Minimally invasive improved peripheral nerve stimulator for obstructive sleep apnea and other applications

Abstract

A neurostimulator system with an external magnetic coil for generating a varying magnetic field is applied to the neck in conjunction with one or more micro-injectable objects that focus induced electric and magnetic fields on the hypoglossal nerve, limiting power output and providing charge balance to protect the user. An additional non-invasive neurostimulator system applies an alternating current at one skin electrode and receives rectified current in the opposite direction at two other skin electrodes. In one embodiment, the system further includes a diode configured to perform the rectification.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 972,815, filed on February 11, 2020; U.S. Provisional Patent Application No. 62 / 972,823, filed on February 11, 2020; U.S. Provisional Patent Application No. 62 / 972,829, filed on February 11, 2020; and U.S. Provisional Patent Application No. 63 / 069,072, filed on August 23, 2020, each of which is incorporated herein by reference in its entirety.

Background Art

[0002] The human body and mammalian bodies use electrical signals to achieve sensory input, muscle movement, thinking, and memory. Over time, these signals are also involved in neuroplasticity, including general wiring, rewiring, and disconnection of wiring in the brain. Electrical signals are represented in the mind and body as electrical potentials (voltages) created by ions, not electrons. However, these ion - transport signals can be initiated, invalidated, or modified by electric fields originating from inside or outside the body. By Faraday's law of electromagnetism, these electric fields can be generated from changing magnetic fields and are thus named "magnetic stimulation". Since these signals are initiated from outside the body, magnetic stimulation can be a non - invasive means for modifying or improving almost all physical and mental functions.

[0003] The signals within the body are pulse-frequency modulated "action potentials," meaning that the number of pulse repetitions is related to the intensity of the perceived input, muscle energy, or neuronal message. The shape of individual pulses is largely the same throughout, with a pulse width of about 1 millisecond and some undershoot after the main pulse. The pulse height is about 70 millivolts for sensory signals and slightly greater for muscle activation. Pulses related to the heart, digestive system, and other organs may have different, unique characteristics. For the most part, when visualized on an oscilloscope, all signals appear similarly, i.e., as "pulse trains," and the pulse repetition frequency indicates the magnitude of the signal being transmitted. The absence of pulse trains can also elicit certain responses, explaining why amputees can still feel parts of their body that no longer exist.

[0004] The meaning of individual signals to the body's nervous system depends on where the pulse train appears. The brain consists of regions that process various neural functions and provide input for thought and sensory processing. The peripheral nervous system includes axons, which act as transmission channels and relays between sensory nerve endings and the spinal cord (ultimately, the brain). The neuromuscular system also consists of axons that transmit in the opposite direction, enabling the brain to trigger various muscle movements. Axons are grouped together into multi-channel peripheral nerves as they approach the spinal cord or brain. Some axons become myelinated, increasing the rate at which pulse trains propagate to and from the limbs of the body.

[0005] Nerve stimulation devices attempt to create, neutralize, or modify these naturally occurring pulse trains at a targeted location to achieve beneficial results. This may involve blocking or stimulating neuronal activity. Ultimately, an electric field is required at that location, which appropriately induces action potentials in ions, and these action potentials can then propagate unassisted through the nervous system to their destination. This electric field can be induced rather than directly generated. For example, conventional magnetic stimulation first creates a time-varying magnetic field from a coil of wire, which then generates an electric field according to Faraday's law. When this electric field is induced over a sensory or neuromuscular system, or part of the neural network of the brain, it can modify the system by depolarizing or hyperpolarizing naturally occurring pulse trains, or by inserting non-existent pulse trains. In the nervous system and brain, these pulse trains are activated continuously, with only the frequency changing to convey intensity information.

[0006] Conventional nerve stimulation devices fall into three categories: (1) magnetic stimulation: a changing magnetic field generated by a coil outside the body creates an electric field inside the body that modifies natural nerve or nerve cell signals; (2) skin electrode stimulation: electrodes are placed on the skin and allow an electric current to flow from one electrode to the other into the body; and (3) implantable wire stimulation: electrodes are implanted at a target site and connected by wires to a driver circuit that is possibly similarly implanted in another part of the body. Inspire Medical's hypoglossal nerve stimulator is an example of implantable wire stimulation. Transcranial magnetic stimulation (TMS) is an example of magnetic stimulation. Transcutaneous electrical nerve stimulation (TENS) is an example of skin electrode stimulation.

[0007] Magnetic stimulation is non-invasive, but unpredictable and ineffective because the stimulation is not targeted and its mechanism of action is not understood. In medical terms, magnetic stimulation has achieved regulatory approval for the treatment of major depression, neuropathic pain, and headaches. According to clinicaltrials.gov, 1,165 clinical studies have been conducted or are being conducted by 427 unique sponsors using “magnetic stimulation” to understand its effects on 450 different medical conditions. Magnetic stimulation may include a single external coil, multiple external coils for better targeting, such as US2012 / 0302821A1 (Patent Document 1), and also wearable coils, such as US9,072,891B1 (Patent Document 2) and US2010 / 0160712A1 (Patent Document 3).

[0008] Skin electrode stimulation is non-invasive, but because the current travels through multiple pathways at varying intensities, it is untargeted and uncontrollable. Transcutaneous electrical nerve stimulation (TENS) devices are approved for very few indications, and their effectiveness is generally low. Many TENS devices recommend applying the highest intensity of electricity the patient can tolerate to maximize effectiveness. The electricity flowing from the skin electrodes must pass through nerve endings in the skin before finally reaching the intended target, peripheral nerve, or muscle. The electric shock sensation or paresthesia from these nerve endings has non-therapeutic adverse effects of pain and discomfort from the electric shock sensation. Even after the patient has dialed up to the maximum tolerable electricity in the skin, the current density at the target nerve is often not sufficient to be therapeutically useful.

[0009] Implanted wire stimulation is highly targeted but also highly invasive and unstable due to electrode displacement from wire traction during body movement. Infection is also a disadvantage, especially when a driver circuit is not implanted. [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] U.S. Patent Application Publication No. 2012 / 0302821 [Patent Document 2] U.S. Patent No. 9,072,891 [Patent Document 3] U.S. Patent Application Publication No. 2010 / 0160712 [Overview of the project] [Means for solving the problem]

[0011] The embodiments described herein address certain limitations of conventional implantable wire stimulation for obstructive sleep apnea (OSA) by replacing the implantable wire with wearable and injectable devices that are wirelessly connected together. Additional embodiments described herein address certain limitations of conventional skin electrode stimulation by reducing or eliminating the sensation of electric shock. Thus, these embodiments are expected to represent a significant advancement of modern technology for the benefit of humankind.

[0012] In one or more embodiments, a wireless nerve modulation system is provided to allow wireless stimulation to eliminate surgery and reduce complexity to a single injection at each desired site of stimulation, and / or to make the injectable component very small so that it does not move around over time in an active human body. These objectives are achieved using these embodiments and are applied to the treatment of obstructive sleep apnea (OSA) via stimulation of the hypoglossal nerve. These embodiments improve respiratory sensing capabilities compared to the prior art while retaining the ability to measure heart rate and blood oxygen levels using a plethysmography sensor. These embodiments also include additional components in the injectable that safely limit the voltage applied to the tissue and ensure a net charge of zero or near zero to prevent electrode corrosion, while maintaining injectability in even smaller needles compared to the prior art. These embodiments also provide full functionality in a wearable for OSA therapy while maintaining a lightweight shape factor and sufficiently long battery life compared to the prior art. This full functionality enables a complete therapeutic protocol for physicians and assistants to implement the therapy. The ultimate outcome is a low-cost treatment for OSA and other conditions that offers the full functionality of conventional devices, which are much larger and more invasive than surgically implanted devices.

[0013] In one or more additional embodiments, novel TENS systems are provided to eliminate or reduce the sensation of electric shock at nerve endings near the skin, allowing stronger electrical currents to reach target nerves, thereby enhancing the effectiveness of multiple therapies involving TENS. These objectives are achieved using these additional embodiments. The reduction of electric shock sensation improves the patient's tolerance of TENS compared to the prior art. This reduction also increases the maximum tolerable stimulation intensity and is therefore expected to enhance the effectiveness of TENS compared to the prior art for many therapies.

[0014] Embodiments of neurostimulators for OSA described herein may use an external coil to generate a variable magnetic field outside the body, in conjunction with one or more micro-injectable objects that concentrate the magnetic field to a highly targeted location. These systems require a low-voltage power source, which may be a wearable battery, while adding a driver circuit for the magnetic coil that enables high voltage and fast pulses within the coil. The coil, driver circuit and battery may also be small enough to be easily implantable and may include a plethysmographic sensor to collect patient data regarding heart rate and oxygen saturation levels. An injectable elongated device is placed inside the body adjacent to the hypoglossal nerve, and the device has a circuit that rectifies the received AC signal, limits the output voltage to a safe level, and reverses the flow of current after stimulation to charge equilibrium the area. A second wearable device that senses respiration, including inhalation and exhalation periods, may be included to more effectively deliver stimulation at an optimal time or amplitude or at an optimal time and amplitude.

[0015] Miniaturization of magnetic field generators can be achieved by using (1) an efficient driver circuit that enables hundreds or thousands of volts in the coil from a low-voltage battery, (2) an injectable electric field concentrate that targets stimuli to areas as small as a few microns, if desired, and / or (3) a fast rise time in the coil current that induces a large electric field to produce an action potential.

[0016] Some of the systems disclosed herein use electronic circuits for driving one or more stimulator coils by stimulating pulses as multiple decay cycles of the resonance of the stimulator coils combined with capacitors. Once the decay of the resonance is complete, the circuit remains off for a desired time for the next pulse.

[0017] By using this approach, the induced energy of the stimulation coil is recirculated through the capacitor and therefore not wasted in each cycle. In addition, the voltage across the capacitor can reach hundreds or thousands of volts, even when the supply voltage is very low. This high voltage inside the capacitor is then used to rapidly change the current in the stimulation coil for the next pulse. The recirculation of induced energy also allows the stimulation coil to have more turns and therefore requires less current flow to create the same magnetic field strength. A preferred embodiment can create the required magnetic field pulses to treat OSA using a power source with a range of 3 to 45 volts DC and an average current flow of 0.001 to 0.1 amperes from the source.

[0018] In some embodiments of the system, in addition to allowing smaller injectable materials, healthcare providers or users / wearers still have the flexibility to set signal parameters as needed for effective stimulation of the hypoglossal nerve. The wearable provides an interface that allows healthcare providers to titrate stimulation intensity and burst frequency and then fix these levels for subsequent use by the user / wearer.

[0019] In one embodiment, the injectable also includes a rectifier diode, a charge-balancing capacitor, a voltage-limiting Zener diode, and a timing resistor. The tissue-exposed surface of the elongated injectable may comprise a material selected from the group consisting of metal and insulating encapsulation for electrodes. The metal surface may be copper, tungsten, chromium, steel, stainless steel, nickel, nichrome, titanium, gold, silver, brass, platinum, iridium, platinum-iridium, or any alloy thereof. The insulating surface may comprise PTFE, nylon, silicone, polyethylene, polyurethane, latex, polyimide, BoPET, or any combination thereof. The elongated injectable may be configured for placement adjacent to the hypoglossal nerve. The elongated injectable may have a cylindrical shape with a certain diameter and a certain length, the diameter may be less than the length. The elongated device may be injected into the body through a guide tube such as a syringe needle or other introduction needle. The magnetic field generator may comprise a coil, which comprises one or more coil windings of wire, possibly stranded wire, where the strands are insulated from each other. A magnetic field generator may be connected in parallel with a capacitor, and the stimulation signal may be generated, derived from, or defined by a portion of the resonant time between the coil and the capacitor. The parallel capacitor and coil may be configured to be activated on one side by a DC power source or battery and on the other side by a switch to ground, the period between switch closed and switch open accumulating current in the coil, and the time after switch open providing a damped resonance that induces bursts of stimulation pulses. The switch may be a combination of a transistor and a rectifier, and the switching action may be configured to occur by turning the transistor on or off by applying a voltage to the gate or base of the transistor. The magnetic field generator may include a stimulation coil, which may be made of a highly permeable material configured to include a fringe field. The highly permeable material may be hard or flexible ferrite, steel, or iron. The coil may further include a conductive ferromagnetic material that reduces the amplitude of the subsequent resonant pulse relative to the preceding pulse.The materials may include iron, cobalt, nickel, steel, or alloys or other combinations thereof. One or more coil windings may be in a plane or multiple adjacent planes. One or more coil windings may comprise magnet wire or bundled strands of magnet wire, each strand being insulated or uninsulated. One or more coil windings may comprise metal deposited on a layered substrate. The substrate may be rigid and optionally consist of FR-4 glass-reinforced epoxy laminate, glass, or rigid plastic. In other embodiments, the substrate may be flexible. Flexible substrates may comprise polyimide, BoPET, polyethylene, polyurethane, nylon, or PTFE. The system may further comprise one or more of the following: a microprocessor, a rechargeable battery, a disposable battery, a user interface, a physician interface, a nurse interface, a data storage device, and network or wired connectivity.

[0020] A network or wired interface may be configured to receive information from another sensor that provides signals indicating physical body movement related to breathing. This sensor may comprise a piezoelectric disk facing a central pivot and an interface circuit to a microprocessor's analog-to-digital converter.

[0021] Wearable devices may include plethysmographic sensors to collect patient health information such as oxygen saturation levels and / or heart rate.

[0022] In another embodiment, a method for treating OSA is provided, comprising identifying an OSA patient, injecting one or more elongated devices into the patient adjacent to the hypoglossal nerve, placing a wearable magnetic field generator on the skin surface near the injection site, and applying a magnetic field to generate therapeutic nerve stimulation.

[0023] In yet another embodiment, a syringe or injector body or introducer, a slide plunger or push rod located within the syringe or injector body, a needle attached to the syringe or injector body having a tip that can apply electrical stimulation, perhaps like a nerve block needle, and at least one discrete elongate injectable located within the syringe or injector body, wherein the syringe or injector body and the needle constrain the orientation of the at least one elongate injectable, and the elongate injectable comprises a resistor, a capacitor, a Zener diode, and a rectifier diode, a treatment device is provided for introducing the injectable into the body.

[0024] In another embodiment, a neuromodulation system is provided that comprises at least one elongate device having a length less than 15 millimeters and a transverse dimension less than 2 millimeters for implantation adjacent to or against the hypoglossal nerve, and a magnetic field generator spaced from the elongate device and configured to generate an induced voltage between pairs of electrodes of the elongate device. The at least one elongate device may be pre-loaded within an injection device and within a hermetically sealed sterile package. The magnetic field generator may further comprise a rechargeable battery or a disposable non-rechargeable battery. The magnetic field generator may be located within a housing that comprises a biocompatible adhesive. The housing may have a height relative to the skin surface at a location on the body that may be less than 3 centimeters.

[0025] In another embodiment, inserting at least one elongated injectable into or adjacent to the hypoglossal nerve, the injectable having a length of less than 15 millimeters and a transverse dimension with respect to a length of less than 2 millimeters, positioning a magnetic field generator at a location spaced apart from the at least one elongated injectable, and using the magnetic field generator to provide an induced voltage between pairs of electrodes on the at least one elongated injectable. A method of treating a patient is provided. This treatment method may also include the use of an ultrasonic imaging system to assist a healthcare provider in placing an injectable into the hypoglossal nerve. This treatment method may also include a device for applying electrical stimulation to the tip of an introducer needle to verify proximity to the hypoglossal nerve prior to placement.

[0026] In another embodiment, the magnetic field generator includes or is connected to sensors including an oxygen saturation level sensor, a plethysmograph sensor, or is connected to a respiratory motion sensor mounted on the chest or abdomen. The oxygen saturation sensor or plethysmograph sensor may include a pair of a light emitting diode and a photosensor that senses tissue erythema or tissue expansion and contraction in response to respiration and heartbeat or both. These sensors may use analog or digital signal processing, or both, including perhaps Fourier transform or other linear transform, filtering, peak detector, amplitude detector, polarity detector, or envelope detector, to process their outputs to monitor body and health parameters such as respiratory rate, respiratory duty cycle, inspiration and expiration discrimination, snoring, partial respiratory obstruction or hypopnea, complete respiratory obstruction or apnea, heart rate, blood pressure, respiratory effects, and blood oxygen level. The information processed from these sensors may be used to determine stimulation on and off times, stimulation amplitude, the user's specific or general health, the effectiveness of the stimulation, or may be collected as general information useful for later processing. This information may be communicated from the magnetic field generator to a secure database directly or through an intermediate base station.

[0027] In additional sets of embodiments, stimulation of a muscle or peripheral nerve is performed without requiring an injectable substance inside the body, reducing or eliminating the sensation of an electric shock in conventional TENS systems. In these embodiments, at least one stimulating electrode is placed on the skin directly above the target muscle or peripheral nerve, and at least two return electrodes rectified in the opposite direction are placed on the skin at a distance from the central electrode. In these embodiments, the central electrode is subjected to an alternating current of a frequency that alternates too quickly to be perceived by the nerve endings beneath it. The two return electrodes receive polarities rectified in the opposite direction of the alternating current, each polarity indicated by a diode. In addition, the surface area of ​​each return electrode is sufficiently large so that the current density flowing through the nerve endings at their locations is not sufficient to cause pain or discomfort.

[0028] In one embodiment, the TENS system is provided using an AC generator, two diodes, one central skin electrode, and two return skin electrodes. This embodiment provides TENS therapy to the muscle or peripheral nerve beneath the central electrode while reducing or eliminating the sensation of an electric shock by rapidly directing AC to the central electrode and directing low-density current to the return electrodes.

[0029] In another embodiment, a method for treating pain is described by applying central electrodes to nerves within the spinal cord to treat central pain.

[0030] In another embodiment, a therapeutic method for stimulating the median nerve is described for treating peripheral pain or carpal tunnel syndrome.

[0031] In another embodiment, a treatment method for migraines is described by applying central electrode stimulation to the supraorbital nerve in the forehead.

[0032] In another embodiment, a treatment method for OSA is described by applying a central electrode to the hypoglossal nerve beneath the tongue.

[0033] In one embodiment, a neuromodulation system for obstructive sleep apnea is provided, comprising an elongated device configured for injection near the hypoglossal nerve, wherein at least one elongated device comprises a stimulating electrode, a return electrode, an elongated receiver coil, a first diode, a second Zener diode, a resistor, and a capacitor, and at least one elongated device comprising an elongated device without a battery and a wearable device comprising a magnetic field generating coil connected to the capacitor and configured together to resonate freely during repeated stimulation of the hypoglossal nerve, wherein the elongated device is configured such that the voltage applied to the stimulating electrode is rectified by one or both diodes, limited by the Zener diode, and configured to average to zero or near zero before the onset of the next free resonance. The wearable device may include at least one button battery, which may or may not be rechargeable. The wearable device may be configured to allow adjustment of the amplitude of stimulation by setting an initial current flowing in the magnetic field generating coil prior to free resonance. Setting the initial current of the wearable device may be based on the length of time the magnetic field generating coil is connected between a power source and ground. The first diode, the second Zener diode, resistors, capacitors, and any interconnections thereto may be coated with a moisture barrier with a thickness of 5 to 50 microns, such as parylene or parylene C. The first diode, the second Zener diode, resistors, capacitors, and any interconnections thereto may be housed inside a tube, which may be made of, for example, polyimide or PEEK, and any empty or vacant spaces within the tube may be filled with epoxy, including biocompatible epoxy. The stimulating and return electrodes may be made of biocompatible metals, such as platinum, iridium, or an alloy of platinum and iridium. The elongated device may further include a tether attached to the elongated device at a distance from the stimulating electrode and configured for detachability. The tether may include a suture, which may be made of polyester, polypropylene, ultra-high molecular weight polyethylene, or a combination thereof. The suture may be made of an absorbable synthetic material.The wearable device may be configured to optionally adjust the amplitude in preset increments, which may comprise a series of fixed percentage increases from the initial muscle single contraction threshold level. The elongated device may comprise, for example, a half-wave rectifier, a full-wave rectifier, or a full-wave rectifier with a center tap. The wearable device may be configured to provide an adjustable repetition rate of free resonance. The neuromodulation system may further comprise an introduction needle, and the elongated device is located inside the introduction needle. The elongated device may be one of at least two elongated devices inside the introduction needle. The introduction needle may be electrically insulated except for its tip, which may be configured to be electrically connected to a stimulating device configured to assist in the placement of an elongated device adjacent to a nerve.

[0034] In another embodiment, a sensor for sensing respiratory movement is provided, comprising a housing or pouch, a piezoelectric disc, a support disc, and a pivot between them contained within the pouch, wherein the support disc is located on a first side of the pouch configured for contact with the user's body, and the piezoelectric disc is located on a second side of the pouch opposite the support disc, configured to be attached toward the body. The sensor may further comprise, for example, an instrumented breathing belt strap, an adhesive tape strap, or an adhesive bandage strap. The piezoelectric disc may be configured to be attached to a clothing waistband. The sensor may be electrically connected to a neuromodulation system by a connector, the neuromodulation system being an elongated device configured for injection near the hypoglossal nerve, where at least one elongated device comprises a stimulating electrode, a return electrode, an elongated receiver coil, a first diode, a second Zener diode, a resistor, and a capacitor, and at least one elongated device comprising a battery-free elongated device and a wearable device comprising a magnetic field generating coil connected to the capacitor and configured together to resonate freely during repeated stimulation of the hypoglossal nerve, the elongated device being configured such that the voltage applied to the stimulating electrode is rectified by one or both diodes, limited by the Zener diode, and on average zero or near zero before the onset of the next free resonance. The connector may be a wire and / or wireless link. The sensor may be configured to transmit the sensor output of the sensor as an analog signal and / or a digital signal. The sensor output of the sensor is connected to a series resistor, which is then connected to an analog-to-digital converter. The resistance of the series resistor may be selected to have an R×C time constant of 0.3 or 0.1 to 0.6 seconds, where C is the capacitance of the piezoelectric disk and R is the sum of the series resistance of the analog-to-digital converter circuit and the load resistance.

[0035] In another variation, a neuromodulation system is provided comprising at least one surface stimulating electrode configured to apply alternating current, and two surface return electrodes configured to receive a component of the alternating current rectified in the opposite direction. The system may further comprise diodes configured to perform rectification. The frequency of the alternating current may be selected to minimize or prevent the sensation of an electric shock at that location on the body, and may be, for example, 1, 10, 100, or 1,000 kilohertz, or any frequency in between. The electrical contact area of ​​the return electrodes may be sized to reduce high current density and electric shock sensation at those locations on the body. The absolute values ​​of the amplitudes of the current components rectified in the opposite direction at each return electrode may be configured to be balanced by a balancer. The balancer may be configured to insert a series resistor, adjust the contact area of ​​the return electrodes, insert a bias voltage in the alternating current of the stimulating electrodes, or any combination thereof. The neuromodulation system may further comprise a microprocessor configured to sense imbalance and control the balancer. The alternating current may be a periodic waveform modulated by a slowly decreasing, slowly increasing, or constant amplitude multiplier. The periodic wave may be, for example, a sine wave, a square wave, or a triangular wave. The stimulating electrode may be configured for placement over a peripheral nerve and not penetrate the skin. The neuromodulation system may be configured to modulate the supraorbital nerve and treat pain from migraines. The peripheral nerve may be the peripheral portion of the hypoglossal nerve, and the neuromodulation system may be configured to treat obstructive sleep apnea; the peripheral nerve may be the median nerve, and the neuromodulation system may be configured to treat carpal tunnel syndrome; the peripheral nerve may be the ulnar nerve, and the neuromodulation system may be configured to treat pain from cubital tunnel syndrome. The neuromodulation system may be configured to treat peripheral pain corresponding to a peripheral nerve. The stimulating electrode may be configured for placement inside the oral cavity, for example, to treat obstructive sleep apnea extending to the spinal cord. An elongated device may be one of at least two elongated devices of the neuromodulation system. A wearable device may be one of at least two wearable devices of the neuromodulation system.

[0036] In yet another example, a method is provided for performing neuromodulation, comprising placing a neuromodulatory device near a nerve, the neuromodulatory device comprising a stimulating electrode and two return electrodes, and applying alternating current using the stimulating electrodes and receiving a component of the alternating current rectified in the opposite direction. The method may further include rectifying the alternating current using a diode located within the neuromodulatory device. The method may further include selecting a frequency of the alternating current within the range of 1 Hz to 1,000 Hz to reduce paresthesia or shock sensation. The method may further include balancing the absolute values ​​of the amplitudes of the current components rectified in the opposite direction at each return electrode. Balancing may be performed by inserting a series resistor, adjusting the contact area of ​​the return electrodes, and / or inserting a bias voltage in the alternating current of the stimulating electrode. The neuromodulatory device further comprises a microprocessor configured to control the balancing. The alternating current may be a periodic waveform modulated by a slowly decreasing, slowly increasing, or constant amplitude multiplier. The periodic wave may be a sine wave, a square wave, or a triangular wave. The nerve may be a peripheral nerve, and the placement of the nerve modulation device may involve non-invasively placing the nerve modulation device on the peripheral nerve relative to the skin. The peripheral nerve may be the supraorbital nerve, and the nerve modulation device may be configured to treat migraines. The peripheral nerve may be the peripheral portion of the hypoglossal nerve, and the nerve modulation device may be configured or used to treat migraines. The peripheral nerve may be the median nerve, and the nerve modulation device may be configured to treat carpal tunnel syndrome, or the peripheral nerve may be the ulnar nerve, and the nerve modulation device may be configured or used to treat cubital tunnel syndrome. The nerve modulation device may also be configured or used to treat peripheral pain. The placement of the nerve modulation device may involve positioning the stimulating electrodes of the nerve modulation device on the spinal cord, or inside the patient's oral cavity to treat obstructive sleep apnea. The present invention provides, for example, the following: (Item 1) A neuromodulation system for obstructive sleep apnea, wherein the neuromodulation system is a. An elongated device configured for injection near the hypoglossal nerve, wherein at least one elongated device comprises a stimulating electrode, a return electrode, an elongated receiver coil, a first diode, a second Zener diode, a resistor, and a capacitor, and the at least one elongated device does not include a battery. b. Wearable devices equipped with magnetic field generating coils Equipped with, The magnetic field generating coil is connected to a capacitor and configured together to resonate freely during repeated stimulation of the hypoglossal nerve. The elongated device is configured such that the voltage applied to the stimulating electrode is rectified by one or both diodes and limited by the Zener diode, and is configured to average to zero or nearly zero before the onset of the next free resonance, in a neuromodulation system. (Item 2) The wearable device is a neuromodulation system as described in item 1, comprising at least one button battery. (Item 3) The aforementioned button battery is rechargeable, and is part of the neuromodulation system described in item 2. (Item 4) The aforementioned button battery is not rechargeable, as described in item 2 for the neuromodulation system. (Item 5) The neuromodulation system according to item 1, wherein the wearable device is configured to allow adjustment of the amplitude of stimulation by setting an initial current flowing in the magnetic field generating coil prior to the free resonance. (Item 6) The setting of the initial current of the wearable device is based on the length of time the magnetic field generating coil is connected between the power source and ground, according to item 5 of the neuromodulation system. (Item 7) The neuromodulation system according to item 1, wherein the first diode, the second Zener diode, the resistor, the capacitor, and any interconnections thereto are coated with a moisture-proof layer having a thickness of 5 to 50 microns. (Item 8) The aforementioned water barrier comprises parylene, the neuromodulation system according to item 7. (Item 9) The aforementioned water barrier is parylene C, as described in item 7, in the neuromodulation system. (Item 10) The neuromodulation system described in item 1, wherein the first diode, the second Zener diode, the resistor, the capacitor, and any interconnections thereto are housed inside a tube. (Item 11) The neuromodulation system according to item 10, wherein the tube comprises polyimide. (Item 12) The tube is a neuromodulation system according to item 10, comprising PEEK. (Item 13) The neuromodulation system described in item 10, wherein any empty spaces within the tube are filled with epoxy. (Item 14) The epoxy is biocompatible, as described in item 13, for the neuromodulation system. (Item 15) The neuromodulation system described in item 1, wherein the stimulating and return electrodes are made from a biocompatible metal. (Item 16) The neuromodulation system according to item 15, wherein the electrode comprises platinum, iridium, or an alloy of platinum and iridium. (Item 17) The neuromodulation system according to item 1, wherein the elongated device further comprises a tether attached to the elongated device at a location spaced apart from the stimulating electrode, the tether being configured for detachability. (Item 18) The tether comprises a suture, as described in item 17, for the neuromodulation system. (Item 19) The neuromodulation system according to item 18, wherein the suture comprises polyester, polypropylene, ultra-high molecular weight polyethylene, or a combination thereof. (Item 20) The nerve modulation system according to item 18, comprising the suture. (Item 21) The wearable device is configured to adjust the amplitude in a preset increment, according to the neuromodulation system described in item 5 or 6. (Item 22) The neuromodulation system according to item 21, wherein the aforementioned pre-set increments comprise a series of fixed percentage increases from the initial muscle single contraction threshold level. (Item 23) The aforementioned elongated device comprises a half-wave rectifier, as described in item 1, for the neuromodulation system. (Item 24) The aforementioned elongated device comprises a full-wave rectifier, as described in item 1, in the neuromodulation system. (Item 25) The aforementioned elongated device comprises a full-wave rectifier with a center tap, as described in item 1, in the neuromodulation system. (Item 26) The wearable device is configured to provide an adjustable repetition rate of free resonance, as described in item 1, for the neuromodulation system. (Item 27) The neuromodulation system according to item 1, further comprising an introduction needle, wherein the elongated device is located inside the introduction needle. (Item 28) The neuromodulation system according to item 1, wherein the elongated device is one of at least two elongated devices inside the introduction needle. (Item 29) The neuromodulation system according to item 27, wherein the introduction needle is electrically insulated except for the tip of the introduction needle. (Item 30) The neuromodulation system according to item 29, wherein the tip of the introduction needle is configured to be electrically connected to a stimulating device, and the stimulating device is configured to assist in the placement of the elongated device adjacent to a nerve. (Item 31) A sensor for sensing respiratory movements, wherein the sensor is Pouch and, Piezoelectric disc and Support disc and, The pivot between them contained within the aforementioned pouch Equipped with, A sensor wherein the support disc is located on a first side of the pouch configured for contact with the user's body, and the piezoelectric disc is located on a second side of the pouch opposite the support disc and configured to be attached toward the body. (Item 32) The sensor described in item 30 is further equipped with an instrumented breathing belt strap. (Item 33) The piezoelectric disc is configured to be attached to the waistband of clothing, as described in item 30. (Item 34) The sensor described in item 30 is further equipped with an adhesive tape strap. (Item 35) The sensor described in item 30 is further equipped with an adhesive bandage strap. (Item 36) The sensor is electrically connected to a neuromodulation system by a connector, and the neuromodulation system is a. An elongated device configured for injection near the hypoglossal nerve, wherein at least one elongated device comprises a stimulating electrode, a return electrode, an elongated receiver coil, a first diode, a second Zener diode, a resistor, and a capacitor, and the at least one elongated device does not include a battery. b. Wearable devices equipped with magnetic field generating coils Equipped with, The magnetic field generating coil is connected to a capacitor and configured together to resonate freely during repeated stimulation of the hypoglossal nerve. The elongated device is configured such that the voltage applied to the stimulating electrode is rectified by one or both diodes and limited by the Zener diode, and is configured to average to zero or nearly zero before the onset of the next free resonance, as described in any one of items 31-35. (Item 37) The aforementioned connector is a wire, as described in item 36. (Item 38) The aforementioned connector is a wireless link, as described in item 36. (Item 39) The sensor according to any one of items 36-38, wherein the sensor is configured to transmit the sensor output of the sensor as an analog signal. (Item 40) The sensor according to any one of items 36-38, wherein the sensor is configured to transmit the sensor output of the sensor as a digital signal. (Item 41) The sensor output of the aforementioned sensor is connected to a series resistor, and the series resistor is then connected to an analog-to-digital converter, as described in any one of items 31-38. (Item 42) The resistance of the series resistor is selected to have an R×C time constant of 0.3 or 0.1 to 0.6 seconds, where C is the capacitance of the piezoelectric disk and R is the sum of the series resistance of the analog-to-digital converter circuit and the load resistance, as described in item 41. (Item 43) A neuromodulation system, wherein the neuromodulation system is A surface stimulation electrode configured to apply alternating current, Two surface return electrodes configured to receive the component rectified in the opposite direction of the AC, A neuromodulation system equipped with these features. (Item 44) The neuromodulation system according to item 43, further comprising a diode configured to perform the aforementioned rectification. (Item 45) The neuromodulation system according to item 43, wherein the frequency of the alternating current is selected to minimize or prevent the sensation of an electric shock at that location on the body. (Item 46) The neuromodulation system described in item 45, wherein the frequency is 1, 10, 100, or 1,000 kilohertz, or any frequency in between. (Item 47) The neuromodulation system according to any one of items 43-46, wherein the electrical contact area of ​​the return electrode is sized to reduce high current density and electric shock sensation at those locations on the body. (Item 48) The neuromodulation system according to any one of items 43-47, wherein the absolute value of the amplitude of the current component rectified in the opposite direction at each return electrode is configured to be balanced by a balancer. (Item 49) The neuromodulation system according to item 48, wherein the equilibrium is configured to insert a series resistor, adjust the contact area of ​​the return electrode, insert a bias voltage in the AC of the stimulating electrode, or any combination thereof. (Item 50) The neuromodulation system according to item 49, further comprising a microprocessor configured to sense non-equilibrium and control the equilibrium. (Item 51) The neuromodulation system described in any one of items 43–50, wherein the alternating current is a periodic waveform modulated by a slowly decreasing, slowly increasing, or constant amplitude multiplier. (Item 52) The neuromodulation system described in item 51, wherein the periodic wave is a sine wave. (Item 53) The periodic wave is a square wave, as described in item 51, in the neuromodulation system. (Item 54) The aforementioned periodic wave is a triangular wave, as described in item 51 of the neuromodulation system. (Item 55) The stimulating electrode is configured for placement on a peripheral nerve and does not penetrate the skin, as described in any one of items 43-54 of the neuromodulation system. (Item 56) The neuromodulation system described in item 55 is configured to modulate the supraorbital nerve and treat pain from migraines. (Item 57) The neuromodulation system according to item 55, wherein the peripheral nerve is the peripheral portion of the hypoglossal nerve, and the neuromodulation system is configured to treat obstructive sleep apnea. (Item 58) The neuromodulation system described in item 55, wherein the peripheral nerve is the median nerve, and the neuromodulation system is configured to treat carpal tunnel syndrome. (Item 59) The nerve modulation system described in item 55, wherein the peripheral nerve is the ulnar nerve, and the nerve modulation system is configured to treat pain from cubital tunnel syndrome. (Item 60) The neuromodulation system according to item 55, configured to treat peripheral pain corresponding to the peripheral nerve. (Item 61) The stimulating electrode is configured for placement on the spinal cord in the neuromodulation system according to any one of items 43-54. (Item 62) The stimulating electrode described in items 55 and 57 is configured for placement inside the oral cavity for the treatment of obstructive sleep apnea. (Item 63) The neuromodulation system according to item 1, wherein the elongated device is one of at least two elongated devices of the neuromodulation system. (Item 64) The wearable device is one of at least two wearable devices of the neuromodulation system according to item 63. (Item 65) A method for performing neuromodulation, wherein the method is The method involves placing a nerve modulation device near a nerve, wherein the nerve modulation device comprises a stimulating electrode and two return electrodes. Applying alternating current using the aforementioned stimulating electrode, To receive the component rectified in the opposite direction of the aforementioned alternating current. Methods that include... (Item 66) The method of item 65, further comprising rectifying the alternating current using a diode located within the neuromodulator. (Item 67) The method according to item 65, further comprising selecting the frequency of the alternating current within the range of 1 Hz to 1,000 Hz in order to reduce paresthesia or shock sensation. (Item 68) The method according to item 43, further comprising balancing the absolute values ​​of the amplitudes of the current components rectified in the opposite direction at each return electrode. (Item 69) The aforementioned balancing is, Insert a series resistor. Adjusting the contact area of ​​the return electrode, and / or, A bias voltage is inserted into the AC current of the aforementioned stimulating electrode. The method described in item 68, as implemented by [company name]. (Item 70) The method according to item 68, wherein the neuromodulator further comprises a microprocessor configured to control the equilibration. (Item 71) The method according to item 65, wherein the alternating current is a periodic waveform modulated by a slowly decreasing, slowly increasing, or constant amplitude multiplier. (Item 72) The method according to item 71, wherein the periodic wave is a sine wave, a square wave, or a triangular wave. (Item 73) The method of item 65, wherein the nerve is a peripheral nerve, and the placement of the nerve modulation device includes non-invasively placing the nerve modulation device on the peripheral nerve relative to the skin. (Item 74) The method according to item 73, wherein the peripheral nerve is the supraorbital nerve, and the nerve modulation device is configured to treat migraines. (Item 75) The method according to item 73, wherein the peripheral nerve is the peripheral portion of the hypoglossal nerve, and the nerve modulation device is configured to treat migraines. (Item 76) The method according to item 73, wherein the peripheral nerve is the median nerve, and the nerve modulation device is configured to treat carpal tunnel syndrome. (Item 77) The method according to item 73, wherein the peripheral nerve is the ulnar nerve, and the nerve modulation device is configured to treat cubital tunnel syndrome. (Item 78) The method according to item 73, wherein the nerve modulation device is configured to treat peripheral pain. (Item 79) The method according to any one of items 65-72, wherein the placement of the neuromodulatory device includes positioning the stimulating electrodes of the neuromodulatory device over the spinal cord location. (Item 80) The method according to any one of items 65-72, wherein the placement of the nerve modulation device includes positioning the stimulating electrode of the nerve modulation device inside the oral cavity of a patient in order to treat obstructive sleep apnea. [Brief explanation of the drawing]

[0037] [Figure 1A] Figure 1A is a graphical representation of patients being treated for OSA while lying down, using a wearable device mounted under the chin and respiratory movement sensors mounted within the chest area.

[0038] [Figure 1B] Figure 1B is a corresponding graphical representation of the patient's head and neck, showing the location of the hypoglossal nerve and the injectable elongated device placed adjacent to it. The tether connecting to the injectable device is partially outside the body.

[0039] [Figure 2A] Figure 2A is an electrical circuit diagram of the power supply, and Figure 2B is a perspective view of an exemplary plethysmographic sensor that can be used with a wearable magnetic field generator. [Figure 2B] Figure 2A is an electrical circuit diagram of the power supply, and Figure 2B is a perspective view of an exemplary plethysmographic sensor that can be used with a wearable magnetic field generator. [Figure 2C] Figure 2C is a schematic diagram of the wearable circuit.

[0040] [Figure 3A] Figure 3A is an isometric graph representation of a wearable magnetic field generator.

[0041] [Figure 3B] Figure 3B is a top view graph representation of the wearable magnetic field generator shown in Figure 3A.

[0042] [Figure 3C] Figure 3C is a cross-sectional side view of the graphical representation of the wearable magnetic field generator shown in Figure 3A.

[0043] [Figure 4] Figure 4 is an XY graph representation of respiratory airflow on the Y axis in OSA patients, in response to hypoglossal nerve stimulation intensity on the X axis.

[0044] [Figure 5A] Figure 5A is a schematic representation of an elongated injectable object employing a full-wave rectifier.

[0045] [Figure 5B]Figure 5B is a schematic representation of an elongated injectable object employing a full-wave rectifier with a center tap.

[0046] [Figure 5C] Figure 5C is a schematic representation of an elongated injectable object employing a half-wave rectifier.

[0047] [Figure 6A] Figure 6A shows a time-series graphical representation of the coil voltage of a wearable magnetic field generator with respect to a fully stimulated burst of free resonance and the start of the next burst.

[0048] [Figure 6B] Figure 6B shows a time-series graph representation of the corresponding voltages between the stimulating electrode and the return electrode in an elongated injectable material.

[0049] [Figure 7A] Figure 7A is a graphical representation of the layout of passive electronic components in an elongated injectable object containing electrodes.

[0050] [Figure 7B] Figure 7B is a graphical representation of the layout of passive electronic components on a circuit board in an elongated injectable device.

[0051] [Figure 7C] Figure 7C is a graphical representation of the layout of passive electronic components, including internal wiring on a circuit board, in an elongated injectable object.

[0052] [Figure 7D] Figure 7D is a photographic representation of an elongated injectable object that can be packaged and sealed within a housing and includes a tether for removal after injection.

[0053] [Figure 8A] Figure 8A shows an embodiment of an injectable and wearable electronic device with one type of magnetic field generating coil.

[0054] [Figure 8B] Figure 8B shows the corresponding oscilloscope trace of the voltage across the electrodes of the injectable material on a given time scale.

[0055] [Figure 8C] Figure 8C shows the corresponding oscilloscope traces of the voltage across the electrodes of the injectable material at different time scales.

[0056] [Figure 9A] Figure 9A shows embodiments of injectables and wearable electronic devices with a different type of magnetic field generating coil.

[0057] [Figure 9B] Figure 9B shows the corresponding oscilloscope trace of the voltage across the electrode of the injectable material.

[0058] [Figure 10A] Figure 10A shows an introduction needle with a connector to the needle tip stimulator and a slide plunger rod containing an elongated injectable with a tether.

[0059] [Figure 10B] Figure 10B shows one embodiment of the corresponding needle tip stimulator.

[0060] [Figure 11A] Figure 11A shows part of the apparatus used to demonstrate the concepts of a radio stimulator and an elongated injectable in animal.

[0061] [Figure 11B] Figure 11B shows another part of the apparatus for demonstrating the concepts of a radiostimulator and an elongated injectable in animal form.

[0062] [Figure 11C]Figure 11C shows the corresponding XY graph representation of animal muscle force measurements versus the distance from the nerve to the wearable, in response to neural stimulation for two different magnetic field generating coils.

[0063] [Figure 12A] Figure 12A shows the entry points for the ultrasound imaging probe and needle along the injection path for an elongated injectable device to reach the hypoglossal nerve.

[0064] [Figure 12B] Figure 12B is a corresponding ultrasound image of the needle reaching the hypoglossal nerve, which is marked up to highlight this important feature and other important features.

[0065] [Figure 13A] Figure 13A shows a stack of components equipped with a respiratory motion sensor.

[0066] [Figure 13B] Figure 13B shows the corresponding container or pouch for the respiratory motion sensor components.

[0067] [Figure 13C] Figure 13C shows two methods and locations for attaching the respiratory motion sensor to the body.

[0068] [Figure 13D] Figure 13D shows another method and location for attaching the respiratory motion sensor to the body.

[0069] [Figure 13E] Figure 13E shows yet another method and location for attaching the respiratory motion sensor to the body.

[0070] [Figure 14A] Figure 14A is a schematic representation of the circuit used to interface the respiratory motion sensor to the analog-to-digital converter input of a wearable magnetic field generator.

[0071] [Figure 14B] Figure 14B shows the oscilloscope trace of the respiratory motion sensor output in response to human respiration.

[0072] [Figure 15] Figure 15 shows an embodiment of a novel and improved transcutaneous electrical nerve stimulation (TENS) system for peripheral nerves and muscles.

[0073] [Figure 16] Figure 16 shows the corresponding TENS system applied to the spinal cord.

[0074] [Figure 17] Figure 17 shows the corresponding TENS system applied to the median nerve.

[0075] [Figure 18] Figure 18 shows the corresponding TENS system applied to the supraorbital nerve.

[0076] [Figure 19] Figure 19 shows the corresponding TENS system applied to the hypoglossal nerve. [Modes for carrying out the invention]

[0077] Figure 1A illustrates an exemplary system configured for neuromodulation therapy, including, but not limited to, the treatment of OSA. Patient 1100 has a battery-powered wearable magnetic field generator 1101 attached to the neck below the jaw to activate an injectable, and a respiratory sensor 1103 attached within the chest or abdominal area. The sensor 1103 transmits signals defining respiratory movements to the wearable 1101 using a wire 1105. The wire 1105 may transmit the sensor output signal in either analog or digital form, if an analog-to-digital converter is included. This wire may be replaced by a wireless link, in which a wireless transmitter in the sensor transmits the sensor output to the wearable. The wearable 1101 transmits magnetic energy via inductive coupling to an injectable receiver 1102 in Figure 1b, which is placed via infusion adjacent to the hypoglossal nerve 1106. The injectable material 1102 may or may not have a tether 1104 attached to it to facilitate the removal of the injectable material.

[0078] In Figure 1B, the device operates by an injectable 1102 applying a series of nerve-modulated pulses from magnetic energy to the hypoglossal nerve, which receives magnetic energy from the wearable 1101, which may or may not be enabled by a sensor 1103 indicating the inspiratory portion of the respiratory cycle. OSA is caused by the patient's tongue being retracted into the airway, blocking the airflow during the inspiratory phase of breathing. Stimulation of the hypoglossal nerve activates the genioglossus muscle, which protrudes the tongue, clearing the airway for breathing and treating OSA. (Explanation of wearables)

[0079] The wearable 1101 has a physical appearance and structure as shown in the schematic representations in Figures 3A-3C and 2C. The wearable is a lightweight device that adheres to the skin at the injection site using the biocompatible adhesive 1307 shown in Figure 3C and generates a magnetic field to activate the injectable for neuromodulation. The wearable has an outer diameter 1308 of 35 mm in Figure 3B and an outer height of 15 mm as shown in Figure 3C. In other modifications, the outer diameter or maximum horizontal dimension may be in the range of 30 mm to 40 mm, 20 mm to 50 mm, or 10 mm to 40 mm, and the height may be in the range of 10 mm to 20 mm, 8 mm to 20 mm, or 5 mm to 20 mm. The main components of the wearable are: the circuit board 1304 in Figure 3C, which has a microprocessor that controls the amplitude and timing of the decaying free-resonant pulses to the magnetic field generating coil 1306 and adjusts the settings from the push button 1301 sequence in Figure 3A; the coil 1306, which generates a magnetic field to activate the injectable 1102 in Figure 1B during neural modulation; and four 2016 button batteries 1305 or other button batteries or battery packs in Figure 3C to power the wearable for more than 10 hours. The circuit board can be rigid or flexible. These button batteries can be either rechargeable or disposable, and in other variations, the number of batteries can range from 1 to 5 and can have standard or custom sizes / shapes. A push button 1301 in Figure 3A to allow the user or physician to communicate with the wearable device; an LED indicator 1302 to indicate the status of the wearable; a connector 1303 to a respiratory sensor to allow stimulation and to be turned on during inhalation and off during exhalation at will; and a 3M 1315 double-sided biocompatible adhesive 1307 or other adhesive film in Figure 3C to hold the wearable in place during sleep. The above components are provided in a housing 1308 having a circular shape, but in other modifications, triangular, square, rectangular, oval, or other shapes may be provided.The cross-sectional profile of the housing 1308 in Figures 3A-3C includes several angled surfaces, but other modifications may include a dome shape, which may reduce the risk of the device 1101 getting caught on clothing and being unintentionally pulled from the user's skin.

[0080] The schematic diagram of the wearable circuit shown in Figure 2C is largely described in U.S. Patent No. 10,744,339 (which is incorporated herein by reference in its entirety). The magnetic field generating coil 1207 in Figures 2B and 2C is connected in parallel with the resonant capacitor 1208 in Figure 2C. This parallel combination is connected on one side to the power source 1209 in Figures 2A and 2C and on the other side to a switch. The switch comprises a MOSFET transistor 1201 and a diode 1208 in Figure 2C. The switch is turned on or off by a microprocessor 1200 driving a logic signal 1205 through a driver circuit 1206. A plethysmography sensor 1204 optionally collects data for the microprocessor regarding the patient's heart rate or blood oxygen saturation level. The power source 1209 is generated from one or more batteries 1202 connected in series as shown in Figure 2A, and this supply voltage can be stepped down to a lower voltage by a voltage converter 1203 as needed throughout the circuit. (Description of injectable materials)

[0081] Injectable devices are expected to be placed using smaller introducer needles, as smaller needles reduce the invasiveness of the injection procedure. Deeper nerves in the body require a larger diameter receiver coil in the injectable, and therefore a lower gauge, larger diameter needle for introducing the injectable into the body. In some variations, the gauge size of the introducer needle may range from 12-16 gauge to reach the deepest nerves up to 10-20 cm, 14-18 gauge for nerves of moderate depth 3-10 cm, or 17-22 gauge for the shallowest nerves up to 3.0 cm. In each case, the diameter of the receiver coil of the injectable is slightly less than the inner diameter of the needle gauge. Functionally, the injectable has a receiver coil, which receives a pulse train of magnetic energy from the wearable and converts it into a pulse train of voltage signals to be applied to the hypoglossal nerve or other target site for nerve modulation. By Faraday's law of induction, small receiver coils can only receive high-frequency alternating currents. Therefore, the rest of the injectable circuit converts the high-frequency alternating current into a series of single-polarity voltage pulses, followed by a longer period of opposite polarity for charge equilibrium.

[0082] The injectable includes a circuit as shown in one schematic diagram in Figures 5A-5C, accompanied by an exemplary component layout and wiring diagram in Figures 7A-7D and an output waveform shown in Figure 6B. Figures 5A-5C show three exemplary schematic diagrams of the injectable circuit. The full-wave rectifier option in Figure 5A injects the largest charge into the nerve for each free resonant cycle, but requires eight passive components when coil 1501 is considered collectively. The center-tapped full-wave rectifier option in Figure 5B produces half the amplitude of Figure 5A and requires seven passive electronic components. The half-wave rectifier option in Figure 5C also has half the charge injection of Figure 5A, but requires only five passive electronic components. Since the circuit in Figure 5C requires the fewest number of components, it can therefore be fabricated in the smallest size. This circuit in Figure 5C has two fewer diodes than Figure 5A, but since it rectifies only half of the wave, it delivers only half of the charge injection per burst.

[0083] The main components of the injectable shown in Figures 5C and 7A-7D are as follows: a custom receiver coil 1501 with a ferromagnetic core that captures the magnetic field generated by the wearable; a Schottky diode 1502 that rectifies the AC signal from the receiver coil into a sinusoidal pulse as shown in Figure 6; a Zener diode 1503 that limits the voltage output of the injectable to 24 volts, as shown by the clipped pulse 1607 in Figure 6B; a 0.22 μF capacitor that charge-balances the output voltage to achieve zero net charge delivered to the tissue over time; and a 10 KOhm resistor 1505 that defines the time constant of the charge rebalancing period 1609 as shown in Figure 6B. These components are mounted on a printed circuit board 1705 in Figures 7B and 7C. Other embodiments use Zener diodes with voltage limits of 2.4 to 5 volts for backward compatibility with unmyelinated nerves or conventional constant voltage limits, or 5 to 24 volts to protect most tissues, or 24 to 100 volts for large-diameter nerves. Other embodiments use capacitors of 0.01–0.22 μF for faster charge equilibrium for higher frequency stimuli or 0.22–10 μF for lower frequency stimuli. Other embodiments use resistors of 2–10 KOhm for higher frequency stimuli (still greater than tissue impedance of 0.5–2 KOhm) or resistors of 10–100 KOhm for lower frequency stimuli.

[0084] The electronic subassembly shown in Figure 7C is coated with parylene C via vacuum deposition, or with another type of parylene or another moisture barrier coating, and then inserted into a biocompatible polyimide tube 1704 in Figure 7D. The tube may be made from PEEK, glass, or other biocompatible materials, or from non-biocompatible materials but coated with a biocompatible coating. The tube and coating act as a moisture barrier, preventing tissue fluid from entering and preventing exposure to non-biocompatible materials within the coated electronic components. Figure 7C also illustrates how the components are electrically connected together to achieve the schematic representation in Figure 5C. Electrode lead wires are spot-welded to platinum-iridium 90%-10% electrodes 1701 and 1702 shown in Figures 7A and 7C. The electrodes may consist of another combination of platinum and iridium or other metals or metallic alloys suitable for use inside the body and for conducting electricity. The tube 1704 is filled with biocompatible epoxy or other epoxy for rigidity. Finally, the tether 1104 is routed through a hole in the return electrode, tied, and epoxy-bonded to the inside of the tube. The tether may be equipped with sutures used to suture the wound, which are made from polyester, polypropylene, ultra-high molecular weight polyethylene, or a combination thereof, or from other biocompatible sutures. The tether may also be made from absorbable synthetic materials, which allow the injectable to be optionally placed inside the body, either temporarily or permanently. (operation)

[0085] The wearable transmits an oscillating, attenuating magnetic field generated by the free-resonant behavior between a primary coil and a low-loss capacitor, as shown in Figure 6A. The initial amplitude of this waveform 1601 in Figure 6A is determined by the length of time that switches 1201 and 1208 are turned on by the microprocessor 1200 in Figure 2C. The longer the switch is turned on, the greater the initial current flowing in the magnetic field generating coil 1207. Then, when the microprocessor turns off this switch, coil 1207 resonates freely with capacitor 1208 and attenuates exponentially due to the losses of these components, as shown in 1603 in Figure 6A. The on time for switch 1201 in Figure 2C in this embodiment is 2 to 30 microseconds, and longer on times may be required for deeper nerves and when the battery is depleted. The on time is adjusted to maintain the same level of stimulation for a given patient as the battery is depleted and its supply voltage decreases with continuous use. Other embodiments relating to wearable coils with deeper nerves and higher inductance may have on-times ranging from 30 microseconds to 1,000 microseconds.

[0086] The secondary (receiver) coil of the injectable picks up a portion of this magnetic field and generates an AC voltage according to Faraday's law of induction. The voltage generated in the injectable is rectified by diode 1502 in Figure 5C and supplied to a high-pass filter, which includes capacitor 1504 and resistor 1505 in Figure 5C to ensure charge-balanced delivery of the current to the stimulating electrodes. The voltage generated by the receiver coil is clipped to 24 volts by Zener diode 1503 in Figure 5C, if necessary, to protect the patient from excessive voltage and / or charge density. The resulting voltage supplied to the electrodes of the injectable is shown in Figure 6B. This circuit generates up to three different waveforms for each free-resonant burst 1603 from the transmission from the wearable coil voltage in Figure 6A. The first waveform is in period 1604 in Figure 6B, where the voltage is a half-wave rectified sinusoidal pulse clipped to amplitude 1607 or 24 volts by the Zener diode. In most embodiments, this first waveform will not be present, as the 24-volt clipping function is for patient safety and is generally not required for therapy. The second waveform period 1605 occurs when the amplitude from the receiver coil naturally falls below the clipping level 1607 or 24 volts and consists of a half-wave rectified sinusoidal pulse without clipping. The third waveform period 1606 is a charge equilibrium period in which the high-pass filter dictates that the net voltage on its output is zero over time and consists mainly of a negative voltage that decays exponentially to zero.

[0087] The waveform in Figure 6B comprises a series of rectified sinusoidal pulses. Peripheral nerves are stimulated extraneuronally by the accumulation of charge near the nerve wall. The charge can be accumulated by a series of unipolar voltage pulses shown in periods 1607 and 1608 of Figure 6B, or by a steady-state unipolar voltage common in the prior art.

[0088] The amplitude of the stimulation is adjusted by the microprocessor 1200 in Figure 2C by increasing or decreasing the on-time of switches 1201 and 1208 prior to free resonance, and can be 3 to 30 microseconds in this embodiment. The burst frequency of the stimulation is adjusted by the microprocessor 1200 by increasing or decreasing the latency between switches, and can be 20 to 40 Hz in this embodiment. Patients report different levels of sensation and discomfort associated with different burst frequencies, and therefore, making this range available is advantageous without impairing the effectiveness of the therapy. Other embodiments relating to other nerve stimulation may have burst frequencies of 5 to 20 Hz or 40 to 1,000 Hz, depending on the electrophysiology and therapy. The effective pulse width of the stimulation is related to the decay time constant of the resonant circuit shown in periods 1607 and 1608 in Figure 6B, and this parameter is fixed by the loss in the resonant circuit. In this embodiment, the effective pulse width is 90 microseconds, while in other embodiments it may be 10 to 100 microseconds or 100 to 1,000 microseconds. Thus, the amplitude and frequency of the stimulation can be easily adjusted by the microprocessor, and these parameters can be set during the titration of the device.

[0089] The microprocessor 1200 in Figure 2C is configured to allow the user to adjust the amplitude and frequency of the stimulus according to Table 1 below. [Table 1]

[0090] The clinical use of the device is intended to follow this sequence: The physician titrates in the “Intensity Setting Mode,” represented by row 1 in Table 1. The titration procedure is described in detail below. If the stimulation sensation is undesirable for the patient, the “Frequency Setting Mode,” represented by row 2 in Table 1, is used to find a more acceptable frequency for the free resonance stimulation. The titration is then repeated. The “Normal Operation” mode, represented by row 3 in Table 1, is used for the first three minutes, ensuring that LED1302 in Figure 3A flashes with the inspiratory portion of the respiratory cycle. This mode is repeatedly restarted until the respiratory sensor is properly installed. The “Normal Operation” mode, represented by row 3 in Table 1, is then used again beyond the first three minutes to provide therapy to the patient during sleep. To turn off the device for any reason, the “Off” sequence in row 4 of Table 1 is exercised.

[0091] The stimulation intensity set by the titration procedure is a critical parameter; if too low, it can easily affect efficacy, and if too high, it can cause discomfort, arousal, or pain. Therefore, the titration method leading to the therapeutic level of stimulation is a crucial step prior to using the device. Figure 4 shows a graph of airflow 1408 on the Y axis versus stimulation amplitude 1407 on the X axis for an OSA patient during sleep. Airflow is at a low plateau 1402 up to the flow capture threshold 1404 when the stimulation amplitude is not sufficient to induce meaningful genioglossal muscle contraction. Airflow is at a high plateau 1403 starting from the peak flow threshold 1405 when the stimulation amplitude causes the tongue to move completely out of the airway. The arousal threshold 1406 in Figure 4 is the level of stimulation amplitude that causes an OSA patient to arouse.

[0092] In Figure 4, the tongue single-contraction threshold 1401 is the observable threshold while the patient is awake. Therefore, the first step of the device titration procedure is to increase the amplitude by pressing button 1301 in Figure 3A on the wearable in the “Intensity Setting” mode in Table 1 until these muscle single contractions are observed. Each time the button is pressed, the amplitude increases by 14.4%. Repeatedly pressing the button generates a series of fixed percentage increases in the stimulation amplitude. Once the initial level of tongue muscle single contractions is observed, the next step is to further increase the amplitude until the expected airflow reaches a higher plateau 1403 in Figure 4, although it is still below the arousal threshold 1406. The titration algorithm is (1.144) of the amplitude. 4 To achieve a 1.712-fold increase, the button is pressed four times. In the example shown in Figure 4, this would increase the stimulation amplitude from 1.4 volts at the single contraction threshold 1401 to 2.4 volts 1410, which is within the high plateau 1403 but far from the arousal threshold of 2.9 volts 1406 in Figure 4. Although below the arousal threshold, this titrated amplitude of 2.4 volts 1410 may still be unfavorable or uncomfortable for the patient. Therefore, the protocol allows the physician to reduce the amplitude by one level (-14.4%) to 2.1 volts 1411 in Figure 4, which is still within the high plateau 1403.

[0093] With respect to the x-axis 1407 in Figure 4, if the stimulating electrode 1702 in Figure 7D is further from the nerve, this scale will change (the stimulation threshold will increase), and the opposite is true if the electrode is closer to the nerve. However, this titration procedure uses the muscle single contraction level threshold 1401 as a reference point and scales from there, and therefore robust results are expected patient-to-patient and across various electrode placements. Depending on these variations, the single contraction threshold may be 0.1 to 10 volts, and the therapeutic level ultimately titrated may be 0.2 to 24 volts. (Bench test results)

[0094] Figure 8A shows an embodiment of the wearable 1101 of Figures 1A and 3A-3C where the components are not integrated into tight packaging. The circuit board 1304, the pack of 2016-size coin batteries 1202, and the magnetic field generating coil 1207 are constructed, connected, and function as intended in Figure 8A. The injectable 1102 circuit is constructed as shown in Figure 5C and positioned 1 centimeter above the wearable coil. The waveform period of Figure 6B is easily observed on the oscilloscope traces of Figures 8B and 8C. The waveform period in which the voltage is clipped by the Zener diode is shown in period 1607 of Figure 8B. The waveform period in which the wearable output undergoes natural exponential decay is shown in period 1608 of Figure 8B. The charge equilibrium period is also shown in period 1609 of Figure 8C. The three periods correspond to and are similar to those in Figure 6B. The wearable coil 1207 in Figure 8A has a diameter of 2 centimeters and consists of two layers of Litz wire windings on a ferrite disk.

[0095] Figure 9A shows a device similar to Figure 8, but with a larger wearable coil 1207 having a diameter of 3.5 centimeters, 9 turns, and wound from 24-gauge Litz wire. The distance between the injectable 1102 and the wearable coil 1207 is 2.5 centimeters, which is the maximum distance expected for hypoglossal nerve stimulation in the OSA patient population. The oscilloscope trace 1608 in Figure 9B shows an amplitude response of 10 volts or more, which is sufficient to completely stimulate the hypoglossal nerve even at this maximum separation distance. (Description of the installation device)

[0096] The injectable material 1102 is intended to be pre-loaded by the manufacturer into the injector needle 2001 as shown in Figure 10A. The needle tip 2002 has stimulating capability and connects to a B Braun HNS12 handheld nerve stimulator 2007 in Figure 10B. This stimulator is designed to stimulate a nerve for nerve block injection during anesthesia. The stimulating capability will be used to verify that the needle tip is actually at the hypoglossal nerve before deploying the injectable material to that location. The connection between the stimulator 2007 and the needle 2001 is made by soldering or crimping (2003) a wire 2006 in Figure 10A to the injector needle near the hub. The injector needle is insulated with a parylene coating or other insulator 1 to 50 microns thick, except for a 1 mm area from the tip 2002 or other distances from the tip, in order to concentrate the stimulation at the tip. The 2002 tip is blunt and has a short 30-degree bevel, allowing for penetration through tissue during injection without damaging nerves or blood vessels if either is unintentionally contacted.

[0097] In Figure 10A, the injectable 1102 is pre-loaded onto the tip of the needle 2002, and the tether 1104 is routed through the needle. Both the tether 1104 and the plunger 2004 are routed through a locking iris valve 2005, which is tightly tightened at the factory to hold the components in place until the injectable is deployed. The locking iris valve 2005 is released by twisting two knobs apart from each other. This mechanism allows the physician performing the injection to ultrasound-guide the needle to the hypoglossal nerve and then allow an assistant to loosen the locking iris valve 2005 immediately before the deployment of the injectable 1102.

[0098] In Figure 10A, the introduction needle 2001 is Bard part number C1813B (BARD MEDICAL, New Providence, NJ), which may then be coated with (insulating) parylene except for the tip to convert it into a stimulating needle. The wire with the stimulator connector 2006 is available from the anesthetic needle B Braun part number 33644. The locking iris valve 2005 may be Merit Medical part number FLO30 (MERIT MEDICAL SYSTEMS, South Jordan, UT). The plunger 2004 is a custom 22 gauge rod. (Injection procedure and wearable device placement protocol)

[0099] The following is an example of a manufacturer's instructions for injecting a device and preparing a patient for neuromodulatory therapy related to OSA.

[0100] 1. The assistant or physician unpacks the pre-loaded introducer 2000 shown in Figure 10A, wraps a sterile shroud around the ultrasound probe, and covers it with sterile gel. Next, the skin electrode is placed near the patient's clavicle and electrically connected to the handheld B Braun HNS 12 stimulator 2007 shown in Figure 10B. The stimulator is also connected to the lead wire 2006 of the introducer needle 2000 as shown in Figure 10A. The handheld stimulator is configured to generate a 1 millisecond pulse at a frequency of 1 Hz. The initial current is set to 0.0 milliamperes.

[0101] 2. The physician places an ultrasound probe, covered with gel, on one side of the neck, below and parallel to the jawbone. The physician moves the ultrasound probe until the parallel trajectories of the submandibular gland and hypoglossal nerve 1106 are visible, as shown in Figure 12B. If the ultrasound probe indicates that the superior trajectory of the hypoglossal nerve is deeper than 2.5 cm, the procedure is stopped and the subject is deemed unsuitable.

[0102] 3. The physician then visualizes the linear pathway 2204 from the hypoglossal nerve to the skin surface, safely avoiding the submandibular gland 2203 in Figure 12B. During visualization, the physician identifies the needle entry point and marks this location on the skin. The physician ensures that the mark is carefully aligned with the central reference 2205 on the side of the probe in Figure 12A.

[0103] 4. The assistant or physician cleans the needle entry site and injects lidocaine, a local anesthetic.

[0104] 5. The doctor waits a few minutes for the anesthetic to take effect, and then uses a surgical needle to create a small hole at the marked entry point.

[0105] 6. The assistant covers the ultrasound probe with sterile gel. The physician will then, with one hand, return the ultrasound probe to the side of the neck, below and parallel to the jawbone. Ensure that the mark is carefully aligned with the central reference point 2205 on the side of the probe in Figure 12A. The physician moves the probe until the submandibular gland is again visible, along with the parallel trajectory of the hypoglossal nerve 1106, slightly beyond it in Figure 12B.

[0106] 7. Next, with the other hand, the physician inserts the introducer needle 2000 (Figure 10A) anteriorly from the submandibular area and guides it along the edge of the submandibular gland toward the hypoglossal nerve. The physician (1) avoids advancing through the submandibular gland, (2) keeps the needle on a linear trajectory toward the nerve target, and (3) maintains a view of the needle, submandibular gland, and hypoglossal nerve at all times. To accomplish these, the physician may reposition, change direction, and / or reinsert the introducer as needed. See Figures 12A and 12B.

[0107] 8. When the tip of the introducer tip 2002 in Figure 10A is within 1-2 millimeters of the hypoglossal nerve, the assistant will increase the current output of the handheld stimulator 2007 in Figure 10B until tongue movement is observed. The assistant will increase the current until tongue displacement appears to saturate until tongue displacement no longer increases. If saturation is not observed with a 2 milliampere stimulation with 1 millisecond pulses at a rate of 1 per second, the physician will move the introducer tip closer to the nerve, if possible.

[0108] 9. The physician positions the injectable by having an assistant loosen the locking iris 2005 of the injector (Figure 10A) while simultaneously withdrawing the injector needle 2000, and holding the plunger 2004 fixed in space. The physician and assistant ensure that the downstream stimulating end of the injectable 1102 (Figure 10A) remains within 1–2 mm of the hypoglossal nerve on the ultrasound display. The injector should now be completely outside the target, and the stimulating electrode of the injectable should be within 1–2 mm of the hypoglossal nerve. With the physician's or assistant's fingers over the tether entry point, the injection site is gently cleansed, and any excess tether 1104 (Figure 10A) is coiled and taped to the target skin away from the injection site. The physician and assistant take care not to pull the injectable away from the nerve. The physician or assistant will place a bandage, such as Tegaderm 3582 from 3M (Minnesota), so that the pad gently covers the injection site. Note that a tether may not be present for the permanent placement of the injectable, or a tether may be made from a synthetic absorbable material.

[0109] 10. This next step is likely performed at some point after the injection is complete, depending on whether the placement is temporary for an overnight trial or permanent. The physician or assistant removes the adhesive cover of the wearable and places the wearable centered on the site of the injectable, but not centered on the needle entry point. The wearable is attached to the skin of the subject and overlaps with a bandage if necessary and still present.

[0110] 11. A physician, presumably different from the one who placed the injectable, sets the wearable to intensity setting mode according to Table 1. In this mode, the stimulation will alternate on and off at 1-second intervals at the lowest level. The physician increases the intensity by one level at a time by quickly pressing the button once for each level, as specified in Table 1. When the physician observes a single-contraction threshold stimulation level of 1409 for the tongue in Figure 4, the physician increases the stimulation by quickly pressing the wearable's button four times, increasing the amplitude to level 1410 in Figure 4. If this level of stimulation is uncomfortable for the patient, the physician may decrease the stimulation by one level, to amplitude level 1411 in Figure 4, by quickly pressing the button twice, as shown in Table 1. The physician then holds the button for 1-2 seconds, as shown in Table 1, to fix this stimulation level in the wearable's memory inside the microprocessor 1200 in Figure 2C.

[0111] If the device is unable to reach a higher intensity level when the button is pressed, the LED will not provide its flashing feedback. If this occurs during the titration process, proper titration is not achievable. This may be due to an excessive distance between the injectable and the nerve or an excessive distance between the injectable and the wearable. The physician will determine whether a second injection attempt is justified. If applicable, the injectable, if present, will be removed via tether, the injectable and all injector components will be discarded, the skin around the injection site will be cleansed, and the above steps will be repeated with a new injector and new injectable.

[0112] The frequency setting modes in Table 1 are used when the patient is still uncomfortable with the stimulation and can be adjusted to a higher or lower frequency. The titration procedure in step 11 must be repeated after changing the frequency.

[0113] Once the wearable parameters are fixed in step 11, the patient may put on the wearable prior to sleep and remove the wearable after sleep. The patient may also recharge or replace the battery 1305 shown in Figure 3C.

[0114] 12. The physician or patient attaches the respiratory sensor 2306 to the chest or abdomen, possibly under a respiratory belt, as shown in Figures 13C, 13D, or 13E, and is typically used in sleep studies. The physician or patient routes and connects the respiratory sensor wire to the wearable through the collar, under a shirt or other upper garment, as shown in Figure 1A. During initial use, the physician will ensure the respiratory sensor is functioning by observing that the wearable's LED turns on during the subject's inhalation. (Animal demonstration in rat sciatic nerve)

[0115] The full functionality of the wearable and injectable device was demonstrated in the rat sciatic nerve using the apparatus shown in Figures 11A and 11B. The rat sciatic nerve is approximately 2 millimeters in diameter and is the same as the hypoglossal nerve in humans. The injectable was implanted in the sciatic nerve of a rat 2100 by surgical means, and the wound was then closed and sutured. The wearable 1101 was placed on a calibrated movable stage 2107. The foot of the rat's corresponding hind limb was attached to a pedal 2102 that was physically connected to a force transducer 2101. This apparatus in Figures 11A and 11B allowed for the measurement of hind limb force as a function of the distance of the wearable from the nerve.

[0116] The results of this study are shown in Figure 11C. Hindlimb force 2103, measured by transducer 2101, is shown on the Y-axis. The distance of the wearable 1101 from the sciatic nerve is shown on the X-axis, and the skin surface was 11 mm from the nerve, as indicated by point 2108. Force was measured with respect to two different coils 1207 in Figure 2B, shown by graph 2106 in Figure 11C, and a second coil 1207 in Figure 9A, shown by graph 2105 in Figure 11C. The hindlimb force exceeded the capacity of the force transducer and flattened graph 2105 before decreasing with distance. The data show that the wearable's distance capability with smaller coils was 15 mm from the nerve and with larger coils it was 27 mm from the nerve. In humans, the hypoglossal nerve is expected to be up to 25 mm from the wearable in the majority population of OSA patients. (Human demonstration of ultrasound-guided injection pathways)

[0117] In two human subjects, an otolaryngologist safely ultrasound-guided a nerve block needle from the skin surface along the expected injection route of the induction device shown in Figure 10A, avoiding the submandibular gland and reaching the vicinity of the hypoglossal nerve. The ultrasound system 2202 in Figure 12A, with an Apple iPad® display showing images as shown in Figure 12B, was manufactured by Butterfly iQ (BUTTERFLY NETWORK, Guilford, CT). The stimulating needle 2201 in Figure 12A was inserted submandibularly at approximately a 30-degree angle to the skin toward the hypoglossal nerve 1106, carefully avoiding the submandibular gland 2203. This needle was guided by a physician holding the ultrasound probe 2202 so that the length of the needle 2204 is within the planar view of the ultrasound display in Figure 12B. The location of the needle tip in the hypoglossal nerve was verified by activating the needle tip using the stimulator in Figure 10B. Tongue protrusion was observed in both human subjects, which is an expected response to hypoglossal nerve stimulation related to OSA. No significant discomfort was reported, even when the Doppler features of the ultrasound system highlighted blood flow, and no blood vessels or other sensitive structures were observed in or around the area imaged in Figure 12B. (Respiration sensor)

[0118] The respiratory sensor is a piezoelectric disc that flexes relative to a pivot, generating a positive voltage when the patient is inhaling and a negative or zero voltage otherwise. The main components of the respiratory sensor are as follows in Figure 13A: a piezoelectric disc 2301, often found in electronic buzzers; the piezoelectric disc having a diameter of 35 mm and available from Murata part number 7BB-35-3L0 or another piezoelectric disc; a support disc 2302 made of brass or another suitable material to provide parallel plates for the swirling motion; a pivot 2303 which is a transparent rubber dome from 3M (St. Paul, MN), electronics part number B073W1B3G1 or another pivot attached to the center of the support disc 2302; a felt pouch shown in Figure 13B for housing a stack of the brass disc 2302, pivot 2303, and piezoelectric disc 2301; and a hook and loop strip 2304 at the opening of the pouch for inserting the stack. The pouch may be made from another suitable material, such as cloth, which is a moisture barrier or can be lined with a moisture barrier layer or coating. The output wire from the piezoelectric disc may be tied using a knot below the hook-and-loop seal 2304 or crimped to the support disc 2302 for strain relief. Other strain relief methods may also be used to attach the wire to the pouch, such as folds attached to the pouch, knot holes in the pouch through which the wire passes, sewn-in attachments, or other suitable means.

[0119] Figure 13A shows a piezoelectric disk 2301 intended for use as a buzzer. This component of the sensor, though not limited to this one, has a diameter of 35 mm and includes a piezoelectric ceramic film on one side. A wire is connected to a ceramic and brass substrate. A capacitance of 30 nanofarads exists between the ceramic and the substrate. In its intended use, a voltage is applied to the wire, causing the disk to vibrate at a fixed frequency, or to produce an audible buzzing sound. In this application relating to the present invention, the disk generates a voltage when the substrate is slightly flexed. An example of this component, though not limited to this one, is 7BB-35-3L0, manufactured by Murata (Kyoto, Japan).

[0120] This respiratory sensor generates a voltage when the piezoelectric disc is deflected as the chest or abdomen expands during inspiration. In the embodiment shown in Figure 13A, the voltage is positive when the piezoelectric disc 2301 is deflected toward the support disc 2302, with the support disc facing the body. The deflection motion accumulates charge across the ceramic film on the piezoelectric disc, generating a voltage. Even while the deflection force remains, the charge is dissipated by the resistance, so the voltage will decrease over time. The time constant for this voltage drop is RC, where R is the total resistance in parallel with the sensor output and C is the intrinsic capacitance of the piezoelectric disc. Thus, this voltage drop time constant can be designed by a predetermined load resistance or series resistor inserted between the sensor output and the load.

[0121] The piezoelectric disc of the sensor will flex with the patient's respiratory movements if the strap is routed across the rear of the sensor, tensioned, and attached to the skin on either side, or routed around the entire circumference of the body. This strap mounting can position the sensor in the upper chest, lower chest, stomach area, abdominal area, and between and including the waistline. Preferably, the sensor is positioned on the chest with respect to the patient who expands the chest when inhaling, and close to the waistline with respect to the patient who expands the stomach when inhaling. In addition, the strap may be a breathing belt as depicted in Figure 13C with the sensor at location 2306, or the strap may be an elastic or fabric waistline portion of clothing or underwear as depicted in Figure 13D with the sensor at location 2306, or the strap may be taped or bandaged from the rear to the skin on either side with adhesive tape or adhesive bandage as depicted in Figure 13E with the sensor at location 2306.

[0122] In Figure 14A, the load resistance is the input impedance of the analog-to-digital converter or preamplifier 2403 downstream of the sensor 2306, plus a series resistor 2401 added to design the desired time constant. In numerous experiments by the inventors, the desired time constant for a sensor capable of accurately detecting the inspiratory phase of respiration is approximately 0.3 seconds for this model of the piezoelectric disk 2301 in Figure 13A. This time constant results in the sensor output being mostly positive when the patient is inhaling or about to inhale, and mostly negative when the patient is not inhaling. Since the intrinsic capacitance of the piezoelectric disk 2301 is 30 nanofarads, a load resistance of 10 MOhm would produce this desired time constant. As shown in Figure 14A, this load resistance can be achieved by adding a series resistor 2401, which has a resistance of 10 MOhm minus the input impedance of the A / D converter on the wearable's microprocessor 1200 in Figure 2C, or the input impedance of a wireless transmitter replacing a wired connection. The selected time constant of the sensor for other patients' respiratory patterns and rates may be 0.1, 0.2, 0.4, 0.5, or 0.6 seconds, or any value in between.

[0123] Figure 14B shows the oscilloscope trace of the voltage from the sensor when mounted as shown in Figure 13D (waistline). The input impedance of the oscilloscope is 1 MOhm, and therefore the series resistor 2401 in Figure 14A was selected to be 9 MOhm for this bench test. In the trace in Figure 14B, inhalation occurs almost exclusively when the voltage output is positive 2404, and otherwise the voltage output is almost exclusively negative 2405. The sharp rising edge of voltage 2404, crossing zero volts just before the inspiratory phase, serves as a strong and reliable signal to activate the hypoglossal nerve stimulator, move the tongue out of the airway, and enable patients with OSA to inhale without obstruction.

[0124] Signals similar to those in Figure 14B, with positive voltages during inhalation and while attempting to inhale, and negative voltages during exhalation, were observed in all sleeping positions, including lying on either side, lying on one's back, and even lying face up with weight on the sensor against the mattress.

[0125] While not limited, the piezoelectric disk 2301 in Figure 13A may be of different sizes, shapes, or capacitances and can still be designed within a respiratory motion sensor by those skilled in the art. While not limited, the desired time constant can be restored with respect to different intrinsic capacitances and / or load resistances by changing the series resistor.

[0126] (Improved TENS device)

[0127] Figure 15 shows the present invention as applied to transcutaneous stimulation at a location on the arm of a human. The configuration in Figure 15 can be placed at any location on the body where nerve or muscle stimulation is desired, though not limited to this. In this case, nerve 3110 is the target for stimulation. Three electrodes 3102, 3103, and 3104 are mounted on the skin 3111. As will be described below, electrode 3102 is the stimulating electrode, and electrodes 3103 and 3104 receive the rectified component of the alternating current in the opposite direction. The rectification circuit or component may be two diodes 3101.

[0128] Although not limited, the stimulating electrode 3102 may be divided into an array of smaller electrodes, some of which provide the positive component of the AC waveform and others providing the negative component. These variations of the present invention are considered to be essentially the same technique as described herein, as the combined effect is the same.

[0129] The alternating current (AC) voltage source 3112 has one terminal connected to the stimulating electrode 3102, and the other terminal is connected to the cathode of one diode 3101 and the anode of another diode 3101. The diodes 3101 ensure different paths through the body for positive pulses versus negative pulses provided by the AC or voltage source 3112. The path of the positive pulse 3113 can be considered the path of the anode current, and the path of the negative pulse 3114 can be considered the path of the cathode current. Since these two paths merge at electrode 3102, this merged region experiences both positive and negative pulses, or full AC stimulation.

[0130] To stimulate nerve 3110, a combination of both intensity or amplitude and current density is required. The nerve can be stimulated by either cathode or anode current, but generally, twice the amplitude of the cathode current is required for the anode current. In Figure 15, the highest cathode current density is at location 3105, which is the target for stimulation. Location 3106 is the location of the highest anode current density, which can provide the desired counteracting of the cathode stimulation at 3105, thereby preventing the creation of brain-connected action potentials in sensory nerve fibers that may coexist with motor fibers in nerve 3110. Alternatively, the cathode and anode currents can be reversed by physically reversing the return electrodes, thereby using a stronger cathode current to mitigate pain signals toward the brain, while the anode current prevents or minimizes the excitation of downstream muscle fiber bundles of the cathode excitation.

[0131] In Figure 15, locations 3107, 3108, and 3109 beneath each electrode are most susceptible to the side effect of an electric shock sensation because they pass through superficial nerve endings where current is easily excited. In conventional TENS devices, these locations would be the source of the shock sensation. However, in the configuration of the present invention shown in Figure 15, none of these locations 3107, 3108, and 3109 need to cause an electric shock sensation.

[0132] At the location of the stimulating electrode 3109, these nerve endings near the skin experience alternating current. The Insurance Agents Laboratory (UL) and the International Electrotechnical Commission (IEC) have published electrical safety data indicating that the human body requires an amplitude 10 times larger than that of lower frequencies or DC voltages to elicit a response to an AC 10 kHz voltage. At a frequency of 100 kHz, an amplitude 100 times greater than that of DC is required for AC, and a frequency of 1 MHz is even safer. Even AC frequencies as low as 1 kHz have a higher sensory threshold than lower frequencies or DC currents. Therefore, as long as the AC voltage source 3112 in Figure 15 has a frequency substantially above 1 kHz, no sensation is expected at location 3109, even if the cathode stimulating region 3105 and / or anode stimulating region 3106 are fully stimulated. The alternating current at the stimulating electrode can be a sine wave, square wave, triangular wave, or other periodic waveform. In addition, the periodic waveform can be slowly modulated upward or downward in amplitude without reintroducing the sensation of an electric shock. For example, the exponentially decaying waveform in Figure 6A is an example of a slowly modulated sine wave, where the modulation is a gradual exponential decay. Thus, the wearable in Figure 3 can generate the alternating current required at the stimulating electrode by replacing the AC source 3112 in Figure 15 with the magnetic field generating coil 1207 in Figure 2B, 1306 in Figure 3C, 1207 in Figure 8A, and 1207 in Figure 9A.

[0133] Locations 3107 and 3108 in Figure 15 are also susceptible to shock sensation. At these two locations, the respective return electrodes 3103 and 3104 can be designed with a sufficiently large electrical contact area to arbitrarily lower the current density at locations 3107 and 3108. In embodiments of the present invention, the electrical contact areas of these electrodes 3103 and 3104 would be sufficiently large so as not to excite nerve endings in regions 3107 and 3108.

[0134] The electrical contact area of the electrode 3102 can be smaller since its nerve endings under the skin are protected by the AC current. Without limitation, the electrode 3102 can have many electrode contact areas, and typically, a larger surface area is more efficient for deeper stimulation targets, and a smaller surface area is more efficient for shallower stimulation targets.

[0135] In the overview of the present invention in FIG. 15, a highly targeted stimulation area 3105 is achieved well below the skin, and the shock sensations are eliminated at locations 3107, 3108, 3109 directly below the three electrodes 3103, 3104, 3102, respectively.

[0136] One assumption in FIG. 15 is that the cathode current 3114 is approximately equal in magnitude to the anode current 3113 but opposite in polarity. If these two magnitudes are not equal, the region 3109 is the net cathode or net anode, and either of them can stimulate the nerve endings at 3109 and cause an electric shock sensation. If the two currents at the return electrodes 3113 and 3114 are not balanced, or are naturally approximately equal in magnitude, some balancing means can correct the imbalance: a canceling DC bias can be introduced to the AC voltage source 3112, or the electrode contact area of either electrode 3103 or 3104 can be increased or decreased to balance the anode and cathode currents, or a series resistor can be inserted into the wire entering electrode 3103 or into the wire entering electrode 3104. Without limitation, a microprocessor can sense the current levels to electrodes 3103 and 3104 by using a current sensor not shown in FIG. 15, calculate the imbalance, and control the balancing means as described by automatically, and perhaps dynamically, adjusting the parameters described above. Again, without limitation, such a microprocessor can continuously sense the anode and cathode currents and turn off the device when they lose balance by an undesirable amount in response to unintended conditions.

[0137] Figure 16 is similar to Figure 15, but this time it shows the configuration of the present invention applied to spinal cord stimulation (SCS). SCS is widely used to treat lower back pain and other types of chronic pain by blocking pain signals to the brain in the spinal cord. Achieving SCS therapy using a TENS device is essentially impossible because the spinal cord is located 2-4 cm deep within the body, and the electric shock experienced at skin electrodes would be unacceptable when the current density is high enough for therapy in the spinal cord. In Figure 16, location 3121 along the spinal cord 3120 is the target site. The target site is deep, but the tissue between the skin 3111 and the spinal cord 3120 is mostly bone, which is very resistant compared to other tissues. Therefore, the current flowing into / out from electrode 3102 will preferentially and preferably flow into the more conductive tissue of the spinal cord, between the vertebrae.

[0138] (Example 1: Improved TENS for median nerve and carpal tunnel syndrome)

[0139] Figure 17 illustrates the present invention used to stimulate the median nerve 3133 in a human subject, which extends centrally along the forearm through the wrist to the hand. This nerve is often stimulated as a therapy for carpal tunnel syndrome. A smaller electrode 3102 is placed on the skin directly above the median nerve, and two return electrodes 3103 and 3104 are placed opposite 3102, with 3103 placed on the back of the hand. A voltage source 3134 generates one burst per second of exponentially decaying AC sine waves. The AC frequency of the voltage source 3134 is 100 kHz, the decay time constant is 25 microseconds, and the peak amplitude is 200 volts. The result is a current peak of approximately 6 milliamperes in source 3134. The RMS voltage at electrodes 3103 and 3104 is approximately 66 volts during the burst. This RMS amplitude is typical for a TENS device. A negative cathode pulse 3131 flows from electrode 3102 to electrode 3103, and a positive anode pulse 3132 flows to electrode 3104. The target stimulus is along the median nerve slightly anterior to electrode 3102.

[0140] In the configuration and stimulation parameters of the present invention, the thumb 3130 of a human subject moved back and forth in synchronization with a burst of decaying sinusoidal waves. The pain level experienced by the subject from any residual electric shock sensation ranged from 1 (barely noticeable) on a scale of 0 to 10, where 0 was painless and 10 was unspeakable pain.

[0141] Next, the same human subjects were fitted with a conventional TENS device (HNS 12 manufactured by B Braun Medical (Bethlehem, PA), not shown in Figure 3), with the return electrode placed at location 3103 in Figure 3 and the stimulating electrode at location 3102. Both of the conventional electrodes had a surface area similar to that of the electrodes of the present invention, and their amplitudes were increased to achieve the same thumb response as 3130 in Figure 17. Using the conventional TENS device, the human subjects reported pain levels 6 (moderately severe and interfering with normal activity).

[0142] Therefore, the TENS of the present invention achieved the same response as conventional TENS, but the pain level caused by the electric shock sensation was reduced from 6 to 1.

[0143] Another nerve near the median nerve in Figure 17 is the ulnar nerve. Stimulation of this nerve in a similar manner can alleviate pain signals that propagate along the ulnar nerve. For example, pain from cubital tunnel syndrome can be relieved in this way.

[0144] While examples have been given only for two types of pain signaled to the brain by the median and ulnar nerves, the present invention can be applied to treat peripheral pain signaled by any peripheral nerve by attaching electrodes to the appropriate locations.

[0145] (Example 2: Improved TENS for supraorbital nerve and migraine)

[0146] Figure 18 shows a configuration similar to Figure 17, except that electrode 3102 was placed on the supraorbital nerve directly above the midpoint of the eyebrow. This nerve is often stimulated as a therapy for migraines. Return electrodes 3103 and 3104 were placed 2 centimeters on either side of the stimulating electrode 3102. The system was operated in the same manner as in the previous example with similar voltage amplitudes. In the human subjects in this study, pain from migraines was reduced from moderate to mild, or mild to absent, depending on the stage of headache progression.

[0147] The same human subjects also used a conventional TENS device available from Cefaly (Seraing, Belgium) during the same migraine episode. The conventional device also reduced headache to moderate to mild, or mild to no headache. However, with respect to supraorbital nerve stimulation, the pain level for the TENS of the present invention was 1, compared to a pain level of 6 for the conventional TENS, again representing a significant improvement over the conventional technology.

[0148] (Example 3: Improved TENS for hypoglossal nerve and obstructive sleep apnea)

[0149] Referring to Figure 19A, the stimulating electrode was divided into two electrically connected electrodes 3102, one of which was placed on one side of the lingual frenulum on the inside of the oral cavity. Return electrodes 3103 and 3104 were placed under the jawbone on both sides. Electrical stimulation at this location activates the genioglossus muscle and hypoglossal nerve located beneath the tongue. When contracted, these muscles pull the posterior part of the tongue toward the mandible. The final result is tongue protrusion. This response has been demonstrated in human subjects, and the tongue protrusion response 3160 is illustrated in Figure 19B. Human subjects experienced 1–2 pain levels as the stimulation amplitude was titrated to increase in order to achieve significant tongue protrusion comparable to Inspire Medical's implantable device. Thus, the present invention achieves the same response as commercially available surgical implants using a completely non-invasive device. The configuration of the present invention in Figure 19A is ideal for treating obstructive sleep apnea (OSA).

[0150] This description and examples clearly demonstrate that the present invention reduces the sensation of electric shock and associated pain, and increases the targeting of TENS stimulation. These improvements also enable higher, tolerable stimulation intensities, indicating a direction toward greater efficacy of the present invention compared to prior art TENS devices. In addition, novel therapies involving non-invasive TENS devices, such as spinal cord stimulation, may be possible for the first time using the present invention.

[0151] The examples illustrating the present invention and human subject studies relate to specific therapies, but are not intended to imply any limitation that the present invention is claimed to relate to other known or currently unknown TENS therapies.

[0152] While this disclosure has been described in relation to various exemplary embodiments, various additional embodiments and modifications of the embodiments described are envisioned within the scope of this disclosure. Therefore, nothing in the foregoing description should be construed as limiting the scope of the invention as described in the following claims. With respect to all embodiments described above, the steps of the method do not need to be performed sequentially.

Claims

1. A neuromodulation system for obstructive sleep apnea, wherein the neuromodulation system is a. An elongated device configured for injection near the hypoglossal nerve, wherein the elongated device comprises a stimulating electrode, a return electrode, an elongated receiver coil, a set of rectifier diodes, a Zener diode, a resistor, and a capacitor, and the elongated device does not include a battery. b. Wearable devices equipped with magnetic field generating coils Equipped with, The magnetic field generating coil is connected to a capacitor and configured together to resonate freely during repeated stimulation of the hypoglossal nerve. The elongated receiver coil is configured to generate a voltage in response to the free resonance, and the capacitor and resistor of the elongated device constitute a high-pass filter. A neuromodulation system in which the elongated device is configured such that the voltage generated by the elongated receiver coil is rectified by the rectifier diode, limited by the Zener diode, filtered by the high-pass filter, and finally applied to the stimulating electrode, and the voltage applied to the stimulating electrode is averaged to zero or near zero before the onset of the next free resonance.

2. The neuromodulation system according to claim 1, wherein the wearable device includes at least one button battery.

3. The neuromodulation system according to claim 1, wherein the wearable device is configured to allow adjustment of the amplitude of stimulation by setting an initial current flowing in the magnetic field generating coil prior to the free resonance.

4. The neural modulation system according to claim 3, wherein the setting of the initial current of the wearable device is based on the length of time the magnetic field generating coil is connected between the power source and ground.

5. The neuromodulation system according to claim 1, wherein the rectifier diode, the Zener diode, the resistor, the capacitor of the elongated device, and any interconnections thereto are coated with a moisture-proof layer having a thickness of 5 to 50 microns and comprising parylene or parylene C.

6. The neuromodulation system according to claim 1, wherein the rectifier diode, the Zener diode, the resistor, the capacitor of the elongated device, and any interconnections thereto are housed inside a tube, the tube comprises polyimide or PEEK, and the tube is filled with biocompatible epoxy.

7. The neuromodulation system according to claim 1, wherein the stimulating electrode and the return electrode are made from a biocompatible metal.

8. The neuromodulation system according to claim 7, wherein the electrode comprises platinum, iridium, or an alloy of platinum and iridium.

9. The neuromodulation system according to claim 1, wherein the elongated device further comprises a tether attached to the elongated device at a location spaced apart from the stimulating electrode, the tether being configured for detachability, and the tether comprising polyester, polypropylene, ultra-high molecular weight polyethylene, tissue-absorbable synthetic material, or a combination thereof.

10. The neuromodulation system according to claim 1, wherein the rectifier diode is configured as a full-wave rectifier or a half-wave rectifier.

11. The neuromodulation system according to claim 1, further comprising an introduction needle, wherein the elongated device is located inside the introduction needle, the tip of the introduction needle is configured to be electrically connected to a stimulating device, the stimulating device is configured to stimulate the hypoglossal nerve with the tip of the introduction needle to verify that the tip of the introduction needle is located at the location of the hypoglossal nerve before deploying the elongated device to the location of the hypoglossal nerve.

12. The device further includes a sensor for sensing respiratory movements, and the sensor is: Pouch and, Piezoelectric disc and Support disc and, The pivot between them contained within the aforementioned pouch Equipped with, The neuromodulation system according to claim 1, wherein the support disc is located on a first side of the pouch configured for contact with the user's body, and the piezoelectric disc is located on a second side of the pouch opposite the support disc and configured to be bound toward the body.

13. The neuromodulation system according to claim 12, wherein the sensor is electrically connected to the wearable device by a connector.

14. The neuromodulation system according to claim 13, wherein the connector is a wire.

15. The neural modulation system according to claim 13, wherein the connector is a wireless link.

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