Implants using ultrasonic communication for neural sensing and stimulation

Abstract

To provide implantable medical devices that are powered by ultrasonic waves.SOLUTION: Provided is an implantable medical device, including: (a) two or more ultrasonic transducers 504 configured to receive ultrasonic waves that power the device and emit an ultrasonic backscatter; (b) an integrated circuit 506 comprising an energy storage circuit comprising a capacitor, wherein the integrated circuit 506 is electrically connected to the first ultrasonic transducer and the second ultrasonic transducer; and (c) one or more of (i) a sensor configured to measure a physiological condition, (ii) two or more electrodes configured to be in electrical communication with a tissue and emit an electrical pulse to the tissue, or (iii) two or more electrodes configured to be in electrical communication with a tissue and detect an electrophysiological signal from the tissue; wherein the sensor or the two or more electrodes are electrically connected to the integrated circuit 506.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 660,112, filed April 19, 2018, which is incorporated herein by reference for all purposes.

[0002] [Technical field] The present invention relates to ultrasonically powered implantable medical devices and methods of using the same. [Background technology]

[0003] An individual's peripheral nervous system operates with strict control over vital organ activity and physiological homeostasis. Electrical pulses transmitted through nerves can, for example, alter pulse rate, inflammation, and bladder or bowel control. Certain pathologies can occur when these nerve signals fail to properly control the body, either through overstimulation or understimulation of target organs.

[0004] Invasive methods have been developed to treat abnormal physiological activity by controlling electrical signals in the peripheral nervous system. Such methods can include implanting electrodes in the patient's body with the tip of the electrode in contact with the target nerve. These electrodes generally have long leads that are attached to an external device, which exposes the patient to a significant risk of infection or displacement of the electrode. Furthermore, many of the methods are so invasive that certain treatments are limited to clinical settings and cannot be used as home therapies. Fully implantable devices have been developed for less invasive treatments, but such devices are too large to be placed in many locations on the body. Thus, implanted devices require the use of long leads that can become displaced or broken. Such implanted devices are also implanted to stimulate upstream nerves, such as the vagus nerve, which results in significant side effects from off-target electrical stimulation.

[0005] There remains a need for implantable devices that can stimulate specific nerves in a controlled manner and with limited risks and side effects.

[0006] The disclosures of all publications, patents, and patent applications referenced herein are each incorporated herein by reference in their entirety. In the event that any reference incorporated by reference conflicts with the present disclosure, the present disclosure shall control. Summary of the Invention

[0007] Described herein is an implantable medical device comprising: (a) a body including an ultrasound transducer configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy that powers the device; (b) two or more electrodes in electrical communication with the ultrasound transducer; and (c) a clip attached to the body configured to at least partially surround a nerve and position the two or more electrodes in electrical communication with the nerve. In some embodiments, the clip is configured to at least partially surround the nerve and threadlike tissue attached to the nerve. In some embodiments, the threadlike tissue is a blood vessel.

[0008] In some embodiments of the implantable medical device, the clip comprises a plurality of flexible legs extending below the body. In some embodiments, the implantable device comprises a hook or loop configured to manipulate at least one of the flexible legs in response to manipulating the hook or loop. In some embodiments, the hook or loop is disposed at an end of one of the flexible legs. In some embodiments, the hook or loop is disposed proximal to the body.

[0009] In some embodiments of the implantable medical device, the flexible legs are curved, hi some embodiments, the legs extend away from the body before curving towards the body as the legs extend down the body.

[0010] In some embodiments of the implantable medical device, the plurality of flexible legs comprises at least one pair of legs, where the pair of legs comprises a first leg and a second leg that extend downwardly away from the body in opposite directions. In some embodiments, the first leg and the second leg are connected by a crossbar connected to the body. In some embodiments, the crossbar is connected to the body of the device via a flexible section. In some embodiments, the flexible section is a hinge. In some embodiments, the device comprises two pairs of legs, where each leg of the pair is disposed on an opposite side of the body. In some embodiments, the legs are attached to the body via a bottom surface of the body. In some embodiments, the legs are attached to the body via a sidewall of the body.

[0011] In some embodiments of this implantable medical device, the legs comprise a metal, metal alloy, ceramic, silicon, or a non-polymeric material. In some embodiments, the legs comprise an elastomeric coating or a non-elastomeric polymeric coating. In some embodiments, the coating is bioinert. In some embodiments, the coating is silicone, a poly(p-xylylene) polymer, or a polyimide. In some embodiments, at least one of the legs comprises an exterior surface coated with an elastomeric or non-elastomeric polymeric coating and an interior surface comprising at least one electrode that is not coated with an elastomeric or non-elastomeric polymeric coating.

[0012] In some embodiments of the implantable medical device, the body includes a bottom surface and the two or more electrodes terminate at the bottom of the body. In some embodiments, the two or more electrodes are disposed on a clip. In some embodiments, the clip includes a plurality of flexible legs extending below the body and the two or more electrodes are disposed on the flexible legs.

[0013] In some embodiments of the implantable medical device, the body comprises a housing. In some embodiments, the housing comprises a bioinert material or is coated with a bioinert material. In some embodiments, the housing comprises a bioinert material, and the bioinert material of the housing comprises titanium or ceramic.

[0014] In some embodiments of the implantable medical device, the body comprises an integrated circuit electrically connected to the ultrasound transducer and the two or more electrodes, hi some embodiments, the integrated circuit comprises an energy storage circuit comprising a capacitor.

[0015] In some embodiments of the implantable medical device, the body is about 5 mm or less in length in its longest dimension.

[0016] In some embodiments of the implantable medical device, the ultrasound transducer is configured to emit ultrasound backscatter that encodes data, hi some embodiments, the data comprises information related to detected neural activity, measured physiological condition, device status, or emitted electrical pulses.

[0017] In some embodiments of the implantable medical device, the implantable medical device is configured to emit an electrical pulse to the nerve.

[0018] In some embodiments of the implantable medical device, the ultrasound transducer is configured to receive ultrasound that encodes instructions for operating the implantable device, hi some embodiments, the instructions comprise a trigger signal that operates the implantable device to emit an electrical pulse to the nerve.

[0019] Also described herein is a method of implanting a medical device in a subject, the device comprising: a body comprising an ultrasound transducer configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy that powers the device; an electrode in electrical communication with the ultrasound transducer; and a clip attached to the body, the clip comprising a plurality of flexible legs, the method comprising: (a) bending one or more legs of the clip outward; (b) placing the electrode in electrical communication with the nerve; and (c) releasing the one or more legs of the clip, where the one or more legs at least partially surround the nerve and maintain the electrode in electrical communication with the nerve upon release. In some embodiments, the plurality of legs at least partially surround the nerve and threadlike tissue attached to the nerve. In some embodiments, the threadlike tissue is a blood vessel. In some embodiments, the device is implanted laparoscopically in the subject. In some embodiments, the clip exerts an inward pressure on the nerve. In some embodiments, the clip allows for rotational movement around the nerve. In some embodiments, the legs exert a pressure of about 1 MPa or less on the nerve or threadlike tissue.

[0020] In some embodiments of the method of implanting a medical device in a subject, the nerve is an autonomic nerve. In some embodiments, the nerve is a sympathetic nerve. In some embodiments, the nerve is a mesenteric nerve, a splenic nerve, a sciatic nerve, a tibial nerve, a celiac ganglion, or a sacral nerve.

[0021] In some embodiments of the method of implanting a medical device in a subject, a plurality of legs extend below the body. In some embodiments, bending one or more legs of the clip outwardly comprises manipulating one or more hooks or loops connected to one or more legs. In some embodiments, the legs are curved. In some embodiments, the legs extend away from the body as the legs extend below the body before curving toward the body. In some embodiments, the plurality of flexible legs comprises at least one pair of legs, where the pair of legs comprises a first leg and a second leg that extend away and downward from the body in opposite directions. In some embodiments, the pair of legs are connected by a crossbar connected to the body. In some embodiments, the crossbar is connected to the body of the device via a flexible portion. In some embodiments, the flexible portion is a hinge. In some embodiments, the device includes two pairs of legs, where the device includes two pairs of legs, each of the legs of the pair being disposed on an opposite side of the body. In some embodiments, the legs are attached to the body via a bottom surface of the body. In some embodiments, the legs are attached to the body via a sidewall of the body. In some embodiments, the legs comprise a metal, a metal alloy, a ceramic, a silicon, or a non-polymeric material. In some embodiments, the legs comprise an elastomeric coating or a non-elastomeric polymer coating. In some embodiments, the coating is bioinert. In some embodiments, the coating is a silicon, a urethane polymer, a poly(p-xylylene) polymer, or a polyimide. In some embodiments, at least one of the legs comprises an outer surface coated with an elastomeric coating or a non-elastomeric polymer coating, and an inner surface comprising at least one electrode that is not coated with an elastomeric coating or a non-elastomeric polymer coating. In some embodiments, the body includes a bottom surface, and the two or more electrodes terminate at the bottom of the body. In some embodiments, the two or more electrodes are disposed on the clip. In some embodiments, the clip comprises a plurality of flexible legs extending below the body, and the two or more electrodes are disposed on the flexible legs.

[0022] In some embodiments of the method of implanting a medical device in a subject, the body comprises a housing. In some embodiments, the housing comprises a bioinert material. In some embodiments, the housing comprises a bioinert material, and the bioinert material of the housing comprises titanium or ceramic.

[0023] In some embodiments of the method of implanting a medical device in a subject, the body comprises an integrated circuit electrically connected to the ultrasound transducer and the two or more electrodes. In some embodiments, the integrated circuit comprises an energy storage circuit comprising a capacitor. In some embodiments, the body is about 5 mm or less in length along its longest dimension.

[0024] Further described herein is an implantable medical device comprising: (a) two or more ultrasound transducers configured to power the device and receive ultrasound waves that emit ultrasound backscatter; (b) an integrated circuit comprising an energy storage circuit comprising a capacitor, the integrated circuit electrically connected to a first ultrasound transducer and a second ultrasound transducer; and (c) one or more of: (i) a sensor configured to measure a physiological condition; (ii) two or more electrodes in electrical communication with tissue and configured to emit electrical pulses to the tissue; and (iii) two or more electrodes in electrical communication with tissue and configured to detect electrophysiological signals from the tissue, wherein the sensor or the two or more electrodes are electrically connected to the integrated circuit. In some embodiments, the two or more ultrasound transducers comprise a first ultrasound transducer having a first polarization axis and a second ultrasound transducer having a second polarization axis, where the second ultrasound transducer is positioned such that the second polarization axis is orthogonal to the first polarization axis, and the first ultrasound transducer and the second ultrasound transducer are configured to receive ultrasound waves that power the device and emit ultrasound backscatter.

[0025] In some embodiments, the implantable device comprises a sensor configured to measure a physiological condition, hi some embodiments, the sensor is a temperature sensor, a pH sensor, a pressure sensor, a strain sensor, a pulse sensor, a blood pressure sensor, an oximeter, a glucose meter, an impedance meter, or is configured to measure an analyte concentration.

[0026] In some embodiments, the implantable device comprises two or more electrodes in electrical communication with the tissue and configured to emit an electrical pulse to the tissue. In some embodiments, the implantable device comprises two or more electrodes in electrical communication with the tissue and configured to detect an electrophysiological signal from the tissue. In some embodiments, the electrophysiological signal is a neural signal. In some embodiments, the ultrasound backscatter encodes information related to the measured physiological condition, the emitted electrical pulse, or the detected electrophysiological signal.

[0027] In some embodiments, the first ultrasonic transducer and the second ultrasonic transducer are electrically connected in parallel to the integrated circuit. In some embodiments, the first ultrasonic transducer, the second ultrasonic transducer, and the integrated circuit are housed within the body, and the device further comprises a clip configured to at least partially encircle the threadlike tissue. In some embodiments, the threadlike tissue comprises a nerve. In some embodiments, the threadlike tissue comprises a nerve attached to a blood vessel. In some embodiments, the clip comprises a plurality of flexible legs extending below the body.

[0028] In some embodiments of any of the above-described implantable medical devices, the implantable medical device does not include a battery.

[0029] In some embodiments of any of the above-described implantable medical devices, the implantable medical device does not include a radio frequency communication system.

[0030] In some embodiments of any of the above-described implantable medical devices, the implantable medical device does not include electrical leads that extend from the body of the device without terminating in the legs of the clip.

[0031] Further herein, a system comprises any one of the implantable medical devices described above and an interrogator comprising one or more ultrasound transducers configured to transmit ultrasound to the implantable medical device, the ultrasound providing power to the implantable medical device. In some embodiments, the interrogator is configured to be externally worn. In some embodiments, the interrogator is configured to receive ultrasound backscatter emitted by the implantable device, where the ultrasound backscatter encodes data. In an embodiment, the interrogator is configured to analyze the data or transmit the data to a computer system. In some embodiments, the ultrasound transmitted by the interrogator encodes instructions for operating the implantable device.

[0032] Also described herein is a method of treating incontinence in a subject, comprising: converting energy from ultrasound into electrical energy that powers a device fully implanted in the subject that includes two or more electrodes in electrical communication with the subject's tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches; and electrically stimulating the subject's tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches using the fully implanted medical device. In some embodiments, the tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches is stimulated by the fully implanted medical device in response to an ultrasound-encoded trigger signal. In some embodiments, electrically stimulating the tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches comprises emitting a plurality of current pulses to the tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches. In some embodiments, electrically stimulating the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches comprises emitting a plurality of voltage pulses to the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches.

[0033] In some embodiments of treating incontinence in a subject, a plurality of current pulses or a plurality of voltage pulses are emitted at a constant frequency. In some embodiments, the frequency of the plurality of current pulses or the plurality of voltage pulses is between about 1 Hz and about 50 Hz. In some embodiments, the method comprises transmitting ultrasound waves to the implanted medical device using an interrogator comprising one or more ultrasound transducers. In some embodiments, the ultrasound waves encode instructions for operating the implantable device.

[0034] In some embodiments, the method comprises emitting ultrasound backscatter that encodes data. In some embodiments, the data comprises a stimulation state that indicates whether the implantable device emitted an electrical pulse or what parameters were used to emit the electrical pulse. In some embodiments, the method comprises receiving the ultrasound backscatter. In some embodiments, the method comprises analyzing the data encoded by the ultrasound backscatter.

[0035] In some embodiments for treating incontinence, the interrogator is an externally worn device. In some embodiments, the interrogator contacts the subject's skin. In some embodiments, the interrogator operates using a handheld device. In some embodiments, the handheld device is wirelessly connected to the interrogator.

[0036] In some embodiments of treating incontinence, the method comprises implanting a medical device in a subject to contact two or more electrodes with the tibial nerve or a branch thereof, the pudendal nerve or a branch thereof, or the sacral nerve or a branch thereof.

[0037] In some embodiments for treating incontinence, two or more electrodes are in electrical communication with the tibial nerve or its branches, hi some embodiments, an interrogator is attached to the subject's ankle.

[0038] In some embodiments for treating incontinence, two or more electrodes are in electrical communication with the sacral nerve or its branches, hi some embodiments, an interrogator is attached to the patient's hip, abdomen, lower back, buttocks, or upper extremity.

[0039] In some embodiments for treating incontinence, the incontinence is overactive bladder, underactive bladder, urinary incontinence, or fecal incontinence.

[0040] In some embodiments for treating incontinence, the subject is a human.

[0041] In some embodiments for treating incontinence, the implantable device is any one of the implantable medical devices described above. [Brief description of the drawings]

[0042] [Figure 1] 1 shows a side view of a body of an implantable device that includes an ultrasound transducer electrically connected to an integrated circuit that includes a power circuit having a capacitor, and further includes a bottom surface that includes a feedthrough that allows the integrated circuit to electrically connect to electrodes located elsewhere on the device.

[0043] [Diagram 2] A top view of the body of the implantable device, including an ultrasound transducer, an integrated circuit, and a capacitor, is shown.

[0044] [Diagram 3] 1 illustrates an exemplary implantable device that includes an ultrasound transducer, an integrated circuit, and a sensor that can be configured to measure a physiological condition.

[0045] [Figure 4] 1 shows an implantable device body including two orthogonally arranged ultrasound transducers, the body further including an integrated circuit having a power circuit including a capacitor.

[0046] [Diagram 5] 1 shows an exemplary implantable device having a body attached to a clip, the body including an ultrasound transducer and integrated circuit electrically connected to an electrode in electrical communication with a nerve, the clip holds the body against the nerve and holds the electrode in place for electrically stimulating or detecting electrophysiological pulses from the nerve.

[0047] [Figure 6]1 illustrates another example of an implantable device that includes a body having a housing that encloses an ultrasound transducer and an integrated circuit, the body attached to a clip that includes legs configured to at least partially surround a nerve and place an electrode in electrical communication with the nerve.

[0048] [Figure 7] FIG. 1 shows a side view of another embodiment of an implantable device having a body attached to a clip having multiple legs. The clip is attached to the body below a bottom surface of the body. The legs are coated with a coating (which may be an elastomeric coating or a non-elastomeric polymeric coating) on ​​the outer surfaces of the legs, but not on the inner surfaces of the legs. The electrodes are uncoated and are disposed on the inner surfaces of the legs.

[0049] [Figure 8A] , [Figure 8B] Two exemplary configurations of legs with electrodes disposed thereon are shown: in Fig. 8A, the leg includes a single electrode disposed along the inner surface of the leg; in Fig. 8B, the leg includes multiple electrodes that terminate at different locations along the inner surface of the leg.

[0050] [Figure 9A] 1 shows an embodiment of a leg having a hook at the end of the leg. [Figure 9B] 9B shows an embodiment of an implantable device having a hook proximal to the body of the device. The hook on the device in FIG. 9B is connected to a leg on the opposite side of the body, allowing the leg to bend outward by manipulating the hook.

[0051] [Figure 10] 1 illustrates an exemplary interrogator that may be used with an implantable device.

[0052] [Figure 11]1 shows an interrogator in communication with an implantable device, the interrogator capable of transmitting ultrasound that can encode a trigger signal, and the implantable device emitting ultrasound backscatter that can be modulated by the implantable device to encode information.

[0053] [Figure 12] 1 shows a schematic diagram of one embodiment of an implantable device showing an ultrasound transducer and electrodes electrically connected to an integrated circuit that includes a power circuit that includes a capacitor capable of storing electrical energy from the ultrasound transducer. The integrated circuit further includes a digital circuit or multi-signal integrated circuit that can operate the power circuit to modulate the current through the ultrasound transducer to encode information.

[0054] [Figure 13A] 1 shows an implantable device with the body fully implanted in a subject and a clip, where the clip attaches the implantable device to the tibial nerve. [Figure 13B] 1 shows an interrogator worn by a subject that can communicate with an implantable device in electrical communication with the tibial nerve.

[0055] [Figure 14] 1 shows a system including an implantable device clipped to the sacral nerve and an interrogator used for sacral nerve stimulation (SNS). The implantable device includes a body having an ultrasound transducer, electrodes, and a clip. The interrogator is optionally controlled by a mobile device such as a smartphone or tablet. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0056] Described herein is a miniature implantable device capable of detecting electrophysiological signals or physiological conditions or emitting electrical pulses to nerves. The implantable device is powered by ultrasound emitted to an external interrogator, which is received by an ultrasound transducer on the implantable device and converted to electrical energy. The ultrasound emitted to the interrogator can further encode instructions for operating the implantable device, which are received by the ultrasound transducer on the implantable device. The ultrasound transmitted by the external transducer can encode, for example, a trigger signal that can signal the implantable device to emit an electrical pulse. In some embodiments, the implantable device emits ultrasonic backscatter waves, which may be received by the interrogator or other external ultrasound receiver. The ultrasonic backscatter waves can encode data, such as data related to electrical pulses (e.g., neural activity) detected by the implantable device, information related to a measured physiological condition, an emitted electrical pulse, or information related to the status of the implantable medical device.

[0057] The implantable device may include electrodes for stimulating the nerve or for detecting neural activity. Because the implantable device may be implanted in a mobile patient, it is necessary to ensure that the electrodes of the implantable device remain in electrical communication with the target nerve, since the patient's movements may cause internal tissue to move. As described further herein, the implantable device may include two or more electrodes that may be configured to detect electrophysiological signals or emit electrical pulses, and a clip configured to at least partially surround the nerve and place the two or more electrodes in electrical communication with the nerve. At some locations on the body, the target nerve may be attached to another thread-like tissue, such as a blood vessel. Thus, in some embodiments, the clip may be configured to at least partially surround the thread-like tissue or blood vessel. By using a clip to place and fasten the electrodes in place, there is no need to suture the implantable device to tissue, which facilitates implantation and avoids surrounding tissue damage. For example, the implantable device may be immediately implanted laparoscopically, while ensuring that the electrodes are in the correct position during use.

[0058] Because the implantable device may move relative to the external interrogator, for example due to movement of the target nerve or repositioning of the external interrogator, an implantable device having a single ultrasound transducer may have a weakened connection to the interrogator if the polarization axis of the ultrasound transducer of the implantable device is no longer aligned with the polarization axis of one or more ultrasound transducers of the interrogator. Thus, as described further herein, an implantable device may include two or more ultrasound transducers with non-parallel polarization axes. For example, in some embodiments, there is an implantable device having a first ultrasound transducer with a first polarization axis and a second ultrasound transducer with a second polarization axis, where the second ultrasound transducer is positioned such that the second polarization axis is orthogonal to the first polarization axis. In this configuration, ultrasound emitted by the external transducer may be received by the implantable device positioned at a different orientation to allow for continuous powering of the implantable device.

[0059] The implantable devices described herein may be used to stimulate nerves to treat medical conditions. Because the implantable devices are small, they can be implanted in a subject with limited invasiveness. Furthermore, the implantable devices can target nerves that are not practically targeted by larger devices and without externally connected body-implanted leads. For example, the implantable devices may be used to treat incontinence in a subject by electrically stimulating the tibial nerve, pudendal nerve, or sacral nerve or their branches, for example, using a fully implanted medical device described herein.

[0060] [Definition] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0061] As used herein, reference to "about" or "approximately" a value or parameter includes (and describes) a variation directed to the value or parameter itself. For example, a description referring to "about X" includes the description of "X."

[0062] It will be understood that aspects and variations of the invention described herein include those that "consist of" and / or "consist essentially of".

[0063] As used herein, the terms "subject" and "patient" are used interchangeably to refer to a vertebrate.

[0064] As used herein, the terms "treat," "treating," and "treatment" refer interchangeably to any act that provides a benefit to a subject suffering from a medical condition or disorder, including amelioration of the disorder through the alleviation, inhibition, suppression, or elimination of at least one symptom, slowing the progression of a disease or disorder, slowing the recurrence of a disease or disorder, or inhibiting a disease or disorder.

[0065] When a range of values ​​is provided, it is to be understood that each intervening value between the upper and lower limit of that range, and any other stated or intervening value in that stated range, is encompassed within the scope of the disclosure. Where a stated range includes an upper or lower limit, ranges excluding either of those limits are also included in the disclosure.

[0066] It should be understood that one, some, or all of the features of the various embodiments described herein may be combined to form other embodiments of the present invention. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0067] The features and preferences described above in connection with the "embodiments" are separate preferences and are not limited to that particular embodiment, but may be freely combined with features from other embodiments where technically feasible to form preferred combinations of features. This description is presented to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a patent application and its requirements. Various modifications to the described embodiments will be readily apparent to those skilled in the art, and the generic principles herein may be applied to other embodiments. Thus, the present invention is not intended to be limited to the embodiments shown, but is to be accorded the widest scope consistent with the principles and features described herein.

[0068] [Implantable devices] The implantable device includes a body housing one or more ultrasound transducers and an integrated circuit for operating the device. The ultrasound transducer receives ultrasound waves and converts the received ultrasound waves into electrical energy that powers the device. The body of the device may include or be connected to two or more electrodes or sensors in electrical communication with the ultrasound transducer (e.g., via an integrated circuit). In some embodiments, the current through the ultrasound transducer may be modulated to encode information into the ultrasound backscattered waves emitted by the ultrasound transducer. The information encoded into the ultrasound backscattered waves may include, for example, information related to a physiological condition detected by the sensor, an electrophysiological signal detected by the electrode, a state of the device (e.g., a state confirming that the device is receiving an ultrasound encoded signal, a state confirming operation of the integrated circuit, or a state confirming that the device is powered), or an electrical pulse emitted by the implantable device. In some embodiments, the implantable device includes a clip attached to the body configured to at least partially surround a nerve and position two or more electrodes in electrical communication with the nerve. In some embodiments, the implantable device comprises a first ultrasound transducer having a first polarization axis and a second ultrasound transducer having a second polarization axis, where the second ultrasound transducer is positioned such that the second polarization axis is orthogonal to the first polarization axis, and the first ultrasound transducer and the second ultrasound transducer are configured to receive ultrasound that powers the device and emits ultrasound backscatter.

[0069] In some embodiments, the implantable device is implanted in a subject. The subject can be, for example, a mammal. In some embodiments, the subject is a human, dog, cat, horse, cow, pig, sheep, goat, monkey, or rodent (such as a rat or mouse).

[0070] [Body of implantable device] The body of the implantable device includes one or more ultrasound transducers and a sensor and / or electrode pair. The electrode pair can be configured to detect an electrophysiological signal from an electrical pulse or to emit an electrical pulse. An exemplary implantable device capable of detecting an electrophysiological signal and encoding information related to the detected electrophysiological signal is described in WO 2018 / 009910 A2. An exemplary implantable device capable of operating using ultrasound to emit an electrical pulse is described in WO 2018 / 009912 A2. The sensor may be, for example, a sensor capable of detecting or measuring a physiological condition (such as a temperature sensor, an oxygen sensor, a pH sensor, a strain sensor, a pressure sensor, an impedance sensor, or a sensor capable of detecting a concentration of an analyte). Exemplary implantable devices powered by ultrasound and capable of emitting ultrasound backscatter encoding a detected physiological condition are described in WO 2018 / 009905 A2 and WO 2018 / 009911 A2. In some embodiments, the implantable device includes both a sensor and an electrode pair. In some embodiments, an integrated circuit is included in the implantable device, which is electrically connected and capable of communicating between the electrodes or sensors and the ultrasound transducers. The integrated circuit can include a modulation circuit that modulates a current through one or more ultrasound transducers to encode data in the current. The modulated current affects the ultrasound backscatter waves emitted by the ultrasound transducers, which encode data.

[0071] FIG. 1 shows a side view of an exemplary implantable device body with an ultrasonic transducer 102 and an integrated circuit 104. In the illustrated embodiment, the integrated circuit 104 includes a power circuit including a capacitor 106. The capacitor can temporarily store electrical energy converted from ultrasonic energy by the ultrasonic transducer and can be operated by the integrated circuit 104 to store or release the energy. The ultrasonic transducer 102, the integrated circuit 104, and the capacitor 106 are mounted on a back plate 108, which may be a printed circuit board. The base 108 is set within a housing including a bottom surface 110 and side walls 112a and 112b. The housing may further include a top (not shown) that seals the body components within the housing. The bottom surface 110 may include one or more feedthroughs 114a, 114b, and 114c that electrically connect the back plate and / or the integrated circuit to one or more electrodes. The one or more electrodes may be located, for example, below the bottom surface 110 of the housing or may be located on a clip as described herein. In this configuration, the electrode can be in electrical communication with the nerve and the body components are positioned over the nerve when the implantable device is implanted and attached to the nerve, for example, using a clip as described herein. The ultrasonic transducer 102 is electrically connected to the integrated circuit 104, which is electrically connected to the electrode via a feedthrough, thereby electrically connecting the ultrasonic transducer 102 to the electrode.

[0072] Figure 2 illustrates a top view of a body similar to that shown in Figure 1, again without the top of the housing. Although the housing is shown with four side walls 112a, 112b, 112c, and 112d, it will be understood that the housing can be of any suitable shape (e.g., having three, four, five, six, or more side walls, or having a single curved side wall that is circular or oval).

[0073] 3 illustrates a schematic diagram of an exemplary implantable device having an ultrasonic transducer 302, an integrated circuit 304, and a sensor 306 (such as a sensor that can detect temperature, pressure, strain, analyte concentration, oxygen, or pH). The ultrasonic transducer 302 is electrically connected to the integrated circuit 304, which is electrically connected to the sensor 306. While the illustrated embodiment is shown with an integrated circuit, it is also envisioned that the sensor may be directly connected to the ultrasonic transducer. Additionally, as described herein, one or more sensors may be included on the implantable device that further has electrodes configured to detect and / or emit electrical pulses.

[0074] The ultrasonic transducer is configured to receive ultrasonic waves and convert energy from the ultrasonic waves into electrical energy. The electrical energy is sent to the integrated circuit to power the device. The implantable device may also be operable to receive or send data via ultrasound. Ultrasound received by the implantable device (e.g., sent by an interrogator) may encode instructions for operating the implantable device. The instructions may include, for example, a trigger signal that instructs the implantable device to emit an electrical pulse through the electrodes. The trigger signal may include, for example, information regarding when the electrical pulse should be emitted, the pulse frequency, the pulse power or voltage, the pulse shape, and / or the pulse duration.

[0075] The implantable device can also operate to transmit data that can be received by the interrogator. An ultrasound transducer on the implantable device can receive ultrasound waves and emit ultrasound backscatter, which can encode data to be transmitted by the implantable device. An electrical current flows through the ultrasound transducer and can be modulated to encode data. The current can be directly modulated, for example, by passing the current through a sensor that modulates the current, or indirectly modulated, for example, by modulating the current using a modulation circuit based on a detected physiological condition or electrophysiological pulse. In some embodiments, the data encoded in the ultrasound includes data that is not related to the detected physiological condition or electrophysiological pulse detected by the implantable device. For example, the data can include information related to the status of the implantable device or a confirmation signal confirming that an electrical pulse was emitted, and optionally the power, frequency, voltage, duration, or other information related to the emitted electrical pulse.

[0076] In some embodiments, the body includes a housing, which may include a base, one or more sidewalls, and a top. The housing may enclose one or more ultrasound transducers and an integrated circuit. The housing may be hermetically sealed (e.g., by soldering or laser welding) to prevent interstitial fluid from contacting the ultrasound transducer and / or the integrated circuit. The electrodes configured to electrically communicate with the nerve are not enclosed by the housing. The housing is preferably made from a bioinert material, such as a bioinert metal (e.g., steel or titanium) or a bioinert ceramic (e.g., titania or alumina). The housing (or the top of the housing) may be thin to allow ultrasound waves to penetrate the housing. In some embodiments, the housing is about 100 μm or less thick, such as about 75 micrometers (μm) or less, about 50 μm or less, about 25 μm or less, or about 10 μm or less. In some embodiments, the housing has a thickness of about 5 μm to about 10 μm, about 10 μm to about 25 μm, about 25 μm to about 50 μm, about 50 μm to about 75 μm, or about 75 μm to about 100 μm.

[0077] In some embodiments, the body includes a material, such as a polymer, within the housing that can fill the empty space within the housing to reduce the acoustic impedance mismatch between the tissue outside the housing and the tissue within the housing. Thus, the body of the device is preferably air-free or evacuated.

[0078] The body of the implantable device is relatively small, which allows for comfortable and long-term implantation while limiting the tissue inflammation often associated with implantable devices. In some embodiments, the longest dimension of the body of the device is about 5 mm or less, about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1 mm or less, about 0.5 mm or less, about 0.3 mm or less, about 0.1 mm or less in length. In some embodiments, the longest dimension of the body of the device is about 0.05 mm or more, about 0.1 mm or more, about 0.3 mm or more, about 0.5 mm or more, about 1 mm or more, about 2 mm or more, or about 3 mm or more in length of the device. In some embodiments, the longest dimension of the body of the device is about 0.04 mm to about 5 mm in length, about 0.05 mm to about 4 mm in length, about 0.07 mm to about 3 mm in length, about 0.08 mm to about 3 mm in length, or about 1 mm to about 2 mm in length.

[0079] In some embodiments, the body of the implantable device is approximately 4 mm 3 Below, 3mm 3 Below, 2mm 3 Less than or equal to 1mm 3 (e.g., below) approx. 5 mm 3 In one embodiment, the body of the implantable device has a volume of about 0.5 mm 3 ~about 5mm 3 , about 1mm 3 ~about 5mm 3 , about 2 mm 3 ~about 5mm 3 , about 3mm 3 ~about 5mm 3 , or about 4 mm 3 ~about 5mm 3The small size of the implantable device allows for laparoscopic implantation of the device, thereby minimizing tissue trauma when the device is implanted.

[0080] The implantable device includes one or more ultrasound transducers, such as one, two, or more than two ultrasound transducers. In some embodiments, the implantable device includes a first ultrasound transducer having a first polarization axis and a second ultrasound transducer having a second polarization axis, where the second ultrasound transducer is positioned such that the second polarization axis is orthogonal to the first polarization axis, and the first ultrasound transducer and the second ultrasound transducer are configured to receive ultrasound waves that power the device and emit ultrasound backscatter. In some embodiments, an implantable medical device includes a first ultrasonic transducer having a first polarization axis, a second ultrasonic transducer having a second polarization axis, and a third ultrasonic transducer having a third polarization axis, the second ultrasonic transducer positioned such that the second polarization axis is orthogonal to the first and third polarization axes, and the third ultrasonic transducer positioned such that the third polarization axis is orthogonal to the first and second polarization axes, and the first and second ultrasonic transducers are configured to receive ultrasonic waves that power the device and emit ultrasonic backscatter. An implantable device having one, two, or more than two ultrasonic transducers may further include a sensor or two or more electrodes configured to electrically communicate with tissue, such as a nerve. Optionally, the implantable device further includes an integrated circuit.

[0081] FIG. 4 shows a body of a device including two orthogonally arranged ultrasonic transducers. The body includes a back plate 402, such as a printed circuit board, and an integrated circuit 404, which is a power circuit including a capacitor 406. The body further includes a first ultrasonic transducer 408 electrically connected to the integrated circuit 404, and a second ultrasonic transducer 410 electrically connected to the integrated circuit 404. The first ultrasonic transducer 408 includes a first polarization axis 412, and the second ultrasonic transducer 410 includes a second polarization axis 414. The first ultrasonic transducer 408 and the second ultrasonic transducer are arranged such that the first polarization axis 412 is orthogonal to the second polarization axis 414. A housing (not shown) surrounds the body components and can optionally be occluded. Additionally, the integrated circuit can be electrically coupled to a sensor or an electrode.

[0082] The ultrasound transducer of the implantable device may be a micromachined ultrasound transducer, such as a capacitive micromachined ultrasound transducer (CMUT) or a piezoelectric micromachined ultrasound transducer (PMUT), or may be a bulk piezoelectric transducer. Bulk piezoelectric transducers may be any natural or synthetic material, such as crystal, ceramic, or polymer. Exemplary bulk piezoelectric transducer data include barium titanate (BaTiO3), lead zirconate titanate (PZT), zinc oxide (ZO), aluminum nitride (AlN), quartz, berlinite (AlPO4), topaz, langasite (La3Ga5SiO4), and other materials. 14 ), gallium orthophosphate (GaPO4), lithium niobate (LiNbO3), lithium tantalate (LiTaO3), potassium niobate (KNbO3), sodium tungstate (Na2Wo3), bismuth ferrite (BiFeO3), polyvinylidene fluoride (PVDF), and lead magnesium niobate-lead titanate (PMN-PT).

[0083] In some embodiments, the bulk piezoelectric transducer is approximately cubic (i.e., an aspect ratio of about 1:1:1 (length:width:height)). In some embodiments, the piezoelectric transducer is plate-like with an aspect ratio of about 5:5:1 or greater, such as about 7:5:1 or greater, or about 10:10:1 or greater, in either the length or width aspect. In some embodiments, the bulk piezoelectric transducer is long and narrow with an aspect ratio of about 3:1:1 or greater, with its longest dimension aligned with the direction of the ultrasonic backscattered waves (i.e., polarization axis). In some embodiments, one dimension of the bulk piezoelectric transducer is equal to ½ of a wavelength (λ) corresponding to the drive frequency or resonant frequency of the transducer. At this resonant frequency, ultrasonic waves impinging on either face of the transducer will undergo a 180° phase shift to reach an antiphase, causing maximum displacement between the two faces. In some embodiments, the height of the piezoelectric transducer is about 10 μm to about 1000 μm (such as about 40 μm to about 400 μm, about 100 μm to about 250 μm, about 250 μm to about 500 μm, or about 500 μm to about 1000 μm). In some embodiments, the height of the piezoelectric transducer is about 5 mm or less (such as about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1 mm or less, about 500 μm or less, about 400 μm or less, 250 μm or less, about 100 μm or less, or about 40 μm or less). In some embodiments, the height of the piezoelectric transducer is about 20 μm or more in length (such as about 40 μm or more, about 100 μm or more, about 250 μm or more, about 400 μm or more, about 500 μm or more, about 1 mm or more, about 2 mm or more, about 3 mm or more, or about 4 mm or more).

[0084] In some embodiments, the ultrasonic transducer has a length of about 5 mm or less in its longest dimension (such as about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1 mm or less, about 500 μm or less, about 400 μm or less, 250 μm or less, about 100 μm or less, or about 40 μm or less). In some embodiments, the ultrasonic transducer has a length of about 20 μm or more in its longest dimension (such as about 40 μm or more, about 100 μm or more, about 250 μm or more, about 400 μm or more, about 500 μm or more, about 1 mm or more, about 2 mm or more, about 3 mm or more, or about 4 mm or more).

[0085] The ultrasonic transducer is connected with two electrodes to enable electrical communication with the integrated circuit. A first electrode is attached to a first surface of the transducer and a second electrode is attached to a second surface of the transducer, where the first surface and the second surface are opposite sides of the transducer along one dimension. In some embodiments, the electrodes include silver, gold, platinum, platinum black, poly(3,4-ethylenedioxythiophene (PEDOT)), a conductive polymer (such as conductive PDMS or polyimide), or nickel. In some embodiments, the axis between the electrodes of the transducer is perpendicular to the motion of the transducer.

[0086] In some embodiments, the implantable device includes two or more electrodes in electrical communication with tissue, such as a nerve. The implantable device can include, for example, a clip as described herein to position and secure the electrodes in electrical communication with the nerve. In some embodiments, the electrical pulse emitted by the implantable device stimulates an action potential in the tissue. In some embodiments, the electrical pulse emitted by the implantable device blocks an action potential in the tissue.

[0087] In some embodiments, the implantable device comprises a plurality of electrodes. In some embodiments, the electrodes are paired. An electrode pair may be formed from two electrodes, so an implantable device having three electrodes may have three electrode pairs. An electrophysiological signal may be detected between the electrodes in the electrode pair, or tissue may be stimulated using any of the electrode pairs. In some embodiments, the implantable device comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more, or 15 or more electrode pairs. In some embodiments, the implantable device comprises 2, 3, 5, 6, 7, 8, 9, 10 or more electrodes. In some embodiments, the implantable device comprises a multiplexer that can select an electrode in the electrode pair to emit an electrical pulse or select an electrode pair to detect an electrical pulse.

[0088] Two or more electrodes electrically connected to a nerve or tissue need not be arranged linearly along the tissue. For example, an electrode may engage a nerve or other tissue along a transverse axis relative to the nerve, which can emit a pulse in a transverse direction. Two or more electrodes can engage a nerve or other tissue at any angle along the transverse axis, such as diametrically opposed (i.e., 180°), or less than 180° (e.g., about 170° or less, about 160° or less, about 150° or less, about 140° or less, about 130° or less, about 120° or less, about 110° or less, about 100° or less, about 90° or less, about 80° or less, about 70° or less, about 60° or less, about 50° or less, about 40° or less, or about 30° or less).

[0089] In some embodiments, the electrodes of an electrode pair are separated by about 5 mm or less (such as about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1.5 mm or less, about 1 mm or less, or about 0.5 mm or less). In some embodiments, the electrodes of an electrode pair are separated by about 0.5 mm or more (such as about 1 mm or more, about 1.5 mm or more, about 2 mm or more, about 3 mm or more, or about 4 mm or more). In some embodiments, the electrodes are separated by about 0.5 mm to about 1 mm, about 1 mm to about 1.5 mm, about 1.5 mm to about 2 mm, about 2 mm to about 3 mm, about 3 mm to about 4 mm, or about 4 mm to about 5 mm.

[0090] The electrodes are electrically coupled to an integrated circuit within the body of the implantable device. In some embodiments, the electrodes are disposed or terminate beneath the body, e.g., on a face of the base of the body housing opposite the body components (e.g., ultrasound transducer, integrated circuit, etc.). In some embodiments, the electrodes terminate along the legs of the clip, as described in more detail herein. In some embodiments, one or more electrodes are exposed along at least a portion of one of the legs.

[0091] The electrodes may be electrically coupled to the integrated circuit through one or more feedthroughs in the base of the housing, which may be, for example, metal (such as metals including silver, copper, gold, platinum, platinum black, or nickel), sapphire, or a conductive ceramic (e.g., indium tin oxide (ITO)). The electrodes may be connected to the feedthroughs using any suitable means, such as soldering, laser welding, or crimping the feedthroughs to the electrodes.

[0092] In some embodiments, the implantable device includes one or more sensors. The sensors are configured to detect a physiological condition, such as temperature, oxygen concentration, pH, an analyte (such as glucose), strain, or pressure. Variations in the physiological condition modulate the impedance, which in turn modulates the current through an ultrasound transducer on the implantable device. As described above, the ultrasound transducer generates ultrasound backscatter that is detected by an interrogator, and changes in the ultrasound backscatter reflect information about the physiological condition. In some embodiments, the system is configured to detect changes in the physiological system. In some embodiments, the system is configured to detect a value or an approximate value of the physiological condition, for example, by calibrating the ultrasound backscatter to a known value. The implantable device may include one or more sensors (e.g., 2, 3, 4, 5, or more), which may detect the same or different physiological conditions. In some embodiments, the implantable device includes 10, 9, 8, 7, 6, or 5 or fewer sensors. For example, in some embodiments, the implantable device includes a first sensor configured to detect temperature and a second sensor configured to detect oxygen. Changes in both physiological conditions can be encoded in the ultrasound backscattered waves, which can be decoded by an external computing system.

[0093] The integrated circuit communicates between the ultrasonic transducer and the sensor and / or electrode. For example, the ultrasonic transducer can receive information encoded in the ultrasonic waves and generate a current encoding the information, which is transmitted to the integrated circuit. The information encoded in the current can include instructions for operating the electrodes and / or sensor, and the integrated circuit can operate the electrodes and / or sensor according to the instructions. The integrated circuit can also receive signals from the sensor and / or electrode, and can modulate the current flowing through the ultrasonic transducer to encode information related to the signals received from the sensor and electrode.

[0094] In some embodiments, the implantable device emits ultrasound backscatter that encodes information. The ultrasound backscatter may be received by an interrogator and decoded, for example, to determine the encoded information. The information may be encoded using a modulation circuit within an integrated circuit of the implantable device. The modulation circuit may modulate a current flowing through the ultrasound transducer to encode information (e.g., information related to a detected electrophysiological pulse or physiological condition, or information related to a device status). The modulated current flows through the ultrasound transducer to modulate the ultrasound backscatter, thereby encoding information in the ultrasound backscattered wave. The modulation circuit includes one or more switches, such as an on / off switch or a field effect transistor (FET). An exemplary FET that may be used with some embodiments of the implantable device is a metal-oxide-semiconductor field effect transistor (MOSFET). The modulation circuit may change the impedance of the current flowing through the ultrasound transducer, and the variation in the current flowing through the transducer encodes the electrophysiological signal. In some embodiments, the information encoded in the ultrasound backscatter includes a unique identifier for the implantable device. This may be useful, for example, to ensure that the interrogator contacts the correct implantable device when multiple implantable devices are implanted in a subject. In some embodiments, the information encoded in the ultrasound backscatter includes a verification signal that verifies the electrical pulse emitted by the implantable device. In some embodiments, the information encoded in the ultrasound backscatter includes the amount of energy or voltage stored in the energy storage circuit (or one or more capacitors in the energy storage circuit). In some embodiments, the information encoded in the ultrasound backscatter includes the detected impedance. Changes in impedance measurements can identify scar tissue or deterioration of the electrodes over time.

[0095] In some embodiments, the modulation circuitry can be operated by a digital circuit or mixed signal integrated circuit to actively encode information in a digitized or analog signal. The digital circuit or mixed signal integrated circuit may include memory and one or more circuit blocks, systems, or processors for operating the implantable device. These systems can include, for example, an on-board microcontroller or processor, a finite state machine implementation, or a digital circuit capable of executing one or more programs stored on the implant or provided via ultrasound communication between the interrogator and the implantable device. In some embodiments, the digital circuit or mixed signal integrated circuit includes an analog-to-digital converter (ADC), which can convert an analog signal encoded in ultrasound emitted from the interrogator so that the signal can be processed by the digital circuit or mixed signal integrated circuit. The digital circuit or mixed signal integrated circuit can also operate the power circuitry to generate an electrical pulse, for example to stimulate tissue. In some embodiments, the digital circuit or mixed signal integrated circuit operates the power circuitry to receive a trigger signal encoded in ultrasound transmitted by the interrogator and discharge an electrical pulse in response to the trigger signal.

[0096] In some embodiments, the integrated circuit includes a power circuit that can include an energy storage circuit. The ultrasound-powered implantable device is preferably battery-free, but the energy storage circuit can include one or more capacitors to temporarily store electrical energy. Energy from the ultrasound is converted to electrical current in the ultrasound transducer and can be stored in the energy storage circuit. This energy can be used to operate the implantable device, such as to power digital circuits, modulation circuits, or one or more amplifiers, or can be used to generate electrical pulses used to stimulate tissue. In some embodiments, the power circuit further includes, for example, a rectifier and / or a charge pump.

[0097] In some embodiments, the integrated circuit includes a driver circuit that provides current to one or more sensors and / or electrodes. Optionally, the driver circuit, if present, is operated by a digital circuit or a mixed signal integrated circuit. In some embodiments, one or more amplifiers are arranged between the driver circuit and the digital circuit. In some embodiments, the integrated circuit includes a front-end circuit (such as a CMOS front-end) that can receive signals from the sensors and / or electrodes. Signals received at the front-end circuit can be relayed to the digital circuit.

[0098] FIG. 12 shows a schematic diagram of an embodiment of an implantable device including an integrated circuit and an electrode configured to emit an electrical pulse. The implantable device includes an ultrasonic transducer, a power circuit including an energy storage circuit (which may include one or more capacitors ("CAPs")), a digital circuit or multi-signal integrated circuit, and a pair of electrodes. The ultrasonic transducer is connected to the power circuit, which allows energy from the ultrasonic waves to be stored in the energy storage circuit. The power circuit is connected to the digital circuit or multi-signal integrated circuit such that the digital circuit or multi-signal integrated circuit can operate the power circuit. The digital circuit or multi-signal integrated circuit is also connected to the ultrasonic transducer. When a trigger signal is encoded in the ultrasonic waves received by the ultrasonic transducer, the digital circuit or multi-signal integrated circuit can detect the trigger signal. The digital circuit or multi-signal integrated circuit can then operate the power circuit to release the energy stored in the energy circuit, thereby emitting an electrical pulse using the electrode. Optionally, the digital circuit or multi-signal integrated circuit can operate or include a modulation circuit that can modulate the current flowing through the ultrasonic transducer to encode information, such as information related to the operation of the implantable device or information related to the electrical pulse detected by the electrode.

[0099] [Clip for embeddable devices] In some embodiments, the implantable medical device comprises a clip attached to the body configured to at least partially surround a nerve to place two or more electrodes in electrical communication with the nerve. Some nerves in the body may be attached to adjacent thread-like tissue (e.g., blood vessels or tendons), and the clip may be configured to at least partially surround the nerve and thread-like tissue.

[0100] The clip holds the implantable device in place on the nerve and / or threadlike tissue. In some embodiments, the clip allows some rotational movement of the implantable device on the nerve and / or threadlike tissue. In some embodiments, the clip grips the nerve and / or threadlike tissue by exerting an inward pressure on the nerve and / or threadlike tissue. The amount of inward pressure exerted by the clip can be determined based on the size and curvature of the clip as well as the spring constant of the clip legs. This inward pressure should be sufficient to hold the implantable device in place while the tissue heals after insertion, but not so high that the epineurium or blood vessel wall contacting the legs is damaged. In some embodiments, the inward pressure on the nerve or threadlike tissue is about 1 MPa or less (such as about 0.7 MPa or less, about 0.5 MPa or less, or about 0.3 MPa or less). In some embodiments, the inward pressure on the nerve or thread tissue is from about 0.1 MPa to about 1 MPa (such as from about 0.1 MPa to about 0.3 MPa, from about 0.3 MPa to about 0.5 MPa, from about 0.5 MPa to about 0.7 MPa, or from about 0.7 MPa to about 1 MPa).

[0101] In some embodiments, an implantable medical device includes a body with an ultrasound transducer configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy that powers the device, two or more electrodes in electrical communication with the ultrasound transducer, and a clip attached to the body configured to at least partially surround a nerve (or the nerve and thread-like tissue, such as a blood vessel attached to the nerve) and position the two or more electrodes in electrical communication with the nerve.

[0102] The clip can include a plurality of flexible legs that extend below the body of the implantable device. In some embodiments, the legs are curved. For example, in some embodiments, the legs extend away from the body as the legs extend below the body before curving toward the body. The clip can include a pair of legs, each leg of the pair extending in an opposite direction away from the body. This configuration allows the legs to wrap around the nerve and / or threadlike tissue (or at least partially wrap around the nerve and / or threadlike tissue). The legs of the pair of legs can be connected by a crossbar that allows the legs to be arranged in a staggered configuration, with one leg of the pair being arranged closer to the body than the other leg. By staggering the legs at different distances from the body of the device, the legs can extend such that the ends of the legs extend past each other to completely surround the nerve and / or threadlike tissue. In some embodiments, the legs and crossbar of a pair of legs are a single piece (e.g., co-extruded or co-printed) of material, such as metal, metal alloy, ceramic, silicon, or non-polymeric material. The legs or crossbar of the device are connected to the body of the device. When an implantable device includes two pairs of legs each connected by a crossbar, the crossbars may be attached to the body at opposite ends of the body. The ends of the crossbars attached to the body may be along the same axis, which may be parallel to the axis of the nerve and / or thread-like tissue.

[0103] In some embodiments, the legs or crossbars of the implantable device are connected to the body of the device via flexible sections, such as hinges (which may be spring hinges). The flexibility of the legs and flexible sections allows the implantable device to be manipulated to a predetermined position on the nerve by bending the legs of the clip, which can return to their default position to precisely place the electrodes of the device in electrical communication with the nerve.

[0104] 5 shows an example of an implantable device with a clip. The implantable device includes a body 502 that includes an ultrasonic transducer 504 and an integrated circuit 506. The ultrasonic transducer 504 can receive ultrasonic waves from an interrogator, and the ultrasonic transducer converts energy from the ultrasonic waves into electrical energy that powers the device. The ultrasonic transducer 504 is electrically connected to the integrated circuit 506, which can encode data in a current that flows through the ultrasonic transducer 504. The ultrasonic transducer 504 emits ultrasonic backscatter based on the received current, which encodes the data encoded in the current.

[0105] The implantable device includes two or more electrodes in electrical communication with the ultrasound transducer 504, for example through an integrated circuit 506. In some configurations, the electrodes are configured to emit electrical pulses to the nerve, for example by being operated by the integrated circuit 506. Optionally, electrophysiological pulses are detected by the electrodes and communicated to the integrated circuit 506, which can adjust the current flowing through the ultrasound transducer 504 based on the detected electrophysiological pulses. The body 502 of the implantable device is attached to a clip 508. The clip is configured to surround a nerve 510 and position the two or more electrodes in electrical communication with the nerve. In the embodiment illustrated in FIG. 5, the electrodes are positioned along the bottom of the body 502 in contact with the nerve 510. In some embodiments, the two or more electrodes are in physical contact with the nerve, although some movement of the implantable device may be tolerated as long as the electrodes remain in electrical communication with the nerve. The electrodes do not need to penetrate the epineurium of the nerve.

[0106] The clip includes a first leg 512 and a second leg 514 disposed on opposite sides of the nerve 510. The legs of the clip are optionally flexible so that they can bend outward to place the clip over the nerve. When the legs are released, they spring back inward, maintaining the electrode in electrical communication with the nerve. The size and spacing of the legs can be set depending on the size of the nerve. In the embodiment illustrated in FIG. 5, the legs 514 have a width that is approximately the same length as the body 502. The legs 514 include a first segment 516 that extends from the body along the side of the nerve 510 down to the nerve 510, and a second segment 518 that extends from the bottom of the first portion down to the nerve 510. A flexible section 520 (such as a hinge, which may be a spring hinge) joins the first segment 516 and the second segment 518, which allows the second segment 518 to bend toward the first segment 516 when the implantable device is placed on the nerve. The end of the second segment 518 is released and the second segment 518 springs back into position below the nerve 510. Optionally, a second flexible section 522 (which may be a hinge, which may be a spring hinge, for example) attaches the legs 508 to the body 502. The second flexible section 522 allows the legs 514 to bend outward when the implantable device is placed on the nerve 510.

[0107] 6 illustrates another example of an implantable device including a body 602 and a clip configured to at least partially surround a nerve, the clip comprising multiple flexible legs 604, 606, 608, and 610. The body 602 includes a housing and houses an ultrasound transducer configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy that powers the implantable device. The implantable device further includes multiple electrodes disposed on a bottom of the body housing. The electrodes are in electrical communication with the ultrasound transducer, for example, via an integrated circuit contained within the body 602 of the implantable device. The electrodes are disposed in electrical communication with the nerve when the clip is placed over the nerve to at least partially surround the nerve.

[0108] The legs 604, 606, 608, and 610 of the implantable device extend below the body 602 and are curved, which allows the legs to wrap around nerves and thread-like tissues (e.g., blood vessels) that may be attached to the nerves. The tops of the legs extend away from the body 602 and curve back toward the body 602 as they extend below the body. The clip illustrated in FIG. 6 includes a first pair of legs 604 and 606 and a second pair of legs 608 and 610. The paired legs extend in opposite directions away from the body. The tops of the legs 604 and 606 are connected by a crossbar 612 and the tops of the legs 608 and 610 are connected by a crossbar 614. The crossbar 612 is connected to the body 602 via a flexible section 616, and the crossbar 614 is connected to the body 602 via a second flexible section (not shown). The flexible portion may be, for example, a hinge (which may be a spring hinge). The crossbars are connected to opposite sides of the body 602 and are oriented in the same direction (i.e., parallel to the nerve) from end to end.

[0109] The size and shape of the clip may depend on the type and size of tissue that is to be engaged by the clip. The clip is designed to allow the legs of the clip to at least partially surround a threadlike tissue such as a nerve or blood vessel. In some embodiments, the inner surface of the legs forms a cylindrical space through which the nerve and / or threadlike tissue passes, such as the clip of the device shown in FIG. 6. The diameter of the cylindrical space formed by the legs depends on the target nerve and / or threadlike tissue that the implantable device engages. In some embodiments, the legs of the device form a cylindrical space having a diameter of about 50 μm to about 15 mm (e.g., about 50 μm to about 100 μm, about 100 μm to about 250 μm, about 250 μm to about 500 μm, about 500 μm to about 1 mm, about 1 mm to about 1.5 mm, about 1.5 mm to about 2.5 mm, about 2.5 mm to about 5 mm, about 5 mm to about 10 mm, or about 10 mm to about 15 mm). For example, a clip designed to at least partially encircle a human splenic nerve can include curved legs that form a cylindrical space having a diameter of about 500 μm to about 1.5 mm. The legs of the device can also be sized to optimally engage the nerve, and in some embodiments can have a width (including any coating material on the legs) of about 100 μm to about 4 mm (such as about 100 μm to about 200 μm, about 200 μm to about 400 μm, about 400 μm to about 1 mm, about 1 mm to about 2 mm, about 2 mm to about 3 mm, or about 3 mm to about 4 mm). In some embodiments, a clip designed to at least partially encircle a human splenic nerve can include legs having a width of about 200 μm to about 2 mm.

[0110] Since some nerves may be attached to thread-like tissue such as blood vessels, clips can be designed to at least partially surround the nerve and thread-like tissue. In some embodiments, clips configured to at least partially surround a nerve attached to thread-like tissue (such as blood vessels) can include curved legs that form a cylindrical space having a diameter of about 1 mm to about 10 mm (e.g., about 1 mm to about 2 mm, about 2 mm to about 3 mm, about 3 mm to about 4 mm, about 4 mm to about 5 mm, about 5 mm to about 6 mm, about 6 mm to about 7 mm, about 7 mm to about 8 mm, about 8 mm to about 9 mm, or about 9 mm to about 10 mm). For example, a clip configured to engage a splenic nerve attached to a splenic artery can include curved legs that form a cylindrical space having a diameter of about 2 mm to about 8 mm. The legs of the device may also be sized to optimally engage nerves and filamentous tissues (such as blood vessels) and in some embodiments may have a width (including any coating material on the legs) of about 100 μm to about 4 mm (such as about 100 μm to about 200 μm, about 200 μm to about 400 μm, about 400 μm to about 1 mm, about 1 mm to about 2 mm, about 2 mm to about 3 mm, or about 3 mm to about 4 mm). In some embodiments, clips designed to at least partially encircle the splenic nerve and splenic artery of a human may include legs having a width of about 500 μm to about 2 mm.

[0111] FIG. 7 illustrates a side view of another embodiment of an implantable device having a clip. Similar to the implantable device illustrated in FIG. 6, the implantable device includes a body 702 having a clip configured to at least partially surround a nerve. The clip includes legs 704 and 706, although it is contemplated that the device may optionally include additional legs and / or one or more crossbars. A bottom surface 708 of the housing 702 includes feedthroughs 710, 712, and 714. The feedthroughs electrically connect an integrated circuit within the device body to the electrodes. For example, the feedthrough 710 is electrically connected to the electrode 716 via connection 718, and the feedthrough 714 is electrically connected to the electrode 720 via connection 722. The connections 718 and 722 may be, for example, solder, welds, or crimps connecting the feedthroughs to the electrodes. The electrode 716 is disposed on the inner surface of the leg 704, and the electrode 720 is disposed on the inner surface of the leg 706. The electrodes are in electrical communication with the ultrasound transducer via an integrated circuit contained within the implantable device body 702, for example via a feedthrough. The electrodes are positioned in electrical communication with the nerve when the clip is placed over the nerve to at least partially surround the nerve. Legs 704 and 706 are secured to the device body 702 via a sealing material 724. This sealing material may also seal connections 718 and 722. In some embodiments, the sealing material is an epoxy or a polymer, such as a silicone or urethane polymer.

[0112] The legs of the implantable device can comprise metal, metal alloy, ceramic, silicon, or non-polymeric materials. In some embodiments, one or more electrodes are disposed on the inner surface of the legs. The legs are flexible and preferably springy so that the legs can be positioned around nerves and / or thread-like tissue. In some embodiments, the legs or portions of the legs are coated with an elastomeric or non-elastomeric coating that is preferably bioinert, such as polydimethylsiloxane (PDMS), silicone, urethane polymer, poly(p-xylylene) polymer (such as the poly(p-xylylene) polymer sold under the trade name PARYLENE®), or polyimide. In some embodiments, the implantable device includes one or more electrodes on the inner surface of the legs. In some embodiments, the one or more electrodes on the inner surface of the legs are not coated with an elastomeric or non-elastomeric polymer coating, but may be coated with a conductive material (e.g., may be electroplated with a PEDOT polymer or metal to improve the electrical properties of the electrodes). Thus, in some embodiments, only the outer surface of the legs is coated with a coating. Optionally, this coating also coats the housing of the body. For example, referring to Figure 7, the exterior surfaces of legs 704 and 706 are coated with a coating 726. However, because electrodes 716 and 720 are on the interior surfaces of legs 704 and 706, coating 726 does not coat the interior surfaces of the legs.

[0113] 8A and 8B illustrate two exemplary configurations with electrodes on the legs of the clip. As shown in FIG. 8A, the legs 802 are coated with a coating 804, such as an elastomeric or non-elastomeric polymer. A single electrode is exposed through the elastomeric or non-elastomeric polymer, which may be in electrical communication with a nerve. FIG. 8B illustrates a leg 806 with multiple electrodes 808 along the inner surface of the leg. In the embodiment illustrated in FIG. 8B, the leg 806 is not coated with an elastomeric or non-elastomeric polymer. However, the leg 806 may be optionally coated with a polymer on the outer surface of the leg 806.

[0114] In some embodiments, the legs include one or more hooks or loops that may be located near the ends of the legs or along the length of the legs. The hooks or loops can be used to help manipulate, bend, or place the clip in place. In some embodiments, the hooks or loops curve toward the body of the implantable device, and in some embodiments, the hooks or loops curve away from the body of the implantable device. FIG. 9A shows an embodiment of a leg with a hook at the end of the leg. The leg 902 connects to the body of the device at a starting end 904 and extends below and away from the body. The leg 902 curves inward at 906 before curving outward at 908 to form a hook 910 at the end 912 of the leg. In some embodiments, the clip includes a hook or loop configured to manipulate the legs of the clip, as shown, for example, in FIG. 9B. The implantable device includes a body 914 attached to a leg 916 that extends below and away from the body 914. The legs 916 are connected to hooks 918 on the opposite side of the body 914, for example, via a continuum (e.g., metal or non-elastomeric plastic). The hooks 918 and legs 916 may be, for example, co-extruded or co-printed to form this continuum. As the hooks 918 are pushed downward, the legs 916 are pushed outward. This mechanism allows the implantable device to be properly positioned over a nerve, for example, by laparoscopic implantation.

[0115] The two or more electrodes of the implantable device are placed in electrical communication with the nerve by the clip. In some embodiments, the two or more electrodes directly contact the nerve. In some embodiments, the two or more electrodes are placed within about 2 mm (within about 1.8 mm, within about 1.6 mm, within about 1.4 mm, within about 1.2 mm, within about 1.0 mm, within about 0.8 mm, within about 0.6 mm, within about 0.4 mm, or within about 0.2 mm) of the nerve. The electrodes may be placed on the bottom of the body or on one or more clip legs. The legs extending downward from the body secure the body to the nerve, and by placing the electrodes on the bottom of the body, the electrodes are placed in electrical communication with the nerve.

[0116] [Interrogator] The interrogator may wirelessly communicate with one or more implantable devices using ultrasound, which is used to power and / or operate the implantable devices. For example, the interrogator may transmit ultrasound that encodes instructions for operating the device, such as a trigger signal commanding the implantable device to emit an electrical pulse. The interrogator may further receive ultrasound backscatter from the implantable device, which encodes information transmitted by the implantable device. This information may include, for example, detected electrophysiological pulses, electrical pulses emitted by the implantable device, and / or information related to a measured physiological condition. The interrogator includes one or more ultrasound transducers that may operate as an ultrasound transmitter and / or an ultrasound receiver (or as a transceiver that may be configured to alternatively transmit or receive ultrasound). One or more of these transducers may be arranged as a transducer array, and the interrogator may optionally include one or more transducer arrays. In some embodiments, the ultrasound transmission function is separate from the ultrasound receiving function on a separate device. That is, optionally, the interrogator comprises a first device for transmitting ultrasound to the implantable device and a second device for receiving ultrasound backscatter from the implantable device. In some embodiments, the transducers in the array can be regularly spaced, irregularly spaced, or sparsely positioned. In some embodiments, the array is flexible. In some embodiments, the array is planar, and in some embodiments, the array is non-planar.

[0117] An exemplary interrogator is shown in Figure 10. The illustrated interrogator shows a transducer array having multiple ultrasonic transducers. In some embodiments, the transducer array includes 1 or more, 2 or more, 3 or more, 5 or more, 7 or more, 10 or more, 15 or more, 20 or more, 25 or more, 50 or more, 100 or more, 250 or more, 500 or more, 1000 or more, 2500 or more, 5000 or more, or 10000 or more transducers. In some embodiments, the transducer array includes 100,000 or less, 50,000 or less, 25,000 or less, 10,000 or less, 5000 or less, 2500 or less, 1000 or less, 500 or less, 200 or less, 150 or less, 100 or less, 90 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less, 30 or less, 25 or less, 20 or less, 15 or less, 10 or less, 7 or less, or 5 or less transducers. The transducer array can be, for example, a chip with 50 or more ultrasound transducer pixels.

[0118] Although the interrogator shown in FIG. 10 illustrates a single transducer array, the interrogator may include one or more, two or more, or three or more separate arrays. In some embodiments, the interrogator includes ten or fewer transducer arrays (such as nine, eight, seven, six, five, four, three, two, or one transducer arrays). The separate arrays may be located at different points on the subject, for example, and may communicate with the same or different implantable devices. In some embodiments, the arrays are placed on opposite sides of the implantable device. The interrogator may include an application specific integrated circuit (ASIC), which includes a channel for each transducer in the transducer array. In some embodiments, the channel includes a switch (denoted in FIG. 10 by "T / Rx"). The switch may alternatively configure the transducer connected to the channel to transmit ultrasound or receive ultrasound. The switch may isolate the ultrasound receive circuitry from the higher voltage ultrasound transmit circuitry.

[0119] In some embodiments, the transducer connected to a channel is configured only to receive ultrasound or only to transmit ultrasound, and the switch is optionally omitted from the channel. The channel may include a delay control operative to control the transmitted ultrasound. The delay control may, for example, control the phase shift, time delay, pulse frequency and / or waveform (including amplitude and wavelength). The delay control may be connected to a level shifter that shifts the input pulse from the delay control to a higher voltage that is used by the transducer to transmit ultrasound. In some embodiments, data representing the waveform and frequency of each channel may be stored in a "wave table." This allows the transmit waveform of each channel to be different. The delay control and level shifter may then be used to "stream" this data into the actual transmit signal to the transducer array. In some embodiments, the transmit waveform for each channel may be generated directly by a high speed serial output of a microcontroller or other digital system and sent to the transducer elements via a level shifter or high voltage amplifier. In some embodiments, the ASIC includes a charge pump (shown in FIG. 10) to convert a first voltage supplied to the ASIC to a higher second voltage applied to the channel. The channels may be controlled by a controller, such as a digital controller, which operates a delay control section.

[0120] In the ultrasound receiver circuit, the received ultrasound is converted to a current by a transducer (set in receive mode) and transmitted to the data acquisition circuit. In some embodiments, an amplifier, an analog-to-digital converter (ADC), a variable gain amplifier, or a time-gain controlled variable gain amplifier to compensate for tissue loss, and / or a bandpass filter are included in the receiver circuit. The ASIC may draw power from a power source such as a battery (preferred for wearable embodiments of the interrogator). In the embodiment illustrated in FIG. 10, the ASIC is powered with 1.8V, which is increased to 32V by a charge pump, although any suitable voltage may be used. In some embodiments, the interrogator includes a processor and non-transitory computer readable memory. In some embodiments, the above-mentioned channels do not include a T / Rx switch, but instead include separate Tx (transmit) and Rx (receive) with a high voltage Rx (receiver circuit) in the form of a low noise amplifier with good saturation recovery. In some embodiments, the T / Rx circuit includes a circulator. In some embodiments, the transducer array contains more transducer elements than processing channels in the interrogator transmit / receive circuitry, and the multiplexer selects a different set of transmit elements for each pulse, for example 64 transmit / receive channels connected to 192 physical transducer elements via a 3:1 multiplexer, with only 64 transducer elements active on a given pulse.

[0121] In some embodiments, the interrogator is implantable. In some embodiments, the interrogator is external (i.e., not implanted). As an example, an external interrogator may be wearable and secured to the body by a strap or adhesive. In another example, an external interrogator may be a wand and held by a user (such as a medical professional). In some embodiments, the interrogator may be held to the body via sutures, simple surface tension, a clothing-based securement device such as a fabric wrap, sleeve, elastic band, or by subcutaneous fixation. The transducer or transducer array of the interrogator may be positioned separately from the remainder of the transducer. For example, the transducer array may be secured to the subject's skin at a first location (e.g., proximal to one or more implanted devices) and the remainder of the interrogator may be positioned at a second location, with wires connecting the transducer or transducer array to the remainder of the interrogator.

[0122] The specific design of the transducer array depends on the desired penetration depth, aperture size, and size of the individual transducers in the array. The Rayleigh distance R of the transducer array is calculated as follows:

number

[0123] Through the process of beamforming or beamsteering, individual transducers in a transducer array can be adjusted to control the Rayleigh distance and the position of the beam of ultrasound emitted by the transducer array. Techniques such as Linear Constrained Minimum Variance (LCMV) beamforming can be used to allow multiple implantable devices to communicate with an external ultrasound transceiver. See, for example, Bertrand et al., Beamforming Approaches for Untethered, Ultrasonic Neural Dust Motes for Cortical Recording (a Simulation Study, IEEE EMBC, August 2014). In some embodiments, beamsteering is performed by adjusting the power or phase of the ultrasound emitted by the transducers in the array.

[0124] In some embodiments, the interrogator includes one or more of instructions for beam steering ultrasound using one or more transducers, instructions for determining a relative position of one or more implantable devices, instructions for monitoring relative movement of one or more implantable devices, instructions for recording relative movement of one or more implantable devices, and instructions for deconvolving backscatter from multiple implantable devices.

[0125] Optionally, the interrogator is controlled using a separate computer system, such as a mobile device (e.g., a smart phone or a table). The computer system may wirelessly communicate with the interrogator, for example, via a network connection, a radio frequency (RF) connection, or Bluetooth. The computer system may, for example, turn the interrogator on or off, or analyze information encoded in ultrasound waves received by the interrogator.

[0126] [Communication between the implantable device and the interrogator] The implantable device and the interrogator communicate with each other wirelessly using ultrasound. The implantable device receives ultrasound from the interrogator via one or more ultrasound transducers on the implantable device, which may encode instructions for operating the implantable device. Vibrations of the ultrasound transducers on the implantable device generate a voltage across the electrical terminals of the transducer, causing a current to flow through the device, which includes an integrated circuit. The current may be used to charge an energy storage circuit, which may store energy that is used to emit an electrical pulse, for example, after receiving a trigger signal. The trigger signal may be transmitted from the interrogator to the implantable device to indicate that an electrical pulse should be emitted. In some embodiments, the trigger signal includes information about the electrical pulse to be emitted, such as frequency, amplitude, pulse length, or pulse shape (e.g., AC, DC, or pulse pattern). Digital circuitry may decode the trigger signal and operate the electrodes and electrical storage circuit to emit the pulse.

[0127] In some embodiments, ultrasound backscatter is emitted from the implantable device, which may encode information about the implantable device, the electrical pulse emitted by the implantable device, the electrophysiological pulse detected by the implantable device, or the detected physiological condition. For example, the ultrasound backscatter may encode a verification signal that verifies that an electrical pulse was emitted. In some embodiments, the implantable device is configured to detect an electrophysiological signal, and information about the detected electrophysiological signal may be transmitted by ultrasound backscatter to an interrogator. To encode a signal in the ultrasound backscatter, a current flowing through the ultrasound transducer of the implantable device is modulated as a function of the encoded information, such as the detected electrophysiological signal or the measured physiological condition. In some embodiments, the modulation of the current may be an analog signal, which may be directly modulated, for example, by the detected electrophysiological signal. In some embodiments, the modulation of the current encodes a digitized signal, which may be controlled by digital circuitry within an integrated circuit. The backscatter is received by an external ultrasound transceiver (which may be the same as or different from the external ultrasound transceiver that transmitted the initial ultrasound). Thus, information from electrophysiological signals can be encoded by changes in the amplitude, frequency, or phase of the backscattered ultrasound waves.

[0128] FIG. 11 shows an interrogator communicating with an implantable device. An external ultrasound transceiver emits ultrasound waves ("carrier waves") that can pass through tissue. The carrier waves cause an ultrasound transducer (e.g., bulk piezoelectric transducer, PUMT, or CMUT) to mechanically vibrate. A voltage is generated across the ultrasound transducer, which imparts a current that flows through an integrated circuit on the implantable device. The current flowing through the ultrasound transducer causes the transducer on the implantable device to emit backscattered ultrasound waves. In some embodiments, the integrated circuit modulates the current flowing through the ultrasound transducer to encode information, and the resulting ultrasound backscattered waves encode the information. The backscattered waves can be detected by the interrogator and analyzed to interpret the information encoded in the ultrasound backscatter.

[0129] Communication between the interrogator and the implantable device can use a pulse-echo method of transmitting and receiving ultrasound. In the pulse-echo method, the interrogator transmits a series of interrogation pulses at a predetermined frequency and then receives backscattered echoes from the implanted device. In some embodiments, the pulses are square, rectangular, triangular, sawtooth, or sinusoidal. In some embodiments, the pulses output can be two-level (GND and POS), three-level (GND, NEG, POS), five-level, or any other multi-level (e.g., when using a 24-bit DAC). In some embodiments, the pulses are transmitted continuously by the interrogator during operation. In some embodiments, when pulses are transmitted continuously by the interrogator, some of the transducers on the interrogator are configured to receive ultrasound and some of the transducers on the interrogator are configured to transmit ultrasound. The transducers configured to receive ultrasound and the transducers configured to transmit ultrasound can be on the same transducer array of the interrogator or on different transducer arrays. In some embodiments, the transducers on the interrogator can be configured to alternatively transmit or receive ultrasound. For example, the transducer may cycle between transmitting one or more pulses and a rest period, where the transducer is configured to transmit ultrasound when transmitting one or more pulses, and then switch to a receive mode during the rest period.

[0130] In some embodiments, the backscattered ultrasound is digitized by the implantable device. For example, the implantable device may include an oscilloscope or an analog-to-digital converter (ADC) and / or memory, which may digitally encode information in the current (or impedance) fluctuations. The digitized current fluctuations, which may encode information, are received by an ultrasound transducer, which then transmits digitized sound waves. The digitized data may be compressed from the analog data, for example, by using singular value decomposition (SVD) and least squares-based compression. In some embodiments, this compression is performed by a correlator or pattern detection algorithm. The backscattered signal may undergo a series of nonlinear transformations, such as a fourth order Butterworth bandpass filter rectified integral of the backscattered region, to generate a reconstructed data point at a single time point. Such transformations may be performed in either hardware (i.e., hard-coded) or software.

[0131] In some embodiments, the digitized data may include a unique identifier. This unique identifier may be useful, for example, in a system with multiple implantable devices and / or implantable devices with multiple electrode pairs. For example, the unique identifier may identify the originating implantable device when from multiple implantable devices, for example, when transmitting information (such as a verification signal) from the implantable device. In some embodiments, the implantable device may include multiple electrode pairs, which may emit electrical pulses simultaneously or alternatively by a single implantable device. Different pairs of electrodes may be configured, for example, to emit electrical pulses at different tissues (e.g., different nerves or different muscles) or different regions of the same tissue. The digitized circuit may encode the unique identifier to identify and / or verify which electrode pair emitted the electrical pulse.

[0132] In some embodiments, the digitized signal compresses the size of the analog signal. The reduced size of the digitized signal can allow for more efficient reporting of information encoded in the ultrasound backscatter. By compressing the size of the information transmitted through digitization, potentially overlapping signals can be transmitted accurately.

[0133] In some embodiments, the interrogator communicates with multiple implantable devices. This can be done, for example, using multiple-input multiple-output (MIMO) system theory. For example, communication between the interrogator and multiple implantable devices using time division multiplexing, spatial multiplexing, or frequency multiplexing. The interrogator can receive combined backscatter from multiple implantable devices that can be deconvoluted, thereby extracting information from each implantable device. In some embodiments, the interrogator focuses transmitted ultrasound from a transducer array to a particular implantable device via beam steering. The interrogator focuses transmitted ultrasound on a first implantable device and receives backscatter from the first implantable device, and focuses transmitted ultrasound on a second implantable device and receives backscatter from the second implantable device. In some embodiments, the interrogator transmits ultrasound to multiple implantable devices and then receives ultrasound from the multiple implantable devices.

[0134] [Method of implanting an implantable device] An implantable device having a body and a clip attached to the body can be implanted in a subject to manipulate the legs of the clip to at least partially encircle a nerve and / or thread-like tissue attached to the nerve, such as a blood vessel or tendon. The body includes one or more ultrasound transducers configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy that powers the device. The device further includes one or more electrodes in electrical communication with the ultrasound transducers, for example, via an integrated circuit as described herein. The electrodes may be located on the legs of the implantable device or on (such as under) the body of the implantable device. In some embodiments, the device is implanted laparoscopically.

[0135] In one example, implanting the device in the subject can include bending one or more of the legs of the clip outwardly and placing an electrode in electrical communication with the nerve. In some embodiments, the electrode is placed in direct contact with the nerve. In some embodiments, two or more electrodes are placed within about 2 mm (within about 1.8 mm, within about 1.6 mm, within about 1.4 mm, within about 1.2 mm, within about 1.0 mm, within about 0.8 mm, within about 0.6 mm, within about 0.4 mm, or within about 0.2 mm) of the nerve. One or more of the bent legs are released to allow the legs of the clip to at least partially surround the nerve and / or thread-like tissue attached to the nerve. Once the legs are released, with the legs partially surrounding the nerve, the electrode remains in electrical communication with the nerve.

[0136] The implantable device may include one or more hooks or loops configured to manipulate one or more legs of the clip. For example, as shown in FIG. 9B, the hooks 918 may be pushed downward to force the legs 916 to bend outward. With the legs 916 bent outward, the implantable device may be positioned to place an electrode (which may be on the legs 916 or on the body 914) in electrical communication with the nerve. The hooks 918 may be released, which releases the legs 916 and allows the legs 916 to close inward, thereby at least partially surrounding the nerve. The hooks or loops may be pushed upward, downward, pushed to the side, or pulled to manipulate the legs of the clip.

[0137] The implantable device may be implanted such that the electrode contacts or the legs of the clip at least partially surround an autonomic nerve, in some embodiments the nerve is a sympathetic nerve, and in some embodiments the nerve is the vagus nerve, mesenteric nerve, splenic nerve, sciatic nerve, tibial nerve, pudendal nerve, celiac ganglion, sacral nerve, or any branch thereof.

[0138] [How to use the implantable device] The implantable device is operated using an interrogator capable of transmitting ultrasound waves that power and operate the implantable device. The implantable device can be used in at least one of three basic modes of operation. First, the implantable device can be operated to emit an electrical pulse into tissue. The electrical pulse may be applied to a nerve to stimulate neural activity or to block neural activity. Optionally, the electrical pulse may be emitted in response to the implantable device receiving a trigger signal encoded in ultrasound transmitted by the interrogator. Additionally, the implantable device optionally encodes information related to the emitted electrical pulse (such as an affirmation that a pulse was emitted, the voltage of the pulse, or the pulse frequency) in the ultrasound backscatter waves, which can be received and analyzed by the interrogator to decode the information. Second, the implantable device can be operated to detect neural activity and transmit information related to the detected neural activity. Electrodes on the implantable device in electrical communication with a nerve can detect an electrophysiological pulse from that nerve, and information related to the electrophysiological pulse (e.g., frequency, voltage, shape, etc.) is encoded in ultrasonic backscatter waves emitted by one or more ultrasonic transducers on the implantable device. The ultrasonic backscatter waves encoding the information can be received by an interrogator and analyzed to decode the information. Third, the implantable device may include a sensor capable of measuring a physiological condition (e.g., pH, temperature, strain, tissue impedance, or concentration of an analyte such as oxygen), and information related to the measured physiological condition may be encoded in ultrasonic backscatter waves emitted by the implantable device. The ultrasonic backscatter waves encoding information related to the measured physiological condition can be received by an interrogator and analyzed to decode information related to the physiological condition.

[0139] In some embodiments, the three modes of operation support each other within the device to safely treat a medical condition. For example, the interrogator may transmit a trigger signal in ultrasound based on information received by the implantable device related to a measured physiological condition or a detected electrophysiological pulse. For example, an irregular electrophysiological pulse or electrophysiological pulse pattern may be treated by emitting one or more electrical pulses from the implantable device. The implantable device may detect one or more electrophysiological pulses from a nerve and emit ultrasound backscatter encoding information related to the electrophysiological pulses. The ultrasound backscatter may be received by the interrogator, which decodes the information and recognizes the electrophysiological pulse or electrophysiological pulse pattern as an indication of the need for an electrical pulse to be applied to the nerve. The interrogator may then transmit an ultrasound encoded trigger signal to the implantable device, which may operate the implantable device to emit an electrical pulse. The measured physiological condition may also affect the decision of whether to operate the implantable device to emit an electrical pulse. For example, a high temperature measured by the implantable device may indicate that an electrical pulse should not be emitted. Thus, the interrogator may transmit a trigger signal based on a detected electrophysiological pulse or electrophysiological pulse pattern and / or a measured physiological condition.

[0140] The trigger signal transmitted by the interrogator may include instructions to emit an electrical pulse, and may include instructions for the type of pulse (e.g., DC or AC pulse), the number of pulses, the dwell time between pulses, the pulse frequency, the pulse amplitude, the pulse shape, or the pulse voltage. As mentioned above, the transmission of the trigger signal may be based on a detected electrophysiological pulse, a detected electrophysiological pulse pattern, or information related to a measured physiological condition.

[0141] In some embodiments, the electrical pulse emitted by the implantable device is a direct current pulse or an alternating current pulse. In some embodiments, the electrical pulse comprises multiple pulses that may be separated by a dwell time. In some embodiments, the electrical pulse is about 1 microsecond (μs) or longer (about 5 μs or longer, about 10 μs or longer, about 20 μs or longer, about 50 μs or longer, about 100 μs or longer, about 250 μs or longer, about 500 μs or longer, about 1 millisecond (ms) or longer, about 5 ms or longer, about 10 ms or longer, about 25 ms or longer, about 50 ms or longer, about 100 ms or longer, about 200 ms or longer, or about 500 ms or longer, etc.). In some embodiments, the electrical pulse is about 1000 ms or less (such as about 500 ms or less, about 200 ms or less, about 100 ms or less, or about 50 ms or less, about 25 ms or less, about 10 ms or less, about 5 ms or less, about 1 ms or less, about 500 μs or less, about 250 μs or less, about 100 μs or less, about 50 μs or less, about 20 μs or less, about 10 μs or less, or about 5 μs or less). In some embodiments, the dwell time is about 1 microsecond (μs) or more (such as about 5 μs or more, about 10 μs or more, about 20 μs or more, about 50 μs or more, about 100 μs or more, about 250 μs or more, about 500 μs or more, about 1 millisecond (ms) or more, about 5 ms or more, about 10 ms or more, about 25 ms or more, or about 50 ms or more). In some embodiments, the residence time is about 100 ms or less (such as about 50 ms or less, about 25 ms or less, about 10 ms or less, about 5 ms or less, about 1 ms or less, about 500 μs or less, about 250 μs or less, about 100 μs or less, about 50 μs or less, about 20 μs or less, about 10 μs or less, or about 5 μs or less).

[0142] In some embodiments, the electrical pulse is about 1 microamp (μA) or more (such as about 5 μA or more, about 10 μA or more, about 25 μA or more, about 50 μA or more, about 100 μA or more, about 250 μA or more, about 500 μA or more, about 1 milliamp (mA) or more, about 5 mA or more, about 10 mA or more, or about 25 mA or more). In some embodiments, the electrical pulse is about 50 mA or less (such as about 25 mA or less, about 10 mA or less, about 5 mA or less, about 1 mA or less, about 500 μA or less, about 250 μA or less, about 100 μA or less, about 50 μA or less, about 25 μA or less, about 10 μA or less, about 5 μA or less, or about 1 μA or less).

[0143] In some embodiments, the electrical pulses have a current frequency of about 0.1 Hz or greater (such as about 0.5 Hz or greater, about 1 Hz or greater, about 5 Hz or greater, about 10 Hz or greater, about 25 Hz or greater, about 50 Hz or greater, about 100 Hz or greater, about 200 Hz or greater, about 300 Hz or greater, about 400 Hz or greater, about 500 Hz or greater, about 600 Hz or greater, about 700 Hz or greater, about 800 Hz or greater, about 1 kHz or greater, about 2 kHz or greater, or about 5 kHz or greater). In some embodiments, the electrical pulses have a current frequency of about 10 kHz or less (e.g., about 5 kHz or less, about 2 kHz or less, about 1 kHz or less, about 800 Hz or less, about 700 Hz or less, about 600 Hz or less, about 500 Hz or less, about 400 Hz or less, about 300 Hz or less, about 200 Hz or less, about 100 Hz or less, about 50 Hz or less, about 25 Hz or less, about 10 Hz or less, about 5 Hz or less, about 1 Hz or less, or about 0.5 Hz or less).

[0144] In some embodiments, the implantable device generates a voltage pulse in the tissue. In some embodiments, the voltage is about 50 mV or more (e.g., about 100 mV or more, about 250 mV or more, about 500 mV or more, about 1 V or more, about 2.5 V or more, about 5 V or more, or about 10 V or more). In some embodiments, the voltage is about 20 V or less (e.g., about 15 V or less, about 10 V or less, about 5 V or less, about 2.5 V or less, about 1 V or less, about 500 mV or less, about 250 mV or less, or about 100 mV or less).

[0145] Characteristics of the electrical pulse, such as frequency, amplitude, and length, can affect the effect of the electrical pulse on neural tissue, for example, lower frequency pulses (such as pulses below about 1 kHz) can stimulate neural activity, while higher frequency pulses (such as pulses above about 1 kHz) can block neural activity.

[0146] [Treatment methods for incontinence] In some embodiments, the implantable device described herein is used to treat a patient's incontinence, such as overactive bladder, underactive bladder, urinary incontinence, or fecal incontinence. The implantable device may be fully implanted in a subject such that the electrodes are in electrical communication with the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches, which nerves may be electrically stimulated using the fully implanted medical device. In some embodiments, the implantable device electrically stimulates the nerve by emitting one or more electrical pulses that block neurological activity of the nerve. In some embodiments, the implantable device electrically stimulates the nerve by emitting one or more electrical pulses that activate neurological activity of the nerve. The electrical stimulation by emitting one or more electrical pulses (e.g., current pulses or voltage pulses) may be responsive to an ultrasound-encoded trigger signal received by the implantable device. As described above, the transmission of the trigger signal may be based on a detected electrophysiological pulse or pulse pattern, or a measured physiological condition, which may be transmitted from the implantable device using ultrasound backscatter.

[0147] The electrical pulses may be emitted by the implantable device at a constant frequency. The length of time the electrical pulses are emitted may be predetermined, or may be based on a detected electrophysiological pulse or pulse pattern, or may depend on a measured physiological condition, as described herein. In some embodiments, the frequency of the electrical pulses is about 0.1 Hz to about 500 Hz, such as about 0.2 Hz to about 250 Hz, about 0.5 Hz to about 100 Hz, about 1 Hz to about 50 Hz, or about 5 Hz to about 30 Hz.

[0148] The interrogator may be worn externally by the subject and may operate and power the implantable device, with the ultrasound transducer on the interrogator preferably contacting the subject's skin. In some embodiments, the ultrasound transducer of the interrogator is about 10 cm or less, about 5 cm or less, about 4 cm or less, about 3 cm or less, about 2 cm or less, or about 1 cm or less from the implantable device. The placement of the interrogator depends on the placement of the implantable device and which nerves are in electrical communication with the electrodes of the implantable device. For example, if the implantable device includes electrodes in electrical communication with the sacral nerve, the interrogator may be placed on the patient's hip, abdomen, lower back, buttocks, or upper extremity. If the implantable device includes electrodes in electrical communication with the tibial nerve, the interrogator may be placed on the subject's lower extremity (e.g., calf) or ankle. The interrogator may be placed using an adhesive, a band that is secured to the subject's skin, or may be a handheld device that is placed at the desired location.

[0149] As an example, transcutaneous tibial nerve stimulation (PTNS) is a known treatment for incontinence and related disorders such as overactive bladder, urinary incontinence, and fecal incontinence. Known devices stimulate the tibial nerve by passing a needle electrode through the skin and placing it near the tibial nerve at the ankle. One lead of the device is connected to the exposed end of the electrode and the other lead is connected to a return electrode, which may be a conductive pad positioned on the patient's skin (such as on the foot). During treatment, current or voltage pulses are delivered at a constant frequency (e.g., between 5 Hz and 30 Hz) and stimulation intensity is increased until there is movement in the patient's toes. Treatment lasts approximately 30 minutes and is typically performed in a clinic once a week for 12 weeks, followed by maintenance treatments at longer intervals. Although this treatment is generally effective, it is inconvenient in that the regular insertion of needles causes significant patient discomfort and requires frequent doctor visits. The system described herein provides a significantly more convenient treatment regimen that can be performed at home and with increased frequencies.

[0150] FIG. 13A shows an implantable device with a body fully implanted in a subject and a clip, where the clip attaches the implantable device to the tibial nerve. The body of the implantable device includes an electrode in electrical communication with the tibial nerve and an ultrasound transducer configured to receive ultrasound waves to power and operate the device. The clip includes a leg that surrounds the tibial nerve and holds the electrode in electrical contact with the nerve. The tibial nerve can be stimulated by converting energy from the ultrasound waves into electrical energy that powers the device and electrically stimulates the tibial nerve in response to an ultrasound-encoded trigger signal. The ultrasound waves received by the device can be transmitted by an interrogator as shown in FIG. 13B. The interrogator is worn by the patient on the ankle. As shown in FIG. 13B, the ultrasound transducer of the interrogator is placed against the skin. Optionally, the interrogator is controlled by a computer system, such as a mobile device.

[0151] Sacral nerve stimulation is another method known to be used to treat certain urinary disorders such as overactive bladder. The treatment involves continuous electrical stimulation of the sacral nerve to lengthen the interval between urination so as to reduce the urgency of urinating from the bladder. Known devices for sacral nerve stimulation generally include leads positioned near the sacral nerve connected to an implanted pulse generator that houses a battery. The device can be surgically positioned under the skin, usually in the lower abdomen near the hip joint. However, because these devices require batteries, the batteries can wear out, necessitating surgery to replace the device. Furthermore, the device leads can break, necessitating another surgery to remove the broken leads and replace the device. Also, the surgical pocket is relatively large and prone to infection. Due to these concerns, many patients choose not to undergo sacral nerve stimulation treatment. However, the implantable devices described herein are much smaller than known devices, thereby minimizing the risk of infection. Furthermore, the small size of the devices described herein allows the implantable devices to be fixed directly onto the sacral nerve, thereby avoiding the need for electrical leads that are prone to breakage. Furthermore, because the device is ultrasonically powered, the device is battery free and there is no need to remove the device due to battery failure.

[0152] FIG. 14 shows a system used for sacral nerve stimulation (SNS). The implantable device includes a body having an ultrasound transducer, an electrode, and a clip. The clip surrounds the sacral nerve to place the electrode in electrical communication with the sacral nerve. The ultrasound transducer on the implantable device is configured to receive ultrasound waves that power and operate the device. For example, the ultrasound waves can optionally include a trigger signal that instructs the device to stimulate the nerve. The implantable device may be configured to continuously stimulate the nerve, and the ultrasound waves can instruct the implantable device to begin to stop the continuous stimulation. The implantable device may also emit ultrasound backscatter that encodes information related to the status of the device or information about the electrical pulses emitted by the device. An external interrogator can be worn by the subject, which can transmit ultrasound waves to the implantable device. The interrogator may include a battery that can be replaced or recharged. Optionally, the interrogator communicates with a computer system, such as a mobile device (e.g., a smartphone or tablet), that can turn the system on or off.

[0153] Exemplary embodiments [Embodiment 1] 1. An implantable medical device, comprising: a body including an ultrasonic transducer configured to receive ultrasonic waves and convert energy from the ultrasonic waves into electrical energy to power the device; The device comprises two or more electrodes in electrical communication with the ultrasound transducer, and a clip attached to the body configured to at least partially surround a nerve and position the two or more electrodes in electrical communication with the nerve.

[0154] [Embodiment 2] 2. The implantable medical device of embodiment 1, wherein the clip is configured to at least partially surround the nerve and the thread-like tissue attached to the nerve.

[0155] [Embodiment 3] The implantable medical device of embodiment 2, wherein the thread-like tissue is a blood vessel.

[0156] [Embodiment 4] An implantable medical device as described in any one of embodiments 1 to 3, wherein the clip comprises a plurality of flexible legs extending below the body.

[0157] [Embodiment 5] An implantable device as described in embodiment 4, wherein the implantable device comprises a hook or loop configured to manipulate at least one of the flexible legs in response to manipulating the hook or loop.

[0158] [Embodiment 6] 6. The implantable device of embodiment 5, wherein the hook or loop is disposed at an end of one of the flexible legs.

[0159] [Embodiment 7] 6. The implantable device of embodiment 5, wherein the hook or loop is located proximally on the body.

[0160] [Embodiment 8] An implantable medical device as described in any one of embodiments 4 to 7, wherein the flexible legs are curved.

[0161] [Embodiment 9] 9. The implantable medical device of embodiment 8, wherein as the legs extend below the body, they extend away from the body before curving towards the body.

[0162] [Embodiment 10] An implantable medical device as described in embodiment 9, wherein the multiple flexible legs include at least one pair of legs comprising a first leg and a second leg extending downwardly away from the body in opposite directions.

[0163] [Embodiment 11] 11. The implantable medical device of embodiment 10, wherein the first leg and the second leg are connected by a crossbar connected to the body.

[0164] [Embodiment 12] 12. An implantable medical device as described in embodiment 11, wherein the crossbar is connected to the body of the device via a flexible portion.

[0165] [Embodiment 13] 13. The implantable medical device of embodiment 12, wherein the flexible portion is a hinge.

[0166] [Embodiment 14] An implantable medical device described in any one of embodiments 10 to 13, wherein the device comprises two pairs of legs, each pair of legs being disposed on opposite sides of the body.

[0167] [Embodiment 15] An implantable medical device described in any one of embodiments 4 to 14, wherein the legs are attached to the body via a bottom surface of the body.

[0168] [Embodiment 16] An implantable medical device as described in any one of embodiments 4 to 14, wherein the legs are attached to the body via a side wall of the body.

[0169] [Embodiment 17] 17. The implantable medical device of any one of embodiments 4 to 16, wherein the legs comprise a metal, a metal alloy, a ceramic, a silicon, or a non-polymeric material.

[0170] [Embodiment 18] 18. The implantable medical device of any one of embodiments 4 to 17, wherein the legs comprise an elastomeric coating or a non-elastomeric polymer coating.

[0171] [Embodiment 19] The implantable medical device of embodiment 18, wherein the coating is bioinert.

[0172] [Embodiment 20] 20. The implantable medical device of embodiment 18 or 19, wherein the coating is silicone, poly(p-xylylene) polymer, or polyimide.

[0173] [Embodiment 21] An implantable medical device as described in any one of embodiments 18 to 20, wherein at least one of the legs has an outer surface coated with an elastomeric coating or a non-elastomeric polymer coating and an inner surface having at least one electrode that is not coated with an elastomeric coating or a non-elastomeric polymer coating.

[0174] [Embodiment 22] An implantable medical device described in any one of embodiments 1 to 21, wherein the body has a bottom surface and the two or more electrodes terminate on the bottom of the body.

[0175] [Embodiment 23] An implantable medical device described in any one of embodiments 1 to 21, wherein two or more electrodes are disposed on the clip.

[0176] [Embodiment 24] 24. An implantable medical device as described in embodiment 23, wherein the clip comprises a plurality of flexible legs extending below the body, and the two or more electrodes are disposed on the flexible legs.

[0177] [Embodiment 25] An implantable medical device described in any one of embodiments 1 to 24, wherein the body includes a housing.

[0178] [Embodiment 26] 18. The implantable medical device of embodiment 17, wherein the housing comprises or is coated with a bioinert material.

[0179] [Embodiment 27] 27. The implantable medical device of embodiment 26, wherein the housing comprises a bioinert material, wherein the bioinert material of the housing comprises titanium or ceramic.

[0180] [Embodiment 28] An implantable medical device described in any one of embodiments 1 to 27, wherein the body comprises an integrated circuit electrically connected to an ultrasonic transducer and two or more electrodes.

[0181] [Embodiment 29] 29. An implantable medical device as described in embodiment 28, wherein the integrated circuit comprises an energy storage circuit comprising a capacitor.

[0182] [Embodiment 30] 30. An implantable medical device as described in any one of embodiments 1 to 29, wherein the body is about 5 mm or less in length in its longest dimension.

[0183] [Embodiment 31] An implantable medical device described in any one of embodiments 1 to 30, wherein the ultrasound transducer is configured to emit ultrasound backscatter that encodes data.

[0184] [Embodiment 32] An implantable medical device as described in embodiment 31, wherein the data includes information regarding detected neural activity, measured physiological condition, device status, or emitted electrical pulses.

[0185] [Embodiment 33] An implantable medical device described in any one of embodiments 1 to 32, wherein the implantable medical device is configured to emit an electrical pulse to a nerve.

[0186] [Embodiment 34] An implantable medical device described in any one of embodiments 1 to 33, wherein the ultrasonic transducer is configured to receive ultrasonic waves encoding instructions for operating the implantable device.

[0187] [Embodiment 35] An implantable medical device as described in embodiment 34, wherein the instructions comprise a trigger signal that operates the implantable device to emit an electrical pulse to a nerve.

[0188] [Embodiment 36] 1. A method of implanting a medical device in a subject, the device comprising: a body including an ultrasound transducer configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy for powering the device; an electrode in electrical communication with the ultrasound transducer; and a clip attached to the body, the clip including a plurality of flexible legs; bending one or more legs of the clip outward; The method includes placing an electrode in electrical communication with the nerve and releasing one or more legs of a clip, the one or more legs at least partially surrounding the nerve and maintaining the electrode in electrical communication with the nerve upon release.

[0189] [Embodiment 37] 37. The method of embodiment 36, wherein the multiple legs at least partially surround the nerve and the thread-like tissue attached to the nerve.

[0190] [Embodiment 38] 38. The method of embodiment 37, wherein the threadlike tissue is a blood vessel.

[0191] [Embodiment 39] The method of any one of embodiments 36 to 38, wherein the device is implanted in the subject laparoscopically.

[0192] [Embodiment 40] The method of any one of embodiments 36 to 39, wherein the clip exerts inward pressure on the nerve.

[0193] [Embodiment 41] The method of any one of embodiments 36 to 40, wherein the clip allows rotational movement around the nerve.

[0194] [Embodiment 42] The method of any one of embodiments 36 to 41, wherein the nerve is an autonomic nerve.

[0195] [Embodiment 43] The method of any one of embodiments 36 to 42, wherein the nerve is a sympathetic nerve.

[0196] [Embodiment 44] The method of any one of embodiments 36 to 43, wherein the nerve is a mesenteric nerve, a splenic nerve, a sciatic nerve, a tibial nerve, a celiac ganglion, or a sacral nerve.

[0197] [Embodiment 45] The method of any one of embodiments 36 to 44, wherein the legs apply a pressure of about 1 MPa or less to the nerve or thread-like tissue.

[0198] [Embodiment 46] 46. ​​The method of any one of embodiments 36 to 45, wherein a plurality of legs extend below the body.

[0199] [Embodiment 47] The method of any one of embodiments 36 to 46, wherein bending one or more legs of the clip outward comprises manipulating one or more hooks or loops connected to the one or more legs.

[0200] [Embodiment 48] The method of any one of embodiments 36 to 47, wherein the legs are curved.

[0201] [Embodiment 49] 49. The method of any one of embodiments 36 to 48, wherein as the legs extend below the body, they extend away from the body before curving towards the body.

[0202] [Embodiment 50] The method of any one of embodiments 36 to 49, wherein the multiple flexible legs include at least one pair of legs, the pair of legs including a first leg and a second leg extending downwardly away from the body in opposite directions.

[0203] [Embodiment 51] 51. The method of embodiment 50, wherein the pair of legs are connected by a crossbar connected to the body.

[0204] [Embodiment 52] 52. The method of embodiment 51, wherein the crossbar is connected to the body of the device via a flexible portion.

[0205] [Embodiment 53] 53. The method of embodiment 52, wherein the flexible portion is a hinge.

[0206] [Embodiment 54] The method of any one of embodiments 36 to 53, wherein the device has two pairs of legs, each pair of legs being positioned on opposite sides of the body.

[0207] [Embodiment 55] The method of any one of embodiments 36 to 54, wherein the legs are attached to the body via a bottom surface of the body.

[0208] [Embodiment 56] The method of any one of embodiments 36 to 54, wherein the legs are attached to the body via a side wall of the body.

[0209] [Embodiment 57] 57. The method of any one of embodiments 36 to 56, wherein the legs comprise a metal, a metal alloy, a ceramic, a silicon, or a non-polymeric material.

[0210] [Embodiment 58] 58. The method of any one of embodiments 36-57, wherein the legs comprise an elastomeric coating or a non-elastomeric polymer coating.

[0211] [Embodiment 59] 60. The method of embodiment 58, wherein the coating is bioinert.

[0212] [Embodiment 60] 60. The method of embodiment 58 or 59, wherein the coating is a silicone, a urethane polymer, a poly(p-xylylene) polymer, or a polyimide.

[0213] [Embodiment 61] The method of any one of embodiments 58 to 60, wherein at least one of the legs has an outer surface coated with an elastomeric coating or a non-elastomeric polymer coating and an inner surface having at least one electrode that is not coated with an elastomeric coating or a non-elastomeric polymer coating.

[0214] [Embodiment 62] The method of any one of embodiments 36 to 61, wherein the body has a bottom surface and the two or more electrodes terminate on the bottom of the body.

[0215] [Embodiment 63] The method of any one of embodiments 36 to 61, wherein two or more electrodes are disposed on the clip.

[0216] [Embodiment 64] 64. The method of embodiment 63, wherein the clip comprises a plurality of flexible legs extending below the body, and the two or more electrodes are disposed on the flexible legs.

[0217] [Embodiment 65] 65. The method of any one of embodiments 36 to 64, wherein the body comprises a housing.

[0218] [Embodiment 66] 66. The method of embodiment 65, wherein the housing comprises a bioinert material.

[0219] [Embodiment 67] 67. The method of embodiment 66, wherein the housing comprises a bioinert material, and the bioinert material of the housing comprises titanium or ceramic.

[0220] [Embodiment 68] The method of any one of embodiments 36 to 67, wherein the body comprises an integrated circuit electrically connected to the ultrasonic transducer and the two or more electrodes.

[0221] [Embodiment 69] 69. The method of embodiment 68, wherein the integrated circuit comprises an energy storage circuit comprising a capacitor.

[0222] [Embodiment 70] 70. The method of any one of embodiments 36 to 69, wherein the body is about 5 mm or less in length in its longest dimension.

[0223] [Embodiment 71] 1. An implantable medical device, comprising: (a) two or more ultrasonic transducers configured to receive ultrasonic waves that power the device and radiate ultrasonic backscatter; (b) an integrated circuit comprising an energy storage circuit including a capacitor, where the integrated circuit is electrically connected to the first ultrasonic transducer and the second ultrasonic transducer; and (c) one or more of: (i) a sensor configured to measure a physiological condition; (ii) two or more electrodes in electrical communication with the tissue and configured to emit an electrical pulse to the tissue; or (iii) two or more electrodes in electrical communication with the tissue and configured to detect an electrophysiological signal from the tissue; An implantable medical device, wherein the sensor or two or more electrodes are electrically connected to an integrated circuit.

[0224] [Embodiment 72] An implantable medical device as described in embodiment 71, wherein the two or more ultrasonic transducers include a first ultrasonic transducer having a first polarization axis and a second ultrasonic transducer having a second polarization axis, wherein the second ultrasonic transducer is positioned such that the second polarization axis is perpendicular to the first polarization axis, and the first ultrasonic transducer and the second ultrasonic transducer are configured to receive ultrasound that powers the device and radiates ultrasonic backscatter.

[0225] [Embodiment 73] An implantable medical device as described in embodiments 71 and 72, wherein the implantable device comprises a sensor configured to measure a physiological condition.

[0226] [Embodiment 74] The implantable medical device of embodiment 73, wherein the sensor is a temperature sensor, a pH sensor, a pressure sensor, a strain sensor, a pulse sensor, a blood pressure sensor, an oxygen meter, a glucose meter, an impedance meter, or is configured to measure an analyte concentration.

[0227] [Embodiment 75] An implantable medical device as described in embodiment 71 or 72, wherein the implantable device comprises two or more electrodes in electrical communication with tissue and configured to emit an electrical pulse to the tissue.

[0228] [Embodiment 76] An implantable medical device as described in embodiment 75, wherein the implantable device comprises two or more electrodes configured to be in electrical communication with the tissue and detect electrophysiological signals from the tissue.

[0229] [Embodiment 77] An implantable medical device as described in embodiment 76, wherein the electrophysiological signal is a neural signal.

[0230] [Embodiment 78] An implantable medical device described in any one of embodiments 71 to 77, wherein ultrasonic backscatter encodes information related to a measured physiological condition, an emitted electrical pulse, or a detected electrophysiological signal.

[0231] [Embodiment 79] An implantable medical device as described in embodiment 78, wherein two or more ultrasonic transducers are electrically connected in parallel to the integrated circuit.

[0232] [Embodiment 80] An implantable medical device described in any one of embodiments 71 to 79, wherein two or more ultrasonic transducers and an integrated circuit are housed within the body, and the device further comprises a clip configured to at least partially surround the thread-like tissue.

[0233] [Embodiment 81] The implantable medical device of embodiment 80, wherein the thread-like tissue comprises a nerve.

[0234] [Embodiment 82] The implantable medical device of embodiment 80, wherein the thread-like tissue comprises a nerve attached to a blood vessel.

[0235] [Embodiment 83] The implantable medical device of embodiment 80, wherein the thread-like tissue comprises a nerve attached to a blood vessel.

[0236] [Embodiment 84] An implantable medical device described in any one of embodiments 80 to 83, wherein the clip has a plurality of flexible legs extending below the body.

[0237] [Embodiment 85] An implantable medical device described in any one of embodiments 1 to 35 and 71 to 84, wherein the implantable medical device does not include a battery.

[0238] [Embodiment 86] An implantable medical device described in any one of embodiments 1 to 35 and 71 to 85, wherein the implantable medical device does not have a radio frequency communication system.

[0239] [Embodiment 87] An implantable medical device described in any one of embodiments 1 to 35 and 71 to 86, wherein the implantable medical device does not have electrical leads extending from the body of the device without terminating in the legs of the clip.

[0240] [Embodiment 88] A system comprising an implantable medical device described in any one of embodiments 1 to 35 and 71 to 87, and an interrogator comprising one or more ultrasonic transducers configured to transmit ultrasound to the implantable medical device, wherein the ultrasound provides power to the implantable medical device.

[0241] [Embodiment 89] The system of embodiment 88, wherein the interrogator is configured to be mounted externally.

[0242] [Embodiment 90] The system of embodiment 88 or 89, wherein the interrogator is configured to receive ultrasound backscatter emitted by the implantable device, where the ultrasound backscatter encodes data.

[0243] [Embodiment 91] 91. The system of embodiment 90, wherein the interrogator is configured to analyze the data or transmit the data to a computer system.

[0244] [Embodiment 92] A system described in any one of embodiments 88 to 91, wherein the ultrasound transmitted by the interrogator encodes instructions for operating the implantable device.

[0245] [Embodiment 93] 1. A method of treating incontinence in a subject, comprising: 1. A method comprising: converting energy from ultrasound into electrical energy that powers a device fully implanted in the subject comprising two or more electrodes in electrical communication with the subject's tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches; and electrically stimulating the subject's tibial nerve or branches, pudendal nerve or branches, or sacral nerve or branches using the fully implanted medical device.

[0246] [Embodiment 94] 94. The method of embodiment 93, wherein the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches are stimulated by a fully implanted medical device in response to an ultrasound-encoded trigger signal.

[0247] [Embodiment 95] 95. The method of embodiment 93 or 94, wherein electrically stimulating the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches comprises emitting a plurality of current pulses to the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches.

[0248] [Embodiment 96] 95. The method of embodiment 93 or 94, wherein electrically stimulating the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches comprises emitting a plurality of current pulses to the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches.

[0249] [Embodiment 97] 97. The method of embodiment 95 or 96, wherein the multiple current pulses or multiple voltage pulses are emitted at a constant frequency.

[0250] [Embodiment 98] 98. The method of embodiment 97, wherein the frequency of the multiple current pulses or multiple voltage pulses is from about 1 Hz to about 50 Hz.

[0251] [Embodiment 99] A method as described in any one of embodiments 93 to 98, comprising transmitting ultrasound to the implanted medical device using an interrogator comprising one or more ultrasound transducers.

[0252] [Embodiment 100] 100. The method of embodiment 99, wherein the ultrasound encodes instructions for operating the implantable device.

[0253] [Embodiment 101] 101. The method of embodiment 99 or 100, comprising emitting ultrasonic backscatter that encodes data.

[0254] [Embodiment 102] The method of embodiment 101, wherein the data comprises a stimulation state indicating whether the implantable device emitted an electrical pulse or what parameters were used to emit the electrical pulse.

[0255] [Embodiment 103] 103. The method of embodiment 101 or 102, comprising receiving ultrasonic backscatter.

[0256] [Embodiment 104] 104. The method of embodiment 103, comprising analyzing ultrasound backscatter encoded data.

[0257] [Embodiment 105] The method of any one of embodiments 93 to 104, wherein the interrogator is an externally worn device.

[0258] [Embodiment 106] The method of any one of embodiments 93 to 105, wherein the interrogator contacts the subject's skin.

[0259] [Embodiment 107] 107. The method of any one of embodiments 93 to 106, wherein the interrogator is operated using a handheld device.

[0260] [Embodiment 108] 108. The method of embodiment 107, wherein the handheld device is wirelessly connected to the interrogator.

[0261] [Embodiment 109] The method of any one of embodiments 93 to 108, comprising implanting a medical device in a subject to contact two or more electrodes with the tibial nerve or a branch thereof, the pudendal nerve or a branch thereof, or the sacral nerve or a branch thereof.

[0262] [Embodiment 110] The method of any one of embodiments 93 to 109, wherein two or more electrodes are in electrical communication with the tibial nerve or its branches.

[0263] [Embodiment 111] 111. The method of embodiment 110, wherein the interrogator is attached to the subject's ankle.

[0264] [Embodiment 112] The method of any one of embodiments 93 to 109, wherein two or more electrodes are in electrical communication with the sacral nerve or its branches.

[0265] [Embodiment 113] The method of embodiment 112, wherein the interrogator is attached to the patient's hip, abdomen, lower back, buttocks, or upper extremity.

[0266] [Embodiment 114] The method of any one of embodiments 93 to 113, wherein the incontinence is overactive bladder, underactive bladder, urinary incontinence, or fecal incontinence.

[0267] [Embodiment 115] The method of any one of embodiments 93 to 114, wherein the subject is a human.

[0268] [Embodiment 116] The method of any one of embodiments 93 to 115, wherein the implantable device is an implantable medical device described in any one of embodiments 1 to 35 and 71 to 87.

Claims

1. 1. An implantable medical device, comprising: a body including an ultrasonic transducer configured to receive ultrasonic waves and convert energy from the ultrasonic waves into electrical energy to power the device; two or more electrodes in electrical communication with the ultrasonic transducer; a clip attached to the body configured to at least partially encircle a nerve and place the two or more electrodes in electrical communication with the nerve; 1. An implantable medical device comprising:

2. The implantable medical device of claim 1 , wherein the clip is configured to at least partially surround the nerve and threadlike tissue attached to the nerve.

3. The implantable medical device of claim 2 , wherein the threadlike tissue is a blood vessel.

4. 4. The implantable medical device of claim 1, wherein the clip comprises a plurality of flexible legs extending below the body.

5. The implantable medical device of claim 4 , wherein the flexible legs are curved.

6. 6. The implantable medical device of claim 5, wherein as the legs extend down the body, they extend away from the body before curving towards the body.

7. 7. The implantable medical device of claim 6, wherein the plurality of flexible legs comprises at least one pair of legs, the pair of legs comprising a first leg and a second leg extending downwardly away from the body in opposite directions.

8. The implantable medical device of claim 7 , wherein the first leg and the second leg are connected by a crossbar connected to the body.

9. The implantable medical device of claim 8 , wherein the crossbar is connected to the body of the device via a flexure.

10. 10. The implantable medical device of claim 4, wherein the legs are attached to the body via a bottom of the body.

11. 11. The implantable medical device of any one of claims 4 to 10, wherein the legs comprise a metal, a metal alloy, a ceramic, a silicon, or a non-polymeric material.

12. 11. The implantable medical device of claim 4, wherein the legs comprise an elastomeric or non-elastomeric polymeric coating.

13. The implantable medical device of claim 11 , wherein at least one of the legs has an outer surface coated with an elastomeric coating or a non-elastomeric polymeric coating and an inner surface comprising at least one electrode that is not coated with the elastomeric coating or the non-elastomeric polymeric coating.

14. 14. The implantable medical device of claim 1, wherein the body has a bottom surface, and the two or more electrodes terminate on the bottom of the body.

15. The implantable medical device of claim 1 , wherein the two or more electrodes are disposed on the clip.

16. 16. The implantable medical device of claim 15, wherein the clip comprises a plurality of flexible legs extending below the body, the two or more electrodes being disposed on the flexible legs.

17. The implantable medical device of claim 1 , wherein the body comprises a housing.

18. 18. The implantable medical device of claim 1, wherein the body comprises an integrated circuit electrically connected to the ultrasound transducer and the two or more electrodes.

19. The implantable medical device of claim 18 , wherein the integrated circuit comprises an energy storage circuit comprising a capacitor.

20. 20. The implantable medical device of any one of claims 1-19, wherein the body is about 5 mm or less in length in its longest dimension.

21. 21. The implantable medical device of claim 1, wherein the ultrasound transducer is configured to emit ultrasound backscatter that encodes data.

22. 22. The implantable medical device of claim 21, wherein the data comprises information related to detected neural activity, measured physiological conditions, device conditions, or emitted electrical pulses.

23. 23. The implantable medical device of claim 1, wherein the implantable medical device is configured to emit an electrical pulse to the nerve.

24. 24. The implantable medical device of claim 1, wherein the ultrasound transducer is configured to receive ultrasound waves encoding instructions for operating the implantable device.

25. 25. The implantable medical device of claim 24, wherein the instructions comprise a trigger signal that operates the implantable device to emit an electrical pulse to the nerve.

26. 1. A method of implanting a medical device in a subject, the method comprising: a body including an ultrasound transducer configured to receive ultrasound waves and convert energy from the ultrasound waves into electrical energy to power the device; an electrode in electrical communication with the ultrasound transducer; and a clip attached to the body, the clip including a plurality of flexible legs, the method comprising: bending one or more legs of the clip outwardly; placing the electrode in electrical communication with a nerve; and releasing the one or more legs of the clip, the one or more legs at least partially surrounding the nerve and maintaining the electrode in electrical communication with the nerve upon release.

27. 1. An implantable medical device, comprising: (a) two or more ultrasonic transducers configured to power the device and to receive ultrasonic waves that radiate ultrasonic backscatter; (b) an integrated circuit comprising an energy storage circuit comprising a capacitor, the integrated circuit electrically connected to a first said ultrasonic transducer and a second said ultrasonic transducer; (c) one or more of: (i) a sensor configured to measure a physiological condition; (ii) two or more electrodes in electrical communication with tissue and configured to emit an electrical pulse to the tissue; or (iii) two or more electrodes in electrical communication with tissue and configured to detect an electrophysiological signal from the tissue; The sensor or the two or more electrodes are electrically connected to the integrated circuit.

28. 28. The implantable medical device of claim 27, wherein the two or more ultrasound transducers comprise a first ultrasound transducer having a first polarization axis and a second ultrasound transducer having a second polarization axis, the second ultrasound transducer being positioned such that the second polarization axis is orthogonal to the first polarization axis, and the first ultrasound transducer and the second ultrasound transducer being configured to receive the ultrasound that powers the device and radiates the ultrasound backscatter.

29. 29. The implantable medical device of claims 27 and 28, wherein the implantable device comprises the sensor configured to measure a physiological condition.

30. 30. The implantable medical device of claim 29, wherein the sensor is a temperature sensor, a pH sensor, a pressure sensor, a strain sensor, a pulse sensor, a blood pressure sensor, an oximeter, a glucose meter, an impedance meter, or configured to measure an analyte concentration.

31. 30. The implantable medical device of claim 27 or 28, wherein the implantable device comprises the two or more electrodes in electrical communication with tissue and configured to emit an electrical pulse to the tissue.

32. 32. The implantable medical device of claim 31, wherein the implantable device comprises the two or more electrodes in electrical communication with tissue and configured to detect electrophysiological signals from the tissue.

33. The implantable medical device of claim 32 , wherein the electrophysiological signal is a neural signal.

34. 34. The implantable medical device of any one of claims 27 to 33, wherein the ultrasonic backscatter encodes information related to the measured physiological condition, the emitted electrical pulse, or the detected electrophysiological signal.

35. 35. The implantable medical device of any one of claims 27 to 34, wherein the two or more ultrasound transducers are electrically connected in parallel to the integrated circuit.

36. 36. The implantable medical device of any one of claims 1-25 and 27-35, wherein the implantable medical device does not include a battery.

37. 37. The implantable medical device of any one of claims 1-25 and 27-36, wherein the implantable medical device does not include a radio frequency communication system.

38. 38. The implantable medical device of any one of claims 1-25 and 27-37, wherein the implanted medical device does not include electrical leads extending from a body of the device without terminating in clip legs.

39. 39. A system comprising the implantable medical device of any one of claims 1 to 25 and 27 to 38, and an interrogator comprising one or more ultrasound transducers configured to transmit ultrasound to the implantable medical device, wherein the ultrasound provides power to the implantable medical device.

40. 40. The system of claim 39, wherein the interrogator is configured to be mounted externally.

41. 41. The system of claim 39 or 40, wherein the interrogator is configured to receive ultrasound backscatter emitted by the implantable device, the ultrasound backscatter encoding data.

42. 42. The system of claim 41, wherein the interrogator is configured to analyze the data or transmit the data to a computer system.

43. 43. The system of any one of claims 39 to 42, wherein the ultrasound transmitted by the interrogator encodes instructions for operating the implantable device.

44. 1. A method of treating incontinence in a subject, comprising: converting energy from the ultrasound waves into electrical energy that powers a medical device fully implanted in the subject, the device comprising two or more electrodes in electrical communication with the subject's tibial nerve or branches thereof, the pudendal nerve or branches thereof, or the sacral nerve or branches thereof; electrically stimulating the tibial nerve or its branches, the pudendal nerve or its branches, or the sacral nerve or its branches of the subject using the fully implanted medical device; 1. A method of treating incontinence in a subject, comprising:

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