System and method for wireless communication with an implanted device

Abstract

Exemplary embodiments of the present disclosure include an apparatus, a system, and a method that utilize a passive, power-efficient backscatter communication system that enables wireless transmission of data between an implanted magneto-electric (ME) device and an external base station. Some embodiments encode transmitted data by modulating the resonant frequency of an ME thin film by digitally adjusting the electrical loading conditions of the ME thin film.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 353,371, filed on June 17, 2022, the entire contents of which are incorporated herein by reference.

[0002] Background Statement Regarding Federally Sponsored Research and Development This invention was made with government support under Grant No. ECCS - 2023849 awarded by the National Science Foundation, Grant No. EB029353 awarded by the National Institutes of Health, and Grant No. FA8650 - 21 - 2 - 7119 awarded by the Defense Advanced Research Projects Agency. The government has certain rights in this invention.

[0003] A. Field The present disclosure relates to apparatus and methods for providing a passive, power - efficient backscatter communication system that enables wireless transmission of data between an implanted magneto - electric (ME) device and an external base station.

Background Art

[0004] B. Related Art Bioelectronic implants can target specific tissue sites for therapeutic purposes without the need for large-scale administration of conventional pharmaceuticals, emerging as a promising option for personalized medicine. However, as these devices become smaller and less invasive, power and data supply become difficult, making it challenging to develop the same functionality as large battery-driven implants. The recent development of small wirelessly powered electrical stimulation devices is promising but often limited to one or two stimulation channels, resulting in a restricted scope of application compared to conventional stimulation devices. Wireless technologies based on ultrasound and inductive coupling have made significant progress in overcoming this by transitioning to a single transmitter / multiple mote configuration. However, these methods have limitations in their spatial distribution due to geometric constraints and / or power limitations.

[0005] Conventional electrical stimulation devices such as pacemakers, deep brain electrodes, and spinal cord stimulation devices are battery-powered and bulky, yet have shown high effectiveness in treating various disorders. To reduce the size, invasiveness, and extend the lifespan of implantable bioelectronics, some form of wireless power supply from an external transmitter to small implanted "motes" is desired.

[0006] Typically, compared to conventional implants with 4 - 10 stimulation channels, many newly proposed small implants are limited to one or two stimulation sites, thus potentially restricting their effectiveness. Also, effective multi-mote systems or multi-channel systems per mote need to include the complexity of data transmission for individually programming each channel, which is an additional challenge for wireless systems where each mote may not be in the same alignment as the transmitter. Summary of the Invention Problems to be Solved by the Invention

[0007] Therefore, there are numerous challenges to successfully implement an implantable power-fed device. For example, a fundamental problem in bioelectronics is the ability to supply power to a small device inside the body. Wires provide efficient power transmission but are a common failure point and limit the placement of the device. Wireless power via electromagnetic waves or ultrasonic waves also has obstacles to overcome. For example, wireless power via electromagnetic waves or ultrasonic waves must overcome absorption by the body and impedance mismatches between air, bone, and tissue. Also, conventional methods of wirelessly powering a nerve implant in the deep tissue region of a freely moving animal or human typically require a large electromagnetic coil or a battery pack with external leads and are usually bulky. Additionally, the ability to provide magnetic electrical charging, data transmission, and stimulation to an implantable wireless nerve stimulation device is not provided in existing systems.

[0008] Therefore, to effectively implement an implantable power-fed device, it is necessary to address not only these problems but also other issues.

Means for Solving the Problems

[0009] Summary Briefly, the present disclosure provides a system for transmitting data using a magnetic field to an implantable device including a nerve stimulation device.

[0010] Exemplary embodiments include a passive, power-efficient backscatter communication system that enables wireless data transmission between an implantable magnetoelectric (ME) device and an external base station.

[0011] One embodiment encodes transmitted data by modulating the resonant frequency of an ME thin film by digitally adjusting the electrical loading conditions of the ME thin film. When the ME thin film is excited by an external pulsed magnetic field, its backscattered magnetic response, electrical response, or acoustic response can be recorded by a magnetic field sensor, an electrode, or a microphone, respectively. In addition, frequency demodulation can be used to decode the data of the received signal.

[0012] Exemplary embodiments of the present disclosure include a hardware platform for a wireless mm-sized bioimplant network that utilizes an innovative approach for adaptive magneto-electric power transmission and efficient bi-directional multiplex access communication. Closed-loop power control mitigates power feed variations caused by distance and alignment changes and avoids redundant power in the external transceiver. The system also enables simultaneous power and time-domain modulated downlink data at 5% peak power transmission efficiency and a maximum data rate of 62.3 kbps at a 340 kHz carrier frequency, and multiplex access uplink for all implants enabled by individual programmed IFs at a maximum data rate of 40 kbps at a 31 MHz carrier frequency, and distances greater than 6 cm between implants and the external transceiver.

[0013] A wireless network of miniaturized battery-free bioimplants that accurately synchronizes sensing and stimulation holds promise for enabling effective and flexible closed-loop and patient-specific control of physiological functions. By dispersing multiple miniaturized implants around the target tissue, exemplary embodiments of the implant network disclosed herein significantly improve device deployment flexibility, superior specificity, and spatial resolution over current battery-powered single-site implants, and achieve less infection risk and surgical complexity [1], [2], [3], [4].

[0014] Possible clinical applications include multi-site spinal cord stimulation, nerve injury rehabilitation, and cardiac pacing.

[0015] Despite decades of research, wireless power transfer (WPT) and telemetry to bioimplants still face significant challenges, which are even more severe for distributed mm-sized implants. First, WPT must be robust to ensure proper operation of all implants placed at different positions and angles and performing different workloads. Simply generating a strong carrier field may increase the in-body absorption rate and shorten the battery life of wearable power transceivers [1], [2], [3], [4], [5], [6]. Although regulated WPT is enabled by non-resonant inductive coupling [7], a k coupling greater than 1 / QRX is required, limiting its application to long-distance WPT for mm-sized implants.

[0016] Closed-loop control using back telemetry can effectively regulate the received voltage [8], [9]. However, all existing proof-of-experiment demonstrations are for receivers on the 1-cm scale. Second, simultaneous power and data transmission is desired for higher power efficiency and smaller receivers, but is typically limited by the trade-off between the quality factor and bandwidth of the antenna / transducer [3],

[10] ,

[11] ,

[12] ,

[13] . Third, in a distributed implant network, efficient and robust multi-access telemetry in both directions is essential.

[0017] Certain embodiments of the present disclosure include a system having an implanted mote and an external hub, where the mote stimulates and / or records electrophysiological activity. In some embodiments, there are one or more motes and a single transmitter, and in other embodiments, there is a single mote for each transmitter. In a specific embodiment, the mote is powered by magneto-electric (ME) thin films, near-infrared communication (NIC), and / or light (e.g., via a photodiode).

[0018] In one embodiment, the stimulus is digitally programmable based on an internal circuit in the form of an application-specific integrated circuit or a microcontroller-based system. In certain embodiments, the mote receives data from an external hub, and the data is transmitted from the hub by a modulated magnetic field, NFC, light, or Bluetooth Low Energy. In a specific embodiment, the external hub receives data from the mote, and the data is transmitted from the mote by ME backscattering, NFC (passive or active backscattering), light, or Bluetooth Low Energy, and the data can include received power. The data can include biomarkers such as local electric field potential, spectrogram of local electric field potential, or power in a specific frequency band such as theta band power, alpha band power, or spike band power.

[0019] In certain embodiments, the stimulus is adjusted based on data received from the mote. In one embodiment, the system is used to administer treatment using electrical stimulation. In some embodiments, the mote is implanted in the middle or upper part of the left dorsolateral prefrontal cortex and / or the right dorsolateral prefrontal cortex of the brain, and in certain embodiments, the mote is implanted in the middle or upper part of the spinal cord.

[0020] In a specific embodiment, the system has a stimulation site. In some embodiments, the device is a leadless stimulation device, and in other embodiments, the device has leads. In certain embodiments, the stimulation device has concentric electrodes. In one embodiment, the stimulation device has a pair of electrodes, and in other embodiments, the stimulation device has multiple electrodes. In some embodiments, multiple devices are arranged in an array or pattern to generate a stimulation pattern between motes.

[0021] One embodiment includes a wireless bioelectronics system comprising an implantable device having an electrical circuit coupled to a magnetoelectric thin film, a magnetic field generator, and a resonance frequency modulator, the magnetoelectric thin film having a resonance frequency, and the electrical circuit configured to modulate the resonance frequency of the magnetoelectric thin film by applying different electrical loading conditions that change the properties of the magnetoelectric thin film.

[0022] In certain embodiments, the properties of the magnetoelectric thin film are the electrical, elastic, or magnetic properties of the magnetoelectric thin film. In some embodiments, the electrical circuit is configured to modulate the voltage, resistive load, inductive load, or capacitive load applied to the magnetoelectric thin film. In a specific embodiment, the magnetoelectric thin film comprises a piezoelectric layer, and the magnetoelectric thin film comprises a magnetostrictive layer coupled to the piezoelectric layer.

[0023] In one embodiment, the magnetoelectric thin film comprises a first magnetostrictive layer and a second magnetostrictive layer, the magnetoelectric thin film comprises a piezoelectric layer, and the piezoelectric layer is positioned between the first magnetostrictive layer and the second magnetostrictive layer. In certain embodiments, the implantable device is a first implantable device, the wireless bioelectronics system comprises a plurality of implantable devices, and each implantable device comprises an electrical circuit coupled to a magnetoelectric thin film.

[0024] In one embodiment, the plurality of implantable devices are configured to provide nerve stimulation. In certain embodiments, the implantable device is coupled to a pair of electrodes. In some embodiments, the implantable device is coupled to a plurality of electrodes. In a specific embodiment, the plurality of electrodes are arranged concentrically. One embodiment includes a plurality of implantable devices, and the plurality of implantable devices are arranged in an array or pattern to generate a stimulation pattern among the plurality of implantable devices.

[0025] Certain embodiments include an external transceiver and a plurality of implantable devices, each implantable device comprising an electrical circuit coupled to a magnetoelectric thin film, the external transceiver being configured to simultaneously transmit a first magnetic field to each of the plurality of implantable devices, each of the plurality of implantable devices being configured to transmit a response to the external transceiver, and each of the plurality of implantable devices being configured to transmit a response to the external transceiver after the first magnetic field has been transmitted from the transceiver, a wireless bioelectronics system.

[0026] In some embodiments, each of the plurality of implantable devices is configured to stimulate and / or record electrophysiological activity. In a specific embodiment, each of the plurality of implantable devices is configured to transmit a response magnetic field to the transceiver. In one embodiment, the response magnetic field is generated by each of the plurality of implantable devices oscillating at the resonant frequency of the implantable device.

[0027] In certain embodiments, the electrical circuit is configured to modulate the resonant frequency of the magnetoelectric thin film by applying different electrical loading conditions that change the properties of the magnetoelectric thin film. In some embodiments, the transceiver comprises a magnetoelectric transmitter, a controller, and a receiver. In a specific embodiment, the receiver is an inductive coil electrode or an ultrasonic transducer.

[0028] In one embodiment, a plurality of implantable devices are configured to be implanted along the spine. In certain embodiments, the response transmitted from each of the plurality of implantable devices includes data. In some embodiments, the data is transmitted from the hub by a modulated magnetic field, near field communication (NFC), light, or Bluetooth Low Energy. In a specific embodiment, the data transmitted from the mote includes received power. In one embodiment, the data transmitted from the mote includes biomarkers. In certain embodiments, the biomarkers include power in a specific frequency band such as local electric field potential, theta band power, or spike band power. In some embodiments, nerve stimulation is adjusted based on data received from the plurality of implantable devices. In a specific embodiment, the plurality of implantable devices are implanted into the left dorsolateral prefrontal cortex and / or the right dorsolateral prefrontal cortex of the brain. In one embodiment, the plurality of implantable devices are implanted into or above the spinal cord.

[0029] Certain embodiments include a wireless bioelectronics system comprising a plurality of external transceivers and a plurality of implantable devices, wherein each of the plurality of external transceivers is uniquely paired with a plurality of implantable devices such that each external transceiver selectively communicates with a single implantable device and not with other implantable devices, each implantable device comprises an electrical circuit coupled to a magnetoelectric thin film, each external transceiver is configured to transmit a first magnetic field to the implantable device of the plurality of implantable devices, each of the implantable devices is configured to transmit a response to the external transceiver, and each of the plurality of implantable devices is configured to transmit a response to the external transceiver after the first magnetic field is transmitted from the transceiver.

[0030] One embodiment includes a method of stimulating neural tissue, the method including providing an apparatus as claimed in claim 28, generating a magnetic field with one or more of a plurality of transceivers, generating an electrical output signal with a magnetoelectric thin film, and modifying the electrical output signal with an electrical circuit.

[0031] A particular embodiment includes a method of stimulating neural tissue, the method including providing an apparatus as claimed in any one of claims 1 to 11, generating a magnetic field with a magnetic field generator, generating an electrical output signal with a magnetoelectric thin film, and modifying the electrical output signal with an electrical circuit.

[0032] One embodiment includes a method of stimulating neural tissue, the method including providing an apparatus as claimed in any one of claims 12 to 27, generating a magnetic field with a transceiver, generating an electrical output signal with a magnetoelectric thin film, and modifying the electrical output signal with an electrical circuit.

[0033] Any embodiment of any of the methods, compositions, kits, and systems does not comprise, include, incorporate, or have the recited steps and / or features, but may consist of or consist essentially of such steps and / or features. Accordingly, in any of the claims, instead of any of the foregoing non-limiting conjunctive verbs, the terms "consisting of" or "consisting essentially of" may be used to alter the scope of a given claim from that which would otherwise result from using its non-limiting conjunctive verb.

[0034] The use of the term "or" in the claims is used to mean "and / or" unless expressly indicated to refer only to alternatives or the alternatives are mutually exclusive, although the disclosure supports definitions that refer only to alternatives and "and / or".

[0035] Throughout this application, the term "about" is used to indicate that a value includes the standard deviation of error of the device or method being employed to determine that value.

[0036] In accordance with longstanding patent law, the term "a" or "an" when used in the claims or specification in conjunction with the word "comprising" indicates one or more, unless otherwise specified.

[0037] Other objects, features and advantages of the present invention will become apparent from the following detailed description. However, while the detailed description and specific examples indicate some embodiments of the present invention, it is to be understood that they are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

[0038] The following drawings form a part of this specification and are included to further demonstrate some aspects of the present invention. The present invention may be better understood by referring to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Patent Office upon request and payment of the necessary fees.

Brief Description of the Drawings

[0039]

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[0040] DETAILED DESCRIPTION OF THE INVENTION Embodiments of the present disclosure include a passive and power-efficient backscatter communication system that enables wireless transmission of data between an implanted magnetoelectric (ME) device and an external base station.

[0041] Embodiments of the present disclosure also include a wireless bioelectronics system comprising a magnetic field generator and an implantable device comprising an electrical circuit coupled to a magnetoelectric thin film. Certain embodiments include a backscatter communication system that exploits the tunability characteristics of magnetoelectric materials to enable a bidirectional wireless communication link for magnetoelectric bioimplants (ME-BITs). The ME-BIT combines (1) an ME thin film fabricated using a piezoelectric layer and a magnetostrictive layer mechanically coupled using an epoxy resin, and (2) an application-specific integrated circuit (ASIC) designed using 180 nm complementary metal-oxide thin-film semiconductor (CMOS) technology.

[0042] As shown in FIG. 1.A, when the ME-BIT is excited by an external pulsed magnetic field, mechanical vibrations are generated in the magnetostrictive layer due to the direct magnetostrictive effect. Due to the inverse magnetostrictive effect, the thin film generates a backscattered magnetic field that can be detected using a pickup coil. The mechanical vibrations form acoustic waves that propagate through the tissue and can be detected using a microphone at the skin surface. Due to the mechanical coupling between the magnetostrictive layer and the piezoelectric layer, the mechanical vibrations transmitted to the piezoelectric layer generate an electric field across the thin film. Due to the conductivity of the tissue, the generated electric field can be detected using a pair of electrodes at the skin surface.

[0043] To eliminate interference between the stimulating magnetic field and the recorded response, measurements are taken during a ring-down period when the external magnetic field is off, and the resonance frequency is determined by calculating the fast Fourier transform (FFT) of the ring-down waveform. To encode the transmitted data from the implant to the external base station, the resonance frequency of the ME thin film is electrically modulated by connecting the terminals of the ME thin film to various electrical loading conditions that change the electrical, elastic, or magnetic properties and thus change its resonance frequency. As shown in FIG. 1.B, a DC voltage, a resistive load, an inductive load, or a capacitive load can shift the resonance frequency of the ME thin film to enable frequency modulation.

[0044] As shown in FIG. 1.C, both analog modulation and digital modulation are possible. For example, to transmit an analog signal, different capacitors are used to continuously change the resonant frequency. In the case of a digital signal, a frequency shift keying method is used, where two capacitive load values are used to represent digital 0 and digital 1 data. In addition to frequency, these load conditions change the response amplitude, so amplitude modulation techniques can be used to encode data. In both cases, the ASIC adjusts the DC voltage, resistive load, inductive load, or capacitive load according to various analog and / or digital modulation schemes.

[0045] In one exemplary embodiment, the ME thin film is fabricated using a sheet in which a 30-μm-thick Metglas layer (magnetostrictive) is attached to a 270-μm-thick PZT-5 layer (piezoelectric) using an epoxy resin, and then cut into miniaturized thin films of 5×1.75 mm 2 using a laser cutter. For implantation, the thin film is encapsulated using a protective material such as parylene, and then the device is surgically delivered to the target site and deployed there. The transmitter system is constructed using a set of rechargeable batteries attached to custom electronics and a resonant coil that can be tuned to match the resonant frequency of the thin film. For the recording system, a pickup coil, a pair of electrodes, or a microphone connected to an electronic circuit is used to demodulate the received signal.

[0046] Other variations incorporate an ASIC chip for the data downlink to provide a bidirectional communication link in addition to supporting wireless power supply and communication using the same implant. Also, amplitude modulation or phase modulation can be used instead of frequency modulation.

[0047] Figures 2 - 4 show recorded data from an exemplary embodiment that includes the resonance frequency of the ME - BIT as a function of the applied DC voltage, resistive load, and capacitive load. Figure 5 shows the FFT of the pickup coil voltage during ME thin - film ring - down for different capacitive loads, and Figure 6 shows the layout of a proof - of - concept ASIC chip design for digital frequency - shift keying (FSK) modulation of a capacitive load to implement backscatter communication. The ASIC supports ME - based power transfer and two - way communication.

[0048] Exemplary embodiments can be used in many different applications, including, for example, closed - loop bioelectronics networks and distributed implant networks. The embodiments disclosed herein provide a safe, reliable, and power - efficient communication system for miniaturized implants. The intensity of the backscattered signal is determined by the size of the ME thin - film, which may limit the operating distance for smaller devices. To address this issue, the design of the receiver circuit (coil, microphone, or electrode) in certain embodiments can be optimized for higher sensitivity.

[0049] Figure 7 shows a prototype of a magneto - electric implant. This implant is shown on a fingertip to demonstrate its miniaturized form factor. This implant integrates an ASIC chip, an ME transducer, and an energy - storage capacitor on a substrate having a volume of 8.2 mm 3 and a weight of 45 mg.

[0050] In one embodiment, a magnetic receiver is used to pick up the backscattered magnetic field generated by the ME thin - film. Also, a capacitive load is used to digitally encode data by shifting the resonance frequency between two different values using frequency - shift keying.

[0051] Figure 8 shows an example of the functions of the ME-BIT. This implant can harvest power for stimulation and communicate sensor data (such as temperature sensor data as an example) using the proposed backscatter ME technology. In particular, Figure 8 shows the measured operating waveform of the implant. The magnetoelectrically powered and programmed implant continuously performs temperature sensing, uplink data transmission, and stimulation, and the enlarged view shows the temperature sensor output, uplink data output, and stimulation pulses of the implant.

[0052] Figure 9 shows the measured waveform of the demodulated signal. In particular, Figure 9 shows an example of demodulating the transmitted signal by a magnetic external transceiver. The uplink data from the implant is transmitted through ME backscatter and recovered by the external transceiver. The frequency of the backscatter signal changes due to the capacitive load shift at the implant terminals, resulting in different pulse widths for data "1" and "0" as shown in the enlarged view. By detecting the change in pulse width, the data is demodulated.

[0053] Figure 10 shows the measured temperature sensor error of the implant. Specifically, Figure 10 shows an example of sensor data (temperature sensor) that can be transmitted back to the receiver. The sensing results are wirelessly transmitted from the implant through ME backscatter. This implant was tested in a temperature chamber of 30°C to 44°C and showed an error smaller than 0.35°C.

[0054] Figure 11 shows an example of the communication system performance regarding the measured signal-to-noise ratio (SNR) and bit error rate (BER) at different distances from the implant. Figure 12 shows the measured BER at different external transceiver (TRX)-implant distances at a data rate of 8 Kbps.

[0055] Figure 13 shows an in vitro demonstration of system performance using 1.5 cm thick porcine tissue. The tissue covered the coil of the TRX, and the implant was placed on the surface of the tissue using a test lead for functional monitoring. Figure 14 shows the BER vs. data rate tested in vitro.

[0056] To address the problems of existing systems, this specification discloses a wireless network of mm-sized implants with closed-loop adaptive magneto-electric power transmission control (which may also be referred to herein as "BioNet"). Referring now to panel (a) of Figure 15, a conceptual diagram of the proposed BioNet is shown, which has adaptive power transmission and bidirectional telemetry. Panel (b) of Figure 15 shows a specific embodiment of an implantable device having a volume of 8.8 mm 3 and a weight of 51 grams.

[0057] The embodiment shown in Figure 15(a) includes a network that includes a scheme for efficient and robust multi-access bidirectional communication. The 8.8 mm implant shown in Figure 15(b) 3 includes: (1) closed-loop magneto-electric wireless power transmission that adapts to the implant's workload, changes in the implant's distance from and misalignment with the external TRX; (2) simultaneous power and time-domain downlink telemetry at 5% peak power transmission efficiency (PTE) and a maximum data rate of 62.3 kbps; (3) multi-access uplink telemetry enabled by individually programmed intermediate frequencies (IFs); (4) robust operation under 2V power supply variations; and (5) a TRX-implant operating distance of over 6 cm to receive a power input of over 1.3V and support a downlink data rate of 62.3 kbps and an uplink data rate of 40 kbps.

[0058] FIG. 16 shows a block diagram of one embodiment of a system 100 including a wearable external transceiver 110 and an implantable device 120. In the illustrated embodiment, the wearable external transceiver 110 includes a magnetic field generator 111, a controller 112, and a backscatter receiver 113. In this embodiment, the implantable device 120 includes an electrical circuit 130 coupled to a magnetoelectric thin film 150, which further includes a magnetostrictive layer 151 coupled to a piezoelectric layer 152. In some embodiments, the magnetoelectric thin film 150 may include additional layers or different configurations. For example, the magnetoelectric thin film 150 may include a piezoelectric layer positioned between two magnetostrictive layers. In other embodiments, the magnetoelectric thin film 150 may include a composite of piezoelectric and magnetostrictive elements intermingled throughout the film.

[0059] In the particular embodiment shown, the electrical circuit 130 is 2 SoC and 4×2mm 2 ME transducer and 2.5mm with conjugate impedance matching 2 A backscatter coil and a 0.25mm 3 , and a 22 μF capacitor. During operation of the system 100, the implantable device 120 can recover multiple power supply voltages from the ME and perform bidirectional telemetry, clock recovery, input voltage sensing, and stimulation under the control of the external transceiver 110. The system 100 is capable of magnetoelectric wireless power transfer (WPT) to alternating current (AC) voltages. Such capability provides tolerance to misalignment, low tissue absorption, and safe mW-level power delivery with a higher PTE than inductive coupling and ultrasound techniques [4],

[10] .

[0060] Downlink data with time domain modulation For implants with a small energy storage, simultaneous power transmission and telemetry are highly desirable. OOK

[11] , ASK-PPM [6], and ASK-PWM [3],

[12] require frequent amplitude switching, resulting in fluctuating input power and being restricted by the high quality factor of the antenna / transducer, leading to a low data rate (panel (a) in FIG. 17). Frequency division FSK has been proposed in recent years for stable power supply and high data rate

[13] . However, this requires a strong coupling that is susceptible to changes in distance and misalignment (panel (b) in FIG. 17). Exemplary embodiments of the present disclosure provide a notch-spacing time-domain modulation scheme in which multiple bits are encoded in the pulse duration to compensate for the low switching speed of the transducer, as shown in panel (c) of FIG. 17. In this scheme, each pulse is defined by two narrow magnetic field notches and can be quickly detected by the comparator of the active rectifier [4]. This method minimizes the reduction of PTE. Considering the trade-off between switching time compensation and duration encoding overhead, each data symbol is designed to contain up to 6 bits. A complete packet includes a header, an ID for individual addressing, and a payload. An accurate clock is essential for accurate demodulation.

[0061] Although it is simple to recover the PVT-invariant clock from the source, it fails in the absence of a carrier field and is thus not compatible with the notch-based scheme. To address this, the LO of each implant is frequency locked to the clock (CLK LO ) recovered from the source as the timing reference (CLK REF ) for demodulation. Frequency locking is autonomously performed using SAR logic before each downlink data transmission session, as shown in FIG. 18.

[0062] Uplink backscattering by FDMA (Frequency Division Multiple Access) Exemplary embodiments of the present disclosure can comprise a plurality of implantable devices. It is important to access the feedback of each implantable device, and for that, a multiple access uplink is required. FDMA is preferred over TDMA (Time Division Multiple Access) [3] because of its high timing efficiency. However, existing FDMA uplinks for multiple implants require different carrier frequencies [1] or input signal frequencies [2] as shown in panels (a), (b), and (c) of FIG. 19, which limits their scalability and compatibility.

[0063] The use of an intermediate frequency (IF) shows advantages in the SNR in inductive backscattering

[14] . In this study, as shown in panel (d) of FIG. 19, the IF is further utilized to realize low-cost and scalable FDMA in backscattering by mixing individually programmed IFs with uplink data. By this mechanism, each of the implants can be simultaneously accessible to an external transceiver

[15] . The data rate of the implant is programmed based on the channel conditions to optimize the signal-to-noise ratio (SNR). In an exemplary embodiment, the uplink module, as shown in panel (a) of FIG. 6, comprises a voltage-controlled oscillator (VCO)-based quantizer for detecting the implant voltage V RECT a time-to-digital converter (TDC), a controller, and an intermediate frequency (IF) generator, which is a programmable current-starved oscillator with uniform tuning steps, as shown in panel (b) of FIG. 20. FIG. 21 shows a block diagram of the proposed closed-loop global power control.

[0064] Adaptive Global Power Transmission Control Using an on-chip physically unclonable function (PUF) implanted device (ID), the functions of each implant can be individually programmed and controlled by an external transceiver, and the transceiver knows the received power of each implant through a multiple access uplink. The transceiver adapts the output power of the power transmitter to adjust the input power of the implant based on the real-time workload and channel efficiency. The proposed closed-loop control of wireless power transmission can significantly mitigate the power supply fluctuations caused by distance changes and misalignments, and avoid unnecessary power consumption of the external transceiver when the workload is light.

[0065] Measurement results In one exemplary embodiment, the implant SoC is fabricated in TSMC 180nm CMOS technology as shown in panel (a) of FIG. 22. In this example, the bio-net system is measured in vitro using 2 cm thick porcine tissue as shown in panels (b) and (c) of FIG. 22.

[0066] The implant continuously receives power during downlink and uplink data transmission as shown in panel (a) of FIG. 23. The device programming downlink data is decoded by a self-calibrated timing reference CLK LO . The LO accurately locks to a carrier frequency of 340.1 kHz at 0.4 ms as shown in panel (b) of FIG. 23. In this embodiment, the measured CLK LO shows a maximum error of 0.2% for a 2V input voltage change in 15 devices, demonstrating its robustness against process and voltage variations as shown in panels (a) and (b) of FIG. 24. For example, the IF oscillator for data uplink can be programmed in the range of 50 - 200 kHz as shown in panel (c) of FIG. 24.

[0067] Figure 25 shows the operating waveform of the uplink telemetry and the detection and reporting of the received voltage of the implant. The uplink of this system achieves a bit error rate (BER) of 5.5E-5 through 2 cm of porcine tissue when transmitting a 40 kbps PRBS with a backscatter receiver coil power of 0 dBm (Figure 26(a)). Further, the multiple access uplink is shown by the spectra of two implants that simultaneously transmit data at separate individually programmed IFs of 83 kHz and 108 kHz (Figure 26(b)).

[0068] Figure 27 shows the continuous closed-loop wireless power transfer control when varying the transceiver-implant distance. When the distance increases by 1.5 cm, the ME voltage drops from 2.8 V to 1.52 V, resulting in a maximum reduction of 1.38 mW in the received power. Subsequently, the implant voltage recovers to the desired 2.8 V after 30 tuning cycles by adaptively controlling the power of the magneto-electric transmitter.

[0069] When the distance decreases from 3.5 cm to 2.5 cm, the adjustment loop saves 1.8 W (i.e., 58%) of the ME TX coil power. As shown in Figure 28, the implant fully functions (i.e., receives power exceeding 1.3 V from the ME WPT and achieves an uplink BER of less than 1E-4) without violating the IEEE safety limit (a maximum TX coil power of 17.6 W at 340 kHz in COMSOL) at a distance of 6 cm from the transceiver. Compared with the state-of-the-art [3], [5],

[11] in mm size, the proposed invention achieves the highest PTE and the maximum operating distance. Due to time-domain modulation, the ratio of its data rate / f in the downlink is much higher than that of [3],

[11] and is comparable to that of

[13] which operates at a much smaller distance. With the proposed invention, FDMA is enabled in the uplink by individually programmed IFs (see Figure 29, including a table showing a comparison with the state-of-the-art integrated power and telemetry platform for wireless bioimplants). carrier The ratio is much higher than that of [3],

[11] and is comparable to that of

[13] which operates at a much smaller distance. With the proposed invention, FDMA is enabled in the uplink by individually programmed IFs (see Figure 29, including a table showing a comparison with the state-of-the-art integrated power and telemetry platform for wireless bioimplants).

[0070] Figure 30 shows a conceptual diagram of one embodiment of a system comprising a computer processor, a hub (e.g., an external transceiver), and a stimulation device (e.g., a magnetoelectric implant) positioned proximal to a patient's skull and brain to deliver neural stimulation (e.g., cortical stimulation) to the brain. Figure 31 shows a conceptual diagram of one embodiment of a system comprising a computer processor, a hub (e.g., an external transceiver), and a stimulation device (e.g., a magnetoelectric implant) positioned proximal to a patient's spine to deliver neural stimulation to the spinal cord.

[0071] Figure 32 shows data indicating that a device can be powered by a magnetoelectric thin film, and Figure 33 shows data indicating that multiple devices can be programmed at once.

[0072] Figure 34 provides an image showing a glass device without leads for cortical stimulation. In one embodiment, a custom glass through electrode (TGV) wafer is obtained, platinum and titanium are deposited and patterned to form electrode contacts on the TGV wafer. In a particular embodiment, a laser is used to cut individual "caps" from the TGV wafer, and an ASIC is adhered to a custom flex-rigid or rigid PCB. The ME thin film is connected to the PCB with wires and conductive silver epoxy. In a specific embodiment, the custom PCB is adhered inside the cap with conductive silver epoxy, the cap is sealed in a glass tube with a medical grade epoxy or laser welding, and caps of the same size are adhered to the top of the glass tube.

[0073] Figure 35 shows alternative options for glass package design and electrode spacing in a particular embodiment. Figure 36 shows a simulation of cooperative stimulation between two glass motes, and Figure 37 provides an image of one embodiment showing an epoxy-encapsulated device with a lead wire for spinal cord stimulation. In this embodiment, the ASIC is adhered to a custom PCB, and the ME thin film is connected to the PCB with wires and conductive silver epoxy. The stimulation lead wire is also connected to the PCB with silver epoxy, and the package is 3D printed with a cavity for the ME thin film. The ME thin film is encapsulated inside a box, and the PCB is encapsulated outside the box with a medical-grade transparent epoxy. Figure 38 is data showing that the stimulation is digitally programmable by the ASIC.

[0074] Figure 39 shows one embodiment of a battery-free wireless stimulation implant according to the present disclosure. The aspects include a computer user interface, a transmitter coil, a modulated alternating magnetic field, an ME thin film (power and data receiver), an ASIC (data decoding and stimulation generation), and a programmed stimulation.

[0075] Figure 40 shows the operating mode of a network of four individually addressable implants. Figure 41 shows that both the implant placement and the coil shape are reconfigurable, including, for example, horizontal or vertical configurations. Figure 42 shows one embodiment implemented to stimulate the spinal cord of a rat, and Figure 43 shows one embodiment implemented as a pacemaker.

[0076] In summary, exemplary embodiments of the present disclosure include a wireless network of mm-sized biomedical implants that utilize adaptive closed-loop control of ME power transmission and a novel scheme for multi-access bidirectional communication. In certain embodiments, the global WPT control employed significantly improves robustness against perturbations in distance and alignment and the overall efficiency of the system. In a specific embodiment, the time-domain modulated downlink operates concurrently with power transmission and can achieve a peak power transmission efficiency of 5% and a maximum data rate of 62.3 kbps. The FDMA uplink is realized by individually programmed IFs at a maximum data rate of 40 kbps. Exemplary embodiments have been tested in vitro, demonstrating a working distance of over 6 cm between the external transceiver and the implant.

[0077] All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that variations may be applied to the methods described herein and in the steps or in the sequence of steps of the method, without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that some chemical and physiological related agents may be used in place of the agents described herein, and that the same or similar results would be obtained. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the scope of the spirit, scope and concept of the invention as defined by the appended claims.

[0078] V. References The following references are hereby specifically incorporated by reference herein to the extent that they provide exemplary procedures or other details that supplement those described herein. [1] A. Khalifa et al., “The Microbead: A Highly Miniaturized Wirelessly “Powered Implantable Neural Stimulating System,” TBioCAS, Jun. 2018. [2] M. M. Ghanbari et al., “A Sub-mm3 Ultrasonic Free-Floating Implant for Multi-Mote Neural Recording,” JSSC, Nov. 2019. [3] V. W. Leung et al., “Distributed Microscale Brain Implants with Wireless Power Transfer and Mbps Bi-directional Networked Communications,” in CICC, Apr. 2019. [4] Z. Yu et al., “Multisite bio-stimulating implants magnetoelectrically powered and individually programmed by a single transmitter,” in CICC, Apr. 2021. [5] D. K. Piech et al., “A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication,” Nat. Biomed. Eng., Feb. 2020. [6] Y. Jia et al., “A mm-sized free-floating wirelessly powered implantable optical stimulating system-on-a-chip,” in ISSCC, Feb. 2018. [7] J. Pan et al., “An inductively-coupled wireless power-transfer system that is immune to distance and load variations,” in ISSCC, Feb. 2017. [8] X. Li et al., “A 13.56 MHz Wireless Power Transfer System With Reconfigurable Resonant Regulating Rectifier and Wireless Power Control for Implantable Medical Devices,” JSSC, Apr. 2015. [9] J. Tang et al., “A Wireless Power Transfer System with Up-to-20% Light- Load Efficiency Enhancement and Instant Dynamic Response by Fully Integrated Wireless Hysteretic Control for Bioimplants,” in ISSCC, Feb. 2021.

[10] Z. Yu et al., “MagNI: A Magnetoelectrically Powered and Controlled Wireless Neurostimulating Implant,” TBioCAS, Dec. 2020.

[11] J. Thimot et al., “A 27-Mbps, 0.08-mm3 CMOS Transceiver with Simultaneous Near-field Power Transmission and Data Telemetry for “Implantable Systems,” in CICC, Mar. 2020.

[12] J. Lim et al., “A Light Tolerant Neural Recording IC for Near-Infrared-Powered Free Floating Motes,” in VLSI, Jun. 2021.

[13] Y. Park et al., “A Frequency-Splitting-Based Wireless Power and Data Transfer IC for Neural Prostheses with Simultaneous 115mW Power and 2.5Mb / s Forward Data Delivery,” in ISSCC, Feb. 2021.

[14] N.-C. Kuo et al., “Inductive Wireless Power Transfer and Uplink Design for a CMOS Tag With 0.01 mm2 Coil Size,” Microw. Wirel. Compon. Lett., Oct. 2016.

[15] D. Yeager, W. Biederman, N. Narevsky, E. Alon, and J. Rabaey, “A fully-integrated 10.5μW miniaturized (0.125mm2) wireless neural sensor,” in Symposium on VLSI Circuits, Jun. 2012. Singer, A., S. Dutta, E. Lewis, Z. Chen, J.C. Chen, N. Verma, B. Avants, A.K. Feldman, J. O'Malley, M. Beierlein, C. Kemere, and J.T. Robinson, Magnetoelectric Materials for Miniature, Wireless Neural Stimulation at Therapeutic Frequencies. Neuron, 2020. Z. Yu, J. C. Chen, F. T. Alrashdan, B. W. Avants, Y. He, A. Singer, J. T. Robinson, and K. Yang, “MagNI: A Magnetoelectrically Powered and Controlled Wireless Neurostimulating Implant,” IEEE Transactions on Biomedical Circuits and Systems, pp. 1-1, 2020. Conference Name: IEEE Transactions on Biomedical Circuits and Systems. Zhu, Dibin. Methods of frequency tuning vibration based micro-generator. Diss. University of Southampton, 2009.

Claims

1. An implantable device comprising an electrical circuit connected to a magnetoelectric thin film, a magnetic field generator, and a resonance frequency modulator, wherein the magnetoelectric thin film has a resonance frequency, and the electrical circuit is configured to modulate the resonance frequency of the magnetoelectric thin film by applying different electrical load conditions that change the characteristics of the magnetoelectric thin film. A wireless bioelectronics system.

2. The characteristics of the magnetoelectric thin film are electrical characteristics, elastic characteristics, or magnetic characteristics of the magnetoelectric thin film. The wireless bioelectronics system according to claim 1.

3. The electrical circuit is configured to modulate a voltage, a resistive load, an inductive load, or a capacitive load applied to the magnetoelectric thin film. The wireless bioelectronics system according to claim 1.

4. The magnetoelectric thin film comprises a piezoelectric layer, and the magnetoelectric thin film comprises a magnetostrictive layer connected to the piezoelectric layer. The wireless bioelectronics system according to claim 1.

5. The magnetoelectric thin film comprises a first magnetostrictive layer and a second magnetostrictive layer, the magnetoelectric thin film comprises a piezoelectric layer, and the piezoelectric layer is positioned between the first magnetostrictive layer and the second magnetostrictive layer. The wireless bioelectronics system according to claim 1.

6. The implantable device is a first implantable device, and the wireless bioelectronics system comprises a plurality of implantable devices, each implantable device comprising an electrical circuit connected to a magnetoelectric thin film. The wireless bioelectronics system according to claim 1.

7. The plurality of implantable devices are configured to provide nerve stimulation. The wireless bioelectronics system according to claim 6.

8. The implantable device is connected to a pair of electrodes. The wireless bioelectronics system according to claim 7.

9. The implantable device is connected to a plurality of electrodes. The wireless bioelectronics system according to claim 7.

10. The plurality of electrodes are arranged concentrically. The wireless bioelectronics system according to claim 9.

11. The wireless bioelectronics system according to claim 1, further comprising a plurality of implantable devices, wherein the plurality of implantable devices are arranged in an array or pattern to generate a stimulation pattern among the plurality of implantable devices.

12. An external transceiver, And a plurality of implantable devices, Each implantable device includes an electrical circuit connected to a magnetoelectric thin film, The external transceiver is configured to simultaneously transmit a first magnetic field to each of the plurality of implantable devices, Each of the plurality of implantable devices is configured to transmit a response to the external transceiver, Each of the plurality of implantable devices is configured to transmit the response to the external transceiver after the first magnetic field is transmitted from the transceiver. The wireless bioelectronics system.

13. The wireless bioelectronics system according to claim 12, wherein each of the plurality of implantable devices is configured to stimulate and / or record electrophysiological activity.

14. The wireless bioelectronics system according to claim 12, wherein each of the plurality of implantable devices is configured to transmit a response magnetic field to the transceiver.

15. The wireless bioelectronics system according to claim 14, wherein the response magnetic field is generated by each of the plurality of implantable devices oscillating at the resonant frequency of the implantable device.

16. The wireless bioelectronics system according to claim 12, wherein the electrical circuit is configured to modulate the resonant frequency of the magnetoelectric thin film by applying different electrical load conditions that change the characteristics of the magnetoelectric thin film.

17. The wireless bioelectronics system according to claim 12, wherein the transceiver includes a magnetoelectric transmitter, a controller, and a receiver.

18. The wireless bioelectronics system according to claim 17, wherein the receiver is an induction coil electrode or an ultrasonic transducer.

19. The wireless bioelectronics system according to claim 12, wherein the plurality of implantable devices are configured to be implanted along the spine.

20. The wireless bioelectronics system according to claim 12, wherein the response transmitted from each of the plurality of implantable devices includes data.

21. The wireless bioelectronics system according to claim 20, wherein the data is transmitted from the hub by a modulated magnetic field, near field communication (NFC), light, or Bluetooth Low Energy.

22. The wireless bioelectronics system according to claim 20, wherein the data includes received power.

23. The wireless bioelectronics system according to claim 20, wherein the data includes biomarkers.

24. The wireless bioelectronics system according to claim 23, wherein the biomarker includes a local electric field potential, a spectrogram of the local electric field potential, or power in a specific frequency band such as theta band power, alpha band power, or spike band power.

25. The wireless bioelectronics system according to claim 12, wherein the nerve stimulation is adjusted based on data received from the plurality of implantable devices.

26. The wireless bioelectronics system according to claim 12, wherein the plurality of implantable devices are implanted in the middle or upper part of the left dorsolateral prefrontal cortex and / or the right dorsolateral prefrontal cortex of the brain.

27. The wireless bioelectronics system according to claim 12, wherein the plurality of implantable devices are implanted in the middle or upper part of the spinal cord.

28. A plurality of external transceivers; A plurality of implantable devices; The plurality of external transceivers are uniquely paired with the plurality of implantable devices such that each of the plurality of external transceivers selectively communicates with a single implantable device and does not communicate with other implantable devices. Each implantable device includes an electrical circuit connected to a magnetoelectric thin film. Each external transceiver is configured to transmit a first magnetic field to the implantable device among the plurality of implantable devices. Each of the implantable devices is configured to transmit a response to the external transceiver. A wireless bioelectronics system, wherein each of the plurality of implanted devices is configured to transmit the response to the external transceiver after the first magnetic field is transmitted from the transceiver.

29. A method of stimulating neural tissue, comprising: providing the device according to claim 28; generating a magnetic field with one or more of the plurality of transceivers; generating an electrical output signal with the magnetoelectric thin film; and modifying the electrical output signal with the electrical circuit.

30. A method of stimulating neural tissue, comprising: providing the device according to any one of claims 1 to 11; generating a magnetic field with the magnetic field generator; generating an electrical output signal with the magnetoelectric thin film; and modifying the electrical output signal with the electrical circuit.

31. A method of stimulating neural tissue, comprising: providing the device according to any one of claims 12 to 27; generating a magnetic field with the transceiver; generating an electrical output signal with the magnetoelectric thin film; and modifying the electrical output signal with the electrical circuit.

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