Polarization-insensitive wide-angle resonant acousto-optic phase modulator.

Phase modulators are commonly used devices in optics. Free-space phase modulators are typically constructed from optically anisotropic crystals exhibiting the Pockels effect. To preserve the light's polarization state as it propagates through the crystal, it is essential to align the polarization and the angle of incidence of the light with respect to the crystal. In this study, we demonstrate the feasibility of constructing free-space resonant phase modulators with a broad acceptance angle and minimal dependence on the polarization state of light using an acousto-optic approach. These modulators operate in the megahertz frequency range, require modest power levels, have aperture sizes exceeding 1 cm2, and feature sub-millimeter thickness.

Optically isotropic longitudinal piezoelectric resonant photoelastic modulator for wide angle polarization modulation at megahertz frequencies.

Polarization modulators have a broad range of applications in optics. The acceptance angle of a free-space polarization modulator is crucial for many applications. Polarization modulators that can achieve a wide acceptance angle are constructed by attaching a piezoelectric transducer to an isotropic material, and utilizing a resonant transverse interaction between light and acoustic waves. Since their demonstration in the 1960s, the design of these modulators has essentially remained the same with minor improvements in the following decades. In this work, we show that a suitable single crystal with the correct crystal orientation, functioning as both the piezoelectric transducer and the acousto-optic interaction medium, could be used for constructing a highly efficient free-space resonant polarization modulator operating at megahertz frequencies and exhibiting a wide acceptance angle. We construct the modulator using gallium arsenide, an optically isotropic and piezoelectric crystal, and demonstrate polarization modulation at 6 MHz with an input aperture of 1 cm in diameter, acceptance angle reaching ±30∘, and modulation efficiency exceeding 50%. Compared to state-of-the-art resonant photoelastic modulators, the modulator reported in this work exhibits greater than 50-fold improvement in modulation frequency for the same input aperture, while simultaneously reducing the thickness by approximately a factor of 80. Increasing the modulation frequency of photoelastic modulators from the kilohertz to the megahertz regime and substantially reducing their thickness lead to significant performance improvements for various use cases. This technological advancement also creates opportunities for utilizing these devices in new applications.

Gut Microbiome Redox Sensors With Ultrasonic Wake-Up and Galvanic Coupling Wireless Links.

Tools to measure in vivo redox activity of the gut microbiome and its influence on host health are lacking. In this paper, we present the design of new in vivo gut oxidation-reduction potential (ORP) sensors for rodents, to study host-microbe and microbe-environment interactions throughout the gut. These are the first in vivo sensors to combine ultrasonic wake-up and galvanic coupling telemetry, allowing for sensor miniaturization, experiment flexibility, and robust wireless measurements in live rodents. A novel study of in situ ORP along the intestine reveals biogeographical redox features that the ORP sensors can uniquely access in future gut microbiome studies.

Y-Z cut lithium niobate longitudinal piezoelectric resonant photoelastic modulator.

The capability to modulate the intensity of an optical beam has scientific and practical significance. In this work, we demonstrate Y-Z cut lithium niobate acousto-optic modulators with record-high modulation efficiency, requiring only 1.5 W/cm2 for 100% modulation at 7 MHz. These modulators use a simple fabrication process; coating the top and bottom surfaces of a thin lithium niobate wafer with transparent electrodes. The fundamental shear acoustic mode of the wafer is excited through the transparent electrodes by applying voltage with frequency corresponding to the resonant frequency of this mode, confining an acoustic standing wave to the electrode region. Polarization of light propagating through this region is modulated at the applied frequency. Polarization modulation is converted to intensity modulation by placing the modulator between polarizers. To showcase an important application space for this modulator, we integrate it with a standard image sensor and demonstrate 4 megapixel time-of-flight imaging.

On-demand electrochemically controlled compound release from an ultrasonically powered implant.

On-demand drug delivery systems are promising for a wide range of therapeutic applications. When combined with wireless implants for controlled drug delivery, they can reduce overall dosage and side effects. Here, we demonstrate release of fluorescein from a novel on-demand release system for negatively charged compounds. The release system is based on a modified electroresponsive polypyrrole nanoparticulate film designed to minimize ion exchange with the stored compound - a major passive leakage mechanism. We further designed an ultrasonically powered mm-sized implant to electronically control the on-demand drug delivery system in vivo. Release kinetics are characterized both in vitro and in vivo in mice using fluorescein as a model drug, demonstrating the feasibility of wireless, controllable drug release using an ultrasonically powered implant.

Longitudinal piezoelectric resonant photoelastic modulator for efficient intensity modulation at megahertz frequencies.

Intensity modulators are an essential component in optics for controlling free-space beams. Many applications require the intensity of a free-space beam to be modulated at a single frequency, including wide-field lock-in detection for sensitive measurements, mode-locking in lasers, and phase-shift time-of-flight imaging (LiDAR). Here, we report a new type of single frequency intensity modulator that we refer to as a longitudinal piezoelectric resonant photoelastic modulator. The modulator consists of a thin lithium niobate wafer coated with transparent surface electrodes. One of the fundamental acoustic modes of the modulator is excited through the surface electrodes, confining an acoustic standing wave to the electrode region. The modulator is placed between optical polarizers; light propagating through the modulator and polarizers is intensity modulated with a wide acceptance angle and record breaking modulation efficiency in the megahertz frequency regime. As an illustration of the potential of our approach, we show that the proposed modulator can be integrated with a standard image sensor to effectively convert it into a time-of-flight imaging system.

An RF-Ultrasound Relay for Adaptive Wireless Powering Across Tissue Interfaces.

Single modality wireless power transfer has limited depth for mm-sized implants across air / tissue or skull / tissue interfaces because they either suffer from high loss in tissue (RF, Optical) or high reflection at the medium interface (Ultrasound (US)). This paper proposes an RF-US relay chip at the media interface avoiding the reflection at the boundary, and enabling efficient wireless powering to mm-sized deep implants across multiple media. The relay chip rectifies the incoming RF power through an 85.5% efficient RF inductive link (across air) using a multi-output regulating rectifier (MORR) with 81% power conversion efficiency (PCE) at 186 mW load, and transmits ultrasound using adiabatic power amplifiers (PAs) to the implant in order to minimize cascaded power loss. To adapt the US focus to implant movement or placement, beamforming was implemented using 6 channels of US PAs with 2-bit phase control (0, 90, 180, and 270°) and 3 different amplitudes (6-29, 4.5, and 1.8 V) from the MORR. The adiabatic PA contributes a 30-40% increase in efficiency over class-D and beamforming increases the efficiency by 251% at 2.5 cm over fixed focusing. The proof-of-concept powering system for a retinal implant, from an external PA on a pair of glasses to a hydrophone with 1.2 cm (air) + 2.9 cm (agar eyeball phantom in mineral oil) separation distance, had a power delivered to the load (PDL) of 946 µW. The 2.3 × 2 mm2 relay chip was fabricated in a 180 nm high-voltage (HV) BCD process.

Design and Analysis of a Sample-and-Hold CMOS Electrochemical Sensor for Aptamer-based Therapeutic Drug Monitoring.

In this paper, we present the design and the analysis of an electrochemical circuit for measuring the concentrations of therapeutic drugs using structure-switching aptamers. Aptamers are single-stranded nucleic acids, whose sequence is selected to exhibit high affinity and specificity toward a molecular target, and change its conformation upon binding. This property, when coupled with a redox reporter and electrochemical detection, enables reagent-free biosensing with a sub-minute temporal resolution for in vivo therapeutic drug monitoring. Specifically, we design a chronoamperometry-based electrochemical circuit that measures the direct changes in the electron transfer (ET) kinetics of a methylene blue reporter conjugated at the distal-end of the aptamer. To overcome the high-frequency noise amplification issue when interfacing with a large-size (> 0.25 mm2) implantable electrode, we present a sample-and-hold (S/H) circuit technique in which the desired electrode potentials are held onto noiseless capacitors during the recording of the redox currents. This allows disconnecting the feedback amplifiers to avoid its noise injection while reducing the total power consumption. A prototype circuit implemented in 65-nm CMOS demonstrates a cell-capacitance-insensitive input-referred noise (IRN) current of 15.2 pArms at a 2.5-kHz filtering bandwidth. We tested our system in human whole blood samples and measured the changes in the ET kinetics from the redox-labeled aptamers at different kanamycin concentrations. By employing principal component analysis (PCA) to compensate for the sampling errors, we report a molecular noise floor (at SNR = 1) of 3.1 µM with sub 1-sec acquisition time at 0.22-mW power consumption.

Time-of-flight imaging based on resonant photoelastic modulation: publisher's note.

This publisher's note corrects the Funding section in Appl. Opt.58, 2235 (2019)APOPAI0003-693510.1364/AO.58.002235.

Assessment of miniaturized ultrasound-powered implants: an in vivo study.

OBJECTIVE: Therapeutic applications of implantable active medical devices have improved the quality of patient life. Numerous on-going research in the field of neuromodulation and bioelectronic medicine are exploring the use of these implants for treating diseases and conditions. Miniaturized implantable medical devices that are wirelessly powered by ultrasound (US) can be placed close to the target sites deep inside the body for effective therapy with less invasiveness. In this study, we assessed the long-term in vivo performance of miniaturized US powered implants (UPI) using a rodent model. APPROACH: Prototype UPI devices were implanted in rodents and powered wirelessly using an unfocused US transmitter over 12 weeks, and the corresponding device output was recorded. Structural integrity of UPI before and after implantation was studied using scanning electron microscopy (SEM). We also conducted qualitative histological assessment of skin and muscle surrounding the UPI and compared it to naïve control and US exposed tissues. MAIN RESULTS: We found that it is feasible to power UPI devices wirelessly with US over long-term. The encapsulation of UPIs did not degrade over time and the tissues surrounding the UPI were comparable to both naïve control and US exposed tissues. SIGNIFICANCE: This study is the first to assess the long-term performance of miniaturized UPI devices using a rodent model over 12-weeks. The set of tests used in this study can be extended to assess other US-powered miniaturized implants.

In Vivo Wireless Sensors for Gut Microbiome Redox Monitoring.

A perturbed gut microbiome has recently been linked with multiple disease processes, yet researchers currently lack tools that can provide in vivo, quantitative, and real-time insight into these processes and associated host-microbe interactions. We propose an in vivo wireless implant for monitoring gastrointestinal tract redox states using oxidation-reduction potentials (ORP). The implant is powered and conveniently interrogated via ultrasonic waves. We engineer the sensor electronics, electrodes, and encapsulation materials for robustness in vivo, and integrate them into an implant that endures autoclave sterilization and measures ORP for 12 days implanted in the cecum of a live rat. The presented implant platform paves the way for long-term experimental testing of biological hypotheses, offering new opportunities for understanding gut redox pathophysiology mechanisms, and facilitating translation to disease diagnosis and treatment applications.

A Microwave-Induced Thermoacoustic Imaging System With Non-Contact Ultrasound Detection.

Portable and easy-to-use imaging systems are in high demand for medical, security screening, nondestructive testing, and sensing applications. We present a new microwave-induced thermoacoustic imaging system with non-contact, airborne ultrasound (US) detection. In this system, a 2.7 GHz microwave excitation causes differential heating at interfaces with dielectric contrast, and the resulting US signal via the thermoacoustic effect travels out of the sample to the detector in air at a standoff. The 65 dB interface loss due to the impedance mismatch at the air-sample boundary is overcome with high-sensitivity capacitive micromachined ultrasonic transducers with minimum detectable pressures (MDPs) as low as 278 µ Pa rms and we explore two different designs-one operating at a center frequency of 71 kHz and another at a center frequency of 910 kHz. We further demonstrate that the air-sample interface presents a tradeoff with the advantage of improved resolution, as the change in wave velocity at the interface creates a strong focusing effect alongside the attenuation, resulting in axial resolutions more than 10× smaller than that predicted by the traditional speed/bandwidth limit. A piecewise synthetic aperture radar (SAR) algorithm modified for US imaging and enhanced with signal processing techniques is used for image reconstruction, resulting in mm-scale lateral and axial image resolution. Finally, measurements are conducted to verify simulations and demonstrate successful system performance.

Time-of-flight imaging based on resonant photoelastic modulation.

A time-of-flight imaging system is proposed and its working principle demonstrated. To realize this system, a new device, a free-space optical mixer, is designed and fabricated. A scene is illuminated (flashed) with a megahertz-level amplitude-modulated light source, and the reflected light from the scene is collected by a receiver. The receiver consists of the free-space optical mixer, comprising a photoelastic modulator sandwiched between polarizers, placed in front of a standard complementary metal-oxide-semiconductor (CMOS) image sensor. This free-space optical mixer downconverts the megahertz-level amplitude modulation frequencies into the temporal bandwidth of the image sensor. A full-scale extension of the demonstrated system will be able to measure phases and Doppler shifts for the beat tones and use signal processing techniques to estimate the distance and velocity of each point in the illuminated scene with high accuracy.

Ultrasonic Implant Localization for Wireless Power Transfer: Active Uplink and Harmonic Backscatter.

Efficient ultrasonic power transfer to implantable devices requires precise transmitter beamforming to the receiver and can quickly degrade with small changes in implant location. Ultrasound localization can be used to find and track implants in the body to maintain an efficient link. We present a framework to calculate localization accuracy showing that sub-mm accuracy is obtainable using only three receive channels. A harmonic backscatter approach, which passively provides contrast in the frequency domain without active load modulation is compared to active uplink from the implant. The localization accuracy using both active uplink and harmonic backscatter from the implant power receiver is characterized using a linear array probe. The measured location standard deviation is nearly two orders of magnitude smaller than the half-power beamwidth of the array focal spot. Finally, beamforming using the measured location information increases the available power by over 20 × compared to an unfocused beam.

Multi-Access Networking with Wireless Ultrasound-Powered Implants.

Multi-access networking with miniaturized wireless implantable devices can enable and advance closed-loop medical applications to deliver precise diagnosis and treatment. Using ultrasound (US) for wireless implant systems is an advantageous approach as US can beamform with high spatial resolution to efficiently power and address multiple implants in the network. To demonstrate these capabilities, we use wirelessly powered mm-sized implants with bidirectional communication links; uplink data communication measurements are performed using time, spatial, and frequency-division multiplexing schemes in tissue phantom. A 32-channel linear transmitter array and an external receiver are used as a base station to network with two implants that are placed 6.5 cm deep and spaced less than 1 cm apart. Successful wireless powering and uplink data communication around 100 kbps with a measured bit error rate below 10-4 are demonstrated for all three networking schemes, validating the multi-access networking feasibility of US wireless implant systems.

Chromatic Properties of Blood During Coagulation.

This paper proposes a method of detecting blood clots by analyzing the chromatic properties of blood. Measurements are performed with a Basler camera on blood during coagulation to determine the changes in red, green, and blue (RGB) values. Results show that there is a significant change in the red value that can be exploited for real-time, early detection of blood clots.

Non-Invasive Remote Temperature Monitoring Using Microwave-Induced Thermoacoustic Imaging.

Non-invasive temperature monitoring of tissue at depth in real-time is critical to hyperthermia therapies such as high-intensity focused ultrasound. Knowledge of temperature allows for monitoring treatment as well as providing real-time feedback to adjust deposited power in order to maintain safe and effective temperatures. Microwave-induced thermoacoustic (TA) imaging, which combines the conductivity/dielectric contrast of microwave imaging with the resolution of ultrasound, shows potential for estimating temperature non-invasively in real-time by indirectly measuring the temperature dependent parameters from reconstructed images. In this work, we study the temperature dependent behavior of the generated pressure in the TA effect and experimentally demonstrate simultaneous imaging and temperature monitoring using TA imaging. The proof-of-concept experiments demonstrate millimeter spatial resolution while achieving degree-level accuracy.

Long-term in vivo performance of novel ultrasound powered implantable devices.

Neuromodulation devices have been approved for the treatment of epilepsy and seizures, with many other applications currently under research investigation. These devices rely on implanted battery powered pulse generators, that require replacement over time. Miniaturized ultrasound powered implantable devices have the potential to eliminate the need for batteries in neuromodulation devices. While these devices have been assessed in vitro, long-term in vivo assessment is required to determine device safety and performance. In this study, we developed a multi-stage long-term test platform to assess the performance of miniaturized ultrasound powered implantable devices.

End-to-End Design of Efficient Ultrasonic Power Links for Scaling Towards Submillimeter Implantable Receivers.

We present an analytical framework for optimizing the efficiency of ultrasonic wireless power links for implantable devices scaled down to sub-mm dimensions. Key design insights and tradeoffs are considered for various parameters including the operating frequency, the transmission depth, the size of the transmitter, the impedance and the aperture efficiency of the miniaturized receiver, and the interface between the receiver and the power recovery chain on the implant. The performance of spherically focused transducers as ultrasonic transmitters is analyzed to study the limits and the tradeoffs. Two optimization methods are presented: "Focal Peak" sets the focus of transducers at target depths, and "Global Maximum" maximizes the efficiency globally with off-focus operation. The results are also compared to phased array implementations. To investigate the efficiency of implants, miniaturized receivers made from single crystalline piezoelectric material, PMN-PT, are used as they have resonances in the derived optimal carrier frequency range (∼1-2 MHz). A methodology to achieve an efficient interface to the power electronics is then provided using an optogenetic stimulator as an example platform. The analytical results are verified through both simulations and measurements. Finally, an example ultrasonic link using a spherical transmitter with a radius of 2 cm is demonstrated; link efficiencies of 1.93-0.23% are obtained at 6-10 cm depths with sub-mm receivers for the optogenetic application.

Thermal analysis of ultrasound-powered miniaturized implants: A tissue-phantom study.

Neurological implants that harvest ultrasound power have the potential to provide long-term stimulation without complications associated with battery power. An important safety question associated with long-term operation of the implant involves the heat generated by the interaction of the device with the ultrasound field. A study was performed in which the temperature rise generated by this interaction was measured. Informed by temperature data from thermocouples outside the ultrasound beam, a mathematical inverse method was used to determine the volume heat source generated by ultrasound absorption within the implant as well as the surface heat source generated within the viscous boundary layer on the surface of the implant. For the test implant used, it was determined that most of the heat was generated in the boundary layer, giving a maximum temperature rise ∼5 times that for absorption in an equivalent volume of soft tissue. This result illustrates that thermal safety guidelines based solely on ultrasound absorption of tissue alone are not sufficient. The method presented represents an alternative approach for quantifying ultrasound thermal effects in the presence of implants. The analysis shows a steady temperature rise of about 0.2 °C for every 100 mW/cm2 for the presented test implant.