System and method for wireless communication with implantable devices

Abstract

This invention provides a system that uses a magnetic field to transmit data to implantable devices, including nerve stimulation devices. [Solution] Exemplary embodiments of the present disclosure include apparatus, systems, and methods utilizing a passive, power-efficient backscatter communication system that enables wireless transmission of data between an implanted magnetoelectric (ME) device and an external base station. One embodiment encodes the transmitted data by modulating the resonant frequency of an ME thin film by digitally adjusting the electrical load conditions of the ME thin film.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 353,371, filed on 17 June 2022, the entirety of which is incorporated herein by reference.

[0002] background Statement on Research and Development Funded by the Federal Government This invention was made possible with government support under grant number ECCS-2023849 from the National Science Foundation, grant number EB029353 from the National Institutes of Health, and grant number FA8650-21-2-7119 from the Defense Advanced Research Projects Agency. The government has certain rights in this invention.

[0003] A. Field This disclosure relates to an apparatus and method for providing a passive, power-efficient backscatter communication system that enables wireless transmission of data between an implanted magnetoelectric (ME) device and an external base station. [Background technology]

[0004] B. Related Technologies Bioelectronic implants, which can target specific tissue sites for therapeutic purposes without administering large doses of conventional drugs, are emerging as a promising option for personalized medicine. However, as these devices become smaller and less invasive, the difficulty in supplying power and data makes it challenging to develop them to perform similarly to larger, battery-powered implants. Recent developments of small, wirelessly powered electrical stimulators are promising, but they are often limited to one or two stimulation channels, which limits their application range compared to conventional stimulators. Wireless technologies based on ultrasound and inductive coupling have made significant progress in overcoming this limitation with the shift to single-transmitter / multiple-moat configurations. However, these methods are limited 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 stimulators have been battery-powered and bulky, yet have shown high efficacy in treating a variety of disorders. To reduce the size and invasiveness of implantable bioelectronics and extend their lifespan, some form of wireless power supply, in which an external transmitter powers a small, implanted "moat," is desirable.

[0006] Compared to conventional implants that typically have 4 to 10 stimulation channels, many of the newly proposed miniature implants are limited to one or two stimulation sites, which may limit their effectiveness. Furthermore, effective multi-move systems or multi-channel systems per move also require the complexity of data transmission to program each channel individually, which is a further challenge for wireless systems where each move may not be aligned with the transmitter. [Overview of the project] [Problems that the invention aims to solve]

[0007] Therefore, there are numerous challenges to overcome in order to successfully implement embedded powered devices. Yes. For example, a fundamental problem in bioelectronics is the ability to power small devices within the body. Wires, while providing efficient power transmission, are a common point of failure and limit device placement. Wireless power via electromagnetic waves or ultrasound also has obstacles to overcome. For example, wireless power via electromagnetic waves or ultrasound must overcome absorption by the body, as well as impedance mismatches between air, bone, and tissue. Furthermore, conventional methods of wirelessly powering nerve implants in the deep tissue areas of freely moving animals or humans are typically bulky due to large electromagnetic coils or battery packs with external leads. In addition, the ability to provide magnetoelectric charging, data transmission, and stimulation to implantable wireless nerve stimulators is not provided by existing systems.

[0008] Therefore, in order to effectively implement embedded power supply devices, it is necessary to address not only these issues but also other problems. [Means for solving the problem]

[0009] overview In short, this disclosure provides a system for transmitting data using a magnetic field to an implantable device, including a nerve stimulation device.

[0010] An exemplary embodiment includes a passive, power-efficient backscatter communication system that enables wireless transmission of data between an implanted magnetoelectric (ME) device and an external base station.

[0011] In one embodiment, transmitted data is encoded by modulating the resonant frequency of the ME thin film by digitally adjusting the electrical load conditions of the ME thin film. When the ME thin film is excited by an external pulsed magnetic field, the posterior scattered magnetic response, electrical response, or acoustic response can be recorded by a magnetic field sensor, electrode, or microphone, respectively. In addition, the data of the received signal can be decoded using frequency demodulation.

[0012] An exemplary embodiment of this disclosure includes a hardware platform for a wireless mm-sized bioimplant network utilizing a novel scheme for adaptive magnetoelectric power transmission and efficient bidirectional multiplex access communication. Closed-loop power control mitigates power supply fluctuations caused by changes in distance and alignment, and avoids redundant power for external transceivers. The system also enables multiplex access uplinks for all implants, with a peak power transmission efficiency of 5% and simultaneous power and time-domain modulated downlink data at a maximum data rate of 62.3 kbps at a 340 kHz carrier frequency, and 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 external transceivers.

[0013] A wireless network of miniaturized, battery-free bioimplants that precisely time and detect and stimulates is expected to enable effective, flexible, closed-loop, and patient-specific control of physiological functions. By distributing multiple miniaturized implants around target tissue, exemplary embodiments of the implant network disclosed herein offer significantly improved device deployment flexibility, greater specificity, and spatial resolution compared to current battery-powered single-site implants, while achieving a lower risk of infection and surgical complexity.[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 transmission (WPT) and telemetry to bioimplants still face significant challenges, which are even more pronounced with distributed mm-sized implants. Firstly, WPT must be robust enough to ensure proper operation of all implants, which are positioned at different locations and angles and perform different workloads. Simply generating a strong carrier field can lead to high bioabsorption rates and shorten the battery life of wearable power transceivers[1][2][3][4][5][6]. Non-resonant inductive coupling enables regulated WPT[7], but with a k² greater than 1 / QRX. coupling This is necessary, and the application of mm-sized implants to long-distance WPT is limited.

[0016] Closed-loop control utilizing back telemetry allows for effective regulation of the received voltage [8], [9]. However, all existing demonstration experiments are for receivers on the 1 cm scale. Secondly, simultaneous transmission of power and data is desirable for higher power efficiency and smaller receivers, but is usually limited by the trade-off between antenna / transducer quality factor and bandwidth [3],

[10] ,

[11] ,

[12] ,

[13] . Thirdly, efficient and robust bidirectional multiple access telemetry is essential in distributed implant networks.

[0017] Certain embodiments of the present disclosure include a system having an implanted mote and an external hub, the mote stimulating and / or recording electrophysiological activity. In some embodiments, there is one or more motes and a single transmitter, and in other embodiments, there is a single mote for each transmitter. In specific embodiments, the mote is powered by a magnetoelectric (ME) thin film, 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 comprises an implantable device with an electrical circuit coupled to a magnetoelectric thin film, A wireless bioelectronics system includes a magnetic field generator and a resonance frequency modulator. 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.

[0022] In certain embodiments, the characteristics 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 the 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] A particular embodiment includes a wireless bioelectronics system comprising an external transceiver and a plurality of implantable devices, each implantable device comprising an electrical circuit connected 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 has been transmitted from the transceiver.

[0026] In some embodiments, each of the multiple implantable devices is configured to stimulate and / or record electrophysiological activity. In specific embodiments, each of the multiple implantable devices is configured to transmit a response magnetic field to a transceiver. In some embodiments, the response magnetic field is generated by each of the multiple 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 a magnetoelectric thin film by applying different electrical load conditions that alter 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 induction coil electrode or an ultrasonic transducer.

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

[0029] A particular embodiment includes 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 the plurality of implantable devices such that each of the plurality of external transceivers selectively communicates with a single implantable device and not with any other implantable devices, each implantable device comprises an electrical circuit connected to a magnetoelectric thin film, each external transceiver is configured to transmit a first magnetic field to an implantable device among the plurality of implantable devices, each implantable device 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 has been transmitted from the transceiver.

[0030] One embodiment includes a method for stimulating nerve tissue, the method of providing the apparatus described in claim 28, which includes 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 for stimulating nerve tissue, the method comprising providing an apparatus according to any one of claims 1 to 11, and including 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 for stimulating nerve tissue, the method comprising providing an apparatus according to any one of claims 12 to 27, which includes 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 described herein may consist of or be essentially comprised of, rather than comprising, including, encompassing, or having, any of the steps and / or features described herein. Accordingly, in any claim, the scope of a given claim may be modified from the scope that would be achieved if the non-restrictive linking verbs were originally used, by using the terms "consisting of" or "essentially derived from" instead of any of the non-restrictive linking verbs described herein.

[0034] The use of the term “or” in the claims is used to mean “and / or” unless it is expressly indicated that it refers only to substitutes, or that the substitutes are not mutually exclusive; however, this disclosure supports the definitions that refer only to substitutes and “and / or”.

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

[0036] In accordance with long-standing patent law, the word "one (a, an)" is used in the claims or When used in a specification with the words "comprising," it refers to 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, it should be understood that the detailed description and specific examples, while illustrating some embodiments of the present invention, are given merely for illustrative purposes, as various variations 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 constitute part of this specification and are included to further illustrate some aspects of the invention. The invention can be better understood by referring to one or more of these drawings in conjunction with the detailed description of the specific embodiments presented herein. The patent or application file includes at least one drawing drawn in color. Copies of this patent or patent application publication containing the color drawings are available from the Japan Patent Office upon request and payment of the necessary fees. [Brief explanation of the drawing]

[0039] [Figure 1] This is a schematic diagram of one embodiment according to the present disclosure. [Figure 2] This figure shows data from the embodiments of this disclosure. [Figure 3] This figure shows data from the embodiments of this disclosure. [Figure 4] This figure shows data from the embodiments of this disclosure. [Figure 5] This figure shows data from the embodiments of this disclosure. [Figure 6] This is a schematic diagram of a chip design according to one embodiment of the present disclosure. [Figure 7] This is a photograph of one embodiment of the present disclosure. [Figure 8] This figure shows various representations of the data associated with the embodiments of this disclosure. [Figure 9] This figure shows various representations of the data associated with the embodiments of this disclosure. [Figure 10] This figure shows various representations of the data associated with the embodiments of this disclosure. [Figure 11] This figure shows various representations of the data associated with the embodiments of this disclosure. [Figure 12] This figure shows various representations of the data associated with the embodiments of this disclosure. [Figure 13] This figure shows an in vitro test demonstration of one embodiment of the present disclosure. [Figure 14] This figure shows data according to one embodiment of the present disclosure. [Figure 15] These are schematic diagrams and photographs of one embodiment of the present disclosure. [Figure 16] This is a block diagram of one embodiment of the present disclosure. [Figure 17] This is a schematic diagram of one embodiment according to the present disclosure. [Figure 18] This figure shows a schematic diagram and operating waveform of local timing reference generation based on frequency locking. [Figure 19] This figure shows an existing multiplex access uplink telemetry strategy and the principle of frequency division multiplex access in one embodiment of the present disclosure. [Figure 20] This is a schematic diagram of one embodiment according to the present disclosure. [Figure 21] This is a block diagram of the proposed closed-loop global power control system. [Figure 22] This figure shows a micrograph of an implant tip and an in vitro test setup of one embodiment according to the present disclosure. [Figure 23] This figure shows a waveform of one embodiment according to the present disclosure. [Figure 24] This figure shows the measured clock CLKLO lock, input voltage fluctuation, and measured frequency of one embodiment according to the present disclosure. [Figure 25] This figure shows the measured waveform of the uplink data implant voltage feedback in one embodiment of the present disclosure. [Figure 26] This figure shows the spectrum of uplink data in one embodiment of the present disclosure. [Figure 27]This figure shows a measured sample operation of global wireless power transmission control in response to device movement according to one embodiment of the present disclosure. [Figure 28] This figure shows the measured received voltage, power transmission efficiency, and uplink BER at various distances between an external transceiver and an implant in one embodiment of the present disclosure. [Figure 29] This table shows a comparison of the latest technologies for wireless bioimplants with integrated power supply and telemetry platforms. [Figure 30] This is a conceptual diagram of one embodiment of the present disclosure, comprising a computer processor, a hub, and a stimulator positioned proximal to the patient's spine for delivering neural stimulation to the brain. [Figure 31] This is a conceptual diagram of one embodiment of the present disclosure, comprising a computer processor, a hub, and a stimulator positioned proximal to the patient's spine for delivering nerve stimulation to the spinal cord. [Figure 32] This is a data diagram showing that power can be supplied by a magnetoelectric thin film in one embodiment of the present disclosure. [Figure 33] This is a data diagram showing that multiple embodiments of this disclosure can be programmed at once. [Figure 34] This figure shows an image of one embodiment of the present disclosure, illustrating a leadless glass device for cortical stimulation. [Figure 35] This figure shows the options for glass package design and electrode spacing in the embodiments of this disclosure. [Figure 36] This figure shows the coordinated stimulation between two glass moats according to one embodiment of the present disclosure. [Figure 37] This figure shows an image of one embodiment of the present disclosure, illustrating an epoxy-sealed device having lead wires for spinal cord stimulation. [Figure 38] This figure shows data demonstrating that stimuli can be digitally programmed by an ASIC according to one embodiment of the present disclosure. [Figure 39]This figure shows one embodiment of a battery-free wireless stimulation implant according to the present disclosure. [Figure 40] This figure shows the operation of a network of four individually addressable implants according to one embodiment of the present disclosure. [Figure 41] This figure shows that both the implant placement and coil shape are reconfigurable, including horizontal or vertical configurations. [Figure 42] This figure shows one embodiment of the present disclosure implemented to stimulate the spinal cord of a rat. [Figure 43] This figure shows one embodiment of the present disclosure implemented as a pacemaker. [Modes for carrying out 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 implanted magnetoelectric (ME) device and an external base station.

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

[0042] As shown in Figure 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 on the skin surface using a microphone. Due to the mechanical connection 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 on the skin surface using a pair of electrodes.

[0043] To eliminate interference between the stimulated magnetic 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 the data transmitted from the implant to the external base station, the resonant frequency of the ME thin film is electrically modulated by connecting the terminals of the ME thin film to various electrical load conditions that change its resonant frequency by altering its electrical, elastic, or magnetic properties. As shown in Figure 1.B, DC voltage, resistive load, inductive load, or capacitive load 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 an analog signal, different capacitors are used to continuously vary the resonant frequency. For digital signals, a frequency shift keying scheme 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 the data. In both cases, the ASIC modulates DC voltage, resistive load, inductive load, or capacitive load by various analog and / or digital modulation schemes.

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

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

[0047] Figures 2–4 show recorded data from exemplary embodiments, including the resonant 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 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 a capacitive load to realize backscatter communication. The ASIC supports ME-based power transmission 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 intensity of the backscatter signal is determined by the size of the ME thin film, which can limit the operating distance in smaller devices. To address this problem, the design of the receiver circuit (coil, microphone, or electrode) in a particular embodiment can be optimized for higher sensitivity.

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

[0051] Figure 8 shows an example of the ME-BIT's functionality. This implant can acquire power for stimulation and communicate sensor data (a temperature sensor, for example) using the proposed backscatter ME technique. In particular, Figure 8 shows the measured operating waveform of the implant. Powered magnetoelectrically and programmed, the implant continuously performs temperature sensing, uplink data transmission, and stimulation. The enlarged view shows the implant's temperature sensor output, uplink data output, and stimulation pulse.

[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 backscattering and recovered by the external transceiver. Capacitive load shift at the implant terminal changes the frequency of the backscattered signal, resulting in different pulse widths for data "1" and "0", as shown in the enlarged view. 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 the receiver. The detection results are transmitted wirelessly from the implant via ME backscattering. This implant was tested in a temperature chamber of 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 performance demonstration of the system using 1.5 cm thick porcine tissue. The tissue covered the TRX coil, and the implant was placed on the surface of the tissue using test leads for functional monitoring. Figure 14 shows the BER vs. data rate tested in vitro.

[0056] To address the shortcomings of existing systems, this specification describes a wireless network for mm-sized implants with closed-loop adaptive magnetoelectric power transmission control (referred to as " We disclose a BioNet (sometimes referred to as BioNet). Referring here to panel (a) of Figure 15, a conceptual diagram of the proposed BioNet having adaptive power transmission and bidirectional telemetry is shown. Panel (b) of Figure 15 shows 8.8 mm3 A specific embodiment of an implantable device having a volume and a weight of 51 grams is shown.

[0057] The embodiment shown in Figure 15(a) includes a network that incorporates a scheme for efficient and robust multiple access bidirectional communication. The 8.8mm shown in Figure 15(b) 3 The implant includes (1) closed-loop magnetoelectric wireless power transmission that adapts to the implant's workload, changes in the implant's distance from the external TRX, and misalignment; (2) simultaneous power and time-domain downlink telemetry with a peak power transmission efficiency (PTE) of 5% and a maximum data rate of 62.3kbps; (3) multiple access uplink telemetry enabled by individually programmed intermediate frequencies (IFs); (4) robust operation under 2V power supply fluctuations; and (5) a TRX-implant working distance of more than 6cm to accept power inputs exceeding 1.3V and support downlink data rates of 62.3kbps and uplink data rates of 40kbps.

[0058] Figure 16 shows a block diagram of one embodiment of a system 100 comprising a wearable external transceiver 110 and an implantable device 120. In the illustrated embodiment, the wearable external transceiver 110 comprises a magnetic field generator 111, a controller 112, and a backscatter receiver 113. In this embodiment, the implantable device 120 comprises an electrical circuit 130 connected to a magnetoelectric thin film 150, further comprising a magnetostrictive layer 151 connected to a piezoelectric layer 152. In one embodiment, the magnetoelectric thin film 150 may comprise additional layers or a different configuration. For example, the magnetoelectric thin film 150 may comprise a piezoelectric layer positioned between two magnetostrictive layers. In another embodiment, the magnetoelectric thin film 150 may comprise a composite of piezoelectric and magnetostrictive elements mixed throughout the thin film.

[0059] In the specific embodiment shown, the electrical circuit 130 is 1 mm 2 SoC and 4×2mm 2ME transducer and a 2.5 mm with conjugate impedance matching 2 backscatter coil and a 0.25 mm that stores a maximum energy of 135 μJ 3 and a 22 μF capacitor. During operation of the system 100, the implantable device 120 can recover multiple power 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 magnetic-electric wireless power transfer (WPT) to an alternating current (AC) voltage. Such capabilities provide a higher PTE than inductive coupling and ultrasonic techniques [4],

[10] , with tolerance to misalignment, low tissue absorption, and safe mW-level power supply.

[0060] Downlink data by time-domain modulation For implants with little energy storage, simultaneous power transfer 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 limited by the high quality factor of the antenna / transducer, leading to a low data rate (panel (a) of 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) of FIG. 17). Exemplary embodiments of the present disclosure provide a notch-spacing time region 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 in PTE. Considering the trade-off between switching time compensation and duration coding overhead, each data symbol contains up to 6 bits. region modulation scheme. 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 in PTE. Considering the trade-off between switching time compensation and duration coding overhead, each data symbol contains up to 6 bits. It is designed that a complete packet includes a header, an ID for individual addressing, and a payload. Accurate clocking is essential for accurate demodulation.

[0061] Recovering the PVT invariant clock from the source is straightforward, but it fails if there is no carrier field, making it incompatible with a notch-based approach. To address this, the LO of each implant is set as the timing reference (CLK) for demodulation. LO ) as the clock (CLK) recovered from the source. REF The frequency is locked to the specified frequency. Frequency locking is performed autonomously before each downlink data transmission session using SAR logic, as shown in Figure 18.

[0062] Uplink backscattering by FDMA (Frequency Division Multiple Access) Exemplary embodiments of the present disclosure may comprise multiple implantable devices. Access to the feedback from each implantable device is important, and this requires multiple access uplinks. FDMA is preferred over TDMA (Time Division Multiple Access) [3] due to its higher 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, which limits their scalability and compatibility.

[0063] The use of an intermediate frequency (IF) has shown advantages in signal-to-noise ratio (SNR) in induced backscattering

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

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

[0064] Adaptive Global Power Transmission Control Using on-chip Physical Unclonable Function (PUF) implantable devices (IDs), the function of each implant can be individually programmed and controlled by an external transceiver, where the received power of each implant is known via multiple access uplinks. The transceiver adapts the output power of the power transmitter to adjust the input power of the implants based on real-time workload and channel efficiency. The proposed closed-loop control of wireless power transmission significantly mitigates power supply fluctuations caused by distance changes and misalignment, and avoids unnecessary power consumption of the external transceiver when the workload is light.

[0065] Measurement results In one exemplary embodiment, the implantable SoC is fabricated using TSMC 180nm 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 continuously receives power during downlink and uplink data transmission, as shown in panel (a) of Figure 23. Device programming downlink data The time is a self-calibrated timing reference CLK. LO It is decoded by LO, which locks precisely to a carrier frequency of 340.1 kHz in 0.4 ms, as shown in panel(b) of Figure 23. In this embodiment, the measured CLK LO The device exhibits 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 panel (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 waveform of the uplink telemetry and the detection 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 pig tissue when transmitting 40 kbps PRBS with a backscatter receiver coil power of 0 dBm (Figure 26(a)). Furthermore, the multiplexed access uplink is shown by the spectra of two implants simultaneously transmitting data at separate, individually programmed IFs of 83 kHz and 108 kHz (Figure 26(b)).

[0068] Figure 27 shows continuous closed-loop wireless power transmission 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 decrease of 1.38 mW in received power. Subsequently, the implant voltage recovers to the desired 2.8 V after 30 tuning cycles by adaptively controlling the power of the magnetoelectric transmitter.

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

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

[11] and comparable to that of

[13] , which operates over much smaller distances. The proposed invention enables FDMA in the uplink via individually programmed IFs (see Figure 29, including 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 the system, comprising a computer processor, a hub (e.g., an external transceiver), and a stimulator (e.g., a magnetoelectric implant) positioned proximally to the patient's skull and brain to deliver nerve stimulation (e.g., cortical stimulation) to the brain. Figure 31 shows a conceptual diagram of one embodiment of the system, comprising a computer processor, a hub (e.g., an external transceiver), and a stimulator (e.g., a magnetoelectric implant) positioned proximally to the patient's spine to deliver nerve stimulation to the spinal cord.

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

[0072] Figure 34 provides an image showing a leadless glass device for cortical stimulation. In one embodiment, a custom through-glass electrode (TGV) wafer is obtained and 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 the ASIC is bonded to a custom flex-rigid or rigid PCB. The ME thin film is wired The PCB is connected with 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 a cap of the same size is bonded to the top of the glass tube.

[0073] Figure 35 shows alternative glass package design and electrode spacing options in a particular embodiment. Figure 36 shows a simulation of coordinated stimulation between two glass moats, and Figure 37 provides an image of one embodiment showing an epoxy-sealed device with lead wires for spinal cord stimulation. In this embodiment, the ASIC is bonded to a custom PCB, and the ME thin film is connected to the PCB with wires and conductive silver epoxy. The stimulation lead wires are also connected to the PCB with silver epoxy, and the package is 3D printed to have a cavity for the ME thin film. The ME thin film is sealed inside a box, and the PCB is sealed on the outside of the box with medical-grade clear epoxy. Figure 38 shows data demonstrating 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 embodiment includes a computer user interface, a transmitter coil, a modulated AC magnetic field, an ME thin film (power and data receiver), an ASIC (data decoding and stimulation generation), and programmed stimulation.

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

[0076] In summary, exemplary embodiments of this disclosure include a wireless network for a mm-sized biomedical implant utilizing adaptive closed-loop control of ME power transmission and a novel scheme for multiple-access bidirectional communication. In certain embodiments, the global WPT control employed significantly improves robustness to distance and alignment perturbations and the overall efficiency of the system. In specific embodiments, a time-domain modulated downlink operates concurrently with power transmission, achieving a peak power transmission efficiency of 5% and a maximum data rate of 62.3 kbps. An FDMA uplink is implemented by individually programmed IFs with a maximum data rate of 40 kbps. Exemplary embodiments have been tested in vitro and have demonstrated working distances of over 6 cm between an external transceiver and the implant.

[0077] All methods disclosed and claimed herein can be prepared and performed without excessive experimentation in view of this disclosure. While preferred embodiments of the compositions and methods of the present invention have been described, it will be apparent to those skilled in the art that modifications can be made to the methods described herein, and to the steps or order of the steps, without departing from the concept, spirit, and scope of the present invention. More specifically, it will be apparent that several chemically and physiologically related agents may be used in place of the agents described herein, and that the same or similar results can be obtained. All such similar substitutions and modifications, apparent to those skilled in the art, are considered to be within the spirit, scope, and concept of the present invention as defined by the appended claims.

[0078] V. References The following references are incorporated herein by reference insofar as 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] MM Ghanbari et al., “A Sub-mm3 Ultrasonic Free-Floating Implant for Multi-Mote Neural Recording,” JSSC, Nov. 2019. [3] VW Leung et al., “Distributed Microscale Brain Implants with Wireless Power Transfer and Mbps Bi-directional Networked Communications,” in CICC, April 2019. [4] Z. Yu et al., “Multisite bio-stimulating implants magnetoelectrically powered and individually programmed by a single transmitter,” in CICC, April 2021. [5] DK Piech et al., “A wireless millimeter-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. U niversity of Southampton, 2009.

Claims

1. An implantable device having an electrical circuit connected to a magnetoelectric thin film, A magnetic field generator, Equipped with a resonant frequency modulator, The aforementioned magnetoelectric thin film has a resonant frequency, A wireless bioelectronics system in which 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.

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

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

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

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

7. The wireless bioelectronic system according to claim 6, wherein the plurality of implantable devices are configured to provide nerve stimulation.

8. The wireless bioelectronic system according to claim 7, wherein the implantable device is connected to a pair of electrodes.

9. The wireless bioelectronic system according to claim 7, wherein the implantable device is connected to a plurality of electrodes.

10. The wireless bioelectronics system according to claim 9, wherein the plurality of electrodes are arranged in a concentric circle.

11. The wireless bioelectronic 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. External transceiver and, Equipped with multiple implantable devices, Each implantable device is equipped with 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 multiple implantable devices. Each of the aforementioned multiple implantable devices is configured to transmit a response to the external transceiver. A wireless bioelectronics system in which each of the plurality of implantable devices is configured to transmit the response to the external transceiver after the first magnetic field has been transmitted from the transceiver.

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 comprises a magnetoelectric transmitter, a controller, and a receiver.

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

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

20. The wireless bioelectronic 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 aforementioned data includes a biomarker in the wireless bioelectronic system according to claim 20.

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. Nerve stimulation is adjusted based on data received from the multiple implantable devices. The wireless bioelectronic system according to claim 12.

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

27. The wireless bioelectronic system according to claim 12, wherein the plurality of implantable devices are implanted in or above the spinal cord.

28. Multiple external transceivers, Equipped with multiple implantable devices, Each of the multiple external transceivers is uniquely paired with the multiple implantable devices such that it selectively communicates with a single implantable device and does not communicate with other implantable devices. Each implantable device is equipped with an electrical circuit connected to a magnetoelectric thin film. Each external transceiver is configured to transmit a first magnetic field to one of the multiple implantable devices. Each of the implantable devices is configured to transmit a response to the external transceiver. A wireless bioelectronics system in which each of the plurality of implantable devices is configured to transmit the response to the external transceiver after the first magnetic field has been transmitted from the transceiver.

29. A method of stimulating nerve tissue, To provide the apparatus described in claim 28, A magnetic field is generated in one or more of the aforementioned transceivers, The magnetoelectric thin film generates an electrical output signal, A method comprising modifying the electrical output signal in the aforementioned electrical circuit.

30. A method of stimulating nerve tissue, To provide the apparatus according to any one of claims 1 to 11, The aforementioned magnetic field generator generates a magnetic field, The magnetoelectric thin film generates an electrical output signal, A method comprising modifying the electrical output signal in the aforementioned electrical circuit.

31. A method of stimulating nerve tissue, To provide the apparatus according to any one of claims 12 to 27, The transceiver generates a magnetic field, The magnetoelectric thin film generates an electrical output signal, A method comprising modifying the electrical output signal in the aforementioned electrical circuit.

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