatibility between conventional rigid, planar electronics and soft, curvy human skin surfaces. E-Tattoos, a unique type of wearable electronics, are defined by their ultrathin and skin-soft characteristics, which enable noninvasive and comfortable lamination on human skin surfaces without causing obstruction or even mechanical perception. This review article offers an exhaustive exploration of e-tattoos, accounting for their materials, structures, manufacturing processes, properties, functionalities, applications, and remaining challenges. We begin by summarizing the properties of human skin and their effects on signal transmission across the e-tattoo-skin interface. Following this is a discussion of the materials, structural designs, manufacturing, and skin attachment processes of e-tattoos. We classify e-tattoo functionalities into electrical, mechanical, optical, thermal, and chemical sensing, as well as wound healing and other treatments. After discussing energy harvesting and storage capabilities, we outline strategies for the system integration of wireless e-tattoos. In the end, we offer personal perspectives on the remaining challenges and future opportunities in the field.

A Wireless Multimodal Physiological Monitoring ASIC for Animal Health Monitoring Injectable Devices.

Utilizing injectable devices for monitoring animal health offers several advantages over traditional wearable devices, including improved signal-to-noise ratio (SNR) and enhanced immunity to motion artifacts. We present a wireless application-specific integrated circuit (ASIC) for injectable devices. The ASIC has multiple physiological sensing modalities including body temperature monitoring, electrocardiography (ECG), and photoplethysmography (PPG). The ASIC fabricated using the CMOS 180 nm process is sized to fit into an injectable microchip implant. The ASIC features a low-power design, drawing an average DC power of 155.3 µW, enabling the ASIC to be wirelessly powered through an inductive link. To capture the ECG signal, we designed the ECG analog frontend (AFE) with 0.3 Hz low cut-off frequency and 45-79 dB adjustable midband gain. To measure PPG, we employ an energy-efficient and safe switched-capacitor-based (SC) light emitting diode (LED) driver to illuminate an LED with milliampere-level current pulses. A SC integrator-based AFE converts the current of photodiode with a programmable transimpedance gain. A resistor-based Wheatstone Bridge (WhB) temperature sensor followed by an instrumentation amplifier (IA) provides 27-47 °C sensing range with 0.02 °C inaccuracy. Recorded physiological signals are sequentially sampled and quantized by a 10-bit analog-to-digital converter (ADC) with the successive approximation register (SAR) architecture. The SAR ADC features an energy-efficient switching scheme and achieves a 57.5 dB signal-to-noise-and-distortion ratio (SNDR) within 1 kHz bandwidth. Then, a back data telemetry transmits the baseband data via a backscatter scheme with intermediate-frequency assistance. The ASIC's overall functionality and performance has been evaluated through an in vivo experiment.

Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in the majority of individuals with obesity, but in a subset of these individuals, it progresses to nonalcoholic steatohepatitis (0NASH) and fibrosis. The mechanisms that prevent NASH and fibrosis in the majority of patients with NAFLD remain unclear. Here, we report that NAD(P)H oxidase 4 (NOX4) and nuclear factor erythroid 2-related factor 2 (NFE2L2) were elevated in hepatocytes early in disease progression to prevent NASH and fibrosis. Mitochondria-derived ROS activated NFE2L2 to induce the expression of NOX4, which in turn generated H2O2 to exacerbate the NFE2L2 antioxidant defense response. The deletion or inhibition of NOX4 in hepatocytes decreased ROS and attenuated antioxidant defense to promote mitochondrial oxidative stress, damage proteins and lipids, diminish insulin signaling, and promote cell death upon oxidant challenge. Hepatocyte NOX4 deletion in high-fat diet-fed obese mice, which otherwise develop steatosis, but not NASH, resulted in hepatic oxidative damage, inflammation, and T cell recruitment to drive NASH and fibrosis, whereas NOX4 overexpression tempered the development of NASH and fibrosis in mice fed a NASH-promoting diet. Thus, mitochondria- and NOX4-derived ROS function in concert to drive a NFE2L2 antioxidant defense response to attenuate oxidative liver damage and progression to NASH and fibrosis in obesity.

Monomeric and dimeric guaianolide sesquiterpenoids with hypoglycemic activity from Achillea alpina.

Three new monomeric (1-3) and two newdimeric guaianolides (4 and 5), along with three known analogues (6-8) were isolated from the aerial part of Achillea alpina L. Compounds 1-3 were three novel 1,10-seco-guaianolides, while 4 and 5 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures were elucidated by analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their hypoglycemic activity with a glucose consumption model in palmitic acid (PA)-induced HepG2-insulin resistance (IR) cells, and compound 1 showed the most promising activity. A mechanistic study revealed that compound 1 appeared to mediate hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.

A highly stable electrode with low electrode-skin impedance for wearable brain-computer interface.

To date, brain-computer interfaces (BCIs) have proved to play a key role in many medical applications, for example, the rehabilitation of stroke patients. For post-stroke rehabilitation, the BCIs require the EEG electrodes to precisely translate the brain signals of patients into intended movements of the paralyzed limb for months. However, the gold standard silver/silver-chloride electrodes cannot satisfy the requirements for long-term stability and preparation-free recording capability in wearable EEG devices, thus limiting the versatility of EEG in wearable BCI applications over time outside the rehabilitation center. Here, we design a long-term stable and low electrode-skin interfacial impedance conductive polymer-hydrogel EEG electrode that maintains a lower impedance value than gel-based electrodes for 29 days. With this technology, EEG-based long-term and wearable BCIs could be realized in the near future. To demonstrate this, our designed electrode is applied for a wireless single-channel EEG device that detects changes in alpha rhythms in eye-open/eye-close conditions. In addition, we validate that the designed electrodes could capture oscillatory rhythms in motor imagery protocols as well as low-frequency time-locked event-related potentials from healthy subjects, with similar or better performance than gel-based electrodes. Finally, we demonstrate the use of the designed electrode in online BCI-based functional electrical stimulation, which could be used for post-stroke rehabilitation.

An Ultrasonic Energy Harvesting IC Providing Adjustable Bias Voltage for Pre-Charged CMUT.

Ultrasonic wireless power transmission (WPT) using pre-charged capacitive micromachined ultrasonic transducers (CMUT) is drawing great attention due to the easy integration of CMUT with CMOS techniques. Here, we present an integrated circuit (IC) that interfaces with a pre-charged CMUT device for ultrasonic energy harvesting. We implemented an adaptive high voltage charge pump (HVCP) in the proposed IC, which features low power, overvoltage stress (OVS) robustness, and a wide output range. The ultrasonic energy harvesting IC is fabricated in the 180 nm HV BCD process and occupies a 2 × 2.5 mm2 silicon area. The adaptive HVCP offers a 2× - 12× voltage conversion ratio (VCR), thereby providing a wide bias voltage range of 4 V-44 V for the pre-charged CMUT. Moreover, a VCR tunning finite state machine (FSM) implemented in the proposed IC can dynamically adjust the VCR to stabilize the HVCP output (i.e., the pre-charged CMUT bias voltage) to a target voltage in a closed-loop manner. Such a closed-loop control mechanism improves the tolerance of the proposed IC to the received power variation caused by misalignments, amount of transmitted power change, and/or load variation. Besides, the proposed ultrasonic energy harvesting IC has an average power consumption of 35 µW-554 µW corresponding to the HVCP output from 4 V-44 V. The CMUT device with a local surface acoustic intensity of 3.78 mW/mm2, which is well below the FDA limit for power flux (7.2 mW/mm2), can deliver sufficient power to the IC.

Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence.

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor involved in metabolism and the aging process. C3G suppressed hepatic gluconeogenesis by reducing the expression of gluconeogenic genes through the phosphorylation inactivation of CRTC2 and HDAC5 coactivators via AMPK. C3G did not directly interact with AMPK but, instead, activated AMPK through the adiponectin receptor signaling pathway, as demonstrated through adiponectin receptor gene knockdown experiments. In addition, C3G increased cellular AMP levels in cultured hepatocytes, and the oral administration of C3G in mice elevated their plasma adiponectin concentrations. These effects collectively contribute to the activation of AMPK. In addition, C3G showed potent antioxidant activity and induced cellular senescence, and apoptosis in oxidative-stress induced senescence in hepatocarcinoma cells. C3G increased senescence-associated ß-galactosidase expression, while increasing the expression levels of P16, P21 and P53, key markers of cellular senescence. These findings demonstrate that anthocyanin C3G achieves hypoglycemic effects via AMPK activation and the subsequent suppression of gluconeogenesis and exhibits anti-cancer activity through the induction of apoptosis and cellular senescence.

Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance.

Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise. However, the precise mechanisms by which exercise and ROS promote metabolic health remain unclear. Here, we demonstrate that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance. Conversely, reductions in skeletal muscle NOX4 in aging and obesity contribute to the development of insulin resistance. NOX4 deletion in skeletal muscle compromised exercise capacity and antioxidant defense and promoted oxidative stress and insulin resistance in aging and obesity. The abrogated adaptive mechanisms, oxidative stress, and insulin resistance could be corrected by deleting the H2O2-detoxifying enzyme GPX-1 or by treating mice with an agonist of NFE2L2, the master regulator of antioxidant defense. These findings causally link NOX4-derived ROS in skeletal muscle with adaptive responses that promote muscle function and insulin sensitivity.

Towards a Self-Powered ECG and PPG Sensing Wearable Device.

This paper presents a multifunctional sensor interface system-on-chip (SoC) for developing self-powered Electrocardiography (ECG) and Photoplethysmography (PPG) sensing wearable devices. The proposed SoC design consists of switch-capacitor-based LED driver and analog front-end (AFE) for PPG sensing, ECG sensing AFE, and power management unit for energy harvesting from Thermoelectric Generator (TEG), all integrated on a 2×2.5 mm2 chip fabricated in 0.18µm standard CMOS process. We have performed post-layout simulation to verify the functionality and performance of the SoC. The LED driver employs the switch-capacitor-based architecture, which charges a storage capacitor up to 2.1 V and discharges accumulated charge to pass instantaneous current up to 40 mA through a selected LED. The PPG AFE converts the resulting photodiode (PD) current to voltage output with adjustable gain of 114-120 dBΩ and input-referred noise of 119 pARMS within 0.4 Hz-10 kHz. The ECG AFE provides adjustable mid-band gain of 47-63 dB, low-cut frequency of 1.5-6.3 Hz, and input-referred noise of 7.83 µVRMS within 1.5 Hz- 1.2 kHz to amplify/filter the recorded ECG signals. The power management unit is able to perform sufficient energy harvesting with the TEG output voltage as low as 350 mV.

A fully transparent, flexible PEDOT:PSS-ITO-Ag-ITO based microelectrode array for ECoG recording.

Integrative neural interfaces combining neurophysiology and optogenetics with neural imaging provide numerous opportunities for neuroscientists to study the structure and function of neural circuits in the brain. Such a comprehensive interface demands miniature electrode arrays with high transparency, mechanical flexibility, electrical conductivity, and biocompatibility. Conventional transparent microelectrodes made of a single material, such as indium tin oxide (ITO), ultrathin metals, graphene and poly-(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS), hardly possess the desired combination of those properties. Herein, ultra-flexible, highly conductive and fully transparent microscale electrocorticogram (µECoG) electrode arrays made of a PEDOT:PSS-ITO-Ag-ITO assembly are constructed on thin parylene C films. The PEDOT:PSS-ITO-Ag-ITO assembly achieves a maximum ∼14% enhancement in light transmission over a broad spectrum (350-650 nm), a significant reduction in electrochemical impedance by 91.25%, and an increase in charge storage capacitance by 1229.78 µC cm-2. Peeling, bending, and Young's modulus tests verify the enhanced mechanical flexibility and robustness of the multilayer assembly. The µECoG electrodes enable electrical recordings with high signal-to-noise ratios (SNRs) (∼35-36 dB) under different color photostimulations, suggesting that the electrodes are resilient to photon-induced artifacts. In vivo animal experiments confirm that our array can successfully record light-evoked ECoG oscillations from the primary visual cortex (V1) of an anesthetized rat.

A Trimodal Wireless Implantable Neural Interface System-on-Chip.

A wireless and battery-less trimodal neural interface system-on-chip (SoC), capable of 16-ch neural recording, 8-ch electrical stimulation, and 16-ch optical stimulation, all integrated on a 5 ×  3 mm2 chip fabricated in 0.35-µm standard CMOS process. The trimodal SoC is designed to be inductively powered and communicated. The downlink data telemetry utilizes on-off keying pulse-position modulation (OOK-PPM) of the power carrier to deliver configuration and control commands at 50 kbps. The analog front-end (AFE) provides adjustable mid-band gain of 55-70 dB, low/high cut-off frequencies of 1-100 Hz/10 kHz, and input-referred noise of 3.46 µVrms within 1 Hz-50 kHz band. AFE outputs of every two-channel are digitized by a 50 kS/s 10-bit SAR-ADC, and multiplexed together to form a 6.78 Mbps data stream to be sent out by OOK modulating a 434 MHz RF carrier through a power amplifier (PA) and 6 cm monopole antenna, which form the uplink data telemetry. Optical stimulation has a switched-capacitor based stimulation (SCS) architecture, which can sequentially charge four storage capacitor banks up to 4 V and discharge them in selected µLEDs at instantaneous current levels of up to 24.8 mA on demand. Electrical stimulation is supported by four independently driven stimulating sites at 5-bit controllable current levels in ±(25-775) µA range, while active/passive charge balancing circuits ensure safety. In vivo testing was conducted on four anesthetized rats to verify the functionality of the trimodal SoC.

A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice.

We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

A mm-Sized Free-Floating Wireless Implantable Opto-Electro Stimulation Device.

Towards a distributed neural interface, consisting of multiple miniaturized implants, for interfacing with large-scale neuronal ensembles over large brain areas, this paper presents a mm-sized free-floating wirelessly-powered implantable opto-electro stimulation (FF-WIOS2) device equipped with 16-ch optical and 4-ch electrical stimulation for reconfigurable neuromodulation. The FF-WIOS2 is wirelessly powered and controlled through a 3-coil inductive link at 60 MHz. The FF-WIOS2 receives stimulation parameters via on-off keying (OOK) while sending its rectified voltage information to an external headstage for closed-loop power control (CLPC) via load-shift-keying (LSK). The FF-WIOS2 system-on-chip (SoC), fabricated in a 0.35-µm standard CMOS process, employs switched-capacitor-based stimulation (SCS) architecture to provide large instantaneous current needed for surpassing the optical stimulation threshold. The SCS charger charges an off-chip capacitor up to 5 V at 37% efficiency. At the onset of stimulation, the capacitor delivers charge with peak current in 1.7-12 mA range to a micro-LED (µLED) array for optical stimulation or 100-700 µA range to a micro-electrode array (MEA) for biphasic electrical stimulation. Active and passive charge balancing circuits are activated in electrical stimulation mode to ensure stimulation safety. In vivo experiments conducted on three anesthetized rats verified the efficacy of the two stimulation mechanisms. The proposed FF-WIOS2 is potentially a reconfigurable tool for performing untethered neuromodulation.

Toward a High-Throughput Wireless Smart Arena for Behavioral Experiments on Small Animals.

This work presents a high-throughput and scalable wirelessly-powered smart arena for behavioral experiments made of multiple EnerCage Homecage (HC) systems, operating in parallel in a way that they can fit in standard racks that are commonly used in animal facilities. The proposed system, which is referred to as the multi-EnerCage-HC (mEHC), increases the volume of data that can be collected from more animal subjects, while lowering the cost and duration of experiments as well as stress-induced bias by minimizing the involvement of human operators. Thus improving the quality, reproducibility, and statistical power of experiment outcomes, while saving precious lab space. The system is equipped with an auto-tuning mechanism to compensate for the resonance frequency shifts caused by the dynamic nature of the mutual inductance between adjacent homecages. A functional prototype of the mEHC system has been implemented with 7 units and analyzed for theoretical design considerations that would minimize the effects of interference and resonance frequency bifurcation. Experiment results demonstrate robust wireless power and data transmissions capabilities of this system within the noisy lab environment.

A Software-Defined Radio Receiver for Wireless Recording From Freely Behaving Animals.

To eliminate tethering effects on the small animals' behavior during electrophysiology experiments, such as neural interfacing, a robust and wideband wireless data link is needed for communicating with the implanted sensing elements without blind spots. We present a software-defined radio (SDR) based scalable data acquisition system, which can be programmed to provide coverage over standard-sized or customized experimental arenas. The incoming RF signal with the highest power among SDRs is selected in real-time to prevent data loss in the presence of spatial and angular misalignments between the transmitter (Tx) and receiver (Rx) antennas. A 32-channel wireless neural recording system-on-a-chip (SoC), known as WINeRS-8, is embedded in a headstage and transmits digitalized raw neural signals, which are sampled at 25 kHz/ch, at 9 Mbps via on-off keying (OOK) of a 434 MHz RF carrier. Measurement results show that the dual-SDR Rx system reduces the packet loss down to 0.12%, on average, by eliminating the blind spots caused by the moving Tx directionality. The system operation is verified in vivo on a freely behaving rat and compared with a commercial hardwired system.

Kaempferol reduces hepatic triglyceride accumulation by inhibiting Akt.

In this paper, we studied the mechanism of the triglyceride (TG)-lowering effect of kaempferol in vitro and in vivo. Kaempferol showed LXR agonistic activities without inducing TGs or the expression of several lipogenic genes in cultured cells. A luciferase and qPCR analysis showed that kaempferol increased the transactivation of PPARα and PPARδ and stimulated gene expression associated with fatty acid oxidation and uptake in hepatocytes. More importantly, kaempferol inhibited protein kinase B (Akt) activity and suppressed SREBP-1 activation via multiple mechanisms, including through increasing Insig-2a expression, reducing SREBP-1 phosphorylation, and increasing GSK-3 phosphorylation. Collectively, these actions inhibited the SREBP-1 activation process. Furthermore, as an Akt/mTOR pathway inhibitor, kaempferol led to the induction of hepatic autophagy and resulted in a decrease in lipid droplet formation in the mouse liver. These findings demonstrate that kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. PRACTICAL APPLICATIONS: Kaempferol is a major dietary flavonoid in various plant-based foods, and it is used as a valuable ingredient in functional foods, with numerous beneficial properties such as anticancer, antioxidant, and anti-atherosclerotic activities. Kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Currently, the number of people with hyperlipidemia is rapidly growing in both developed and developing societies; thus, we propose that kaempferol could be used for therapeutic interventions aimed at the treatment of these individuals.

Inductively coupled, mm-sized, single channel optical neuro-stimulator with intensity enhancer.

We introduce a single channel neuro-stimulator consisting of a reflector-coupled microscale light emitting diode (µLED) with an integrated mm-sized wireless receiver (Rx) coil for free-floating, battery-free, untethered optogenetics neuromodulation. The system utilizes a two-coil inductive link to deliver instantaneous power at a low operating frequency (<100 MHz) for continuous optical stimulation with minimized invasiveness and tissue exposure to electromagnetic radiation. Coupling a microscale reflector to the µLED provides significant light intensity enhancement compared to a bare µLED. Our activated stimulators have an operational temperature increase of <1 °C, well below the safety limit of biomedical implants. In vivo experiment and histological analysis verify the efficacy of wireless optical stimulation in the primary visual cortex of rats, using c-Fos biomarker as a reporter of light-evoked neuronal activity.

A Dual-Band Wireless Power Transmission System for Evaluating mm-Sized Implants.

Distributed neural interfaces made of many mm-sized implantable medical devices (IMDs) are poised to play a key role in future brain-computer interfaces because of less damage to the surrounding tissue. Evaluating them wirelessly at preclinical stage (e.g., in a rodent model), however, is a major challenge due to weak coupling and significant losses, resulting in limited power delivery to the IMD within a nominal experimental arena, like a homecage, without surpassing the specific absorption rate limit. To address this problem, we present a dual-band EnerCage system with two multi-coil inductive links, which first deliver power at 13.56 MHz from the EnerCage (46 × 24 × 20 cm3) to a headstage (18 × 18 × 15 mm3, 4.8 g) that is carried by the animal via a 4-coil inductive link. Then, a 60 MHz 3-coil inductive link from the headstage powers up the small IMD (2.5 × 2.5 × 1.5 mm3, 15 mg), which in this case is a free floating, wirelessly powered, implantable optical stimulator (FF-WIOS). The power transfer efficiency and power delivered to the load (PDL) from EnerCage to the headstage at 7 cm height were 14.9%-22.7% and 122 mW; and from headstage to FF-WIOS at 5 mm depth were 18% and 2.7 mW, respectively. Bidirectional data connectivity between EnerCage-headstage was established via bluetooth low energy. Between headstage and FF-WIOS, on-off keying and load-shift-keying were used for downlink and uplink data, respectively. Moreover, a closed-loop power controller stabilized PDL to both the headstage and the FF-WIOS against misalignments.