Systems and methods for wireless communication with implantable devices

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 June 17, 2022, the entire contents of which are incorporated herein by reference.

[0002] background STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR 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 an apparatus and method for providing a passive, power-efficient backscatter communication system that enables wireless transmission of data between an implantable magnetoelectric (ME) device and an external base station. [Background technology]

[0004] B. Related Technologies Bioelectronic implants, which can therapeutically target specific tissue sites without administering large amounts of traditional pharmaceuticals, have emerged as a promising option for personalized medicine. However, as these devices become smaller and less invasive, difficulties in providing power and data make it difficult to develop functionality similar to that of larger, battery-powered implants. Recent developments of miniaturized, wirelessly powered electrical stimulators, while promising, are often limited to one or two stimulation channels, which limits their range of applications compared to traditional stimulators. Wireless technologies based on ultrasound and inductive coupling have made significant progress in overcoming this by moving to a single-transmitter / multiple-mote topology. However, these methods are limited in their spatial distribution due to geometric constraints and / or power limitations.

[0005] While conventional electrical stimulation devices such as pacemakers, deep brain electrodes, and spinal cord stimulators are battery-powered and bulky, they have proven highly effective in treating a variety of disorders. To reduce the size, invasiveness, and longevity of implantable bioelectronics, some form of wireless power transfer, in which an external transmitter provides power to tiny implanted "motes," is desirable.

[0006] Compared to conventional implants, which typically have 4–10 stimulation channels, many newly proposed miniature implants are limited to one or two stimulation sites, potentially limiting their effectiveness. Effective multi-mote or multi-channel-per-mote systems must also include the complexity of data transmission to program each channel individually, an additional challenge for wireless systems where each mote may not be in the same alignment as the transmitter. Summary of the Invention [Problem to be solved by the invention]

[0007] Thus, there are numerous challenges to successfully implementing implantable powered devices. For example, a fundamental problem in bioelectronics is the ability to power small devices within the body. While electrical wires provide efficient power transmission, they are a common failure point and limit device placement. Wireless power via electromagnetic waves or ultrasound must also overcome obstacles. For example, they must overcome absorption by the body and impedance mismatches between air, bone, and tissue. Furthermore, conventional methods for wirelessly powering neural implants located in deep tissue regions of freely moving animals or humans are typically bulky due to large electromagnetic coils or battery packs with external leads. Additionally, the ability to provide magnetoelectric charging, data transmission, and stimulation to implantable wireless neurostimulators is not available in existing systems.

[0008] Therefore, these and other issues must be addressed for effective implementation of implantably powered devices. [Means for solving the problem]

[0009] overview Briefly, the present disclosure provides a system for transmitting data to implantable devices, including neurostimulator devices, using magnetic fields.

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

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

[0012] An exemplary embodiment of the present disclosure includes a hardware platform for a wireless mm-sized bio-implant network that utilizes adaptive magnetoelectric power transfer and a novel scheme for efficient bidirectional multiple-access communication. Closed-loop power control mitigates power supply fluctuations caused by changes in distance and alignment and avoids redundant power in the external transceiver. The system also enables simultaneous power- and time-domain modulated downlink data with a peak power transfer efficiency of 5% and a maximum data rate of 62.3 kbps at a 340 kHz carrier frequency, and multiple-access uplink for all implants enabled by separate programmed IFs at a maximum data rate of 40 kbps at a 31 MHz carrier frequency, at distances of over 6 cm between the implants and the external transceiver.

[0013] Wireless networks of miniaturized, battery-free bioimplants with precisely timed sensing and stimulation promise to enable effective, flexible, closed-loop, and patient-specific control of physiological functions. By distributing multiple miniaturized implants around target tissues, exemplary embodiments of the implant networks disclosed herein significantly improve device deployment flexibility, greater specificity, and spatial resolution, with less infection risk and surgical complexity than current battery-powered, single-site implants [1], [2], [3], [4].

[0014] Potential 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, even more so for distributed, mm-sized implants. First, WPT must be robust to ensure proper operation of all implants, which may be placed at different positions and angles and perform different workloads. Simply generating a strong carrier field can result in high body absorption rates and reduced battery life for wearable power transceivers [1], [2], [3], [4], [5], [6]. Non-resonant inductive coupling enables regulated WPT [7], but requires a k larger than 1 / QRX. coupling This limits the application of mm-sized implants to long-distance WPT.

[0016] Closed-loop control utilizing back-transmission telemetry can effectively regulate the receiving voltage [8], [9]. However, all existing demonstration experiments are for 1-cm-scale receivers. Second, for higher power efficiency and smaller receivers, simultaneous power and data transmission is desirable, but is usually limited by the tradeoff between the antenna / transducer quality factor and bandwidth [3],

[10] ,

[11] ,

[12] ,

[13] . Third, efficient and robust multiple-access telemetry in both directions is essential for distributed implant networks.

[0017] Certain embodiments of the present disclosure include systems having implanted motes and an external hub, where the motes stimulate and / or record 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 specific embodiments, the motes are powered by magnetoelectric (ME) thin films, near-infrared communication (NIC), and / or light (e.g., via photodiodes).

[0018] In some embodiments, the stimulation is digitally programmable based on internal circuitry in the form of an application-specific integrated circuit or microcontroller-based system. In certain embodiments, the mote receives data from an external hub, and the data is transmitted from the hub via modulated magnetic field, NFC, light, or Bluetooth Low Energy. In specific embodiments, the external hub receives data from the mote, and the data is transmitted from the mote via ME backscatter, NFC (passive or active backscatter), light, or Bluetooth Low Energy, and the data can include received power. The data can include biomarkers such as local field potentials, spectrograms of local field potentials, or power in specific frequency bands such as theta-band power, alpha-band power, or spike-band power.

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

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

[0021] Certain embodiments include a wireless bioelectronic system comprising an implantable device comprising an electrical circuit coupled to a magnetoelectric film, a magnetic field generator, and a resonant frequency modulator, wherein the magnetoelectric film has a resonant frequency, and the electrical circuit is configured to modulate the resonant frequency of the magnetoelectric film by applying different electrical load conditions that change the properties of the magnetoelectric film.

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

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

[0024] In certain embodiments, the multiple implantable devices are configured to provide neural stimulation. In specific embodiments, the implantable devices are coupled to a pair of electrodes. In some embodiments, the implantable devices are coupled to multiple electrodes. In specific embodiments, the multiple electrodes are arranged concentrically. Some embodiments include multiple implantable devices arranged in an array or pattern to generate a stimulation pattern among the multiple implantable devices.

[0025] Certain embodiments include a wireless bioelectronic system comprising 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 configured to simultaneously transmit a first magnetic field to each of the plurality of implantable devices, each of the plurality of implantable devices configured to transmit a response to the external transceiver, and each of the plurality of implantable devices configured to transmit a response to the external transceiver after the first magnetic field is transmitted from the transceiver.

[0026] In some embodiments, each of the plurality of implantable devices is configured to stimulate and / or record electrophysiological activity. In specific embodiments, each of the plurality of implantable devices is configured to transmit a responsive magnetic field to the transceiver. In certain embodiments, the responsive magnetic field is generated by each of the plurality of implantable devices oscillating at a 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 load 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 specific embodiments, the receiver is an inductive coil electrode or an ultrasonic transducer.

[0028] In some embodiments, the plurality of implantable devices are configured to be implanted along the spinal column. 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 via 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 some embodiments, the data transmitted from the mote includes a biomarker. In certain embodiments, the biomarker includes power in a specific frequency band, such as local field potential, theta band power, or spike band power. In some embodiments, the neurostimulation is adjusted based on the data received from the plurality of implantable devices. In a specific embodiment, the plurality of implantable devices are implanted in the left dorsolateral prefrontal cortex and / or the right dorsolateral prefrontal cortex of the brain. In some embodiments, the plurality of implantable devices are implanted in or above the spinal cord.

[0029] Certain embodiments include a wireless bioelectronic system comprising a plurality of external transceivers and a plurality of implantable devices, wherein 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 not with other implantable devices, each implantable device comprising an electrical circuit coupled to a magnetoelectric thin film, wherein each external transceiver is configured to transmit a first magnetic field to an implantable device of the plurality of implantable devices, each of the 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 is transmitted from the transceiver.

[0030] An embodiment includes a method of stimulating neural tissue, the method including providing an apparatus as described 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] Certain embodiments include a method of stimulating neural tissue, the method comprising providing an apparatus as defined 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] An embodiment includes a method of stimulating neural tissue, the method comprising providing an apparatus as defined 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 present methods, compositions, kits, and systems may consist of or consist essentially of the recited steps and / or features, rather than comprising / including / including / having such steps and / or features. Thus, in any of the claims, the term "consisting of" or "consisting essentially of" can be used in place of any of the open-ended linking verbs set forth above to modify the scope of a given claim from the scope that would otherwise result from the use of that open-ended linking verb.

[0034] Use of the term "or" in the claims is used to mean "and / or" unless expressly indicated to refer to alternatives only or unless the alternatives are mutually exclusive; however, the present disclosure supports a definition that refers to alternatives only and "and / or."

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

[0036] In accordance with long-standing patent law, the words "a" and "an," when used in conjunction with the word "comprising" in the claims or specification, indicate one or more, unless the context clearly indicates otherwise.

[0037] Other objects, features, and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples, while indicating certain embodiments of the present invention, 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 part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference 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 containing color drawing(s) will be provided by the Office upon request and payment of the necessary fee. [Brief explanation of the drawings]

[0039] [Figure 1] FIG. 1 is a schematic diagram of an embodiment according to the present disclosure. [Figure 2] FIG. 1 illustrates data from an embodiment of the present disclosure. [Figure 3] FIG. 1 illustrates data from an embodiment of the present disclosure. [Figure 4] FIG. 1 illustrates data from an embodiment of the present disclosure. [Figure 5] FIG. 1 illustrates data from an embodiment of the present disclosure. [Figure 6]FIG. 1 is a schematic diagram of an embodiment of a chip design according to the present disclosure. [Figure 7] 1 is a photograph of an embodiment according to the present disclosure. [Figure 8] 1A-1C illustrate various representations of data associated with embodiments of the present disclosure. [Figure 9] 1A-1C illustrate various representations of data associated with embodiments of the present disclosure. [Figure 10] 1A-1C illustrate various representations of data associated with embodiments of the present disclosure. [Figure 11] 1A-1C illustrate various representations of data associated with embodiments of the present disclosure. [Figure 12] 1A-1C illustrate various representations of data associated with embodiments of the present disclosure. [Figure 13] FIG. 1 illustrates an in vitro testing demonstration of one embodiment according to the present disclosure. [Figure 14] FIG. 1 illustrates data according to one embodiment of the present disclosure. [Figure 15] 1 is a schematic diagram and photograph of one embodiment according to the present disclosure. [Figure 16] FIG. 1 is a block diagram of one embodiment of the present disclosure. [Figure 17] FIG. 1 is a schematic diagram of an embodiment according to the present disclosure. [Figure 18] FIG. 1 shows a schematic diagram and operating waveforms of local timing reference generation based on frequency locking. [Figure 19] 1 illustrates an existing multiple access uplink telemetry strategy and the principle of frequency division multiple access of one embodiment according to the present disclosure. [Figure 20] FIG. 1 is a schematic diagram of an embodiment according to the present disclosure. [Figure 21] FIG. 1 is a block diagram of the proposed closed-loop global power control. [Figure 22] FIG. 1 shows a micrograph of an implant tip and an in vitro test setup of one embodiment according to the present disclosure. [Figure 23] FIG. 10 illustrates waveforms of one embodiment according to the present disclosure. [Figure 24] FIG. 1 illustrates measured clock CLKLO lock, input voltage variation, and measured frequency for one embodiment according to the present disclosure. [Figure 25] FIG. 10 illustrates a measured waveform of an uplink data implant voltage feedback of one embodiment according to the present disclosure. [Figure 26] FIG. 2 illustrates an uplink data spectrum for one embodiment according to the present disclosure. [Figure 27] FIG. 10 illustrates sample measured behavior of global wireless power transfer control with respect to device movement for one embodiment according to the present disclosure. [Figure 28] FIG. 10 illustrates the measured received voltage, power transfer efficiency, and uplink BER at various distances between an external transceiver and an implant in one embodiment according to the present disclosure. [Figure 29] 1 is a table showing a comparison of state-of-the-art integrated power and telemetry platforms for wireless bioimplants. [Figure 30] FIG. 1 is a conceptual diagram of an embodiment according to the present disclosure comprising a computer processor, a hub, and a stimulator positioned proximal to a patient's spine to provide neurostimulation to the brain. [Figure 31] FIG. 1 is a conceptual diagram of one embodiment according to the present disclosure comprising a computer processor, a hub, and a stimulator positioned proximal to a patient's spine to provide neural stimulation to the spinal cord. [Figure 32] FIG. 10 is a diagram of data showing that one embodiment according to the present disclosure can be powered by a magnetoelectric thin film. [Figure 33] FIG. 10 is a diagram of data illustrating that multiple embodiments according to the present disclosure can be programmed at once. [Figure 34] FIG. 1 shows an image of an embodiment according to the present disclosure showing a leadless glass device for cortical stimulation. [Figure 35] 1A-1C illustrate glass package design and electrode spacing options in embodiments according to the present disclosure. [Figure 36] FIG. 10 illustrates coordinated stimulation between two glass moats in one embodiment according to the present disclosure. [Figure 37] FIG. 10 shows an image of an embodiment according to the present disclosure showing an epoxy sealed device with spinal cord stimulation leads. [Figure 38] FIG. 10 illustrates data showing that stimulation can be digitally programmable by an ASIC according to one embodiment of the present disclosure. [Figure 39] FIG. 1 illustrates an embodiment of a battery-free wireless stimulation implant according to the present disclosure. [Figure 40] FIG. 1 illustrates the operation of a network of four individually addressable implants, according to one embodiment of the present disclosure. [Figure 41] FIG. 10 illustrates that both the implant placement and coil shape are reconfigurable, including horizontal or vertical configurations. [Figure 42] FIG. 1 illustrates an embodiment of the present disclosure implemented to stimulate the spinal cord of a rat. [Figure 43] FIG. 1 illustrates an embodiment of the present disclosure implemented as a pacemaker. DETAILED DESCRIPTION OF THE INVENTION

[0040] Detailed Description of the Invention Embodiments of the present disclosure include a passive, power-efficient backscatter communication system that enables wireless transmission of data between an implantable magnetoelectric (ME) device and an external base station.

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

[0042] As shown in Figure 1A, 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 travel 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 electrical 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 stimulation field and the recorded response, measurements are taken during the ring-down period when the external magnetic field is off, and the resonant frequency is determined by calculating the fast Fourier transform (FFT) of the ring-down waveform. To encode data transmitted from the implant to an external base station, the resonant frequency of the ME thin film is electrically modulated by connecting the ME thin film's terminals to various electrical load conditions that alter its electrical, elastic, or magnetic properties, thereby changing its resonant frequency. As shown in Figure 1B, DC voltage, resistive loads, inductive loads, or capacitive loads can shift the resonant frequency of the ME thin film, enabling frequency modulation.

[0044] As shown in Figure 1.C, both analog and digital modulation are possible. For example, to transmit analog signals, different capacitors are used to continuously change the resonant frequency. For digital signals, a frequency-shift keying scheme is used, in which 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 the data. In both cases, the ASIC regulates DC voltage, resistive loads, inductive loads, or capacitive loads through various analog and / or digital modulation methods.

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

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

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

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

[0049] Figure 7 shows a prototype of the magnetoelectric implant. The implant is shown on a fingertip to demonstrate its miniaturized form factor. The implant measures 8.2 mm 3 The ASIC chip, ME transducer, and energy storage capacitor are integrated on a substrate with a volume of 1000 sq. m 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, and a capacitive load is used to digitally encode data by shifting the resonant frequency between two different values ​​using frequency shift keying.

[0051] Figure 8 shows an example of ME-BIT functionality. The implant can harvest power for stimulation and communicate sensor data (temperature sensor, for example) using the proposed backscatter ME technology. In particular, Figure 8 shows the implant's measured operating waveforms. The magnetoelectrically powered and programmed implant continuously performs temperature sensing, uplink data transmission, and stimulation; the close-up view shows the implant's temperature sensor output, uplink data output, and stimulation pulses.

[0052] Figure 9 shows the measured waveform of the demodulated signal. In particular, Figure 9 shows an example of demodulating a transmitted signal by a magnetic external transceiver. Uplink data from the implant is transmitted through ME backscatter and recovered by the external transceiver. Capacitive load shifts at the implant terminals change the frequency of the backscattered signal, resulting in different pulse widths for data "1" and "0," as shown in the close-up. The data is demodulated by detecting the change in pulse width.

[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 a receiver. The sensing results are transmitted wirelessly from the implant through ME backscatter. This implant was tested in a temperature chamber ranging from 30°C to 44°C and showed an error of less than 0.35°C.

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

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

[0056] To address the shortcomings of existing systems, a wireless network of mm-sized implants with closed-loop adaptive magnetoelectric power transfer control (sometimes referred to herein as "BioNet") is disclosed. Referring now to panel (a) of FIG. 15, a conceptual diagram of the proposed BioNet with adaptive power transfer and bidirectional telemetry is shown. Panel (b) of FIG. 15 shows a wireless network of mm-sized implants with closed-loop adaptive magnetoelectric power transfer control (sometimes referred to herein as "BioNet"). 3 1 shows a specific embodiment of an implantable device having a volume of 1000 psi 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 multiple access two-way communication. 3 The implant includes (1) closed-loop magnetoelectric wireless power transfer that adapts to implant workload, changes in distance and misalignment of the implant relative to the external TRX; (2) simultaneous power and time domain downlink telemetry with a peak power transfer efficiency (PTE) of 5% and a maximum data rate of 62.3 kbps; (3) multiple-access uplink telemetry enabled by an independently programmed intermediate frequency (IF); (4) robust operation under 2 V power supply fluctuations; and (5) a TRX-to-implant working distance of greater than 6 cm to receive a power input greater than 1.3 V 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 a different configuration. 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 intermixed throughout the film.

[0059] In the specific embodiment shown, the electrical circuit 130 is 2 SoC and 4x2mm 2 ME transducer and 2.5mm with conjugate impedance matching 2 Backscatter coil and 0.25mm sieve storing a maximum energy of 135μJ 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, under the control of the external transceiver 110, perform bidirectional telemetry, clock recovery, input voltage sensing, and stimulation. 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 Simultaneous power transmission and telemetry are highly desirable for implants with limited energy storage. OOK

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

[12] require frequent amplitude switching, resulting in input power fluctuations and low data rates constrained by the high quality factor of the antenna / transducer (panel (a) of Figure 17). Frequency-division FSK was recently proposed for stable power delivery and high data rates

[13] . However, it requires strong coupling, which is susceptible to distance changes and misalignment (panel (b) of Figure 17). An exemplary embodiment of the present disclosure provides a notch-spacing time-domain modulation scheme, in which multiple bits are encoded into the pulse duration, to amortize the transducer's slow switching speed, as shown in panel (c) of Figure 17. In this scheme, each pulse is defined by two narrow magnetic field notches and can be quickly detected by the active rectifier comparator [4]. This method minimizes PTE degradation. To trade off switching time amortization and duration coding overhead, each data symbol is designed to contain a maximum of six bits. A complete packet includes a header, an ID for individual addressing, and a payload. Accurate clocking is essential for accurate demodulation.

[0061] While recovering a PVT-invariant clock from a source is straightforward, it fails in the absence of a carrier field and is therefore incompatible with notch-based schemes. To address this, the LO of each implant provides a timing reference (CLK LO ) as the clock recovered from the source (CLK REF ) Frequency locking is performed autonomously before each downlink data transmission session using SAR logic as shown in FIG.

[0062] Uplink backscatter with FDMA (Frequency Division Multiple Access) Exemplary embodiments of the present disclosure can include multiple implantable devices. Accessing feedback from each implantable device is important, which requires a multiple-access uplink. FDMA is preferred over TDMA (Time Division Multiple Access) [3] due to its 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 Figure 19, limiting their scalability and compatibility.

[0063] The use of intermediate frequencies (IFs) has shown advantages in SNR in stimulated backscatter

[14] . In this work, IFs are further utilized by mixing individually programmed IFs with uplink data, as shown in panel (d) of Figure 19, to achieve low-cost, scalable FDMA in backscatter. This mechanism allows each implant to simultaneously access the external transceiver

[15] . The implant data rate is programmed based on channel conditions to optimize the signal-to-noise ratio (SNR). In an exemplary embodiment, the uplink module controls the implant voltage V as shown in panel (a) of Figure 6. RECT It comprises a voltage-controlled oscillator (VCO)-based quantizer for detecting the ,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 the block diagram of the proposed closed-loop global power control.

[0064] Adaptive Global Power Transfer Control Using an on-chip Physical Unclonable Function (PUF) implantable device (ID), each implant's functionality can be individually programmed and controlled by an external transceiver, which knows the received power of each implant through a multiple-access uplink. The transceiver adapts the output power of the power transmitter to regulate the implant's input power based on real-time workload and channel efficiency. The proposed closed-loop control of wireless power transmission can significantly mitigate power fluctuations caused by distance changes and misalignment, avoiding unnecessary power consumption of the external transceiver during light workloads.

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

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

[0067] Figure 25 shows the operating waveforms of the uplink telemetry and the sensing and reporting of the implant's received voltage. 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)). Furthermore, the multiple access uplink is demonstrated by the spectrum of two implants simultaneously transmitting data at separate, independently programmed IFs of 83 kHz and 108 kHz (Figure 26(b)).

[0068] Figure 27 shows continuous closed-loop wireless power transfer control as the transceiver-implant distance is varied. As the distance increases by 1.5 cm, the ME voltage drops from 2.8 V to 1.52 V, resulting in a maximum 1.38 mW reduction in received power. The implant voltage is then restored to the desired 2.8 V after 30 tuning cycles by adaptively controlling the magnetoelectric transmitter power.

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

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

[11] and comparable to

[13] , which operates at much smaller distances. The proposed invention enables FDMA with individually programmed IFs in the uplink (see Figure 29, which includes a table showing a comparison with state-of-the-art integrated power and telemetry platforms 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 stimulator (e.g., a magnetoelectric implant) positioned proximal to a patient's skull and brain to provide neurostimulation (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 stimulator (e.g., a magnetoelectric implant) positioned proximal to a patient's spine to provide neurostimulation to the spinal cord.

[0071] FIG. 32 presents data showing that devices can be powered by magnetoelectric thin films, and FIG. 33 presents data showing that multiple devices can be programmed at once.

[0072] Figure 34 provides an image showing a leadless glass device for cortical stimulation. In one embodiment, a custom-made through-glass via (TGV) wafer is obtained, and platinum and titanium are deposited and patterned to form electrode contacts on the TGV wafer. In a specific embodiment, a laser is used to cut individual "caps" from the TGV wafer, and the ASIC is bonded 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 bonded to the inside of the cap with conductive silver epoxy, the cap is sealed to the glass tube with medical-grade epoxy or laser welding, and an identically sized cap is bonded to the top of the glass tube.

[0073] Figure 35 shows alternative glass package designs and electrode spacing options for certain embodiments. Figure 36 shows a simulation of coordinated stimulation between two glass motes, and Figure 37 provides an image of one embodiment showing an epoxy-encapsulated device with leads for spinal cord stimulation. In this embodiment, the ASIC is glued to a custom PCB, and the ME membrane is connected to the PCB with wires and conductive silver epoxy. The stimulation leads are also connected to the PCB with silver epoxy, and the package is 3D printed to include a cavity for the ME membrane. The ME membrane is sealed inside a box, and the PCB is sealed to the outside of the box with medical-grade transparent epoxy. Figure 38 provides data showing that stimulation can be digitally programmed by the ASIC.

[0074] 39 illustrates one embodiment of a battery-free wireless stimulation implant according to the present disclosure. Aspects include a computer user interface, a transmitter coil, a modulated AC magnetic field, an ME membrane (power and data receiver), an ASIC (data decoding and stimulus generation), and programmed stimulation.

[0075] Figure 40 shows the operation of a network of four individually addressable implants. Figure 41 shows that both the placement of the implants 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 multiple-access bidirectional communication. In certain embodiments, the employed global WPT control significantly improves robustness to distance and alignment perturbations and overall system efficiency. In specific embodiments, a time-domain modulated downlink operates simultaneously 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 a separately programmed IF with a maximum data rate of 40 kbps. Exemplary embodiments have been tested in vitro, demonstrating a working distance of more than 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 can be made in the methods described herein and in the steps or sequence of steps of the methods without departing from the concept, spirit, and scope of the invention. More specifically, it will be apparent that certain agents that are chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope, and concept of the invention as defined by the appended claims.

[0078] V. References The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference. [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. 1. A wireless bioelectronic system, comprising: an implantable device comprising an electrical circuit coupled to the magnetoelectric thin film; the magnetoelectric thin film is configured to generate a backscattering magnetic field when excited by an external pulsed magnetic field; The wireless bioelectronic system comprises: further comprising an external transceiver; the external transceiver is configured to transmit the external pulsed magnetic field to the implantable device; the implantable device is configured to transmit a response signal corresponding to the backscattered magnetic field to the external transceiver using one or more modulation techniques; the magnetoelectric thin film has a characteristic that changes the resonant frequency of the magnetoelectric thin film; The electrical circuit is configured to apply different electrical load conditions that change the properties of the magnetoelectric thin film.

2. The wireless bioelectronic system of claim 1 , wherein the property of the magnetoelectric thin film is an electric property, an elastic property, or a magnetic property of the magnetoelectric thin film.

3. The wireless bioelectronic system of claim 1 , wherein 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.

4. the magnetoelectric thin film comprises a piezoelectric layer; The wireless bioelectronic system of claim 1 , wherein the magnetoelectric thin film comprises a magnetostrictive layer coupled to the piezoelectric layer.

5. the magnetoelectric thin film comprises a first magnetostrictive layer and a second magnetostrictive layer; the magnetoelectric thin film comprises a piezoelectric layer; The wireless bioelectronic system of claim 1 , wherein the piezoelectric layer is positioned between the first magnetostrictive layer and the second magnetostrictive layer.

6. the implantable device is a first implantable device; The wireless bioelectronic system of claim 1 , wherein the wireless bioelectronic system comprises a plurality of implantable devices, each implantable device comprising an electrical circuit coupled to a magnetoelectric thin film.

7. The wireless bioelectronic system of claim 1 , wherein the implantable device is configured to provide neural stimulation.

8. The wireless bioelectronic system of claim 1 , wherein the implantable device is coupled to a pair of electrodes.

9. The wireless bioelectronic system of claim 1 , wherein the implantable device is coupled to a plurality of electrodes.

10. The wireless bioelectronic system of claim 9 , wherein the plurality of electrodes are arranged concentrically.

11. 10. The wireless bioelectronic system of claim 1, further comprising a set of other implantable devices, the implantable device and the set of other implantable devices positioned in an array or pattern to generate a stimulation pattern.

12. 1. A method comprising: providing a wireless bioelectronic system; The wireless bioelectronic system comprises: an implantable device comprising an electrical circuit coupled to a magnetoelectric film, the magnetoelectric film configured to generate a backscattering magnetic field when excited by an external pulsed magnetic field; The wireless bioelectronic system further comprises: an external transceiver; the external transceiver is configured to transmit the external pulsed magnetic field to the implantable device; the implantable device is configured to transmit a response signal corresponding to the backscattered magnetic field to the external transceiver using one or more modulation techniques; The wireless bioelectronic system further comprises: a magnetic field generator; the magnetoelectric thin film has a characteristic that changes the resonant frequency of the magnetoelectric thin film; the electrical circuit is configured to apply different electrical load conditions that change the properties of the magnetoelectric thin film; The method further comprises: generating a magnetic field with the magnetic field generator; generating an electrical output signal with the magnetoelectric thin film; and modifying said property of said magnetoelectric thin film with said electrical circuit.

13. The method of claim 12 , wherein the property of the magnetoelectric thin film is an electric property, an elastic property, or a magnetic property of the magnetoelectric thin film.

14. The method of claim 12 , wherein altering the property of the magnetoelectric thin film comprises modulating a voltage, a resistive load, an inductive load, or a capacitive load applied to the magnetoelectric thin film.

15. the magnetoelectric thin film comprises a piezoelectric layer; The method of claim 12 , wherein the magnetoelectric thin film comprises a magnetostrictive layer coupled to the piezoelectric layer.

16. the magnetoelectric thin film comprises a first magnetostrictive layer and a second magnetostrictive layer; the magnetoelectric thin film comprises a piezoelectric layer; The method of claim 12 , wherein the piezoelectric layer is positioned between the first magnetostrictive layer and the second magnetostrictive layer.

17. the implantable device is a first implantable device; 13. The method of claim 12, wherein the wireless bioelectronic system comprises a plurality of implantable devices, each implantable device comprising an electrical circuit coupled to a magnetoelectric thin film.

18. The method of claim 12 , wherein the implantable device is configured to provide neural stimulation.

19. The method of claim 12 , wherein the implantable device is coupled to a pair of electrodes.

20. The method of claim 12 , wherein the implantable device is coupled to multiple electrodes.

21. The method of claim 20 , wherein the plurality of electrodes are arranged concentrically.

22. 13. The method of claim 12, wherein the wireless bioelectronic system further comprises a set of other implantable devices, and wherein the implantable device and the set of other implantable devices are positioned in an array or pattern to generate the stimulation pattern.

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